1	22180794	WBPaper00042241.bma.rs.paper	N.A.	N.A.	1	A deep sequencing approach to comparatively analyze the transcriptome of lifecycle stages of the filarial worm, Brugia malayi.	BACKGROUND: Developing intervention strategies for the control of parasitic nematodes continues to be a significant challenge. Genomic and post-genomic approaches play an increasingly important role for providing fundamental molecular information about these parasites, thus enhancing basic as well as translational research. Here we report a comprehensive genome-wide survey of the developmental transcriptome of the human filarial parasite Brugia malayi. METHODOLOGY/PRINCIPAL FINDINGS: Using deep sequencing, we profiled the transcriptome of eggs and embryos, immature (3 days of age) and mature microfilariae (MF), third- and fourth-stage larvae (L3 and L4), and adult male and female worms. Comparative analysis across these stages provided a detailed overview of the molecular repertoires that define and differentiate distinct lifecycle stages of the parasite. Genome-wide assessment of the overall transcriptional variability indicated that the cuticle collagen family and those implicated in molting exhibit noticeably dynamic stage-dependent patterns. Of particular interest was the identification of genes displaying sex-biased or germline-enriched profiles due to their potential involvement in reproductive processes. The study also revealed discrete transcriptional changes during larval development, namely those accompanying the maturation of MF and the L3 to L4 transition that are vital in establishing successful infection in mosquito vectors and vertebrate hosts, respectively. CONCLUSIONS/SIGNIFICANCE: Characterization of the transcriptional program of the parasite's lifecycle is an important step toward understanding the developmental processes required for the infectious cycle. We find that the transcriptional program has a number of stage-specific pathways activated during worm development. In addition to advancing our understanding of transcriptome dynamics, these data will aid in the study of genome structure and organization by facilitating the identification of novel transcribed elements and splice variants.	14	11673	Choi YJ	Choi YJ, Ghedin E, Berriman M, McQuillan J, Holroyd N, Mayhew GF, Christensen BM, Michalski ML	A deep sequencing approach to comparatively analyze the transcriptome of lifecycle stages of the filarial worm, Brugia malayi.	PLoS Negl Trop Dis	2011	RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.ERP000948.ERX026028~RNASeq.brugia.WBStrain00041073.WBls:0000083.Male.WBbt:0007833.ERP000948.ERX026029~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.ERP000948.ERX026030~RNASeq.brugia.WBStrain00041073.WBls:0000662.Unknown.WBbt:0007833.ERP000948.ERX026031~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.ERP000948.ERX026032~RNASeq.brugia.WBStrain00041073.WBls:0000082.Unknown.WBbt:0007833.ERP000948.ERX026033~RNASeq.brugia.WBStrain00041073.WBls:0000094.Male.WBbt:0007833.ERP000948.ERX026034~RNASeq.brugia.WBStrain00041073.WBls:0000094.Male.WBbt:0007833.ERP000948.ERX026035~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.ERP000948.ERX026036~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.ERP000948.ERX026037~RNASeq.brugia.WBStrain00041073.WBls:0000663.Unknown.WBbt:0007833.ERP000948.ERX026038~RNASeq.brugia.WBStrain00041073.WBls:0000082.Unknown.WBbt:0007833.ERP000948.ERX026039~RNASeq.brugia.WBStrain00041073.WBls:0000662.Unknown.WBbt:0007833.ERP000948.ERX026040~RNASeq.brugia.WBStrain00041073.WBls:0000082.Unknown.WBbt:0007833.ERP000948.ERX026041	Method: RNAseq|Species: Brugia malayi
2	26727204	WBPaper00049086.bma.rs.paper	N.A.	N.A.	1	The Effect of In Vitro Cultivation on the Transcriptome of Adult Brugia malayi.	BACKGROUND: Filarial nematodes cause serious and debilitating infections in human populations of tropical countries, contributing to an entrenched cycle of poverty. Only one human filarial parasite, Brugia malayi, can be maintained in rodents in the laboratory setting. It has been a widely used model organism in experiments that employ culture systems, the impact of which on the worms is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using Illumina RNA sequencing, we characterized changes in gene expression upon in vitro maintenance of adult B. malayi female worms at four time points: immediately upon removal from the host, immediately after receipt following shipment, and after 48 h and 5 days in liquid culture media. The dramatic environmental change and the 24 h time lapse between removal from the host and establishment in culture caused a globally dysregulated gene expression profile. We found a maximum of 562 differentially expressed genes based on pairwise comparison between time points. After an initial shock upon removal from the host and shipping, a few stress fingerprints remained after 48 h in culture and until the experiment was stopped. This was best illustrated by a strong and persistent up-regulation of several genes encoding cuticle collagens, as well as serpins. CONCLUSIONS/SIGNIFICANCE: These findings suggest that B. malayi can be maintained in culture as a valid system for pharmacological and biological studies, at least for several days after removal from the host and adaptation to the new environment. However, genes encoding several stress indicators remained dysregulated until the experiment was stopped.	24	11673	Ballesteros C	Ballesteros C, Tritten L, O'Neill M, Burkman E, Zaky WI, Xia J, Moorhead A, Williams SA, Geary TG	The Effect of In Vitro Cultivation on the Transcriptome of Adult Brugia malayi.	PLoS Negl Trop Dis	2016	RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176947~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176948~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176949~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176950~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176951~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176952~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176953~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176954~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176955~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176956~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176957~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176958~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176959~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176960~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176961~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176962~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176963~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176964~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176965~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176966~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176967~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176968~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176969~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP063061.SRX1176970	Method: RNAseq|Species: Brugia malayi
3	27529747	WBPaper00049974.bma.rs.paper	N.A.	N.A.	1	The Effects of Ivermectin on Brugia malayi Females In Vitro: A Transcriptomic Approach.	BACKGROUND: Lymphatic filariasis and onchocerciasis are disabling and disfiguring neglected tropical diseases of major importance in developing countries. Ivermectin is the drug of choice for mass drug administration programs for the control of onchocerciasis and lymphatic filariasis in areas where the diseases are co-endemic. Although ivermectin paralyzes somatic and pharyngeal muscles in many nematodes, these actions are poorly characterized in adult filariae. We hypothesize that paralysis of pharyngeal pumping by ivermectin in filariae could result in deprivation of essential nutrients, especially iron, inducing a wide range of responses evidenced by altered gene expression, changes in metabolic pathways, and altered developmental states in embryos. Previous studies have shown that ivermectin treatment significantly reduces microfilariae release from females within four days of exposure in vivo, while not markedly affecting adult worms. However, the mechanisms responsible for reduced production of microfilariae are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed transcriptomic profiles from Brugia malayi adult females, an important model for other filariae, using RNAseq technology after exposure in culture to ivermectin at various concentrations (100 nM, 300 nM and 1 M) and time points (24, 48, 72 h, and 5 days). Our analysis revealed drug-related changes in expression of genes involved in meiosis, as well as oxidative phosphorylation, which were significantly down-regulated as early as 24 h post-exposure. RNA interference phenotypes of the orthologs of these down-regulated genes in C. elegans include &quot;maternal sterile&quot;, &quot;embryonic lethal&quot;, &quot;larval arrest&quot;, &quot;larval lethal&quot; and &quot;sick&quot;. CONCLUSION/SIGNIFICANCE: These changes provide insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development.	34	11673	Ballesteros C	Ballesteros C, Tritten L, O'Neill M, Burkman E, Zaky WI, Xia J, Moorhead A, Williams SA, Geary TG	The Effects of Ivermectin on Brugia malayi Females In Vitro: A Transcriptomic Approach.	PLoS Negl Trop Dis	2016	RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447440~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447441~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447442~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447443~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447444~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447445~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447446~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447447~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447448~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447449~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447450~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447451~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447452~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066610.SRX1447453~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447454~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447455~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447456~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447457~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447458~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447459~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447460~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447461~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447462~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447463~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447464~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447465~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447466~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447467~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447468~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447469~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447470~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447471~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447472~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP066611.SRX1447473	Method: RNAseq|Species: Brugia malayi
4	28358880	WBPaper00051007.bma.rs.paper	N.A.	N.A.	1	Defining Brugia malayi and Wolbachia symbiosis by stage-specific dual RNA-seq.	BACKGROUND: Filarial nematodes currently infect up to 54 million people worldwide, with millions more at risk for infection, representing the leading cause of disability in the developing world. Brugia malayi is one of the causative agents of lymphatic filariasis and remains the only human filarial parasite that can be maintained in small laboratory animals. Many filarial nematode species, including B. malayi, carry an obligate endosymbiont, the alpha-proteobacteria Wolbachia, which can be eliminated through antibiotic treatment. Elimination of the endosymbiont interferes with development, reproduction, and survival of the worms within the mamalian host, a clear indicator that the Wolbachia are crucial for survival of the parasite. Little is understood about the mechanism underlying this symbiosis. METHODOLOGY/ PRINCIPLE FINDINGS: To better understand the molecular interplay between these two organisms we profiled the transcriptomes of B. malayi and Wolbachia by dual RNA-seq across the life cycle of the parasite. This helped identify functional pathways involved in this essential symbiotic relationship provided by the co-expression of nematode and bacterial genes. We have identified significant stage-specific and gender-specific differential expression in Wolbachia during the nematode's development. For example, during female worm development we find that Wolbachia upregulate genes involved in ATP production and purine biosynthesis, as well as genes involved in the oxidative stress response. CONCLUSIONS/ SIGNIFICANCE: This global transcriptional analysis has highlighted specific pathways to which both Wolbachia and B. malayi contribute concurrently over the life cycle of the parasite, paving the way for the development of novel intervention strategies.	14	11673	Grote A	Grote A, Voronin D, Ding T, Twaddle A, Unnasch TR, Lustigman S, Ghedin E	Defining Brugia malayi and Wolbachia symbiosis by stage-specific dual RNA-seq.	PLoS Negl Trop Dis	2017	RNASeq.brugia.WBStrain00041073.WBls:0000083.female.WBbt:0007833.SRP090644.SRX2200117~RNASeq.brugia.WBStrain00041073.WBls:0000083.female.WBbt:0007833.SRP090644.SRX2200118~RNASeq.brugia.WBStrain00041073.WBls:0000083.male.WBbt:0007833.SRP090644.SRX2200119~RNASeq.brugia.WBStrain00041073.WBls:0000083.male.WBbt:0007833.SRP090644.SRX2200120~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP090644.SRX2200121~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP090644.SRX2200122~RNASeq.brugia.WBStrain00041073.WBls:0000083.male.WBbt:0007833.SRP090644.SRX2200123~RNASeq.brugia.WBStrain00041073.WBls:0000083.male.WBbt:0007833.SRP090644.SRX2200124~RNASeq.brugia.WBStrain00041073.WBls:0000083.female.WBbt:0007833.SRP090644.SRX2200125~RNASeq.brugia.WBStrain00041073.WBls:0000083.female.WBbt:0007833.SRP090644.SRX2200126~RNASeq.brugia.WBStrain00041073.WBls:0000083.male.WBbt:0007833.SRP090644.SRX2200127~RNASeq.brugia.WBStrain00041073.WBls:0000083.male.WBbt:0007833.SRP090644.SRX2200128~RNASeq.brugia.WBStrain00041073.WBls:0000083.female.WBbt:0007833.SRP090644.SRX2200129~RNASeq.brugia.WBStrain00041073.WBls:0000083.female.WBbt:0007833.SRP090644.SRX2200130	Method: RNAseq|Species: Brugia malayi
5	30533772	WBPaper00061189.bma.rs.paper	N.A.	N.A.	1	Multispecies Transcriptomics Data Set of Brugia malayi, Its <i>Wolbachia</i> Endosymbiont <i>w</i>Bm, and Aedes aegypti across the B. malayi Life Cycle.	Here, we present a comprehensive transcriptomics data set of Brugia malayi, its Wolbachia endosymbiont <i>w</i>Bm, and its vector host. This study samples from 16 stages across the entire B. malayi life cycle, including stage 1 through 4 larvae, adult males and females, embryos, immature microfilariae, and mature microfilariae.	47	11671	Chung M	Chung M, Teigen L, Libro S, Bromley RE, Kumar N, Sadzewicz L, Tallon LJ, Foster JM, Michalski ML, Dunning Hotopp JC	Multispecies Transcriptomics Data Set of Brugia malayi, Its <i>Wolbachia</i> Endosymbiont <i>w</i>Bm, and Aedes aegypti across the B. malayi Life Cycle.	Microbiol Resour Announc	2018	RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP068692.SRX1539085~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP068692.SRX1539707~RNASeq.brugia.WBStrain00041073.WBls:0000083.female.WBbt:0007833.SRP068692.SRX1539730~RNASeq.brugia.WBStrain00041073.WBls:0000083.Female.WBbt:0007833.SRP068692.SRX1539734~RNASeq.brugia.WBStrain00041073.WBls:0000083.Male.WBbt:0007833.SRP068692.SRX1539737~RNASeq.brugia.WBStrain00041073.WBls:0000083.Male.WBbt:0007833.SRP068692.SRX1539740~RNASeq.brugia.WBStrain00041073.WBls:0000092.Unknown.WBbt:0007833.SRP068692.SRX1539746~RNASeq.brugia.WBStrain00041073.WBls:0000092.Unknown.WBbt:0007833.SRP068692.SRX1539751~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX1539755~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX1539758~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX1539799~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX1539813~RNASeq.brugia.WBStrain00041073.WBls:0000097.Unknown.WBbt:0007833.SRP068692.SRX1539817~RNASeq.brugia.WBStrain00041073.WBls:0000097.L3\/L4.WBbt:0007833.SRP068692.SRX1539819~RNASeq.brugia.WBStrain00041073.WBls:0000081.male.WBbt:0007833.SRP068692.SRX1539862~RNASeq.brugia.WBStrain00041073.WBls:0000081.Male.WBbt:0007833.SRP068692.SRX1539865~RNASeq.brugia.WBStrain00041073.WBls:0000082.Female.WBbt:0007833.SRP068692.SRX1539869~RNASeq.brugia.WBStrain00041073.WBls:0000082.female.WBbt:0007833.SRP068692.SRX1539871~RNASeq.brugia.WBStrain00041073.WBls:0000078.Unknown.WBbt:0007833.SRP068692.SRX1539873~RNASeq.brugia.WBStrain00041073.WBls:0000078.Unknown.WBbt:0007833.SRP068692.SRX1539874~RNASeq.brugia.WBStrain00041073.WBls:0000078.Unknown.WBbt:0007833.SRP068692.SRX1539875~RNASeq.brugia.WBStrain00041073.WBls:0000097.Unknown.WBbt:0007833.SRP068692.SRX1539876~RNASeq.brugia.WBStrain00041073.WBls:0000097.Unknown.WBbt:0007833.SRP068692.SRX1539886~RNASeq.brugia.WBStrain00041073.WBls:0000080.Unknown.WBbt:0007833.SRP068692.SRX1539947~RNASeq.brugia.WBStrain00041073.WBls:0000080.Unknown.WBbt:0007833.SRP068692.SRX1539949~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX1539952~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX1539954~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX2409229~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX2409230~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX2414981~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX2414982~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX2415043~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX2415044~RNASeq.brugia.WBStrain00041073.WBls:0000078.Unknown.WBbt:0007833.SRP068692.SRX2415908~RNASeq.brugia.WBStrain00041073.WBls:0000078.Unknown.WBbt:0007833.SRP068692.SRX2415909~RNASeq.brugia.WBStrain00041073.WBls:0000078.Unknown.WBbt:0007833.SRP068692.SRX2415910~RNASeq.brugia.WBStrain00041073.WBls:0000078.Unknown.WBbt:0007833.SRP068692.SRX2415911~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX2416292~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX2416293~RNASeq.brugia.WBStrain00041073.WBls:0000097.Unknown.WBbt:0007833.SRP068692.SRX2505170~RNASeq.brugia.WBStrain00041073.WBls:0000097.Unknown.WBbt:0007833.SRP068692.SRX2505171~RNASeq.brugia.WBStrain00041073.WBls:0000097.Unknown.WBbt:0007833.SRP068692.SRX2505769~RNASeq.brugia.WBStrain00041073.WBls:0000080.Unknown.WBbt:0007833.SRP068692.SRX2505770~RNASeq.brugia.WBStrain00041073.WBls:0000080.Unknown.WBbt:0007833.SRP068692.SRX2505771~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX2505953~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX2505954~RNASeq.brugia.WBStrain00041073.WBls:0000081.Unknown.WBbt:0007833.SRP068692.SRX2505955	Method: RNAseq|Species: Brugia malayi
6	19181841	WBPaper00032529.cbn.rs.paper	N.A.	N.A.	1	Massively parallel sequencing of the polyadenylated transcriptome of C. elegans.	Using massively parallel sequencing by synthesis methods, we have surveyed the poly-A+ transcripts from four stages of the nematode C. elegans to an unprecedented depth. Using novel statistical approaches, we evaluated the coverage of annotated features of the genome and of candidate processed transcripts, including splice junctions, trans-spliced leader sequences and poly-adenylation tracts. The data provide experimental support for more than 85% of the annotated protein coding transcripts in WormBase (WS170) and confirm additional details of processing. For example, the total number of confirmed splice junctions was raised from 70,911 to over 98,000. The data also suggest thousands of modifications to WormBase annotations, and identify new spliced junctions and genes not part of any WormBase annotation, including at least 80 putative genes not found in any of three predicted gene sets. The quantitative nature of the data also suggests that mRNA levels may be measured by this approach with unparalleled precision. Although most sequences align with protein coding genes, a small fraction fall in introns and intergenic regions. One notable region on the X chromosome encodes a noncoding transcript of greater than 10 kb localized to somatic nuclei.	14	33282	Hillier LW	Hillier LW, Reinke V, Green P, Hirst M, Marra MA, Waterston RH	Massively parallel sequencing of the polyadenylated transcriptome of C. elegans.	Genome Res	2009	RNASeq.brenneri.WBStrain00041997.WBls:0000004.Unknown.WBbt:0007833.SRP006033.SRX100769~RNASeq.brenneri.WBStrain00041997.WBls:0000004.Unknown.WBbt:0007833.SRP006033.SRX100770~RNASeq.brenneri.WBStrain00041997.WBls:0000038.Unknown.WBbt:0007833.SRP006033.SRX100771~RNASeq.brenneri.WBStrain00041997.WBls:0000038.Unknown.WBbt:0007833.SRP006033.SRX100772~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Female.WBbt:0007833.SRP006033.SRX100773~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Female.WBbt:0007833.SRP006033.SRX100774~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Female.WBbt:0007833.SRP006033.SRX100775~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Female.WBbt:0007833.SRP006033.SRX100776~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Male.WBbt:0007833.SRP006033.SRX100777~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Male.WBbt:0007833.SRP006033.SRX100778~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Male.WBbt:0007833.SRP006033.SRX100779~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Male.WBbt:0007833.SRP006033.SRX100780~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Female.WBbt:0007833.SRP006033.SRX103654~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Male.WBbt:0007833.SRP006033.SRX103657	Method: RNAseq|Species: Caenorhabditis brenneri|Tissue Specific
7	23103191	WBPaper00041689.cbn.rs.paper	GSE41367	GPL13776,GPL13657,GPL13776,GPL16135,GPL16136,GPL16137,GPL16138,GPL16139,GPL16140,GPL16141	1	Simplification and desexualization of gene expression in self-fertile nematodes.	Evolutionary transitions between sexual modes could be potent forces in genome evolution. Several Caenorhabditis nematode species have evolved self-fertile hermaphrodites from the obligately outcrossing females of their ancestors. We explored the relationship between sexual mode and global gene expression by comparing two selfing species, C. elegans and C. briggsae, with three phylogenetically informative outcrossing relatives, C. remanei, C. brenneri, and C. japonica. Adult transcriptome assemblies from the selfing species are consistently and strikingly smaller than those of the outcrossing species. Against this background of overall simplification, genes conserved in multiple outcrossing species with strong sex-biased expression are even more likely to be missing from the genomes of the selfing species. In addition, the sexual regulation of remaining transcripts has diverged markedly from the ancestral pattern in both selfing lineages, though in distinct ways. Thus, both the complexity and the sexual specialization of transciptomes are rapidly altered in response to the evolution of self-fertility. These changes may result from the combination of relaxed sexual selection and a recently reported genetic mechanism favoring genome shrinkage in partial selfers.	6	33282	Thomas CG	Thomas CG, Li R, Smith HE, Woodruff GC, Oliver B, Haag ES	Simplification and desexualization of gene expression in self-fertile nematodes.	Curr Biol	2012	RNASeq.brenneri.WBStrain00041997.WBls:0000041.Female.WBbt:0007833.SRP016006.SRX191965~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Female.WBbt:0007833.SRP016006.SRX191966~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Female.WBbt:0007833.SRP016006.SRX191967~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191968~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191969~RNASeq.brenneri.WBStrain00041997.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191970	Method: RNAseq|Species: Caenorhabditis brenneri
8	24098135	WBPaper00045465.cbn.rs.paper	N.A.	N.A.	1	Conserved translatome remodeling in nematode species executing a shared developmental transition.	Nematodes of the genus Caenorhabditis enter a developmental diapause state after hatching in the absence of food. To better understand the relative contributions of distinct regulatory modalities to gene expression changes associated with this developmental transition, we characterized genome-wide changes in mRNA abundance and translational efficiency associated with L1 diapause exit in four species using ribosome profiling and mRNA-seq. We found a strong tendency for translational regulation and mRNA abundance processes to act synergistically, together effecting a dramatic remodeling of the gene expression program. While gene-specific differences were observed between species, overall translational dynamics were broadly and functionally conserved. A striking, conserved feature of the response was strong translational suppression of ribosomal protein production during L1 diapause, followed by activation upon resumed development. On a global scale, ribosome footprint abundance changes showed greater similarity between species than changes in mRNA abundance, illustrating a substantial and genome-wide contribution of translational regulation to evolutionary maintenance of stable gene expression.	6	33282	Stadler M	Stadler M, Fire A	Conserved translatome remodeling in nematode species executing a shared developmental transition.	PLoS Genet	2013	RNASeq.brenneri.WBStrain00041997.WBls:0000024.Unknown.WBbt:0007833.SRP026198.SRX311810~RNASeq.brenneri.WBStrain00041997.WBls:0000024.Unknown.WBbt:0007833.SRP026198.SRX311811~RNASeq.brenneri.WBStrain00041997.WBls:0000024.Unknown.WBbt:0007833.SRP026198.SRX311812~RNASeq.brenneri.WBStrain00041997.WBls:0000024.Unknown.WBbt:0007833.SRP026198.SRX311813~RNASeq.brenneri.WBStrain00041997.WBls:0000024.Unknown.WBbt:0007833.SRP026198.SRX311814~RNASeq.brenneri.WBStrain00041997.WBls:0000024.Unknown.WBbt:0007833.SRP026198.SRX311815	Method: RNAseq|Species: Caenorhabditis brenneri
9	25141177	WBPaper00046067.cbn.rs.paper	N.A.	N.A.	1	Comparative population genomics in animals uncovers the determinants of genetic diversity.	Genetic diversity is the amount of variation observed between DNA sequences from distinct individuals of a given species. This pivotal concept of population genetics has implications for species health, domestication, management and conservation. Levels of genetic diversity seem to vary greatly in natural populations and species, but the determinants of this variation, and particularly the relative influences of species biology and ecology versus population history, are still largely mysterious. Here we show that the diversity of a species is predictable, and is determined in the first place by its ecological strategy. We investigated the genome-wide diversity of 76 non-model animal species by sequencing the transcriptome of two to ten individuals in each species. The distribution of genetic diversity between species revealed no detectable influence of geographic range or invasive status but was accurately predicted by key species traits related to parental investment: long-lived or low-fecundity species with brooding ability were genetically less diverse than short-lived or highly fecund ones. Our analysis demonstrates the influence of long-term life-history strategies on species response to short-term environmental perturbations, a result with immediate implications for conservation policies.	10	33282	Romiguier J	Romiguier J, Gayral P, Ballenghien M, Bernard A, Cahais V, Chenuil A, Chiari Y, Dernat R, Duret L, Faivre N, Loire E, Lourenco JM, Nabholz B, Roux C, Tsagkogeorga G, Weber AA, Weinert LA, Belkhir K, Bierne N, Glemin S, Galtier N	Comparative population genomics in animals uncovers the determinants of genetic diversity.	Nature	2014	RNASeq.brenneri.WBStrain00041997.WBls:0000002.Unknown.WBbt:0007833.SRP042651.SRX565023~RNASeq.brenneri.WBStrain00041997.WBls:0000002.Unknown.WBbt:0007833.SRP042651.SRX565024~RNASeq.brenneri.WBStrain00041997.WBls:0000002.Unknown.WBbt:0007833.SRP042651.SRX565025~RNASeq.brenneri.WBStrain00041997.WBls:0000002.Unknown.WBbt:0007833.SRP042651.SRX565026~RNASeq.brenneri.WBStrain00041997.WBls:0000002.Unknown.WBbt:0007833.SRP042651.SRX565027~RNASeq.brenneri.WBStrain00041997.WBls:0000002.Unknown.WBbt:0007833.SRP042651.SRX565028~RNASeq.brenneri.WBStrain00041997.WBls:0000002.Unknown.WBbt:0007833.SRP042651.SRX565029~RNASeq.brenneri.WBStrain00041997.WBls:0000002.Unknown.WBbt:0007833.SRP042651.SRX565030~RNASeq.brenneri.WBStrain00041997.WBls:0000002.Unknown.WBbt:0007833.SRP042651.SRX565031~RNASeq.brenneri.WBStrain00041997.WBls:0000002.Unknown.WBbt:0007833.SRP042651.SRX565032	Method: RNAseq|Species: Caenorhabditis brenneri
10	19181841	WBPaper00032529.cbg.rs.paper	N.A.	N.A.	1	Massively parallel sequencing of the polyadenylated transcriptome of C. elegans.	Using massively parallel sequencing by synthesis methods, we have surveyed the poly-A+ transcripts from four stages of the nematode C. elegans to an unprecedented depth. Using novel statistical approaches, we evaluated the coverage of annotated features of the genome and of candidate processed transcripts, including splice junctions, trans-spliced leader sequences and poly-adenylation tracts. The data provide experimental support for more than 85% of the annotated protein coding transcripts in WormBase (WS170) and confirm additional details of processing. For example, the total number of confirmed splice junctions was raised from 70,911 to over 98,000. The data also suggest thousands of modifications to WormBase annotations, and identify new spliced junctions and genes not part of any WormBase annotation, including at least 80 putative genes not found in any of three predicted gene sets. The quantitative nature of the data also suggests that mRNA levels may be measured by this approach with unparalleled precision. Although most sequences align with protein coding genes, a small fraction fall in introns and intergenic regions. One notable region on the X chromosome encodes a noncoding transcript of greater than 10 kb localized to somatic nuclei.	16	23163	Hillier LW	Hillier LW, Reinke V, Green P, Hirst M, Marra MA, Waterston RH	Massively parallel sequencing of the polyadenylated transcriptome of C. elegans.	Genome Res	2009	RNASeq.briggsae.WBStrain00040935.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP006033.SRX052079~RNASeq.briggsae.WBStrain00040935.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP006033.SRX052081~RNASeq.briggsae.WBStrain00040935.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP006033.SRX053351~RNASeq.briggsae.WBStrain00040935.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP006033.SRX089069~RNASeq.briggsae.WBStrain00040935.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP006033.SRX089070~RNASeq.briggsae.WBStrain00040935.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP006033.SRX089119~RNASeq.briggsae.WBStrain00040935.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP006033.SRX089120~RNASeq.briggsae.WBStrain00040935.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP006033.SRX100086~RNASeq.briggsae.WBStrain00040935.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP006033.SRX100087~RNASeq.briggsae.WBStrain00040935.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP006033.SRX100088~RNASeq.briggsae.WBStrain00040935.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP006033.SRX100089~RNASeq.briggsae.WBStrain00040935.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP006033.SRX103655~RNASeq.briggsae.WBStrain00040935.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP006033.SRX103656~RNASeq.briggsae.WBStrain00040935.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP006033.SRX103666~RNASeq.briggsae.WBStrain00040935.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP006033.SRX103667~RNASeq.briggsae.WBStrain00040935.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP006033.SRX103668	Method: RNAseq|Species: Caenorhabditis briggsae|Tissue Specific
11	22772596	WBPaper00041271.cbg.rs.paper	N.A.	N.A.	1	RNA-seq analysis of the C. briggsae transcriptome.	Curation of a high-quality gene set is the critical first step in genome research, enabling subsequent analyses such as ortholog assignment, cis-regulatory element finding, and synteny detection. In this project, we have reannotated the genome of Caenorhabditis briggsae, the best studied sister species of the model organism Caenorhabditis elegans. First, we applied a homology-based gene predictor genBlastG to annotate the C. briggsae genome. We then validated and further improved the C. briggsae gene annotation through RNA-seq analysis of the C. briggsae transcriptome, which resulted in the first validated C. briggsae gene set (23,159 genes), among which 7347 genes (33.9% of all genes with introns) have all of their introns confirmed. Most genes (14,812, or 68.3%) have at least one intron validated, compared with only 3.9% in the most recent WormBase release (WS228). Of all introns in the revised gene set (103,083), 61,503 (60.1%) have been confirmed. Additionally, we have identified numerous trans-splicing leaders (SL1 and SL2 variants) in C. briggsae, leading to the first genome-wide annotation of operons in C. briggsae (1105 operons). The majority of the annotated operons (564, or 51.0%) are perfectly conserved in C. elegans, with an additional 345 operons (or 31.2%) somewhat divergent. Additionally, RNA-seq analysis revealed over 10 thousand small-size assembly errors in the current C. briggsae reference genome that can be readily corrected. The revised C. briggsae genome annotation represents a solid platform for comparative genomics analysis and evolutionary studies of Caenorhabditis species.	2	23162	Uyar B	Uyar B, Chu JS, Vergara IA, Chua SY, Jones MR, Wong T, Baillie DL, Chen N	RNA-seq analysis of the C. briggsae transcriptome.	Genome Res	2012	RNASeq.briggsae.WBStrain00040935.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP011366.SRX127748~RNASeq.briggsae.WBStrain00040935.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP011366.SRX127749	Method: RNAseq|Species: Caenorhabditis briggsae
12	23103191	WBPaper00041689.cbg.rs.paper	GSE41367	GPL13776,GPL13657,GPL13776,GPL16135,GPL16136,GPL16137,GPL16138,GPL16139,GPL16140,GPL16141	1	Simplification and desexualization of gene expression in self-fertile nematodes.	Evolutionary transitions between sexual modes could be potent forces in genome evolution. Several Caenorhabditis nematode species have evolved self-fertile hermaphrodites from the obligately outcrossing females of their ancestors. We explored the relationship between sexual mode and global gene expression by comparing two selfing species, C. elegans and C. briggsae, with three phylogenetically informative outcrossing relatives, C. remanei, C. brenneri, and C. japonica. Adult transcriptome assemblies from the selfing species are consistently and strikingly smaller than those of the outcrossing species. Against this background of overall simplification, genes conserved in multiple outcrossing species with strong sex-biased expression are even more likely to be missing from the genomes of the selfing species. In addition, the sexual regulation of remaining transcripts has diverged markedly from the ancestral pattern in both selfing lineages, though in distinct ways. Thus, both the complexity and the sexual specialization of transciptomes are rapidly altered in response to the evolution of self-fertility. These changes may result from the combination of relaxed sexual selection and a recently reported genetic mechanism favoring genome shrinkage in partial selfers.	6	23160	Thomas CG	Thomas CG, Li R, Smith HE, Woodruff GC, Oliver B, Haag ES	Simplification and desexualization of gene expression in self-fertile nematodes.	Curr Biol	2012	RNASeq.briggsae.WBStrain00040935.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP016006.SRX191953~RNASeq.briggsae.WBStrain00040935.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP016006.SRX191954~RNASeq.briggsae.WBStrain00040935.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP016006.SRX191955~RNASeq.briggsae.WBStrain00040935.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191956~RNASeq.briggsae.WBStrain00040935.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191957~RNASeq.briggsae.WBStrain00040935.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191958	Method: RNAseq|Species: Caenorhabditis briggsae
13	24462290	WBPaper00044760.cbg.rs.paper	GSE53359	GPL13776	1	Conservation of mRNA and protein expression during development of C. elegans.	Spatiotemporal control of gene expression is crucial for development and subject to evolutionary changes. Although proteins are the final product of most genes, the developmental proteome of an animal has not yet been comprehensively defined, and the correlation between mRNA and protein abundance during development is largely unknown. Here, we globally measured and compared protein and mRNA expression changes during the life cycle of the nematodes C. elegans and C. briggsae, separated by ~30 million years of evolution. We observed that developmental mRNA and protein changes were highly conserved to a surprisingly similar degree but were poorly correlated within a species, suggesting important and widespread posttranscriptional regulation. Posttranscriptional control was particularly well conserved if mRNA fold changes were buffered on the protein level, indicating a predominant repressive function. Finally, among divergently expressed genes, we identified insulin signaling, a pathway involved in lifespan determination, as a putative target of adaptive evolution.	13	23163	Grun D	Grun D, Kirchner M, Thierfelder N, Stoeckius M, Selbach M, Rajewsky N	Conservation of mRNA and protein expression during development of C. elegans.	Cell Rep	2014	RNASeq.briggsae.WBStrain00040935.WBls:0000003.Hermaphrodite.WBbt:0007833.SRP034522.SRX392706~RNASeq.briggsae.WBStrain00040935.WBls:0000003.Hermaphrodite.WBbt:0007833.SRP034522.SRX392707~RNASeq.briggsae.WBStrain00040935.WBls:0000003.Hermaphrodite.WBbt:0007833.SRP034522.SRX392708~RNASeq.briggsae.WBStrain00040935.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP034522.SRX392709~RNASeq.briggsae.WBStrain00040935.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP034522.SRX392710~RNASeq.briggsae.WBStrain00040935.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP034522.SRX392711~RNASeq.briggsae.WBStrain00040935.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP034522.SRX392712~RNASeq.briggsae.WBStrain00040935.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP034522.SRX392713~RNASeq.briggsae.WBStrain00040935.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP034522.SRX392714~RNASeq.briggsae.WBStrain00040935.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP034522.SRX392715~RNASeq.briggsae.WBStrain00040935.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP034522.SRX392716~RNASeq.briggsae.WBStrain00040935.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP034522.SRX392717~RNASeq.briggsae.WBStrain00040935.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP034522.SRX392718	Method: RNAseq|Species: Caenorhabditis briggsae
14	24098135	WBPaper00045465.cbg.rs.paper	N.A.	N.A.	1	Conserved translatome remodeling in nematode species executing a shared developmental transition.	Nematodes of the genus Caenorhabditis enter a developmental diapause state after hatching in the absence of food. To better understand the relative contributions of distinct regulatory modalities to gene expression changes associated with this developmental transition, we characterized genome-wide changes in mRNA abundance and translational efficiency associated with L1 diapause exit in four species using ribosome profiling and mRNA-seq. We found a strong tendency for translational regulation and mRNA abundance processes to act synergistically, together effecting a dramatic remodeling of the gene expression program. While gene-specific differences were observed between species, overall translational dynamics were broadly and functionally conserved. A striking, conserved feature of the response was strong translational suppression of ribosomal protein production during L1 diapause, followed by activation upon resumed development. On a global scale, ribosome footprint abundance changes showed greater similarity between species than changes in mRNA abundance, illustrating a substantial and genome-wide contribution of translational regulation to evolutionary maintenance of stable gene expression.	6	23163	Stadler M	Stadler M, Fire A	Conserved translatome remodeling in nematode species executing a shared developmental transition.	PLoS Genet	2013	RNASeq.briggsae.WBStrain00040935.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP026198.SRX311786~RNASeq.briggsae.WBStrain00040935.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP026198.SRX311787~RNASeq.briggsae.WBStrain00040935.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP026198.SRX311788~RNASeq.briggsae.WBStrain00040935.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP026198.SRX311789~RNASeq.briggsae.WBStrain00040935.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP026198.SRX311790~RNASeq.briggsae.WBStrain00040935.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP026198.SRX311791	Method: RNAseq|Species: Caenorhabditis briggsae
15	11030340	WBPaper00004349.ce.mr.paper	GSE5	GPL14	2	A global profile of germline gene expression in C. elegans.	We used DNA microarrays to profile gene expression patterns in the C. elegans germline and identified 1416 germline-enriched transcripts that define three groups. The sperm-enriched group contains an unusually large number of protein kinases and phosphatases. The oocyte-enriched group includes potentially new components of embryonic signaling pathways. The germline-intrinsic group, defined as genes expressed similarly in germlines making only sperm or only oocytes, contains a family of piwi-related genes that may be important for stem cell proliferation. Finally, examination of the chromosomal location of germline transcripts revealed that sperm-enriched and germline-intrinsic genes are nearly absent from the X chromosome, but oocyte-enriched genes are not.	13	11178	Reinke V	Reinke V, Smith HE, Nance JF, Wang JL, Van Doren C, Begley RR, Jones SJM, Davis EB, Scherer S, Ward S, Kim SK	A global profile of germline gene expression in C. elegans.	Mol Cell	2000	[cgc4349]:fem-3_fem-1~[cgc4349]:glp-4_reference_adult~[cgc4349]:glp-4_reference_L2~[cgc4349]:glp-4_reference_L3~[cgc4349]:glp-4_reference_L4~[cgc4349]:WT_glp-4_adult~[cgc4349]:WT_glp-4_L2~[cgc4349]:WT_glp-4_L3~[cgc4349]:WT_glp-4_L4~[cgc4349]:WT_reference_adult~[cgc4349]:WT_reference_L2~[cgc4349]:WT_reference_L3~[cgc4349]:WT_reference_L4	Method: microarray|Species: Caenorhabditis elegans
16	11052945	WBPaper00004386.ce.mr.paper	N.A.	N.A.	1	Genomic analysis of gene expression in C. elegans.	Until now, genome-wide transcriptional profiling has been limited to single-cell organisms. The nematode Caenorhabditis elegans is a well-characterized metazoan in which the expression of all genes can be monitored by oligonucleotide arrays. We used such arrays to quantitate the expression of C. elegans genes throughout the development of this organism. The results provide an estimate of the number of expressed genes in the nematode, reveal relations between gene function and gene expression that can guide analysis of uncharacterized worm genes, and demonstrate a shift in expression from evolutionarily conserved genes to worm-specific genes over the course of development.	8	16494	Hill AA	Hill AA, Hunter CP, Tsung BT, Tucker-Kellogg G, Brown EL	Genomic analysis of gene expression in C. elegans.	Science	2000	Hill_2000_0hr~Hill_2000_12hr~Hill_2000_24hr~Hill_2000_2weeks~Hill_2000_36hr~Hill_2000_48hr~Hill_2000_60hr~Hill_2000_oocytes	Method: microarray|Species: Caenorhabditis elegans|Topic: developmental process|Topic: developmental growth|Topic: regulation of developmental growth|Topic: regulation of developmental process|Tissue Specific
17	11134517	WBPaper00004489.ce.mr.paper	GSE3633	GPL3096,GPL3097,GPL3098	2	Genome-wide analysis of developmental and sex-regulated gene expression profiles in Caenorhabditis elegans.	We have constructed DNA microarrays containing 17,871 genes, representing about 94% of the 18,967 genes currently annotated in the Caenorhabditis elegans genome. These DNA microarrays can be used as a tool to define a nearly complete molecular profile of gene expression levels associated with different developmental stages, growth conditions, or worm strains. Here, we used these full-genome DNA microarrays to show the relative levels of gene expression for nearly every gene during development, from eggs through adulthood. These expression data can help reveal when a gene may act during development. We also compared gene expression in males to that of hermaphrodites and found a total of 2,171 sex-regulated genes (P < 0.05). The sex-regulated genes provide a global view of the differences between the sexes at a molecular level and identify many genes likely to be involved in sex-specific differentiation and behavior.	7	15866	Jiang M	Jiang M, Ryu J, Kiraly M, Duke KK, Reinke V, Kim SK	Genome-wide analysis of developmental and sex-regulated gene expression profiles in Caenorhabditis elegans.	Proc Natl Acad Sci U S A	2001	cgc4489_adult~cgc4489_egg~cgc4489_L1~cgc4489_L2~cgc4489_L3~cgc4489_L4~cgc4489_male_herm	Method: microarray|Species: Caenorhabditis elegans|Topic: Wnt signaling pathway|Topic: canonical Wnt signaling pathway
18	11823633	WBPaper00005056.ce.mr.paper	GSE3681	GPL3177,GPL3178	2	Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4.	The pha-4 locus encodes a forkhead box A (FoxA/HNF3) transcription factor homolog that specifies organ identity for Caenorhabditis elegans pharyngeal cells. We used microarrays to identify pharyngeal genes and analyzed those genes to determine which were direct PHA-4 targets. Our data suggest that PHA-4 directly activates most or all pharyngeal genes. Furthermore, the relative affinity of PHA-4 for different TRTTKRY (R=A/G, K=T/G, Y=T/C) elements modulates the onset of gene expression, providing a mechanism to activate pharyngeal genes at different developmental stages. We suggest that direct transcriptional regulation of entire gene networks may be a common feature of organ identity genes.	1	8691	Gaudet J	Gaudet J, Mango SE	Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4.	Science	2002	[cgc5056]:par-1_skn-1_ratio	Method: microarray|Species: Caenorhabditis elegans
19	12097338	WBPaper00005280.ce.mr.paper	N.A.	N.A.	2	Identification of a novel cis-regulatory element involved in the heat shock response in Caenorhabditis elegans using microarray gene expression and computational methods.	We report here the identification of a previously unknown transcription regulatory element for heat shock (HS) genes in Caenorhabditis elegans. We monitored the expression pattern of 11,917 genes from C elegans to determine the genes that were up-regulated on HS. Twenty eight genes were observed to be consistently up-regulated in several different repetitions of the experiments. We analyzed the upstream regions of these genes using computational DNA pattern recognition methods. Two potential cis-regulatory motifs were identified in this way. One of these motifs (TTCTAGAA) was the DNA binding motif for the heat shock factor (HSF), whereas the other (GGGTGTC) was previously unreported in the literature. We determined the significance of these motifs for the HS genes using different statistical tests and parameters. Comparative sequence analysis of orthologous HS genes from C elegans and Caenorhabditis briggsae indicated that the identified DNA regulatory motifs are conserved across related species. The role of the identified DNA sites in regulation of HS genes was tested by in vitro mutagenesis of a green fluorescent protein (GFP) reporter transgene driven by the C elegans hsp-16-2 promoter. DNA sites corresponding to both motifs are shown to play a significant role in up-regulation of the hsp-16-2 gene oil HS. This is one of the rare instances in which a novel regulatory element, identified using computational methods, is shown to be biologically active. The contributions of individual sites toward induction of transcription on HS are nonadditive, which indicates interaction and cross-talk between the sites, possibly through the transcription factors (TFs) binding to these sites.	5	12265	GuhaThakurta D	GuhaThakurta D, Palomar L, Stormo GD, Tedesco P, Johnson TE, Walker DW, Lithgow G, Kim S, Link CD	Identification of a novel cis-regulatory element involved in the heat shock response in Caenorhabditis elegans using microarray gene expression and computational methods.	Genome Res	2002	[cgc5280]:age-1_immediate_response~[cgc5280]:age-1_recovery_response~[cgc5280]:N2_immediate_response~[cgc5280]:N2_recovery_response_1~[cgc5280]:N2_recovery_response_2	Method: microarray|Species: Caenorhabditis elegans
20	12075352	WBPaper00005303.ce.mr.paper	GSE2975	GPL2653,GPL2655	2	A global analysis of Caenorhabditis elegans operons.	The nematode worm Caenorhabditis elegans and its relatives are unique among animals in having operons. Operons are regulated multigene transcription units, in which polycistronic pre-messenger RNA (pre-mRNA coding for multiple peptides) is processed to monocistronic mRNAs. This occurs by 3' end formation and trans-splicing using the specialized SL2 small nuclear ribonucleoprotein particle for downstream mRNAs. Previously, the correlation between downstream location in an operon and SL2 trans-splicing has been strong, but anecdotal. Although only 28 operons have been reported, the complete sequence of the C. elegans genome reveals numerous gene clusters. To determine how many of these clusters represent operons, we probed full-genome microarrays for SL2-containing mRNAs. We found significant enrichment for about 1,200 genes, including most of a group of several hundred genes represented by complementary DNAs that contain SL2 sequence. Analysis of their genomic arrangements indicates that >90% are downstream genes, falling in 790 distinct operons. Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes. Numerous examples of co-transcription of genes encoding functionally related proteins are evident. Inspection of the operon list should reveal previously unknown functional relationships.	1	15680	Blumenthal T	Blumenthal T, Evans D, Link CL, Guffanti A, Lawson D, Thierry-Mieg J, Thierry-Mieg D, Chiu WL, Duke K, Kiraly M, Kim SK	A global analysis of Caenorhabditis elegans operons.	Nature	2002	[cgc5303]:SL2_enriched	Method: microarray|Species: Caenorhabditis elegans
21	12124626	WBPaper00005356.ce.mr.paper	GSE3121	GPL2646,GPL2754	2	Identification of genes expressed in C. elegans touch receptor neurons.	The extent of gene regulation in cell differentiation is poorly understood. We previously used saturation mutagenesis to identify 18 genes that are needed for the development and function of a single type of sensory neuron--the touch receptor neuron for gentle touch in Caenorhabditis elegans. One of these genes, mec-3, encodes a transcription factor that controls touch receptor differentiation. By culturing and isolating wild-type and mec-3 mutant cells from embryos and applying their amplified RNA to DNA microarrays, here we have identified genes that are known to be expressed in touch receptors, a previously uncloned gene (mec-17) that is needed for maintaining touch receptor differentiation, and more than 50 previously unknown mec-3-dependent genes. These genes are randomly distributed in the genome and under-represented both for genes that are co-expressed in operons and for multiple members of gene families. Using regions 5' of the start codon of the first 20 genes, we have also identified an over-represented heptanucleotide, AATGCAT, that is needed for the expression of touch receptor genes.	1	15565	Zhang Y	Zhang Y, Ma C, Delohery T, Nasipak B, Foat BC, Bounoutas A, Bussemaker HJ, Kim SK, Chalfie M	Identification of genes expressed in C. elegans touch receptor neurons.	Nature	2002	[cgc5356]:mec-3_wt	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
22	12074557	WBPaper00005376.ce.mr.paper	GSE2974	GPL2653	2	Downstream targets of let-60 Ras in Caenorhabditis elegans.	In Caenorhabditis elegans, let-60 Ras controls many cellular processes, such as differentiation of vulval epithelial cells, function of chemosensory neurons, and meiotic progression in the germ line. Although much is known about the let-60 Ras signaling pathway, relatively little is understood about the target genes induced by let-60 Ras signaling that carry out terminal effector functions leading to morphological change. We have used DNA microarrays to identify 708 genes that change expression in response to activated let-60 Ras.	29	15979	Romagnolo B	Romagnolo B, Jiang M, Kiraly M, Breton C, Begley R, Wang J, Lund J, Kim SK	Downstream targets of let-60 Ras in Caenorhabditis elegans.	Dev Biol	2002	[cgc5376]:let-23(sy1)_32h~[cgc5376]:let-23(sy1)_34h~[cgc5376]:let-23(sy1)_36h~[cgc5376]:let-23(sy1)_38h~[cgc5376]:let-23(sy1)_40h~[cgc5376]:let-23(sy1)_42h~[cgc5376]:let-23(sy1)_44h~[cgc5376]:let-60(n1046)_32h~[cgc5376]:let-60(n1046)_34h~[cgc5376]:let-60(n1046)_36h~[cgc5376]:let-60(n1046)_38h~[cgc5376]:let-60(n1046)_40h~[cgc5376]:let-60(n1046)_42h~[cgc5376]:let-60(n1046)_44h~[cgc5376]:let-60_heat_shock_T0~[cgc5376]:let-60_heat_shock_T0_5~[cgc5376]:let-60_heat_shock_T1~[cgc5376]:let-60_heat_shock_T2~[cgc5376]:WT_32h~[cgc5376]:WT_34h~[cgc5376]:WT_36h~[cgc5376]:WT_38h~[cgc5376]:WT_40h~[cgc5376]:WT_42h~[cgc5376]:WT_44h~[cgc5376]:WT_heat_shock_T0~[cgc5376]:WT_heat_shock_T0_5~[cgc5376]:WT_heat_shock_T1~[cgc5376]:WT_heat_shock_T2	Method: microarray|Species: Caenorhabditis elegans|Topic: vulval development|Topic: vulval cell fate commitment|Topic: vulval cell fate determination|Topic: vulval cell fate specification|Topic: regulation of vulval development|Topic: positive regulation of vulval development|Topic: negative regulation of vulval development
23	12186849	WBPaper00005432.ce.mr.paper	N.A.	N.A.	2	A survival pathway for Caenorhabditis elegans with a blocked unfolded protein response.	The unfolded protein response (UPR) counteracts stress caused by unprocessed ER client proteins. A genome-wide survey showed impaired induction of many UPR target genes in xbp-1 mutant Caenorhabditis elegans that are unable to signal in the highly conserved IRE1-dependent UPR pathway. However a family of genes, abu (activated in blocked UPR), was induced to higher levels in ER-stressed xbp-1 mutant animals than in ER-stressed wild-type animals. RNA-mediated interference (RNAi) inactivation of a representative abu family member, abu-1 (AC3.3), activated the ER stress marker hsp-4:.gfp in otherwise normal animals and killed 50% of ER-stressed ire-1 and xbp-1 mutant animals. Abu-1(RNAi) also enhanced the effect of inactivation of sel-1, an ER-associated protein degradation gene. The nine abu genes encode highly related type I transmembrane proteins whose lumenal domains have sequence similarity to a mammalian cell surface scavenger receptor of endothelial cells that binds chemically modified extracellular proteins and directs their lysosomal degradation. Our findings that ABU-1 is an intracellular protein located within the endomembrane system that is induced by ER stress in xbp-1 mutant animals suggest that ABU proteins may interact with abnormal ER client proteins and this function may be particularly important in animals with an impaired UPR.	2	15693	Urano F	Urano F, Calfon M, Yoneda T, Yun C, Kiraly M, Clark SG, Ron D	A survival pathway for Caenorhabditis elegans with a blocked unfolded protein response.	J Cell Biol	2002	[cgc5432]:WT~[cgc5432]:xbp-1	Method: microarray|Species: Caenorhabditis elegans|Topic: obsolete mRNA splicing via endonucleolytic cleavage and ligation involved in unfolded protein response|Topic: endoplasmic reticulum unfolded protein response|Topic: endoplasmic reticulum|Topic: obsolete ER-associated misfolded protein catabolic process|Topic: response to unfolded protein|Topic: mitochondrion|Topic: cytosol
24	12372248	WBPaper00005475.ce.mr.paper	GSE4005	GPL2653,GPL2655,GPL3096,GPL3097,GPL3098	2	Transcriptional profile of aging in C. elegans.	Background: Numerous gerontogene mutants leading to dramatic life extensions have been identified in the nematode Caenorhabditis elegans over the last 20 years. Analysis of these mutants has provided a basis for understanding the mechanisms driving the aging process(es). Several distinct mechanisms including an altered rate of aging, increased resistance to stress, decreased metabolic rate, or alterations in a program causing organismic aging and death have been proposed to underlie these mutants. Results: Whole-genome analysis of gene expression during chronological aging of the worm provides a rich database of age-specific changes in gene expression and represents one way to distinguish among these models. Using a rigorous statistical model with multiple replicates, we find that a relatively small number of genes (only 164) show statistically significant changes in transcript levels as aging occurs (<1 % of the genome). Expression of heat shock proteins decreases, while expression of certain transposases increases in older worms, and these findings are consistent with a higher mortality risk due to a failure in homeostenosis and destabilization of the genome in older animals. Finally, a specific subset of genes is coordinately altered both during chronological aging and in the transition from the reproductive form to the dauer, demonstrating a mechanistic overlap in aging between these two processes. Conclusions: We have performed a whole-genome analysis of changes in gene expression during aging in C. elegans that provides a molecular description of C. elegans senescence.	6	16715	Lund J	Lund J, Tedesco P, Duke K, Wang J, Kim SK, Johnson TE	Transcriptional profile of aging in C. elegans.	Curr Biol	2002	[cgc5475]:day12-14~[cgc5475]:day16-19~[cgc5475]:day3~[cgc5475]:day4~[cgc5475]:day6-7~[cgc5475]:day9-11	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging
25	12538516	WBPaper00005767.ce.mr.paper	N.A.	N.A.	1	Composition and dynamics of the Caenorhabditis elegans early embryonic transcriptome.	Temporal profiles of transcript abundance during embryonic development were obtained by whole-genome expression analysis from precisely staged C. elegans embryos. The result is a highly resolved time course that commences with the zygote and extends into midgastrulation, spanning the transition from maternal to embryonic control of development and including the presumptive specification of most major cell fates. Transcripts for nearly half (8890) of the predicted open reading frames are detected and expression levels for the majority of them (>70%) change over time. The transcriptome is stable up to the four-cell stage where it begins rapidly changing until the rate of change plateaus before gastrulation. At gastrulation temporal patterns of maternal degradation and embryonic expression intersect indicating a mid-blastula. transition from maternal to embryonic control of development. In addition, we find that embryonic genes tend to be expressed transiently on a time scale consistent with developmental decisions being made with each cell cycle. Furthermore, overall rates of synthesis and degradation are matched such that the transcriptome maintains a steady-state frequency distribution. Finally, a versatile analytical platform based on cluster analysis and developmental classification of genes is provided.	12	8302	Baugh LR	Baugh LR, Hill AA, Slonim DK, Brown EL, Hunter CP	Composition and dynamics of the Caenorhabditis elegans early embryonic transcriptome.	Development	2003	[cgc5767]:0_min~[cgc5767]:101_min~[cgc5767]:122_min~[cgc5767]:143_min~[cgc5767]:186_min~[cgc5767]:23_min~[cgc5767]:41_min~[cgc5767]:53_min~[cgc5767]:66_min~[cgc5767]:83_min~[cgc5767]:PC32~[cgc5767]:PC6	Method: microarray|Species: Caenorhabditis elegans|Topic: embryo development|Topic: gene expression
26	12620986	WBPaper00005859.ce.mr.paper	GSE3169	GPL2653,GPL2655,GPL2754,GPL276	2	Global analysis of dauer gene expression in Caenorhabditis elegans.	The dauer is a developmental stage in C. elegans that exhibits increased longevity, stress resistance, nictation and altered metabolism compared with normal worms. We have used DNA microarrays to profile gene expression differences during the transition from the dauer state to the non-dauer state and after feeding of starved L1 animals, and have identified 1984 genes that show significant expression changes. This analysis includes genes that encode transcription factors and components of signaling pathways that could regulate the entry to and exit from the dauer state, and genes that encode components of metabolic pathways important for dauer survival and longevity. Homologs of C elegans dauer-enriched genes may be involved in the disease process in parasitic nematodes.	22	15757	Wang J	Wang J, Kim SK	Global analysis of dauer gene expression in Caenorhabditis elegans.	Development	2003	[cgc5859]:dauer_0hr~[cgc5859]:dauer_10hr~[cgc5859]:dauer_12hr~[cgc5859]:dauer_1hr~[cgc5859]:dauer_2hr~[cgc5859]:dauer_3hr~[cgc5859]:dauer_4hr~[cgc5859]:dauer_5hr~[cgc5859]:dauer_6hr~[cgc5859]:dauer_7hr~[cgc5859]:dauer_8hr~[cgc5859]:starvation_0hr~[cgc5859]:starvation_10hr~[cgc5859]:starvation_12hr~[cgc5859]:starvation_1hr~[cgc5859]:starvation_2hr~[cgc5859]:starvation_3hr~[cgc5859]:starvation_4hr~[cgc5859]:starvation_5hr~[cgc5859]:starvation_6hr~[cgc5859]:starvation_7hr~[cgc5859]:starvation_8hr	Method: microarray|Species: Caenorhabditis elegans
27	12845331	WBPaper00005976.ce.mr.paper	N.A.	N.A.	2	Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans.	Ageing is a fundamental, unsolved mystery in biology. DAF-16, a FOXO-family transcription factor, influences the rate of ageing of Caenorhabditis elegans in response to insulin/insulin-like growth factor 1 (IGF-I) signalling. Using DNA microarray analysis, we have found that DAF-16 affects expression of a set of genes during early adulthood, the time at which this pathway is known to control ageing. Here we find that many of these genes influence the ageing process. The insulin/IGF-I pathway functions cell non-autonomously to regulate lifespan, and our findings suggest that it signals other cells, at least in part, by feedback regulation of an insulin/IGF-I homologue. Furthermore, our findings suggest that the insulin/IGF-I pathway ultimately exerts its effect on lifespan by upregulating a wide variety of genes, including cellular stress-response, antimicrobial and metabolic genes, and by downregulating specific life-shortening genes.	60	15871	Murphy CT	Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H, Kenyon C	Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans.	Nature	2003	[cgc5976]:age-1_A~[cgc5976]:age-1_B~[cgc5976]:daf-16_GFP~[cgc5976]:daf-2(mu150)_A~[cgc5976]:daf-2(mu150)_B~[cgc5976]:daf-2_0_of_48_hrs~[cgc5976]:daf-2_12_of_48_hrs~[cgc5976]:daf-2_144_of_192_hrs~[cgc5976]:daf-2_192_of_192_hrs~[cgc5976]:daf-2_1_of_48_hrs~[cgc5976]:daf-2_24_of_48_hrs~[cgc5976]:daf-2_28_of_192_hrs~[cgc5976]:daf-2_3_of_48_hrs~[cgc5976]:daf-2_40_of_192_hrs~[cgc5976]:daf-2_4_of_48_hrs~[cgc5976]:daf-2_6_of_48_hrs~[cgc5976]:daf-2_72_of_192_hrs~[cgc5976]:daf-2_8_of_48_hrs~[cgc5976]:daf-2_96_of_192_hrs~[cgc5976]:daf-2_daf-16_0_of_48_hrs~[cgc5976]:daf-2_daf-16_1_of_48_hrs~[cgc5976]:daf-2_daf-16_3_of_48_hrs~[cgc5976]:daf-2_daf-16_48_of_48_hrs~[cgc5976]:daf-2_daf-16_4_of_48_hrs~[cgc5976]:daf-2_daf-16_6_of_48_hrs~[cgc5976]:daf-2_daf-16_8_of_48_hrs~[cgc5976]:daf-2_daf_16_0_of_192_hrs~[cgc5976]:daf-2_daf_16_144_of_192_hrs~[cgc5976]:daf-2_daf_16_40_of_192_hrs~[cgc5976]:daf-2_daf_16_72_of_192_hrs~[cgc5976]:daf-2_daf_16_96_of_192_hrs~[cgc5976]:vector_0_of_192_hrs~[cgc5976]:vector_144_of_192_hrs~[cgc5976]:vector_16_of_192_hrs~[cgc5976]:vector_1_of_48_hrs~[cgc5976]:vector_24_of_48_hrs~[cgc5976]:vector_2_of_48_hrs~[cgc5976]:vector_3_of_48_hrs~[cgc5976]:vector_40_of_192_hrs~[cgc5976]:vector_48_of_48_hrs~[cgc5976]:vector_4_of_48_hrs~[cgc5976]:vector_52_of_192_hrs~[cgc5976]:vector_6_of_48_hrs~[cgc5976]:vector_72_of_192_hrs~[cgc5976]:vector_8_of_192_hrs~[cgc5976]:vector_8_of_48_hrs~[cgc5976]:vector_96_of_192_hrs~[cgc5976]:daf-2_0_of_192_hrs~[cgc5976]:daf-2_16_of_192_hrs~[cgc5976]:daf-2_48_of_48_hrs~[cgc5976]:daf-2_52_of_192_hrs~[cgc5976]:daf-2_8_of_192_hrs~[cgc5976]:daf-2_daf_16_16_of_192_hrs~[cgc5976]:daf-2_daf_16_192_of_192_hrs~[cgc5976]:daf-2_daf_16_28_of_192_hrs~[cgc5976]:daf-2_daf_16_52_of_192_hrs~[cgc5976]:daf-2_daf_16_8_of_192_hrs~[cgc5976]:vector_192_of_192_hrs~[cgc5976]:vector_28_of_192_hrs~[cgc5976]:vector_0_of_48_hrs	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging
28	14668411	WBPaper00006390.ce.mr.paper	GSE696,GSE715,GSE716,GSE717,GSE718,GSE719,GSE720,GSE721,GSE722,GSE723,GSE724,GSE725,GSE726,GSE727,GSE728,GSE729,GSE730,GSE731,GSE732,GSE733,GSE734,GSE735,GSE736,GSE737	GPL446,GPL539,GPL540	2	Genome-wide germline-enriched and sex-biased expression profiles in Caenorhabditis elegans.	We performed a genome-wide analysis of gene expression in C. elegans to identify germline- and sex-regulated genes. Using mutants that cause defects in germ cell proliferation or gametogenesis, we identified sets of genes with germline-enriched expression in either hermaphrodites or males, or in both sexes. Additionally, we compared gene expression profiles between males and hermaphrodites lacking germline tissue to define genes with sex-biased expression in terminally differentiated somatic tissues. Cross-referencing hermaphrodite germline and somatic gene sets with in situ hybridization data demonstrates that the vast majority of these genes have appropriate spatial expression patterns. Additionally, we examined gene expression at multiple times during wild-type germline development to define temporal expression profiles for these genes. Sex- and germline-regulated genes have a non-random distribution in the genome, with especially strong biases for and against the X chromosome. Comparison with data from large-scale RNAi screens demonstrates that genes expressed in the oogenic germline display visible phenotypes more frequently than expected.	18	16230	Reinke V	Reinke V, San Gil I, Ward S, Kazmer K	Genome-wide germline-enriched and sex-biased expression profiles in Caenorhabditis elegans.	Development	2004	[cgc6390]:adult_WT_vs_glp-4~[cgc6390]:fem-3(gf)_vs_fem-1(lf)~[cgc6390]:glp-4_hermaphrodites_vs_glp-4_him-5_males~[cgc6390]:hermaphrodites_vs_him-5_males~[cgc6390]:him-5_vs_glp-4_him-5~[cgc6390]:L4_WT_vs_glp-4~[cgc6390]:TP10_27_hr~[cgc6390]:TP11_30_hr~[cgc6390]:TP12_33_hr~[cgc6390]:TP1_0_hr~[cgc6390]:TP2_3_hr~[cgc6390]:TP3_6_hr~[cgc6390]:TP4_9_hr~[cgc6390]:TP5_12_hr~[cgc6390]:TP6_15_hr~[cgc6390]:TP7_18_hr~[cgc6390]:TP8_21_hr~[cgc6390]:TP9_24_hr	Method: microarray|Species: Caenorhabditis elegans
29	15153179	WBPaper00013462.ce.mr.paper	N.A.	N.A.	2	Microarray analysis of gene expression with age in individual nematodes.	We compare the aging of wild-type and long-lived C. elegans by gene expression profiling of individual nematodes. Using a custom cDNA array, we have characterized the gene expression of 4-5 individuals at 4 distinct ages throughout the adult lifespan of wild-type N2 nematodes, and at the same ages for individuals of the long-lived strain daf-2(e1370). Using statistical tools developed for microarray data analysis, we identify genes that differentiate aging N2 from aging daf-2, as well as classes of genes that change with age in a similar way in both genotypes. Our novel approach of studying individual nematodes provides practical advantages, since it obviates the use of mutants or drugs to block reproduction, as well as the use of stressful mass-culturing procedures, that have been required for previous microarray studies of C. elegans. In addition, this approach has the potential to uncover the molecular variability between individuals of a population, variation that is missed when studying pools of thousands of individuals.	37	899	Golden TR	Golden TR, Melov S	Microarray analysis of gene expression with age in individual nematodes.	Aging Cell	2004	WBPaper00013462:14_days_daf-2_1~WBPaper00013462:14_days_daf-2_2~WBPaper00013462:14_days_daf-2_3~WBPaper00013462:14_days_daf-2_4~WBPaper00013462:14_days_N2_1~WBPaper00013462:14_days_N2_2~WBPaper00013462:14_days_N2_3~WBPaper00013462:14_days_N2_4~WBPaper00013462:14_days_N2_5~WBPaper00013462:19_days_daf-2_1~WBPaper00013462:19_days_daf-2_2~WBPaper00013462:19_days_daf-2_3~WBPaper00013462:19_days_daf-2_4~WBPaper00013462:19_days_N2_1~WBPaper00013462:19_days_N2_2~WBPaper00013462:19_days_N2_3~WBPaper00013462:19_days_N2_4~WBPaper00013462:19_days_N2_5~WBPaper00013462:4_days_daf-2_1~WBPaper00013462:4_days_daf-2_2~WBPaper00013462:4_days_daf-2_3~WBPaper00013462:4_days_daf-2_4~WBPaper00013462:4_days_daf-2_5~WBPaper00013462:4_days_N2_1~WBPaper00013462:4_days_N2_2~WBPaper00013462:4_days_N2_3~WBPaper00013462:4_days_N2_4~WBPaper00013462:9_days_daf-2_1~WBPaper00013462:9_days_daf-2_2~WBPaper00013462:9_days_daf-2_3~WBPaper00013462:9_days_daf-2_4~WBPaper00013462:9_days_daf-2_5~WBPaper00013462:9_days_N2_1~WBPaper00013462:9_days_N2_2~WBPaper00013462:9_days_N2_3~WBPaper00013462:9_days_N2_4~WBPaper00013462:9_days_N2_5	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging
30	15308663	WBPaper00024278.ce.mr.paper	GSE1762	GPL200	1	Shared transcriptional signature in Caenorhabditis elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance.	In the nematode Caenorhabditis elegans, formation of the long-lived dauer larva, and adult aging are both controlled by insulin/IGF-1 signaling (IIS). Potentially, increased adult lifespan in daf-2 insulin/IGF-1 receptor mutants results from mis-expression in the adult of a dauer larva longevity program. Using oligonucleotide microarray analysis we identify a dauer transcriptional signature in daf-2 mutant adults. By means of a non-biased statistical approach we identify gene classes whose expression is altered similarly in dauers and daf-2 mutants, which represent potential determinants of lifespan. These include known determinants of longevity: the small heat shock protein (smHSP)/a-crystallins are up-regulated in both milieus. The cytochrome P450, short-chain dehydrogenase/reductase, UDP-glucuronosyltransferase and (in daf-2 mutants) glutathione S-transferase gene classes were also up-regulated. These four gene classes act together in metabolism and excretion of toxic endobiotic and xenobiotic metabolites. This suggests that diverse toxic lipophilic and electrophilic metabolites, disposed of by phase 1 and phase 2 drug metabolism, may be major determinants of the molecular damage that causes aging. In addition, we observed down-regulation of genes linked to nutrient uptake, including nhx-2 and pep-2. These work together in uptake of dipeptides in the intestine, implying dietary restriction in daf-2 mutants. Some gene groups up-regulated in dauers and/or daf-2 were enriched for certain promoter elements: the daf-16-binding element, the heat shock response element, the heat shock-associated sequence or the hif-1 response element. By contrast, the daf-16-associated element was enriched in genes down-regulated in dauers and daf-2 mutants. Thus, particular promoter elements appear longevity or aging associated.	20	17637	McElwee JJ	McElwee JJ, Schuster E, Blanc E, Thomas JH, Gems D	Shared transcriptional signature in Caenorhabditis elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance.	J Biol Chem	2004	WBPaper00024278:e1370df50_1~WBPaper00024278:e1370df50_2~WBPaper00024278:e1370df50_3~WBPaper00024278:e1370df50_4~WBPaper00024278:e1370df50_5~WBPaper00024278:e1370_1~WBPaper00024278:e1370_2~WBPaper00024278:e1370_3~WBPaper00024278:e1370_4~WBPaper00024278:e1370_5~WBPaper00024278:m577df50_1~WBPaper00024278:m577df50_2~WBPaper00024278:m577df50_3~WBPaper00024278:m577df50_4~WBPaper00024278:m577df50_5~WBPaper00024278:m577_1~WBPaper00024278:m577_2~WBPaper00024278:m577_3~WBPaper00024278:m577_4~WBPaper00024278:m577_5	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging
31	15380030	WBPaper00024393.ce.mr.paper	GSE4164	GPL2646,GPL2653,GPL2754,GPL3178	2	Regulation of signaling genes by TGFbeta during entry into dauer diapause in C. elegans.	BACKGROUND:  When resources are scant, C. elegans larvae arrest as long-lived dauers under the control of insulin/IGF- and TGFbeta-related signaling pathways. However, critical questions remain regarding the regulation of this developmental event. How do three dozen insulin-like proteins regulate one tyrosine kinase receptor to control complex events in dauer, metabolism and aging? How are signals from the TGFbeta and insulin/IGF pathways integrated? What gene expression programs do these pathways regulate, and how do they control complex downstream events?RESULTS:  We have identified genes that show different levels of expression in a comparison of wild-type L2 or L3 larvae (non-dauer) to TGFbeta mutants at similar developmental stages undergoing dauer formation. Many insulin/IGF pathway and other known dauer regulatory genes have changes in expression that suggest strong positive feedback by the TGFbeta pathway. In addition, many insulin-like ligand and novel genes with similarity to the extracellular domain of insulin/IGF receptors have altered expression. We have identified a large group of regulated genes with putative binding sites for the FOXO transcription factor, DAF-16. Genes with DAF-16 sites upstream of the transcription start site tend to be upregulated, whereas genes with DAF-16 sites downstream of the coding region tend to be downregulated. Finally, we also see strong regulation of many novel hedgehog- and patched-related genes, hormone biosynthetic genes, cell cycle genes, and other regulatory genes.CONCLUSIONS:  The feedback regulation of insulin/IGF pathway and other dauer genes that we observe would be predicted to amplify signals from the TGFbeta pathway; this amplification may serve to ensure a decisive choice between "dauer" and "non-dauer", even if environmental cues are ambiguous. Up and down regulation of insulin-like ligands and novel genes with similarity to the extracellular domain of insulin/IGF receptors suggests opposing roles for several members of these large gene families. Unlike in adults, most genes with putative DAF-16 binding sites are upregulated during dauer entry, suggesting that DAF-16 has different activity in dauer versus adult metabolism and aging. However, our observation that the position of putative DAF-16 binding sites is correlated with the direction of regulation suggests a novel method of achieving gene-specific regulation from a single pathway. We see evidence of TGFbeta-mediated regulation of several other classes of regulatory genes, and we discuss possible functions of these genes in dauer formation.	3	15579	Liu T	Liu T, Zimmerman KK, Patterson GI	Regulation of signaling genes by TGFbeta during entry into dauer diapause in C. elegans.	BMC Dev Biol	2004	WBPaper00024393:daf-14_vs_WT~WBPaper00024393:daf-7_vs_WT~WBPaper00024393:daf-8_vs_WT	Method: microarray|Species: Caenorhabditis elegans|Topic: dauer larval development
32	15340492	WBPaper00024532.ce.mr.paper	N.A.	N.A.	1	Monomethyl branched-chain fatty acids play an essential role in Caenorhabditis elegans development.	Monomethyl branched-chain fatty acids (mmBCFAs) are commonly found in many organisms from bacteria to mammals. In humans, they have been detected in skin, brain, blood, and cancer cells. Despite a broad distribution, mmBCFAs remain exotic in eukaryotes, where their origin and physiological roles are not understood. Here we report our study of the function and regulation of mmBCFAs in Caenorhabditis elegans, combining genetics, gas chromatography, and DNA microarray analysis. We show that C. elegans synthesizes mmBCFAs de novo and utilizes the long-chain fatty acid elongation enzymes ELO-5 and ELO-6 to produce two mmBCFAs, C15ISO and C17ISO. These mmBCFAs are essential for C. elegans growth and development, as suppression of their biosynthesis results in a growth arrest at the first larval stage. The arrest is reversible and can be overcome by feeding the arrested animals with mmBCFA supplements. We show not only that the levels of C15ISO and C17ISO affect the expression of several genes, but also that the activities of some of these genes affect biosynthesis of mmBCFAs, suggesting a potential feedback regulation. One of the genes, lpd-1, encodes a homolog of a mammalian sterol regulatory element-binding protein (SREBP 1c). We present results suggesting that elo-5 and elo-6 may be transcriptional targets of LPD-1. This study exposes unexpected and crucial physiological functions of C15ISO and C17ISO in C. elegans and suggests a potentially important role for mmBCFAs in other eukaryotes.	4	6212	Kniazeva M	Kniazeva M, Crawford QT, Seiber M, Wang CY, Han M	Monomethyl branched-chain fatty acids play an essential role in Caenorhabditis elegans development.	PLoS Biol	2004	WBPaper00024532:elo-5_RNAi_1~WBPaper00024532:elo-5_RNAi_2~WBPaper00024532:N2_1~WBPaper00024532:N2_2	Method: microarray|Species: Caenorhabditis elegans
33	15601834	WBPaper00024654.ce.mr.paper	N.A.	N.A.	1	Translation of a small subset of Caenorhabditis elegans mRNAs is dependent on a specific eukaryotic translation initiation factor 4E isoform.	The mRNA cap-binding protein eukaryotic translation initiation factor 4E (eIF4E) participates in protein synthesis initiation, translational repression of specific mRNAs, and nucleocytoplasmic shuttling. Multiple isoforms of eIF4E are expressed in a variety of organisms, but their specific roles are poorly understood. We investigated one Caenorhabditis elegans isoform, IFE-4, which has homologues in plants and mammals. IFE-4::green fluorescent protein (GFP) was expressed in pharyngeal and tail neurons, body wall muscle, spermatheca, and vulva. Knockout of ife-4 by RNA interference (RNAi) or a null mutation produced a pleiotropic phenotype that included egg-laying defects. Sedimentation analysis demonstrated that IFE-4, but not IFE-1, was present in 48S initiation complexes, indicating that it participates in protein synthesis initiation. mRNAs affected by ife-4 knockout were determined by DNA microarray analysis of polysomal distribution. Polysome shifts, in the absence of total mRNA changes, were observed for only 33 of the 18,967 C. elegans mRNAs tested, of which a disproportionate number were related to egg laying and were expressed in neurons and/or muscle. Translational regulation was confirmed by reduced levels of DAF-12, EGL-15, and KIN-29. The functions of these proteins can explain some phenotypes observed in ife-4 knockout mutants. These results indicate that translation of a limited subset of mRNAs is dependent on a specific isoform of eIF4E.	18	11576	Dinkova TD	Dinkova TD, Keiper BD, Korneeva NL, Aamodt EJ, Rhoads RE	Translation of a small subset of Caenorhabditis elegans mRNAs is dependent on a specific eukaryotic translation initiation factor 4E isoform.	Mol Cell Biol	2005	WBPaper00024654:Heavy_polysomes_ife-4(k320)_1~WBPaper00024654:Heavy_polysomes_ife-4(k320)_2~WBPaper00024654:Heavy_polysomes_ife-4(k320)_3~WBPaper00024654:Heavy_polysomes_N2_1~WBPaper00024654:Heavy_polysomes_N2_2~WBPaper00024654:Heavy_polysomes_N2_3~WBPaper00024654:Light_polysomes_ife-4(k320)_1~WBPaper00024654:Light_polysomes_ife-4(k320)_2~WBPaper00024654:Light_polysomes_ife-4(k320)_3~WBPaper00024654:Light_polysomes_N2_1~WBPaper00024654:Light_polysomes_N2_2~WBPaper00024654:Light_polysomes_N2_3~WBPaper00024654:Total_RNA_ife-4(k320)_1~WBPaper00024654:Total_RNA_ife-4(k320)_2~WBPaper00024654:Total_RNA_ife-4(k320)_3~WBPaper00024654:Total_RNA_N2_1~WBPaper00024654:Total_RNA_N2_2~WBPaper00024654:Total_RNA_N2_3	Method: microarray|Species: Caenorhabditis elegans
34	15620651	WBPaper00024671.ce.mr.paper	N.A.	N.A.	1	Identification of thermosensory and olfactory neuron-specific genes via expression profiling of single neuron types.	Most C. elegans sensory neuron types consist of a single bilateral pair of neurons, and respond to a unique set of sensory stimuli. Although genes required for the development and function of individual sensory neuron types have been identified in forward genetic screens, these approaches are unlikely to identify genes that when mutated result in subtle or pleiotropic phenotypes. Here, we describe a complementary approach to identify sensory neuron type-specific genes via microarray analysis using RNA from sorted AWB olfactory and AFD thermosensory neurons. The expression patterns of subsets of these genes were further verified in vivo. Genes identified by this analysis encode 7-transmembrane receptors, kinases, and nuclear factors including dac-1, which encodes a homolog of the highly conserved Dachshund protein . dac-1 is expressed in a subset of sensory neurons including the AFD neurons and is regulated by the TTX-1 OTX homeodomain protein . On thermal gradients, dac-1 mutants fail to suppress a cryophilic drive but continue to track isotherms at the cultivation temperature, representing the first genetic separation of these AFD-mediated behaviors. Expression profiling of single neuron types provides a rapid, powerful, and unbiased method for identifying neuron-specific genes whose functions can then be investigated in vivo.	11	17637	Colosimo ME	Colosimo ME, Brown A, Mukhopadhyay S, Gabel C, Lanjuin AE, Samuel AD, Sengupta P	Identification of thermosensory and olfactory neuron-specific genes via expression profiling of single neuron types.	Curr Biol	2004	WBPaper00024671:AFD_1~WBPaper00024671:AFD_2~WBPaper00024671:AFD_3~WBPaper00024671:AFD_4~WBPaper00024671:AWB_1~WBPaper00024671:AWB_2~WBPaper00024671:AWB_3~WBPaper00024671:AWB_4~WBPaper00024671:unsorted_1~WBPaper00024671:unsorted_2~WBPaper00024671:unsorted_3	Method: microarray|Species: Caenorhabditis elegans|Topic: sensory perception of smell|Topic: defecation|Topic: defecation rhythm|Tissue Specific
35	15772128	WBPaper00025032.ce.mr.paper	GSE2180	GPL200	1	The homeodomain protein PAL-1 specifies a lineage-specific regulatory network in the C. elegans embryo.	Maternal and zygotic activities of the homeodomain protein PAL-1 specify the identity and maintain the development of the multipotent C blastomere lineage in the C. elegans embryo. To identify PAL-1 regulatory target genes, we used microarrays to compare transcript abundance in wild-type embryos with mutant embryos lacking a C blastomere and to mutant embryos with extra C blastomeres. pal-1-dependent C-lineage expression was verified for select candidate target genes by reporter gene analysis, though many of the target genes are expressed in additional lineages as well. The set of validated target genes includes 12 transcription factors, an uncharacterized wingless ligand and five uncharacterized genes. Phenotypic analysis demonstrates that the identified PAL-1 target genes affect specification, differentiation and morphogenesis of C-lineage cells. In particular, we show that cell fate-specific genes (or tissue identity genes) and a posterior HOX gene are activated in lineage-specific fashion. Transcription of targets is initiated in four temporal phases, which together with their spatial expression patterns leads to a model of the regulatory network specified by PAL-1.	30	17638	Baugh LR	Baugh LR, Hill AA, Claggett JM, Hill-Harfe K, Wen JC, Slonim DK, Brown EL, Hunter CP	The homeodomain protein PAL-1 specifies a lineage-specific regulatory network in the C. elegans embryo.	Development	2005	WBPaper00025032:mex-3_skn-1_0_min~WBPaper00025032:mex-3_skn-1_101_min~WBPaper00025032:mex-3_skn-1_122_min~WBPaper00025032:mex-3_skn-1_143_min~WBPaper00025032:mex-3_skn-1_186_min~WBPaper00025032:mex-3_skn-1_23_min~WBPaper00025032:mex-3_skn-1_41_min~WBPaper00025032:mex-3_skn-1_53_min~WBPaper00025032:mex-3_skn-1_66_min~WBPaper00025032:mex-3_skn-1_83_min~WBPaper00025032:N2_0_min~WBPaper00025032:N2_101_min~WBPaper00025032:N2_122_min~WBPaper00025032:N2_143_min~WBPaper00025032:N2_186_min~WBPaper00025032:N2_23_min~WBPaper00025032:N2_41_min~WBPaper00025032:N2_53_min~WBPaper00025032:N2_66_min~WBPaper00025032:N2_83_min~WBPaper00025032:pie-1_0_min~WBPaper00025032:pie-1_101_min~WBPaper00025032:pie-1_122_min~WBPaper00025032:pie-1_143_min~WBPaper00025032:pie-1_186_min~WBPaper00025032:pie-1_23_min~WBPaper00025032:pie-1_41_min~WBPaper00025032:pie-1_53_min~WBPaper00025032:pie-1_66_min~WBPaper00025032:pie-1_83_min	Method: microarray|Species: Caenorhabditis elegans|Topic: cell fate specification|Topic: cell differentiation
36	15780142	WBPaper00025141.ce.mr.paper	GSE8159	GPL200	1	A gene expression fingerprint of C. elegans embryonic motor neurons.	BACKGROUND: Differential gene expression specifies the highly diverse cell types that constitute the nervous system. With its sequenced genome and simple, well-defined neuroanatomy, the nematode, C. elegans is useful model system in which to correlate gene expression with neuron identity. The UNC-4 transcription factor is expressed in thirteen embryonic motor neurons where it specifies axonal morphology and synaptic function. These cells can be marked with an unc-4::GFP reporter transgene. Here we describe a new, powerful strategy, Micro-Array Profiling of C. elegans cells (MAPCeL) for fingerprinting isolated C. elegans cells and confirm that this approach provides a comprehensive gene expression profile of unc-4::GFP motor neurons in vivo. RESULTS: Fluorescence Activated Cell Sorting (FACS) was used to isolate unc-4::GFP neurons from primary cultures of C. elegans embryonic cells. Microarray experiments detected 6,217 unique transcripts of which ~1,000 are enriched in unc-4::GFP neurons relative to the average nematode embryonic cell. The reliability of these data was validated by the detection of known cell-specific transcripts and by expression in UNC-4 motor neurons of GFP reporters derived from the enriched data set. In addition to genes involved in neurotransmitter packaging and release, the microarray data include transcripts for receptors to a remarkably wide variety of signaling molecules. The added presence of a robust array of G-protein pathway components is indicative of complex and highly integrated mechanisms for modulating motor neuron activity. Over half of the enriched genes (537) have human homologs, a finding that could reflect substantial overlap with the gene expression repertoire of mammalian motor neurons. CONCLUSIONS: We have described a microarray-based method, MAPCeL, for profiling gene expression in specific C. elegans motor neurons and provide evidence that this approach can reveal candidate genes for key roles in the differentiation and function of these cells. These methods can now be applied to generate a gene expression map of the C. elegans nervous system.	7	17637	Fox RM	Fox RM, Von Stetina SE, Barlow SJ, Shaffer C, Olszewski KL, Moore JH, Dupuy D, Vidal M, Miller DM	A gene expression fingerprint of C. elegans embryonic motor neurons.	BMC Genomics	2005	WBPaper00025040:DM39_unc-4::GFP_1~WBPaper00025040:DM51_unc-4::GFP_2~WBPaper00025040:DM59_unc-4::GFP_3~WBPaper00025040:DMR28_N2_1~WBPaper00025040:DMR30_N2_2~WBPaper00025040:DMR32_N2_3~WBPaper00025040:DMR34_N2_4	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
37	16103915	WBPaper00026714.ce.mr.paper	GSE2210	GPL200	1	Using microarrays to facilitate positional cloning: identification of tomosyn as an inhibitor of neurosecretion.	Forward genetic screens have been used as a powerful strategy to dissect complex biological pathways in many model systems. A significant limitation of this approach has been the time-consuming and costly process of positional cloning and molecular characterization of the mutations isolated in these screens. Here, the authors describe a strategy using microarray hybridizations to facilitate positional cloning. This method relies on the fact that premature stop codons (i.e., nonsense mutations) constitute a frequent class of mutations isolated in screens and that nonsense mutant messenger RNAs are efficiently degraded by the conserved nonsense-mediated decay pathway. They validate this strategy by identifying two previously uncharacterized mutations: (1) tom-1, a mutation found in a forward genetic screen for enhanced acetylcholine secretion in Caenorhabditis elegans, and (2) an apparently spontaneous mutation in the hif-1 transcription factor gene. They further demonstrate the broad applicability of this strategy using other known mutants in C. elegans, Arabidopsis, and mouse. Characterization of tom-1 mutants suggests that TOM-1, the C. elegans ortholog of mammalian tomosyn, functions as an endogenous inhibitor of neurotransmitter secretion. These results also suggest that microarray hybridizations have the potential to significantly reduce the time and effort required for positional cloning.	9	17638	Dybbs M	Dybbs M, Ngai J, Kaplan JM	Using microarrays to facilitate positional cloning: identification of tomosyn as an inhibitor of neurosecretion.	PLoS Genet	2005	WBPaper00026714:tom-1(nu468)_1~WBPaper00026714:tom-1(nu468)_2~WBPaper00026714:unc-43(n1186)_1~WBPaper00026714:unc-43(n1186)_2~WBPaper00026714:unc-43(n1186)_3~WBPaper00026714:wt_1~WBPaper00026714:wt_2~WBPaper00026714:wt_3~WBPaper00026714:wt_4	Method: microarray|Species: Caenorhabditis elegans
38	16168746	WBPaper00026820.ce.mr.paper	GSE4111	GPL2646,GPL2655,GPL2766,GPL3097,GPL3396	2	Expression profiling of five different xenobiotics using a Caenorhabditis elegans whole genome microarray.	The soil nematode Caenorhabditis elegans is frequently used in ecotoxicological studies due to its wide distribution in terrestrial habitats, its easy handling in the laboratory, and its sensitivity against different kinds of stress. Since its genome has been completely sequenced, more and more studies are investigating the functional relation of gene expression and phenotypic response. For these reasons C. elegans seems to be an attractive animal for the development of a new, genome based, ecotoxicological test system. In recent years, the DNA array technique has been established as a powerful tool to obtain distinct gene expression patterns in response to different experimental conditions. Using a C. elegans whole genome DNA microarray in this study, the effects of five different xenobiotics on the gene expression of the nematode were investigated. The exposure time for the following five applied compounds beta-NF (5mg/l), Fla (0.5mg/l), atrazine (25mg/l), clofibrate (10mg/l) and DES (0.5mg/l) was 48+/-5h. The analysis of the data showed a clear induction of 203 genes belonging to different families like the cytochromes P450, UDP-glucoronosyltransferases (UDPGT), glutathione S-transferases (GST), carboxylesterases, collagenes, C-type lectins and others. Under the applied conditions, fluoranthene was able to induce most of the induceable genes, followed by clofibrate, atrazine, beta-naphthoflavone and diethylstilbestrol. A decreased expression could be shown for 153 genes with atrazine having the strongest effect followed by fluoranthene, diethylstilbestrol, beta-naphthoflavone and clofibrate. For upregulated genes a change ranging from approximately 2.1- till 42.3-fold and for downregulated genes from approximately 2.1 till 6.6-fold of gene expression could be affected through the applied xenobiotics. The results confirm the applicability of the gene expression for the development of an ecotoxicological test system. Compared to classical tests the main advantages of this new approach will be the increased sensitivity and it''s potential for a substance class specific effect determination as well as the large numbers of genes that can be screened rapidly at the same time and the selection of well regulated marker genes to study more in detail.	12	16775	Reichert K	Reichert K, Menzel R	Expression profiling of five different xenobiotics using a Caenorhabditis elegans whole genome microarray.	Chemosphere	2005	WBPaper00026820:atrazine_1~WBPaper00026820:atrazine_2~WBPaper00026820:B-naphthoflavone_1~WBPaper00026820:B-naphthoflavone_2~WBPaper00026820:B-naphthoflavone_3~WBPaper00026820:clofibrate_1~WBPaper00026820:clofibrate_2~WBPaper00026820:clofibrate_3~WBPaper00026820:diethylstilbestrol_1~WBPaper00026820:fluoranthen_3~WBPaper00026820:fluoranthen_1~WBPaper00026820:fluoranthen_2	Method: microarray|Species: Caenorhabditis elegans
39	16184190	WBPaper00026830.ce.mr.paper	N.A.	N.A.	1	Genetic interactions due to constitutive and inducible gene regulation mediated by the unfolded protein response in C. elegans.	The unfolded protein response (UPR) is an adaptive signaling pathway utilized to sense and alleviate the stress of protein folding in the endoplasmic reticulum (ER). In mammals, the UPR is mediated through three proximal sensors PERK/PEK, IRE1, and ATF6. PERK/PEK is a protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 to inhibit protein synthesis. Activation of IRE1 induces splicing of XBP1 mRNA to produce a potent transcription factor. ATF6 is a transmembrane transcription factor that is activated by cleavage upon ER stress. We show that in Caenorhabditis elegans, deletion of either ire-1 or xbp-1 is synthetically lethal with deletion of either atf-6 or pek-1, both producing a developmental arrest at larval stage 2. Therefore, in C. elegans, atf-6 acts synergistically with pek-1 to complement the developmental requirement for ire-1 and xbp-1. Microarray analysis identified inducible UPR (i-UPR) genes, as well as numerous constitutive UPR (c-UPR) genes that require the ER stress transducers during normal development. Although ire-1 and xbp-1 together regulate transcription of most i-UPR genes, they are each required for expression of nonoverlapping sets of c-UPR genes, suggesting that they have distinct functions. Intriguingly, C. elegans atf-6 regulates few i-UPR genes following ER stress, but is required for the expression of many c-UPR genes, indicating its importance during development and homeostasis. In contrast, pek-1 is required for induction of approximately 23% of i-UPR genes but is dispensable for the c-UPR. As pek-1 and atf-6 mainly act through sets of nonoverlapping targets that are different from ire-1 and xbp-1 targets, at least two coordinated responses are required to alleviate ER stress by distinct mechanisms. Finally, our array study identified the liver-specific transcription factor CREBh as a novel UPR gene conserved during metazoan evolution.	29	17637	Shen X	Shen X, Ellis RE, Sakaki K, Kaufman RJ	Genetic interactions due to constitutive and inducible gene regulation mediated by the unfolded protein response in C. elegans.	PLoS Genet	2005	WBPaper00026830:atf-6_no_tunicamycin_1~WBPaper00026830:atf-6_no_tunicamycin_2~WBPaper00026830:atf-6_no_tunicamycin_3~WBPaper00026830:atf-6_tunicamycin_1~WBPaper00026830:atf-6_tunicamycin_2~WBPaper00026830:atf-6_tunicamycin_3~WBPaper00026830:ire-1_no_tunicamycin_1~WBPaper00026830:ire-1_no_tunicamycin_2~WBPaper00026830:ire-1_no_tunicamycin_3~WBPaper00026830:ire-1_tunicamycin_1~WBPaper00026830:ire-1_tunicamycin_2~WBPaper00026830:ire-1_tunicamycin_3~WBPaper00026830:N2_no_tunicamycin_1~WBPaper00026830:N2_no_tunicamycin_2~WBPaper00026830:N2_no_tunicamycin_3~WBPaper00026830:N2_tunicamycin_1~WBPaper00026830:N2_tunicamycin_2~WBPaper00026830:N2_tunicamycin_3~WBPaper00026830:pek-1_no_tunicamycin_1~WBPaper00026830:pek-1_no_tunicamycin_2~WBPaper00026830:pek-1_no_tunicamycin_3~WBPaper00026830:pek-1_tunicamycin_1~WBPaper00026830:pek-1_tunicamycin_2~WBPaper00026830:pek-1_tunicamycin_3~WBPaper00026830:xbp-1_no_tunicamycin_1~WBPaper00026830:xbp-1_no_tunicamycin_2~WBPaper00026830:xbp-1_no_tunicamycin_3~WBPaper00026830:xbp-1_tunicamycin_1~WBPaper00026830:xbp-1_tunicamycin_2	Method: microarray|Species: Caenorhabditis elegans|Topic: obsolete mRNA splicing via endonucleolytic cleavage and ligation involved in unfolded protein response|Topic: endoplasmic reticulum unfolded protein response|Topic: endoplasmic reticulum|Topic: response to unfolded protein|Topic: mitochondrion|Topic: cytosol
40	0	WBPaper00026950.ce.mr.paper	N.A.	N.A.	1	Comparative analysis of SAGE and microarray technologies for global transcription profiling of development in Caenorhabditis elegans	N.A.	16	17638	Kim Wong	Kim Wong, Sheldon J. McKay, Jaswinder Khattra, Susanna Chan, Jennifer Asano, Anna Go, Pawan Pandoh, Helen MacDonald, Peter Huang, Peter Ruzanov, Michael Hogan, Nathan Pofahl, Roland Green, Courtney Mills, Adam Warner, David L. Baillie, Rob Holt, Steven J. M. Jones, Marco A. Marra, Donald. G. Moerman	Comparative analysis of SAGE and microarray technologies for global transcription profiling of development in Caenorhabditis elegans	N.A.	0	WBPaper00026950:Em_N2-1~WBPaper00026950:Em_N2-2~WBPaper00026950:Em_N2-3~WBPaper00026950:L1_N2-1~WBPaper00026950:L1_N2-2~WBPaper00026950:L1_starved_N2-1~WBPaper00026950:L1_starved_N2-2~WBPaper00026950:L2_N2-1~WBPaper00026950:L2_N2-2~WBPaper00026950:L3_N2-1~WBPaper00026950:L3_N2-2~WBPaper00026950:L4_N2-1~WBPaper00026950:L4_N2-2~WBPaper00026950:Oocyte_N2~WBPaper00026950:YA_N2-1~WBPaper00026950:YA_N2-2	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
41	16354718	WBPaper00026980.ce.mr.paper	GSE4150	GPL2766,GPL3390,GPL3411	2	Chromosomal clustering and GATA transcriptional regulation of intestine-expressed genes in C. elegans.	We used mRNA tagging to identify genes expressed in the intestine of C. elegans. Animals expressing an epitope-tagged protein that binds the poly-A tail of mRNAs (FLAG::PAB-1) from an intestine-specific promoter (ges-1) were used to immunoprecipitate FLAG::PAB-1/mRNA complexes from the intestine. A total of 1938 intestine-expressed genes (P&lt;0.001) were identified using DNA microarrays. First, we compared the intestine-expressed genes with those expressed in the muscle and germline, and identified 510 genes enriched in all three tissues and 624 intestine-, 230 muscle- and 1135 germ line-enriched genes. Second, we showed that the 1938 intestine-expressed genes were physically clustered on the chromosomes, suggesting that the order of genes in the genome is influenced by the effect of chromatin domains on gene expression. Furthermore, the commonly expressed genes showed more chromosomal clustering than the tissue-enriched genes, suggesting that chromatin domains may influence housekeeping genes more than tissue-specific genes. Third, in order to gain further insight into the regulation of intestinal gene expression, we searched for regulatory motifs. This analysis found that the promoters of the intestine genes were enriched for the GATA transcription factor consensus binding sequence. We experimentally verified these results by showing that the GATA motif is required in cis and that GATA transcription factors are required in trans for expression of these intestinal genes.	8	16661	Pauli F	Pauli F, Liu Y, Kim YA, Chen PJ, Kim SK	Chromosomal clustering and GATA transcriptional regulation of intestine-expressed genes in C. elegans.	Development	2006	WBPaper00026980:ges-1_IP_vs_total_RNA_1~WBPaper00026980:ges-1_IP_vs_total_RNA_2~WBPaper00026980:ges-1_IP_vs_total_RNA_3~WBPaper00026980:ges-1_IP_vs_total_RNA_4~WBPaper00026980:ges-1_IP_vs_total_RNA_5~WBPaper00026980:ges-1_IP_vs_total_RNA_6~WBPaper00026980:ges-1_IP_vs_total_RNA_7~WBPaper00026980:ges-1_IP_vs_total_RNA_8	Method: microarray|Species: Caenorhabditis elegans|Topic: gene expression|Topic: metabolic process
42	16480708	WBPaper00027104.ce.mr.paper	GSE2862	GPL200	1	Identification of novel target genes of CeTwist and CeE/DA.	Twist, a basic helix-loop-helix (bHLH) transcription factor, plays an important role in mesoderm development in many organisms, including C. elegans where CeTwist is required to direct cell fate specifications of a subset of mesodermal cells. Although several target genes of CeTwist have been identified, how this protein accomplishes its function is unclear. In addition, several human genes whose mutations cause different syndromes of craniosynostosis (premature fusion of cranial sutures) have homologues in the CeTwist pathway. Identification of novel target genes of CeTwist will shed more light on the functions of CeTwist in mesoderm development, and the corresponding human homologues will be good candidates for related syndromes with unidentified mutated genes. In our study, both CeTwist and its heterodimeric partner, CeE/DA, were overexpressed from the inducible heat-shock promoter, and potential target genes were detected with Affymetrix(R) oligonucleotide microarrays. Using transcriptional GFP reporters, we found 11 genes were expressed in cells coincident with known CeTwist target gene products. Based on subsequent validation experiments, 9 genes were defined as novel CeTwist and CeE/DA targets. Human homologues of two of these genes might be involved in craniofacial diseases, which further validates C. elegans as a good model organism for providing insights into these disorders.	12	17637	Wang P	Wang P, Zhao J, Corsi AK	Identification of novel target genes of CeTwist and CeE/DA.	Dev Biol	2006	WBPaper00027104:Cont(+)_1~WBPaper00027104:Cont(+)_2~WBPaper00027104:Cont(+)_3~WBPaper00027104:Cont(-)_1~WBPaper00027104:Cont(-)_2~WBPaper00027104:Cont(-)_3~WBPaper00027104:Expt(+)_1~WBPaper00027104:Expt(+)_2~WBPaper00027104:Expt(+)_3~WBPaper00027104:Expt(-)_1~WBPaper00027104:Expt(-)_2~WBPaper00027104:Expt(-)_3	Method: microarray|Species: Caenorhabditis elegans
43	16489184	WBPaper00027111.ce.mr.paper	N.A.	N.A.	1	Interacting endogenous and exogenous RNAi pathways in Caenorhabditis elegans.	C. elegans contains numerous small RNAs of ~21-24 nt in length. The microRNAs (miRNAs) are small noncoding RNAs produced by DCR-1- and ALG-dependent processing of self-complementary hairpin transcripts. Endogenous small interfering RNAs (endo-siRNAs), associated with ongoing silencing of protein-coding genes in normal worms, are produced by mechanisms that involve DCR-1 but, unlike miRNAs, also involve RDE-2, RDE-3, RDE-4, RRF-1, and RRF-3. The tiny noncoding (tncRNAs) are similar to endo-siRNAs in their biogenesis except that they are derived from noncoding sequences. These endo-siRNA- and tncRNA-based endogenous RNAi pathways involve some components, including DCR-1 and RDE-4, that are shared with exogenous RNAi, and some components, including RRF-3 and ERI-1, that are specific to endogenous RNAi. rrf-3 and eri-1 mutants are enhanced for some silencing processes and defective for others, suggesting cross-regulatory interactions between RNAi pathways in C. elegans. Microarray expression profiling of RNAi-defective mutant worms further suggests diverse endogenous RNAi pathways for silencing different sets of genes.	21	16301	Lee RC	Lee RC, Hammell CM, Ambros V	Interacting endogenous and exogenous RNAi pathways in Caenorhabditis elegans.	RNA	2006	WBPaper00027111:eri-1(mg366)_1~WBPaper00027111:eri-1(mg366)_2~WBPaper00027111:eri-1(mg366)_3~WBPaper00027111:N2_1~WBPaper00027111:N2_2~WBPaper00027111:N2_3~WBPaper00027111:rde-3(ne298)_1~WBPaper00027111:rde-3(ne298)_2~WBPaper00027111:rde-3(ne298)_3~WBPaper00027111:rde-3(r459)_1~WBPaper00027111:rde-3(r459)_2~WBPaper00027111:rde-3(r459)_3~WBPaper00027111:rrf-1(pk1417)_1~WBPaper00027111:rrf-1(pk1417)_2~WBPaper00027111:rrf-1(pk1417)_3~WBPaper00027111:rrf-2(ok210)_1~WBPaper00027111:rrf-2(ok210)_2~WBPaper00027111:rrf-2(ok210)_3~WBPaper00027111:rrf-3(pk1426)_1~WBPaper00027111:rrf-3(pk1426)_2~WBPaper00027111:rrf-3(pk1426)_3	Method: microarray|Species: Caenorhabditis elegans
44	16809667	WBPaper00027722.ce.mr.paper	N.A.	N.A.	1	Genomic clusters, putative pathogen recognition molecules, and antimicrobial genes are induced by infection of C. elegans with M. nematophilum.	The interaction between the nematode Caenorhabditis elegans and a Gram-positive bacterial pathogen, Microbacterium nematophilum, provides a model for an innate immune response in nematodes. This pathogen adheres to the rectal and post-anal cuticle of the worm, causing slowed growth, constipation, and a defensive swelling response of rectal hypodermal cells. To explore the genomic responses that the worm activates after pathogenic attack we used microarray analysis of transcriptional changes induced after 6-h infection, comparing virulent with avirulent infection. We defined 89 genes with statistically significant expression changes of at least twofold, of which 68 were up-regulated and 21 were down-regulated. Among the former, those encoding C-type lectin domains were the most abundant class. Many of the 89 genes exhibit genomic clustering, and we identified one large cluster of 62 genes, of which most were induced in response to infection. We tested 41 of the induced genes for involvement in immunity using mutants or RNAi, finding that six of these are required for the swelling response and five are required more generally for defense. Our results indicate that C-type lectins and other putative pathogen-recognition molecules are important for innate immune defense in C. elegans. We also found significant induction of genes encoding lysozymes, proteases, and defense-related proteins, as well as various domains of unknown function. The genes induced during infection by M. nematophilum appear largely distinct from genes induced by other pathogens, suggesting that C. elegans mounts pathogen-specific responses to infection.	6	17637	O'Rourke D	O'Rourke D, Baban D, Demidova M, Mott R, Hodgkin J	Genomic clusters, putative pathogen recognition molecules, and antimicrobial genes are induced by infection of C. elegans with M. nematophilum.	Genome Res	2006	WBPaper00027722:1C1inf6hr~WBPaper00027722:1C3uninf6hr~WBPaper00027722:2C1inf6hr~WBPaper00027722:2C3uninf6hr~WBPaper00027722:3C1inf6hr~WBPaper00027722:3C3uninf6hr	Method: microarray|Species: Caenorhabditis elegans
45	16854972	WBPaper00027758.ce.mr.paper	GSE5071	GPL3859,GPL3860	2	Promotion of oogenesis and embryogenesis in the C. elegans gonad by EFL-1/DPL-1 (E2F) does not require LIN-35 (pRB).	In Caenorhabditis elegans, EFL-1 (E2F), DPL-1 (DP) and LIN-35 (pRb) act coordinately in somatic tissues to inhibit ectopic cell division, probably by repressing the expression of target genes. EFL-1, DPL-1 and LIN-35 are also present in the germline, but do not always act together. Strong loss-of-function mutations in either efl-1 or dpl-1 cause defects in oogenesis that result in sterility, while lin-35 mutants are fertile with reduced broods. Microarray-based expression profiling of dissected gonads from efl-1, dpl-1 and lin-35 mutants reveals that EFL-1 and DPL-1 promote expression of an extensively overlapping set of target genes, consistent with the expectation that these two proteins function as a heterodimer. Regulatory regions upstream of many of these target genes have a canonical E2F-binding site, suggesting that their regulation by EFL-1/DPL-1 is direct. Many EFL-1/DPL-1 responsive genes encode proteins required for oogenesis and early embryogenesis, rather than cell cycle components. By contrast, LIN-35 appears to function primarily as a repressor of gene expression in the germline, and the genes that it acts on are for the most part distinct from those regulated by EFL-1 and/or DPL-1. Thus, in vivo, C. elegans E2F directly promotes oogenesis and embryogenesis through the activation of a tissue-specific transcriptional program that does not require LIN-35.	10	16732	Chi W	Chi W, Reinke V	Promotion of oogenesis and embryogenesis in the C. elegans gonad by EFL-1/DPL-1 (E2F) does not require LIN-35 (pRB).	Development	2006	WBPaper00027758:dpl-1(n3316)_unc-4(e120)_vs_unc-4(e120)_1~WBPaper00027758:dpl-1(n3316)_unc-4(e120)_vs_unc-4(e120)_2~WBPaper00027758:dpl-1(n3316)_unc-4(e120)_vs_unc-4(e120)_3~WBPaper00027758:efl-1(n3639)_vs_N2_1~WBPaper00027758:efl-1(n3639)_vs_N2_2~WBPaper00027758:efl-1(n3639)_vs_N2_3~WBPaper00027758:efl-1(n3639)_vs_N2_4~WBPaper00027758:lin-35(n745)_vs_N2_1~WBPaper00027758:lin-35(n745)_vs_N2_2~WBPaper00027758:lin-35(n745)_vs_N2_3	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
46	16968778	WBPaper00028482.ce.mr.paper	GSE5584	GPL4206,GPL4207,GPL4208	2	A conserved role for a GATA transcription factor in regulating epithelial innate immune responses.	Innate immunity is an ancient and conserved defense mechanism. Although host responses toward various pathogens have been delineated, how these responses are orchestrated in a whole animal is less understood. Through an unbiased genome-wide study performed in Caenorhabditis elegans, we identified a conserved function for endodermal GATA transcription factors in regulating local epithelial innate immune responses. Gene expression and functional RNAi-based analyses identified the tissue-specific GATA transcription factor ELT-2 as a major regulator of an early intestinal protective response to infection with the human bacterial pathogen Pseudomonas aeruginosa. In the adult worm, ELT-2 is required specifically for infection responses and survival on pathogen but makes no significant contribution to gene expression associated with intestinal maintenance or to resistance to cadmium, heat, and oxidative stress. We further demonstrate that this function is conserved, because the human endodermal transcription factor GATA6 has a protective function in lung epithelial cells exposed to P. aeruginosa. These findings expand the repertoire of innate immunity mechanisms and illuminate a yet-unknown function of endodermal GATA proteins.	18	16718	Shapira M	Shapira M, Hamlin BJ, Rong J, Chen K, Ronen M, Tan MW	A conserved role for a GATA transcription factor in regulating epithelial innate immune responses.	Proc Natl Acad Sci U S A	2006	WBPaper00028482:op50_12hrs_4/24_n2~WBPaper00028482:op50_12hr_4/25_n2~WBPaper00028482:op50_12hr_4/26_n2~WBPaper00028482:op50_4/21_n2_24hr~WBPaper00028482:op50_4/22_n2_24hr~WBPaper00028482:op50_5/07_N2_4hr~WBPaper00028482:op50_5/29_new_N2_4hrs~WBPaper00028482:op50_6/29_N2_4hrs~WBPaper00028482:op50_n2_11/19_24hr~WBPaper00028482:pa14_12hrs_4/24_n2~WBPaper00028482:pa14_12hr_4/25_n2~WBPaper00028482:pa14_12hr_4/26_n2~WBPaper00028482:pa14_4/21_n2_24hrs~WBPaper00028482:pa14_4/22_n2_24hrs~WBPaper00028482:pa14_4/23_n2_24hrs~WBPaper00028482:pa14_5/29_n2_4hr~WBPaper00028482:pa14_5/7_n2_4hr~WBPaper00028482:pa14_629new_4hr	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response
47	17023606	WBPaper00028564.ce.mr.paper	GSE6057	GPL3411	2	Delayed development and lifespan extension as features of metabolic lifestyle alteration in C. elegans under dietary restriction.	Studies of the model organism Caenorhabditis elegans have almost exclusively utilized growth on a bacterial diet. Such culturing presents a challenge to automation of experimentation and introduces bacterial metabolism as a secondary concern in drug and environmental toxicology studies. Axenic cultivation of C. elegans can avoid these problems, yet past work suggests that axenic growth is unhealthy for C. elegans. Here we employ a chemically defined liquid medium to culture C. elegans and find development slows, fecundity declines, lifespan increases, lipid and protein stores decrease, and gene expression changes relative to that on a bacterial diet. These changes do not appear to be random pathologies associated with malnutrition, as there are no developmental delays associated with starvation, such as L1 or dauer diapause. Additionally, development and reproductive period are fixed percentages of lifespan regardless of diet, suggesting that these alterations are adaptive. We propose that C. elegans can exist as a healthy animal with at least two distinct adult life histories. One life history maximizes the intrinsic rate of population increase, the other maximizes the efficiency of exploitation of the carrying capacity of the environment. Microarray analysis reveals increased transcript levels of daf-16 and downstream targets and past experiments demonstrate that DAF-16 (FOXO) acting on downstream targets can influence all of the phenotypes we see altered in maintenance medium. Thus, life history alteration in response to diet may be modulated by DAF-16. Our observations introduce a powerful system for automation of experimentation on healthy C. elegans and for systematic analysis of the profound impact of diet on animal physiology.	3	12109	Szewczyk NJ	Szewczyk NJ, Udranszky IA, Kozak E, Sunga J, Kim SK, Jacobson LA, Conley CA	Delayed development and lifespan extension as features of metabolic lifestyle alteration in C. elegans under dietary restriction.	J Exp Biol	2006	WBPaper00028564:NGM_vs_CeMM_1~WBPaper00028564:NGM_vs_CeMM_2~WBPaper00028564:NGM_vs_CeMM_3	Method: microarray|Species: Caenorhabditis elegans
48	17096597	WBPaper00028789.ce.mr.paper	GSE5801,GSE5793	GPL200	1	p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans.	The PMK-1 p38 mitogen-activated protein kinase pathway and the DAF-2-DAF-16 insulin signaling pathway control Caenorhabditis elegans intestinal innate immunity. pmk-1 loss-of-function mutants have enhanced sensitivity to pathogens, while daf-2 loss-of-function mutants have enhanced resistance to pathogens that requires upregulation of the DAF-16 transcription factor. We used genetic analysis to show that the pathogen resistance of daf-2 mutants also requires PMK-1. However, genome-wide microarray analysis indicated that there was essentially no overlap between genes positively regulated by PMK-1 and DAF-16, suggesting that they form parallel pathways to promote immunity. We found that PMK-1 controls expression of candidate secreted antimicrobials, including C-type lectins, ShK toxins, and CUB-like genes. Microarray analysis demonstrated that 25% of PMK-1 positively regulated genes are induced by Pseudomonas aeruginosa infection. Using quantitative PCR, we showed that PMK-1 regulates both basal and infection-induced expression of pathogen response genes, while DAF-16 does not. Finally, we used genetic analysis to show that PMK-1 contributes to the enhanced longevity of daf-2 mutants. We propose that the PMK-1 pathway is a specific, indispensable immunity pathway that mediates expression of secreted immune response genes, while the DAF-2-DAF-16 pathway appears to regulate immunity as part of a more general stress response. The contribution of the PMK-1 pathway to the enhanced lifespan of daf-2 mutants suggests that innate immunity is an important determinant of longevity.	27	17638	Troemel ER	Troemel ER, Chu SW, Reinke V, Lee SS, Ausubel FM, Kim DH	p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans.	PLoS Genet	2006	WBPaper00028789:Celegans_gacA_4hours_RepA~WBPaper00028789:Celegans_gacA_4hours_RepB~WBPaper00028789:Celegans_gacA_4hours_RepC~WBPaper00028789:Celegans_gacA_8hours_RepA~WBPaper00028789:Celegans_gacA_8hours_RepB~WBPaper00028789:Celegans_gacA_8hours_RepC~WBPaper00028789:Celegans_OP50_4hours_RepA~WBPaper00028789:Celegans_OP50_4hours_RepB~WBPaper00028789:Celegans_OP50_4hours_RepC~WBPaper00028789:Celegans_OP50_8hours_RepA~WBPaper00028789:Celegans_OP50_8hours_RepB~WBPaper00028789:Celegans_OP50_8hours_RepC~WBPaper00028789:Celegans_PA14_4hours_RepA~WBPaper00028789:Celegans_PA14_4hours_RepB~WBPaper00028789:Celegans_PA14_4hours_RepC~WBPaper00028789:Celegans_PA14_8hours_RepA~WBPaper00028789:Celegans_PA14_8hours_RepB~WBPaper00028789:Celegans_PA14_8hours_RepC~WBPaper00028789:daf2daf16_RepA~WBPaper00028789:daf2daf16_RepB~WBPaper00028789:daf2daf16_RepC~WBPaper00028789:daf2pmk1_RepA~WBPaper00028789:daf2pmk1_RepB~WBPaper00028789:daf2pmk1_RepC~WBPaper00028789:daf2_RepA~WBPaper00028789:daf2_RepB~WBPaper00028789:daf2_RepC	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging|Topic: defense response|Topic: defense response to other organism
49	17187676	WBPaper00028949.ce.mr.paper	GSE6563	GPL200	1	Identification of ciliary and ciliopathy genes in Caenorhabditis elegans through comparative genomics.	ABSTRACT: BACKGROUND: The recent availability of genome sequences of multiple related Caenorhabditis species has made it possible to identify, using comparative genomics, similarly transcribed genes in Caenorhabditis elegans and its sister species. Taking this approach, we have identified numerous novel ciliary genes in C. elegans, some of which may be orthologs of unidentified human ciliopathy genes. RESULTS: By screening for genes possessing canonical X-box sequences in promoters of three Caenorhabditis species, namely C. elegans, C. briggsae and C. remanei, we identified 93 genes (including known X-box regulated genes) that encode putative components of ciliated neurons in C. elegans and are subject to the same regulatory control. For many of these genes, restricted anatomical expression in ciliated cells was confirmed, and control of transcription by the ciliogenic DAF-19 RFX transcription factor was demonstrated by comparative transcriptional profiling of daf-19(+) and daf 19(-) animals. Finally, we demonstrate that the dye-filling defect of dyf-5 (mn400) animals, which is indicative of compromised exposure of cilia to the environment, is caused by a nonsense mutation in the serine/threonine protein kinase gene M04C9.5. CONCLUSION: Our comparative genomics-based predictions may be useful for identifying genes involved in human ciliopathies, including Bardet-Biedl Syndrome (BBS), since the C. elegans orthologs of known human BBS genes contain X-box motifs and are required for normal dye filling in C. elegans ciliated neurons.	4	17638	Chen N	Chen N, Mah A, Blacque OE, Chu J, Phgora K, Bakhoum MW, Newbury RH, Khattra J, Chan S, Go A, Efimenko E, Johnsen R, Phirke P, Swoboda P, Marra M, Moerman DG, Leroux MR, Baillie DL, Stein LD	Identification of ciliary and ciliopathy genes in Caenorhabditis elegans through comparative genomics.	Genome Biol	2006	WBPaper00028949:daf-12(sa204)_rep1~WBPaper00028949:daf-12(sa204)_rep2~WBPaper00028949:daf-19(m86)_daf-12(sa204)_rep1~WBPaper00028949:daf-19(m86)_daf-12(sa204)_rep2	Method: microarray|Species: Caenorhabditis elegans
50	17196041	WBPaper00028962.ce.mr.paper	GSE5395	GPL4038	2	Mapping determinants of gene expression plasticity by genetical genomics in C. elegans.	Recent genetical genomics studies have provided intimate views on gene regulatory networks. Gene expression variations between genetically different individuals have been mapped to the causal regulatory regions, termed expression quantitative trait loci. Whether the environment-induced plastic response of gene expression also shows heritable difference has not yet been studied. Here we show that differential expression induced by temperatures of 16 degrees C and 24 degrees C has a strong genetic component in Caenorhabditis elegans recombinant inbred strains derived from a cross between strains CB4856 (Hawaii) and N2 (Bristol). No less than 59% of 308 trans-acting genes showed a significant eQTL-by-environment interaction, here termed plasticity quantitative trait loci. In contrast, only 8% of an estimated 188 cis-acting genes showed such interaction. This indicates that heritable differences in plastic responses of gene expression are largely regulated in trans. This regulation is spread over many different regulators. However, for one group of trans-genes we found prominent evidence for a common master regulator: a transband of 66 coregulated genes appeared at 24 degrees C. Our results suggest widespread genetic variation of differential expression responses to environmental impacts and demonstrate the potential of genetical genomics for mapping the molecular determinants of phenotypic plasticity.	80	16997	Li Y	Li Y, Alvarez OA, Gutteling EW, Tijsterman M, Fu J, Riksen JA, Hazendonk E, Prins P, Plasterk RH, Jansen RC, Breitling R, Kammenga JE	Mapping determinants of gene expression plasticity by genetical genomics in C. elegans.	PLoS Genet	2006	WBPaper00028962:C25_Y82_16C~WBPaper00028962:C25_Y82_24C~WBPaper00028962:D1_W120_16C~WBPaper00028962:D1_W120_24C~WBPaper00028962:D25_G36_16C~WBPaper00028962:D25_G36_24C~WBPaper00028962:D49_Y25_16C~WBPaper00028962:D49_Y25_24C~WBPaper00028962:D73_J25_16C~WBPaper00028962:D73_J25_24C~WBPaper00028962:E33_M50_16C~WBPaper00028962:E33_M50_24C~WBPaper00028962:E49_W77_16C~WBPaper00028962:E49_W77_24C~WBPaper00028962:F1_G33_16C~WBPaper00028962:F1_G33_24C~WBPaper00028962:F25_F83_16C~WBPaper00028962:F25_W89_24C~WBPaper00028962:F32_L49_16C~WBPaper00028962:F32_L49_24C~WBPaper00028962:F49_L33_16C~WBPaper00028962:F49_L33_24C~WBPaper00028962:F73_L25_16C~WBPaper00028962:F73_L25_24C~WBPaper00028962:G1_W39_16C~WBPaper00028962:G1_W39_24C~WBPaper00028962:G25_W15_16C~WBPaper00028962:G25_W15_24C~WBPaper00028962:H74_W105_16C~WBPaper00028962:H74_W105_24C~WBPaper00028962:K1_W44_16C~WBPaper00028962:K1_W44_24C~WBPaper00028962:K33_Y71_16C~WBPaper00028962:K33_Y71_24C~WBPaper00028962:K73_M54_16C~WBPaper00028962:K73_M54_24C~WBPaper00028962:M1_Y21_16C~WBPaper00028962:M1_Y21_24C~WBPaper00028962:M29_W1_16C~WBPaper00028962:M29_W1_24C~WBPaper00028962:M52_E65_16C~WBPaper00028962:M52_E65_24C~WBPaper00028962:M53_M49_16C~WBPaper00028962:M53_M49_24C~WBPaper00028962:N1_E73_16C~WBPaper00028962:N1_E73_24C~WBPaper00028962:N24_Y10_16C~WBPaper00028962:N24_Y10_24C~WBPaper00028962:W106_K25_16C~WBPaper00028962:W106_K25_24C~WBPaper00028962:W109_Y30_16C~WBPaper00028962:W109_Y30_24C~WBPaper00028962:W19_E1_16C~WBPaper00028962:W19_E1_24C~WBPaper00028962:W45_L1_16C~WBPaper00028962:W45_L1_24C~WBPaper00028962:W56_M29_16C~WBPaper00028962:W56_M29_24C~WBPaper00028962:W71_M33_16C~WBPaper00028962:W71_M33_24C~WBPaper00028962:W7_Y60_16C~WBPaper00028962:W7_Y60_24C~WBPaper00028962:W87_W82_16C~WBPaper00028962:W87_W82_24C~WBPaper00028962:W89_K49_16C~WBPaper00028962:W89_K49_24C~WBPaper00028962:W93_J33_16C~WBPaper00028962:W93_J33_24C~WBPaper00028962:Y112_W103_16C~WBPaper00028962:Y112_W103_24C~WBPaper00028962:Y17_Y72_16C~WBPaper00028962:Y17_Y72_24C~WBPaper00028962:Y1_M25_16C~WBPaper00028962:Y1_M25_24C~WBPaper00028962:Y35_W91_16C~WBPaper00028962:Y35_W91_24C~WBPaper00028962:Y4_W69_16C~WBPaper00028962:Y4_W69_24C~WBPaper00028962:Y82_E25_16C~WBPaper00028962:Y82_E25_24C	Method: microarray|Species: Caenorhabditis elegans
51	17368442	WBPaper00029190.ce.mr.paper	GSE6547	GPL200	1	Transcriptome profiling of the C. elegans Rb ortholog reveals diverse developmental roles.	LIN-35 is the single C. elegans ortholog of the mammalian pocket protein family members, pRb, p107, and p130. To gain insight into the roles of pocket proteins during development, a microarray analysis was performed with lin-35 mutants. Stage-specific regulation patterns were revealed, indicating that LIN-35 plays diverse roles at distinct developmental stages. LIN-35 was found to repress the expression of many genes involved in cell proliferation in larvae, an activity that is carried out in conjunction with E2F. In addition, LIN-35 was found to regulate neuronal genes during embryogenesis and targets of the intestinal-specific GATA transcription factor, ELT-2, at multiple developmental stages. Additional findings suggest that LIN-35 functions in cell cycle regulation in embryos in a manner that is independent of E2F. A comparison of LIN-35-regulated genes with known fly and mammalian pocket protein targets revealed a high degree of overlap, indicating strong conservation of pocket protein functions in diverse phyla. Based on microarray results and our refinement of the C. elegans E2F consensus sequence, we were able to generate a comprehensive list of putative E2F-regulated genes in C. elegans. These results implicate a large number of genes previously unconnected to cell cycle control as having potential roles in this process.	18	17638	Kirienko NV	Kirienko NV, Fay DS	Transcriptome profiling of the C. elegans Rb ortholog reveals diverse developmental roles.	Dev Biol	2007	WBPaper00029190:lin-35(n745)_worms_at_embryonic_stage_rep1~WBPaper00029190:lin-35(n745)_worms_at_embryonic_stage_rep2~WBPaper00029190:lin-35(n745)_worms_at_embryonic_stage_rep3~WBPaper00029190:lin-35(n745)_worms_at_L1_stage_rep1~WBPaper00029190:lin-35(n745)_worms_at_L1_stage_rep2~WBPaper00029190:lin-35(n745)_worms_at_L1_stage_rep3~WBPaper00029190:lin-35(n745)_worms_at_L4_stage_rep1~WBPaper00029190:lin-35(n745)_worms_at_L4_stage_rep2~WBPaper00029190:lin-35(n745)_worms_at_L4_stage_rep3~WBPaper00029190:N2_worms_at_embryonic_stage_rep1~WBPaper00029190:N2_worms_at_embryonic_stage_rep2~WBPaper00029190:N2_worms_at_embryonic_stage_rep3~WBPaper00029190:N2_worms_at_L1_stage_rep1~WBPaper00029190:N2_worms_at_L1_stage_rep2~WBPaper00029190:N2_worms_at_L1_stage_rep3~WBPaper00029190:N2_worms_at_L4_stage_rep1~WBPaper00029190:N2_worms_at_L4_stage_rep2~WBPaper00029190:N2_worms_at_L4_stage_rep3	Method: microarray|Species: Caenorhabditis elegans
52	17397820	WBPaper00029226.ce.mr.paper	N.A.	N.A.	1	Transcriptional repressor and activator activities of SMA-9 contribute differentially to BMP-related signaling outputs.	In the nematode Caenorhabditis elegans, the BMP-related growth factor DBL-1 regulates body size and male tail morphogenesis via a conserved receptor/Smad signaling pathway. Smads are transcription factors, but rely on transcription cofactors for appropriate regulation of target genes in response to TGF-beta- and BMP-related signals. In the DBL-1 pathway, sma-9 encodes multiple zinc finger transcription factors homologous to Drosophila Schnurri, which functions in Dpp/BMP signaling. We have studied the molecular functions of SMA-9 as a model for transcription cofactor-dependent regulation of gene expression. Using SMA-9 fusions to known transcriptional activators and repressors, we demonstrate that SMA-9 acts primarily as a transcriptional repressor in body size regulation in vivo. In contrast, both activator and repressor functions contribute to male tail patterning. We further show that different SMA-9 regions have intrinsic repressor and activator activities using a yeast transcription assay. We use microarray analysis to identify transcriptional target genes in body size regulation. Consistent with the importance of repression in mediating body size regulation, we find more repressed genes than activated genes in this pool. Finally, we identify five transcriptional targets with body size and/or male tail patterning phenotypes, including transcription factors related to Runx and fos and signaling molecules related to hedgehog and patched. Our results thus suggest that SMA-9 products function differentially as transcriptional repressors and activators in DBL-1/BMP pathway regulated body size and male tail morphogenesis.	8	17638	Liang J	Liang J, Yu L, Yin J, Savage-Dunn C	Transcriptional repressor and activator activities of SMA-9 contribute differentially to BMP-related signaling outputs.	Dev Biol	2007	WBPaper00029226:dbl-1_1~WBPaper00029226:dbl-1_2~WBPaper00029226:N2_1~WBPaper00029226:N2_2~WBPaper00029226:N2_3~WBPaper00029226:sma-9_1~WBPaper00029226:sma-9_2~WBPaper00029226:sma-9_3	Method: microarray|Species: Caenorhabditis elegans|Topic: developmental process|Topic: developmental growth|Topic: regulation of developmental growth|Topic: regulation of developmental process|Topic: post-anal tail morphogenesis
53	17472752	WBPaper00029334.ce.mr.paper	GSE4766	GPL200	1	Decline of nucleotide excision repair capacity in aging Caenorhabditis elegans.	ABSTRACT: BACKGROUND: Although Caenorhabditis elegans is an important model for the study of DNA damage- and repair-related processes such as aging, neurodegeneration and carcinogenesis, DNA repair is poorly characterized in this organism. We adapted a quantitative PCR assay to characterize repair of UVC radiation-induced DNA damage in C elegans, and then tested whether DNA repair rates were affected by age in adults. RESULTS: UVC radiation induced lesions in young adult C elegans with a slope of 0.4-0.5 lesions per 10kb DNA per 100 Joules/m2, in both nuclear and mitochondrial targets. L1 and dauer larvae were &gt;5-fold more sensitive to lesion formation than young adults. Nuclear repair kinetics in a well-expressed nuclear gene were biphasic in non-gravid adult nematodes: a faster, first order (t1/2 ~16 h) phase lasting ~24 h and resulting in removal of ~60% of the photoproducts was followed by a much slower phase. Repair in 10 nuclear DNA regions was 15% and 50% higher in more actively transcribed regions in young and aging adults, respectively. Finally, repair was reduced 30-50% in each of the 10 nuclear regions in older adults. However, this decrease in repair could not be explained by a reduction in expression of nucleotide excision repair genes, and we present a plausible mechanism, based on gene expression data, to explain this decrease. CONCLUSIONS: Repair of UVC-induced DNA damage in C elegans is similar kinetically and genetically to repair in humans. Furthermore, this important repair process slows significantly in aging C elegans, the first whole organism in which this question has been addressed.	8	17637	Meyer JN	Meyer JN, Boyd WA, Azzam GA, Haugen AC, Freedman JH, Van Houten B	Decline of nucleotide excision repair capacity in aging Caenorhabditis elegans.	Genome Biol	2007	WBPaper00029334:glp-1_embryos_rep1~WBPaper00029334:glp-1_embryos_rep2~WBPaper00029334:glp-1_embryos_rep3~WBPaper00029334:glp-1_old_adults_rep1~WBPaper00029334:glp-1_old_adults_rep2~WBPaper00029334:glp-1_young_adults_rep1~WBPaper00029334:glp-1_young_adults_rep2~WBPaper00029334:glp-1_young_adults_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging|Topic: DNA repair|Topic: global genome nucleotide-excision repair|Topic: obsolete DNA damage response, detection of DNA damage
54	17526642	WBPaper00029437.ce.mr.paper	N.A.	N.A.	1	Genes misregulated in C. elegans deficient in Dicer, RDE-4, or RDE-1 are enriched for innate immunity genes.	We describe the first microarray analysis of a whole animal containing a mutation in the Dicer gene. We used adult Caenorhabditis elegans and, to distinguish among different roles of Dicer, we also performed microarray analyses of animals with mutations in rde-4 and rde-1, which are involved in silencing by siRNA, but not miRNA. Surprisingly, we find that the X chromosome is greatly enriched for genes regulated by Dicer. Comparison of all three microarray data sets indicates the majority of Dicer-regulated genes are not dependent on RDE-4 or RDE-1, including the X-linked genes. However, all three data sets are enriched in genes important for innate immunity and, specifically, show increased expression of innate immunity genes.	5	17638	Welker NC	Welker NC, Habig JW, Bass BL	Genes misregulated in C. elegans deficient in Dicer, RDE-4, or RDE-1 are enriched for innate immunity genes.	RNA	2007	WBPaper00029437:dcr-1_unc-32~WBPaper00029437:N2~WBPaper00029437:rde-1~WBPaper00029437:rde-4~WBPaper00029437:unc-32	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response
55	17592649	WBPaper00030811.ce.mr.paper	GSE7535	GPL2875	2	Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity.	ABSTRACT: BACKGROUND: Exposure to cadmium is associated with a variety of human diseases. At low concentrations, cadmium activates the transcription of stress-responsive genes, which can prevent or repair the adverse effects caused by this metal. RESULTS: Using C. elegans, 290 genes were identified that are differentially expressed ([greater than or equal to]1.5-fold) following a 4 or 24 hour exposure to cadmium. Several of these genes are known to be involved in metal detoxification, including mtl-1, mtl-2, cdr-1 and ttm-1, confirming the efficacy of the study. The majority, however, were not previously associated with metal-responsiveness and are novel. Gene Ontology analysis mapped these genes to cellular/ion trafficking, metabolic enzymes and proteolysis categories. RNA interference-mediated inhibition of 50 cadmium-responsive genes resulted in an increased sensitivity to cadmium toxicity, demonstrating that these genes are involved in the resistance to cadmium toxicity. Several functional protein interacting networks were identified by interactome analysis. Within one network, the signaling protein KEL-8 was identified. Kel-8 protects C. elegans from cadmium toxicity in a mek-1 (MAPKK)-dependent manner. CONCLUSIONS: Because many C. elegans genes and signal transduction pathways are evolutionarily conserved, these results may contribute to the understanding of the functional roles of various genes in cadmium toxicity in higher organisms.	36	17532	Cui Y	Cui Y, McBride SJ, Boyd WA, Alper S, Freedman JH	Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity.	Genome Biol	2007	WBPaper00030811:C.elegans_Cd_24h_rep1~WBPaper00030811:C.elegans_Cd_24h_rep10~WBPaper00030811:C.elegans_Cd_24h_rep11~WBPaper00030811:C.elegans_Cd_24h_rep12~WBPaper00030811:C.elegans_Cd_24h_rep13~WBPaper00030811:C.elegans_Cd_24h_rep14~WBPaper00030811:C.elegans_Cd_24h_rep15~WBPaper00030811:C.elegans_Cd_24h_rep16~WBPaper00030811:C.elegans_Cd_24h_rep17~WBPaper00030811:C.elegans_Cd_24h_rep18~WBPaper00030811:C.elegans_Cd_24h_rep2~WBPaper00030811:C.elegans_Cd_24h_rep3~WBPaper00030811:C.elegans_Cd_24h_rep4~WBPaper00030811:C.elegans_Cd_24h_rep5~WBPaper00030811:C.elegans_Cd_24h_rep6~WBPaper00030811:C.elegans_Cd_24h_rep7~WBPaper00030811:C.elegans_Cd_24h_rep8~WBPaper00030811:C.elegans_Cd_24h_rep9~WBPaper00030811:C.elegans_Cd_4h_rep1~WBPaper00030811:C.elegans_Cd_4h_rep10~WBPaper00030811:C.elegans_Cd_4h_rep11~WBPaper00030811:C.elegans_Cd_4h_rep12~WBPaper00030811:C.elegans_Cd_4h_rep13~WBPaper00030811:C.elegans_Cd_4h_rep14~WBPaper00030811:C.elegans_Cd_4h_rep15~WBPaper00030811:C.elegans_Cd_4h_rep16~WBPaper00030811:C.elegans_Cd_4h_rep17~WBPaper00030811:C.elegans_Cd_4h_rep18~WBPaper00030811:C.elegans_Cd_4h_rep2~WBPaper00030811:C.elegans_Cd_4h_rep3~WBPaper00030811:C.elegans_Cd_4h_rep4~WBPaper00030811:C.elegans_Cd_4h_rep5~WBPaper00030811:C.elegans_Cd_4h_rep6~WBPaper00030811:C.elegans_Cd_4h_rep7~WBPaper00030811:C.elegans_Cd_4h_rep8~WBPaper00030811:C.elegans_Cd_4h_rep9	Method: microarray|Species: Caenorhabditis elegans|Topic: stress response to metal ion
56	17848203	WBPaper00031003.ce.mr.paper	GSE8462	GPL200	1	The embryonic muscle transcriptome of Caenorhabditis elegans.	ABSTRACT: BACKGROUND: The force generating mechanism of muscle is evolutionarily ancient; the fundamental structural and functional components of the sarcomere are common to motile animals throughout phylogeny. Recent evidence suggests that the transcription factors that regulate muscle development are also conserved. Thus, a comprehensive description of muscle gene expression in a simple model organism should define a basic muscle transcriptome that is also found in animals with more complex body plans. To this end, we have applied Micro-Array Profiling of C. elegans Cells (MAPCeL) to muscle cell populations extracted from developing C. elegans embryos. RESULTS: Fluorescence Activated Cell Sorting (FACS) was used to isolate myo-3::GFP-positive muscle cells, and their cultured derivatives, from dissociated early C. elegans embryos. Microarray analysis identified 7,070 expressed genes, 1,312 of which are enriched in the myo-3::GFP positive cell population relative to the average embryonic cell. The muscle-enriched gene set was validated by comparisons to known muscle markers, independently derived expression data, and GFP reporters in transgenic strains. These results confirm the utility of MAPCeL for cell type-specific expression profiling and reveal that 60% of these transcripts have human homologs. CONCLUSIONS: This study provides a comprehensive description of gene expression in developing C. elegans embryonic muscle cells. The finding that over half of these muscle-enriched transcripts encode proteins with human homologs suggests that mutant analysis of these genes in C. elegans could reveal evolutionarily conserved models of muscle gene function with ready application to human muscle pathologies.	25	17638	Fox RM	Fox RM, Watson JD, Von Stetina SE, McDermott J, Brodigan TM, Fukushige T, Kraus M, Miller DM	The embryonic muscle transcriptome of Caenorhabditis elegans.	Genome Biol	2007	WBPaper00031003:DM100_myo3_24hr_2~WBPaper00031003:DM102_myo3_24hr_3~WBPaper00031003:DM18_N2_0hr_1~WBPaper00031003:DM19_myo3_0hr_1~WBPaper00031003:DM22_N2_0hr_2~WBPaper00031003:DM32_N2_0hr_3~WBPaper00031003:DM33_myo3_0hr_2~WBPaper00031003:DM53_myo3_0hr_3~WBPaper00031003:DM92_myo3_24hr_1~WBPaper00031003:DMR28_N2_24hr_1~WBPaper00031003:DMR30_N2_24hr_2~WBPaper00031003:DMR32_N2_24hr_3~WBPaper00031003:DMR34_N2_24hr_4~WBPaper00031003:HLH-1_induction_0_hour_A~WBPaper00031003:HLH-1_induction_0_hour_B~WBPaper00031003:HLH-1_induction_0_hour_C~WBPaper00031003:HLH-1_induction_2_hour_A~WBPaper00031003:HLH-1_induction_2_hour_B~WBPaper00031003:HLH-1_induction_2_hour_C~WBPaper00031003:HLH-1_induction_4_hour_A~WBPaper00031003:HLH-1_induction_4_hour_B~WBPaper00031003:HLH-1_induction_4_hour_C~WBPaper00031003:HLH-1_induction_6_hour_A~WBPaper00031003:HLH-1_induction_6_hour_B~WBPaper00031003:HLH-1_induction_6_hour_C	Method: microarray|Species: Caenorhabditis elegans|Topic: somatic muscle development|Tissue Specific
57	18392117	WBPaper00031662.ce.mr.paper	N.A.	N.A.	2	Genomic response of the nematode Caenorhabditis elegans to spaceflight.	On Earth, it is common to employ laboratory animals such as the nematode Caenorhabditis elegans to help understand human health concerns. Similar studies in Earth orbit should help understand and address the concerns associated with spaceflight. The "International Caenorhabditis elegans Experiment FIRST" (ICE FIRST), was carried out onboard the Dutch Taxiflight in April of 2004 by an international collaboration of laboratories in France, Canada, Japan and the United States. With the exception of a slight movement defect upon return to Earth, the result of altered muscle development, no significant abnormalities were detected in spaceflown C. elegans. Work from Japan revealed apoptosis proceeds normally and work from Canada revealed no significant increase in the rate of mutation. These results suggest that C. elegans can be used to study non-lethal responses to spaceflight and can possibly be developed as a biological sensor. To further our understanding of C. elegans response to spaceflight, we examined the gene transcription response to the 10 days in space using a near full genome microarray analysis. The transcriptional response is consistent with the observed normal developmental timing, apoptosis, DNA repair, and altered muscle development. The genes identified as altered in response to spaceflight are enriched for genes known to be regulated, in C. elegans, in response to altered environmental conditions (Insulin and TGF-beta regulated). These results demonstrate C. elegans can be used to study the effects of altered gravity and suggest that C. elegans responds to spaceflight by altering the expression of at least some of the same metabolic genes that are altered in response to differing terrestrial environments.	15	13198	Selch F	Selch F, Higashibata A, Imamizo-Sato M, Higashitani A, Ishioka N, Szewczyk NJ, Conley CA	Genomic response of the nematode Caenorhabditis elegans to spaceflight.	Adv Space Res	2008	WBPaper00031662:Ground_4_1~WBPaper00031662:solid_vs_liquid~WBPaper00031662:Flight_22_1~WBPaper00031662:Flight_22_2~WBPaper00031662:Flight_22_3~WBPaper00031662:Flight_23_1~WBPaper00031662:Flight_23_2~WBPaper00031662:Flight_4~WBPaper00031662:Ground_22_1~WBPaper00031662:Ground_22_2~WBPaper00031662:Ground_22_3~WBPaper00031662:Ground_23_1~WBPaper00031662:Ground_23_3~WBPaper00031662:Ground_4_2~WBPaper00031662:Ground_23_2	Method: microarray|Species: Caenorhabditis elegans
58	18662544	WBPaper00032062.ce.mr.paper	GSE12094,GSE12166,GSE12167,GSE12168	GPL7065,GPL7066,GPL7067,GPL7068	2	An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans.	To define the C. elegans aging process at the molecular level, we used DNA microarray experiments to identify a set of 1294 age-regulated genes and found that the GATA transcription factors ELT-3, ELT-5, and ELT-6 are responsible for age regulation of a large fraction of these genes. Expression of elt-5 and elt-6 increases during normal aging, and both of these GATA factors repress expression of elt-3, which shows a corresponding decrease in expression in old worms. elt-3 regulates a large number of downstream genes that change expression in old age, including ugt-9, col-144, and sod-3. elt-5(RNAi) and elt-6(RNAi) worms have extended longevity, indicating that elt-3, elt-5, and elt-6 play an important functional role in the aging process. These results identify a transcriptional circuit that guides the rapid aging process in C. elegans and indicate that this circuit is driven by drift of developmental pathways rather than accumulation of damage.	4	16718	Budovskaya YV	Budovskaya YV, Wu K, Southworth LK, Jiang M, Tedesco P, Johnson TE, Kim SK	An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans.	Cell	2008	WBPaper00032062:day_11~WBPaper00032062:day_2~WBPaper00032062:day_5~WBPaper00032062:day_8	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging
59	18778409	WBPaper00032165.ce.mr.paper	GSE12290	GPL5859	2	Age-related behaviors have distinct transcriptional profiles in Caenorhabditis elegans.	There has been a great deal of interest in identifying potential biomarkers of aging. Biomarkers of aging would be useful to predict potential vulnerabilities in an individual that may arise well before they are chronologically expected, due to idiosyncratic aging rates that occur between individuals. Prior attempts to identify biomarkers of aging have often relied on the comparisons of long-lived animals to a wild-type control. However, the effect of interventions in model systems that prolong lifespan (such as single gene mutations or caloric restriction) can sometimes be difficult to interpret due to the manipulation itself having multiple unforeseen consequences on physiology, unrelated to aging itself. The search for predictive biomarkers of aging therefore is problematic, and the identification of metrics that can be used to predict either physiological or chronological age would be of great value. One methodology that has been used to identify biomarkers for numerous pathologies is gene expression profiling. Here, we report whole-genome expression profiles of individual wild-type Caenorhabditis elegans covering the entire wild-type nematode lifespan. Individual nematodes were scored for either age-related behavioral phenotypes, or survival, and then subsequently associated with their respective gene expression profiles. This facilitated the identification of transcriptional profiles that were highly associated with either physiological or chronological age. Overall, our approach serves as a paradigm for identifying potential biomarkers of aging in higher organisms that can be repeatedly sampled throughout their lifespan.	104	16997	Golden TR	Golden TR, Hubbard A, Dando C, Herren MA, Melov S	Age-related behaviors have distinct transcriptional profiles in Caenorhabditis elegans.	Aging Cell	2008	WBPaper00032165:12_days_old_tg115~WBPaper00032165:12_days_old_tg122~WBPaper00032165:12_days_old_tg132~WBPaper00032165:12_days_old_tg133~WBPaper00032165:12_days_old_tg139~WBPaper00032165:12_days_old_tg28~WBPaper00032165:12_days_old_tg29~WBPaper00032165:12_days_old_tg32~WBPaper00032165:12_days_old_tg36~WBPaper00032165:12_days_old_tg45~WBPaper00032165:12_days_old_tg6~WBPaper00032165:12_days_old_tg76~WBPaper00032165:12_days_old_tg77~WBPaper00032165:12_days_old_tg85~WBPaper00032165:12_days_old_tg90~WBPaper00032165:12_days_old_tg96~WBPaper00032165:12_days_old_tg98~WBPaper00032165:14_days_old_tg101~WBPaper00032165:14_days_old_tg11~WBPaper00032165:14_days_old_tg117~WBPaper00032165:14_days_old_tg126~WBPaper00032165:14_days_old_tg131~WBPaper00032165:14_days_old_tg24~WBPaper00032165:14_days_old_tg40~WBPaper00032165:14_days_old_tg43~WBPaper00032165:14_days_old_tg48~WBPaper00032165:14_days_old_tg50~WBPaper00032165:14_days_old_tg54~WBPaper00032165:14_days_old_tg56~WBPaper00032165:14_days_old_tg67~WBPaper00032165:14_days_old_tg82~WBPaper00032165:14_days_old_tg86~WBPaper00032165:14_days_old_tg93~WBPaper00032165:14_days_old_tg94~WBPaper00032165:16_days_old_tg103~WBPaper00032165:16_days_old_tg108~WBPaper00032165:16_days_old_tg113~WBPaper00032165:16_days_old_tg120~WBPaper00032165:16_days_old_tg128~WBPaper00032165:16_days_old_tg136~WBPaper00032165:16_days_old_tg137~WBPaper00032165:16_days_old_tg26~WBPaper00032165:16_days_old_tg30~WBPaper00032165:16_days_old_tg41~WBPaper00032165:16_days_old_tg46~WBPaper00032165:16_days_old_tg49~WBPaper00032165:16_days_old_tg60~WBPaper00032165:16_days_old_tg75~WBPaper00032165:16_days_old_tg79~WBPaper00032165:16_days_old_tg8~WBPaper00032165:16_days_old_tg88~WBPaper00032165:20_days_old_tg116~WBPaper00032165:20_days_old_tg121~WBPaper00032165:20_days_old_tg124~WBPaper00032165:20_days_old_tg129~WBPaper00032165:20_days_old_tg14~WBPaper00032165:20_days_old_tg20~WBPaper00032165:20_days_old_tg31~WBPaper00032165:20_days_old_tg35~WBPaper00032165:20_days_old_tg42~WBPaper00032165:20_days_old_tg44~WBPaper00032165:20_days_old_tg53~WBPaper00032165:20_days_old_tg58~WBPaper00032165:20_days_old_tg92~WBPaper00032165:20_days_old_tg97~WBPaper00032165:24_days_old_tg102~WBPaper00032165:24_days_old_tg105~WBPaper00032165:24_days_old_tg106~WBPaper00032165:24_days_old_tg114~WBPaper00032165:24_days_old_tg130~WBPaper00032165:24_days_old_tg33~WBPaper00032165:24_days_old_tg38~WBPaper00032165:24_days_old_tg59~WBPaper00032165:24_days_old_tg64~WBPaper00032165:4_days_old_tg100~WBPaper00032165:4_days_old_tg110~WBPaper00032165:4_days_old_tg111~WBPaper00032165:4_days_old_tg119~WBPaper00032165:4_days_old_tg123~WBPaper00032165:4_days_old_tg134~WBPaper00032165:4_days_old_tg138~WBPaper00032165:4_days_old_tg34~WBPaper00032165:4_days_old_tg52~WBPaper00032165:4_days_old_tg62~WBPaper00032165:4_days_old_tg87~WBPaper00032165:4_days_old_tg91~WBPaper00032165:4_days_old_tg95~WBPaper00032165:8_days_old_tg10~WBPaper00032165:8_days_old_tg104~WBPaper00032165:8_days_old_tg109~WBPaper00032165:8_days_old_tg112~WBPaper00032165:8_days_old_tg118~WBPaper00032165:8_days_old_tg125~WBPaper00032165:8_days_old_tg127~WBPaper00032165:8_days_old_tg135~WBPaper00032165:8_days_old_tg23~WBPaper00032165:8_days_old_tg37~WBPaper00032165:8_days_old_tg39~WBPaper00032165:8_days_old_tg47~WBPaper00032165:8_days_old_tg51~WBPaper00032165:8_days_old_tg57~WBPaper00032165:8_days_old_tg61~WBPaper00032165:8_days_old_tg83~WBPaper00032165:8_days_old_tg89	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging
60	19251593	WBPaper00032948.ce.mr.paper	GSE11055,GSE14009	GPL200	1	RNA Pol II accumulates at promoters of growth genes during developmental arrest.	When Caenorhabditis elegans larvae hatch from the egg case in the absence of food, their development is arrested (L1 arrest), and they show increased stress resistance until food becomes available. To study nutritional control of larval development, we analyzed growth and gene expression profiles during L1 arrest and recovery. Larvae that were fed responded relatively slowly to starvation compared with the rapid response of arrested larvae to feeding. Chromatin immunoprecipitation of RNA polymerase II (Pol II) followed by deep sequencing showed that during L1 arrest, Pol II continued transcribing starvation-response genes, but the enzyme accumulated on the promoters of growth and development genes. In response to feeding, promoter accumulation decreased, and elongation and messenger RNA levels increased. Therefore, accumulation of Pol II at promoters anticipates nutritionally controlled gene expression during C. elegans development.	18	17638	Baugh LR	Baugh LR, DeModena J, Sternberg PW	RNA Pol II accumulates at promoters of growth genes during developmental arrest.	Science	2009	WBPaper00032948:emb_2hr~WBPaper00032948:L1_0hr_fed~WBPaper00032948:L1_0hr_starve~WBPaper00032948:L1_12hr_fed~WBPaper00032948:L1_12hr_fed_3hr_starve~WBPaper00032948:L1_12hr_starve~WBPaper00032948:L1_12hr_starve_3hr_fed~WBPaper00032948:L1_15hr_fed~WBPaper00032948:L1_15hr_starve~WBPaper00032948:L1_1hr_fed~WBPaper00032948:L1_1hr_starve~WBPaper00032948:L1_24hr_fed~WBPaper00032948:L1_24hr_starve~WBPaper00032948:L1_3hr_fed~WBPaper00032948:L1_3hr_starve~WBPaper00032948:L1_3hr_starve_alteM9~WBPaper00032948:L1_6hr_fed~WBPaper00032948:L1_6hr_starve	Method: microarray|Species: Caenorhabditis elegans
61	19615088	WBPaper00034739.ce.mr.paper	N.A.	N.A.	1	Natural variation in gene expression in the early development of dauer larvae of Caenorhabditis elegans.	BACKGROUND: The free-living nematode Caenorhabditis elegans makes a developmental decision based on environmental conditions: larvae either arrest as dauer larva, or continue development into reproductive adults. There is natural variation among C. elegans lines in the sensitivity of this decision to environmental conditions; that is, there is variation in the phenotypic plasticity of dauer larva development. We hypothesised that these differences may be transcriptionally controlled in early stage larvae. We investigated this by microarray analysis of different C. elegans lines under different environmental conditions, specifically the presence and absence of dauer larva-inducing pheromone. RESULTS: There were substantial transcriptional differences between four C. elegans lines under the same environmental conditions. The expression of approximately 2,000 genes differed between genetically different lines, with each line showing a largely line-specific transcriptional profile. The expression of genes that are markers of larval moulting suggested that the lines may be developing at different rates. The expression of a total of 89 genes was putatively affected by dauer larva or non-dauer larva-inducing conditions. Among the upstream regions of these genes there was an over-representation of DAF-16-binding motifs. CONCLUSION: Under the same environmental conditions genetically different lines of C. elegans had substantial transcriptional differences. This variation may be due to differences in the developmental rates of the lines. Different environmental conditions had a rather smaller effect on transcription. The preponderance of DAF-16-binding motifs upstream of these genes was consistent with these genes playing a key role in the decision between development into dauer or into non-dauer larvae. There was little overlap between the genes whose expression was affected by environmental conditions and previously identified loci involved in the plasticity of dauer larva development.	24	12586	Harvey SC	Harvey SC, Barker GL, Shorto A, Viney ME	Natural variation in gene expression in the early development of dauer larvae of Caenorhabditis elegans.	BMC Genomics	2009	WBPaper00034739:DR1350_dauer_1~WBPaper00034739:DR1350_dauer_2~WBPaper00034739:DR1350_dauer_3~WBPaper00034739:DR1350_non_dauer_1~WBPaper00034739:DR1350_non_dauer_2~WBPaper00034739:DR1350_non_dauer_3~WBPaper00034739:N2_dauer_1~WBPaper00034739:N2_dauer_2~WBPaper00034739:N2_dauer_3~WBPaper00034739:N2_non_dauer_1~WBPaper00034739:N2_non_dauer_2~WBPaper00034739:N2_non_dauer_3~WBPaper00034739:RIL14_dauer_1~WBPaper00034739:RIL14_dauer_2~WBPaper00034739:RIL14_dauer_3~WBPaper00034739:RIL14_non_dauer_1~WBPaper00034739:RIL14_non_dauer_2~WBPaper00034739:RIL14_non_dauer_3~WBPaper00034739:RIL17_dauer_1~WBPaper00034739:RIL17_dauer_2~WBPaper00034739:RIL17_dauer_3~WBPaper00034739:RIL17_non_dauer_1~WBPaper00034739:RIL17_non_dauer_2~WBPaper00034739:RIL17_non_dauer_3	Method: microarray|Species: Caenorhabditis elegans|Topic: dauer larval development
62	17116281	WBPaper00028809.ce.mr.paper	N.A.	N.A.	1	BIR-1, the homologue of human Survivin, regulates expression of developmentally active collagen genes in C. elegans.	BIR-1 and Survivin are highly conserved members of the inhibitor of apoptosis protein family that regulate cell division in nematodes and mammals and inhibit apoptosis in mammals. In the C. elegans genome, bir-1 is organized in an operon together with transcription and splicing cofactor CeSKIP (skp-1) and is highly expressed during embryogenesis as well as in non-dividing cells during larval development. Previously we have shown that BIR-1 regulates transcription and development and its loss-of-function phenotype overlaps with loss of function of CeSKIP and nuclear hormone receptor CHR3 (NHR-23). Here we searched for genes whose expression is affected by BIR-1 loss of function using whole-genome microarray experiments and identified several collagen genes as candidate targets of bir-1 inhibition in L1 larval stage. The decreased expression of selected collagen genes in bir-l-inhibited larvae was confirmed by quantitative RT-PCR. Next, we generated transgenic lines expressing bir-1 mRNA under a heat shock-regulated promoter and tested whether bir-1 overexpression has the potential to augment the expression of genes that showed decreased expression in worms treated with bir-1 RNAi. Overexpression of bir-1 resulted in a pronounced increase (2 to 5 times) of the expression of these genes. Our findings support the concept that BIR-1, a protein generally regarded as a mitotic factor, is involved in the regulation of transcription during normal development of C. elegans and has a strong ability to affect transcription of developmentally active genes if overexpressed.	6	17638	Liby P	Liby P, Pohludka M, Vohanka J, Kostrouchova M, Kostrouch D, Rall JE, Kostrouch Z	BIR-1, the homologue of human Survivin, regulates expression of developmentally active collagen genes in C. elegans.	Folia Biol (Praha)	2006	WBPaper00028809:control_rep1~WBPaper00028809:control_rep2~WBPaper00028809:control_rep3~WBPaper00028809:bir-1(RNAi)_rep1~WBPaper00028809:bir-1(RNAi)_rep2~WBPaper00028809:bir-1(RNAi)_rep3	Method: microarray|Species: Caenorhabditis elegans
63	17289921	WBPaper00029115.ce.mr.paper	GSE32467	GPL200	1	UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans.	In Caenorhabditis elegans, VA and VB motor neurons arise as lineal sisters but synapse with different interneurons to regulate locomotion. VA-specific inputs are defined by the UNC-4 homeoprotein and its transcriptional corepressor, UNC-37/Groucho, which function in the VAs to block the creation of chemical synapses and gap junctions with interneurons normally reserved for VBs. To reveal downstream genes that control this choice, we have employed a cell-specific microarray strategy that has now identified unc-4-regulated transcripts. One of these genes, ceh-12, a member of the HB9 family of homeoproteins, is normally restricted to VBs. We show that expression of CEH-12/HB9 in VA motor neurons in unc-4 mutants imposes VB-type inputs. Thus, this work reveals a developmental switch in which motor neuron input is defined by differential expression of transcription factors that select alternative presynaptic partners. The conservation of UNC-4, HB9, and Groucho expression in the vertebrate motor circuit argues that similar mechanisms may regulate synaptic specificity in the spinal cord.	6	17637	Von Stetina SE	Von Stetina SE, Fox RM, Watkins KL, Starich TA, Shaw JE, Miller DM	UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans.	Genes Dev	2007	WBPaper00029115:N2_A-class_rep1~WBPaper00029115:N2_A-class_rep2~WBPaper00029115:N2_A-class_rep3~WBPaper00029115:unc-37(e262)_A-class_rep1~WBPaper00029115:unc-37(e262)_A-class_rep2~WBPaper00029115:unc-37(e262)_A-class_rep3	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
64	17612406	WBPaper00030839.ce.mr.paper	GSE8004	GPL200	1	Cell-specific microarray profiling experiments reveal a comprehensive picture of gene expression in the C. elegans nervous system.	ABSTRACT: BACKGROUND: With its fully sequenced genome and simple, well-defined nervous system, the nematode C. elegans offers a unique opportunity to correlate gene expression with neuronal differentiation. The lineal origin, cellular morphology and synaptic connectivity of each of the 302 neurons are known. In many instances, specific behaviors can be attributed to particular neurons or circuits. Here we describe microarray-based methods that monitor gene expression in C. elegans neurons and thereby link comprehensive profiles of neuronal transcription to key developmental and functional properties of the nervous system. RESULTS: We employed complementary microarray-based strategies to profile gene expression in the embryonic and larval nervous systems. In the MAPCeL (Microarray Profiling C. elegans cells) method, we used Fluorescence Activated Cell Sorting (FACS) to isolate GFP-tagged embryonic neurons for microarray analysis. To profile the larval nervous system, we used the mRNA-tagging technique in which an epitope-labeled mRNA binding protein (FLAG-PAB-1) was transgenically expressed in neurons for immunoprecipitation of cell-specific transcripts. These combined approaches identified approximately 2,500 mRNAs that are highly enriched in either the embryonic or larval C. elegans nervous system. These data are validated in part by the detection of gene classes (e.g. transcription factors, ion channels, synaptic vesicle components) with established roles in neuronal development or function. Of particular interest are 19 conserved transcripts of unknown function that are also expressed in the mammalian brain. In addition to utilizing these profiling approaches to define stage-specific gene expression, we also applied the mRNA-tagging method to fingerprint a specific neuron type, the A-class group of cholinergic motor neurons, during early larval development. A comparison of these data to a MAPCeL profile of Embryonic A-class motor neurons identified genes with common functions in both types of A-class motor neurons as well as transcripts with roles specific to each motor neuron type. Conclusion: We describe microarray-based strategies for generating expression profiles of embryonic and larval C. elegans neurons. These methods can be applied to particular neurons at specific developmental stages and therefore provide an unprecedented opportunity to obtain spatially and temporally defined snapshots of gene expression in a simple model nervous system.	24	17638	Von Stetina SE	Von Stetina SE, Watson JD, Fox RM, Olszewski KL, Spencer WC, Roy PJ, Miller DM	Cell-specific microarray profiling experiments reveal a comprehensive picture of gene expression in the C. elegans nervous system.	Genome Biol	2007	WBPaper00030839:Embryonic_Reference_Rep1_Set1~WBPaper00030839:Embryonic_Reference_Rep2_Set1~WBPaper00030839:Embryonic_Reference_Rep3_Set1~WBPaper00030839:Embryonic_Reference_Rep4_Set1~WBPaper00030839:Embryonic_Pan-neural_Rep1_Set1~WBPaper00030839:Embryonic_Pan-neural_Rep2_Set1~WBPaper00030839:Embryonic_Pan-neural_Rep3_Set1~WBPaper00030839:Larval_Reference_Rep1_Set1~WBPaper00030839:Larval_Reference_Rep2_Set1~WBPaper00030839:Larval_Reference_Rep3_Set1~WBPaper00030839:Larval_Reference_Rep4_Set2~WBPaper00030839:Larval_Reference_Rep5_Set2~WBPaper00030839:Larval_Pan-neural_Rep1_Set2~WBPaper00030839:Larval_Pan-neural_Rep2_Set2~WBPaper00030839:Larval_Pan-neural_Rep3_Set2~WBPaper00030839:Larval_A-class_Rep1_Set3~WBPaper00030839:Larval_A-class_Rep2_Set3~WBPaper00030839:Larval_A-class_Rep3_Set3~WBPaper00030839:Larval_A-class_Rep4_Set3~WBPaper00030839:Larval_Reference_Rep1_Set3~WBPaper00030839:Larval_Reference_Rep2_Set3~WBPaper00030839:Larval_Reference_Rep3_Set3~WBPaper00030839:Larval_Reference_Rep4_Set3~WBPaper00030839:Larval_Reference_Rep5_Set3	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
65	17919598	WBPaper00031070.ce.mr.paper	GSE8659	GPL200	1	Whole genome microarray analysis of C. elegans rrf-3 and eri-1 mutants.	We performed genome wide gene expression analysis on L4 stage Caenorhabditis elegans rrf-3(pk1426) and eri-1(mg366) mutant strains to study the effects caused by loss of their encoded proteins, which are required for the accumulation of endogenous secondary siRNAs. Mutant rrf-3 and eri-1 strains exhibited 72 transcripts that were co-over-expressed and 4 transcripts co-under-expressed (&gt;2-fold, P&lt;0.05) compared to N2 wild type strain. Ontology analysis indicated these transcripts were over represented for protein phosphorylation and sperm function genes. These results provide additional support for the hypothesis that RRF-3 and ERI-1 act together in the endo-siRNA pathway, and furthermore suggests their involvement in additional biological processes.	9	17638	Asikainen S	Asikainen S, Storvik M, Lakso M, Wong G	Whole genome microarray analysis of C. elegans rrf-3 and eri-1 mutants.	FEBS Lett	2007	WBPaper00031070:N2_1~WBPaper00031070:N2_2~WBPaper00031070:N2_3~WBPaper00031070:NL2099_1~WBPaper00031070:NL2099_2~WBPaper00031070:NL2099_3~WBPaper00031070:GR1373_1~WBPaper00031070:GR1373_2~WBPaper00031070:GR1373_3	Method: microarray|Species: Caenorhabditis elegans
66	18178500	WBPaper00031379.ce.mr.paper	GSE9896,GSE9897	GPL200	1	Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans.	Caenorhabditis elegans affords a model of primary mitochondrial dysfunction that provides insight into cellular adaptations which accompany mutations in nuclear genes that encode mitochondrial proteins. To this end, we characterized genome-wide expression profiles of C. elegans strains with mutations in nuclear-encoded subunits of respiratory chain complexes. Our goal was to detect concordant changes among clusters of genes that comprise defined metabolic pathways. Results indicate that respiratory chain mutants significantly upregulate a variety of basic cellular metabolic pathways involved in carbohydrate, amino acid, and fatty acid metabolism, as well as cellular defense pathways such as the metabolism of P450 and glutathione. To further confirm and extend expression analysis findings, quantitation of whole worm free amino acid levels was performed in C. elegans mitochondrial mutants for subunits of complexes I, II, and III. Significant differences were seen for 13 of 16 amino acid levels in complex I mutants compared with controls, as well as overarching similarities among profiles of complex I, II, and III mutants compared with controls. The specific pattern of amino acid alterations observed provides novel evidence to suggest that an increase in glutamate-linked transamination reactions caused by the failure of NAD(+)-dependent ketoacid oxidation occurs in primary mitochondrial respiratory chain mutants. Recognition of consistent alterations both among patterns of nuclear gene expression for multiple biochemical pathways and in quantitative amino acid profiles in a translational genetic model of mitochondrial dysfunction allows insight into the complex pathogenesis underlying primary mitochondrial disease. Such knowledge may enable the development of a metabolomic profiling diagnostic tool applicable to human mitochondrial disease.	20	17638	Falk MJ	Falk MJ, Zhang Z, Rosenjack JR, Nissim I, Daikhin E, Sedensky MM, Yudkoff M, Morgan PG	Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans.	Mol Genet Metab	2008	WBPaper00031379:gas-1(fc21)_OP50_1~WBPaper00031379:gas-1(fc21)_OP50_2~WBPaper00031379:gas-1(fc21)_OP50_3~WBPaper00031379:gas-1(fc21)_OP50_4~WBPaper00031379:gas-1(fc21)_OP50_5~WBPaper00031379:WT_OP50_1~WBPaper00031379:WT_OP50_2~WBPaper00031379:WT_OP50_3~WBPaper00031379:WT_OP50_4~WBPaper00031379:WT_OP50_5~WBPaper00031379:WT_control_K12~WBPaper00031379:WT_control_RNAi~WBPaper00031379:gas-1(fc21)_K12~WBPaper00031379:mev-1(kn1)_K12~WBPaper00031379:isp-1(qm150)_K12~WBPaper00031379:F22D6.4_RNAi_1~WBPaper00031379:F22D6.4_RNAi_2~WBPaper00031379:F22D6.4_RNAi_3~WBPaper00031379:F22D6.4_RNAi_4~WBPaper00031379:F22D6.4_RNAi_5	Method: microarray|Species: Caenorhabditis elegans
67	18277379	WBPaper00031525.ce.mr.paper	GSE9665	GPL200	1	Pairing of competitive and topologically distinct regulatory modules enhances patterned gene expression.	Biological networks are inherently modular, yet little is known about how modules are assembled to enable coordinated and complex functions. We used RNAi and time series, whole-genome microarray analyses to systematically perturb and characterize components of a Caenorhabditis elegans lineage-specific transcriptional regulatory network. These data are supported by selected reporter gene analyses and comprehensive yeast one-hybrid and promoter sequence analyses. Based on these results, we define and characterize two modules composed of muscle- and epidermal-specifying transcription factors that function together within a single cell lineage to robustly specify multiple cell types. The expression of these two modules, although positively regulated by a common factor, is reliably segregated among daughter cells. Our analyses indicate that these modules repress each other, and we propose that this cross-inhibition coupled with their relative time of induction function to enhance the initial asymmetry in their expression patterns, thus leading to the observed invariant gene expression patterns and cell lineage. The coupling of asynchronous and topologically distinct modules may be a general principle of module assembly that functions to potentiate genetic switches.	74	17638	Yanai I	Yanai I, Baugh LR, Smith JJ, Roehrig C, Shen-Orr SS, Claggett JM, Hill AA, Slonim DK, Hunter CP	Pairing of competitive and topologically distinct regulatory modules enhances patterned gene expression.	Mol Syst Biol	2008	WBPaper00031525:mex-3_143_A~WBPaper00031525:mex-3_143_B~WBPaper00031525:mex-3_186_A~WBPaper00031525:mex-3_186_B~WBPaper00031525:mex-3_230_A~WBPaper00031525:mex-3_230_B~WBPaper00031525:mex-3_scrt-1_186_A~WBPaper00031525:mex-3_tbx-8_tbx-9_143_A~WBPaper00031525:mex-3_tbx-8_tbx-9_143_B~WBPaper00031525:mex-3_tbx-8_tbx-9_143_C~WBPaper00031525:mex-3_tbx-8_tbx-9_186_A~WBPaper00031525:mex-3_elt-1_143_A~WBPaper00031525:mex-3_elt-1_143_B~WBPaper00031525:mex-3_elt-1_143_C~WBPaper00031525:mex-3_elt-1_186_A~WBPaper00031525:mex-3_elt-1_186_B~WBPaper00031525:mex-3_elt-1_186_C~WBPaper00031525:mex-3_vab-7_186_A~WBPaper00031525:mex-3_vab-7_230_A~WBPaper00031525:mex-3_vab-7_230_B~WBPaper00031525:mex-3_vab-7_230_C~WBPaper00031525:mex-3_hlh-1_186_A~WBPaper00031525:mex-3_hlh-1_186_B~WBPaper00031525:mex-3_hlh-1_230_A~WBPaper00031525:mex-3_nhr-25_186_A~WBPaper00031525:mex-3_nhr-25_186_B~WBPaper00031525:mex-3_nhr-25_186_C~WBPaper00031525:mex-3_nhr-25_230_A~WBPaper00031525:mex-3_nhr-25_230_B~WBPaper00031525:mex-3_elt-3_186_A~WBPaper00031525:mex-3_elt-3_230_A~WBPaper00031525:mex-3_elt-3_230_B~WBPaper00031525:mex-3_elt-3_230_C~WBPaper00031525:mex-3_nob-1_186_A~WBPaper00031525:mex-3_nob-1_186_B~WBPaper00031525:mex-3_nob-1_186_C~WBPaper00031525:mex-3_nob-1_230_A~WBPaper00031525:mex-3_nob-1_230_B~WBPaper00031525:mex-3_nob-1_230_C~WBPaper00031525:mex-3_unc-120_186_A~WBPaper00031525:mex-3_unc-120_186_B~WBPaper00031525:mex-3_unc-120_186_C~WBPaper00031525:mex-3_unc-120_230_A~WBPaper00031525:mex-3_unc-120_230_B~WBPaper00031525:mex-3_unc-120_230_C~WBPaper00031525:mex-3_hnd-1_143_A~WBPaper00031525:mex-3_hnd-1_143_B~WBPaper00031525:mex-3_hnd-1_143_C~WBPaper00031525:mex-3_hnd-1_186_A~WBPaper00031525:mex-3_hnd-1_186_B~WBPaper00031525:mex-3_lin-26_186_A~WBPaper00031525:mex-3_lin-26_186_B~WBPaper00031525:mex-3_lin-26_230_A~WBPaper00031525:mex-3_lin-26_230_B~WBPaper00031525:mex-3_scrt-1_143_A~WBPaper00031525:mex-3_scrt-1_143_B~WBPaper00031525:mex-3_scrt-1_186_B~WBPaper00031525:mex-3_pal-1_143_A~WBPaper00031525:mex-3_scrt-1_186_C~WBPaper00031525:mex-3_vab-7_186_B~WBPaper00031525:mex-3_vab-7_186_C~WBPaper00031525:mex-3_hlh-1_230_B~WBPaper00031525:mex-3_nhr-25_230_C~WBPaper00031525:mex-3_elt-3_186_B~WBPaper00031525:mex-3_elt-3_186_C~WBPaper00031525:mex-3_hnd-1_186_C~WBPaper00031525:mex-3_pal-1_101_A~WBPaper00031525:mex-3_pal-1_143_B~WBPaper00031525:mex-3_pal-1_143_C~WBPaper00031525:mex-3_pal-1_186_A~WBPaper00031525:mex-3_pal-1_186_B~WBPaper00031525:mex-3_pal-1_186_C~WBPaper00031525:mex-3_pal-1_230_A~WBPaper00031525:mex-3_pal-1_230_B	Method: microarray|Species: Caenorhabditis elegans
68	18284693	WBPaper00031532.ce.mr.paper	GSE9485	GPL200	1	Complementary RNA amplification methods enhance microarray identification of transcripts expressed in the C. elegans nervous system.	ABSTRACT: BACKGROUND: DNA microarrays provide a powerful method for global analysis of gene expression. The application of this technology to specific cell types and tissues, however, is typically limited by small amounts of available mRNA, thereby necessitating amplification. Here we compare microarray results obtained with two different methods of RNA amplification to profile gene expression in the C. elegans larval nervous system. RESULTS: We used the mRNA-tagging strategy to isolate transcripts specifically from C. elegans larval neurons. The WT-Ovation Pico System (WT-Pico) was used to amplify 2 ng of pan-neural RNA to produce labeled cDNA for microarray analysis. These WT-Pico-derived data were compared to microarray results obtained with a labeled aRNA target generated by two rounds of In Vitro Transcription (IVT) of 25 ng of pan-neural RNA. WT-Pico results in a higher fraction of present calls than IVT, a finding consistent with the proposal that DNA-DNA hybridization results in lower mismatch signals than the RNA-DNA heteroduplexes produced by IVT amplification. Microarray data sets from these samples were compared to a Reference profile of all larval cells to identify transcripts with elevated expression in neurons. These results were validated by the high proportion of known neuron-expressed genes detected in these profiles and by promoter-GFP constructs for previously uncharacterized genes in these data sets. Together, the IVT and WT-Pico methods identified 2,173 unique neuron-enriched transcripts. Only about half of these transcripts (1,044), however, are detected as enriched by both IVT and WT-Pico amplification. CONCLUSION: We show that two different methods of RNA amplification, IVT and WT-Pico, produce valid microarray profiles of gene expression in the C. elegans larval nervous system with a low rate of false positives. However, our results also show that each method of RNA amplification detects a unique subset of bona fide neural-enriched transcripts and thus a wider array of authentic neural genes are identified by the combination of these data sets than by the microarray profiles obtained with either method of RNA amplification alone. With its relative ease of implementation and greater sensitivity, WT-Pico is the preferred method of amplification for cases in which sample RNA is limiting.	8	17637	Watson JD	Watson JD, Wang S, Von Stetina SE, Spencer WC, Levy S, Dexheimer PJ, Kurn N, Heath JD, Miller DM	Complementary RNA amplification methods enhance microarray identification of transcripts expressed in the C. elegans nervous system.	BMC Genomics	2008	WBPaper00031532:Larval_Pan-neural_rep_1~WBPaper00031532:Larval_Pan-neural_rep_2~WBPaper00031532:Larval_Pan-neural_rep_3~WBPaper00031532:Larval_Pan-neural_rep_4~WBPaper00031532:Larval_Pan-neural_rep_5~WBPaper00031532:Larval_Reference_rep_1~WBPaper00031532:Larval_Reference_rep_2~WBPaper00031532:Larval_Reference_rep_3	Method: microarray|Species: Caenorhabditis elegans
69	18418376	WBPaper00031703.ce.mr.paper	GSE8696	GPL200	1	Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins.	Haems are metalloporphyrins that serve as prosthetic groups for various biological processes including respiration, gas sensing, xenobiotic detoxification, cell differentiation, circadian clock control, metabolic reprogramming and microRNA processing. With a few exceptions, haem is synthesized by a multistep biosynthetic pathway comprising defined intermediates that are highly conserved throughout evolution. Despite our extensive knowledge of haem biosynthesis and degradation, the cellular pathways and molecules that mediate intracellular haem trafficking are unknown. The experimental setback in identifying haem trafficking pathways has been the inability to dissociate the highly regulated cellular synthesis and degradation of haem from intracellular trafficking events. Caenorhabditis elegans and related helminths are natural haem auxotrophs that acquire environmental haem for incorporation into haemoproteins, which have vertebrate orthologues. Here we show, by exploiting this auxotrophy to identify HRG-1 proteins in C. elegans, that these proteins are essential for haem homeostasis and normal development in worms and vertebrates. Depletion of hrg-1, or its paralogue hrg-4, in worms results in the disruption of organismal haem sensing and an abnormal response to haem analogues. HRG-1 and HRG-4 are previously unknown transmembrane proteins, which reside in distinct intracellular compartments. Transient knockdown of hrg-1 in zebrafish leads to hydrocephalus, yolk tube malformations and, most strikingly, profound defects in erythropoiesis-phenotypes that are fully rescued by worm HRG-1. Human and worm proteins localize together, and bind and transport haem, thus establishing an evolutionarily conserved function for HRG-1. These findings reveal conserved pathways for cellular haem trafficking in animals that define the model for eukaryotic haem transport. Thus, uncovering the mechanisms of haem transport in C. elegans may provide insights into human disorders of haem metabolism and reveal new drug targets for developing anthelminthics to combat worm infestations.	9	17638	Rajagopal A	Rajagopal A, Rao AU, Amigo J, Tian M, Upadhyay SK, Hall C, Uhm S, Mathew MK, Fleming MD, Paw BH, Krause M, Hamza I	Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins.	Nature	2008	WBPaper00031703:4uM_hemin_A~WBPaper00031703:4uM_hemin_B~WBPaper00031703:4uM_hemin_C~WBPaper00031703:20uM_hemin_A~WBPaper00031703:20uM_hemin_B~WBPaper00031703:20uM_hemin_C~WBPaper00031703:500uM_hemin_A~WBPaper00031703:500uM_hemin_B~WBPaper00031703:500uM_hemin_C	Method: microarray|Species: Caenorhabditis elegans
70	18437219	WBPaper00031832.ce.mr.paper	GSE9246	GPL200	1	Coordinated regulation of intestinal functions in C. elegans by LIN-35/Rb and SLR-2.	LIN-35 is the sole C. elegans representative of the pocket protein family, which includes the mammalian Retinoblastoma protein pRb and its paralogs p107 and p130. In addition to having a well-established and central role in cell cycle regulation, pocket proteins have been increasingly implicated in the control of critical and diverse developmental and cellular processes. To gain a greater understanding of the roles of pocket proteins during development, we have characterized a synthetic genetic interaction between lin-35 and slr-2, which we show encodes a C2H2-type Zn-finger protein. Whereas animals harboring single mutations in lin-35 or slr-2 are viable and fertile, lin-35; slr-2 double mutants arrest uniformly in early larval development without obvious morphological defects. Using a combination of approaches including transcriptome profiling, mosaic analysis, starvation assays, and expression analysis, we demonstrate that both LIN-35 and SLR-2 act in the intestine to regulate the expression of many genes required for normal nutrient utilization. These findings represent a novel role for pRb family members in the maintenance of organ function. Our studies also shed light on the mechanistic basis of genetic redundancy among transcriptional regulators and suggest that synthetic interactions may result from the synergistic misregulation of one or more common targets.	6	17638	Kirienko NV	Kirienko NV, McEnerney JD, Fay DS	Coordinated regulation of intestinal functions in C. elegans by LIN-35/Rb and SLR-2.	PLoS Genet	2008	WBPaper00031832:N2_1~WBPaper00031832:N2_2~WBPaper00031832:N2_3~WBPaper00031832:slr-2_1~WBPaper00031832:slr-2_2~WBPaper00031832:slr-2_3	Method: microarray|Species: Caenorhabditis elegans|Topic: metabolic process
71	18627611	WBPaper00032022.ce.mr.paper	N.A.	N.A.	1	Transcriptional profiling in C. elegans suggests DNA damage dependent apoptosis as an ancient function of the p53 family.	ABSTRACT: BACKGROUND: In contrast to the three mammalian p53 family members, p53, which is generally involved in DNA damage responses, and p63 and p73 which are primarily needed for developmental regulation, cep-1 encodes for the single C. elegans p53-like gene. cep-1 acts as a transcription activator in a primordial p53 pathway that involves CEP-1 activation and the CEP-1 dependent transcriptional induction of the worm BH3 only domain encoding genes egl-1 and ced-13 to induce germ cell apoptosis. EGL-1 and CED-13 proteins inactivate Bcl-2 like CED-9 to trigger CED-4 and CED-3 caspase dependent germ cell apoptosis. To address the function of p53 in global transcriptional regulation we investigate genome-wide transcriptional responses upon DNA damage and cep-1 deficiency. RESULTS: Examining C. elegans expression profiles using whole genome Affymetrix GeneChip arrays, we found that 83 genes were induced more than two fold upon ionizing radiation (IR). None of these genes, with exception of an ATP ribosylase homolog, encode for known DNA repair genes. Using two independent cep-1 loss if function alleles we did not find genes regulated by cep-1 in the absence of IR. Among the IR-induced genes only three are dependent on cep-1, namely egl-1, ced-13 and a novel C. elegans specific gene. The majority of IR-induced genes appear to be involved in general stress responses, and qRT-PCR experiments indicate that they are mainly expressed in somatic tissues. Interestingly, we reveal an extensive overlap of gene expression changes occurring in response to DNA damage and in response to bacterial infection. Furthermore, many genes induced by IR are also transcriptionally regulated in longevity mutants suggesting that DNA damage and aging induce an overlapping stress response. CONCLUSIONS: We performed genome-wide gene expression analyses which indicate that only a surprisingly small number of genes are regulated by CEP-1 and that DNA damage induced apoptosis via the transcriptional induction of BH3 domain proteins is likely to be an ancient DNA damage response function of the p53 family. Interestingly, although the apoptotic response to DNA damage is regulated through transcriptional activity of CEP-1, other DNA damage responses do not appear to be regulated on the transcriptional level and do not require the p53 like gene cep-1.	28	17638	Greiss S	Greiss S, Schumacher B, Grandien K, Rothblatt J, Gartner A	Transcriptional profiling in C. elegans suggests DNA damage dependent apoptosis as an ancient function of the p53 family.	BMC Genomics	2008	WBPaper00032022:N2_nonX-Ray_2h_rep1~WBPaper00032022:N2_nonX-Ray_2h_rep2~WBPaper00032022:N2_nonX-Ray_2h_rep3~WBPaper00032022:N2_X-Ray_2h_rep1~WBPaper00032022:N2_X-Ray_2h_rep2~WBPaper00032022:N2_X-Ray_2h_rep3~WBPaper00032022:cep-1(lg12501)_nonX-Ray_2h_rep1~WBPaper00032022:cep-1(lg12501)_nonX-Ray_2h_rep2~WBPaper00032022:cep-1(lg12501)_nonX-Ray_2h_rep3~WBPaper00032022:cep-1(lg12501)_X-Ray_2h_rep1~WBPaper00032022:cep-1(lg12501)_X-Ray_2h_rep2~WBPaper00032022:cep-1(lg12501)_X-Ray_2h_rep3~WBPaper00032022:N2_nonGamma-Ray_2h_rep1~WBPaper00032022:N2_nonGamma-Ray_2h_rep2~WBPaper00032022:N2_Gamma-Ray_2h_rep1~WBPaper00032022:N2_Gamma-Ray_2h_rep2~WBPaper00032022:N2_nonGamma-Ray_6h_rep1~WBPaper00032022:N2_nonGamma-Ray_6h_rep2~WBPaper00032022:N2_nonGamma-Ray_6h_rep3~WBPaper00032022:N2_Gamma-Ray_6h_rep1~WBPaper00032022:N2_Gamma-Ray_6h_rep2~WBPaper00032022:N2_Gamma-Ray_6h_rep3~WBPaper00032022:cep-1(lg12501)_nonGamma-Ray_6h_rep1~WBPaper00032022:cep-1(lg12501)_nonGamma-Ray_6h_rep2~WBPaper00032022:cep-1(lg12501)_nonGamma-Ray_6h_rep3~WBPaper00032022:cep-1(lg12501)_Gamma-Ray_6h_rep1~WBPaper00032022:cep-1(lg12501)_Gamma-Ray_6h_rep2~WBPaper00032022:cep-1(lg12501)_Gamma-Ray_6h_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: programmed cell death|Topic: apoptotic DNA fragmentation|Topic: apoptotic process|Topic: engulfment of apoptotic cell
72	19073934	WBPaper00032425.ce.mr.paper	GSE13258	GPL200	1	RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans.	In Caenorhabditis elegans, a vast number of endogenous short RNAs corresponding to thousands of genes have been discovered recently. This finding suggests that these short interfering RNAs (siRNAs) may contribute to regulation of many developmental and other signaling pathways in addition to silencing viruses and transposons. Here, we present a microarray analysis of gene expression in RNA interference (RNAi)-related mutants rde-4, zfp-1, and alg-1 and the retinoblastoma (Rb) mutant lin-35. We found that a component of Dicer complex RDE-4 and a chromatin-related zinc finger protein ZFP-1, not implicated in endogenous RNAi, regulate overlapping sets of genes. Notably, genes a) up-regulated in the rde-4 and zfp-1 mutants and b) up-regulated in the lin-35(Rb) mutant, but not the down-regulated genes are highly represented in the set of genes with corresponding endogenous siRNAs (endo-siRNAs). Our study suggests that endogenous siRNAs cooperate with chromatin factors, either C. elegans ortholog of acute lymphoblastic leukemia-1 (ALL-1)-fused gene from chromosome 10 (AF10), ZFP-1, or tumor suppressor Rb, to regulate overlapping sets of genes and predicts a large role for RNAi-based chromatin silencing in control of gene expression in C. elegans.	15	17638	Grishok A	Grishok A, Hoersch S, Sharp PA	RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans.	Proc Natl Acad Sci U S A	2008	WBPaper00032425:WT_1~WBPaper00032425:WT_2~WBPaper00032425:WT_3~WBPaper00032425:alg-1_1~WBPaper00032425:alg-1_2~WBPaper00032425:alg-1_3~WBPaper00032425:zfp-1_1~WBPaper00032425:zfp-1_2.1~WBPaper00032425:zfp-1_2.2~WBPaper00032425:rde-4_1~WBPaper00032425:rde-4_2~WBPaper00032425:rde-4_3~WBPaper00032425:lin-35_1~WBPaper00032425:lin-35_2.1~WBPaper00032425:lin-35_2.2	Method: microarray|Species: Caenorhabditis elegans
73	19079239	WBPaper00032430.ce.mr.paper	GSE9682	GPL200	1	Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans.	Dietary restriction is the most effective and reproducible intervention to extend lifespan in divergent species. In mammals, two regimens of dietary restriction, intermittent fasting (IF) and chronic caloric restriction, have proven to extend lifespan and reduce the incidence of age-related disorders. An important characteristic of IF is that it can increase lifespan even when there is little or no overall decrease in calorie intake. The molecular mechanisms underlying IF-induced longevity, however, remain largely unknown. Here we establish an IF regimen that effectively extends the lifespan of Caenorhabditis elegans, and show that the low molecular weight GTPase RHEB-1 has a dual role in lifespan regulation; RHEB-1 is required for the IF-induced longevity, whereas inhibition of RHEB-1 mimics the caloric-restriction effects. RHEB-1 exerts its effects in part by the insulin/insulin growth factor (IGF)-like signalling effector DAF-16 in IF. Our analyses demonstrate that most fasting-induced upregulated genes require RHEB-1 function for their induction, and that RHEB-1 and TOR signalling are required for the fasting-induced downregulation of an insulin-like peptide, INS-7. These findings identify the essential role of signalling by RHEB-1 in IF-induced longevity and gene expression changes, and suggest a molecular link between the IF-induced longevity and the insulin/IGF-like signalling pathway.	24	17638	Honjoh S	Honjoh S, Yamamoto T, Uno M, Nishida E	Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans.	Nature	2009	WBPaper00032430:N2-controlRNAi-fed_1~WBPaper00032430:N2-controlRNAi-fed_2~WBPaper00032430:N2-controlRNAi-fed_3~WBPaper00032430:N2-controlRNAi-fed_4~WBPaper00032430:N2-controlRNAi-fed_5~WBPaper00032430:N2-controlRNAi-fasting_1~WBPaper00032430:N2-controlRNAi-fasting_2~WBPaper00032430:N2-controlRNAi-fasting_3~WBPaper00032430:N2-controlRNAi-fasting_4~WBPaper00032430:N2-controlRNAi-fasting_5~WBPaper00032430:N2-Cel-RhebRNAi-fed_1~WBPaper00032430:N2-Cel-RhebRNAi-fed_2~WBPaper00032430:N2-Cel-RhebRNAi-fed_3~WBPaper00032430:N2-Cel-RhebRNAi-fed_4~WBPaper00032430:N2-Cel-RhebRNAi-fasting_1~WBPaper00032430:N2-Cel-RhebRNAi-fasting_2~WBPaper00032430:N2-Cel-RhebRNAi-fasting_3~WBPaper00032430:N2-Cel-RhebRNAi-fasting_4~WBPaper00032430:N2-Cel-TORRNAi-fed_1~WBPaper00032430:N2-Cel-TORRNAi-fed_2~WBPaper00032430:N2-Cel-TORRNAi-fed_3~WBPaper00032430:N2-Cel-TORRNAi-fasting_1~WBPaper00032430:N2-Cel-TORRNAi-fasting_2~WBPaper00032430:N2-Cel-TORRNAi-fasting_3	Method: microarray|Species: Caenorhabditis elegans
74	19182803	WBPaper00032528.ce.mr.paper	N.A.	N.A.	1	Differential chromatin marking of introns and expressed exons by H3K36me3.	Variation in patterns of methylations of histone tails reflects and modulates chromatin structure and function. To provide a framework for the analysis of chromatin function in Caenorhabditis elegans, we generated a genome-wide map of histone H3 tail methylations. We find that C. elegans genes show distributions of histone modifications that are similar to those of other organisms, with H3K4me3 near transcription start sites, H3K36me3 in the body of genes and H3K9me3 enriched on silent genes. We also observe a novel pattern: exons are preferentially marked with H3K36me3 relative to introns. H3K36me3 exon marking is dependent on transcription and is found at lower levels in alternatively spliced exons, supporting a splicing-related marking mechanism. We further show that the difference in H3K36me3 marking between exons and introns is evolutionarily conserved in human and mouse. We propose that H3K36me3 exon marking in chromatin provides a dynamic link between transcription and splicing.	3	17638	Kolasinska-Zwierz P	Kolasinska-Zwierz P, Down T, Latorre I, Liu T, Liu XS, Ahringer J	Differential chromatin marking of introns and expressed exons by H3K36me3.	Nat Genet	2009	WBPaper00032528:N2-2~WBPaper00032528:N2-3~WBPaper00032528:N2-1	Method: microarray|Species: Caenorhabditis elegans
75	19270160	WBPaper00032976.ce.mr.paper	GSE14640,GSE14649	GPL200	1	A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome.	In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X-gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the Caenorhabditis elegans X chromosome for repression by the DCC. The DCC binds to discrete, dispersed sites on X of two types. rex sites (recruitment elements on X) recruit the DCC in an autonomous, DNA sequence-dependent manner using a 12-base-pair (bp) consensus motif that is enriched on X. This motif is critical for DCC binding, is clustered in rex sites, and confers much of X-chromosome specificity. Motif variants enriched on X by 3.8-fold or more are highly predictive (95%) for rex sites. In contrast, dox sites (dependent on X) lack the X-enriched variants and cannot bind the DCC when detached from X. dox sites are more prevalent than rex sites and, unlike rex sites, reside preferentially in promoters of some expressed genes. These findings fulfill predictions for a targeting model in which the DCC binds to recruitment sites on X and disperses to discrete sites lacking autonomous recruitment ability. To relate DCC binding to function, we identified dosage-compensated and noncompensated genes on X. Unexpectedly, many genes of both types have bound DCC, but many do not, suggesting the DCC acts over long distances to repress X-gene expression. Remarkably, the DCC binds to autosomes, but at far fewer sites and rarely at consensus motifs. DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome.	26	17637	Jans J	Jans J, Gladden JM, Ralston EJ, Pickle CS, Michel AH, Pferdehirt RR, Eisen MB, Meyer BJ	A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome.	Genes Dev	2009	WBPaper00032976:XO_TY2222-E-080307_A~WBPaper00032976:XO_TY2222-E-080307_B~WBPaper00032976:XO_TY2222-E-080307_C~WBPaper00032976:XO_TY2222-E-022208_A~WBPaper00032976:XO_TY2222-E-022208_B~WBPaper00032976:XO_TY2222-E-022208_C~WBPaper00032976:XO_TY2222-E-022208_D~WBPaper00032976:XO_TY2222-E-022208_E~WBPaper00032976:XX_WT-E-080307_A~WBPaper00032976:XX_WT-E-080307_B~WBPaper00032976:XX_WT-E-080307_C~WBPaper00032976:XX_WT-E-090707_A~WBPaper00032976:XX_WT-E-090707_B~WBPaper00032976:XX_WT-E-090707_C~WBPaper00032976:XX_SDC2Y93R-P-022208_A~WBPaper00032976:XX_SDC2Y93R-P-022208_B~WBPaper00032976:XX_SDC2Y93R-P-022208_C~WBPaper00032976:XX_WT-P-081407_A~WBPaper00032976:XX_WT-P-081407_B~WBPaper00032976:XX_WT-P-081407_C~WBPaper00032976:XX_DPY27-N-042807_A~WBPaper00032976:XX_DPY27-N-042807_B~WBPaper00032976:XX_DPY27-N-042807_C~WBPaper00032976:XX_WT-N-080307_A~WBPaper00032976:XX_WT-N-080307_B~WBPaper00032976:XX_WT-N-080307_C	Method: microarray|Species: Caenorhabditis elegans|Topic: dosage compensation by hypoactivation of X chromosome|Topic: sex-chromosome dosage compensation
76	19402892	WBPaper00033099.ce.mr.paper	GSE12298	GPL200	1	Distinct patterns of gene and protein expression elicited by organophosphorus pesticides in Caenorhabditis elegans.	BACKGROUND: The wide use of organophosphorus (OP) pesticides makes them an important public health concern. Persistent effects of exposure and the mechanism of neuronal degeneration are continuing issues in OP toxicology. To elucidate early steps in the mechanisms of OP toxicity, we studied alterations in global gene and protein expression in Caenorhabditis elegans exposed to OPs using microarrays and mass spectrometry. We tested two structurally distinct OPs (dichlorvos and fenamiphos) and employed a mechanistically different third neurotoxicant, mefloquine, as an out-group for analysis. Treatment levels used concentrations of chemical sufficient to prevent the development of 10%, 50% or 90% of mid-vulval L4 larvae into early gravid adults (EGA) at 24 h after exposure in a defined, bacteria-free medium. RESULTS: After 8 h of exposure, the expression of 87 genes responded specifically to OP treatment. The abundance of 34 proteins also changed in OP-exposed worms. Many of the genes and proteins affected by the OPs are expressed in neuronal and muscle tissues and are involved in lipid metabolism, cell adhesion, apoptosis/cell death, and detoxification. Twenty-two genes were differentially affected by the two OPs; a large proportion of these genes encode cytochrome P450s, UDP-glucuronosyl/UDP-glucosyltransferases, or P-glycoproteins. The abundance of transcripts and the proteins they encode were well correlated. CONCLUSION: Exposure to OPs elicits a pattern of changes in gene expression in exposed worms distinct from that of the unrelated neurotoxicant, mefloquine. The functional roles and the tissue location of the genes and proteins whose expression is modulated in response to exposure is consistent with the known effects of OPs, including damage to muscle due to persistent hypercontraction, neuronal cell death, and phase I and phase II detoxification. Further, the two different OPs evoked distinguishable changes in gene expression; about half the differences are in genes involved in detoxification, likely reflecting differences in the chemical structure of the two OPs. Changes in the expression of a number of sequences of unknown function were also discovered, and these molecules could provide insight into novel mechanisms of OP toxicity or adaptation in future studies.	36	17638	Lewis JA	Lewis JA, Szilagyi M, Gehman E, Dennis WE, Jackson DA	Distinct patterns of gene and protein expression elicited by organophosphorus pesticides in Caenorhabditis elegans.	BMC Genomics	2009	WBPaper00033099:mefloquine_control-rep1~WBPaper00033099:mefloquine_low_dose-rep1~WBPaper00033099:mefloquine_mid_dose-rep1~WBPaper00033099:mefloquine_high_dose-rep1~WBPaper00033099:mefloquine_control-rep2~WBPaper00033099:mefloquine_low_dose-rep2~WBPaper00033099:mefloquine_mid_dose-rep2~WBPaper00033099:mefloquine_high_dose-rep2~WBPaper00033099:mefloquine_control-rep3~WBPaper00033099:mefloquine_low_dose-rep3~WBPaper00033099:mefloquine_mid_dose-rep3~WBPaper00033099:mefloquine_high_dose-rep3~WBPaper00033099:dichlorvos_control-rep1~WBPaper00033099:dichlorvos_low_dose-rep1~WBPaper00033099:dichlorvos_mid_dose-rep1~WBPaper00033099:dichlorvos_high_dose-rep1~WBPaper00033099:dichlorvos_control-rep2~WBPaper00033099:dichlorvos_low_dose-rep2~WBPaper00033099:dichlorvos_mid_dose-rep2~WBPaper00033099:dichlorvos_high_dose-rep2~WBPaper00033099:dichlorvos_control-rep3~WBPaper00033099:dichlorvos_low_dose-rep3~WBPaper00033099:dichlorvos_mid_dose-rep3~WBPaper00033099:dichlorvos_high_dose-rep3~WBPaper00033099:fenamiphos_control-rep1~WBPaper00033099:fenamiphos_low_dose-rep1~WBPaper00033099:fenamiphos_mid_dose-rep1~WBPaper00033099:fenamiphos_high_dose-rep1~WBPaper00033099:fenamiphos_control-rep2~WBPaper00033099:fenamiphos_low_dose-rep2~WBPaper00033099:fenamiphos_mid_dose-rep2~WBPaper00033099:fenamiphos_high_dose-rep2~WBPaper00033099:fenamiphos_control-rep3~WBPaper00033099:fenamiphos_low_dose-rep3~WBPaper00033099:fenamiphos_mid_dose-rep3~WBPaper00033099:fenamiphos_high_dose-rep3	Method: microarray|Species: Caenorhabditis elegans
77	19533680	WBPaper00034636.ce.mr.paper	GSE10787	GPL200	1	Low-intensity microwave irradiation does not substantially alter gene expression in late larval and adult Caenorhabditis elegans.	Reports that low-intensity microwave radiation induces heat-shock reporter gene expression in the nematode, Caenorhabditis elegans, have recently been reinterpreted as a subtle thermal effect caused by slight heating. This study used a microwave exposure system (1.0 GHz, 0.5 W power input; SAR 0.9-3 mW kg(-1) for 6-well plates) that minimises temperature differentials between sham and exposed conditions (&lt; or =0.1 degrees C). Parallel measurement and simulation studies of SAR distribution within this exposure system are presented. We compared five Affymetrix gene arrays of pooled triplicate RNA populations from sham-exposed L4/adult worms against five gene arrays of pooled RNA from microwave-exposed worms (taken from the same source population in each run). No genes showed consistent expression changes across all five comparisons, and all expression changes appeared modest after normalisation (&lt; or =40% up- or down-regulated). The number of statistically significant differences in gene expression (846) was less than the false-positive rate expected by chance (1131). We conclude that the pattern of gene expression in L4/adult C. elegans is substantially unaffected by low-intensity microwave radiation; the minor changes observed in this study could well be false positives. As a positive control, we compared RNA samples from N2 worms subjected to a mild heat-shock treatment (30 degrees C) against controls at 26 degrees C (two gene arrays per condition). As expected, heat-shock genes are strongly up-regulated at 30 degrees C, particularly an hsp-70 family member (C12C8.1) and hsp-16.2. Under these heat-shock conditions, we confirmed that an hsp-16.2::GFP transgene was strongly up-regulated, whereas two non-heat-inducible transgenes (daf-16::GFP; cyp-34A9::GFP) showed little change in expression.	14	17638	Dawe AS	Dawe AS, Bodhicharla RK, Graham NS, May ST, Reader T, Loader B, Gregory A, Swicord M, Bit-Babik G, de Pomerai DI	Low-intensity microwave irradiation does not substantially alter gene expression in late larval and adult Caenorhabditis elegans.	Bioelectromagnetics	2009	WBPaper00034636:Sham__1_S1~WBPaper00034636:Microwave__2_E1~WBPaper00034636:Sham__3_S2~WBPaper00034636:Microwave__4_E2~WBPaper00034636:Sham__5_S3~WBPaper00034636:Microwave__6_E3~WBPaper00034636:Sham__7_S4~WBPaper00034636:Microwave__8_E4~WBPaper00034636:Sham__9_S5~WBPaper00034636:Microwave__10_E5~WBPaper00034636:heat_control__1~WBPaper00034636:heat_control__2~WBPaper00034636:mild_heat_shock__1~WBPaper00034636:mild_heat_shock__2	Method: microarray|Species: Caenorhabditis elegans
78	19544910	WBPaper00034661.ce.mr.paper	GSE14932	GPL200	1	Ecotoxicity of silver nanoparticles on the soil nematode Caenorhabditis elegans using functional ecotoxicogenomics.	In the present study, the ecotoxicity of silver nanoparticles (AgNPs) was investigated in Caenorhabditis elegans using survival, growth, and reproduction, as the ecotoxicological endpoints, as well as stress response gene expression. Whole genome microarray was used to screen global changes in C. elegans transcription profiles after AgNPs exposure, followed by quantitative analysis of selected genes. The integration of gene expression with organism and population level endpoints was investigated using C. elegans functional genomics tools, to test the ecotoxicological relevance of AgNPs-induced gene expression. AgNPs exerted considerable toxicity in C. elegans, most clearly as dramatically decreased reproduction potential. Increased expression of the superoxide dismutases-3 (sod-3) and abnormal dauer formation protein (daf-12) genes with 0.1 and 0.5 mg/L of AgNPs exposures occurred concurrently with significant decreases in reproduction ability. Overall results of functional genomic studies using mutant analyses suggested that the sod-3 and daf-12 gene expressions may have been related to the AgNPs-induced reproductive failure in C. elegans and that oxidative stress may have been an important mechanism in AgNPs toxicity.	2	17638	Roh JY	Roh JY, Sim SJ, Yi J, Park K, Chung KH, Ryu DY, Choi J	Ecotoxicity of silver nanoparticles on the soil nematode Caenorhabditis elegans using functional ecotoxicogenomics.	Environ Sci Technol	2009	WBPaper00034661:24hr_AgNPs_exposure~WBPaper00034661:no_exposure	Method: microarray|Species: Caenorhabditis elegans|Topic: stress response to metal ion
79	19627265	WBPaper00034757.ce.mr.paper	GSE9301	GPL200	1	Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1.	Oxidative stress has been hypothesized to play a role in normal aging. The response to oxidative stress is regulated by the SKN-1 transcription factor, which also is necessary for intestinal development in Caenorhabditis elegans. Almost a thousand genes including the antioxidant and heat-shock responses, as well as genes responsible for xenobiotic detoxification were induced by the oxidative stress which was found using transcriptome analysis. There were also 392 down-regulated genes including many involved in metabolic homeostasis, organismal development, and reproduction. Many of these oxidative stress-induced transcriptional changes are dependent on SKN-1 action; the induction of the heat-shock response is not. When RNAi to inhibit genes was used, most had no effect on either resistance to oxidative stress or longevity; however two SKN-1-dependent genes, nlp-7 and cup-4, that were up-regulated by oxidative stress were found to be required for resistance to oxidative stress and for normal lifespan. nlp-7 encodes a neuropeptide-like protein, expressed in neurons, while cup-4 encodes a coelomocyte-specific, ligand-gated ion channel. RNAi of nlp-7 or cup-4 increased sensitivity to oxidative stress and reduced lifespan. Among down-regulated genes, only inhibition of ent-1, a nucleoside transporter, led to increased resistance to oxidative stress; inhibition had no effect on lifespan. In contrast, RNAi of nhx-2, a Na(+)/H(+) exchanger, extended lifespan significantly without affecting sensitivity to oxidative stress. These findings showed that a transcriptional shift from growth and maintenance towards the activation of cellular defense mechanisms was caused by the oxidative stress; many of these transcriptional alterations are SKN-1 dependent.	11	17638	Park SK	Park SK, Tedesco PM, Johnson TE	Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1.	Aging Cell	2009	WBPaper00034757:control_no_stress_1~WBPaper00034757:control_no_stress_2~WBPaper00034757:control_no_stress_3~WBPaper00034757:control_no_stress_4~WBPaper00034757:oxidative_stress_1~WBPaper00034757:oxidative_stress_2~WBPaper00034757:oxidative_stress_3~WBPaper00034757:oxidative_stress_4~WBPaper00034757:skn-1_RNAi_oxidative_stress_1~WBPaper00034757:skn-1_RNAi_oxidative_stress_2~WBPaper00034757:skn-1_RNAi_oxidative_stress_3	Method: microarray|Species: Caenorhabditis elegans
80	19632181	WBPaper00034761.ce.mr.paper	GSE15762	GPL200	1	A multiparameter network reveals extensive divergence between C. elegans bHLH transcription factors.	Differences in expression, protein interactions, and DNA binding of paralogous transcription factors ("TF parameters") are thought to be important determinants of regulatory and biological specificity. However, both the extent of TF divergence and the relative contribution of individual TF parameters remain undetermined. We comprehensively identify dimerization partners, spatiotemporal expression patterns, and DNA-binding specificities for the C. elegans bHLH family of TFs, and model these data into an integrated network. This network displays both specificity and promiscuity, as some bHLH proteins, DNA sequences, and tissues are highly connected, whereas others are not. By comparing all bHLH TFs, we find extensive divergence and that all three parameters contribute equally to bHLH divergence. Our approach provides a framework for examining divergence for other protein families in C. elegans and in other complex multicellular organisms, including humans. Cross-species comparisons of integrated networks may provide further insights into molecular features underlying protein family evolution. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.	6	17638	Grove CA	Grove CA, De Masi F, Barrasa MI, Newburger DE, Alkema MJ, Bulyk ML, Walhout AJ	A multiparameter network reveals extensive divergence between C. elegans bHLH transcription factors.	Cell	2009	WBPaper00034761:N2_1~WBPaper00034761:N2_2~WBPaper00034761:N2_3~WBPaper00034761:hlh-30(tm1978)_1~WBPaper00034761:hlh-30(tm1978)_2~WBPaper00034761:hlh-30(tm1978)_3	Method: microarray|Species: Caenorhabditis elegans
81	19755517	WBPaper00035197.ce.mr.paper	GSE16753	GPL200	1	C. elegans dysferlin homolog fer-1 is expressed in muscle, and fer-1 mutations initiate altered gene expression of muscle enriched genes.	Mutations in the human dysferlin gene cause Limb Girdle Muscular Dystrophy 2B (LGMD2B). The Caenorhabditis elegans dysferlin homolog, fer-1, affects sperms development but is not known to be expressed in or have a functional roles outside of the male germline. Using several approaches, we show that fer-1 mRNA is present in C. elegans muscle cells but is absent from neurons. In mammals, loss of muscle-expressed dysferlin causes transcriptional deregulation of muscle expressed genes. To determine if similar alterations in gene expression are initiated in C. elegans due to loss of muscle-expressed fer-1, we performed whole genome Affymetrix microarray analysis of two loss-of-function fer-1 mutants. Both mutants gave rise to highly similar changes in gene expression and altered the expression of 337 genes. Using multiple analysis methods, we show that this gene set is enriched for genes known to regulate the structure and function of muscle. However, these transcriptional changes do not appear to be in response to gross sarcomeric damage, since genetically sensitized fer-1 mutants exhibit normal thin filament organization. Our data suggest that processes other than sarcomere stability may be affected by loss of fer-1 in C. elegans muscle. Therefore, C. elegans may be an attractive model system in which to explore new muscle-specific functions of the dysferlin protein and gain insights into the molecular pathogenesis of LGMD2B.	12	17638	Krajacic P	Krajacic P, Hermanowski J, Lozynska O, Khurana TS, Lamitina T	C. elegans dysferlin homolog fer-1 is expressed in muscle, and fer-1 mutations initiate altered gene expression of muscle enriched genes.	Physiol Genomics	2009	WBPaper00035197:N2_3~WBPaper00035197:N2_4~WBPaper00035197:N2_5~WBPaper00035197:N2_6~WBPaper00035197:fer-1(hc1ts)_1~WBPaper00035197:fer-1(hc1ts)_2~WBPaper00035197:fer-1(hc1ts)_5~WBPaper00035197:fer-1(hc1ts)_6~WBPaper00035197:fer-1(hc24ts)_1~WBPaper00035197:fer-1(hc24ts)_2~WBPaper00035197:fer-1(hc24ts)_3~WBPaper00035197:fer-1(hc24ts)_4	Method: microarray|Species: Caenorhabditis elegans|Topic: gene expression|Topic: somatic muscle development
82	19776148	WBPaper00035227.ce.mr.paper	GSE16915	GPL200	1	Bio-electrospraying the nematode Caenorhabditis elegans: studying whole-genome transcriptional responses and key life cycle parameters.	Bio-electrospray, the direct jet-based cell handling approach, is able to handle a wide range of cells (spanning immortalized, primary to stem cells). Studies at the genomic, genetic and the physiological levels have shown that, post-treatment, cellular integrity is unperturbed and a high percentage (more than 70%, compared with control) of cells remain viable. Although, these results are impressive, it may be argued that cell-based systems are oversimplistic. Therefore, it is important to evaluate the bio-electrospray technology using sensitive and dynamically developing multi-cellular organisms that share, at least some, similarities with multi-cell microenvironments encountered with tissues and organs. This study addressed this issue by using a well-characterized model organism, the non-parasitic nematode Caenorhabditis elegans. Nematode cultures were subjected to bio-electrospraying and compared with positive (heat shock) and negative controls (appropriate laboratory culture controls). Overall, bio-electrospraying did not modulate the reproductive output or induce significant changes in in vivo stress-responsive biomarkers (heat shock proteins). Likewise, whole-genome transcriptomics could not identify any biological processes, cellular components or molecular functions (gene ontology terms) that were significantly enriched in response to bio-electrospraying. This demonstrates that bio-electrosprays can be safely applied directly to nematodes and underlines its potential future use in the creation of multi-cellular environments within clinical applications.	3	17638	Mongkoldhumrongkul N	Mongkoldhumrongkul N, Swain SC, Jayasinghe SN, Sturzenbaum S	Bio-electrospraying the nematode Caenorhabditis elegans: studying whole-genome transcriptional responses and key life cycle parameters.	J R Soc Interface	2010	WBPaper00035227:control_exposure~WBPaper00035227:bio-electrospray~WBPaper00035227:heat_shock_exposure	Method: microarray|Species: Caenorhabditis elegans
83	19879883	WBPaper00035429.ce.mr.paper	GSE15159	GPL200	1	Nucleotide excision repair genes are expressed at low levels and are not detectably inducible in Caenorhabditis elegans somatic tissues, but their function is required for normal adult life after UVC exposure.	We performed experiments to characterize the inducibility of nucleotide excision repair (NER) in Caenorhabditis elegans, and to examine global gene expression in NER-deficient and -proficient strains as well as germline vs. somatic tissues, with and without genotoxic stress. We also carried out experiments to elucidate the importance of NER in the adult life of C. elegans under genotoxin-stressed and control conditions. Adult lifespan was not detectably different between wild-type and NER-deficient xpa-1 nematodes under control conditions. However, exposure to 6J/m(2)/day of ultraviolet C radiation (UVC) decreased lifespan in xpa-1 nematodes more than a dose of 100 J/m(2)/day in wild-type. Similar differential sensitivities were observed for adult size and feeding. Remarkably, global gene expression was nearly identical in young adult wild-type and xpa-1 nematodes, both in control conditions and 3h after exposure to 50 J/m(2) UVC. Neither NER genes nor repair activity were detectably inducible in young adults that lacked germ cells and developing embryos (glp-1 strain). However, expression levels of dozens of NER and other DNA damage response genes were much (5-30-fold) lower in adults lacking germ cells and developing embryos, suggesting that somatic and post-mitotic cells have a much lower DNA repair ability. Finally, we describe a refinement of our DNA damage assay that allows damage measurement in single nematodes.	24	17637	Boyd WA	Boyd WA, Crocker TL, Rodriguez AM, Leung MC, Lehmann DW, Freedman JH, Van Houten B, Meyer JN	Nucleotide excision repair genes are expressed at low levels and are not detectably inducible in Caenorhabditis elegans somatic tissues, but their function is required for normal adult life after UVC exposure.	Mutat Res	2010	WBPaper00035429:glp-1_UV_2008_rep1~WBPaper00035429:glp-1_UV_2008_rep2~WBPaper00035429:N2_control_2007_rep2~WBPaper00035429:N2_control_2007_rep1~WBPaper00035429:N2_UV_2007_rep2~WBPaper00035429:N2_UV_2007_rep1~WBPaper00035429:glp-1_control_2007_rep1~WBPaper00035429:glp-1_control_2007_rep2~WBPaper00035429:glp-1_UV_2007_rep1~WBPaper00035429:glp-1_UV_2007_rep2~WBPaper00035429:xpa-1_control_2007_rep1~WBPaper00035429:xpa-1_control_2007_rep2~WBPaper00035429:xpa-1_UV_2007_rep2~WBPaper00035429:xpa-1_UV_2007_rep1~WBPaper00035429:xpa-1_control_2008_rep1~WBPaper00035429:xpa-1_control_2008_rep2~WBPaper00035429:xpa-1_UV_2008_rep1~WBPaper00035429:xpa-1_UV_2008_rep2~WBPaper00035429:N2_control_2008_rep1~WBPaper00035429:N2_control_2008_rep2~WBPaper00035429:N2_UV_2008_rep2~WBPaper00035429:N2_UV_2008_rep1~WBPaper00035429:glp-1_control_2008_rep1~WBPaper00035429:glp-1_control_2008_rep2	Method: microarray|Species: Caenorhabditis elegans
84	20062054	WBPaper00035588.ce.mr.paper	GSE19138	GPL200	1	Comprehensive discovery of endogenous Argonaute binding sites in Caenorhabditis elegans.	MicroRNAs (miRNAs) regulate gene expression by guiding Argonaute proteins to specific target mRNA sequences. Identification of bona fide miRNA target sites in animals is challenging because of uncertainties regarding the base-pairing requirements between miRNA and target as well as the location of functional binding sites within mRNAs. Here we present the results of a comprehensive strategy aimed at isolating endogenous mRNA target sequences bound by the Argonaute protein ALG-1 in C. elegans. Using cross-linking and ALG-1 immunoprecipitation coupled with high-throughput sequencing (CLIP-seq), we identified extensive ALG-1 interactions with specific 3' untranslated region (UTR) and coding exon sequences and discovered features that distinguish miRNA complex binding sites in 3' UTRs from those in other genic regions. Furthermore, our analyses revealed a striking enrichment of Argonaute binding sites in genes important for miRNA function, suggesting an autoregulatory role that may confer robustness to the miRNA pathway.	6	17638	Zisoulis DG	Zisoulis DG, Lovci MT, Wilbert ML, Hutt KR, Liang TY, Pasquinelli AE, Yeo GW	Comprehensive discovery of endogenous Argonaute binding sites in Caenorhabditis elegans.	Nat Struct Mol Biol	2010	WBPaper00035588:ALG-1(-)_1~WBPaper00035588:ALG-1(-)_2~WBPaper00035588:ALG-1(-)_3~WBPaper00035588:WT_1~WBPaper00035588:WT_2~WBPaper00035588:WT_3	Method: microarray|Species: Caenorhabditis elegans
85	20126308	WBPaper00035873.ce.mr.paper	GSE19310	GPL200	1	Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans.	The soil-dwelling nematode C. elegans is a powerful system for comparative molecular analyses of environmental stress response mechanisms. Infection of worms with bacterial and fungal pathogens causes the activation of well-characterized innate immune transcriptional programs in pathogen-exposed hypodermal and intestinal tissues. However, the pathophysiological events that drive such transcriptional responses are not understood. Here, we show that infection-activated transcriptional responses are, in large part, recapitulated by either physiological or genetic activation of the osmotic stress response. Microarray profiling of wild type worms exposed to non-lethal hypertonicity identified a suite of genes that were also regulated by infection. Expression profiles of five different osmotic stress resistant (osr) mutants under isotonic conditions reiterated the wild type transcriptional response to osmotic stress and also showed substantial similarity to infection-induced gene expression under isotonic conditions. Computational, transgenic, and functional approaches revealed that two GATA transcription factors previously implicated in infection-induced transcriptional responses, elt-2 and elt-3, are also essential for coordinated tissue-specific activation of osmosensitive gene expression and promote survival under osmotically stressful conditions. Together, our data suggest infection and osmotic adaptation share previously unappreciated transcriptional similarities which might be controlled via regulation of tissue-specific GATA transcription factors.	30	17638	Rohlfing AK	Rohlfing AK, Miteva Y, Hannenhalli S, Lamitina T	Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans.	PLoS One	2010	WBPaper00035873:N2_isotonic_1~WBPaper00035873:N2_isotonic_2~WBPaper00035873:N2_isotonic_3~WBPaper00035873:15min_N2_hypertonic_1~WBPaper00035873:15min_N2_hypertonic_2~WBPaper00035873:15min_N2_hypertonic_3~WBPaper00035873:1hr_N2_hypertonic_1~WBPaper00035873:1hr_N2_hypertonic_2~WBPaper00035873:1hr_N2_hypertonic_3~WBPaper00035873:6hr_N2_hypertonic_1~WBPaper00035873:6hr_N2_hypertonic_2~WBPaper00035873:6hr_N2_hypertonic_3~WBPaper00035873:96hr_N2_hypertonic_1~WBPaper00035873:96hr_N2_hypertonic_2~WBPaper00035873:96hr_N2_hypertonic_3~WBPaper00035873:osm-7_isotonic_1~WBPaper00035873:osm-7_isotonic_2~WBPaper00035873:osm-7_isotonic_3~WBPaper00035873:osm-8_isotonic_1~WBPaper00035873:osm-8_isotonic_2~WBPaper00035873:osm-8_isotonic_3~WBPaper00035873:osm-11_isotonic_1~WBPaper00035873:osm-11_isotonic_2~WBPaper00035873:osm-11_isotonic_3~WBPaper00035873:dpy-9_isotonic_1~WBPaper00035873:dpy-9_isotonic_2~WBPaper00035873:dpy-9_isotonic_3~WBPaper00035873:dpy-10_isotonic_1~WBPaper00035873:dpy-10_isotonic_2~WBPaper00035873:dpy-10_isotonic_3	Method: microarray|Species: Caenorhabditis elegans
86	20133860	WBPaper00035891.ce.mr.paper	GSE50513	GPL200	1	bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans.	Very little is known about how animals discriminate pathogens from innocuous microbes. To address this question, we examined infection-response gene induction in the nematode Caenorhabditis elegans. We focused on genes that are induced in C. elegans by infection with the bacterial pathogen Pseudomonas aeruginosa, but are not induced by an isogenic attenuated gacA mutant. Most of these genes are induced independently of known immunity pathways. We generated a GFP reporter for one of these genes, infection response gene 1 (irg-1), which is induced strongly by wild-type P. aeruginosa strain PA14, but not by other C. elegans pathogens or by other wild-type P. aeruginosa strains that are weakly pathogenic to C. elegans. To identify components of the pathway that induces irg-1 in response to infection, we performed an RNA interference screen of C. elegans transcription factors. This screen identified zip-2, a bZIP transcription factor that is required for inducing irg-1, as well as several other genes, and is important for defense against infection by P. aeruginosa. These data indicate that zip-2 is part of a specialized pathogen response pathway that is induced by virulent strains of P. aeruginosa and provides defense against this pathogen.	12	17638	Estes KA	Estes KA, Dunbar TL, Powell JR, Ausubel FM, Troemel ER	bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans.	Proc Natl Acad Sci U S A	2010	WBPaper00035891:control_OP50_rep1~WBPaper00035891:control_PA14_rep1~WBPaper00035891:zip-2(RNAi)_OP50_rep1~WBPaper00035891:zip-2(RNAi)_PA14_rep1~WBPaper00035891:control_OP50_rep2~WBPaper00035891:control_PA14_rep2~WBPaper00035891:zip-2(RNAi)_OP50_rep2~WBPaper00035891:zip-2(RNAi)_PA14_rep2~WBPaper00035891:control_OP50_rep3~WBPaper00035891:control_PA14_rep3~WBPaper00035891:zip-2(RNAi)_OP50_rep3~WBPaper00035891:zip-2(RNAi)_PA14_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response
87	20133945	WBPaper00035892.ce.mr.paper	GSE20053	GPL200	1	A conserved PMK-1/p38 MAPK is required in caenorhabditis elegans tissue-specific immune response to Yersinia pestis infection.	Yersinia pestis has acquired a variety of complex strategies that enable the bacterium to overcome defenses in different hosts and ensure its survival and successful transmission. A full-genome microarray analysis on Caenorhabditis elegans infected with Y. pestis shows enrichment in genes that are markers of innate immune responses and regulated by a conserved PMK-1/p38 MAPK. Consistent with a role in regulating expression of immune effectors, inhibition of PMK-1/p38 by mutation or RNA interference enhances susceptibility to Y. pestis. Further studies of mosaic animals where PMK-1/p38 is exclusively inhibited or overexpressed in a tissue-specific manner indicate that PMK-1/p38 controls expression of a CUB-like family of immune genes at the cell-autonomous level. Given the conserved nature of PMK-1/p38 MAPK-mediated signaling and innate immune responses, PMK-1/p38 MAPK may play a role in the immune response against Y. pestis in natural hosts.	6	17638	Bolz DD	Bolz DD, Tenor JL, Aballay A	A conserved PMK-1/p38 MAPK is required in caenorhabditis elegans tissue-specific immune response to Yersinia pestis infection.	J Biol Chem	2010	WBPaper00035892:N2_KIM5_24h_A~WBPaper00035892:N2_KIM5_24h_B~WBPaper00035892:N2_KIM5_24h_C~WBPaper00035892:N2_OP50_24h_A~WBPaper00035892:N2_OP50_24h_B~WBPaper00035892:N2_OP50_24h_C	Method: microarray|Species: Caenorhabditis elegans
88	20142496	WBPaper00035905.ce.mr.paper	GSE19922	GPL200	1	Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator.	Stem cells are essential for tissue generation during the development of multicellular creatures, and for tissue homeostasis in adults. The great therapeutic promise of stem cells makes understanding their regulation a high priority. PUF RNA-binding proteins have a conserved role in promoting self-renewal of germline stem cells. Here we use a genome-wide approach to identify putative target mRNAs for the Caenorhabditis elegans PUF protein known as FBF. We find that putative FBF targets represent approximately 7% of all protein-coding genes in C. elegans, implicating FBF as a broad-spectrum gene regulator. These putative FBF targets are enriched for regulators of meiotic entry and other components of the meiotic program as well as regulators of key developmental pathways. We suggest that these targets may be critical for FBF's role in stem cell maintenance. Comparison of likely FBF target mRNAs with putative PUF target mRNAs from Drosophila and humans reveals 40 shared targets, including several established stem cell regulators. We speculate that shared PUF targets represent part of a broadly used module of stem cell control.	8	17638	Kershner AM	Kershner AM, Kimble J	Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator.	Proc Natl Acad Sci U S A	2010	WBPaper00035905:FBF-1_GFP_mRNA_IP_1~WBPaper00035905:tubulin_GFP_mRNA_IP_1~WBPaper00035905:FBF-1_GFP_mRNA_IP_2~WBPaper00035905:tubulin_GFP_mRNA_IP_2~WBPaper00035905:FBF-1_GFP_mRNA_IP_3~WBPaper00035905:tubulin_GFP_mRNA_IP_3~WBPaper00035905:FBF-1_GFP_mRNA_IP_4~WBPaper00035905:tubulin_GFP_mRNA_IP_4	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
89	20176573	WBPaper00035973.ce.mr.paper	GSE16050	GPL200	1	The microRNA miR-124 controls gene expression in the sensory nervous system of Caenorhabditis elegans.	miR-124 is a highly conserved microRNA (miRNA) whose in vivo function is poorly understood. Here, we identify miR-124 targets based on the analysis of the first mir-124 mutant in any organism. We find that miR-124 is expressed in many sensory neurons in Caenorhabditis elegans and onset of expression coincides with neuronal morphogenesis. We analyzed the transcriptome of miR-124 expressing and nonexpressing cells from wild-type and mir-124 mutants. We observe that many targets are co-expressed with and actively repressed by miR-124. These targets are expressed at reduced relative levels in sensory neurons compared to the rest of the animal. Our data from mir-124 mutant animals show that this effect is due to a large extent to the activity of miR-124. Genes with nonconserved target sites show reduced absolute expression levels in sensory neurons. In contrast, absolute expression levels of genes with conserved sites are comparable to control genes, suggesting a tuning function for many of these targets. We conclude that miR-124 contributes to defining cell-type-specific gene activity by repressing a diverse set of co-expressed genes.	12	17638	Clark AM	Clark AM, Goldstein LD, Tevlin M, Tavare S, Shaham S, Miska EA	The microRNA miR-124 controls gene expression in the sensory nervous system of Caenorhabditis elegans.	Nucleic Acids Res	2010	WBPaper00035973:MT_GFPp_rep1~WBPaper00035973:MT_GFPm_rep1~WBPaper00035973:WT_GFPp_rep1~WBPaper00035973:WT_GFPm_rep1~WBPaper00035973:MT_GFPp_rep2~WBPaper00035973:MT_GFPm_rep2~WBPaper00035973:WT_GFPp_rep2~WBPaper00035973:WT_GFPm_rep2~WBPaper00035973:MT_GFPp_rep3~WBPaper00035973:MT_GFPm_rep3~WBPaper00035973:WT_GFPp_rep3~WBPaper00035973:WT_GFPm_rep3	Method: microarray|Species: Caenorhabditis elegans
90	20368426	WBPaper00036090.ce.mr.paper	GSE18132,GSE18131,GSE18130	GPL200	1	Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity.	Nutrient-driven O-GlcNAcylation of key components of the transcription machinery may epigenetically modulate gene expression in metazoans. The global effects of GlcNAcylation on transcription can be addressed directly in C. elegans because knockouts of the O-GlcNAc cycling enzymes are viable and fertile. Using anti-O-GlcNAc ChIP-on-chip whole-genome tiling arrays on wild-type and mutant strains, we detected over 800 promoters where O-GlcNAc cycling occurs, including microRNA loci and multigene operons. Intriguingly, O-GlcNAc-marked promoters are biased toward genes associated with PIP3 signaling, hexosamine biosynthesis, and lipid/carbohydrate metabolism. These marked genes are linked to insulin-like signaling, metabolism, aging, stress, and pathogen-response pathways in C. elegans. Whole-genome transcriptional profiling of the O-GlcNAc cycling mutants confirmed dramatic deregulation of genes in these key pathways. As predicted, the O-GlcNAc cycling mutants show altered lifespan and UV stress susceptibility phenotypes. We propose that O-GlcNAc cycling at promoters participates in a molecular program impacting nutrient-responsive pathways in C. elegans, including stress, pathogen response, and adult lifespan. The observed impact of O-GlcNAc cycling on both signaling and transcription in C. elegans has important implications for human diseases of aging, including diabetes and neurodegeneration.	18	17638	Love DC	Love DC, Ghosh S, Mondoux MA, Fukushige T, Wang P, Wilson MA, Iser WB, Wolkow CA, Krause MW, Hanover JA	Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity.	Proc Natl Acad Sci U S A	2010	WBPaper00036090:WT_Starved_L1_bio_rep1~WBPaper00036090:WT_Starved_L1_bio_rep2~WBPaper00036090:WT_Starved_L1_bio_rep3~WBPaper00036090:Ogt_starved_L1_bio_rep1~WBPaper00036090:Ogt_starved_L1_bio_rep2~WBPaper00036090:Ogt_starved_L1_bio_rep3~WBPaper00036090:Oga_starved_L1_bio_rep1~WBPaper00036090:Oga_starved_L1_bio_rep2~WBPaper00036090:Oga_starved_L1_bio_rep3~WBPaper00036090:WT_Fed_L4_bio_rep1~WBPaper00036090:WT_Fed_L4_bio_rep2~WBPaper00036090:WT_Fed_L4_bio_rep3~WBPaper00036090:Ogt_Fed_L4_bio_rep1~WBPaper00036090:Ogt_Fed_L4_bio_rep2~WBPaper00036090:Ogt_Fed_L4_bio_rep3~WBPaper00036090:Oga_Fed_L4_bio_rep1~WBPaper00036090:Oga_Fed_L4_bio_rep2~WBPaper00036090:Oga_Fed_L4_bio_rep3	Method: microarray|Species: Caenorhabditis elegans
91	20382984	WBPaper00036135.ce.mr.paper	GSE16405	GPL200	1	A two-tiered compensatory response to loss of DNA repair modulates aging and stress response pathways.	Activation of oxidative stress-responses and downregulation of insulin-like signaling (ILS) is seen in Nucleotide Excision Repair (NER) deficient segmental progeroid mice. Evidence suggests that this is a survival response to persistent transcription-blocking DNA damage, although the relevant lesions have not been identified. Here we show that loss of NTH-1, the only Base Excision Repair (BER) enzyme known to initiate repair of oxidative DNA damage inC. elegans, restores normal lifespan of the short-lived NER deficient xpa-1 mutant. Loss of NTH-1 leads to oxidative stress and global expression profile changes that involve upregulation of genes responding to endogenous stress and downregulation of ILS. A similar, but more extensive, transcriptomic shift is observed in the xpa-1 mutant whereas loss of both NTH-1 and XPA-1 elicits a different profile with downregulation of Aurora-B and Polo-like kinase 1 signaling networks as well as DNA repair and DNA damage response genes. The restoration of normal lifespan and absence oxidative stress responses in nth-1;xpa-1 indicate that BER contributes to generate transcription blocking lesions from oxidative DNA damage. Hence, our data strongly suggests that the DNA lesions relevant for aging are repair intermediates resulting from aberrant or attempted processing by BER of lesions normally repaired by NER.	9	17638	Fensgard O	Fensgard O, Kassahun H, Bombik I, Rognes T, Lindvall JM, Nilsen H	A two-tiered compensatory response to loss of DNA repair modulates aging and stress response pathways.	Aging (Albany NY)	2010	WBPaper00036135:nth-1__1~WBPaper00036135:nth-1__2~WBPaper00036135:nth-1__3~WBPaper00036135:nth-1_xpa-1__1~WBPaper00036135:nth-1_xpa-1__2~WBPaper00036135:xpa-1__1~WBPaper00036135:xpa-1__2~WBPaper00036135:N2__1~WBPaper00036135:N2__2	Method: microarray|Species: Caenorhabditis elegans
92	20493785	WBPaper00036291.ce.mr.paper	GSE21467	GPL200	1	Loss of Caenorhabditis elegans UNG-1 uracil-DNA glycosylase affects apoptosis in response to DNA damaging agents.	The nematode Caenorhabditis elegans has been used extensively to study responses to DNA damage. In contrast, little is known about DNA repair in this organism. C. elegans is unusual in that it encodes few DNA glycosylases and the uracil-DNA glycosylase (UDG) encoded by the ung-1 gene is the only known UDG. C. elegans could therefore become a valuable model organism for studies of the genetic interaction networks involving base excision repair (BER). As a first step towards characterization of BER in C. elegans, we show that the UNG-1 protein is an active uracil-DNA glycosylase. We demonstrate that an ung-1 mutant has reduced ability to repair uracil-containing DNA but that an alternative Ugi-inhibited activity is present in ung-1 nuclear extracts. Finally, we demonstrate that ung-1 mutants show altered levels of apoptotic cell corpses formed in response to DNA damaging agents. Increased apoptosis in the ung-1 mutant in response to ionizing radiation (IR) suggests that UNG-1 contributes to repair of IR-induced DNA base damage in vivo. Following treatment with paraquat however, the apoptotic corpse-formation was reduced. Gene expression profiling suggests that this phenotype is a consequence of compensatory transcriptomic shifts that modulate oxidative stress responses in the mutant and not an effect of reduced DNA damage signaling.	6	17638	Skjeldam HK	Skjeldam HK, Kassahun H, Fensgard O, SenGupta T, Babaie E, Lindvall JM, Arczewska K, Nilsen H	Loss of Caenorhabditis elegans UNG-1 uracil-DNA glycosylase affects apoptosis in response to DNA damaging agents.	DNA Repair (Amst)	2010	WBPaper00036291:ung-1_bio_rep1~WBPaper00036291:ung-1_bio_rep2~WBPaper00036291:ung-1_bio_rep3~WBPaper00036291:N2_bio_rep1~WBPaper00036291:N2_bio_rep2~WBPaper00036291:N2_bio_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: programmed cell death|Topic: apoptotic DNA fragmentation|Topic: apoptotic process|Topic: engulfment of apoptotic cell
93	20537990	WBPaper00036375.ce.mr.paper	GSE21162	GPL200	1	Time-lapse imaging and cell-specific expression profiling reveal dynamic branching and molecular determinants of a multi-dendritic nociceptor in C. elegans.	Nociceptive neurons innervate the skin with complex dendritic arbors that respond to pain-evoking stimuli such as harsh mechanical force or extreme temperatures. Here we describe the structure and development of a model nociceptor, the PVD neuron of C. elegans, and identify transcription factors that control morphogenesis of the PVD dendritic arbor. The two PVD neuron cell bodies occupy positions on either the right (PVDR) or left (PVDL) sides of the animal in posterior-lateral locations. Imaging with a GFP reporter revealed a single axon projecting from the PVD soma to the ventral cord and an elaborate, highly branched arbor of dendritic processes that envelop the animal with a web-like array directly beneath the skin. Dendritic branches emerge in a step-wise fashion during larval development and may use an existing network of peripheral nerve cords as guideposts for key branching decisions. Time-lapse imaging revealed that branching is highly dynamic with active extension and withdrawal and that PVD branch overlap is prevented by a contact-dependent self-avoidance, a mechanism that is also employed by sensory neurons in other organisms. With the goal of identifying genes that regulate dendritic morphogenesis, we used the mRNA-tagging method to produce a gene expression profile of PVD during late larval development. This microarray experiment identified&gt;2,000 genes that are 1.5X elevated relative to all larval cells. The enriched transcripts encode a wide range of proteins with potential roles in PVD function (e.g., DEG/ENaC and Trp channels) or development (e.g., UNC-5 and LIN-17/frizzled receptors). We used RNAi and genetic tests to screen 86 transcription factors from this list and identified eleven genes that specify PVD dendritic structure. These transcription factors appear to control discrete steps in PVD morphogenesis and may either promote or limit PVD branching at specific developmental stages. For example, time-lapse imaging revealed that MEC-3 (LIM homeodomain) is required for branch initiation in early larval development whereas EGL-44 (TEAD domain) prevents ectopic PVD branching in the adult. A comparison of PVD-enriched transcripts to a microarray profile of mammalian nociceptors revealed homologous genes with potentially shared nociceptive functions. We conclude that PVD neurons display striking structural, functional and molecular similarities to nociceptive neurons from more complex organisms and can thus provide a useful model system in which to identify evolutionarily conserved determinants of nociceptor fate.	6	17638	Smith CJ	Smith CJ, Watson JD, Spencer WC, O'Brien T, Cha B, Albeg A, Treinin M, Miller DM	Time-lapse imaging and cell-specific expression profiling reveal dynamic branching and molecular determinants of a multi-dendritic nociceptor in C. elegans.	Dev Biol	2010	WBPaper00036375:PVD_OLL_rep1~WBPaper00036375:PVD_OLL_rep2~WBPaper00036375:PVD_OLL_rep3~WBPaper00036375:L3_L4_whole_animal_ref_rep1~WBPaper00036375:L3_L4_whole_animal_ref_rep2~WBPaper00036375:L3_L4_whole_animal_ref_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: cell fate specification|Topic: cell differentiation
94	20555324	WBPaper00036383.ce.mr.paper	GSE30505	GPL200	1	Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans.	The plasticity of ageing suggests that longevity may be controlled epigenetically by specific alterations in chromatin state. The link between chromatin and ageing has mostly focused on histone deacetylation by the Sir2 family, but less is known about the role of other histone modifications in longevity. Histone methylation has a crucial role in development and in maintaining stem cell pluripotency in mammals. Regulators of histone methylation have been associated with ageing in worms and flies, but characterization of their role and mechanism of action has been limited. Here we identify the ASH-2 trithorax complex, which trimethylates histone H3 at lysine 4 (H3K4), as a regulator of lifespan in Caenorhabditis elegans in a directed RNA interference (RNAi) screen in fertile worms. Deficiencies in members of the ASH-2 complex-ASH-2 itself, WDR-5 and the H3K4 methyltransferase SET-2-extend worm lifespan. Conversely, the H3K4 demethylase RBR-2 is required for normal lifespan, consistent with the idea that an excess of H3K4 trimethylation-a mark associated with active chromatin-is detrimental for longevity. Lifespan extension induced by ASH-2 complex deficiency requires the presence of an intact adult germline and the continuous production of mature eggs. ASH-2 and RBR-2 act in the germline, at least in part, to regulate lifespan and to control a set of genes involved in lifespan determination. These results indicate that the longevity of the soma is regulated by an H3K4 methyltransferase/demethylase complex acting in the C. elegans germline.	23	17637	Greer EL	Greer EL, Maures TJ, Hauswirth AG, Green EM, Leeman DS, Maro GS, Han S, Banko MR, Gozani O, Brunet A	Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans.	Nature	2010	WBPaper00036383:L3_N2_EV_rep1~WBPaper00036383:L3_N2_EV_rep2~WBPaper00036383:L3_N2_EV_rep3~WBPaper00036383:L3_N2_ash-2(RNAi)_rep1~WBPaper00036383:L3_N2_ash-2(RNAi)_rep2~WBPaper00036383:L3_N2_ash-2(RNAi)_rep3~WBPaper00036383:L3_glp-1_EV_rep1~WBPaper00036383:L3_glp-1_EV_rep2~WBPaper00036383:L3_glp-1_EV_rep3~WBPaper00036383:L3_glp-1_ash-2(RNAi)_rep1~WBPaper00036383:L3_glp-1_ash-2(RNAi)_rep2~WBPaper00036383:L3_glp-1_ash-2(RNAi)_rep3~WBPaper00036383:Day8_N2_EV_rep1~WBPaper00036383:Day8_N2_EV_rep2~WBPaper00036383:Day8_N2_ash-2(RNAi)_rep1~WBPaper00036383:Day8_N2_ash-2(RNAi)_rep2~WBPaper00036383:Day8_N2_ash-2(RNAi)_rep3~WBPaper00036383:Day8_glp-1_EV_rep1~WBPaper00036383:Day8_glp-1_EV_rep2~WBPaper00036383:Day8_glp-1_EV_rep3~WBPaper00036383:Day8_glp-1_ash-2(RNAi)_rep1~WBPaper00036383:Day8_glp-1_ash-2(RNAi)_rep2~WBPaper00036383:Day8_glp-1_ash-2(RNAi)_rep3	Method: microarray|Species: Caenorhabditis elegans
95	20617181	WBPaper00036464.ce.mr.paper	GSE21819	GPL200	1	Distinct pathogenesis and host responses during infection of C. elegans by P. aeruginosa and S. aureus.	The genetically tractable model host Caenorhabditis elegans provides a valuable tool to dissect host-microbe interactions in vivo. Pseudomonas aeruginosa and Staphylococcus aureus utilize virulence factors involved in human disease to infect and kill C. elegans. Despite much progress, virtually nothing is known regarding the cytopathology of infection and the proximate causes of nematode death. Using light and electron microscopy, we found that P. aeruginosa infection entails intestinal distention, accumulation of an unidentified extracellular matrix and P. aeruginosa-synthesized outer membrane vesicles in the gut lumen and on the apical surface of intestinal cells, the appearance of abnormal autophagosomes inside intestinal cells, and P. aeruginosa intracellular invasion of C. elegans. Importantly, heat-killed P. aeruginosa fails to elicit a significant host response, suggesting that the C. elegans response to P. aeruginosa is activated either by heat-labile signals or pathogen-induced damage. In contrast, S. aureus infection causes enterocyte effacement, intestinal epithelium destruction, and complete degradation of internal organs. S. aureus activates a strong transcriptional response in C. elegans intestinal epithelial cells, which aids host survival during infection and shares elements with human innate responses. The C. elegans genes induced in response to S. aureus are mostly distinct from those induced by P. aeruginosa. In contrast to P. aeruginosa, heat-killed S. aureus activates a similar response as live S. aureus, which appears to be independent of the single C. elegans Toll-Like Receptor (TLR) protein. These data suggest that the host response to S. aureus is possibly mediated by pathogen-associated molecular patterns (PAMPs). Because our data suggest that neither the P. aeruginosa nor the S. aureus-triggered response requires canonical TLR signaling, they imply the existence of unidentified mechanisms for pathogen detection in C. elegans, with potentially conserved roles also in mammals.	6	17638	Irazoqui JE	Irazoqui JE, Troemel ER, Feinbaum RL, Luhachack LG, Cezairliyan BO, Ausubel FM	Distinct pathogenesis and host responses during infection of C. elegans by P. aeruginosa and S. aureus.	PLoS Pathog	2010	WBPaper00036464:OP50_8H_REP1~WBPaper00036464:OP50_8H_REP2~WBPaper00036464:OP50_8H_REP3~WBPaper00036464:RN6390_8H_REP1~WBPaper00036464:RN6390_8H_REP2~WBPaper00036464:RN6390_8H_REP3	Method: microarray|Species: Caenorhabditis elegans
96	20798549	WBPaper00037086.ce.mr.paper	GSE18157	GPL200	1	Biotin starvation with adequate glucose provision causes paradoxical changes in fuel metabolism gene expression similar in rat (Rattus norvegicus), nematode (Caenorhabditis elegans) and yeast (Saccharomyces cerevisiae).	BACKGROUND/AIM: Biotin affects the genetic expression of several glucose metabolism enzymes, besides being a cofactor of carboxylases. To explore how extensively biotin affects the expression of carbon metabolism genes, we studied the effects of biotin starvation and replenishment in 3 distantly related eukaryotes: yeast Saccharomyces cerevisiae, nematode Caenorhabditis elegans and rat Rattus norvegicus. METHODS: Biotin starvation was produced in Wistar rats, in C. elegans N2 and S. cerevisiae W303A fed with abundant glucose. High-density oligonucleotide microarrays were used to find gene expression changes. Glucose consumption, lactate and ethanol were measured by conventional tests. RESULTS: In spite of abundant glucose provision, the expression of fatty oxidation and gluconeogenic genes was augmented, and the transcripts for glucose utilization and lipogenesis were diminished in biotin starvation. These results were associated with diminished glucose consumption and glycolysis products (lactate and ethanol in yeast), which was consistent across 3 very different eukaryotes. CONCLUSION: The results point toward a strongly selected role of biotin in the control of carbon metabolism, and in adaptations to variable availability of carbon, conceivably mediated by signal transduction including soluble guanylate cyclase, cGMP and a cGMP-dependent protein kinase (PKG) and/or biotin-dependent processes.	5	17638	Ortega-Cuellar D	Ortega-Cuellar D, Hernandez-Mendoza A, Moreno-Arriola E, Carvajal-Aguilera K, Perez-Vazquez V, Gonzalez-Alvarez R, Velazquez-Arellano A	Biotin starvation with adequate glucose provision causes paradoxical changes in fuel metabolism gene expression similar in rat (Rattus norvegicus), nematode (Caenorhabditis elegans) and yeast (Saccharomyces cerevisiae).	J Nutrigenet Nutrigenomics	2010	WBPaper00037086:elegans_sufficient_Biotin__1~WBPaper00037086:elegans_sufficient_Biotin__2~WBPaper00037086:elegans_biotin_deficiency__1~WBPaper00037086:elegans_biotin_deficiency__2~WBPaper00037086:elegans_biotin_deficiency__3	Method: microarray|Species: Caenorhabditis elegans
97	20855596	WBPaper00037611.ce.mr.paper	GSE23843	GPL200	1	GLD-2/RNP-8 cytoplasmic poly(A) polymerase is a broad-spectrum regulator of the oogenesis program.	Regulated polyadenylation is a broadly conserved mechanism that controls key events during oogenesis. Pivotal to that mechanism is GLD-2, a catalytic subunit of cytoplasmic poly(A) polymerase (PAP). Caenorhabditis elegans GLD-2 forms an active PAP with multiple RNA-binding partners to regulate diverse aspects of germline and early embryonic development. One GLD-2 partner, RNP-8, was previously shown to influence oocyte fate specification. Here we use a genomic approach to identify transcripts selectively associated with both GLD-2 and RNP-8. Among the 335 GLD-2/RNP-8 potential targets, most were annotated as germline mRNAs and many as maternal mRNAs. These targets include gld-2 and rnp-8 themselves, suggesting autoregulation. Removal of either GLD-2 or RNP-8 resulted in shortened poly(A) tails and lowered abundance of four target mRNAs (oma-2, egg-1, pup-2, and tra-2); GLD-2 depletion also lowered the abundance of most GLD-2/RNP-8 putative target mRNAs when assayed on microarrays. Therefore, GLD-2/RNP-8 appears to polyadenylate and stabilize its target mRNAs. We also provide evidence that rnp-8 influences oocyte development; rnp-8 null mutants have more germ cell corpses and fewer oocytes than normal. Furthermore, RNP-8 appears to work synergistically with another GLD-2-binding partner, GLD-3, to ensure normal oogenesis. We propose that the GLD-2/RNP-8 enzyme is a broad-spectrum regulator of the oogenesis program that acts within an RNA regulatory network to specify and produce fully functional oocytes.	21	17638	Kim KW	Kim KW, Wilson TL, Kimble J	GLD-2/RNP-8 cytoplasmic poly(A) polymerase is a broad-spectrum regulator of the oogenesis program.	Proc Natl Acad Sci U S A	2010	WBPaper00037611:GLD-2_wt-IP_bio_rep1~WBPaper00037611:GLD-2_wt-IP_bio_rep2~WBPaper00037611:GLD-2_wt-IP_bio_rep3~WBPaper00037611:GLD-2_wt-IP_bio_rep4~WBPaper00037611:GLD-2_gld-2(RNAi)-IP_bio_rep1~WBPaper00037611:GLD-2_gld-2(RNAi)-IP_bio_rep2~WBPaper00037611:GLD-2_gld-2(RNAi)-IP_bio_rep3~WBPaper00037611:GLD-2_gld-2(RNAi)-IP_bio_rep4~WBPaper00037611:RNP-8_wt-IP_bio_rep1~WBPaper00037611:RNP-8_wt-IP_bio_rep2~WBPaper00037611:RNP-8_wt-IP_bio_rep3~WBPaper00037611:RNP-8_rnp-8(q784)-IP_bio_rep1~WBPaper00037611:RNP-8_rnp-8(q784)-IP_bio_rep2~WBPaper00037611:RNP-8_rnp-8(q784)-IP_bio_rep3~WBPaper00037611:wt_total_RNA_bio_rep1~WBPaper00037611:wt_total_RNA_bio_rep2~WBPaper00037611:wt_total_RNA_bio_rep3~WBPaper00037611:wt_total_RNA_bio_rep4~WBPaper00037611:gld-2(RNAi)_bio_rep1~WBPaper00037611:gld-2(RNAi)_bio_rep2~WBPaper00037611:gld-2(RNAi)_bio_rep3	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
98	20967231	WBPaper00037695.ce.mr.paper	GSE23528	GPL200	1	Genome-wide analysis of light- and temperature-entrained circadian transcripts in Caenorhabditis elegans.	Most organisms have an endogenous circadian clock that is synchronized to environmental signals such as light and temperature. Although circadian rhythms have been described in the nematode Caenorhabditis elegans at the behavioral level, these rhythms appear to be relatively non-robust. Moreover, in contrast to other animal models, no circadian transcriptional rhythms have been identified. Thus, whether this organism contains a bona fide circadian clock remains an open question. Here we use genome-wide expression profiling experiments to identify light- and temperature-entrained oscillating transcripts in C. elegans. These transcripts exhibit rhythmic expression with temperature-compensated 24-h periods. In addition, their expression is sustained under constant conditions, suggesting that they are under circadian regulation. Light and temperature cycles strongly drive gene expression and appear to entrain largely nonoverlapping gene sets. We show that mutations in a cyclic nucleotide-gated channel required for sensory transduction abolish both light- and temperature-entrained gene expression, implying that environmental cues act cell nonautonomously to entrain circadian rhythms. Together, these findings demonstrate circadian-regulated transcriptional rhythms in C. elegans and suggest that further analyses in this organism will provide new information about the evolution and function of this biological clock.	89	17638	van der Linden AM	van der Linden AM, Beverly M, Kadener S, Rodriguez J, Wasserman S, Rosbash M, Sengupta P	Genome-wide analysis of light- and temperature-entrained circadian transcripts in Caenorhabditis elegans.	PLoS Biol	2010	WBPaper00037695:T2_LD_3~WBPaper00037695:T6_LD_3~WBPaper00037695:T10_LD_3~WBPaper00037695:T14_LD_3~WBPaper00037695:T18_LD_3~WBPaper00037695:T22_LD_3~WBPaper00037695:T26_DD_2~WBPaper00037695:T30_DD_2~WBPaper00037695:T34_DD_2~WBPaper00037695:T38_DD_2~WBPaper00037695:T42_DD_2~WBPaper00037695:T46_DD_2~WBPaper00037695:T2_LD_4~WBPaper00037695:T6_LD_4~WBPaper00037695:T10_LD_4~WBPaper00037695:T14_LD_4~WBPaper00037695:T18_LD_4~WBPaper00037695:T22_LD_4~WBPaper00037695:T26_DD_4~WBPaper00037695:T30_DD_4~WBPaper00037695:T34_DD_4~WBPaper00037695:T38_DD_4~WBPaper00037695:T42_DD_4~WBPaper00037695:T46_DD_4~WBPaper00037695:T2_LD_6~WBPaper00037695:T6_LD_6~WBPaper00037695:T10_LD_6~WBPaper00037695:T14_LD_6~WBPaper00037695:T18_LD_6~WBPaper00037695:T22_LD_6~WBPaper00037695:T26_DD_6~WBPaper00037695:T30_DD_6~WBPaper00037695:T34_DD_6~WBPaper00037695:T38_DD_6~WBPaper00037695:T42_DD_6~WBPaper00037695:T46_DD_6~WBPaper00037695:T2_control_4~WBPaper00037695:T6_control_4~WBPaper00037695:T1_control_4~WBPaper00037695:T2_control_6~WBPaper00037695:T1_control_6~WBPaper00037695:T2_WC_1~WBPaper00037695:T6_WC_1~WBPaper00037695:T10_WC_1~WBPaper00037695:T14_WC_1~WBPaper00037695:T18_WC_1~WBPaper00037695:T22_WC_1~WBPaper00037695:T2_WC_2~WBPaper00037695:T6_WC_2~WBPaper00037695:T10_WC_2~WBPaper00037695:T14_WC_2~WBPaper00037695:T18_WC_2~WBPaper00037695:T22_WC_2~WBPaper00037695:T2_WC_3~WBPaper00037695:T6_WC_3~WBPaper00037695:T10_WC_3~WBPaper00037695:T14_WC_3~WBPaper00037695:T18_WC_3~WBPaper00037695:T22_WC_3~WBPaper00037695:T26_CC_3~WBPaper00037695:T30_CC_3~WBPaper00037695:T34_CC_3~WBPaper00037695:T38_CC_3~WBPaper00037695:T42_CC_3~WBPaper00037695:T46_CC_3~WBPaper00037695:T2_WC_4~WBPaper00037695:T6_WC_4~WBPaper00037695:T10_WC_4~WBPaper00037695:T14_WC_4~WBPaper00037695:T18_WC_4~WBPaper00037695:T22_WC_4~WBPaper00037695:T26_CC_4~WBPaper00037695:T30_CC_4~WBPaper00037695:T34_CC_4~WBPaper00037695:T38_CC_4~WBPaper00037695:T42_CC_4~WBPaper00037695:T46_CC_4~WBPaper00037695:T2_WC_6~WBPaper00037695:T6_WC_6~WBPaper00037695:T10_WC_6~WBPaper00037695:T14_WC_6~WBPaper00037695:T18_WC_6~WBPaper00037695:T22_WC_6~WBPaper00037695:T26_CC_6~WBPaper00037695:T30_CC_6~WBPaper00037695:T34_CC_6~WBPaper00037695:T38_CC_6~WBPaper00037695:T42_CC_6~WBPaper00037695:T46_CC_6	Method: microarray|Species: Caenorhabditis elegans
99	20929438	WBPaper00037704.ce.mr.paper	GSE21747	GPL200	1	Characterization of the xenobiotic response of Caenorhabditis elegans to the anthelmintic drug albendazole and the identification of novel drug glucoside metabolites.	Knowledge of how anthelmintics are metabolized and excreted in nematodes is an integral part of understanding the factors that determine their potency, spectrum of activity and for investigating mechanisms of resistance. Although there is remarkably little information on these processes in nematodes, it is often suggested that they are of minimal importance for the major anthelmintic drugs. Consequently, we have investigated how the model nematode Caenorhabditis elegans responds to and metabolizes albendazole, one of the most important anthelmintic drugs for human and animal use. Using a mutant strain lacking the -tubulin drug target to minimize generalized stress responses, we show that the transcriptional response is dominated by genes encoding XMEs (xenobiotic-metabolizing enzymes), particularly cytochrome P450s and UGTs (UDP-glucuronosyl transferases). The most highly induced genes are predominantly expressed in the worm intestine, supporting their role in drug metabolism. HPLC-MS/MS revealed the production of two novel glucoside metabolites in C. elegans identifying a major difference in the biotransformation of this drug between nematodes and mammals. This is the first demonstration of metabolism of a therapeutic anthelmintic in C. elegans and provides a framework for its use to functionally investigate nematode anthelmintic metabolism.	6	17638	Laing ST	Laing ST, Ivens A, Laing R, Ravikumar SP, Butler V, Woods DJ, Gilleard JS	Characterization of the xenobiotic response of Caenorhabditis elegans to the anthelmintic drug albendazole and the identification of novel drug glucoside metabolites.	Biochem J	2010	WBPaper00037704:albendazole_rep1~WBPaper00037704:albendazole_rep2~WBPaper00037704:albendazole_rep3~WBPaper00037704:no_albendazole_rep1~WBPaper00037704:no_albendazole_rep2~WBPaper00037704:no_albendazole_rep3	Method: microarray|Species: Caenorhabditis elegans
100	21060680	WBPaper00037765.ce.mr.paper	GSE21376	GPL200	1	Different Mi-2 complexes for various developmental functions in Caenorhabditis elegans.	Biochemical purifications from mammalian cells and Xenopus oocytes revealed that vertebrate Mi-2 proteins reside in multisubunit NuRD (Nucleosome Remodeling and Deacetylase) complexes. Since all NuRD subunits are highly conserved in the genomes of C. elegans and Drosophila, it was suggested that NuRD complexes also exist in invertebrates. Recently, a novel dMec complex, composed of dMi-2 and dMEP-1 was identified in Drosophila. The genome of C. elegans encodes two highly homologous Mi-2 orthologues, LET-418 and CHD-3. Here we demonstrate that these proteins define at least three different protein complexes, two distinct NuRD complexes and one MEC complex. The two canonical NuRD complexes share the same core subunits HDA-1/HDAC, LIN-53/RbAp and LIN-40/MTA, but differ in their Mi-2 orthologues LET-418 or CHD-3. LET-418 but not CHD-3, interacts with the Kruppel-like protein MEP-1 in a distinct complex, the MEC complex. Based on microarrays analyses, we propose that MEC constitutes an important LET-418 containing regulatory complex during C. elegans embryonic and early larval development. It is required for the repression of germline potential in somatic cells and acts when blastomeres are still dividing and differentiating. The two NuRD complexes may not be important for the early development, but may act later during postembryonic development. Altogether, our data suggest a considerable complexity in the composition, the developmental function and the tissue-specificity of the different C. elegans Mi-2 complexes.	9	17637	Passannante M	Passannante M, Marti CO, Pfefferli C, Moroni PS, Kaeser-Pebernard S, Puoti A, Hunziker P, Wicky C, Muller F	Different Mi-2 complexes for various developmental functions in Caenorhabditis elegans.	PLoS One	2010	WBPaper00037765:L1_let-418_RNAi_rep_3~WBPaper00037765:L1_mep-1_RNAi_rep_3~WBPaper00037765:L1_gfp_RNAi_rep_3~WBPaper00037765:L1_let-418_RNAi_rep_2~WBPaper00037765:L1_mep-1_RNAi_rep_2~WBPaper00037765:L1_gfp_RNAi_rep_2~WBPaper00037765:L1_let-418_RNAi_rep_1~WBPaper00037765:L1_mep-1_RNAi_rep_1~WBPaper00037765:L1_gfp_RNAi_rep_1	Method: microarray|Species: Caenorhabditis elegans
101	21169991	WBPaper00037901.ce.mr.paper	GSE21591	GPL200	1	A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1.	RNA-binding proteins (RBPs) are critical regulators of gene expression. To understand and predict the outcome of RBP-mediated regulation a comprehensive analysis of their interaction with RNA is necessary. The signal transduction and activation of RNA (STAR) family of RBPs includes developmental regulators and tumour suppressors such as Caenorhabditis elegans GLD-1, which is a key regulator of germ cell development. To obtain a comprehensive picture of GLD-1 interactions with the transcriptome, we identified GLD-1-associated mRNAs by RNA immunoprecipitation followed by microarray detection. Based on the computational analysis of these mRNAs we generated a predictive model, where GLD-1 association with mRNA is determined by the strength and number of 7-mer GLD-1-binding motifs (GBMs) within UTRs. We verified this quantitative model both in vitro, by competition GLD-1/GBM-binding experiments to determine relative affinity, and in vivo, by 'transplantation' experiments, where 'weak' and 'strong' GBMs imposed translational repression of increasing strength on a non-target mRNA. This study demonstrates that transcriptome-wide identification of RBP mRNA targets combined with quantitative computational analysis can generate highly predictive models of post-transcriptional regulatory networks.	15	17638	Wright JE	Wright JE, Gaidatzis D, Senften M, Farley BM, Westhof E, Ryder SP, Ciosk R	A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1.	EMBO J	2011	WBPaper00037901:Input_rep1~WBPaper00037901:Input_rep2~WBPaper00037901:Input_rep3~WBPaper00037901:aMYC_rep1~WBPaper00037901:aMYC_rep2~WBPaper00037901:aMYC_rep3~WBPaper00037901:aFLAG_rep1~WBPaper00037901:aFLAG_rep2~WBPaper00037901:aFLAG_rep3~WBPaper00037901:N2_aFLAG_rep1~WBPaper00037901:N2_aFLAG_rep2~WBPaper00037901:N2_aFLAG_rep3~WBPaper00037901:GGF_aFLAG_rep1~WBPaper00037901:GGF_aFLAG_rep2~WBPaper00037901:GGF_aFLAG_rep3	Method: microarray|Species: Caenorhabditis elegans
102	21253676	WBPaper00038060.ce.mr.paper	GSE19972	GPL200	1	Overexpression of SUMO perturbs the growth and development of Caenorhabditis elegans.	Small ubiquitin-related modifiers (SUMOs) are important regulator proteins. Caenorhabditis elegans contains a single SUMO ortholog, SMO-1, necessary for the reproduction of C. elegans. In this study, we constructed transgenic C. elegans strains expressing human SUMO-1 under the control of pan-neuronal (aex-3) or pan-muscular (myo-4) promoter and SUMO-2 under the control of myo-4 promoter. Interestingly, muscular overexpression of SUMO-1 or -2 resulted in morphological changes of the posterior part of the nematode. Movement, reproduction and aging of C. elegans were perturbed by the overexpression of SUMO-1 or -2. Genome-wide expression analyses revealed that several genes encoding components of SUMOylation pathway and ubiquitin-proteasome system were upregulated in SUMO-overexpressing nematodes. Since muscular overexpression of SMO-1 also brought up reproductive and mobility perturbations, our results imply that the phenotypes were largely due to an excess of SUMO, suggesting that a tight control of SUMO levels is important for the normal development of multicellular organisms.	9	17638	Rytinki MM	Rytinki MM, Lakso M, Pehkonen P, Aarnio V, Reisner K, Perakyla M, Wong G, Palvimo JJ	Overexpression of SUMO perturbs the growth and development of Caenorhabditis elegans.	Cell Mol Life Sci	2011	WBPaper00038060:N2_1~WBPaper00038060:N2_2~WBPaper00038060:N2_3~WBPaper00038060:aex-3p-his-SUMO-1-JS62_1~WBPaper00038060:aex-3p-his-SUMO-1-JS62_2~WBPaper00038060:aex-3p-his-SUMO-1-JS62_3~WBPaper00038060:myo-4p-his-SUMO-1-JS63_1~WBPaper00038060:myo-4p-his-SUMO-1-JS63_2~WBPaper00038060:myo-4p-his-SUMO-1-JS63_3	Method: microarray|Species: Caenorhabditis elegans
103	21331044	WBPaper00038172.ce.mr.paper	GSE25513	GPL200	1	Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB.	Activating AMPK or inactivating calcineurin slows ageing in Caenorhabditis elegans and both have been implicated as therapeutic targets for age-related pathology in mammals. However, the direct targets that mediate their effects on longevity remain unclear. In mammals, CREB-regulated transcriptional coactivators (CRTCs) are a family of cofactors involved in diverse physiological processes including energy homeostasis, cancer and endoplasmic reticulum stress. Here we show that both AMPK and calcineurin modulate longevity exclusively through post-translational modification of CRTC-1, the sole C. elegans CRTC. We demonstrate that CRTC-1 is a direct AMPK target, and interacts with the CREB homologue-1 (CRH-1) transcription factor in vivo. The pro-longevity effects of activating AMPK or deactivating calcineurin decrease CRTC-1 and CRH-1 activity and induce transcriptional responses similar to those of CRH-1 null worms. Downregulation of crtc-1 increases lifespan in a crh-1-dependent manner and directly reducing crh-1 expression increases longevity, substantiating a role for CRTCs and CREB in ageing. Together, these findings indicate a novel role for CRTCs and CREB in determining lifespan downstream of AMPK and calcineurin, and illustrate the molecular mechanisms by which an evolutionarily conserved pathway responds to low energy to increase longevity.	12	17638	Mair W	Mair W, Morantte I, Rodrigues AP, Manning G, Montminy M, Shaw RJ, Dillin A	Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB.	Nature	2011	WBPaper00038172:WT_1~WBPaper00038172:WT_2~WBPaper00038172:WT_3~WBPaper00038172:crh-1null_1~WBPaper00038172:crh-1null_2~WBPaper00038172:crh-1null_3~WBPaper00038172:tax-6null_1~WBPaper00038172:tax-6null_2~WBPaper00038172:tax-6null_3~WBPaper00038172:aak-2overexpress_1~WBPaper00038172:aak-2overexpress_2~WBPaper00038172:aak-2overexpress_3	Method: microarray|Species: Caenorhabditis elegans
104	21363964	WBPaper00038180.ce.mr.paper	GSE25831,GSE25834	GPL200	1	An MLL/COMPASS subunit functions in the C. elegans dosage compensation complex to target X chromosomes for transcriptional regulation of gene expression.	Here we analyze the essential process of X-chromosome dosage compensation (DC) to elucidate mechanisms that control the assembly, genome-wide binding, and function of gene regulatory complexes that act over large chromosomal territories. We demonstrate that a subunit of Caenorhabditis elegans MLL/COMPASS, a gene activation complex, acts within the DC complex (DCC), a condensin complex, to target the DCC to both X chromosomes of hermaphrodites for chromosome-wide reduction of gene expression. The DCC binds to two categories of sites on X: rex (recruitment element on X) sites that recruit the DCC in an autonomous, sequence-dependent manner, and dox (dependent on X) sites that reside primarily in promoters of expressed genes and bind the DCC robustly only when attached to X. We find that DC mutations that abolish rex site binding greatly reduce dox site binding but do not eliminate it. Instead, binding is diminished to the low level observed at autosomal sites in wild-type animals. Changes in DCC binding to these non-rex sites occur throughout development and correlate directly with transcriptional activity of adjacent genes. Moreover, autosomal DCC binding is enhanced by rex site binding in cis in X-autosome fusion chromosomes. Thus, dox and autosomal sites have similar binding potential but are distinguished by linkage to rex sites. We propose a model for DCC binding in which low-level DCC binding at dox sites is dictated by intrinsic properties correlated with high transcriptional activity. Sex-specific DCC recruitment to rex sites then enhances the magnitude of DCC binding to dox sites in cis, which lack high affinity for the DCC on their own. We also show that the DCC balances X-chromosome gene expression between sexes by controlling transcription.	6	17638	Pferdehirt RR	Pferdehirt RR, Kruesi WS, Meyer BJ	An MLL/COMPASS subunit functions in the C. elegans dosage compensation complex to target X chromosomes for transcriptional regulation of gene expression.	Genes Dev	2011	WBPaper00038180:WT_fedL1_rep1~WBPaper00038180:WT_fedL1_rep2~WBPaper00038180:WT_fedL1_rep3~WBPaper00038180:XX_mixedEmbryo-WT-N_080307_A~WBPaper00038180:XX_mixedEmbryo-WT-N_080307_B~WBPaper00038180:XX_mixedEmbryo-WT-N_080307_C	Method: microarray|Species: Caenorhabditis elegans
105	21474712	WBPaper00038304.ce.mr.paper	GSE27867	GPL200	1	Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes.	The unfolded protein response (UPR), which is activated when unfolded or misfolded proteins accumulate in the endoplasmic reticulum, has been implicated in the normal physiology of immune defense and in several human diseases, including diabetes, cancer, neurodegenerative disease, and inflammatory disease. In this study, we found that the nervous system controlled the activity of a noncanonical UPR pathway required for innate immunity in Caenorhabditis elegans. OCTR-1, a putative octopamine G protein-coupled catecholamine receptor (GPCR, G protein-coupled receptor), functioned in sensory neurons designated ASH and ASI to actively suppress innate immune responses by down-regulating the expression of noncanonical UPR genes pqn/abu in nonneuronal tissues. Our findings suggest a molecular mechanism by which the nervous system may sense inflammatory responses and respond by controlling stress-response pathways at the organismal level.	6	17638	Sun J	Sun J, Singh V, Kajino-Sakamoto R, Aballay A	Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes.	Science	2011	WBPaper00038304:wt_rep1~WBPaper00038304:wt_rep2~WBPaper00038304:wt_rep3~WBPaper00038304:tag-24_rep1~WBPaper00038304:tag-24_rep2~WBPaper00038304:tag-24_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response|Topic: response to unfolded protein|Topic: endoplasmic reticulum|Topic: mitochondrion|Topic: cytosol
106	21589891	WBPaper00038427.ce.mr.paper	GSE28853	GPL200	1	Chromosome-biased binding and gene regulation by the Caenorhabditis elegans DRM complex.	DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we describe new aspects of DRM binding and function revealed through genome-wide analyses of the Caenorhabditis elegans DRM subunit LIN-54. We show that LIN-54 DNA-binding activity recruits DRM to promoters enriched for adjacent putative E2F/DP and LIN-54 binding sites, suggesting that these two DNA-binding moieties together direct DRM to its target genes. Chromatin immunoprecipitation and gene expression profiling reveals conserved roles for DRM in regulating genes involved in cell division, development, and reproduction. We find that LIN-54 promotes expression of reproduction genes in the germline, but prevents ectopic activation of germline-specific genes in embryonic soma. Strikingly, C. elegans DRM does not act uniformly throughout the genome: the DRM recruitment motif, DRM binding, and DRM-regulated embryonic genes are all under-represented on the X chromosome. However, germline genes down-regulated in lin-54 mutants are over-represented on the X chromosome. We discuss models for how loss of autosome-bound DRM may enhance germline X chromosome silencing. We propose that autosome-enriched binding of DRM arose in C. elegans as a consequence of germline X chromosome silencing and the evolutionary redistribution of germline-expressed and essential target genes to autosomes. Sex chromosome gene regulation may thus have profound evolutionary effects on genome organization and transcriptional regulatory networks.	12	17260	Tabuchi TM	Tabuchi TM, Deplancke B, Osato N, Zhu LJ, Barrasa MI, Harrison MM, Horvitz HR, Walhout AJ, Hagstrom KA	Chromosome-biased binding and gene regulation by the Caenorhabditis elegans DRM complex.	PLoS Genet	2011	WBPaper00038427:N2_embryo_rep1~WBPaper00038427:N2_embryo_rep2~WBPaper00038427:N2_embryo_rep3~WBPaper00038427:lin-54(n2990)_embryo_rep1~WBPaper00038427:lin-54(n2990)_embryo_rep2~WBPaper00038427:lin-54(n2990)_embryo_rep3~WBPaper00038427:N2_germline_rep1~WBPaper00038427:N2_germline_rep2~WBPaper00038427:N2_germline_rep3~WBPaper00038427:lin-54(n3423)_germline_rep1~WBPaper00038427:lin-54(n3423)_germline_rep2~WBPaper00038427:lin-54(n3423)_germline_rep3	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
107	21625567	WBPaper00038462.ce.mr.paper	GSE21784	GPL200	1	A decline in p38 MAPK signaling underlies immunosenescence in Caenorhabditis elegans.	The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging in Caenorhabditis elegans, intestinal tissue deterioration and the increased intestinal proliferation of bacteria are observed, but how innate immunity changes during C. elegans aging has not been defined. Here we show that C. elegans exhibits increased susceptibility to bacterial infection with age, and we establish that aging is associated with a decline in the activity of the conserved PMK-1 p38 mitogen-activated protein kinase pathway, which regulates innate immunity in C. elegans. Our data define the phenomenon of innate immunosenescence in C. elegans in terms of the age-dependent dynamics of the PMK-1 innate immune signaling pathway, and they suggest that a cycle of intestinal tissue aging, immunosenescence, and bacterial proliferation leads to death in aging C. elegans.	9	17638	Youngman MJ	Youngman MJ, Rogers ZN, Kim DH	A decline in p38 MAPK signaling underlies immunosenescence in Caenorhabditis elegans.	PLoS Genet	2011	WBPaper00038462:L4_rep1~WBPaper00038462:L4_rep2~WBPaper00038462:L4_rep3~WBPaper00038462:day_6_adults_rep1~WBPaper00038462:day_6_adults_rep2~WBPaper00038462:day_6_adults_rep3~WBPaper00038462:day_15_adults_rep1~WBPaper00038462:day_15_adults_rep2~WBPaper00038462:day_15_adults_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response
108	21706021	WBPaper00039792.ce.mr.paper	GSE28856	GPL200	1	Regulation of behavioral plasticity by systemic temperature signaling in Caenorhabditis elegans.	Animals cope with environmental changes by altering behavioral strategy. Environmental information is generally received by sensory neurons in the neural circuit that generates behavior. However, although environmental temperature inevitably influences an animal's entire body, the mechanism of systemic temperature perception remains largely unknown. We show here that systemic temperature signaling induces a change in a memory-based behavior in C. elegans. During behavioral conditioning, non-neuronal cells as well as neuronal cells respond to cultivation temperature through a heat-shock transcription factor that drives newly identified gene expression dynamics. This systemic temperature signaling regulates thermosensory neurons non-cell-autonomously through the estrogen signaling pathway, producing thermotactic behavior. We provide a link between systemic environmental recognition and behavioral plasticity in the nervous system.	12	17637	Sugi T	Sugi T, Nishida Y, Mori I	Regulation of behavioral plasticity by systemic temperature signaling in Caenorhabditis elegans.	Nat Neurosci	2011	WBPaper00039792:WT_0_h_rep1~WBPaper00039792:WT_4_h_rep1~WBPaper00039792:WT_0_h_rep2~WBPaper00039792:WT_4_h_rep2~WBPaper00039792:WT_0_h_rep3~WBPaper00039792:WT_4_h_rep3~WBPaper00039792:WT_0_h_rep4~WBPaper00039792:WT_4_h_rep4~WBPaper00039792:WT_1_h_rep1~WBPaper00039792:WT_2_h_rep1~WBPaper00039792:WT_1_h_rep2~WBPaper00039792:WT_2_h_rep2	Method: microarray|Species: Caenorhabditis elegans
109	21731485	WBPaper00039851.ce.mr.paper	GSE27401	GPL200	1	Candida albicans infection of Caenorhabditis elegans induces antifungal immune defenses.	Candida albicans yeast cells are found in the intestine of most humans, yet this opportunist can invade host tissues and cause life-threatening infections in susceptible individuals. To better understand the host factors that underlie susceptibility to candidiasis, we developed a new model to study antifungal innate immunity. We demonstrate that the yeast form of C. albicans establishes an intestinal infection in Caenorhabditis elegans, whereas heat-killed yeast are avirulent. Genome-wide, transcription-profiling analysis of C. elegans infected with C. albicans yeast showed that exposure to C. albicans stimulated a rapid host response involving 313 genes (124 upregulated and 189 downregulated, ~1.6% of the genome) many of which encode antimicrobial, secreted or detoxification proteins. Interestingly, the host genes affected by C. albicans exposure overlapped only to a small extent with the distinct transcriptional responses to the pathogenic bacteria Pseudomonas aeruginosa or Staphylococcus aureus, indicating that there is a high degree of immune specificity toward different bacterial species and C. albicans. Furthermore, genes induced by P. aeruginosa and S. aureus were strongly over-represented among the genes downregulated during C. albicans infection, suggesting that in response to fungal pathogens, nematodes selectively repress the transcription of antibacterial immune effectors. A similar phenomenon is well known in the plant immune response, but has not been described previously in metazoans. Finally, 56% of the genes induced by live C. albicans were also upregulated by heat-killed yeast. These data suggest that a large part of the transcriptional response to C. albicans is mediated through "pattern recognition," an ancient immune surveillance mechanism able to detect conserved microbial molecules (so-called pathogen-associated molecular patterns or PAMPs). This study provides new information on the evolution and regulation of the innate immune response to divergent pathogens and demonstrates that nematodes selectively mount specific antifungal defenses at the expense of antibacterial responses.	9	16571	Pukkila-Worley R	Pukkila-Worley R, Ausubel FM, Mylonakis E	Candida albicans infection of Caenorhabditis elegans induces antifungal immune defenses.	PLoS Pathog	2011	WBPaper00039851:C_albicans_alive_rep1~WBPaper00039851:C_albicans_alive_rep2~WBPaper00039851:C_albicans_alive_rep3~WBPaper00039851:Heat_Killed_C_albicans_rep1~WBPaper00039851:Heat_Killed_C_albicans_rep2~WBPaper00039851:Heat_Killed_C_albicans_rep3~WBPaper00039851:Heat_Killed_E_coli_rep1~WBPaper00039851:Heat_Killed_E_coli_rep2~WBPaper00039851:Heat_Killed_E_coli_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response
110	21740898	WBPaper00039866.ce.mr.paper	GSE25633	GPL200	1	Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport.	Cilia are ubiquitous cell surface projections that mediate various sensory- and motility-based processes and are implicated in a growing number of multi-organ genetic disorders termed ciliopathies. To identify new components required for cilium biogenesis and function, we sought to further define and validate the transcriptional targets of DAF-19, the ciliogenic C. elegans RFX transcription factor. Transcriptional profiling of daf-19 mutants (which do not form cilia) and wild-type animals was performed using embryos staged to when the cell types developing cilia in the worm, the ciliated sensory neurons (CSNs), still differentiate. Comparisons between the two populations revealed 881 differentially regulated genes with greater than a 1.5-fold increase or decrease in expression. A subset of these was confirmed by quantitative RT-PCR. Transgenic worms expressing transcriptional GFP fusions revealed CSN-specific expression patterns for 11 of 14 candidate genes. We show that two uncharacterized candidate genes, termed dyf-17 and dyf-18 because their corresponding mutants display dye-filling (Dyf) defects, are important for ciliogenesis. DYF-17 localizes at the base of cilia and is specifically required for building the distal segment of sensory cilia. DYF-18 is an evolutionarily conserved CDK7/CCRK/LF2p-related serine/threonine kinase that is necessary for the proper function of intraflagellar transport, a process critical for cilium biogenesis. Together, our microarray study identifies targets of the evolutionarily conserved RFX transcription factor, DAF-19, providing a rich dataset from which to uncover-in addition to DYF-17 and DYF-18-cellular components important for cilium formation and function.	12	17638	Phirke P	Phirke P, Efimenko E, Mohan S, Burghoorn J, Crona F, Bakhoum MW, Trieb M, Schuske K, Jorgensen EM, Piasecki BP, Leroux MR, Swoboda P	Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport.	Dev Biol	2011	WBPaper00039866:daf-19_daf-12_rep1~WBPaper00039866:daf-19_daf-12_rep2~WBPaper00039866:daf-19_daf-12_rep3~WBPaper00039866:daf-19_daf-12_rep4~WBPaper00039866:daf-12_rep1~WBPaper00039866:daf-12_rep2~WBPaper00039866:daf-12_rep3~WBPaper00039866:daf-12_rep4~WBPaper00039866:WT_rep1~WBPaper00039866:WT_rep2~WBPaper00039866:WT_rep3~WBPaper00039866:WT_rep4	Method: microarray|Species: Caenorhabditis elegans
111	21910973	WBPaper00040185.ce.mr.paper	GSE32031	GPL200	1	NHR-23 dependent collagen and hedgehog-related genes required for molting.	NHR-23, a conserved member of the nuclear receptor family of transcription factors, is required for normal development in Caenorhabditis elegans where it plays a critical role in growth and molting. In a search for NHR-23 dependent genes, we performed whole genome comparative expression microarrays on both control and nhr-23 inhibited synchronized larvae. Genes that decreased in response to nhr-23 RNAi included several collagen genes. Unexpectedly, several hedgehog-related genes were also down-regulated after nhr-23 RNAi. A homozygous nhr-23 deletion allele was used to confirm the RNAi knockdown phenotypes and the changes in gene expression. Our results indicate that NHR-23 is a critical co-regulator of functionally linked genes involved in growth and molting and reveal evolutionary parallels among the ecdysozoa.	6	17638	Kouns NA	Kouns NA, Nakielna J, Behensky F, Krause MW, Kostrouch Z, Kostrouchova M	NHR-23 dependent collagen and hedgehog-related genes required for molting.	Biochem Biophys Res Commun	2011	WBPaper00040185:Control_rep1~WBPaper00040185:Control_rep2~WBPaper00040185:Control_rep3~WBPaper00040185:nhr-23(RNAi)_rep1~WBPaper00040185:nhr-23(RNAi)_rep2~WBPaper00040185:nhr-23(RNAi)_rep3	Method: microarray|Species: Caenorhabditis elegans
112	22012258	WBPaper00040327.ce.mr.paper	GSE31043	GPL200	1	Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans.	Chromatin modifiers regulate lifespan in several organisms, raising the question of whether changes in chromatin states in the parental generation could be incompletely reprogrammed in the next generation and thereby affect the lifespan of descendants. The histone H3 lysine 4 trimethylation (H3K4me3) complex, composed of ASH-2, WDR-5 and the histone methyltransferase SET-2, regulates Caenorhabditis elegans lifespan. Here we show that deficiencies in the H3K4me3 chromatin modifiers ASH-2, WDR-5 or SET-2 in the parental generation extend the lifespan of descendants up until the third generation. The transgenerational inheritance of lifespan extension by members of the ASH-2 complex is dependent on the H3K4me3 demethylase RBR-2, and requires the presence of a functioning germline in the descendants. Transgenerational inheritance of lifespan is specific for the H3K4me3 methylation complex and is associated with epigenetic changes in gene expression. Thus, manipulation of specific chromatin modifiers only in parents can induce an epigenetic memory of longevity in descendants.	35	16718	Greer EL	Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, Benayoun BA, Shi Y, Brunet A	Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans.	Nature	2011	WBPaper00040327:F4__+_+__from_+_+__rep1~WBPaper00040327:F4__+_+__from_+_+__rep2~WBPaper00040327:F4__+_+__from_+_+__rep3~WBPaper00040327:F4__+_+__from_+_+__rep4~WBPaper00040327:F4__+_+__from_+_+__rep5~WBPaper00040327:F4__+_+__from_+_+__rep6~WBPaper00040327:F4__+_+__from_wdr-5__rep1~WBPaper00040327:F4__+_+__from_wdr-5__rep2~WBPaper00040327:F4__+_+__from_wdr-5__rep3~WBPaper00040327:F4__+_+__from_wdr-5__rep4~WBPaper00040327:F4__+_+__from_wdr-5__rep5~WBPaper00040327:F4__+_+__from_wdr-5__rep6~WBPaper00040327:F4__wdr-5_wdr-5__rep1~WBPaper00040327:F4__wdr-5_wdr-5__rep2~WBPaper00040327:F4__wdr-5_wdr-5__rep3~WBPaper00040327:F4__wdr-5_wdr-5__rep4~WBPaper00040327:F4__wdr-5_wdr-5__rep5~WBPaper00040327:F4__wdr-5_wdr-5__rep6~WBPaper00040327:F5__+_+__from_+_+__rep1~WBPaper00040327:F5__+_+__from_+_+__rep2~WBPaper00040327:F5__+_+__from_+_+__rep3~WBPaper00040327:F5__+_+__from_+_+__rep4~WBPaper00040327:F5__+_+__from_+_+__rep5~WBPaper00040327:F5__+_+__from_+_+__rep6~WBPaper00040327:F5__+_+__from_wdr-5__rep1~WBPaper00040327:F5__+_+__from_wdr-5__rep2~WBPaper00040327:F5__+_+__from_wdr-5__rep4~WBPaper00040327:F5__+_+__from_wdr-5__rep5~WBPaper00040327:F5__+_+__from_wdr-5__rep6~WBPaper00040327:F5__wdr-5_wdr-5__rep1~WBPaper00040327:F5__wdr-5_wdr-5__rep2~WBPaper00040327:F5__wdr-5_wdr-5__rep3~WBPaper00040327:F5__wdr-5_wdr-5__rep4~WBPaper00040327:F5__wdr-5_wdr-5__rep5~WBPaper00040327:F5__wdr-5_wdr-5__rep6	Method: microarray|Species: Caenorhabditis elegans
113	22087002	WBPaper00040420.ce.mr.paper	N.A.	N.A.	1	Shared gene expression in distinct neurons expressing common selector genes.	Expression of the mec-3/unc-86 selector gene complex induces the differentiation of the touch receptor neurons (TRNs) of Caenorhabditis elegans. These genes are also expressed in another set of embryonically derived mechanosensory neurons, the FLP neurons, but these cells do not share obvious TRN traits or proteins. We have identified ~300 genes in each cell type that are up-regulated at least threefold using DNA microarrays. Twenty-three percent of these genes are up-regulated in both cells. Surprisingly, some of the common genes had previously been identified as TRN-specific. Although the FLP neurons contain low amounts of the mRNAs for these TRN genes, they do not have detectable proteins. These results suggest that transcription control is relatively inexact but that these apparent errors of transcription are tolerated and do not alter cell fate. Previous studies showed that loss of the EGL-44 and EGL-46 transcription factors cause the FLP neurons to acquire TRN-like traits. Here, we show that similar changes occur (e.g., the expression of both the TRN mRNAs and proteins) when the FLP neurons ectopically express the auxiliary transcription factor ALR-1 (Aristaless related), which ensures, but does not direct, TRN differentiation. Thus, the FLP neurons can acquire a TRN-like fate but use multiple levels of regulation to ensure they do not. Our data indicate that expression of common master regulators in different cell types can result in inappropriate expression of effector genes. This misexpression makes these cells vulnerable to influences that could cause them to acquire alternative fates.	11	17638	Topalidou I	Topalidou I, Chalfie M	Shared gene expression in distinct neurons expressing common selector genes.	Proc Natl Acad Sci U S A	2011	WBPaper00040420:FLP_1~WBPaper00040420:FLP_2~WBPaper00040420:FLP_3~WBPaper00040420:TRN_1~WBPaper00040420:TRN_2~WBPaper00040420:TRN_3~WBPaper00040420:TRN_4~WBPaper00040420:WholeAnimal_1~WBPaper00040420:WholeAnimal_2~WBPaper00040420:WholeAnimal_3~WBPaper00040420:WholeAnimal_4	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
114	22232551	WBPaper00040603.ce.mr.paper	GSE34113	GPL200	1	Caenorhabditis elegans RNA-processing protein TDP-1 regulates protein homeostasis and life span.	Transactive response DNA-binding protein (TARDBP/TDP-43), a heterogeneous nuclear ribonucleoprotein (hnRNP) with diverse activities, is a common denominator in several neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Orthologs of TDP-43 exist in animals ranging from mammals to invertebrates. Here, we systematically studied mutant Caenorhabditis elegans lacking the nematode TDP-43 ortholog, TDP-1. Heterologous expression of human TDP-43 rescued the defects in C. elegans lacking TDP-1, suggesting their functions are conserved. Although the tdp-1 mutants exhibited deficits in fertility, growth, and locomotion, loss of tdp-1 attenuated defects in several C. elegans models of proteotoxicity. Loss of tdp-1 suppressed defects in transgenic C. elegans expressing TDP-43 or CuZn superoxide dismutase, both of which are associated with proteotoxicity in neurodegenerative diseases. Loss of tdp-1 also reduced defects in mutant animals lacking the heat shock factor HSF-1. Transcriptional profiling demonstrated that the loss of TDP-1 altered expression of genes functioning in RNA processing and protein folding. Furthermore, the absence of tdp-1 extended the life span in C. elegans. The life span extension required a FOXO transcriptional factor DAF-16 but not HSF-1. These results suggest that the C. elegans TDP-1 has a role in the regulation of protein homeostasis and aging.	6	17638	Zhang T	Zhang T, Hwang HY, Hao H, Talbot C, Wang J	Caenorhabditis elegans RNA-processing protein TDP-1 regulates protein homeostasis and life span.	J Biol Chem	2012	WBPaper00040603:wild-type_1~WBPaper00040603:wild-type_2~WBPaper00040603:wild-type_3~WBPaper00040603:tdp-1(ok803)_1~WBPaper00040603:tdp-1(ok803)_2~WBPaper00040603:tdp-1(ok803)_3	Method: microarray|Species: Caenorhabditis elegans
115	22303006	WBPaper00040730.ce.mr.paper	GSE34471	GPL200	1	Heme utilization in the Caenorhabditis elegans hypodermal cells is facilitated by heme-responsive gene-2.	The roundworm Caenorhabditis elegans is a heme auxotroph that requires the coordinated actions of HRG-1 heme permeases to transport environmental heme into the intestine and HRG-3, a secreted protein, to deliver intestinal heme to other tissues including the embryo. Here we show that heme homeostasis in the extraintestinal hypodermal tissue was facilitated by the transmembrane protein HRG-2. Systemic heme deficiency up-regulated hrg-2 mRNA expression over 200-fold in the main body hypodermal syncytium, hyp 7. HRG-2 is a type I membrane protein that binds heme and localizes to the endoplasmic reticulum and apical plasma membrane. Cytochrome heme profiles are aberrant in HRG-2-deficient worms, a phenotype that was partially suppressed by heme supplementation. A heme-deficient yeast strain, ectopically expressing worm HRG-2, revealed significantly improved growth at submicromolar concentrations of exogenous heme. Taken together, our results implicate HRG-2 as a facilitator of heme utilization in the Caenorhabditis elegans hypodermis and provide a mechanism for the regulation of heme homeostasis in an extraintestinal tissue.	12	17638	Chen C	Chen C, Samuel TK, Krause M, Dailey HA, Hamza I	Heme utilization in the Caenorhabditis elegans hypodermal cells is facilitated by heme-responsive gene-2.	J Biol Chem	2012	WBPaper00040730:4uM-Heme-N2_rep1~WBPaper00040730:4uM-Heme-N2_rep2~WBPaper00040730:4uM-Heme-N2_rep3~WBPaper00040730:20uM-Heme-N2_rep1~WBPaper00040730:20uM-Heme-N2_rep2~WBPaper00040730:20uM-Heme-N2_rep3~WBPaper00040730:4uM-Heme-hrg-2(tm3978)_rep1~WBPaper00040730:4uM-Heme-hrg-2(tm3978)_rep2~WBPaper00040730:4uM-Heme-hrg-2(tm3978)_rep3~WBPaper00040730:20uM-Heme-hrg-2(tm3978)_rep1~WBPaper00040730:20uM-Heme-hrg-2(tm3978)_rep2~WBPaper00040730:20uM-Heme-hrg-2(tm3978)_rep3	Method: microarray|Species: Caenorhabditis elegans
116	22348077	WBPaper00040808.ce.mr.paper	GSE22660	GPL200	1	The transcriptional response of Caenorhabditis elegans to Ivermectin exposure identifies novel genes involved in the response to reduced food intake.	We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short-term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms.	20	17155	Laing ST	Laing ST, Ivens A, Butler V, Ravikumar SP, Laing R, Woods DJ, Gilleard JS	The transcriptional response of Caenorhabditis elegans to Ivermectin exposure identifies novel genes involved in the response to reduced food intake.	PLoS One	2012	WBPaper00040808:0.1uM_ivermectin_exposure_rep1~WBPaper00040808:0.1uM_ivermectin_exposure_rep2~WBPaper00040808:0.1uM_ivermectin_exposure_rep3~WBPaper00040808:0.1uM_ivermectin_exposure_rep4~WBPaper00040808:0.1uM_ivermectin_exposure_rep5~WBPaper00040808:0.1uM_DMSO_control_rep1~WBPaper00040808:0.1uM_DMSO_control_rep2~WBPaper00040808:0.1uM_DMSO_control_rep3~WBPaper00040808:0.1uM_DMSO_control_rep4~WBPaper00040808:0.1uM_DMSO_control_rep5~WBPaper00040808:1.1uM_ivermectin_exposure_rep1~WBPaper00040808:1.1uM_ivermectin_exposure_rep2~WBPaper00040808:1.1uM_ivermectin_exposure_rep3~WBPaper00040808:1.1uM_ivermectin_exposure_rep4~WBPaper00040808:1.1uM_ivermectin_exposure_rep5~WBPaper00040808:1.1uM_DMSO_control_rep1~WBPaper00040808:1.1uM_DMSO_control_rep2~WBPaper00040808:1.1uM_DMSO_control_rep3~WBPaper00040808:1.1uM_DMSO_control_rep4~WBPaper00040808:1.1uM_DMSO_control_rep5	Method: microarray|Species: Caenorhabditis elegans
117	22372763	WBPaper00040821.ce.mr.paper	GSE32521	GPL200	1	Toxicogenomic responses of the model organism Caenorhabditis elegans to gold nanoparticles.	We used Au nanoparticles (Au-NPs) as a model for studying particle-specific effects of manufactured nanomaterials (MNMs) by examining the toxicogenomic responses in a model soil organism, Caenorhabditis elegans . Global genome expression for nematodes exposed to 4-nm citrate-coated Au-NPs at the LC(10) level (5.9 mg-L(-1)) revealed significant differential expression of 797 genes. The levels of expression for five genes (apl-1, dyn-1, act-5, abu-11, and hsp-4) were confirmed independently with qRT-PCR. Seven common biological pathways associated with 38 of these genes were identified. Up-regulation of 26 pqn/abu genes from noncanonical unfolded protein response (UPR) pathway and molecular chaperones (hsp-16.1, hsp-70, hsp-3, and hsp-4) were observed and are likely indicative of endoplasmic reticulum stress. Significant increase in sensitivity to Au-NPs in a mutant from noncanonical UPR (pqn-5) suggests possible involvement of the genes from this pathway in a protective mechanism against Au-NPs. Significant responses to Au-NPs in endocytosis mutants (chc-1 and rme-2) provide evidence for endocytosis pathway being induced by Au-NPs. These results demonstrate that Au-NPs are bioavailable and cause adverse effects to C. elegans by activating both general and specific biological pathways. The experiments with mutants further support involvement of several of these pathways in Au-NP toxicity and/or detoxification.	6	17638	Tsyusko O	Tsyusko O, Unrine JM, Spurgeon DJ, Blalock EM, Starnes D, Tseng MT, Joice G, Bertsch PM	Toxicogenomic responses of the model organism Caenorhabditis elegans to gold nanoparticles.	Environ Sci Technol	2012	WBPaper00040821:Control_Replicate1~WBPaper00040821:Control_Replicate2~WBPaper00040821:Control_Replicate3~WBPaper00040821:Au-NP_Replicate1~WBPaper00040821:Au-NP_Replicate2~WBPaper00040821:Au-NP_Replicate3	Method: microarray|Species: Caenorhabditis elegans|Topic: programmed cell death|Topic: apoptotic DNA fragmentation|Topic: apoptotic process|Topic: engulfment of apoptotic cell|Topic: response to unfolded protein|Topic: endoplasmic reticulum|Topic: mitochondrion|Topic: cytosol|Topic: stress response to metal ion
118	22454234	WBPaper00040925.ce.mr.paper	GSE32941,GSE32943,GSE32944	GPL14724	1	RIP-chip-SRM--a new combinatorial large-scale approach identifies a set of translationally regulated bantam/miR-58 targets in C. elegans.	MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression. As miRNAs are involved in a wide range of biological processes and diseases, much effort has been invested in identifying their mRNA targets. Here, we present a novel combinatorial approach, RIP-chip-SRM (RNA-binding protein immunopurification + microarray + targeted protein quantification via selected reaction monitoring), to identify de novo high-confidence miRNA targets in the nematode Caenorhabditis elegans. We used differential RIP-chip analysis of miRNA-induced silencing complexes from wild-type and miRNA mutant animals, followed by quantitative targeted proteomics via selected reaction monitoring to identify and validate mRNA targets of the C. elegans bantam homolog miR-58. Comparison of total mRNA and protein abundance changes in mir-58 mutant and wild-type animals indicated that the direct bantam/miR-58 targets identified here are mainly regulated at the level of protein abundance, not mRNA stability.	6	12754	Jovanovic M	Jovanovic M, Reiter L, Clark A, Weiss M, Picotti P, Rehrauer H, Frei A, Neukomm L, Kaufman E, Wollscheid B, Simard MJ, Miska E, Aebersold R, Gerber AP, Hengartner MO	RIP-chip-SRM--a new combinatorial large-scale approach identifies a set of translationally regulated bantam/miR-58 targets in C. elegans.	Genome Res	2012	WBPaper00040925:WS5041_Rep1~WBPaper00040925:WS4303_Rep1~WBPaper00040925:WS5041_Rep2~WBPaper00040925:WS4303_Rep2~WBPaper00040925:WS5041_Rep3~WBPaper00040925:WS4303_Rep3	Method: microarray|Species: Caenorhabditis elegans
119	22493606	WBPaper00040963.ce.mr.paper	GSE35354	GPL200	1	Meta-Analysis of Global Transcriptomics Suggests that Conserved Genetic Pathways are Responsible for Quercetin and Tannic Acid Mediated Longevity in C. elegans.	Recent research has highlighted that the polyphenols Quercetin and Tannic acid are capable of extending the lifespan of Caenorhabditis elegans. To gain a deep understanding of the underlying molecular genetics, we analyzed the global transcriptional patterns of nematodes exposed to three concentrations of Quercetin or Tannic acid, respectively. By means of an intricate meta-analysis it was possible to compare the transcriptomes of polyphenol exposure to recently published datasets derived from (i) longevity mutants or (ii) infection. This detailed comparative in silico analysis facilitated the identification of compound specific and overlapping transcriptional profiles and allowed the prediction of putative mechanistic models of Quercetin and Tannic acid mediated longevity. Lifespan extension due to Quercetin was predominantly driven by the metabolome, TGF-beta signaling, Insulin-like signaling, and the p38 MAPK pathway and Tannic acid's impact involved, in part, the amino acid metabolism and was modulated by the TGF-beta and the p38 MAPK pathways. DAF-12, which integrates TGF-beta and Insulin-like downstream signaling, and genetic players of the p38 MAPK pathway therefore seem to be crucial regulators for both polyphenols. Taken together, this study underlines how meta-analyses can provide an insight of molecular events that go beyond the traditional categorization into gene ontology-terms and Kyoto encyclopedia of genes and genomes-pathways. It also supports the call to expand the generation of comparative and integrative databases, an effort that is currently still in its infancy.	24	17638	Pietsch K	Pietsch K, Saul N, Swain SC, Menzel R, Steinberg CE, Sturzenbaum SR	Meta-Analysis of Global Transcriptomics Suggests that Conserved Genetic Pathways are Responsible for Quercetin and Tannic Acid Mediated Longevity in C. elegans.	Front Genet	2012	WBPaper00040963:Q_Control_rep1~WBPaper00040963:Q_Control_rep2~WBPaper00040963:Q_Control_rep3~WBPaper00040963:Q_50_rep1~WBPaper00040963:Q_50_rep2~WBPaper00040963:Q_50_rep3~WBPaper00040963:Q_100_rep1~WBPaper00040963:Q_100_rep2~WBPaper00040963:Q_100_rep3~WBPaper00040963:Q_200_rep1~WBPaper00040963:Q_200_rep2~WBPaper00040963:Q_200_rep3~WBPaper00040963:TA_Control_rep1~WBPaper00040963:TA_Control_rep2~WBPaper00040963:TA_Control_rep3~WBPaper00040963:TA_100_rep1~WBPaper00040963:TA_100_rep2~WBPaper00040963:TA_100_rep3~WBPaper00040963:TA_200_rep1~WBPaper00040963:TA_200_rep2~WBPaper00040963:TA_200_rep3~WBPaper00040963:TA_300_rep1~WBPaper00040963:TA_300_rep2~WBPaper00040963:TA_300_rep3	Method: microarray|Species: Caenorhabditis elegans
120	22529848	WBPaper00041002.ce.mr.paper	GSE35360	GPL200	1	The Nematode Caenorhabditis elegans, Stress and Aging: Identifying the Complex Interplay of Genetic Pathways Following the Treatment with Humic Substances.	Low concentrations of the dissolved leonardite humic acid HuminFeed() (HF) prolonged the lifespan and enhanced the thermal stress resistance of the model organism Caenorhabditis elegans. However, growth was impaired and reproduction delayed, effects which have also been identified in response to other polyphenolic monomers, including Tannic acid, Rosmarinic acid, and Caffeic acid. Moreover, a chemical modification of HF, which increases its phenolic/quinonoid moieties, magnified the biological impact on C. elegans. To gain a deep insight into the molecular basis of these effects, we performed global transcriptomics on young adult (3days) and old adult (11days) nematodes exposed to two different concentrations of HF. We also studied several C. elegans mutant strains in respect to HF derived longevity and compared all results with data obtained for the chemically modified HF. The gene expression pattern of young HF-treated nematodes displayed a significant overlap to other conditions known to provoke longevity, including various plant polyphenol monomers. Besides the regulation of parts of the metabolism, transforming growth factor-beta signaling, and Insulin-like signaling, lysosomal activities seem to contribute most to HF's and modified HF's lifespan prolonging action. These results support the notion that the phenolic/quinonoid moieties of humic substances are major building blocks that drive the physiological effects observed in C. elegans.	27	17638	Menzel R	Menzel R, Menzel S, Swain SC, Pietsch K, Tiedt S, Witczak J, Sturzenbaum SR, Steinberg CE	The Nematode Caenorhabditis elegans, Stress and Aging: Identifying the Complex Interplay of Genetic Pathways Following the Treatment with Humic Substances.	Front Genet	2012	WBPaper00041002:HF_3d_control_rep1~WBPaper00041002:HF_3d_control_rep2~WBPaper00041002:HF_3d_control_rep3~WBPaper00041002:HF_3d_0.2_rep1~WBPaper00041002:HF_3d_0.2_rep2~WBPaper00041002:HF_3d_0.2_rep3~WBPaper00041002:HF_3d_2.0_rep1~WBPaper00041002:HF_3d_2.0_rep2~WBPaper00041002:HF_3d_2.0_rep3~WBPaper00041002:HF_11d_control_rep1~WBPaper00041002:HF_11d_control_rep2~WBPaper00041002:HF_11d_control_rep3~WBPaper00041002:HF_11d_0.2_rep1~WBPaper00041002:HF_11d_0.2_rep2~WBPaper00041002:HF_11d_0.2_rep3~WBPaper00041002:HF_11d_2.0_rep1~WBPaper00041002:HF_11d_2.0_rep2~WBPaper00041002:HF_11d_2.0_rep3~WBPaper00041002:HFHQ_3d_control_rep1~WBPaper00041002:HFHQ_3d_control_rep2~WBPaper00041002:HFHQ_3d_control_rep3~WBPaper00041002:HFHQ_3d_0.2_rep1~WBPaper00041002:HFHQ_3d_0.2_rep2~WBPaper00041002:HFHQ_3d_0.2_rep3~WBPaper00041002:HFHQ_3d_2.0_rep1~WBPaper00041002:HFHQ_3d_2.0_rep2~WBPaper00041002:HFHQ_3d_2.0_rep3	Method: microarray|Species: Caenorhabditis elegans
121	22675448	WBPaper00041163.ce.mr.paper	GSE34026	GPL200	1	Genomic analysis of immune response against Vibrio cholerae hemolysin in Caenorhabditis elegans.	Vibrio cholerae cytolysin (VCC) is among the accessory V. cholerae virulence factors that may contribute to disease pathogenesis in humans. VCC, encoded by hlyA gene, belongs to the most common class of bacterial toxins, known as pore-forming toxins (PFTs). V. cholerae infects and kills Caenorhabditis elegans via cholerae toxin independent manner. VCC is required for the lethality, growth retardation and intestinal cell vacuolation during the infection. However, little is known about the host gene expression responses against VCC. To address this question we performed a microarray study in C. elegans exposed to V. cholerae strains with intact and deleted hlyA genes.Many of the VCC regulated genes identified, including C-type lectins, Prion-like (glutamine [Q]/asparagine [N]-rich)-domain containing genes, genes regulated by insulin/IGF-1-mediated signaling (IIS) pathway, were previously reported as mediators of innate immune response against other bacteria in C. elegans. Protective function of the subset of the genes up-regulated by VCC was confirmed using RNAi. By means of a machine learning algorithm called FastMEDUSA, we identified several putative VCC induced immune regulatory transcriptional factors and transcription factor binding motifs. Our results suggest that VCC is a major virulence factor, which induces a wide variety of immune response- related genes during V. cholerae infection in C. elegans.	15	17638	Sahu SN	Sahu SN, Lewis J, Patel I, Bozdag S, Lee JH, Leclerc JE, Cinar HN	Genomic analysis of immune response against Vibrio cholerae hemolysin in Caenorhabditis elegans.	PLoS One	2012	WBPaper00041163:N2_CVD109_rep1~WBPaper00041163:N2_CVD109_rep2~WBPaper00041163:N2_CVD109_rep3~WBPaper00041163:N2_CVD110_rep1~WBPaper00041163:N2_CVD110_rep2~WBPaper00041163:N2_CVD110_rep3~WBPaper00041163:N2_hemolysin-E7946_rep1~WBPaper00041163:N2_hemolysin-E7946_rep2~WBPaper00041163:N2_hemolysin-E7946_rep3~WBPaper00041163:N2_E7946_rep1~WBPaper00041163:N2_E7946_rep2~WBPaper00041163:N2_E7946_rep3~WBPaper00041163:N2_OP50_rep1~WBPaper00041163:N2_OP50_rep2~WBPaper00041163:N2_OP50_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response|Topic: response to unfolded protein|Topic: endoplasmic reticulum|Topic: mitochondrion|Topic: cytosol
122	22700655	WBPaper00041191.ce.mr.paper	GSE37432,GSE37433	GPL200	1	Function, targets, and evolution of Caenorhabditis elegans piRNAs.	Piwi-interacting RNAs (piRNAs) are small RNAs required to maintain germline integrity and fertility, but their mechanism of action is poorly understood. Here we demonstrate that Caenorhabditis elegans piRNAs silence transcripts in trans through imperfectly complementary sites. Target silencing is independent of Piwi endonuclease activity or &quot;slicing.&quot; Instead, piRNAs initiate a localized secondary endogenous small interfering RNA (endo-siRNA) response. Endogenous protein-coding gene and transposon transcripts exhibit Piwi-dependent endo-siRNAs at sites complementary to piRNAs and are derepressed in Piwi mutants. Genomic loci of piRNA biogenesis are depleted of protein-coding genes and tend to overlap the start and end of transposons in sense and antisense, respectively. Our data suggest that nematode piRNA clusters are evolving to generate piRNAs against active mobile elements. Thus, piRNAs provide heritable, sequence-specific triggers for RNA interference in C. elegans.	9	17638	Bagijn MP	Bagijn MP, Goldstein LD, Sapetschnig A, Weick EM, Bouasker S, Lehrbach NJ, Simard MJ, Miska EA	Function, targets, and evolution of Caenorhabditis elegans piRNAs.	Science	2012	WBPaper00041191:N2_rep1~WBPaper00041191:N2_rep2~WBPaper00041191:N2_rep3~WBPaper00041191:piwi_n4357_n4358_rep1~WBPaper00041191:piwi_n4357_n4358_rep2~WBPaper00041191:piwi_n4357_n4358_rep3~WBPaper00041191:piwi_n4503_nDf57_rep1~WBPaper00041191:piwi_n4503_nDf57_rep2~WBPaper00041191:piwi_n4503_nDf57_rep3	Method: microarray|Species: Caenorhabditis elegans
123	22719261	WBPaper00041211.ce.mr.paper	GSE37266	GPL200	1	Stimulation of host immune defenses by a small molecule protects C. elegans from bacterial infection.	The nematode Caenorhabditis elegans offers currently untapped potential for carrying out high-throughput, live-animal screens of low molecular weight compound libraries to identify molecules that target a variety of cellular processes. We previously used a bacterial infection assay in C. elegans to identify 119 compounds that affect host-microbe interactions among 37,214 tested. Here we show that one of these small molecules, RPW-24, protects C. elegans from bacterial infection by stimulating the host immune response of the nematode. Using transcriptome profiling, epistasis pathway analyses with C. elegans mutants, and an RNAi screen, we show that RPW-24 promotes resistance to Pseudomonas aeruginosa infection by inducing the transcription of a remarkably small number of C. elegans genes (1.3% of all genes) in a manner that partially depends on the evolutionarily-conserved p38 MAP kinase pathway and the transcription factor ATF-7. These data show that the immunostimulatory activity of RPW-24 is required for its efficacy and define a novel C. elegans-based strategy to identify compounds with activity against antibiotic-resistant bacterial pathogens.	6	17638	Pukkila-Worley R	Pukkila-Worley R, Feinbaum R, Kirienko NV, Larkins-Ford J, Conery AL, Ausubel FM	Stimulation of host immune defenses by a small molecule protects C. elegans from bacterial infection.	PLoS Genet	2012	WBPaper00041211:DMSO_G~WBPaper00041211:DMSO_H~WBPaper00041211:DMSO_I~WBPaper00041211:RPW-24_G~WBPaper00041211:RPW-24_H~WBPaper00041211:RPW-24_I	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
124	22768380	WBPaper00041267.ce.mr.paper	GSE36358	GPL200	1	Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans.	How microgravitational space environments affect aging is not well understood. We observed that, in Caenorhabditis elegans, spaceflight suppressed the formation of transgenically expressed polyglutamine aggregates, which normally accumulate with increasing age. Moreover, the inactivation of each of seven genes that were down-regulated in space extended lifespan on the ground. These genes encode proteins that are likely related to neuronal or endocrine signaling: acetylcholine receptor, acetylcholine transporter, choline acetyltransferase, rhodopsin-like receptor, glutamate-gated chloride channel, shaker family of potassium channel, and insulin-like peptide. Most of them mediated lifespan control through the key longevity-regulating transcription factors DAF-16 or SKN-1 or through dietary-restriction signaling, singly or in combination. These results suggest that aging in C. elegans is slowed through neuronal and endocrine response to space environmental cues.	5	17637	Honda Y	Honda Y, Higashibata A, Matsunaga Y, Yonezawa Y, Kawano T, Higashitani A, Kuriyama K, Shimazu T, Tanaka M, Szewczyk NJ, Ishioka N, Honda S	Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans.	Sci Rep	2012	WBPaper00041267:GroundControl_OperationSite~WBPaper00041267:GroundControl_TsukubaSpaceCenter~WBPaper00041267:SpaceFlight~WBPaper00041267:ClinoRotation~WBPaper00041267:HyperGravity	Method: microarray|Species: Caenorhabditis elegans
125	22700657	WBPaper00041370.ce.mr.paper	GSE38196	GPL200	1	Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation.	To better understand the response to mitochondrial dysfunction, we examined the mechanism by which ATFS-1 (activating transcription factor associated with stress-1) senses mitochondrial stress and communicates with the nucleus during the mitochondrial unfolded protein response (UPR(mt)) in Caenorhabditis elegans. We found that the key point of regulation is the mitochondrial import efficiency of ATFS-1. In addition to a nuclear localization sequence, ATFS-1 has an N-terminal mitochondrial targeting sequence that is essential for UPR(mt) repression. Normally, ATFS-1 is imported into mitochondria and degraded. However, during mitochondrial stress, we found that import efficiency was reduced, allowing a percentage of ATFS-1 to accumulate in the cytosol and traffic to the nucleus. Our results show that cells monitor mitochondrial import efficiency via ATFS-1 to coordinate the level of mitochondrial dysfunction with the protective transcriptional response.	12	17638	Nargund AM	Nargund AM, Pellegrino MW, Fiorese CJ, Baker BM, Haynes CM	Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation.	Science	2012	WBPaper00041370:wild-type-control_Rep1~WBPaper00041370:wild-type-spg-7(RNAi)_Rep1~WBPaper00041370:atfs-1(tm4525)-control_Rep1~WBPaper00041370:atfs-1(tm4525)-spg-7(RNAi)_Rep1~WBPaper00041370:wild-type-control_Rep2~WBPaper00041370:wild-type-spg-7(RNAi)_Rep2~WBPaper00041370:atfs-1(tm4525)-control_Rep2~WBPaper00041370:atfs-1(tm4525)-spg-7(RNAi)_Rep2~WBPaper00041370:wild-type-control_Rep3~WBPaper00041370:wild-type-spg-7(RNAi)_Rep3~WBPaper00041370:atfs-1(tm4525)-control_Rep3~WBPaper00041370:atfs-1(tm4525)-spg-7(RNAi)_Rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: mitochondrial unfolded protein response|Topic: mitochondrion|Topic: response to unfolded protein|Topic: endoplasmic reticulum|Topic: cytosol
126	23300685	WBPaper00041906.ce.mr.paper	GSE42192	GPL200	1	Anti-inflammatory Lactobacillus rhamnosus CNCM I-3690 strain protects against oxidative stress and increases lifespan in Caenorhabditis elegans.	Numerous studies have shown that resistance to oxidative stress is crucial to stay healthy and to reduce the adverse effects of aging. Accordingly, nutritional interventions using antioxidant food-grade compounds or food products are currently an interesting option to help improve health and quality of life in the elderly. Live lactic acid bacteria (LAB) administered in food, such as probiotics, may be good antioxidant candidates. Nevertheless, information about LAB-induced oxidative stress protection is scarce. To identify and characterize new potential antioxidant probiotic strains, we have developed a new functional screening method using the nematode Caenorhabditis elegans as host. C. elegans were fed on different LAB strains (78 in total) and nematode viability was assessed after oxidative stress (3 mM and 5 mM H(2)O(2)). One strain, identified as Lactobacillus rhamnosus CNCM I-3690, protected worms by increasing their viability by 30% and, also, increased average worm lifespan by 20%. Moreover, transcriptomic analysis of C. elegans fed with this strain showed that increased lifespan is correlated with differential expression of the DAF-16/insulin-like pathway, which is highly conserved in humans. This strain also had a clear anti-inflammatory profile when co-cultured with HT-29 cells, stimulated by pro-inflammatory cytokines, and co-culture systems with HT-29 cells and DC in the presence of LPS. Finally, this Lactobacillus strain reduced inflammation in a murine model of colitis. This work suggests that C. elegans is a fast, predictive and convenient screening tool to identify new potential antioxidant probiotic strains for subsequent use in humans.	18	17638	Grompone G	Grompone G, Martorell P, Llopis S, Gonzalez N, Genoves S, Mulet AP, Fernandez-Calero T, Tiscornia I, Bollati-Fogolin M, Chambaud I, Foligne B, Montserrat A, Ramon D	Anti-inflammatory Lactobacillus rhamnosus CNCM I-3690 strain protects against oxidative stress and increases lifespan in Caenorhabditis elegans.	PLoS One	2012	WBPaper00041906:E-coli_OP50_3d_rep1~WBPaper00041906:E-coli_OP50_3d_rep2~WBPaper00041906:E-coli_OP50_3d_rep3~WBPaper00041906:CNCM_I-3690_3d_rep1~WBPaper00041906:CNCM_I-3690_3d_rep2~WBPaper00041906:CNCM_I-3690_3d_rep3~WBPaper00041906:CNCM_I-4317_3d_rep1~WBPaper00041906:CNCM_I-4317_3d_rep2~WBPaper00041906:CNCM_I-4317_3d_rep3~WBPaper00041906:E-coli_OP50_10d_rep1~WBPaper00041906:E-coli_OP50_10d_rep2~WBPaper00041906:E-coli_OP50_10d_rep3~WBPaper00041906:CNCM_I-3690_10d_rep1~WBPaper00041906:CNCM_I-3690_10d_rep2~WBPaper00041906:CNCM_I-3690_10d_rep3~WBPaper00041906:CNCM_I-4317_10d_rep1~WBPaper00041906:CNCM_I-4317_10d_rep2~WBPaper00041906:CNCM_I-4317_10d_rep3	Method: microarray|Species: Caenorhabditis elegans
127	23374645	WBPaper00041939.ce.mr.paper	GSE38997	GPL200	1	Effects of early life exposure to ultraviolet C radiation on mitochondrial DNA content, transcription, ATP production, and oxygen consumption in developing Caenorhabditis elegans.	BACKGROUND: Mitochondrial DNA (mtDNA) is present in multiple copies per cell and undergoes dramatic amplification during development. The impacts of mtDNA damage incurred early in development are not well understood, especially in the case of types of mtDNA damage that are irreparable, such as ultraviolet C radiation (UVC)-induced photodimers. METHODS: We exposed first larval stage nematodes to UVC using a protocol that results in accumulated mtDNA damage but permits nuclear DNA (nDNA) repair. We then measured the transcriptional response, as well as oxygen consumption, ATP levels, and mtDNA copy number through adulthood. RESULTS: Although the mtDNA damage persisted to the fourth larval stage, we observed only a relatively minor ~40% decrease in mtDNA copy number. Transcriptomic analysis suggested an inhibition of aerobic metabolism and developmental processes; mRNA levels for mtDNA-encoded genes were reduced ~50% at 3 hours post-treatment, but recovered and, in some cases, were upregulated at 24 and 48 hours post-exposure. The mtDNA polymerase  was also induced ~8-fold at 48 hours post-exposure. Moreover, ATP levels and oxygen consumption were reduced in response to UVC exposure, with marked reductions of ~50% at the later larval stages. CONCLUSIONS: These results support the hypothesis that early life exposure to mitochondrial genotoxicants could result in mitochondrial dysfunction at later stages of life, thereby highlighting the potential health hazards of time-delayed effects of these genotoxicants in the environment.	69	17638	Leung MC	Leung MC, Rooney JP, Ryde IT, Bernal AJ, Bess AS, Crocker TL, Ji AQ, Meyer JN	Effects of early life exposure to ultraviolet C radiation on mitochondrial DNA content, transcription, ATP production, and oxygen consumption in developing Caenorhabditis elegans.	BMC Pharmacol Toxicol	2013	WBPaper00041939:control_48h_exp1_1c48~WBPaper00041939:UVC-exposed_48h_exp1_1u48~WBPaper00041939:EtBr-exposed_48h_exp1_1e48~WBPaper00041939:UVC-EtBr-exposed_48h_exp1_1eu48~WBPaper00041939:control_51h_exp1_1c51~WBPaper00041939:UVC-exposed_51h_exp1_1u51~WBPaper00041939:EtBr-exposed_51h_exp1_1e51~WBPaper00041939:UVC-EtBr-exposed_51h_exp1_1eu51~WBPaper00041939:control_51h_exp2_2c51~WBPaper00041939:EtBr-exposed_51h_exp2_2e51~WBPaper00041939:UVC-EtBr-exposed_51h_exp2_2eu51~WBPaper00041939:control_3h_exp4_4c3~WBPaper00041939:UVC-exposed_3h_exp4_4u3~WBPaper00041939:EtBr-exposed_3h_exp4_4e3~WBPaper00041939:UVC-EtBr-exposed_3h_exp4_4eu3~WBPaper00041939:control_24h_exp4_4c24~WBPaper00041939:UVC-exposed_24h_exp4_4u24~WBPaper00041939:EtBr-exposed_24h_exp4_4e24~WBPaper00041939:UVC-EtBr-exposed_24h_exp4_4eu24~WBPaper00041939:control_48h_exp4_4c48~WBPaper00041939:UVC-exposed_48h_exp4_4u48~WBPaper00041939:EtBr-exposed_48h_exp4_4e48~WBPaper00041939:UVC-EtBr-exposed_48h_exp4_4eu48~WBPaper00041939:control_51h_exp4_4c51~WBPaper00041939:UVC-exposed_51h_exp4_4u51~WBPaper00041939:EtBr-exposed_51h_exp4_4e51~WBPaper00041939:UVC-EtBr-exposed_51h_exp4_4eu51~WBPaper00041939:control_3h_exp5_5c3~WBPaper00041939:UVC-exposed_3h_exp5_5u3~WBPaper00041939:EtBr-exposed_3h_exp5_5e3~WBPaper00041939:UVC-EtBr-exposed_3h_exp5_5eu3~WBPaper00041939:control_24h_exp5_5c24~WBPaper00041939:UVC-exposed_24h_exp5_5u24~WBPaper00041939:EtBr-exposed_24h_exp5_5e24~WBPaper00041939:UVC-EtBr-exposed_24h_exp5_5eu24~WBPaper00041939:control_48h_exp5_5c48~WBPaper00041939:UVC-exposed_48h_exp5_5u48~WBPaper00041939:UVC-EtBr-exposed_48h_exp5_5Eu48~WBPaper00041939:control_51h_exp5~WBPaper00041939:UVC-exposed_51h_exp5_5u51~WBPaper00041939:EtBr-exposed_51h_exp5_5e51~WBPaper00041939:UVC-EtBr-exposed_51h_exp5_5Eu51~WBPaper00041939:control_3h_exp6_6c3~WBPaper00041939:UVC-exposed_3h_exp6~WBPaper00041939:EtBr-exposed_3h_exp6~WBPaper00041939:UVC-EtBr-exposed_3h_exp6~WBPaper00041939:control_24h_exp6_6c24~WBPaper00041939:UVC-exposed_24h_exp6_6u24~WBPaper00041939:EtBr-exposed_24h_exp6_6e24~WBPaper00041939:UVC-EtBr-exposed_24h_exp6_6Eu24~WBPaper00041939:EtBr-exposed_48h_exp6_6e48~WBPaper00041939:UVC-EtBr-exposed_48h_exp6_6Eu48~WBPaper00041939:EtBr-exposed_51h_exp6_6e51~WBPaper00041939:UVC-EtBr-exposed_51h_exp6_6Eu51~WBPaper00041939:control_3h_exp7_7c3~WBPaper00041939:UVC-exposed_3h_exp7_7u3~WBPaper00041939:EtBr-exposed_3h_exp7_7e3~WBPaper00041939:UVC-EtBr-exposed_3h_exp7_7eu3~WBPaper00041939:control_24h_exp7_7c24~WBPaper00041939:UVC-exposed_24h_exp7_7u24~WBPaper00041939:EtBr-exposed_24h_exp7_7e24~WBPaper00041939:UVC-EtBr-exposed_24h_exp7_7eu24~WBPaper00041939:control_48h_exp7_7c48~WBPaper00041939:UVC-exposed_48h_exp7_7u48~WBPaper00041939:EtBr-exposed_48h_exp7_7e48~WBPaper00041939:UVC-EtBr-exposed_48h_exp7_7eu48~WBPaper00041939:control_51h_exp7_7c51~WBPaper00041939:UVC-exposed_51h_exp7_7u51~WBPaper00041939:UVC-EtBr-exposed_51h_exp7_7eu51	Method: microarray|Species: Caenorhabditis elegans
128	23352664	WBPaper00041960.ce.mr.paper	GSE27677,GSE42689	GPL200	1	A fasting-responsive signaling pathway that extends life span in C. elegans.	Intermittent fasting is one of the most effective dietary restriction regimens that extend life span in C. elegans and mammals. Fasting-stimulus responses are key to the longevity response; however, the mechanisms that sense and transduce the fasting stimulus remain largely unknown. Through a comprehensive transcriptome analysis in C. elegans, we find that along with the FOXO transcription factor DAF-16, AP-1 (JUN-1/FOS-1) plays a central role in fasting-induced transcriptional changes. KGB-1, one of the C. elegans JNKs, acts as an activator of AP-1 and is activated in response to fasting. KGB-1 and AP-1 are involved in intermittent fasting-induced longevity. Fasting-induced upregulation of the components of the SCF E3 ubiquitin ligase complex via AP-1 and DAF-16 enhances protein ubiquitination and reduces protein carbonylation. Our results thus identify a fasting-responsive KGB-1/AP-1 signaling pathway, which, together with DAF-16, causes transcriptional changes that mediate longevity, partly through regulating proteostasis.	56	17638	Uno M	Uno M, Honjoh S, Matsuda M, Hoshikawa H, Kishimoto S, Yamamoto T, Ebisuya M, Matsumoto K, Nishida E	A fasting-responsive signaling pathway that extends life span in C. elegans.	Cell Rep	2013	WBPaper00041960:N2_fed_0h_rep1~WBPaper00041960:N2_fed_0h_rep2~WBPaper00041960:N2_fed_24h_rep1~WBPaper00041960:N2_fed_24h_rep2~WBPaper00041960:N2_fed_48h_rep1~WBPaper00041960:N2_fed_48h_rep2~WBPaper00041960:N2_fasted_3h_rep1~WBPaper00041960:N2_fasted_3h_rep2~WBPaper00041960:N2_fasted_6h_rep1~WBPaper00041960:N2_fasted_6h_rep2~WBPaper00041960:N2_fasted_9h_rep1~WBPaper00041960:N2_fasted_9h_rep2~WBPaper00041960:N2_fasted_12h_rep1~WBPaper00041960:N2_fasted_12h_rep2~WBPaper00041960:N2_fasted_18h_rep1~WBPaper00041960:N2_fasted_18h_rep2~WBPaper00041960:N2_fasted_24h_rep1~WBPaper00041960:N2_fasted_24h_rep2~WBPaper00041960:N2_fasted_36h_rep1~WBPaper00041960:N2_fasted_36h_rep2~WBPaper00041960:N2_fasted_48h_rep1~WBPaper00041960:N2_fasted_48h_rep2~WBPaper00041960:N2_fed_rep1~WBPaper00041960:N2_fed_rep2~WBPaper00041960:N2_fed_rep3~WBPaper00041960:N2_fasted_rep1~WBPaper00041960:N2_fasted_rep2~WBPaper00041960:N2_fasted_rep3~WBPaper00041960:kgb-1_fed_rep1~WBPaper00041960:kgb-1_fed_rep2~WBPaper00041960:kgb-1_fed_rep3~WBPaper00041960:kgb-1_fasted_rep1~WBPaper00041960:kgb-1_fasted_rep2~WBPaper00041960:kgb-1_fasted_rep3~WBPaper00041960:jun-1_fed_rep1~WBPaper00041960:jun-1_fed_rep2~WBPaper00041960:jun-1_fed_rep3~WBPaper00041960:jun-1_fasted_rep1~WBPaper00041960:jun-1_fasted_rep2~WBPaper00041960:jun-1_fasted_rep3~WBPaper00041960:daf-16_fed_rep1~WBPaper00041960:daf-16_fed_rep2~WBPaper00041960:daf-16_fed_rep3~WBPaper00041960:daf-16_fasted_rep1~WBPaper00041960:daf-16_fasted_rep2~WBPaper00041960:daf-16_fasted_rep3~WBPaper00041960:mek-1_fed_rep1~WBPaper00041960:mek-1_fed_rep2~WBPaper00041960:mek-1_fed_rep3~WBPaper00041960:mek-1_fasted_rep1~WBPaper00041960:mek-1_fasted_rep2~WBPaper00041960:mek-1_fasted_rep3~WBPaper00041960:mlk-1_fed_rep1~WBPaper00041960:mlk-1_fed_rep2~WBPaper00041960:mlk-1_fasted_rep1~WBPaper00041960:mlk-1_fasted_rep2	Method: microarray|Species: Caenorhabditis elegans
129	23437011	WBPaper00042067.ce.mr.paper	GSE42703	GPL200	1	The Caenorhabditis elegans JNK signaling pathway activates expression of stress response genes by derepressing the Fos/HDAC repressor complex.	MAP kinases are integral to the mechanisms by which cells respond to a wide variety of environmental stresses. In Caenorhabditis elegans, the KGB-1 JNK signaling pathway regulates the response to heavy metal stress. In this study, we identified FOS-1, a bZIP transcription factor, as a target of KGB-1-mediated phosphorylation. We further identified two transcriptional targets of the KGB-1 pathway, kreg-1 and kreg-2/lys-3, which are required for the defense against heavy metal stress. FOS-1 plays a critical role in the transcriptional repression of the kreg-1 gene by recruiting histone deacetylase (HDAC) to its promoter. KGB-1 phosphorylation prevents FOS-1 dimerization and promoter binding, resulting in promoter derepression. Thus, HDAC behaves as a co-repressor modulating FOS-1-mediated transcriptional regulation. This study describes the direct link from JNK signaling, Fos phosphorylation, and regulation of kreg gene transcription, which modulates the stress response in C. elegans.	4	17638	Hattori A	Hattori A, Mizuno T, Akamatsu M, Hisamoto N, Matsumoto K	The Caenorhabditis elegans JNK signaling pathway activates expression of stress response genes by derepressing the Fos/HDAC repressor complex.	PLoS Genet	2013	WBPaper00042067:WT_H2O_rep1~WBPaper00042067:WT_CopperSulfate_rep1~WBPaper00042067:kgb-1_H2O_rep1~WBPaper00042067:kgb-1_CopperSulfate_rep1	Method: microarray|Species: Caenorhabditis elegans
130	23484030	WBPaper00042128.ce.mr.paper	GSE40127	GPL200	1	GEI-8, a homologue of vertebrate nuclear receptor corepressor NCoR/SMRT, regulates gonad development and neuronal functions in Caenorhabditis elegans.	NCoR and SMRT are two paralogous vertebrate proteins that function as corepressors with unliganded nuclear receptors. Although C. elegans has a large number of nuclear receptors, orthologues of the corepressors NCoR and SMRT have not unambiguously been identified in Drosophila or C. elegans. Here, we identify GEI-8 as the closest homologue of NCoR and SMRT in C. elegans and demonstrate that GEI-8 is expressed as at least two isoforms throughout development in multiple tissues, including neurons, muscle and intestinal cells. We demonstrate that a homozygous deletion within the gei-8 coding region, which is predicted to encode a truncated protein lacking the predicted NR domain, results in severe mutant phenotypes with developmental defects, slow movement and growth, arrested gonadogenesis and defects in cholinergic neurotransmission. Whole genome expression analysis by microarrays identified sets of de-regulated genes consistent with both the observed mutant phenotypes and a role of GEI-8 in regulating transcription. Interestingly, the upregulated transcripts included a predicted mitochondrial sulfide:quinine reductase encoded by Y9C9A.16. This locus also contains non-coding, 21-U RNAs of the piRNA class. Inhibition of the expression of the region coding for 21-U RNAs leads to irregular gonadogenesis in the homozygous gei-8 mutants, but not in an otherwise wild-type background, suggesting that GEI-8 may function in concert with the 21-U RNAs to regulate gonadogenesis. Our results confirm that GEI-8 is the orthologue of the vertebrate NCoR/SMRT corepressors and demonstrate important roles for this putative transcriptional corepressor in development and neuronal function.	6	17638	Mikolas P	Mikolas P, Kollarova J, Sebkova K, Saudek V, Yilma P, Kostrouchova M, Krause MW, Kostrouch Z	GEI-8, a homologue of vertebrate nuclear receptor corepressor NCoR/SMRT, regulates gonad development and neuronal functions in Caenorhabditis elegans.	PLoS One	2013	WBPaper00042128:N2_rep1~WBPaper00042128:gei-8(ok1671)_rep1~WBPaper00042128:N2_rep2~WBPaper00042128:gei-8(ok1671)_rep2~WBPaper00042128:N2_rep4~WBPaper00042128:gei-8(ok1671)_rep4	Method: microarray|Species: Caenorhabditis elegans
131	23533643	WBPaper00042178.ce.mr.paper	GSE65417	GPL200	1	Genome-wide microarrray analysis reveals roles for the REF-1 family member HLH-29 in ferritin synthesis and peroxide stress response.	In Caenorhabditis elegans, the six proteins that make up the REF-1 family have been identified as functional homologs of the Hairy/Enhancer of Split (HES) proteins. These transcription factors act in both Notch dependent and Notch-independent pathways to regulate embryonic events during development; however, their post-embryonic functions are not well defined. As a first step toward understanding how the REF-1 family works together to coordinate post-embryonic events, we used gene expression microarray analysis to identify transcriptional targets of HLH-29 in L4/young adult stage animals. Here we show that HLH-29 targets are genes needed for the regulation of growth and lifespan, including genes required for oxidative stress response and fatty acid metabolism, and the ferritin genes, ftn-1 and ftn-2. We show that HLH-29 regulates ftn-1 expression via promoter sequences upstream of the iron-dependent element that is recognized by the hypoxia inducible factor, HIF-1. Additionally, hlh-29 mutants are more resistant to peroxide stress than wild-type animals and ftn-1(RNAi) animals, even in the presence of excess iron. Finally we show that HLH-29 acts parallel to DAF-16 but upstream of the microphthalmia transcription factor ortholog, HLH-30, to regulate ftn-1 expression under normal growth conditions.	9	17638	Quach TK	Quach TK, Chou HT, Wang K, Milledge GZ, Johnson CM	Genome-wide microarrray analysis reveals roles for the REF-1 family member HLH-29 in ferritin synthesis and peroxide stress response.	PLoS One	2013	WBPaper00042178:N2_rep1~WBPaper00042178:N2_rep2~WBPaper00042178:N2_rep3~WBPaper00042178:hlh-25(ok1710)_rep1~WBPaper00042178:hlh-25(ok1710)_rep2~WBPaper00042178:hlh-25(ok1710)_rep3~WBPaper00042178:hlh-29(tm284)_rep1~WBPaper00042178:hlh-29(tm284)_rep2~WBPaper00042178:hlh-29(tm284)_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: stress response to metal ion
132	23540702	WBPaper00042204.ce.mr.paper	GSE43952	GPL200	1	Integration of metabolic and gene regulatory networks modulates the C. elegans dietary response.	Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network composed of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several transcription factors (TFs) that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus.	9	17638	Watson E	Watson E, MacNeil LT, Arda HE, Zhu LJ, Walhout AJ	Integration of metabolic and gene regulatory networks modulates the C. elegans dietary response.	Cell	2013	WBPaper00042204:N2_fed_DA1877_rep1~WBPaper00042204:N2_fed_DA1877_rep2~WBPaper00042204:N2_fed_DA1877_rep3~WBPaper00042204:metr-1(ok521)_fed_DA1877_rep1~WBPaper00042204:metr-1(ok521)_fed_DA1877_rep2~WBPaper00042204:metr-1(ok521)_fed_DA1877_rep3~WBPaper00042204:pcca-1(ok2282)_fed_DA1877_rep1~WBPaper00042204:pcca-1(ok2282)_fed_DA1877_rep2~WBPaper00042204:pcca-1(ok2282)_fed_DA1877_rep3	Method: microarray|Species: Caenorhabditis elegans
133	23580547	WBPaper00042234.ce.mr.paper	GSE39252	GPL200	1	Active transcriptomic and proteomic reprogramming in the C. elegans nucleotide excision repair mutant xpa-1.	Transcription-blocking oxidative DNA damage is believed to contribute to aging and to underlie activation of oxidative stress responses and down-regulation of insulin-like signaling (ILS) in Nucleotide Excision Repair (NER) deficient mice. Here, we present the first quantitative proteomic description of the Caenorhabditis elegans NER-defective xpa-1 mutant and compare the proteome and transcriptome signatures. Both methods indicated activation of oxidative stress responses, which was substantiated biochemically by a bioenergetic shift involving increased steady-state reactive oxygen species (ROS) and Adenosine triphosphate (ATP) levels. We identify the lesion-detection enzymes of Base Excision Repair (NTH-1) and global genome NER (XPC-1 and DDB-1) as upstream requirements for transcriptomic reprogramming as RNA-interference mediated depletion of these enzymes prevented up-regulation of genes over-expressed in the xpa-1 mutant. The transcription factors SKN-1 and SLR-2, but not DAF-16, were identified as effectors of reprogramming. As shown in human XPA cells, the levels of transcription-blocking 8,5'-cyclo-2'-deoxyadenosine lesions were reduced in the xpa-1 mutant compared to the wild type. Hence, accumulation of cyclopurines is unlikely to be sufficient for reprogramming. Instead, our data support a model where the lesion-detection enzymes NTH-1, XPC-1 and DDB-1 play active roles to generate a genomic stress signal sufficiently strong to result in transcriptomic reprogramming in the xpa-1 mutant.	10	17638	Arczewska KD	Arczewska KD, Tomazella GG, Lindvall JM, Kassahun H, Maglioni S, Torgovnick A, Henriksson J, Matilainen O, Marquis BJ, Nelson BC, Jaruga P, Babaie E, Holmberg CI, Burglin TR, Ventura N, Thiede B, Nilsen H	Active transcriptomic and proteomic reprogramming in the C. elegans nucleotide excision repair mutant xpa-1.	Nucleic Acids Res	2013	WBPaper00042234:N2_rep1~WBPaper00042234:N2_rep2~WBPaper00042234:N2_rep3~WBPaper00042234:N2_rep4~WBPaper00042234:N2_rep5~WBPaper00042234:xpa-1_rep1~WBPaper00042234:xpa-1_rep2~WBPaper00042234:xpa-1_rep3~WBPaper00042234:xpa-1_rep4~WBPaper00042234:xpa-1_rep5	Method: microarray|Species: Caenorhabditis elegans
134	23540701	WBPaper00042258.ce.mr.paper	GSE43959,GSE43953,GSE43954	GPL200	1	Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.	Dietary composition has major effects on physiology. Here, we show that developmental rate, reproduction, and lifespan are altered in C.elegans fed Comamonas DA1877 relative to those fed a standard E.coli OP50 diet. We identify a set of genes that change in expression in response to this diet and use the promoter of one of these (acdh-1) as a dietary sensor. Remarkably, the effects on transcription anddevelopment occur even when Comamonas DA1877 is diluted with another diet, suggesting that Comamonas DA1877 generates a signal that is sensed by the nematode. Surprisingly, the developmental effect is independent from TOR and insulin signaling. Rather, Comamonas DA1877 affects cyclic gene expression during molting, likely through the nuclear hormone receptor NHR-23. Altogether, our findings indicate that different bacteria elicit various responses via distinct mechanisms, which has implications for diseases such as obesity and the interactions between the human microbiome and intestinal cells.	18	17638	MacNeil LT	MacNeil LT, Watson E, Arda HE, Zhu LJ, Walhout AJ	Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.	Cell	2013	WBPaper00042258:N2_gravid-adult_DA1877_rep1~WBPaper00042258:N2_gravid-adult_DA1877_rep2~WBPaper00042258:N2_gravid-adult_DA1877_rep3~WBPaper00042258:N2_gravid-adult_diluted-DA1877_rep1~WBPaper00042258:N2_gravid-adult_diluted-DA1877_rep2~WBPaper00042258:N2_gravid-adult_diluted-DA1877_rep3~WBPaper00042258:N2_gravid-adult_OP50_rep1~WBPaper00042258:N2_gravid-adult_OP50_rep2~WBPaper00042258:N2_gravid-adult_OP50_rep3~WBPaper00042258:N2_young-adult_OP50_rep1~WBPaper00042258:N2_young-adult_OP50_rep2~WBPaper00042258:N2_young-adult_OP50_rep3~WBPaper00042258:N2_young-adult_HT115_rep1~WBPaper00042258:N2_young-adult_HT115_rep2~WBPaper00042258:N2_young-adult_HT115_rep3~WBPaper00042258:N2_young-adult_DA1877_rep1~WBPaper00042258:N2_young-adult_DA1877_rep2~WBPaper00042258:N2_young-adult_DA1877_rep3	Method: microarray|Species: Caenorhabditis elegans
135	23623425	WBPaper00042331.ce.mr.paper	GSE41486	GPL200	1	Molecular characterization of toxicity mechanism of single-walled carbon nanotubes.	Carbon nanotubes (CNTs) are one of widely used nanomaterials in industry and biomedicine. The potential impact of single-walled carbon nanotubes (SWCNTs) was evaluated using Caenorhabditis elegans (C. elegans) as a toxicological animal model. SWCNTs are extremely hydrophobic to form large agglomerates in aqueous solutions. Highly soluble amide-modified SWCNTs (a-SWCNTs) were therefore used in the present study so that the exact impact of SWCNTs could be studied. No significant toxicity was observed in C. elegans due to the amide modification. a-SWCNTs were efficiently taken up by worms and caused acute toxicity, including retarded growth, shortened lifespan and defective embryogenesis. The resulting toxicity was reversible since C. elegans could recover from a-SWCNT-induced toxicity once the exposure terminates. Chronic exposure to low doses of a-SWCNTs during all development stages could also cause a toxic accumulation in C. elegans. Genome-wide gene expression analysis was performed to investigate the toxic molecular mechanisms. Functional genomic analysis and molecular biology validation suggest that defective endocytosis, the decreased activity of the citrate cycle and the reduced nuclear translocation of DAF-16 transcription factor play key roles in inducing the observed a-SWCNT toxicity in worms. The present study presents an integrated approach to evaluating the toxicity of nanomaterials at the organism and molecular level for human and environmental health and demonstrates that traditional toxicological endpoints associated with functional genomic analysis can provide global and thorough insight into toxicity.	2	17638	Chen PH	Chen PH, Hsiao KM, Chou CC	Molecular characterization of toxicity mechanism of single-walled carbon nanotubes.	Biomaterials	2013	WBPaper00042331:Without-SWCNT-48hr-22C~WBPaper00042331:With-SWCNT-48hr-22C	Method: microarray|Species: Caenorhabditis elegans
136	23631360	WBPaper00042340.ce.mr.paper	GSE41366	GPL200	1	Alterations in gene expression in Caenorhabditis elegans associated with organophosphate pesticide intoxication and recovery.	BACKGROUND: The principal toxicity of acute organophosphate (OP) pesticide poisoning is the disruption of neurotransmission through inhibition of acetylcholinesterase (AChE). However, other mechanisms leading to persistent effects and neurodegeneration remain controversial and difficult to detect. Because Caenorhabditis elegans is relatively resistant to OP lethality--particularly through the inhibition of AChE--studies in this nematode provide an opportunity to observe alterations in global gene expression following OP exposure that cannot be readily observed in less resistant organisms. RESULTS: We exposed cultures of worms in axenic, defined medium to dichlorvos under three exposure protocols. In the first, worms were exposed continuously throughout the experiment. In the second and third, the worms were exposed for either 2 or 8 h, the dichlorvos was washed out of the culture, and the worms were allowed to recover. We then analyzed gene expression using whole genome microarrays from RNA obtained from worms sampled at multiple time points throughout the exposure. The worms showed a time-dependent increase in the expression of genes involved in stress responses. Early in the exposure, the predominant effect was on metabolic processes, while at later times, an immune-like response and cellular repair mechanisms dominated the expression pattern. Following removal of dichlorvos, the gene expression in the worms appeared to relatively rapidly return to steady-state levels. CONCLUSION: The changes in gene expression observed in the worms following exposure to dichlorvos point towards two potential mechanisms of toxicity: inhibition of AChE and mitochondrial disruption.	146	17638	Lewis JA	Lewis JA, Gehman EA, Baer CE, Jackson DA	Alterations in gene expression in Caenorhabditis elegans associated with organophosphate pesticide intoxication and recovery.	BMC Genomics	2013	WBPaper00042340:0uM-DDVP_continuous-expose_2h-harvest_rep1~WBPaper00042340:0.6uM-DDVP_continuous-expose_2h-harvest_rep1~WBPaper00042340:15uM-DDVP_continuous-expose_2h-harvest_rep1~WBPaper00042340:0uM-DDVP_2h-expose_8h-harvest_rep1~WBPaper00042340:0.6uM-DDVP_2h-expose_8h-harvest_rep1~WBPaper00042340:15uM-DDVP_2h-expose_8h-harvest_rep1~WBPaper00042340:0uM-DDVP_2h-expose_14h-harvest_rep1~WBPaper00042340:0.6uM-DDVP_2h-expose_14h-harvest_rep1~WBPaper00042340:15uM-DDVP_2h-expose_14h-harvest_rep1~WBPaper00042340:0uM-DDVP_2h-expose_20h-harvest_rep1~WBPaper00042340:0.6uM-DDVP_2h-expose_20h-harvest_rep1~WBPaper00042340:15uM-DDVP_2h-expose_20h-harvest_rep1~WBPaper00042340:0uM-DDVP_2h-expose_26h-harvest_rep1~WBPaper00042340:0.6uM-DDVP_2h-expose_26h-harvest_rep1~WBPaper00042340:15uM-DDVP_2h-expose_26h-harvest_rep1~WBPaper00042340:0uM-DDVP_continuous-expose_8h-harvest_rep1~WBPaper00042340:0.6uM-DDVP_continuous-expose_8h-harvest_rep1~WBPaper00042340:15uM-DDVP_continuous-expose_8h-harvest_rep1~WBPaper00042340:0uM-DDVP_8h-expose_14h-harvest_rep1~WBPaper00042340:0.6uM-DDVP_8h-expose_14h-harvest_rep1~WBPaper00042340:15uM-DDVP_8h-expose_14h-harvest_rep1~WBPaper00042340:0uM-DDVP_8h-expose_20h-harvest_rep1~WBPaper00042340:0.6uM-DDVP_8h-expose_20h-harvest_rep1~WBPaper00042340:15uM-DDVP_8h-expose_20h-harvest_rep1~WBPaper00042340:0uM-DDVP_8h-expose_26h-harvest_rep1~WBPaper00042340:0.6uM-DDVP_8h-expose_26h-harvest_rep1~WBPaper00042340:15uM-DDVP_8h-expose_26h-harvest_rep1~WBPaper00042340:0uM-DDVP_continuous-expose_14h-harvest_rep1~WBPaper00042340:0.6uM-DDVP_continuous-expose_14h-harvest_rep1~WBPaper00042340:15uM-DDVP_continuous-expose_14h-harvest_rep1~WBPaper00042340:0uM-DDVP_continuous-expose_20h-harvest_rep1~WBPaper00042340:0.6uM-DDVP_continuous-expose_20h-harvest_rep1~WBPaper00042340:15uM-DDVP_continuous-expose_20h-harvest_rep1~WBPaper00042340:0uM-DDVP_continuous-expose_26h-harvest_rep1~WBPaper00042340:0.6uM-DDVP_continuous-expose_26h-harvest_rep1~WBPaper00042340:15uM-DDVP_continuous-expose_26h-harvest_rep1~WBPaper00042340:0uM-DDVP_continuous-expose_0h-harvest_rep2~WBPaper00042340:0uM-DDVP_continuous-expose_2h-harvest_rep2~WBPaper00042340:0.6uM-DDVP_continuous-expose_2h-harvest_rep2~WBPaper00042340:15uM-DDVP_continuous-expose_2h-harvest_rep2~WBPaper00042340:0uM-DDVP_2h-expose_8h-harvest_rep2~WBPaper00042340:0.6uM-DDVP_2h-expose_8h-harvest_rep2~WBPaper00042340:15uM-DDVP_2h-expose_8h-harvest_rep2~WBPaper00042340:0uM-DDVP_2h-expose_14h-harvest_rep2~WBPaper00042340:0.6uM-DDVP_2h-expose_14h-harvest_rep2~WBPaper00042340:15uM-DDVP_2h-expose_14h-harvest_rep2~WBPaper00042340:0uM-DDVP_2h-expose_20h-harvest_rep2~WBPaper00042340:0.6uM-DDVP_2h-expose_20h-harvest_rep2~WBPaper00042340:15uM-DDVP_2h-expose_20h-harvest_rep2~WBPaper00042340:0uM-DDVP_2h-expose_26h-harvest_rep2~WBPaper00042340:0.6uM-DDVP_2h-expose_26h-harvest_rep2~WBPaper00042340:15uM-DDVP_2h-expose_26h-harvest_rep2~WBPaper00042340:0uM-DDVP_continuous-expose_8h-harvest_rep2~WBPaper00042340:0.6uM-DDVP_continuous-expose_8h-harvest_rep2~WBPaper00042340:15uM-DDVP_continuous-expose_8h-harvest_rep2~WBPaper00042340:0uM-DDVP_8h-expose_14h-harvest_rep2~WBPaper00042340:0.6uM-DDVP_8h-expose_14h-harvest_rep2~WBPaper00042340:15uM-DDVP_8h-expose_14h-harvest_rep2~WBPaper00042340:0uM-DDVP_8h-expose_20h-harvest_rep2~WBPaper00042340:0.6uM-DDVP_8h-expose_20h-harvest_rep2~WBPaper00042340:15uM-DDVP_8h-expose_20h-harvest_rep2~WBPaper00042340:0uM-DDVP_8h-expose_26h-harvest_rep2~WBPaper00042340:0.6uM-DDVP_8h-expose_26h-harvest_rep2~WBPaper00042340:15uM-DDVP_8h-expose_26h-harvest_rep2~WBPaper00042340:0uM-DDVP_continuous-expose_14h-harvest_rep2~WBPaper00042340:0.6uM-DDVP_continuous-expose_14h-harvest_rep2~WBPaper00042340:15uM-DDVP_continuous-expose_14h-harvest_rep2~WBPaper00042340:0uM-DDVP_continuous-expose_20h-harvest_rep2~WBPaper00042340:0.6uM-DDVP_continuous-expose_20h-harvest_rep2~WBPaper00042340:15uM-DDVP_continuous-expose_20h-harvest_rep2~WBPaper00042340:0uM-DDVP_continuous-expose_26h-harvest_rep2~WBPaper00042340:0.6uM-DDVP_continuous-expose_26h-harvest_rep2~WBPaper00042340:15uM-DDVP_continuous-expose_26h-harvest_rep2~WBPaper00042340:0uM-DDVP_continuous-expose_0h-harvest_rep3~WBPaper00042340:0uM-DDVP_continuous-expose_2h-harvest_rep3~WBPaper00042340:0.6uM-DDVP_continuous-expose_2h-harvest_rep3~WBPaper00042340:15uM-DDVP_continuous-expose_2h-harvest_rep3~WBPaper00042340:0uM-DDVP_2h-expose_8h-harvest_rep3~WBPaper00042340:0.6uM-DDVP_2h-expose_8h-harvest_rep3~WBPaper00042340:15uM-DDVP_2h-expose_8h-harvest_rep3~WBPaper00042340:0uM-DDVP_2h-expose_14h-harvest_rep3~WBPaper00042340:0.6uM-DDVP_2h-expose_14h-harvest_rep3~WBPaper00042340:15uM-DDVP_2h-expose_14h-harvest_rep3~WBPaper00042340:0uM-DDVP_2h-expose_20h-harvest_rep3~WBPaper00042340:0.6uM-DDVP_2h-expose_20h-harvest_rep3~WBPaper00042340:15uM-DDVP_2h-expose_20h-harvest_rep3~WBPaper00042340:0uM-DDVP_2h-expose_26h-harvest_rep3~WBPaper00042340:0.6uM-DDVP_2h-expose_26h-harvest_rep3~WBPaper00042340:15uM-DDVP_2h-expose_26h-harvest_rep3~WBPaper00042340:0uM-DDVP_continuous-expose_8h-harvest_rep3~WBPaper00042340:0.6uM-DDVP_continuous-expose_8h-harvest_rep3~WBPaper00042340:0uM-DDVP_8h-expose_14h-harvest_rep3~WBPaper00042340:0.6uM-DDVP_8h-expose_14h-harvest_rep3~WBPaper00042340:15uM-DDVP_8h-expose_14h-harvest_rep3~WBPaper00042340:0uM-DDVP_8h-expose_20h-harvest_rep3~WBPaper00042340:0.6uM-DDVP_8h-expose_20h-harvest_rep3~WBPaper00042340:15uM-DDVP_8h-expose_20h-harvest_rep3~WBPaper00042340:0uM-DDVP_8h-expose_26h-harvest_rep3~WBPaper00042340:0.6uM-DDVP_8h-expose_26h-harvest_rep3~WBPaper00042340:15uM-DDVP_8h-expose_26h-harvest_rep3~WBPaper00042340:0uM-DDVP_continuous-expose_14h-harvest_rep3~WBPaper00042340:0.6uM-DDVP_continuous-expose_14h-harvest_rep3~WBPaper00042340:15uM-DDVP_continuous-expose_14h-harvest_rep3~WBPaper00042340:0uM-DDVP_continuous-expose_20h-harvest_rep3~WBPaper00042340:0.6uM-DDVP_continuous-expose_20h-harvest_rep3~WBPaper00042340:15uM-DDVP_continuous-expose_20h-harvest_rep3~WBPaper00042340:0uM-DDVP_continuous-expose_26h-harvest_rep3~WBPaper00042340:0.6uM-DDVP_continuous-expose_26h-harvest_rep3~WBPaper00042340:15uM-DDVP_continuous-expose_26h-harvest_rep3~WBPaper00042340:0uM-DDVP_continuous-expose_0h-harvest_rep4~WBPaper00042340:0uM-DDVP_continuous-expose_2h-harvest_rep4~WBPaper00042340:0.6uM-DDVP_continuous-expose_2h-harvest_rep4~WBPaper00042340:15uM-DDVP_continuous-expose_2h-harvest_rep4~WBPaper00042340:0uM-DDVP_2h-expose_8h-harvest_rep4~WBPaper00042340:0.6uM-DDVP_2h-expose_8h-harvest_rep4~WBPaper00042340:15uM-DDVP_2h-expose_8h-harvest_rep4~WBPaper00042340:0uM-DDVP_2h-expose_14h-harvest_rep4~WBPaper00042340:0.6uM-DDVP_2h-expose_14h-harvest_rep4~WBPaper00042340:15uM-DDVP_2h-expose_14h-harvest_rep4~WBPaper00042340:0uM-DDVP_2h-expose_20h-harvest_rep4~WBPaper00042340:0.6uM-DDVP_2h-expose_20h-harvest_rep4~WBPaper00042340:15uM-DDVP_2h-expose_20h-harvest_rep4~WBPaper00042340:0uM-DDVP_2h-expose_26h-harvest_rep4~WBPaper00042340:0.6uM-DDVP_2h-expose_26h-harvest_rep4~WBPaper00042340:15uM-DDVP_2h-expose_26h-harvest_rep4~WBPaper00042340:0uM-DDVP_continuous-expose_8h-harvest_rep4~WBPaper00042340:0.6uM-DDVP_continuous-expose_8h-harvest_rep4~WBPaper00042340:15uM-DDVP_continuous-expose_8h-harvest_rep4~WBPaper00042340:0uM-DDVP_8h-expose_14h-harvest_rep4~WBPaper00042340:0.6uM-DDVP_8h-expose_14h-harvest_rep4~WBPaper00042340:15uM-DDVP_8h-expose_14h-harvest_rep4~WBPaper00042340:0uM-DDVP_8h-expose_20h-harvest_rep4~WBPaper00042340:0.6uM-DDVP_8h-expose_20h-harvest_rep4~WBPaper00042340:15uM-DDVP_8h-expose_20h-harvest_rep4~WBPaper00042340:0uM-DDVP_8h-expose_26h-harvest_rep4~WBPaper00042340:0.6uM-DDVP_8h-expose_26h-harvest_rep4~WBPaper00042340:15uM-DDVP_8h-expose_26h-harvest_rep4~WBPaper00042340:0uM-DDVP_continuous-expose_14h-harvest_rep4~WBPaper00042340:0.6uM-DDVP_continuous-expose_14h-harvest_rep4~WBPaper00042340:15uM-DDVP_continuous-expose_14h-harvest_rep4~WBPaper00042340:0uM-DDVP_continuous-expose_20h-harvest_rep4~WBPaper00042340:0.6uM-DDVP_continuous-expose_20h-harvest_rep4~WBPaper00042340:15uM-DDVP_continuous-expose_20h-harvest_rep4~WBPaper00042340:0uM-DDVP_continuous-expose_26h-harvest_rep4~WBPaper00042340:0.6uM-DDVP_continuous-expose_26h-harvest_rep4~WBPaper00042340:15uM-DDVP_continuous-expose_26h-harvest_rep4	Method: microarray|Species: Caenorhabditis elegans
137	23675471	WBPaper00042404.ce.mr.paper	GSE44318	GPL200	1	A cocoa peptide protects Caenorhabditis elegans from oxidative stress and -amyloid peptide toxicity.	BACKGROUND: Cocoa and cocoa-based products contain different compounds with beneficial properties for human health. Polyphenols are the most frequently studied, and display antioxidant properties. Moreover, protein content is a very interesting source of antioxidant bioactive peptides, which can be used therapeutically for the prevention of age-related diseases. METHODOLOGY/PRINCIPAL FINDINGS: A bioactive peptide, 13L (DNYDNSAGKWWVT), was obtained from a hydrolyzed cocoa by-product by chromatography. The in vitro inhibition of prolyl endopeptidase (PEP) was used as screening method to select the suitable fraction for peptide identification. Functional analysis of 13L peptide was achieved using the transgenic Caenorhabditis elegans strain CL4176 expressing the human A peptide as a pre-clinical in vivo model for Alzheimer's disease. Among the peptides isolated, peptide 13L (1 g/mL) showed the highest antioxidant activity (P0.001) in the wild-type strain (N2). Furthermore, 13L produced a significant delay in body paralysis in strain CL4176, especially in the 24-47 h period after A peptide induction (P0.0001). This observation is in accordance with the reduction of A deposits in CL4176 by western blot. Finally, transcriptomic analysis in wild-type nematodes treated with 13L revealed modulation of the proteosomal and synaptic functions as the main metabolic targets of the peptide. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the cocoa 13L peptide has antioxidant activity and may reduce A deposition in a C. elegans model of Alzheimer's disease; and therefore has a putative therapeutic potential for prevention of age-related diseases. Further studies in murine models and humans will be essential to analyze the effectiveness of the 13L peptide in higher animals.	7	17638	Martorell P	Martorell P, Bataller E, Llopis S, Gonzalez N, Alvarez B, Monton F, Ortiz P, Ramon D, Genoves S	A cocoa peptide protects Caenorhabditis elegans from oxidative stress and -amyloid peptide toxicity.	PLoS One	2013	WBPaper00042404:NGM_SL1~WBPaper00042404:NGM_SL5~WBPaper00042404:NGM_SL9~WBPaper00042404:NGM_SL69~WBPaper00042404:13L-cocoa-peptide_SL4~WBPaper00042404:13L-cocoa-peptide_SL8~WBPaper00042404:13L-cocoa-peptide_SL12	Method: microarray|Species: Caenorhabditis elegans
138	23811144	WBPaper00042574.ce.mr.paper	GSE41056,GSE41058	GPL200	1	Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.	Positive-strand RNA viruses encompass more than one-third of known virus genera and include many medically and agriculturally relevant human, animal, and plant pathogens. The nematode Caenorhabditis elegans and its natural pathogen, the positive-strand RNA virus Orsay, have recently emerged as a new animal model to understand the mechanisms and evolution of innate immune responses. In particular, the RNA interference (RNAi) pathway is required for C. elegans resistance to viral infection. Here we report the first genome-wide analyses of gene expression upon viral infection in C. elegans. Using the laboratory strain N2, we identify a novel C. elegans innate immune response specific to viral infection. A subset of these changes is driven by the RNAi response to the virus, which redirects the Argonaute protein RDE-1 from its endogenous small RNA cofactors, leading to loss of repression of endogenous RDE-1 targets. Additionally, we show that a C. elegans wild isolate, JU1580, has a distinct gene expression signature in response to viral infection. This is associated with a reduction in microRNA (miRNA) levels and an up-regulation of their target genes. Intriguingly, alterations in miRNA levels upon JU1580 infection are associated with a transformation of the antiviral transcriptional response into an antibacterial-like response. Together our data support a model whereby antiviral RNAi competes with endogenous small RNA pathways, causing widespread transcriptional changes. This provides an elegant mechanism for C. elegans to orchestrate its antiviral response, which may have significance for the relationship between small RNA pathways and immune regulation in other organisms.	20	17638	Sarkies P	Sarkies P, Ashe A, Le Pen J, McKie MA, Miska EA	Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.	Genome Res	2013	WBPaper00042574:N2_Control_rep1~WBPaper00042574:N2_Control_rep2~WBPaper00042574:N2_Control_rep3~WBPaper00042574:N2_Control_rep4~WBPaper00042574:N2_OrsayVirus_rep1~WBPaper00042574:N2_OrsayVirus_rep2~WBPaper00042574:N2_OrsayVirus_rep3~WBPaper00042574:N2_OrsayVirus_rep4~WBPaper00042574:JU1580_Control_rep1~WBPaper00042574:JU1580_Control_rep2~WBPaper00042574:JU1580_Control_rep3~WBPaper00042574:JU1580_OrsayVirus_rep1~WBPaper00042574:JU1580_OrsayVirus_rep2~WBPaper00042574:JU1580_OrsayVirus_rep3~WBPaper00042574:rde-1(ne219)_Control_rep1~WBPaper00042574:rde-1(ne219)_Control_rep2~WBPaper00042574:rde-1(ne219)_Control_rep3~WBPaper00042574:rde-1(ne219)_OrsayVirus_rep1~WBPaper00042574:rde-1(ne219)_OrsayVirus_rep2~WBPaper00042574:rde-1(ne219)_OrsayVirus_rep3	Method: microarray|Species: Caenorhabditis elegans
139	23894281	WBPaper00043980.ce.mr.paper	GSE39012	GPL200	1	Genomic analysis of stress response against arsenic in Caenorhabditis elegans.	Arsenic, a known human carcinogen, is widely distributed around the world and found in particularly high concentrations in certain regions including Southwestern US, Eastern Europe, India, China, Taiwan and Mexico. Chronic arsenic poisoning affects millions of people worldwide and is associated with increased risk of many diseases including arthrosclerosis, diabetes and cancer. In this study, we explored genome level global responses to high and low levels of arsenic exposure in Caenorhabditis elegans using Affymetrix expression microarrays. This experimental design allows us to do microarray analysis of dose-response relationships of global gene expression patterns. High dose (0.03%) exposure caused stronger global gene expression changes in comparison with low dose (0.003%) exposure, suggesting a positive dose-response correlation. Biological processes such as oxidative stress, and iron metabolism, which were previously reported to be involved in arsenic toxicity studies using cultured cells, experimental animals, and humans, were found to be affected in C. elegans. We performed genome-wide gene expression comparisons between our microarray data and publicly available C. elegans microarray datasets of cadmium, and sediment exposure samples of German rivers Rhine and Elbe. Bioinformatics analysis of arsenic-responsive regulatory networks were done using FastMEDUSA program. FastMEDUSA analysis identified cancer-related genes, particularly genes associated with leukemia, such as dnj-11, which encodes a protein orthologous to the mammalian ZRF1/MIDA1/MPP11/DNAJC2 family of ribosome-associated molecular chaperones. We analyzed the protective functions of several of the identified genes using RNAi. Our study indicates that C. elegans could be a substitute model to study the mechanism of metal toxicity using high-throughput expression data and bioinformatics tools such as FastMEDUSA.	9	17638	Sahu SN	Sahu SN, Lewis J, Patel I, Bozdag S, Lee JH, Sprando R, Cinar HN	Genomic analysis of stress response against arsenic in Caenorhabditis elegans.	PLoS One	2013	WBPaper00043980:L3_arsenic_.003_rep1~WBPaper00043980:L3_arsenic_.003_rep2~WBPaper00043980:L3_arsenic_.003_rep3~WBPaper00043980:L3_arsenic_.03_rep1~WBPaper00043980:L3_arsenic_.03_rep2~WBPaper00043980:L3_arsenic_.03_rep3~WBPaper00043980:L3_arsenic_Control_rep1~WBPaper00043980:L3_arsenic_Control_rep2~WBPaper00043980:L3_arsenic_Control_rep3	Method: microarray|Species: Caenorhabditis elegans
140	24013725	WBPaper00044163.ce.mr.paper	GSE39145	GPL200	1	DNA damage leads to progressive replicative decline but extends the life span of long-lived mutant animals.	Human-nucleotide-excision repair (NER) deficiency leads to different developmental and segmental progeroid symptoms of which the pathogenesis is only partially understood. To understand the biological impact of accumulating spontaneous DNA damage, we studied the phenotypic consequences of DNA-repair deficiency in Caenorhabditis elegans. We find that DNA damage accumulation does not decrease the adult life span of post-mitotic tissue. Surprisingly, loss of functional ERCC-1/XPF even further extends the life span of long-lived daf-2 mutants, likely through an adaptive activation of stress signaling. Contrariwise, NER deficiency leads to a striking transgenerational decline in replicative capacity and viability of proliferating cells. DNA damage accumulation induces severe, stochastic impairment of development and growth, which is most pronounced in NER mutants that are also impaired in their response to ionizing radiation and inter-strand crosslinks. These results suggest that multiple DNA-repair pathways can protect against replicative decline and indicate that there might be a direct link between the severity of symptoms and the level of DNA-repair deficiency in patients.	8	17637	Lans H	Lans H, Lindvall JM, Thijssen K, Karambelas AE, Cupac D, Fensgard O, Jansen G, Hoeijmakers JH, Nilsen H, Vermeulen W	DNA damage leads to progressive replicative decline but extends the life span of long-lived mutant animals.	Cell Death Differ	2013	WBPaper00044163:ercc-1_I~WBPaper00044163:ercc-1_II~WBPaper00044163:ercc-1_III~WBPaper00044163:ercc-1_IV~WBPaper00044163:N2_I~WBPaper00044163:N2_II~WBPaper00044163:N2_III~WBPaper00044163:N2_IV	Method: microarray|Species: Caenorhabditis elegans
141	24043781	WBPaper00044197.ce.mr.paper	GSE48347	GPL200	1	SUMOylation is essential for sex-specific assembly and function of the Caenorhabditis elegans dosage compensation complex on X chromosomes.	The essential process of dosage compensation equalizes X-chromosome gene expression between Caenorhabditis elegans XO males and XX hermaphrodites through a dosage compensation complex (DCC) that is homologous to condensin. The DCC binds to both X chromosomes of hermaphrodites to repress transcription by half. Here, we show that posttranslational modification by the SUMO (small ubiquitin-like modifier) conjugation pathway is essential for sex-specific assembly and function of the DCC on X. Depletion of SUMO in vivo severely disrupts binding of particular DCC subunits and causes changes in X-linked gene expression similar to those caused by deleting genes encoding DCC subunits. Three DCC subunits are SUMOylated, and SUMO depletion preferentially reduces their binding to X, suggesting that SUMOylation of DCC subunits is essential for robust association with X. DCC SUMOylation is triggered by the signal that initiates DCC assembly onto X. The initial step of assembly-binding of X-targeting factors to recruitment sites on X-is independent of SUMOylation, but robust binding of the complete complex requires SUMOylation. SUMOylated DCC subunits are enriched at recruitment sites, and SUMOylation likely enhances interactions between X-targeting factors and condensin subunits that facilitate DCC binding beyond the low level achieved without SUMOylation. DCC subunits also participate in condensin complexes essential for chromosome segregation, but their SUMOylation occurs only in the context of the DCC. Our results reinforce a newly emerging theme in which multiple proteins of a complex are collectively SUMOylated in response to a specific stimulus, leading to accelerated complex formation and enhanced function.	9	17638	Pferdehirt RR	Pferdehirt RR, Meyer BJ	SUMOylation is essential for sex-specific assembly and function of the Caenorhabditis elegans dosage compensation complex on X chromosomes.	Proc Natl Acad Sci U S A	2013	WBPaper00044197:N2_rep1~WBPaper00044197:N2_rep2~WBPaper00044197:N2_rep3~WBPaper00044197:smo-1(RNAi)_rep1~WBPaper00044197:smo-1(RNAi)_rep2~WBPaper00044197:smo-1(RNAi)_rep3~WBPaper00044197:sdc-2(RNAi)_rep1~WBPaper00044197:sdc-2(RNAi)_rep2~WBPaper00044197:sdc-2(RNAi)_rep3	Method: microarray|Species: Caenorhabditis elegans
142	24292626	WBPaper00044535.ce.mr.paper	GSE51691	GPL200	1	Males shorten the life span of C. elegans hermaphrodites via secreted compounds.	How an individual's longevity is affected by the opposite sex is still largely unclear. In the nematode Caenorhabditis elegans, the presence of males accelerated aging and shortened the life span of individuals of the opposite sex (hermaphrodites), including long-lived or sterile hermaphrodites. The male-induced demise could occur without mating and required only exposure of hermaphrodites to medium in which males were once present. Such communication through pheromones or other diffusible substances points to a nonindividual autonomous mode of aging regulation. The male-induced demise also occurred in other species of nematodes, suggesting an evolutionary conserved process whereby males may induce the disposal of the opposite sex to save resources for the next generation or to prevent competition from other males.	11	17638	Maures TJ	Maures TJ, Booth LN, Benayoun BA, Izrayelit Y, Schroeder FC, Brunet A	Males shorten the life span of C. elegans hermaphrodites via secreted compounds.	Science	2014	WBPaper00044535:glp-1(e2141)_no_males_rep1~WBPaper00044535:glp-1(e2141)_no_males_rep2~WBPaper00044535:glp-1(e2141)_no_males_rep3~WBPaper00044535:glp-1(e2141)_with_males_rep1~WBPaper00044535:glp-1(e2141)_with_males_rep2~WBPaper00044535:glp-1(e2141)_with_males_rep3~WBPaper00044535:glp-1(e2141)_utx-1(RNAi)_no_males_rep1~WBPaper00044535:glp-1(e2141)_utx-1(RNAi)_no_males_rep2~WBPaper00044535:glp-1(e2141)_utx-1(RNAi)_no_males_rep3~WBPaper00044535:glp-1(e2141)_utx-1(RNAi)_with_males_rep1~WBPaper00044535:glp-1(e2141)_utx-1(RNAi)_with_males_rep3	Method: microarray|Species: Caenorhabditis elegans
143	24281426	WBPaper00044545.ce.mr.paper	GSE52064	GPL200	1	Opposing activities of DRM and MES-4 tune gene expression and X-chromosome repression in Caenorhabditis elegans germ cells.	During animal development, gene transcription is tuned to tissue-appropriate levels. Here we uncover antagonistic regulation of transcript levels in the germline of Caenorhabditis elegans hermaphrodites. The histone methyltransferase MES-4 (Maternal Effect Sterile-4) marks genes expressed in the germline with methylated lysine on histone H3 (H3K36me) and promotes their transcription; MES-4 also represses genes normally expressed in somatic cells and genes on the X chromosome. The DRM transcription factor complex, named for its Dp/E2F, Retinoblastoma-like, and MuvB subunits, affects germline gene expression and prevents excessive repression of X-chromosome genes. Using genome-scale analyses of germline tissue, we show that common germline-expressed genes are activated by MES-4 and repressed by DRM, and that MES-4 and DRM co-bind many germline-expressed genes. Reciprocally, MES-4 represses and DRM activates a set of autosomal soma-expressed genes and overall X-chromosome gene expression. Mutations in mes-4 and the DRM subunit lin-54 oppositely skew the transcript levels of their common targets and cause sterility. A double mutant restores target gene transcript levels closer to wild type, and the concomitant loss of lin-54 suppresses the severe germline proliferation defect observed in mes-4 single mutants. Together, &quot;yin-yang&quot; regulation by MES-4 and DRM ensures transcript levels appropriate for germ-cell function, elicits robust but not excessive dampening of X-chromosome-wide transcription, and may poise genes for future expression changes. Our study reveals that conserved transcriptional regulators implicated in development and cancer counteract each other to fine-tune transcript dosage.	12	17638	Tabuchi TM	Tabuchi TM, Rechtsteiner A, Strome S, Hagstrom KA	Opposing activities of DRM and MES-4 tune gene expression and X-chromosome repression in Caenorhabditis elegans germ cells.	G3 (Bethesda)	2014	WBPaper00044545:N2_1~WBPaper00044545:N2_2~WBPaper00044545:N2_3~WBPaper00044545:lin-54(n3423)_1~WBPaper00044545:lin-54(n3423)_2~WBPaper00044545:lin-54(n3423)_3~WBPaper00044545:mes-4(ok2326)_1~WBPaper00044545:mes-4(ok2326)_2~WBPaper00044545:mes-4(ok2326)_3~WBPaper00044545:lin-54(n3423);mes-4(ok2326)_1~WBPaper00044545:lin-54(n3423);mes-4(ok2326)_2~WBPaper00044545:lin-54(n3423);mes-4(ok2326)_3	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
144	24569038	WBPaper00044857.ce.mr.paper	GSE51502	GPL200	1	Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.	The Wnt signaling pathway plays a fundamental role during metazoan development, where it regulates diverse processes, including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin-dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway regulates several processes during larval development; however, few target genes of this pathway have been identified. To address this deficit, we used a novel approach of conditionally activated Wnt signaling during a defined stage of larval life by overexpressing an activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared with control animals. We identified 166 differentially expressed genes, of which 104 were up-regulated. A subset of the up-regulated genes was shown to have altered expression in mutants with decreased or increased Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway targets. Among these was a group of six genes, including the cuticular collagen genes, bli-1 col-38, col-49, and col-71. These genes show a peak of expression in the mid L4 stage during normal development, suggesting a role in adult cuticle formation. Consistent with this finding, reduction of function for several of the genes causes phenotypes suggestive of defects in cuticle function or integrity. Therefore, this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle.	6	17638	Jackson BM	Jackson BM, Abete-Luzi P, Krause MW, Eisenmann DM	Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.	G3 (Bethesda)	2014	WBPaper00044857:hs-bar-1_3A~WBPaper00044857:hs-bar-1_2A~WBPaper00044857:hs-bar-1_1A~WBPaper00044857:hs-control_1b~WBPaper00044857:hs-control_2b~WBPaper00044857:hs-control_3b	Method: microarray|Species: Caenorhabditis elegans|Topic: Wnt signaling pathway|Topic: canonical Wnt signaling pathway
145	24813612	WBPaper00045263.ce.mr.paper	GSE54024	GPL200	1	The intrinsic apoptosis pathway mediates the pro-longevity response to mitochondrial ROS in C. elegans.	The increased longevity of the C. elegans electron transport chain mutants isp-1 and nuo-6 is mediated by mitochondrial ROS (mtROS) signaling. Here we show that the mtROS signal is relayed by the conserved, mitochondria-associated, intrinsic apoptosis signaling pathway (CED-9/Bcl2, CED-4/Apaf1, and CED-3/Casp9) triggered by CED-13, an alternative BH3-only protein. Activation of the pathway by an elevation of mtROS does not affect apoptosis but protects from the consequences of mitochondrial dysfunction by triggering a unique pattern of gene expression that modulates stress sensitivity and promotes survival. In vertebrates, mtROS induce apoptosis through the intrinsic pathway to protect from severely damaged cells. Our observations in nematodes demonstrate that sensing of mtROS by the apoptotic pathway can, independently of apoptosis, elicit protective mechanisms that keep the organism alive under stressful conditions. This results in extended longevity when mtROS generation is inappropriately elevated. These findings clarify the relationships between mitochondria, ROS, apoptosis, and aging.	22	17638	Yee C	Yee C, Yang W, Hekimi S	The intrinsic apoptosis pathway mediates the pro-longevity response to mitochondrial ROS in C. elegans.	Cell	2014	WBPaper00045263:N2_rep1~WBPaper00045263:N2_rep2~WBPaper00045263:N2_rep3~WBPaper00045263:N2_rep4~WBPaper00045263:isp-1(qm150)_rep1~WBPaper00045263:isp-1(qm150)_rep2~WBPaper00045263:isp-1(qm150)_rep3~WBPaper00045263:nuo-6(qm200)_rep1~WBPaper00045263:nuo-6(qm200)_rep2~WBPaper00045263:nuo-6(qm200)_rep3~WBPaper00045263:0.1mM-paraquat_rep1~WBPaper00045263:0.1mM-paraquat_rep2~WBPaper00045263:0.1mM-paraquat_rep3~WBPaper00045263:ced-4(n1162)_rep1~WBPaper00045263:ced-4(n1162)_rep2~WBPaper00045263:ced-4(n1162)_rep3~WBPaper00045263:isp-1(qm150)ced-4(n1162)_rep1~WBPaper00045263:isp-1(qm150)ced-4(n1162)_rep2~WBPaper00045263:isp-1(qm150)ced-4(n1162)_rep3~WBPaper00045263:nuo-6(qm200);ced-4(n1162)_rep1~WBPaper00045263:nuo-6(qm200);ced-4(n1162)_rep2~WBPaper00045263:nuo-6(qm200);ced-4(n1162)_rep3	Method: microarray|Species: Caenorhabditis elegans
146	24846693	WBPaper00045374.ce.mr.paper	GSE24923,GSE23013,GSE24845,GSE24846	GPL200	1	Integrative assessment of benzene exposure to Caenorhabditis elegans using computational behavior and toxicogenomic analyses.	In this study, we investigated the toxic effects of benzene to the nematode Caenorhabditis elegans in an integrative manner, using computational behavior and toxicogenomics analyses, along with survival and reproduction. Benzene exposure led to changes in locomotive behavior and reproduction decline in C. elegans. Microarray followed by pathway analysis revealed that 228 genes were differentially expressed by benzene exposure, and cyp-35a2, pmk-1, and cep-1 were selected for further reproduction and multiparametric behavior analysis. Mutant analysis showed that benzene induced reproduction decline was rescued in cyp-35a2(gk317) mutant, whereas it was significantly exacerbated in pmk-1(km25) mutant, compared with the wildtype. The multiparametric behavior analysis on the mutants of selected genes revealed that each strain exhibits different response patterns, particularly, enhanced linear movement in the cyp-35a2(gk317) mutant, whereas the changes in partial body movement were observed in the pmk-1(km25) mutant by benzene exposure. A self-organizing map revealed that the pmk-1(km25) mutant group was the most densely clustered and located on the opposite side of the map of the cyp-35a2(gk317) mutant, each crossing that of the wildtype. Overall results suggest distinct roles of cyp-35a2 and pmk-1 genes in benzene-induced alterations in behavior and reproduction in C. elegans. This study also suggests computational behavior analysis is a suitable tool for addressing the integrative impact of chemical stress alongside with toxicogenomic approach.	5	17638	Eom HJ	Eom HJ, Kim H, Kim BM, Chon TS, Choi J	Integrative assessment of benzene exposure to Caenorhabditis elegans using computational behavior and toxicogenomic analyses.	Environ Sci Technol	2014	WBPaper00045374:control_rep1~WBPaper00045374:24hr_Benzene_exposure_rep1~WBPaper00045374:24hr_Toluene_exposure_rep1~WBPaper00045374:24hr_Formaldehyde_exposure_rep1~WBPaper00045374:24hr_BTFmix_exposure_rep1	Method: microarray|Species: Caenorhabditis elegans
147	24971995	WBPaper00045437.ce.mr.paper	GSE54011	GPL200	1	Toxic-selenium and low-selenium transcriptomes in Caenorhabditis elegans: toxic selenium up-regulates oxidoreductase and down-regulates cuticle-associated genes.	Selenium (Se) is an element that in trace quantities is both essential in mammals but also toxic to bacteria, yeast, plants and animals, including C. elegans. Our previous studies showed that selenite was four times as toxic as selenate to C. elegans, but that deletion of thioredoxin reductase did not modulate Se toxicity. To characterize Se regulation of the full transcriptome, we conducted a microarray study in C. elegans cultured in axenic media supplemented with 0, 0.05, 0.1, 0.2, and 0.4 mM Se as selenite. C. elegans cultured in 0.2 and 0.4 mM Se displayed a significant delay in growth as compared to 0, 0.05, or 0.1 mM Se, indicating Se-induced toxicity, so worms were staged to mid-L4 larval stage for these studies. Relative to 0.1 mM Se treatment, culturing C. elegans at these Se concentrations resulted in 1.9, 9.7, 5.5, and 2.3%, respectively, of the transcriptome being altered by at least 2-fold. This toxicity altered the expression of 295 overlapping transcripts, which when filtered against gene sets for sulfur and cadmium toxicity, identified a dataset of 182 toxic-Se specific genes that were significantly enriched in functions related to oxidoreductase activity, and significantly depleted in genes related to structural components of collagen and the cuticle. Worms cultured in low Se (0 mM Se) exhibited no signs of deficiency, but low Se was accompanied by a transcriptional response of 59 genes changed 2-fold when compared to all other Se concentrations, perhaps due to decreases in Se-dependent TRXR-1 activity. Overall, these results suggest that Se toxicity in C. elegans causes an increase in ROS and stress responses, marked by increased expression of oxidoreductases and reduced expression of cuticle-associated genes, which together underlie the impaired growth observed in these studies.	5	9823	Boehler CJ	Boehler CJ, Raines AM, Sunde RA	Toxic-selenium and low-selenium transcriptomes in Caenorhabditis elegans: toxic selenium up-regulates oxidoreductase and down-regulates cuticle-associated genes.	PLoS One	2014	WBPaper00045437:0mM_Se~WBPaper00045437:0.05mM_Se~WBPaper00045437:0.1mM_Se~WBPaper00045437:0.2mM_Se~WBPaper00045437:0.4mM_Se	Method: microarray|Species: Caenorhabditis elegans
148	25261697	WBPaper00045802.ce.mr.paper	GSE54513,GSE54517,GSE54518	GPL200	1	Translational control of the oogenic program by components of OMA ribonucleoprotein particles in Caenorhabditis elegans.	The oocytes of most sexually reproducing animals arrest in meiotic prophase I. Oocyte growth, which occurs during this period of arrest, enables oocytes to acquire the cytoplasmic components needed to produce healthy progeny and to gain competence to complete meiosis. In the nematode Caenorhabditis elegans, the major sperm protein hormone promotes meiotic resumption (also called meiotic maturation) and the cytoplasmic flows that drive oocyte growth. Prior work established that two related TIS11 zinc-finger RNA-binding proteins, OMA-1 and OMA-2, are redundantly required for normal oocyte growth and meiotic maturation. We affinity purified OMA-1 and identified associated mRNAs and proteins using genome-wide expression data and mass spectrometry, respectively. As a class, mRNAs enriched in OMA-1 ribonucleoprotein particles (OMA RNPs) have reproductive functions. Several of these mRNAs were tested and found to be targets of OMA-1/2-mediated translational repression, dependent on sequences in their 3'-untranslated regions (3'-UTRs). Consistent with a major role for OMA-1 and OMA-2 in regulating translation, OMA-1-associated proteins include translational repressors and activators, and some of these proteins bind directly to OMA-1 in yeast two-hybrid assays, including OMA-2. We show that the highly conserved TRIM-NHL protein LIN-41 is an OMA-1-associated protein, which also represses the translation of several OMA-1/2 target mRNAs. In the accompanying article in this issue, we show that LIN-41 prevents meiotic maturation and promotes oocyte growth in opposition to OMA-1/2. Taken together, these data support a model in which the conserved regulators of mRNA translation LIN-41 and OMA-1/2 coordinately control oocyte growth and the proper spatial and temporal execution of the meiotic maturation decision.	12	17638	Spike CA	Spike CA, Coetzee D, Nishi Y, Guven-Ozkan T, Oldenbroek M, Yamamoto I, Lin R, Greenstein DI	Translational control of the oogenic program by components of OMA ribonucleoprotein particles in Caenorhabditis elegans.	Genetics	2014	WBPaper00045802:spe-9_OMA-1-IP_rep1~WBPaper00045802:spe-9_OMA-1-IP_rep2~WBPaper00045802:spe-9_OMA-1-IP_rep3~WBPaper00045802:spe-9_totalRNA_rep1~WBPaper00045802:spe-9_totalRNA_rep2~WBPaper00045802:spe-9_totalRNA_rep3~WBPaper00045802:fog-1_OMA-1-IP_rep1~WBPaper00045802:fog-1_OMA-1-IP_rep2~WBPaper00045802:fog-1_OMA-1-IP_rep3~WBPaper00045802:fog-1_totalRNA_rep1~WBPaper00045802:fog-1_totalRNA_rep2~WBPaper00045802:fog-1_totalRNA_rep3	Method: microarray|Species: Caenorhabditis elegans
149	25257166	WBPaper00045807.ce.mr.paper	N.A.	N.A.	1	Neurotoxic action of microcystin-LR is reflected in the transcriptional stress response of Caenorhabditis elegans.	Cyanobacterial blooms in aquatic environments are frequently characterized by elevated levels of microcystins, a potent hepatotoxin. Here we exposed the nematode Caenorhabditis elegans with environmentally realistic concentrations of MC-LR to explore its non-hepatic toxicity. Lifespan, reproduction and growth assays confirmed the toxic potential of 100 g/L MC-LR even in this liver-lacking invertebrate. Whole-genome microarray analysis revealed that a neuromodulating action was the dominant response in nematodes challenged with 100 g/L MC-LR. Indeed, most of the 201 differentially expressed genes were associated with neurobehavior, neurogenesis, and signaling associated pathways. In addition, a whole-genome miRNA-microarray highlighted that, in particular, members of the let-7 family were differentially regulated. These miRNAs are involved in the developmental timing of cell fates, including neurons, and are probably also part of the stress response system. To conclude, neurological modulation is the main transcriptional stress response in C. elegans exposed to MC-LR.	6	17638	Saul N	Saul N, Chakrabarti S, Sturzenbaum SR, Menzel R, Steinberg CE	Neurotoxic action of microcystin-LR is reflected in the transcriptional stress response of Caenorhabditis elegans.	Chem Biol Interact	2014	WBPaper00045807:Control-mRNA_Rep1~WBPaper00045807:microcystin-LR-mRNA_Rep1~WBPaper00045807:Control-mRNA_Rep2~WBPaper00045807:microcystin-LR-mRNA_Rep2~WBPaper00045807:Control-mRNA_Rep3~WBPaper00045807:microcystin-LR-mRNA_Rep3	Method: microarray|Species: Caenorhabditis elegans
150	25361578	WBPaper00045960.ce.mr.paper	GSE46291,GSE46288,GSE46289	GPL200	1	Dynamically-expressed prion-like proteins form a cuticle in the pharynx of Caenorhabditis elegans.	In molting animals, a cuticular extracellular matrix forms the first barrier to infection and other environmental insults. In the nematode Caenorhabditis elegans there are two types of cuticle: a well-studied collagenous cuticle lines the body, and a poorly-understood chitinous cuticle lines the pharynx. In the posterior end of the pharynx is the grinder, a tooth-like cuticular specialization that crushes food prior to transport to the intestine for digestion. We here show that the grinder increases in size only during the molt. To gain molecular insight into the structure of the grinder and pharyngeal cuticle, we performed a microarray analysis to identify mRNAs increased during the molt. We found strong transcriptional induction during the molt of 12 of 15 previously identified abu genes encoding Prion-like (P) glutamine (Q) and asparagine (N) rich PQN proteins, as well as 15 additional genes encoding closely related PQN proteins. abu/pqn genes, which we name the abu/pqn paralog group (APPG) genes, were expressed in pharyngeal cells and the proteins encoded by two APPG genes we tested localized to the pharyngeal cuticle. Deleting the APPG gene abu-14 caused abnormal pharyngeal cuticular structures and knocking down other APPG genes resulted in abnormal cuticular function. We propose that APPG proteins promote the assembly and function of a unique cuticular structure. The strong developmental regulation of the APPG genes raises the possibility that such genes would be identified in transcriptional profiling experiments in which the animals' developmental stage is not precisely staged.	21	17638	George-Raizen JB	George-Raizen JB, Shockley KR, Trojanowski NF, Lamb AL, Raizen DM	Dynamically-expressed prion-like proteins form a cuticle in the pharynx of Caenorhabditis elegans.	Biol Open	2014	WBPaper00045960:L3_rep1~WBPaper00045960:L3_rep2~WBPaper00045960:L3_rep3~WBPaper00045960:L3-lethargus_rep1~WBPaper00045960:L3-lethargus_rep2~WBPaper00045960:L3-lethargus_rep3~WBPaper00045960:L4_rep1~WBPaper00045960:L4_rep2~WBPaper00045960:L4_rep3~WBPaper00045960:L4_rep4~WBPaper00045960:L4_rep5~WBPaper00045960:L4-lethargus_rep1~WBPaper00045960:L4-lethargus_rep2~WBPaper00045960:L4-lethargus_rep3~WBPaper00045960:L4-lethargus_rep4~WBPaper00045960:L4-lethargus_rep5~WBPaper00045960:Adult_rep1~WBPaper00045960:Adult_rep2~WBPaper00045960:Adult_rep3~WBPaper00045960:Adult_rep4~WBPaper00045960:Adult_rep5	Method: microarray|Species: Caenorhabditis elegans
151	25474640	WBPaper00046083.ce.mr.paper	GSE53732	GPL200	1	Conserved nutrient sensor O-GlcNAc transferase is integral to C. elegans pathogen-specific immunity.	Discriminating pathogenic bacteria from bacteria used as a food source is key to Caenorhabidits elegans immunity. Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. Genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved -catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. Moreover, whole genome transcriptional profiling revealed that O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes. The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response.	36	17638	Bond MR	Bond MR, Ghosh SK, Wang P, Hanover JA	Conserved nutrient sensor O-GlcNAc transferase is integral to C. elegans pathogen-specific immunity.	PLoS One	2014	WBPaper00046083:pmk-1(km25)_OP50_sample1~WBPaper00046083:pmk-1(km25)_OP50_sample2~WBPaper00046083:pmk-1(km25)_OP50_sample3~WBPaper00046083:ogt-1(ok1474)_OP50_sample4~WBPaper00046083:ogt-1(ok1474)_OP50_sample5~WBPaper00046083:ogt-1(ok1474)_OP50_sample6~WBPaper00046083:oga-1(ok1207)_OP50_sample7~WBPaper00046083:oga-1(ok1207)_OP50_sample8~WBPaper00046083:oga-1(ok1207)_OP50_sample9~WBPaper00046083:N2_OP50_sample10~WBPaper00046083:N2_OP50_sample11~WBPaper00046083:N2_OP50_sample12~WBPaper00046083:pmk-1(km25)_S.aureus_sample13~WBPaper00046083:pmk-1(km25)_S.aureus_sample14~WBPaper00046083:pmk-1(km25)_S.aureus_sample15~WBPaper00046083:ogt-1(ok1474)_S.aureus_sample16~WBPaper00046083:ogt-1(ok1474)_S.aureus_sample17~WBPaper00046083:ogt-1(ok1474)_S.aureus_sample18~WBPaper00046083:oga-1(ok1207)_S.aureus_sample19~WBPaper00046083:oga-1(ok1207)_S.aureus_sample20~WBPaper00046083:oga-1(ok1207)_S.aureus_sample21~WBPaper00046083:N2_S.aureus_sample22~WBPaper00046083:N2_S.aureus_sample23~WBPaper00046083:N2_S.aureus_sample24~WBPaper00046083:pmk-1(km25)_P.aeruginosa_sample25~WBPaper00046083:pmk-1(km25)_P.aeruginosa_sample26~WBPaper00046083:pmk-1(km25)_P.aeruginosa_sample27~WBPaper00046083:ogt-1(ok1474)_P.aeruginosa_sample28~WBPaper00046083:ogt-1(ok1474)_P.aeruginosa_sample29~WBPaper00046083:ogt-1(ok1474)_P.aeruginosa_sample30~WBPaper00046083:oga-1(ok1207)_P.aeruginosa_sample31~WBPaper00046083:oga-1(ok1207)_P.aeruginosa_sample32~WBPaper00046083:oga-1(ok1207)_P.aeruginosa_sample33~WBPaper00046083:N2_P.aeruginosa_sample34~WBPaper00046083:N2_P.aeruginosa_sample35~WBPaper00046083:N2_P.aeruginosa_sample36	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
152	25457027	WBPaper00046102.ce.mr.paper	GSE65851	GPL200	1	Identifying A-specific pathogenic mechanisms using a nematode model of Alzheimer's disease.	Multiple gene expression alterations have been linked to Alzheimer's disease (AD), implicating multiple metabolic pathways in its pathogenesis. However, a clear distinction between AD-specific gene expression changes and those resulting from nonspecific responses to toxic aggregating proteins has not been made. We investigated alterations in gene expression induced by human beta-amyloid peptide (A) in a Caenorhabditis elegans AD model. A-induced gene expression alterations were compared with those caused by a synthetic aggregating protein to identify A-specific effects. Both A-specific and nonspecific alterations were observed. Among A-specific genes were those involved in aging, proteasome function, and mitochondrial function. An intriguing observation was the significant overlap between gene expression changes induced by A and those induced by Cry5B, a bacterial pore-forming toxin. This led us to hypothesize that A exerts its toxic effect, at least in part, by causing damage to biological membranes. We provide in vivo evidence consistent with this hypothesis. This study distinguishes between A-specific and nonspecific mechanisms and provides potential targets for therapeutics discovery.	47	17638	Hassan WM	Hassan WM, Dostal V, Huemann BN, Yerg JE, Link CD	Identifying A-specific pathogenic mechanisms using a nematode model of Alzheimer's disease.	Neurobiol Aging	2015	WBPaper00046102:GFP_0hr_rep1~WBPaper00046102:GFP_4hr_rep1~WBPaper00046102:GFP_8hr_rep1~WBPaper00046102:GFP_8hr_rep2~WBPaper00046102:GFP_8hr_rep3~WBPaper00046102:GFP_8hr_rep4~WBPaper00046102:GFP_12hr_rep1~WBPaper00046102:GFP_12hr_rep2~WBPaper00046102:GFP_12hr_rep3~WBPaper00046102:GFP_12hr_rep4~WBPaper00046102:GFP_12hr_rep5~WBPaper00046102:GFP_16hr_rep1~WBPaper00046102:GFP_16hr_rep2~WBPaper00046102:GFP_16hr_rep3~WBPaper00046102:GFP_16hr_rep4~WBPaper00046102:GFP_20hr_rep1~WBPaper00046102:GFP-degron_0hr_rep1~WBPaper00046102:GFP-degron_4hr_rep1~WBPaper00046102:GFP-degron_8hr_rep1~WBPaper00046102:GFP-degron_8hr_rep2~WBPaper00046102:GFP-degron_8hr_rep3~WBPaper00046102:GFP-degron_8hr_rep4~WBPaper00046102:GFP-degron_12hr_rep1~WBPaper00046102:GFP-degron_12hr_rep2~WBPaper00046102:GFP-degron_12hr_rep3~WBPaper00046102:GFP-degron_12hr_rep4~WBPaper00046102:GFP-degron_12hr_rep5~WBPaper00046102:GFP-degron_16hr_rep1~WBPaper00046102:GFP-degron_16hr_rep2~WBPaper00046102:GFP-degron_16hr_rep3~WBPaper00046102:GFP-degron_16hr_rep4~WBPaper00046102:GFP-degron_20hr_rep1~WBPaper00046102:Abeta_0hr_rep1~WBPaper00046102:Abeta_4hr_rep1~WBPaper00046102:Abeta_8hr_rep1~WBPaper00046102:Abeta_8hr_rep2~WBPaper00046102:Abeta_8hr_rep3~WBPaper00046102:Abeta_8hr_rep4~WBPaper00046102:Abeta_12hr_rep1~WBPaper00046102:Abeta_12hr_rep2~WBPaper00046102:Abeta_12hr_rep3~WBPaper00046102:Abeta_12hr_rep4~WBPaper00046102:Abeta_16hr_rep1~WBPaper00046102:Abeta_16hr_rep2~WBPaper00046102:Abeta_16hr_rep3~WBPaper00046102:Abeta_16hr_rep4~WBPaper00046102:Abeta_20hr_rep1	Method: microarray|Species: Caenorhabditis elegans
153	25720500	WBPaper00046496.ce.mr.paper	GSE45292	GPL200	1	Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.	Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions.	4	17638	Golegaonkar S	Golegaonkar S, Tabrez SS, Pandit A, Sethurathinam S, Jagadeeshaprasad MG, Bansode S, Sampathkumar SG, Kulkarni MJ, Mukhopadhyay A	Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.	Aging Cell	2015	WBPaper00046496:DMSO_rep1~WBPaper00046496:DMSO_rep2~WBPaper00046496:Rifampicin_rep1~WBPaper00046496:Rifampicin_rep2	Method: microarray|Species: Caenorhabditis elegans
154	25744875	WBPaper00046523.ce.mr.paper	N.A.	N.A.	1	Pharmacologic targeting of sirtuin and PPAR signaling improves longevity and mitochondrial physiology in respiratory chain complex I mutant Caenorhabditis elegans.	Mitochondrial respiratory chain (RC) diseases are highly morbid multi-systemic conditions for which few effective therapies exist. Given the essential role of sirtuin and PPAR signaling in mediating both mitochondrial physiology and the cellular response to metabolic stress in RC complex I (CI) disease, we postulated that drugs that alter these signaling pathways either directly (resveratrol for sirtuin, rosiglitazone for PPAR, fenofibrate for PPAR), or indirectly by increasing NAD(+) availability (nicotinic acid), might offer effective treatment strategies for primary RC disease. Integrated effects of targeting these cellular signaling pathways on animal lifespan and multi-dimensional in vivo parameters were studied in gas-1(fc21) relative to wild-type (N2 Bristol) worms. Specifically, animal lifespan, transcriptome profiles, mitochondrial oxidant burden, mitochondrial membrane potential, mitochondrial content, amino acid profiles, stable isotope-based intermediary metabolic flux, and total nematode NADH and NAD(+) concentrations were compared. Shortened gas-1(fc21) mutant lifespan was rescued with either resveratrol or nicotinic acid, regardless of whether treatments were begun at the early larval stage or in young adulthood. Rosiglitazone administration beginning in young adult stage animals also rescued lifespan. All drug treatments reversed the most significant transcriptome alterations at the biochemical pathway level relative to untreated gas-1(fc21) animals. Interestingly, increased mitochondrial oxidant burden in gas-1(fc21) was reduced with nicotinic acid but exacerbated significantly by resveratrol and modestly by fenofibrate, with little change by rosiglitazone treatment. In contrast, the reduced mitochondrial membrane potential of mutant worms was further decreased by nicotinic acid but restored by either resveratrol, rosiglitazone, or fenofibrate. Using a novel HPLC assay, we discovered that gas-1(fc21) worms have significant deficiencies of NAD(+) and NADH. Whereas resveratrol restored concentrations of both metabolites, nicotinic acid only restored NADH. Characteristic branched chain amino acid elevations in gas-1(fc21) animals were normalized completely by nicotinic acid and largely by resveratrol, but not by either rosiglitazone or fenofibrate. We developed a visualization system to enable objective integration of these multi-faceted physiologic endpoints, an approach that will likely be useful to apply in future drug treatment studies in human patients with mitochondrial disease. Overall, these data demonstrate that direct or indirect pharmacologic restoration of altered sirtuin and PPAR signaling can yield significant health and longevity benefits, although by divergent bioenergetic mechanism(s), in a nematode model of mitochondrial RC complex I disease. Thus, these animal model studies introduce important, integrated insights that may ultimately yield rational treatment strategies for human RC disease.	64	10247	McCormack S	McCormack S, Polyak E, Ostrovsky J, Dingley SD, Rao M, Kwon YJ, Xiao R, Zhang Z, Nakamaru-Ogiso E, Falk MJ	Pharmacologic targeting of sirtuin and PPAR signaling improves longevity and mitochondrial physiology in respiratory chain complex I mutant Caenorhabditis elegans.	Mitochondrion	2015	WBPaper00046523:N2_untreated_S-basal_YoungAdult_rep1~WBPaper00046523:N2_untreated_S-basal_YoungAdult_rep2~WBPaper00046523:N2_untreated_S-basal_YoungAdult_rep3~WBPaper00046523:N2_untreated_S-basal_YoungAdult_rep4~WBPaper00046523:N2_untreated_S-basal_L1_rep1~WBPaper00046523:N2_untreated_S-basal_L1_rep2~WBPaper00046523:N2_untreated_S-basal_L1_rep3~WBPaper00046523:N2_untreated_S-basal_L1_rep4~WBPaper00046523:gas-1(fc21)_untreated_S-basal_YoungAdult_rep1~WBPaper00046523:gas-1(fc21)_untreated_S-basal_YoungAdult_rep2~WBPaper00046523:gas-1(fc21)_untreated_S-basal_YoungAdult_rep3~WBPaper00046523:gas-1(fc21)_untreated_S-basal_YoungAdult_rep4~WBPaper00046523:gas-1(fc21)_untreated_S-basal_L1_rep1~WBPaper00046523:gas-1(fc21)_untreated_S-basal_L1_rep2~WBPaper00046523:gas-1(fc21)_untreated_S-basal_L1_rep3~WBPaper00046523:gas-1(fc21)_untreated_S-basal_L1_rep4~WBPaper00046523:N2_untreated_DMSO_YoungAdult_rep1~WBPaper00046523:N2_untreated_DMSO_YoungAdult_rep2~WBPaper00046523:N2_untreated_DMSO_YoungAdult_rep3~WBPaper00046523:N2_untreated_DMSO_YoungAdult_rep4~WBPaper00046523:N2_untreated_DMSO_L1_rep1~WBPaper00046523:N2_untreated_DMSO_L1_rep2~WBPaper00046523:N2_untreated_DMSO_L1_rep3~WBPaper00046523:N2_untreated_DMSO_L1_rep4~WBPaper00046523:gas-1(fc21)_untreated_DMSO_YoungAdult_rep1~WBPaper00046523:gas-1(fc21)_untreated_DMSO_YoungAdult_rep2~WBPaper00046523:gas-1(fc21)_untreated_DMSO_YoungAdult_rep3~WBPaper00046523:gas-1(fc21)_untreated_DMSO_YoungAdult_rep4~WBPaper00046523:gas-1(fc21)_untreated_DMSO_L1_rep1~WBPaper00046523:gas-1(fc21)_untreated_DMSO_L1_rep2~WBPaper00046523:gas-1(fc21)_untreated_DMSO_L1_rep3~WBPaper00046523:gas-1(fc21)_untreated_DMSO_L1_rep4~WBPaper00046523:gas-1(fc21)_nicotinic-acid_S-basal_L1_rep1~WBPaper00046523:gas-1(fc21)_nicotinic-acid_S-basal_L1_rep2~WBPaper00046523:gas-1(fc21)_nicotinic-acid_S-basal_L1_rep3~WBPaper00046523:gas-1(fc21)_nicotinic-acid_S-basal_L1_rep4~WBPaper00046523:gas-1(fc21)_nicotinic-acid_S-basal_YoungAdult_rep1~WBPaper00046523:gas-1(fc21)_nicotinic-acid_S-basal_YoungAdult_rep2~WBPaper00046523:gas-1(fc21)_nicotinic-acid_S-basal_YoungAdult_rep3~WBPaper00046523:gas-1(fc21)_nicotinic-acid_S-basal_YoungAdult_rep4~WBPaper00046523:gas-1(fc21)_resveratrol_DMSO_L1_rep1~WBPaper00046523:gas-1(fc21)_resveratrol_DMSO_L1_rep2~WBPaper00046523:gas-1(fc21)_resveratrol_DMSO_L1_rep3~WBPaper00046523:gas-1(fc21)_resveratrol_DMSO_L1_rep4~WBPaper00046523:gas-1(fc21)_resveratrol_DMSO_YoungAdult_rep1~WBPaper00046523:gas-1(fc21)_resveratrol_DMSO_YoungAdult_rep2~WBPaper00046523:gas-1(fc21)_resveratrol_DMSO_YoungAdult_rep3~WBPaper00046523:gas-1(fc21)_resveratrol_DMSO_YoungAdult_rep4~WBPaper00046523:gas-1(fc21)_rosiglitazone_DMSO_L1_rep1~WBPaper00046523:gas-1(fc21)_rosiglitazone_DMSO_L1_rep2~WBPaper00046523:gas-1(fc21)_rosiglitazone_DMSO_L1_rep3~WBPaper00046523:gas-1(fc21)_rosiglitazone_DMSO_L1_rep4~WBPaper00046523:gas-1(fc21)_rosiglitazone_DMSO_YoungAdult_rep1~WBPaper00046523:gas-1(fc21)_rosiglitazone_DMSO_YoungAdult_rep2~WBPaper00046523:gas-1(fc21)_rosiglitazone_DMSO_YoungAdult_rep3~WBPaper00046523:gas-1(fc21)_rosiglitazone_DMSO_YoungAdult_rep4~WBPaper00046523:gas-1(fc21)_fenofibrate_DMSO_YoungAdult_rep1~WBPaper00046523:gas-1(fc21)_fenofibrate_DMSO_YoungAdult_rep2~WBPaper00046523:gas-1(fc21)_fenofibrate_DMSO_YoungAdult_rep3~WBPaper00046523:gas-1(fc21)_fenofibrate_DMSO_YoungAdult_rep4~WBPaper00046523:gas-1(fc21)_fenofibrate_DMSO_L1_rep1~WBPaper00046523:gas-1(fc21)_fenofibrate_DMSO_L1_rep2~WBPaper00046523:gas-1(fc21)_fenofibrate_DMSO_L1_rep3~WBPaper00046523:gas-1(fc21)_fenofibrate_DMSO_L1_rep4	Method: microarray|Species: Caenorhabditis elegans
155	25774872	WBPaper00046548.ce.mr.paper	N.A.	N.A.	1	The nuclear receptor DAF-12 regulates nutrient metabolism and reproductive growth in nematodes.	Appropriate nutrient response is essential for growth and reproduction. Under favorable nutrient conditions, the C. elegans nuclear receptor DAF-12 is activated by dafachronic acids, hormones that commit larvae to reproductive growth. Here, we report that in addition to its well-studied role in controlling developmental gene expression, the DAF-12 endocrine system governs expression of a gene network that stimulates the aerobic catabolism of fatty acids. Thus, activation of the DAF-12 transcriptome coordinately mobilizes energy stores to permit reproductive growth. DAF-12 regulation of this metabolic gene network is conserved in the human parasite, Strongyloides stercoralis, and inhibition of specific steps in this network blocks reproductive growth in both of the nematodes. Our study provides a molecular understanding for metabolic adaptation of nematodes to their environment, and suggests a new therapeutic strategy for treating parasitic diseases.	4	17637	Wang Z	Wang Z, Stoltzfus J, You YJ, Ranjit N, Tang H, Xie Y, Lok JB, Mangelsdorf DJ, Kliewer SA	The nuclear receptor DAF-12 regulates nutrient metabolism and reproductive growth in nematodes.	PLoS Genet	2015	WBPaper00046548:Etoh-control_rep1~WBPaper00046548:Etoh-control_rep2~WBPaper00046548:delta7-dafachronic-acid_rep1~WBPaper00046548:delta7-dafachronic-acid_rep2	Method: microarray|Species: Caenorhabditis elegans
156	25804201	WBPaper00046639.ce.mr.paper	GSE57664	GPL200	1	Gene expression profiling to investigate tyrosol-induced lifespan extension in Caenorhabditis elegans.	PURPOSE: We have previously reported that tyrosol (TYR) promotes lifespan extension in the nematode Caenorhabditis elegans, also inducing a stronger resistance to thermal and oxidative stress in vivo. In this study, we performed a whole-genome DNA microarray in order to narrow down the search for candidate genes or signaling pathways potentially involved in TYR effects on C. elegans longevity. METHODS: Nematodes were treated with 0 or 250M TYR, total RNA was isolated at the adult stage, and derived cDNA probes were hybridized to Affymetrix C. elegans expression arrays. Microarray data analysis was performed, and relative mRNA expression of selected genes was validated using qPCR. RESULTS: Microarray analysis identified 208 differentially expressed genes (206 over-expressed and two under-expressed) when comparing TYR-treated nematodes with vehicle-treated controls. Many of these genes are linked to processes such as regulation of growth, transcription, reproduction, lipid metabolism and body morphogenesis. Moreover, we detected an interesting overlap between the expression pattern elicited by TYR and those induced by other dietary polyphenols known to extend lifespan in C. elegans, such as quercetin and tannic acid. CONCLUSIONS: Our results suggest that important cellular mechanisms directly related to longevity are influenced by TYR treatment in C. elegans, supporting our previous notion that this phenol might act on conserved genetic pathways to increase lifespan in a whole organism.	6	17638	Canuelo A	Canuelo A, Esteban FJ, Peragon J	Gene expression profiling to investigate tyrosol-induced lifespan extension in Caenorhabditis elegans.	Eur J Nutr	2015	WBPaper00046639:control_rep1~WBPaper00046639:control_rep2~WBPaper00046639:control_rep3~WBPaper00046639:tyrosol-treated_rep1~WBPaper00046639:tyrosol-treated_rep2~WBPaper00046639:tyrosol-treated_rep3	Method: microarray|Species: Caenorhabditis elegans
157	25892013	WBPaper00046678.ce.mr.paper	GSE64973	GPL200	1	A Lipid-TORC1 Pathway Promotes Neuronal Development and Foraging Behavior under Both Fed and Fasted Conditions in C.elegans.	Food deprivation suppresses animal growth and development but spares the systems essential for foraging. The mechanisms underlying this selective development, and potential roles of lipids in it, are unclear. When C. elegans hatch in a food-free environment, postembryonic growth and development stall, but sensory neuron differentiation and neuronal development required for food responses continue. Here, we show that monomethyl branched-chain fatty acids (mmBCFAs) and their derivative, d17iso-glucosylceramide, function in the intestine to promote foraging behavior and sensory neuron maturation through both TORC1-dependent and -independent mechanisms. We show that mmBCFAs impact the expression of a subset of genes, including ceh-36/Hox, which we show to play a key role in mediating the regulation of the neuronal functions by this lipid pathway. This study uncovers that a lipid pathway promotes neuronal functions involved in foraging under both fed and fasting conditions and adds critical insight into the physiological functions of TORC1.	6	17637	Kniazeva M	Kniazeva M, Zhu H, Sewell AK, Han M	A Lipid-TORC1 Pathway Promotes Neuronal Development and Foraging Behavior under Both Fed and Fasted Conditions in C.elegans.	Dev Cell	2015	WBPaper00046678:elo-5(gk208)_C17ISO-deficient-C13ISO_rep1~WBPaper00046678:elo-5(gk208)_C17ISO-deficient-C13ISO_rep2~WBPaper00046678:elo-5(gk208)_C17ISO_rep1~WBPaper00046678:elo-5(gk208)_C17ISO_rep2~WBPaper00046678:N2_C13ISO_rep1~WBPaper00046678:N2_C13ISO_rep2	Method: microarray|Species: Caenorhabditis elegans
158	25994267	WBPaper00046853.ce.mr.paper	N.A.	N.A.	1	Adsorbable organic bromine compounds (AOBr) in aquatic samples: a nematode-based toxicogenomic assessment of the exposure hazard.	Elevated levels of adsorbable organic bromine compounds (AOBr) have been detected in German lakes, and cyanobacteria like Microcystis, which are known for the synthesis of microcystins, are one of the main producers of natural organobromines. However, very little is known about how environmental realistic concentrations of organobromines impact invertebrates. Here, the nematode Caenorhabditis elegans was exposed to AOBr-containing surface water samples and to a Microcystis aeruginosa-enriched batch culture (MC-BA) and compared to single organobromines and microcystin-LR exposures. Stimulatory effects were observed in certain life trait variables, which were particularly pronounced in nematodes exposed to MC-BA. A whole genome DNA-microarray revealed that MC-BA led to the differential expression of more than 2000 genes, many of which are known to be involved in metabolic, neurologic, and morphologic processes. Moreover, the upregulation of cyp- and the downregulation of abu-genes suggested the presence of chronic stress. However, the nematodes were not marked by negative phenotypic responses. The observed difference in MC-BA and microcystin-LR (which impacted lifespan, growth, and reproduction) exposed nematodes was hypothesized to be likely due to other compounds within the batch culture. Most likely, the exposure to low concentrations of organobromines appears to buffer the effects of toxic substances, like microcystin-LR.	15	17638	Saul N	Saul N, Sturzenbaum SR, Chakrabarti S, Baberschke N, Lieke T, Putschew A, Kochan C, Menzel R, Steinberg CE	Adsorbable organic bromine compounds (AOBr) in aquatic samples: a nematode-based toxicogenomic assessment of the exposure hazard.	Environ Sci Pollut Res Int	2015	WBPaper00046853:Water(Control)_rep1~WBPaper00046853:Water(Control)_rep2~WBPaper00046853:Water(Control)_rep3~WBPaper00046853:Z-Medium(Control)_rep1~WBPaper00046853:Z-Medium(Control)_rep2~WBPaper00046853:Z-Medium(Control)_rep3~WBPaper00046853:Lake-Stobensee-sample-August_rep1~WBPaper00046853:Lake-Stobensee-sample-August_rep2~WBPaper00046853:Lake-Stobensee-sample-August_rep3~WBPaper00046853:Lake-Stobensee-sample-October_rep1~WBPaper00046853:Lake-Stobensee-sample-October_rep2~WBPaper00046853:Lake-Stobensee-sample-October_rep3~WBPaper00046853:M.aeruginosa-batch-culture_rep1~WBPaper00046853:M.aeruginosa-batch-culture_rep2~WBPaper00046853:M.aeruginosa-batch-culture_rep3	Method: microarray|Species: Caenorhabditis elegans
159	26048561	WBPaper00046887.ce.mr.paper	GSE52747	GPL200	1	Identification of Wnt Pathway Target Genes Regulating the Division and Differentiation of Larval Seam Cells and Vulval Precursor Cells in Caenorhabditis elegans.	The evolutionarily conserved Wnt/-catenin signaling pathway plays a fundamental role during metazoan development, regulating numerous processes including cell fate specification, cell migration, and stem cell renewal. Wnt ligand binding leads to stabilization of the transcriptional effector -catenin and upregulation of target gene expression to mediate a cellular response. During larval development of the nematode Caenorhabditis elegans, Wnt/-catenin pathways act in fate specification of two hypodermal cell types, the ventral vulval precursor cells (VPCs) and the lateral seam cells. Because little is known about targets of the Wnt signaling pathways acting during larval VPC and seam cell differentiation, we sought to identify genes regulated by Wnt signaling in these two hypodermal cell types. We conditionally activated Wnt signaling in larval animals and performed cell type-specific &quot;mRNA tagging&quot; to enrich for VPC and seam cell-specific mRNAs, and then used microarray analysis to examine gene expression compared to control animals. Two hundred thirty-nine genes activated in response to Wnt signaling were identified, and we characterized 50 genes further. The majority of these genes are expressed in seam and/or vulval lineages during normal development, and reduction of function for nine genes caused defects in the proper division, fate specification, fate execution, or differentiation of seam cells and vulval cells. Therefore, the combination of these techniques was successful at identifying potential cell type-specific Wnt pathway target genes from a small number of cells and at increasing our knowledge of the specification and behavior of these C. elegans larval hypodermal cells.	8	17638	Gorrepati L	Gorrepati L, Krause MW, Chen W, Brodigan TM, Correa-Mendez M, Eisenmann DM	Identification of Wnt Pathway Target Genes Regulating the Division and Differentiation of Larval Seam Cells and Vulval Precursor Cells in Caenorhabditis elegans.	G3 (Bethesda)	2015	WBPaper00046887:N2_rep2~WBPaper00046887:N2_rep3~WBPaper00046887:N2_rep4~WBPaper00046887:huIs1_rep1~WBPaper00046887:DeltaNTPOP1_rep2~WBPaper00046887:huIs1_rep3~WBPaper00046887:huIs1_rep4~WBPaper00046887:DeltaNTPOP1_rep5	Method: microarray|Species: Caenorhabditis elegans|Topic: Wnt signaling pathway|Topic: canonical Wnt signaling pathway
160	26111764	WBPaper00047021.ce.mr.paper	GSE24847	GPL200	1	A systems toxicology approach on the mechanism of uptake and toxicity of MWCNT in Caenorhabditis elegans.	The increased volumes of carbon nanotubes (CNTs) being utilized in industrial and biomedical processes carries with it an increased risk of unintentional release into the environment, requiring a thorough hazard and risk assessment. In this study, the toxicity of pristine and hydroxylated (OH-) multiwall CNTs (MWCNTs) was investigated in the nematode Caenorhabditis elegans using an integrated systems toxicology approach. To gain an insight into the toxic mechanism of MWCNTs, microarray and proteomics were conducted for C. elegans followed by pathway analyses. The results of pathway analyses suggested endocytosis, phagocytosis, oxidative stress and endoplasmic reticulum (ER) stress, as potential mechanisms of uptake and toxicity, which were subsequently investigated using loss-of-function mutants of genes of those pathways. The expression of phagocytosis related genes (i.e. ced-10 and rab-7) were significantly increased upon exposure to OH-MWCNT, concomitantly with the rescued toxicity by loss-of-function mutants of those genes, such as ced-10(n3246) and rab-7(ok511). An increased sensitivity of the hsp-4(gk514) mutant by OH-MWCNT, along with a decreased expression of hsp-4 at both gene and protein level suggests that MWCNTs may affect ER stress response in C. elegans. Collectively, the results implied phagocytosis to be a potential mechanism of uptake of MWCNTs, and ER and oxidative stress as potential mechanisms of toxicity. The integrated systems toxicology approach applied in this study provided a comprehensive insight into the toxic mechanism of MWCNTs in C. elegans, which may eventually be used to develop an &quot;Adverse Outcome Pathway (AOP)&quot;, a recently introduced concept as a conceptual framework to link molecular level responses to higher level effects.	3	17638	Eom HJ	Eom HJ, Roca CP, Roh JY, Chatterjee N, Jeong JS, Shim I, Kim HM, Kim PJ, Choi K, Giralt F, Choi J	A systems toxicology approach on the mechanism of uptake and toxicity of MWCNT in Caenorhabditis elegans.	Chem Biol Interact	2015	WBPaper00047021:0hr_MWCNT-exposure_rep1~WBPaper00047021:4hr_MWCNT-exposure_rep1~WBPaper00047021:24hr_MWCNT-exposure_rep1	Method: microarray|Species: Caenorhabditis elegans
161	25419847	WBPaper00047070_1.ce.mr.paper	GSE47778,GSE51161,GSE51162	GPL200	1	DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.	Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature ageing. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with ageing. Here we show that the FOXO transcription factor DAF-16 is activated in response to DNA damage during development, whereas the DNA damage responsiveness of DAF-16 declines with ageing. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA-damage-induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16-mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.	15	17638	Mueller MM	Mueller MM, Castells-Roca L, Babu V, Ermolaeva MA, Muller RU, Frommolt P, Williams AB, Greiss S, Schneider JI, Benzing T, Schermer B, Schumacher B	DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.	Nat Cell Biol	2014	WBPaper00047070:N2_untreated_rep1~WBPaper00047070:N2_untreated_rep2~WBPaper00047070:N2_untreated_rep3~WBPaper00047070:N2_60mJ-UV_rep1~WBPaper00047070:N2_60mJ-UV_rep2~WBPaper00047070:N2_60mJ-UV_rep3~WBPaper00047070:N2_starvation_rep1~WBPaper00047070:N2_starvation_rep2~WBPaper00047070:N2_starvation_rep3~WBPaper00047070:xpa-1(ok698)_untreated_rep1~WBPaper00047070:xpa-1(ok698)_untreated_rep2~WBPaper00047070:xpa-1(ok698)_untreated_rep3~WBPaper00047070:xpa-1(ok698)_10mJ-UV_rep1~WBPaper00047070:xpa-1(ok698)_10mJ-UV_rep2~WBPaper00047070:xpa-1(ok698)_10mJ-UV_rep3	Method: microarray|Species: Caenorhabditis elegans
162	25419847	WBPaper00047070_2.ce.mr.paper	GSE47778,GSE51161,GSE51162	GPL200	1	DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.	Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature ageing. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with ageing. Here we show that the FOXO transcription factor DAF-16 is activated in response to DNA damage during development, whereas the DNA damage responsiveness of DAF-16 declines with ageing. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA-damage-induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16-mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.	36	17638	Mueller MM	Mueller MM, Castells-Roca L, Babu V, Ermolaeva MA, Muller RU, Frommolt P, Williams AB, Greiss S, Schneider JI, Benzing T, Schermer B, Schumacher B	DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.	Nat Cell Biol	2014	WBPaper00047070:N2_untreated_rep4~WBPaper00047070:N2_untreated_rep5~WBPaper00047070:N2_untreated_rep6~WBPaper00047070:N2_60mJ-UV_rep4~WBPaper00047070:N2_60mJ-UV_rep5~WBPaper00047070:N2_60mJ-UV_rep6~WBPaper00047070:N2_starvation_rep4~WBPaper00047070:N2_starvation_rep5~WBPaper00047070:N2_starvation_rep6~WBPaper00047070:daf-16(mu86)_untreated_rep1~WBPaper00047070:daf-16(mu86)_untreated_rep2~WBPaper00047070:daf-16(mu86)_untreated_rep3~WBPaper00047070:daf-16(mu86)_60mJ-UV_rep1~WBPaper00047070:daf-16(mu86)_60mJ-UV_rep2~WBPaper00047070:daf-16(mu86)_60mJ-UV_rep3~WBPaper00047070:daf-16(mu86)_starvation_rep1~WBPaper00047070:daf-16(mu86)_starvation_rep2~WBPaper00047070:daf-2(e1370)_untreated_rep1~WBPaper00047070:daf-2(e1370)_untreated_rep2~WBPaper00047070:daf-2(e1370)_untreated_rep3~WBPaper00047070:daf-2(e1370)_60mJ-UV_rep1~WBPaper00047070:daf-2(e1370)_60mJ-UV_rep2~WBPaper00047070:daf-2(e1370)_60mJ-UV_rep3~WBPaper00047070:daf-2(e1370)_starvation_rep1~WBPaper00047070:daf-2(e1370)_starvation_rep2~WBPaper00047070:daf-2(e1370)_starvation_rep3~WBPaper00047070:daf-2(e1370);daf-16(mu86)_untreated_rep1~WBPaper00047070:daf-2(e1370);daf-16(mu86)_60mJ-UV_rep1~WBPaper00047070:daf-2(e1370);daf-16(mu86)_60mJ-UV_rep2~WBPaper00047070:daf-2(e1370);daf-16(mu86)_60mJ-UV_rep3~WBPaper00047070:daf-2(e1370);daf-16(mu86)_starvation_rep1~WBPaper00047070:daf-2(e1370);daf-16(mu86)_starvation_rep2~WBPaper00047070:daf-2(e1370);daf-16(mu86)_starvation_rep3~WBPaper00047070:daf-2(e1370);daf-16(mu86)_starvation_rep4~WBPaper00047070:daf-2(e1370);daf-16(mu86)_untreated_rep2~WBPaper00047070:daf-2(e1370);daf-16(mu86)_untreated_rep3	Method: microarray|Species: Caenorhabditis elegans
163	26321661	WBPaper00048490.ce.mr.paper	GSE70692	GPL19230	1	s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways.	s-adenosylmethionine (SAM) is the sole methyl donor modifying histones, nucleic acids, and phospholipids. Its fluctuation affects hepatic phosphatidylcholine (PC) synthesis or may be linked to variations in DNA or histone methylation. Physiologically, low SAM is associated with lipid accumulation, tissue injury, and immune responses in fatty liver disease. However, molecular connections among SAM limitation, methyltransferases, and disease-associated phenotypes are unclear. We find that low SAM can activate or attenuate Caenorhabditis elegans immune responses. Immune pathways are stimulated downstream of PC production on a non-pathogenic diet. In contrast, distinct SAM-dependent mechanisms limit survival on pathogenic Pseudomonas aeruginosa. C. elegans undertakes a broad transcriptional response to pathogens and we find that low SAM restricts H3K4me3 at Pseudomonas-responsive promoters, limiting their expression. Furthermore, this response depends on the H3K4 methyltransferase set-16/MLL. Thus, our studies provide molecular links between SAM and innate immune functions and suggest that SAM depletion may limit stress-induced gene expression.	12	17638	Ding W	Ding W, Smulan LJ, Hou NS, Taubert S, Watts JL, Walker AK	s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways.	Cell Metab	2015	WBPaper00048490:empty-vector_repA~WBPaper00048490:empty-vector_repB~WBPaper00048490:empty-vector_repC~WBPaper00048490:empty-vector_choline_repA~WBPaper00048490:empty-vector_choline_repB~WBPaper00048490:empty-vector_choline_repC~WBPaper00048490:sams-1(RNAi)_repA~WBPaper00048490:sams-1(RNAi)_repB~WBPaper00048490:sams-1(RNAi)_repC~WBPaper00048490:sams-1(RNAi)_choline_repA~WBPaper00048490:sams-1(RNAi)_choline_repB~WBPaper00048490:sams-1(RNAi)_choline_repC	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
164	26360906	WBPaper00048530.ce.mr.paper	GSE72029	GPL200	1	The Conserved G-Protein Coupled Receptor FSHR-1 Regulates Protective Host Responses to Infection and Oxidative Stress.	The innate immune system's ability to sense an infection is critical so that it can rapidly respond if pathogenic microorganisms threaten the host, but otherwise maintain a quiescent baseline state to avoid causing damage to the host or to commensal microorganisms. One important mechanism for discriminating between pathogenic and non-pathogenic bacteria is the recognition of cellular damage caused by a pathogen during the course of infection. In Caenorhabditis elegans, the conserved G-protein coupled receptor FSHR-1 is an important constituent of the innate immune response. FSHR-1 activates the expression of antimicrobial infection response genes in infected worms and delays accumulation of the ingested pathogen Pseudomonas aeruginosa. FSHR-1 is central not only to the worm's survival of infection by multiple pathogens, but also to the worm's survival of xenobiotic cadmium and oxidative stresses. Infected worms produce reactive oxygen species to fight off the pathogens; FSHR-1 is required at the site of infection for the expression of detoxifying genes that protect the host from collateral damage caused by this defense response. Finally, the FSHR-1 pathway is important for the ability of worms to discriminate pathogenic from benign bacteria and subsequently initiate an aversive learning program that promotes selective pathogen avoidance.	12	17638	Miller EV	Miller EV, Grandi LN, Giannini JA, Robinson JD, Powell JR	The Conserved G-Protein Coupled Receptor FSHR-1 Regulates Protective Host Responses to Infection and Oxidative Stress.	PLoS One	2015	WBPaper00048530:N2_OP50_prep9~WBPaper00048530:N2_OP50_prep15~WBPaper00048530:N2_OP50_prep30~WBPaper00048530:N2_PA14_prep9~WBPaper00048530:N2_PA14_prep15~WBPaper00048530:N2_PA14_prep30~WBPaper00048530:fshr-1(ok778)_OP50_prep9~WBPaper00048530:fshr-1(ok778)_OP50_prep15~WBPaper00048530:fshr-1(ok778)_OP50_prep30~WBPaper00048530:fshr-1(ok778)_PA14_prep9~WBPaper00048530:fshr-1(ok778)_PA14_prep15~WBPaper00048530:fshr-1(ok778)_PA14_prep30	Method: microarray|Species: Caenorhabditis elegans
165	26387713	WBPaper00048563.ce.mr.paper	GSE71618	GPL200	1	Transcriptional Control of Synaptic Remodeling through Regulated Expression of an Immunoglobulin Superfamily Protein.	Neural circuits are actively remodeled during brain development, but the molecular mechanisms that trigger circuit refinement are poorly understood. Here, we describe a transcriptional program in C.elegans that regulates expression of an Ig domain protein, OIG-1, to control the timing of synaptic remodeling. DD GABAergic neurons reverse polarity during larval development by exchanging the locations of pre- and postsynaptic components. In newly born larvae, DDs receive cholinergic inputs in the dorsal nerve cord. These inputs are switched to the ventral side by the end of the first larval (L1) stage. VD class GABAergic neurons are generated in the late L1 and are postsynaptic to cholinergic neurons in the dorsal nerve cord but do not remodel. We investigated remodeling of the postsynaptic apparatus in DD and VD neurons using targeted expression of the acetylcholine receptor (AChR) subunit, ACR-12::GFP. We determined that OIG-1 antagonizes the relocation of ACR-12 from the dorsal side in L1 DD neurons. During the L1/L2 transition, OIG-1 is downregulated in DD neurons by the transcription factor IRX-1/Iroquois, allowing the repositioning of synaptic inputs to the ventral side. In VD class neurons, which normally do not remodel, the transcription factor UNC-55/COUP-TF turns off IRX-1, thus maintaining high levels of OIG-1 to block the removal of dorsally located ACR-12 receptors. OIG-1 is secreted from GABA neurons, but its anti-plasticity function is cell autonomous and may not require secretion. Our study provides a novel mechanism by which synaptic remodeling is set in motion through regulated expression of an Ig domain protein.	7	17638	He S	He S, Philbrook A, McWhirter R, Gabel CV, Taub DG, Carter MH, Hanna IM, Francis MM, Miller DM	Transcriptional Control of Synaptic Remodeling through Regulated Expression of an Immunoglobulin Superfamily Protein.	Curr Biol	2015	WBPaper00048563:L1_DD-neuron_rep1~WBPaper00048563:L1_DD-neuron_rep2~WBPaper00048563:L1_DD-neuron_rep3~WBPaper00048563:L1_DD-neuron_rep4~WBPaper00048563:L1_all-cells_rep1~WBPaper00048563:L1_all-cells_rep2~WBPaper00048563:L1_all-cells_rep3	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
166	23664972	WBPaper00048637.ce.mr.paper	GSE45651	GPL200	1	The tumor suppressor Rb critically regulates starvation-induced stress response in C. elegans.	How animals coordinate gene expression in response to starvation is an outstanding problem closely linked to aging, obesity, and cancer. Newly hatched Caenorhabditis elegans respond to food deprivation by halting development and promoting long-term survival (L1 diapause), thereby providing an excellent model for the study of starvation response. Through a genetic search, we have discovered that the tumor suppressor Rb critically promotes survival during L1 diapause and most likely does so by regulating the expression of genes in both insulin-IGF-1 signaling (IIS)-dependent and -independent pathways mainly in neurons and the intestine. Global gene expression analyses suggested that Rb maintains the &quot;starvation-induced&quot; transcriptome and represses the &quot;refeeding-induced&quot; transcriptome, including the repression of many pathogen-, toxin-, and oxidative-stress-inducible and metabolic genes, as well as the activation of many other stress-resistant genes, mitochondrial respiratory chain genes, and potential IIS receptor antagonists. Notably, the majority of genes dysregulated in starved L1 Rb(-) animals were not found to be dysregulated in fed conditions. Altogether, these findings identify Rb as a critical regulator of the starvation response and suggest a link between functions of tumor suppressors and starvation survival. These results may provide mechanistic insights into why cancer cells are often hypersensitive to starvation treatment.	6	17638	Cui M	Cui M, Cohen ML, Teng C, Han M	The tumor suppressor Rb critically regulates starvation-induced stress response in C. elegans.	Curr Biol	2013	WBPaper00048637:N2_rep1~WBPaper00048637:N2_rep2~WBPaper00048637:N2_rep3~WBPaper00048637:lin-35(n745)_rep1~WBPaper00048637:lin-35(n745)_rep2~WBPaper00048637:lin-35(n745)_rep3	Method: microarray|Species: Caenorhabditis elegans
167	26564160	WBPaper00048762.ce.mr.paper	GSE73070	GPL200	1	Genomic Analyses of Sperm Fate Regulator Targets Reveal a Common Set of Oogenic mRNAs in Caenorhabditis elegans.	Germ cell specification as sperm or oocyte is an ancient cell fate decision, but its molecular regulation is poorly understood. In Caenorhabditis elegans, the FOG-1 and FOG-3 proteins behave genetically as terminal regulators of sperm fate specification. Both are homologous to well-established RNA regulators, suggesting that FOG-1 and FOG-3 specify the sperm fate post-transcriptionally. We predicted that FOG-1 and FOG-3, as terminal regulators of the sperm fate, might regulate a battery of gamete-specific differentiation genes. Here we test that prediction by exploring on a genomic scale the messenger RNAs (mRNAs) associated with FOG-1 and FOG-3. Immunoprecipitation of the proteins and their associated mRNAs from spermatogenic germlines identifies 81 FOG-1 and 722 FOG-3 putative targets. Importantly, almost all FOG-1 targets are also FOG-3 targets, and these common targets are strongly biased for oogenic mRNAs. The discovery of common target mRNAs suggested that FOG-1 and FOG-3 work together. Consistent with that idea, we find that FOG-1 and FOG-3 proteins co-immunoprecipitate from both intact nematodes and mammalian tissue culture cells and that they colocalize in germ cells. Taking our results together, we propose a model in which FOG-1 and FOG-3 work in a complex to repress oogenic transcripts and thereby promote the sperm fate.	40	17638	Noble D	Noble D, Aoki ST, Ortiz MA, Kim KW, Verheyden JM, Kimble J	Genomic Analyses of Sperm Fate Regulator Targets Reveal a Common Set of Oogenic mRNAs in Caenorhabditis elegans.	Genetics	2016	WBPaper00048762:Myc-FOG-1_Myc-IP_rep1~WBPaper00048762:Myc-FOG-1_Myc-IP_rep2~WBPaper00048762:Myc-FOG-1_Myc-IP_rep3~WBPaper00048762:Myc-FOG-1_Myc-IP_rep4~WBPaper00048762:Myc-FOG-1_Myc-IP_rep5~WBPaper00048762:Myc-FOG-1_Myc-IP_rep6~WBPaper00048762:Myc-FOG-1_Myc-IP_rep7~WBPaper00048762:N2_Myc-IP_rep1~WBPaper00048762:N2_Myc-IP_rep2~WBPaper00048762:N2_Myc-IP_rep3~WBPaper00048762:N2_Myc-IP_rep4~WBPaper00048762:N2_Myc-IP_rep5~WBPaper00048762:N2_Myc-IP_rep6~WBPaper00048762:N2_Myc-IP_rep7~WBPaper00048762:FOG-3-FLAG_FLAG-IP_rep1~WBPaper00048762:FOG-3-FLAG_FLAG-IP_rep2~WBPaper00048762:FOG-3-FLAG_FLAG-IP_rep3~WBPaper00048762:FOG-3-FLAG_FLAG-IP_rep4~WBPaper00048762:FOG-3-FLAG_FLAG-IP_rep5~WBPaper00048762:FOG-3-FLAG_FLAG-IP_rep6~WBPaper00048762:FOG-3-FLAG_FLAG-IP_rep7~WBPaper00048762:N2_FLAG-IP_rep1~WBPaper00048762:N2_FLAG-IP_rep2~WBPaper00048762:N2_FLAG-IP_rep3~WBPaper00048762:N2_FLAG-IP_rep4~WBPaper00048762:N2_FLAG-IP_rep5~WBPaper00048762:N2_FLAG-IP_rep6~WBPaper00048762:N2_FLAG-IP_rep7~WBPaper00048762:Myc-FOG-1_Myc-WholeAnimal_rep1~WBPaper00048762:Myc-FOG-1_Myc-WholeAnimal_rep2~WBPaper00048762:Myc-FOG-1_Myc-WholeAnimal_rep3~WBPaper00048762:N2_Myc-WholeAnimal_rep1~WBPaper00048762:N2_Myc-WholeAnimal_rep2~WBPaper00048762:N2_Myc-WholeAnimal_rep3~WBPaper00048762:FOG-3-FLAG_FLAG-WholeAnimal_rep1~WBPaper00048762:FOG-3-FLAG_FLAG-WholeAnimal_rep2~WBPaper00048762:FOG-3-FLAG_FLAG-WholeAnimal_rep3~WBPaper00048762:N2_FLAG-WholeAnimal_rep1~WBPaper00048762:N2_FLAG-WholeAnimal_rep2~WBPaper00048762:N2_FLAG-WholeAnimal_rep3	Method: microarray|Species: Caenorhabditis elegans
168	26542024	WBPaper00048771.ce.mr.paper	GSE74459	GPL200	1	Spatial and temporal translational control of germ cell mRNAs via an eIF4E isoform, IFE-1.	Regulated mRNA translation is vital for germ cells to produce new proteins in the spatial and temporal patterns that drive gamete development. Translational control involves the de-repression of stored mRNAs and their recruitment by initiation factors (eIF's) to ribosomes. C. elegans expresses five eIF4Es (IFE-1-5); several were shown to selectively recruit unique pools of mRNA. Individual IFE knockouts yield unique phenotypes due to inefficient translation of certain mRNAs. We identified mRNAs preferentially translated via a germline-specific eIF4E isoform, IFE-1. Differential polysome microarray analysis identified 77 mRNAs recruited by IFE-1. Among the IFE-1-dependent mRNAs are several required for late germ cell differentiation and maturation. Polysome association of gld-1, vab-1, vpr-1, rab-7, and rnp-3 mRNAs relies on IFE-1. Live animal imaging showed IFE-1-dependent selectivity in spatial and temporal translation of germline mRNAs. Altered MAPK activation in oocytes suggests dual roles for IFE-1, both promoting and suppressing oocyte maturation at different stages. This single eIF4E isoform exerts positive, selective translational control during germ cell differentiation.	12	10701	Friday AJ	Friday AJ, Henderson MA, Morrison JK, Hoffman JL, Keiper BD	Spatial and temporal translational control of germ cell mRNAs via an eIF4E isoform, IFE-1.	J Cell Sci	2015	WBPaper00048771:non-polysomal_ife-1(bn127)_rep1~WBPaper00048771:polysomal_ife-1(bn127)_rep1~WBPaper00048771:non-polysomal_N2_rep1~WBPaper00048771:polysomal_N2_rep1~WBPaper00048771:non-polysomal_ife-1(bn127)_rep2~WBPaper00048771:polysomal_ife-1(bn127)_rep2~WBPaper00048771:non-polysomal_N2_rep2~WBPaper00048771:polysomal_N2_rep2~WBPaper00048771:non-polysomal_ife-1(bn127)_rep3~WBPaper00048771:polysomal_ife-1(bn127)_rep3~WBPaper00048771:non-polysomal_N2_rep3~WBPaper00048771:polysomal_N2_rep3	Method: microarray|Species: Caenorhabditis elegans
169	26676933	WBPaper00048989.ce.mr.paper	GSE64336	GPL200	1	A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans.	Caloric restriction (CR), a reduction in calorie intake without malnutrition, retards aging in several animal models from worms to mammals. Developing CR mimetics, compounds that reproduce the longevity benefits of CR without its side effects, is of widespread interest. Here, we employed the Connectivity Map to identify drugs with overlapping gene expression profiles with CR. Eleven statistically significant compounds were predicted as CR mimetics using this bioinformatics approach. We then tested rapamycin, allantoin, trichostatin A, LY-294002 and geldanamycin in Caenorhabditis elegans. An increase in lifespan and healthspan was observed for all drugs except geldanamycin when fed to wild-type worms, but no lifespan effects were observed in eat-2 mutant worms, a genetic model of CR, suggesting that life-extending effects may be acting via CR-related mechanisms. We also treated daf-16 worms with rapamycin, allantoin or trichostatin A, and a lifespan extension was observed, suggesting that these drugs act via DAF-16-independent mechanisms, as would be expected from CR mimetics. Supporting this idea, an analysis of predictive targets of the drugs extending lifespan indicates various genes within CR and longevity networks. We also assessed the transcriptional profile of worms treated with either rapamycin or allantoin and found that both drugs use several specific pathways that do not overlap, indicating different modes of action for each compound. The current work validates the capabilities of this bioinformatic drug repositioning method in the context of longevity and reveals new putative CR mimetics that warrant further studies.	15	17638	Calvert S	Calvert S, Tacutu R, Sharifi S, Teixeira R, Ghosh P, de Magalhaes JP	A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans.	Aging Cell	2015	WBPaper00048989:N2_control_rep1~WBPaper00048989:N2_control_rep2~WBPaper00048989:N2_control_rep3~WBPaper00048989:N2_rapamycin_rep1~WBPaper00048989:N2_rapamycin_rep2~WBPaper00048989:N2_rapamycin_rep3~WBPaper00048989:N2_allantoin_rep1~WBPaper00048989:N2_allantoin_rep2~WBPaper00048989:N2_allantoin_rep3~WBPaper00048989:eat-2(ad465)_control_rep1~WBPaper00048989:eat-2(ad465)_control_rep2~WBPaper00048989:eat-2(ad465)_control_rep3~WBPaper00048989:eat-2(ad465)_rapamycin_rep1~WBPaper00048989:eat-2(ad465)_rapamycin_rep2~WBPaper00048989:eat-2(ad465)_rapamycin_rep3	Method: microarray|Species: Caenorhabditis elegans
170	26925754	WBPaper00049311.ce.mr.paper	GSE70509	GPL200	1	Distinct transcriptomic responses of Caenorhabditis elegans to pristine and sulfidized silver nanoparticles.	Manufactured nanoparticles (MNP) rapidly undergo aging processes once released from products. Silver sulfide (Ag2S) is the major transformation product formed during the wastewater treatment process for Ag-MNP. We examined toxicogenomic responses of pristine Ag-MNP, sulfidized Ag-MNP (sAg-MNP), and AgNO3 to a model soil organism, Caenorhabditis elegans. Transcriptomic profiling of nematodes which were exposed at the EC30 for reproduction for AgNO3, Ag-MNP, and sAg-MNP resulted in 571 differentially expressed genes. We independently verified expression of 4 genes (numr-1, rol-8, col-158, and grl-20) using qRT-PCR. Only 11% of differentially expressed genes were common among the three treatments. Gene ontology enrichment analysis also revealed that Ag-MNP and sAg-MNP had distinct toxicity mechanisms and did not share any of the biological processes. The processes most affected by Ag-MNP relate to metabolism, while those processes most affected by sAg-MNP relate to molting and the cuticle, and the most impacted processes for AgNO3 exposed nematodes was stress related. Additionally, as observed from qRT-PCR and mutant experiments, the responses to sAg-MNP were distinct from AgNO3 while some of the effects of pristine MNP were similar to AgNO3, suggesting that effects from Ag-MNP is partially due to dissolved silver ions.	12	17638	Starnes DL	Starnes DL, Lichtenberg SS, Unrine JM, Starnes CP, Oostveen EK, Lowry GV, Bertsch PM, Tsyusko OV	Distinct transcriptomic responses of Caenorhabditis elegans to pristine and sulfidized silver nanoparticles.	Environ Pollut	2016	WBPaper00049311:Control_Rep1~WBPaper00049311:Control_Rep2~WBPaper00049311:Control_Rep3~WBPaper00049311:AgedParticles_Rep1~WBPaper00049311:AgedParticles_Rep2~WBPaper00049311:AgedParticles_Rep3~WBPaper00049311:PristineParticles_Rep1~WBPaper00049311:PristineParticles_Rep2~WBPaper00049311:PristineParticles_Rep3~WBPaper00049311:SilverNitrate_Rep1~WBPaper00049311:SilverNitrate_Rep2~WBPaper00049311:SilverNitrate_Rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: stress response to metal ion
171	26959186	WBPaper00049364.ce.mr.paper	GSE77109,GSE77110,GSE77111	GPL200	1	A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction.	Dietary restriction (DR) is the most powerful natural means to extend lifespan. Although several genes can mediate responses to alternate DR regimens, no single genetic intervention has recapitulated the full effects of DR, and no unified system is known for different DR regimens. Here we obtain temporally resolved transcriptomes during calorie restriction and intermittent fasting in Caenorhabditis elegans and find that early and late responses involve metabolism and cell cycle/DNA damage, respectively. We uncover three network modules of DR regulators by their target specificity. By genetic manipulations of nodes representing discrete modules, we induce transcriptomes that progressively resemble DR as multiple nodes are perturbed. Targeting all three nodes simultaneously results in extremely long-lived animals that are refractory to DR. These results and dynamic simulations demonstrate that extensive feedback controls among regulators may be leveraged to drive the regulatory circuitry to a younger steady state, recapitulating the full effect of DR.	35	17638	Hou L	Hou L, Wang D, Chen D, Liu Y, Zhang Y, Cheng H, Xu C, Sun N, McDermott J, Mair WB, Han JD	A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction.	Cell Metab	2016	WBPaper00049364:aak-2;daf-2(e1370)rsks-1(ok1255)_control_rep1~WBPaper00049364:aak-2;daf-2(e1370)rsks-1(ok1255)_control_rep2~WBPaper00049364:aak-2_control_rep1~WBPaper00049364:aak-2_control_rep2~WBPaper00049364:daf-2(e1370)_control_rep1~WBPaper00049364:daf-2(e1370)_control_rep2~WBPaper00049364:daf-2(e1370)_tax-6(RNAi)_rep1~WBPaper00049364:daf-2(e1370)_tax-6(RNAi)_rep2~WBPaper00049364:daf-2(e1370)rsks-1(ok1255)_control_rep1~WBPaper00049364:daf-2(e1370)rsks-1(ok1255)_control_rep2~WBPaper00049364:daf-2(e1370)rsks-1(ok1255)_tax-6(RNAi)_rep1~WBPaper00049364:daf-2(e1370)rsks-1(ok1255)_tax-6(RNAi)_rep2~WBPaper00049364:N2_control_rep1~WBPaper00049364:N2_control_rep2~WBPaper00049364:N2_tax-6(RNAi)_rep1~WBPaper00049364:N2_tax-6(RNAi)_rep2~WBPaper00049364:rsks-1(ok1255)_control_rep1~WBPaper00049364:rsks-1(ok1255)_control_rep2~WBPaper00049364:rsks-1(ok1255)_tax-6(RNAi)_rep1~WBPaper00049364:rsks-1(ok1255)_tax-6(RNAi)_rep2~WBPaper00049364:N2_free-feeding_AdultDay2~WBPaper00049364:N2_free-feeding_AdultDay4~WBPaper00049364:N2_calorie-restriction_AdultDay4~WBPaper00049364:N2_intermittent-fasting_AdultDay4~WBPaper00049364:N2_free-feeding_AdultDay6~WBPaper00049364:N2_calorie-restriction_AdultDay6~WBPaper00049364:N2_intermittent-fasting_AdultDay6~WBPaper00049364:N2_free-feeding_AdultDay8~WBPaper00049364:N2_calorie-restriction_AdultDay8~WBPaper00049364:N2_intermittent-fasting_AdultDay8~WBPaper00049364:N2_free-feeding_AdultDay10~WBPaper00049364:N2_calorie-restriction_AdultDay10~WBPaper00049364:N2_intermittent-fasting_AdultDay10~WBPaper00049364:N2_intermittent-fasting_AdultDay12~WBPaper00049364:N2_intermittent-fasting_AdultDay14	Method: microarray|Species: Caenorhabditis elegans
172	27054371	WBPaper00049417.ce.mr.paper	GSE63531	GPL200	1	The Probiotic Strain Bifidobacterium animalis subsp. lactis CECT 8145 Reduces Fat Content and Modulates Lipid Metabolism and Antioxidant Response in Caenorhabditis elegans.	Recently, microbial changes in the human gut have been proposed as a possible cause of obesity. Therefore, modulation of microbiota through probiotic supplements is of great interest to support obesity therapeutics. The present study examines the functional effect and metabolic targets of a bacterial strain, Bifidobacterium animalis subsp. lactis CECT 8145, selected from a screening in Caenorhabditis elegans. This strain significantly reduced total lipids (40.5% +/- 2.4) and triglycerides (TG) (27.6%+/-0.5), exerting antioxidant effects in the nematode (30% +/- 2.8 increase in survival vs. control); activities also preserved in a final food matrix (milk). Furthermore, transcriptomic and metabolomic analyses in nematodes fed with strain CECT 8145 revealed modulation of the energy and lipid metabolism, as well as the tryptophan metabolism (satiety) as the main metabolic targets of the probiotic. In conclusion, our study describes for the first time a new B. animalis subsp. lactis strain, CECT 8145, as a promising probiotic for obesity disorders. Furthermore, data supports future studies in obesity murine model.	8	17638	Martorell P	Martorell P, Llopis S, Gonzalez N, Chenoll E, Lopez-Carreras N, Aleixandre A, Chen Y, Karoly ED, Ramon D, Genoves S	The Probiotic Strain Bifidobacterium animalis subsp. lactis CECT 8145 Reduces Fat Content and Modulates Lipid Metabolism and Antioxidant Response in Caenorhabditis elegans.	J Agric Food Chem	2016	WBPaper00049417:NGM_SL112~WBPaper00049417:NGM_SL114~WBPaper00049417:NGM_SL116~WBPaper00049417:NGM_SL118~WBPaper00049417:B.animalis_SL113~WBPaper00049417:B.animalis_SL115~WBPaper00049417:B.animalis_SL117~WBPaper00049417:B.animalis_SL119	Method: microarray|Species: Caenorhabditis elegans
173	27135930	WBPaper00049538.ce.mr.paper	GSE73669	GPL200	1	Maintenance and propagation of a deleterious mitochondrial genome by the mitochondrial unfolded protein response.	Mitochondrial genomes (mitochondrial DNA, mtDNA) encode essential oxidative phosphorylation (OXPHOS) components. Because hundreds of mtDNAs exist per cell, a deletion in a single mtDNA has little impact. However, if the deletion genome is enriched, OXPHOS declines, resulting in cellular dysfunction. For example, Kearns-Sayre syndrome is caused by a single heteroplasmic mtDNA deletion. More broadly, mtDNA deletion accumulation has been observed in individual muscle cells and dopaminergic neurons during ageing. It is unclear how mtDNA deletions are tolerated or how they are propagated in somatic cells. One mechanism by which cells respond to OXPHOS dysfunction is by activating the mitochondrial unfolded protein response (UPR(mt)), a transcriptional response mediated by the transcription factor ATFS-1 that promotes the recovery and regeneration of defective mitochondria. Here we investigate the role of ATFS-1 in the maintenance and propagation of a deleterious mtDNA in a heteroplasmic Caenorhabditis elegans strain that stably expresses wild-type mtDNA and mtDNA with a 3.1-kilobase deletion (mtDNA) lacking four essential genes. The heteroplasmic strain, which has 60% mtDNA, displays modest mitochondrial dysfunction and constitutive UPR(mt) activation. ATFS-1 impairment reduced the mtDNA nearly tenfold, decreasing the total percentage to 7%. We propose that in the context of mtDNA heteroplasmy, UPR(mt) activation caused by OXPHOS defects propagates or maintains the deleterious mtDNA in an attempt to recover OXPHOS activity by promoting mitochondrial biogenesis and dynamics.	6	17638	Lin YF	Lin YF, Schulz AM, Pellegrino MW, Lu Y, Shaham S, Haynes CM	Maintenance and propagation of a deleterious mitochondrial genome by the mitochondrial unfolded protein response.	Nature	2016	WBPaper00049538:N2_rep1~WBPaper00049538:atfs-1(et18)_rep1~WBPaper00049538:N2_rep2~WBPaper00049538:atfs-1(et18)_rep2~WBPaper00049538:N2_rep3~WBPaper00049538:atfs-1(et18)_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: mitochondrial unfolded protein response|Topic: mitochondrion
174	27579370	WBPaper00050079.ce.mr.paper	GSE85342	GPL200	1	A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence.	Pseudomonas aeruginosa is an opportunistic pathogen that causes severe health problems. Despite intensive investigation, many aspects of microbial virulence remain poorly understood. We used a high-throughput, high-content, whole-organism, phenotypic screen to identify small molecules that inhibit P.aeruginosa virulence in Caenorhabditis elegans. Approximately half of the hits were known antimicrobials. A large number of hits were nonantimicrobial bioactive compounds, including the cancer chemotherapeutic 5-fluorouracil. We determined that 5-fluorouracil both transiently inhibits bacterial growth and reduces pyoverdine biosynthesis. Pyoverdine is a siderophore that regulates the expression of several virulence determinants and is critical for pathogenesis in mammals. We show that 5-fluorouridine, a downstream metabolite of 5-fluorouracil, is responsible for inhibiting pyoverdine biosynthesis. We also show that 5-fluorouridine, in contrast to 5-fluorouracil, is a genuine antivirulence compound, with no bacteriostatic or bactericidal activity. To our knowledge, this is the first report utilizing a whole-organism screen to identify novel compounds with antivirulent properties effective against P.aeruginosa. IMPORTANCE Despite intense research effort from scientists and the advent of the molecular age of biomedical research, many of the mechanisms that underlie pathogenesis are still understood poorly, if at all. The opportunistic human pathogen Pseudomonas aeruginosa causes a variety of soft tissue infections and is responsible for over 50,000 hospital-acquired infections per year. In addition, P.aeruginosa exhibits a striking degree of innate and acquired antimicrobial resistance, complicating treatment. It is increasingly important to understand P.aeruginosa virulence. In an effort to gain this information in an unbiased fashion, we used a high-throughput phenotypic screen to identify small molecules that disrupted bacterial pathogenesis and increased host survival using the model nematode Caenorhabditis elegans. This method led to the unexpected discovery that addition of a modified nucleotide, 5-fluorouridine, disrupted bacterial RNA metabolism and inhibited synthesis of pyoverdine, a critical toxin. Our results demonstrate that this compound specifically functions as an antivirulent.	6	17638	Kirienko DR	Kirienko DR, Revtovich AV, Kirienko NV	A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence.	mSphere	2016	WBPaper00050079:N2_DMSO_RepA~WBPaper00050079:N2_DMSO_RepB~WBPaper00050079:N2_DMSO_RepC~WBPaper00050079:N2_5FU_RepA~WBPaper00050079:N2_5FU_RepB~WBPaper00050079:N2_5FU_RepC	Method: microarray|Species: Caenorhabditis elegans
175	27610574	WBPaper00050407.ce.mr.paper	GSE83722	GPL200	1	Lipid Biosynthesis Coordinates a Mitochondrial-to-Cytosolic Stress Response.	Defects in mitochondrial metabolism have been increasingly linked with age-onset protein-misfolding diseases such as Alzheimer's, Parkinson's, and Huntington's. In response to protein-folding stress, compartment-specific unfolded protein responses (UPRs) within the ER, mitochondria, and cytosol work in parallel to ensure cellular protein homeostasis. While perturbation of individual compartments can make other compartments more susceptible to protein stress, the cellular conditions that trigger cross-communication between the individual UPRs remain poorly understood. We have uncovered a conserved, robust mechanism linking mitochondrial protein homeostasis and the cytosolic folding environment through changes in lipid homeostasis. Metabolic restructuring caused by mitochondrial stress or small-molecule activators trigger changes in gene expression coordinated uniquely by both the mitochondrial and cytosolic UPRs, protecting the cell from disease-associated proteins. Our data suggest an intricate and unique system of communication between UPRs in response to metabolic changes that could unveil new targets for diseases of protein misfolding.	12	17638	Kim HE	Kim HE, Grant AR, Simic MS, Kohnz RA, Nomura DK, Durieux J, Riera CE, Sanchez M, Kapernick E, Wolff S, Dillin A	Lipid Biosynthesis Coordinates a Mitochondrial-to-Cytosolic Stress Response.	Cell	2016	WBPaper00050407:control(RNAi)_rep1~WBPaper00050407:control(RNAi)_rep2~WBPaper00050407:control(RNAi)_rep3~WBPaper00050407:hsp-6(RNAi)_rep1~WBPaper00050407:hsp-6(RNAi)_rep2~WBPaper00050407:hsp-6(RNAi)_rep3~WBPaper00050407:hsp-6(RNAi);hsf-1(RNAi)_rep1~WBPaper00050407:hsp-6(RNAi);hsf-1(RNAi)_rep2~WBPaper00050407:hsp-6(RNAi);hsf-1(RNAi)_rep3~WBPaper00050407:hsp-6(RNAi);dve-1(RNAi)_rep1~WBPaper00050407:hsp-6(RNAi);dve-1(RNAi)_rep2~WBPaper00050407:hsp-6(RNAi);dve-1(RNAi)_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: mitochondrial unfolded protein response|Topic: mitochondrion
176	27901397	WBPaper00050494.ce.mr.paper	GSE84489	GPL200	1	A systems toxicology approach reveals the Wnt-MAPK crosstalk pathway mediated reproductive failure in Caenorhabditis elegans exposed to graphene oxide (GO) but not to reduced graphene oxide (rGO).	The potential hazards of graphene nanomaterials were investigated by exposing the nematode Caenorhabditis elegans to graphene oxide (GO) and reduced graphene oxide (rGO). The underlying mechanisms of the nano-bio interaction were addressed with an integrated systems toxicology approach using global transcriptomics, network-based pathway analysis, and experimental validation of the in-silico-derived hypotheses. Graphene oxide was found to reduce the worms' reproductive health to a greater degree than rGO, but it did not affect survival (24h endpoint). Comparative analysis of GO vs. rGO effects found that the wingless-type MMTV integration site family (Wnt) pathway and the mitogen-activated protein kinase (MAPK) pathway were evoked in GO- but not in rGO-exposed worms. We therefore hypothesized that crosstalk between the Wnt and MAPK pathways is responsible for C. elegans' reproductive sensitivity to GO exposure. By targeting the individual components of the Wnt-MAPK crosstalk pathway (with qPCR gene expression and mutant reproduction analysis), we found a signaling cascade of MOM-2  MOM-5  MOM-4  LIT-1  POP-1  EGL-5. Specifically, the activation of POP-1 (the TCF protein homologue) and subsequent repression of the Wnt/-catenin target gene (EGL-5), analyzed with target-gene-specific RNAi in POP-1 mutant [pop-1(q645)] worms, were the central mechanisms of reduced reproductive potential in the worms exposed to GO. Our results highlight the distinct biological and molecular mechanisms of GO and rGO exposure and the role of Wnt-MAPK pathway crosstalk in regulating GO-induced reproductive failure in in vivo systems, and they will contribute to the development of efficient and innocuous graphene applications as well to improvements in mechanism-based risk assessment.	3	17638	Chatterjee N	Chatterjee N, Kim YH, Yang J, Roca CP, Joo SW, Choi J	A systems toxicology approach reveals the Wnt-MAPK crosstalk pathway mediated reproductive failure in Caenorhabditis elegans exposed to graphene oxide (GO) but not to reduced graphene oxide (rGO).	Nanotoxicology	2016	WBPaper00050494:Control~WBPaper00050494:24h-GO-exposure_rep1~WBPaper00050494:24h-rGO-exposure_rep1	Method: microarray|Species: Caenorhabditis elegans
177	27927200	WBPaper00050515.ce.mr.paper	GSE87052	GPL200	1	Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a Caenorhabditis elegans intestinal immune surveillance pathway.	BACKGROUND: Many pathogens secrete toxins that target key host processes resulting in the activation of immune pathways. The secreted Pseudomonas aeruginosa toxin Exotoxin A (ToxA) disrupts intestinal protein synthesis, which triggers the induction of a subset of P. aeruginosa-response genes in the nematode Caenorhabditis elegans. RESULTS: We show here that one ToxA-induced C. elegans gene, the Tribbles pseudokinase ortholog nipi-3, is essential for host survival following exposure to P. aeruginosa or ToxA. We find that NIPI-3 mediates the post-developmental expression of intestinal immune genes and proteins and primarily functions in parallel to known immune pathways, including p38 MAPK signaling. Through mutagenesis screening, we identify mutants of the bZIP C/EBP transcription factor cebp-1 that suppress the hypersusceptibility defects of nipi-3 mutants. CONCLUSIONS: NIPI-3 is a negative regulator of CEBP-1, which in turn negatively regulates protective immune mechanisms. This pathway represents a previously unknown innate immune signaling pathway in intestinal epithelial cells that is involved in the surveillance of cellular homeostasis. Because NIPI-3 and CEBP-1 are also essential for C. elegans development, NIPI-3 is analogous to other key innate immune signaling molecules such as the Toll receptors in Drosophila that have an independent role during development.	9	17638	McEwan DL	McEwan DL, Feinbaum RL, Stroustrup N, Haas W, Conery AL, Anselmo A, Sadreyev R, Ausubel FM	Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a Caenorhabditis elegans intestinal immune surveillance pathway.	BMC Biol	2016	WBPaper00050515:N2_rep1_2176A~WBPaper00050515:N2_rep2_2176B~WBPaper00050515:N2_rep3_2176C~WBPaper00050515:nipi-3(fr4)_rep1_2176D~WBPaper00050515:nipi-3(fr4)_rep2_2176E~WBPaper00050515:nipi-3(fr4)_rep3_2176F~WBPaper00050515:pmk-1(km25)_rep1_2176G~WBPaper00050515:pmk-1(km25)_rep2_2176H~WBPaper00050515:pmk-1(km25)_rep3_2176I	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response
178	27974500	WBPaper00050520.ce.mr.paper	GSE84894	GPL200	1	Starvation-Induced Stress Response Is Critically Impacted by Ceramide Levels in Caenorhabditis elegans.	Our understanding of the cellular mechanisms by which animals regulate their response to starvation is limited despite the strong relevance of the problem to major human health issues. The L1 diapause of Caenorhabditis elegans, where first-stage larvae arrest in response to a food-less environment, is an excellent system to study this mechanism. We found through genetic manipulation and lipid analysis that ceramide biosynthesis, particularly those with longer fatty acid side chains, critically impacts animal survival during L1 diapause. Genetic interaction analysis suggests that ceramide may act in both Insulin-IGF-1 signaling (IIS)-dependent and IIS-independent pathways to affect starvation survival. Genetic and expression analyses indicate that ceramide is required for maintaining the proper expression of previously characterized starvation responsive genes, genes that are regulated by the IIS pathway and tumor suppressor Rb, and genes responsive to pathogen. These findings provide an important insight into the roles of sphingolipid metabolism in not only starvation response, but also aging and food-response related human health problems.	6	17638	Cui M	Cui M, Wang Y, Cavaleri J, Kelson T, Teng Y, Han M	Starvation-Induced Stress Response Is Critically Impacted by Ceramide Levels in Caenorhabditis elegans.	Genetics	2016	WBPaper00050520:N2_starved-L1_rep1~WBPaper00050520:N2_starved-L1_rep2~WBPaper00050520:N2_starved-L1_rep3~WBPaper00050520:hyl-1(ok976);lagr-1(gk327)_starved-L1_rep1~WBPaper00050520:hyl-1(ok976);lagr-1(gk327)_starved-L1_rep2~WBPaper00050520:hyl-1(ok976);lagr-1(gk327)_starved-L1_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: ceramide biosynthetic process
179	27989925	WBPaper00050538.ce.mr.paper	GSE51046	GPL200	1	Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C. elegans.	Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity. Here, we show that cholesterol deprivation suppresses longevity induced by intermittent fasting, which is one of the dietary restriction regimens that effectively extend lifespan. We also found that cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16 and that cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16. Moreover, knockdown of the cholesterol-binding protein NSBP-1, which has been shown to bind to DAF-16 in a cholesterol-dependent manner and to regulate DAF-16 activity, suppresses both fasting-induced longevity and DAF-16 nuclear accumulation. Furthermore, this suppression was not additive to the cholesterol deprivation-induced suppression, which suggests that NSBP-1 mediates, at least in part, the action of cholesterol to promote fasting-induced longevity and DAF-16 nuclear accumulation. These findings identify a novel role for cholesterol in the regulation of lifespan.	8	17638	Ihara A	Ihara A, Uno M, Miyatake K, Honjoh S, Nishida E	Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C. elegans.	Exp Gerontol	2016	WBPaper00050538:Cholesterol-presence_fed_rep1~WBPaper00050538:Cholesterol-presence_fasting_rep1~WBPaper00050538:Cholesterol-deprivation_fed_rep1~WBPaper00050538:Cholesterol-deprivation_fasting_rep1~WBPaper00050538:Cholesterol-presence_fed_rep2~WBPaper00050538:Cholesterol-presence_fasting_rep2~WBPaper00050538:Cholesterol-deprivation_fed_rep2~WBPaper00050538:Cholesterol-deprivation_fasting_rep2	Method: microarray|Species: Caenorhabditis elegans
180	28105749	WBPaper00050767.ce.mr.paper	GSE89731	GPL200	1	Octopamine enhances oxidative stress resistance through the fasting-responsive transcription factor DAF-16/FOXO inC.elegans.	Dietary restriction regimens lead to enhanced stress resistance and extended life span in many species through the regulation of fasting and/or diet-responsive mechanisms. The fasting stimulus is perceived by sensory neurons and causes behavioral and metabolic adaptations. Octopamine (OA), one of the Caenorhabditis elegans neurotransmitters, is involved in behavioral adaptations, and its levels are increased under fasting conditions. However, it remains largely unknown how OA contributes to the fasting responses. In this study, we found that OA administration enhanced organismal resistance to oxidative stress. This enhanced resistance was suppressed by a mutation of the OA receptors, SER-3 and SER-6. Moreover, we found that OA administration promoted the nuclear translocation of DAF-16, the key transcription factor in fasting responses, and that the OA-induced enhancement of stress resistance required DAF-16. Altogether, our results suggest that OA signaling, which is triggered by the absence of food, shifts the organismal state to a more protective one to prepare for environmental stresses.	6	17638	Hoshikawa H	Hoshikawa H, Uno M, Honjoh S, Nishida E	Octopamine enhances oxidative stress resistance through the fasting-responsive transcription factor DAF-16/FOXO inC.elegans.	Genes Cells	2017	WBPaper00050767:N2_Octopamine(-)_rep1~WBPaper00050767:N2_Octopamine(+)_rep1~WBPaper00050767:daf-16(mu86)_Octopamine(-)_rep1~WBPaper00050767:daf-16(mu86)_Octopamine(+)_rep1~WBPaper00050767:ser-3(ok2007);ser-6(tm2146)_Octopamine(-)_rep1~WBPaper00050767:ser-3(ok2007);ser-6(tm2146)_Octopamine(+)_rep1	Method: microarray|Species: Caenorhabditis elegans
181	28279983	WBPaper00050903.ce.mr.paper	GSE94701,GSE94702,GSE94704	GPL200	1	A microRNA family exerts maternal control on sex determination in C. elegans.	Gene expression in early animal embryogenesis is in large part controlled post-transcriptionally. Maternally contributed microRNAs may therefore play important roles in early development. We elucidated a major biological role of the nematode mir-35 family of maternally contributed essential microRNAs. We show that this microRNA family regulates the sex determination pathway at multiple levels, acting both upstream of and downstream from her-1 to prevent aberrantly activated male developmental programs in hermaphrodite embryos. Both of the predicted target genes that act downstream from the mir-35 family in this process, suppressor-26 (sup-26) and NHL (NCL-1, HT2A, and LIN-41 repeat) domain-containing-2 (nhl-2), encode RNA-binding proteins, thus delineating a previously unknown post-transcriptional regulatory subnetwork within the well-studied sex determination pathway of Caenorhabditis elegans Repression of nhl-2 by the mir-35 family is required for not only proper sex determination but also viability, showing that a single microRNA target site can be essential. Since sex determination in C. elegans requires zygotic gene expression to read the sex chromosome karyotype, early embryos must remain gender-naive; our findings show that the mir-35 family microRNAs act in the early embryo to function as a developmental timer that preserves naivete and prevents premature deleterious developmental decisions.	12	17638	McJunkin K	McJunkin K, Ambros V	A microRNA family exerts maternal control on sex determination in C. elegans.	Genes Dev	2017	WBPaper00050903:mir-35-41(nDf50)_20C_rep1~WBPaper00050903:mir-35-41(nDf50)_20C_rep2~WBPaper00050903:mir-35-41(nDf50)_20C_rep3~WBPaper00050903:N2_20C_rep1~WBPaper00050903:N2_20C_rep2~WBPaper00050903:N2_20C_rep3~WBPaper00050903:mir-35-41(nDf50)_25C_rep1~WBPaper00050903:mir-35-41(nDf50)_25C_rep2~WBPaper00050903:mir-35-41(nDf50)_25C_rep3~WBPaper00050903:N2_25C_rep1~WBPaper00050903:N2_25C_rep2~WBPaper00050903:N2_25C_rep3	Method: microarray|Species: Caenorhabditis elegans
182	28507100	WBPaper00051247.ce.mr.paper	GSE89624,GSE89614	GPL200	1	The MicroRNA Machinery Regulates Fasting-Induced Changes in Gene Expression and Longevity in Caenorhabditis elegans.	Intermittent fasting (IF) is a dietary restriction regimen that extends the lifespans of Caenorhabditis elegans and mammals by inducing changes in gene expression. However, how IF induces these changes and promotes longevity remains unclear. One proposed mechanism involves gene regulation by microRNAs (miRNAs), small non-coding RNAs (approximately 22 nucleotides) that repress gene expression and whose expression can be altered by fasting. To test this proposition, we examined the role of the miRNA machinery in fasting-induced transcriptional changes and longevity in C. elegans We revealed that fasting up-regulated the expression of miRNA-induced silencing complex (miRISC) components, including Argonaute and GW182, and of the miRNA-processing enzyme DRSH-1 (the ortholog of the Drosophila Drosha enzyme). Our lifespan measurements demonstrated that IF-induced longevity was suppressed by knockout or knockdown of miRISC components and was completely inhibited by drsh-1 ablation. Remarkably, drsh-1 ablation inhibited the fasting-induced changes in the expression of the target genes of DAF-16, the insulin/IGF-1 signaling effector in C. elegans Fasting-induced transcriptome alterations were substantially and modestly suppressed in the drsh-1 null mutant and the null mutant of ain-1, a gene encoding GW182, respectively. Moreover, miRNA array analyses revealed that the expression levels of numerous miRNAs changed after 2 days of fasting. These results indicate that components of the miRNA machinery, especially the miRNA-processing enzyme DRSH-1, play an important role in mediating IF-induced longevity via the regulation of fasting-induced changes in gene expression.	8	17638	Kogure A	Kogure A, Uno M, Ikeda T, Nishida E	The MicroRNA Machinery Regulates Fasting-Induced Changes in Gene Expression and Longevity in Caenorhabditis elegans.	J Biol Chem	2017	WBPaper00051247:N2_fed~WBPaper00051247:N2_fasting~WBPaper00051247:drsh-1(ok369)_fed~WBPaper00051247:drsh-1(ok369)_fasting~WBPaper00051247:ain-1(tm3681)_fed~WBPaper00051247:ain-1(tm3681)_fasting~WBPaper00051247:daf-16(mu86)_fed~WBPaper00051247:daf-16(mu86)_fasting	Method: microarray|Species: Caenorhabditis elegans
183	28673184	WBPaper00051437.ce.mr.paper	GSE93186,GSE93187,GSE93188	GPL19230	1	Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.	We present a mechanistic study of the effect of iron oxide nanoparticles (SPIONs) in Caenorhabditis elegans combining a genome-wide analysis with the investigation of specific molecular markers frequently linked to nanotoxicity. The effects of two different coatings were explored: citrate, an anionic stabilizer, and bovine serum albumin, as a pre-formed protein corona. The transcriptomic study identified differentially expressed genes following an exposure to SPIONs. The expression of genes involved in oxidative stress, metal detoxification response, endocytosis, intestinal integrity and iron homeostasis was quantitatively evaluated. The role of oxidative stress was confirmed by gene expression analysis and by synchrotron Fourier Transform infrared microscopy based on the higher tissue oxidation of NP-treated animals. The observed transcriptional modulation of key signaling pathways such as MAPK and Wnt suggests that SPIONs might be endocytosed by clathrin-mediated processes, a putative mechanism of nanotoxicity which deserves further mechanistic investigations.	12	26351	Gonzalez-Moragas L	Gonzalez-Moragas L, Yu SM, Benseny-Cases N, Sturzenbaum S, Roig A, Laromaine A	Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.	Nanotoxicology	2017	WBPaper00051437:BSA-control_rep1~WBPaper00051437:BSA-control_rep2~WBPaper00051437:BSA-control_rep3~WBPaper00051437:BSA-SPIONs_rep1~WBPaper00051437:BSA-SPIONs_rep2~WBPaper00051437:BSA-SPIONs_rep3~WBPaper00051437:Cit-control_rep1~WBPaper00051437:Cit-control_rep2~WBPaper00051437:Cit-control_rep3~WBPaper00051437:Cit-SPIONs_rep1~WBPaper00051437:Cit-SPIONs_rep2~WBPaper00051437:Cit-SPIONs_rep3	Method: microarray|Species: Caenorhabditis elegans
184	28662060	WBPaper00051448.ce.mr.paper	GSE55422	GPL200	1	A conserved mitochondrial surveillance pathway is required for defense against Pseudomonas aeruginosa.	All living organisms exist in a precarious state of homeostasis that requires constant maintenance. A wide variety of stresses, including hypoxia, heat, and infection by pathogens perpetually threaten to imbalance this state. Organisms use a battery of defenses to mitigate damage and restore normal function. Previously, we described a Caenorhabditis elegans-Pseudomonas aeruginosa assay (Liquid Killing) in which toxicity to the host is dependent upon the secreted bacterial siderophore pyoverdine. Although pyoverdine is also indispensable for virulence in mammals, its cytological effects are unclear. We used genetics, transcriptomics, and a variety of pathogen and chemical exposure assays to study the interactions between P. aeruginosa and C. elegans. Although P. aeruginosa can kill C. elegans through at least 5 different mechanisms, the defense responses activated by Liquid Killing are specific and selective and have little in common with innate defense mechanisms against intestinal colonization. Intriguingly, the defense response utilizes the phylogenetically-conserved ESRE (Ethanol and Stress Response Element) network, which we and others have previously shown mitigates damage from a variety of abiotic stresses. This is the first report of this network's involvement in innate immunity, and indicates that host innate immune responses overlap with responses to abiotic stresses. The upregulation of the ESRE network in C. elegans is mediated in part by a family of bZIP proteins (including ZIP-2, ZIP-4, CEBP-1, and CEBP-2) that have overlapping and unique functions. Our data convincingly show that, following infection by P. aeruginosa, the ESRE defense network is activated by mitochondrial damage, and that mitochondrial damage also leads to ESRE activation in mammals. This establishes a role for ESRE in a phylogenetically-conserved mitochondrial surveillance system important for stress response and innate immunity.	21	17638	Tjahjono E	Tjahjono E, Kirienko NV	A conserved mitochondrial surveillance pathway is required for defense against Pseudomonas aeruginosa.	PLoS Genet	2017	WBPaper00051448:glp-4(bn2ts)_OP50_NGM-agar_RepA~WBPaper00051448:glp-4(bn2ts)_OP50_NGM-agar_RepB~WBPaper00051448:glp-4(bn2ts)_OP50_NGM-agar_RepC~WBPaper00051448:glp-4(bn2ts)_OP50_SK-agar_RepA~WBPaper00051448:glp-4(bn2ts)_OP50_SK-agar_RepB~WBPaper00051448:glp-4(bn2ts)_OP50_SK-agar_RepC~WBPaper00051448:glp-4(bn2ts)_OP50_LK_RepA~WBPaper00051448:glp-4(bn2ts)_OP50_LK_RepB~WBPaper00051448:glp-4(bn2ts)_OP50_LK_RepC~WBPaper00051448:glp-4(bn2ts)_PA14_SK-agar_RepA~WBPaper00051448:glp-4(bn2ts)_PA14_SK-agar_RepB~WBPaper00051448:glp-4(bn2ts)_PA14_SK-agar_RepC~WBPaper00051448:glp-4(bn2ts)_PA14_LK_RepA~WBPaper00051448:glp-4(bn2ts)_PA14_LK_RepB~WBPaper00051448:glp-4(bn2ts)_PA14_LK_RepC~WBPaper00051448:glp-4(bn2ts)_OP50_DMSO_RepA~WBPaper00051448:glp-4(bn2ts)_OP50_DMSO_RepB~WBPaper00051448:glp-4(bn2ts)_OP50_DMSO_RepC~WBPaper00051448:glp-4(bn2ts)_OP50_Phe_RepA~WBPaper00051448:glp-4(bn2ts)_OP50_Phe_RepB~WBPaper00051448:glp-4(bn2ts)_OP50_Phe_RepC	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
185	28760744	WBPaper00052845.ce.mr.paper	GSE81854	GPL200	1	Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid desaturation in Caenorhabditis elegans.	The incidence of obesity is rising at an alarming rate. Despite its recognition as an urgent healthcare concern, obesity remains largely an unsolved medical problem. A comprehensive screen for functional dietary phytochemicals identified proanthocyanidins as putative targets to ameliorate obesity. A full-scale purification of oligomeric proanthocyanidins (OPCs) derived from grape seed extract, yielded pure OPC dimer, trimer, tetramer, and their gallates (pOPCs). Forward chemical screening conducted in Caenorhabditis elegans suggested that pOPCs reduced the activity of lipase in vitro and triglyceride storage capacity in vivo Proanthocyanidin trimer gallate in particular modified lipid desaturation in C. elegans, revealed by hyperspectral coherent anti-Stokes Raman scattering microscopy. Exposure to trimer gallate resulted in the transcriptional down-regulation of nhr-49 (an ortholog of the human peroxisome proliferator-activated receptor-), and a key regulator of fat metabolism, and 2 downstream genes: fat-5 and acs-2 A combination exposure of 2 or 3 pOPCs (dimer gallate, trimer and/or trimer gallate) suggested the absence of synergistic potential. By using the whole-organism C. elegans coupled with versatile biochemical, biophysical, and genetic tools, we provide an account of the composition and bioactivity of individual OPCs and more generally highlight the potential of traditional Chinese medicine-derived drug leads.-Nie, Y., Littleton, B., Kavanagh, T., Abbate, V., Bansal, S. S., Richards, D., Hylands, P., Sturzenbaum, S. R. Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid desaturation in Caenorhabditis elegans.	2	17638	Nie Y	Nie Y, Littleton B, Kavanagh T, Abbate V, Bansal SS, Richards D, Hylands P, Sturzenbaum SR	Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid desaturation in Caenorhabditis elegans.	FASEB J	2017	WBPaper00052845:L4_control~WBPaper00052845:L4_pOPC7	Method: microarray|Species: Caenorhabditis elegans
186	28874466	WBPaper00053020.ce.mr.paper	GSE99586	GPL19230	1	An Alternative STAT Signaling Pathway Acts in Viral Immunity in Caenorhabditis elegans.	Across metazoans, innate immunity is vital in defending organisms against viral infection. In mammals, antiviral innate immunity is orchestrated by interferon signaling, activating the STAT transcription factors downstream of the JAK kinases to induce expression of antiviral effector genes. In the nematode Caenorhabditiselegans, which lacks the interferon system, the major antiviral response so far described is RNA interference (RNAi), but whether additional gene expression responses are employed is not known. Here we show that, despite the absence of both interferon and JAK, the C.elegans STAT homolog STA-1 orchestrates antiviral immunity. Intriguingly, mutants lacking STA-1 are less permissive to antiviral infection. Using gene expression analysis and chromatin immunoprecipitation, we show that, in contrast to the mammalian pathway, STA-1 acts mostly as a transcriptional repressor. Thus, STA-1 might act to suppress a constitutive antiviral response in the absence of infection. Additionally, using a reverse genetic screen, we identify the kinase SID-3 as a new component of the response to infection, which, along with STA-1, participates in the transcriptional regulatory network of the immune response. Our work uncovers novel physiological roles for two factors in viral infection: a SID protein acting independently of RNAi and a STAT protein acting in C.elegans antiviral immunity. Together, these results illustrate the complex evolutionary trajectory displayed by innate immune signaling pathways across metazoan organisms.IMPORTANCE Since innate immunity was discovered, a diversity of pathways has arisen as powerful first-line defense mechanisms to fight viral infection. RNA interference, reported mostly in invertebrates and plants, as well as the mammalian interferon response and JAK/STAT pathway are key in RNA virus innate immunity. We studied infection by the Orsay virus in Caenorhabditis elegans, where RNAi is known to be a potent antiviral defense. We show that, in addition to its RNAi pathway, C.elegans utilizes an alternative STAT pathway to control the levels of viral infection. We identify the transcription factor STA-1 and the kinase SID-3 as two components of this response. Our study defines C.elegans as a new example of the diversity of antiviral strategies.	24	26351	Tanguy M	Tanguy M, Veron L, Stempor P, Ahringer J, Sarkies P, Miska EA	An Alternative STAT Signaling Pathway Acts in Viral Immunity in Caenorhabditis elegans.	MBio	2017	WBPaper00053020:N2_OrsayVirus-infected_rep1~WBPaper00053020:N2_OrsayVirus-infected_rep2~WBPaper00053020:N2_OrsayVirus-infected_rep3~WBPaper00053020:N2_control_rep1~WBPaper00053020:N2_control_rep2~WBPaper00053020:N2_control_rep3~WBPaper00053020:drh-1(ok3495)_OrsayVirus-infected_rep1~WBPaper00053020:drh-1(ok3495)_OrsayVirus-infected_rep2~WBPaper00053020:drh-1(ok3495)_OrsayVirus-infected_rep3~WBPaper00053020:drh-1(ok3495)_control_rep1~WBPaper00053020:drh-1(ok3495)_control_rep2~WBPaper00053020:drh-1(ok3495)_control_rep3~WBPaper00053020:JU1580_OrsayVirus-infected_rep1~WBPaper00053020:JU1580_OrsayVirus-infected_rep2~WBPaper00053020:JU1580_OrsayVirus-infected_rep3~WBPaper00053020:JU1580_control_rep1~WBPaper00053020:JU1580_control_rep2~WBPaper00053020:JU1580_control_rep3~WBPaper00053020:JU1580-DRH1_OrsayVirus-infected_rep1~WBPaper00053020:JU1580-DRH1_OrsayVirus-infected_rep2~WBPaper00053020:JU1580-DRH1_OrsayVirus-infected_rep3~WBPaper00053020:JU1580-DRH1_control_rep1~WBPaper00053020:JU1580-DRH1_control_rep2~WBPaper00053020:JU1580-DRH1_control_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response
187	28926584	WBPaper00053092.ce.mr.paper	GSE101680	GPL19230	1	Transcriptome analysis reveals molecular anthelmintic effects of procyanidins in C. elegans.	Worldwide, more than 1 billion people are affected by infestations with soil-transmitted helminths and also in veterinary medicine helminthiases are a severe threat to livestock due to emerging resistances against the common anthelmintics. Proanthocyanidins have been increasingly investigated for their anthelmintic properties, however, except for an interaction with certain proteins of the nematodes, not much is known about their mode of action. To investigate the anthelmintic activity on a molecular level, a transcriptome analysis was performed in Caenorhabditis elegans after treatment with purified and fully characterized oligomeric procyanidins (OPC). The OPCs had previously been obtained from a hydro-ethanolic (1:1) extract from the leaves of Combretum mucronatum, a plant which is traditionally used in West Africa for the treatment of helminthiasis, therefore, also the crude extract was included in the study. Significant changes in differential gene expression were observed mainly for proteins related to the intestine, many of which were located extracellularly or within cellular membranes. Among the up-regulated genes, several hitherto undescribed orthologues of structural proteins in humans were identified, but also genes that are potentially involved in the worms' defense against tannins. For example, T22D1.2, an orthologue of human basic salivary proline-rich protein (PRB) 2, and numr-1 (nuclear localized metal responsive) were found to be strongly up-regulated. Down-regulated genes were mainly associated with lysosomal activity, glycoside hydrolysis or the worms' innate immune response. No major differences were found between the groups treated with purified OPCs versus the crude extract. Investigations using GFP reporter gene constructs of T22D1.2 and numr-1 corroborated the intestine as the predominant site of the anthelmintic activity. The current findings support previous hypotheses of OPCs interacting with intestinal surface proteins and provide the first insights into the nematode's response to OPCs on a molecular level as a base for the identification of future drug targets.	15	26351	Spiegler V	Spiegler V, Hensel A, SeggewiB J, Lubisch M, Liebau E	Transcriptome analysis reveals molecular anthelmintic effects of procyanidins in C. elegans.	PLoS One	2017	WBPaper00053092:C.mucronatum-H3-fraction_0.02_rep1~WBPaper00053092:C.mucronatum-H3-fraction_2_rep1~WBPaper00053092:Control_rep1~WBPaper00053092:C.mucronatum-H3-fraction_0.02_rep2~WBPaper00053092:C.mucronatum-H3-fraction_0.2_rep1~WBPaper00053092:C.mucronatum-H3-fraction_2_rep2~WBPaper00053092:C.mucronatum-extract_0.2_rep1~WBPaper00053092:Control_rep2~WBPaper00053092:C.mucronatum-H3-fraction_0.02_rep3~WBPaper00053092:C.mucronatum-H3-fraction_0.2_rep2~WBPaper00053092:C.mucronatum-H3-fraction_2_rep3~WBPaper00053092:C.mucronatum-extract_0.2_rep2~WBPaper00053092:Control_rep3~WBPaper00053092:C.mucronatum-H3-fraction_0.2_rep3~WBPaper00053092:C.mucronatum-extract_0.2_rep3	Method: microarray|Species: Caenorhabditis elegans
188	29063832	WBPaper00053236.ce.mr.paper	GSE99201	GPL200	1	daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival.	daf-16/FoxO is required to survive starvation in Caenorhabditis elegans, but how daf-16IFoxO promotes starvation resistance is unclear. We show that daf-16/FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input. Furthermore, we provide evidence that metabolic cycling between trehalose and glucose is necessary for this dual function of trehalose. This work demonstrates that daf-16/FoxO promotes starvation resistance by shifting carbon metabolism to drive trehalose synthesis, which in turn supports survival by providing an energy source and acting as a stress protectant.	12	17638	Hibshman JD	Hibshman JD, Doan AE, Moore BT, Kaplan RE, Hung A, Webster AK, Bhatt DP, Chitrakar R, Hirschey MD, Baugh LR	daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival.	Elife	2017	WBPaper00053236:N2_Fed_RepE~WBPaper00053236:N2_Starved_RepE~WBPaper00053236:daf-16(mgDf50)_Fed_RepE~WBPaper00053236:daf-16(mgDf50)_Starved_RepE~WBPaper00053236:N2_Fed_RepF~WBPaper00053236:N2_Starved_RepF~WBPaper00053236:daf-16(mgDf50)_Fed_RepF~WBPaper00053236:daf-16(mgDf50)_Starved_RepF~WBPaper00053236:N2_Fed_RepG~WBPaper00053236:N2_Starved_RepG~WBPaper00053236:daf-16(mgDf50)_Fed_RepG~WBPaper00053236:daf-16(mgDf50)_Starved_RepG	Method: microarray|Species: Caenorhabditis elegans
189	29078207	WBPaper00053254.ce.mr.paper	GSE105030	GPL19230	1	Hsp90-downregulation influences the heat-shock response, innate immune response and onset of oocyte development in nematodes.	Hsp90 is a molecular chaperone involved in the regulation and maturation of kinases and transcription factors. In Caenorhabditis elegans, it contributes to the development of fertility, maintenance of muscle structure, the regulation of heat-shock response and dauer state. To understand the consequences of Hsp90-depletion, we studied Hsp90 RNAi-treated nematodes by DNA microarrays and mass spectrometry. We find that upon development of phenotypes the levels of chaperones and Hsp90 cofactors are increased, while specific proteins related to the innate immune response are depleted. In microarrays, we further find many differentially expressed genes related to gonad and larval development. These genes form an expression cluster that is regulated independently from the immune response implying separate pathways of Hsp90-involvement. Using fluorescent reporter strains for the differentially expressed immune response genes skr-5, dod-24 and clec-60 we observe that their activity in intestinal tissues is influenced by Hsp90-depletion. Instead, effects on the development are evident in both gonad arms. After Hsp90-depletion, changes can be observed in early embryos and adults containing fluorescence-tagged versions of SEPA-1, CAV-1 or PUD-1, all of which are downregulated after Hsp90-depletion. Our observations identify molecular events for Hsp90-RNAi induced phenotypes during development and immune responses, which may help to separately investigate independent Hsp90-influenced processes that are relevant during the nematode's life and development.	6	26351	Eckl J	Eckl J, Sima S, Marcus K, Lindemann C, Richter K	Hsp90-downregulation influences the heat-shock response, innate immune response and onset of oocyte development in nematodes.	PLoS One	2017	WBPaper00053254:Control_rep1~WBPaper00053254:Control_rep2~WBPaper00053254:Control_rep3~WBPaper00053254:hsp-90(RNAi)_rep1~WBPaper00053254:hsp-90(RNAi)_rep2~WBPaper00053254:hsp-90(RNAi)_rep3	Method: microarray|Species: Caenorhabditis elegans
190	29281814	WBPaper00053481.ce.mr.paper	GSE37303	GPL200	1	The Sexual Dimorphism of Dietary Restriction Responsiveness in Caenorhabditis elegans.	Organismal lifespan is highly plastic in response to environmental cues, and dietary restriction (DR) is the most robust way to extend lifespan in various species. Recent studies have shown that sex also is an important factor for lifespan regulation; however, it remains largely unclear how these two factors, food and sex, interact in lifespan regulation. The nematode Caenorhabditis elegans has two sexes, hermaphrodite and male, and only the hermaphrodites are essential for the short-term succession of the species. Here, we report an extreme sexual dimorphism in the responsiveness to DR in C.elegans; the essential hermaphrodites show marked longevity responses to various forms of DR, but the males show few longevity responses and sustain reproductive ability. Our analysis reveals that the sex determination pathway and the steroid hormone receptor DAF-12 regulate the sex-specificDR responsiveness, integrating sex and environmental cues to determine organismal lifespan.	12	17638	Honjoh S	Honjoh S, Ihara A, Kajiwara Y, Yamamoto T, Nishida E	The Sexual Dimorphism of Dietary Restriction Responsiveness in Caenorhabditis elegans.	Cell Rep	2017	WBPaper00053481:Hermaphrodite_N2_fed_rep1~WBPaper00053481:Hermaphrodite_N2_fed_rep2~WBPaper00053481:Hermaphrodite_N2_fed_rep3~WBPaper00053481:Hermaphrodite_N2_fasting_rep1~WBPaper00053481:Hermaphrodite_N2_fasting_rep2~WBPaper00053481:Hermaphrodite_N2_fasting_rep3~WBPaper00053481:Male_N2_fed_rep1~WBPaper00053481:Male_N2_fed_rep2~WBPaper00053481:Male_N2_fed_rep3~WBPaper00053481:Male_N2_fasting_rep1~WBPaper00053481:Male_N2_fasting_rep2~WBPaper00053481:Male_N2_fasting_rep3	Method: microarray|Species: Caenorhabditis elegans
191	29259193	WBPaper00053505.ce.mr.paper	GSE84441	GPL200	1	JAK/STAT and TGF-B activation as potential adverse outcome pathway of TiO2NPs phototoxicity in Caenorhabditis elegans.	Titanium dioxide nanoparticles (TiO2NPs) are widely used nanoparticles, whose catalytic activity is mainly due to photoactivation. In this study, the toxicity of TiO2NPs was investigated on the nematode Caenorhabditis elegans, with and without UV activation. Comparative analyses across the four treatments revealed that UV-activated TiO2NPs led to significant reproductive toxicity through oxidative stress. To understand the underlying molecular mechanism, transcriptomics and metabolomics analyses were conducted, followed by whole-genome network-based pathway analyses. Differential expression analysis from microarray data revealed only 4 DEGs by exposure to TiO2NPs alone, compared to 3,625 and 3,286 DEGs by UV alone and UV-activated TiO2NPs, respectively. Pathway analyses suggested the possible involvement of the JAK/STAT and TGF-B pathways in the phototoxicity of TiO2NPs, which correlated with the observation of increased gene expression of those pathways. Comparative analysis of C. elegans response across UV activation and TiO2NPs exposure was performed using loss-of-function mutants of genes in these pathways. Results indicated that the JAK/STAT pathway was specific to TiO2NPs, whereas the TGF-B pathway was specific to UV. Interestingly, crosstalk between these pathways was confirmed by further mutant analysis. We consider that these findings will contribute to understand the molecular mechanisms of toxicity of TiO2NPs in the natural environment.	12	17638	Kim H	Kim H, Jeong J, Chatterjee N, Roca CP, Yoon D, Kim S, Kim Y, Choi J	JAK/STAT and TGF-B activation as potential adverse outcome pathway of TiO2NPs phototoxicity in Caenorhabditis elegans.	Sci Rep	2017	WBPaper00053505:Control_rep1~WBPaper00053505:Control_rep2~WBPaper00053505:Control_rep3~WBPaper00053505:UV_rep1~WBPaper00053505:UV_rep2~WBPaper00053505:UV_rep3~WBPaper00053505:TiO2_rep1~WBPaper00053505:TiO2_rep2~WBPaper00053505:TiO2_rep3~WBPaper00053505:UV-TiO2_rep1~WBPaper00053505:UV-TiO2_rep2~WBPaper00053505:UV-TiO2_rep3	Method: microarray|Species: Caenorhabditis elegans
192	29301909	WBPaper00053550.ce.mr.paper	GSE96068	GPL200	1	An Expanded Role for the RFX Transcription Factor DAF-19, with Dual Functions in Ciliated and Non-ciliated Neurons.	Regulatory Factor X transcription factors (RFX TFs) are best known for activating genes required for ciliogenesis in both vertebrates and invertebrates. In humans, eight RFX TFs have a variety of tissue-specific functions, while in the worm Caenorhabditis elegans, the sole RFX gene, daf-19, encodes a set of nested isoforms. Null alleles of daf-19 confer pleiotropic effects including altered development with a dauer constitutive phenotype, complete absence of cilia and ciliary proteins, and defects in synaptic protein maintenance. We sought to identify RFX/daf-19 target genes associated with neuronal functions other than ciliogenesis using comparative transcriptome analyses at different life stages of the worm. Subsequent characterization of gene expression patterns revealed one set of genes activated in the presence of DAF-19 in ciliated sensory neurons and whose activation requires the daf-19c isoform, also required for ciliogenesis. A second set of genes is down-regulated in the presence of DAF-19, primarily in non-sensory neurons. The human orthologs of some of these neuronal genes are associated with human diseases. We report the novel finding that daf-19a is directly or indirectly responsible for down-regulation of these neuronal genes in C. elegans by characterizing a new mutation affecting the daf-19a isoform (tm5562) and not associated with ciliogenesis, but which confers synaptic and behavioral defects. We have thus identified a new regulatory role for RFX TFs in the nervous system. The new daf-19 candidate target genes we have identified by transcriptomics will serve to uncover the molecular underpinnings of the pleiotropic effects daf-19 exerts on nervous system function.	14	17638	De Stasio EA	De Stasio EA, Mueller KP, Bauer RJ, Hurlburt AJ, Bice SA, Scholtz SL, Phirke P, Sugiaman-Trapman D, Stinson LA, Olson HB, Vogel SL, Ek-Vazquez Z, Esemen Y, Korzynski J, Wolfe K, Arbuckle BN, Zhang H, Lombard-Knapp G, Piasecki BP, Swoboda P	An Expanded Role for the RFX Transcription Factor DAF-19, with Dual Functions in Ciliated and Non-ciliated Neurons.	Genetics	2018	WBPaper00053550:L1_daf-19(m86);daf-12(sa204)_rep1~WBPaper00053550:L1_daf-19(m86);daf-12(sa204)_rep2~WBPaper00053550:L1_daf-19(m86);daf-12(sa204)_rep3~WBPaper00053550:L1_daf-19(m86);daf-12(sa204)_rep4~WBPaper00053550:L1_daf-12(sa204)_rep1~WBPaper00053550:L1_daf-12(sa204)_rep2~WBPaper00053550:L1_daf-12(sa204)_rep3~WBPaper00053550:L1_daf-12(sa204)_rep4~WBPaper00053550:2-Day-Adult_daf-19(m86);daf-12(sa204)_rep1~WBPaper00053550:2-Day-Adult_daf-19(m86);daf-12(sa204)_rep2~WBPaper00053550:2-Day-Adult_daf-19(m86);daf-12(sa204)_rep3~WBPaper00053550:2-Day-Adult_daf-12(sa204)_rep1~WBPaper00053550:2-Day-Adult_daf-12(sa204)_rep2~WBPaper00053550:2-Day-Adult_daf-12(sa204)_rep3	Method: microarray|Species: Caenorhabditis elegans
193	29436902	WBPaper00053688.ce.mr.paper	GSE95636	GPL200	1	Both live and dead Enterococci activate Caenorhabditis elegans host defense via immune and stress pathways.	The innate immune response of the nematode Caenorhabditis elegans has been extensively studied and a variety of Toll-independent immune response pathways have been identified. Surprisingly little, however, is known about how pathogens activate the C. elegans immune response. Enterococcus faecalis and Enterococcus faecium are closely related enterococcal species that exhibit significantly different levels of virulence in C. elegans infection models. Previous work has shown that activation of the C. elegans immune response by Pseudomonas aeruginosa involves P. aeruginosa-mediated host damage. Through ultrastructural imaging, we report that infection with either E. faecalis or E. faecium causes the worm intestine to become distended with proliferating bacteria in the absence of extensive morphological changes and apparent physical damage. Genetic analysis, whole-genome transcriptional profiling, and multiplexed gene expression analysis demonstrate that both enterococcal species, whether live or dead, induce a rapid and similar transcriptional defense response dependent upon previously described immune signaling pathways. The host response to E. faecium shows a stricter dependence upon stress response signaling pathways than the response to E. faecalis. Unexpectedly, we find that E. faecium is a C. elegans pathogen and that an active wild-type host defense response is required to keep an E. faecium infection at bay. These results provide new insights into the mechanisms underlying the C. elegans immune response to pathogen infection.	13	17638	Yuen GJ	Yuen GJ, Ausubel FM	Both live and dead Enterococci activate Caenorhabditis elegans host defense via immune and stress pathways.	Virulence	2018	WBPaper00053688:fed_heat-killed-E.coli_rep1~WBPaper00053688:fed_heat-killed-E.coli_rep2~WBPaper00053688:fed_B.subtilis_rep1~WBPaper00053688:fed_B.subtilis_rep2~WBPaper00053688:fed_B.subtilis_rep3~WBPaper00053688:infected_E.faecalis_rep1~WBPaper00053688:infected_E.faecalis_rep2~WBPaper00053688:infected_E.faecalis_rep3~WBPaper00053688:infected_E.faecium_rep1~WBPaper00053688:infected_E.faecium_rep2~WBPaper00053688:infected_E.faecium_rep3~WBPaper00053688:fed_heat-killed-E.coli_rep3~WBPaper00053688:fed_heat-killed-E.coli_rep4	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response
194	29465730	WBPaper00053736.ce.mr.paper	GSE102802	GPL19230	1	Dihomo-gamma-linolenic acid induces fat loss in C. elegans in an omega-3-independent manner by promoting peroxisomal fatty acid -oxidation.	Bioactive compounds, including some fatty acids (FAs), can induce beneficial effects on body fat-content and metabolism. In this work, we have used C. elegans as a model to examine the effects of several FAs on body fat accumulation. Both omega-3 and omega-6 fatty acids induced a reduction of fat content in C. elegans, with linoleic, gamma-linolenic and dihomo-gamma-linolenic acids being the most effective ones. These three FAs are sequential metabolites especially in omega-6 PUFA synthesis pathway and the effects seem to be primarily due to dihomo-gamma-linolenic acid, and independent of its transformation into omega-3 or arachidonic acid. Gene expression analyses suggest that peroxisomal beta oxidation is the main mechanism involved in the observed effect. These results point out the importance of further analysis of the activity of these omega-6 FAs, due to their potential application in obesity and related diseases.	12	26351	Navarro-Herrera D	Navarro-Herrera D, Aranaz P, Eder-Azanza L, Zabala M, Hurtado C, Romo-Hualde A, Martinez JA, Gonzalez-Navarro CJ, Vizmanos JL	Dihomo-gamma-linolenic acid induces fat loss in C. elegans in an omega-3-independent manner by promoting peroxisomal fatty acid -oxidation.	Food Funct	2018	WBPaper00053736:NGMcontrol_rep1~WBPaper00053736:NGMcontrol_rep2~WBPaper00053736:NGMcontrol_rep3~WBPaper00053736:LNA_rep1~WBPaper00053736:LNA_rep2~WBPaper00053736:LNA_rep3~WBPaper00053736:GLA_rep1~WBPaper00053736:GLA_rep2~WBPaper00053736:GLA_rep3~WBPaper00053736:DGLA_rep1~WBPaper00053736:DGLA_rep2~WBPaper00053736:DGLA_rep3	Method: microarray|Species: Caenorhabditis elegans
195	29464946	WBPaper00053737.ce.mr.paper	GSE95603	GPL200	1	Uptake of TiO2 Nanoparticles into C. elegans Neurons Negatively Affects Axonal Growth and Worm Locomotion Behavior.	We employ the model organism Caenorhabditis elegans to effectively study the toxicology of anatase and rutile phase titanium dioxide (TiO2) nanoparticles (NPs). The experimental results show that the nematode C. elegans can take up fluorescein isothiocyanate (FITC)-labeled TiO2 NPs and that both anatase and rutile TiO2 NPs can be detected in the cytoplasm of cultured primary neurons imaged by transmission electron microscopy (TEM). After TiO2 NPs exposure, these neurons also grow shorter axons, which may be related to the detected impeded worm locomotion behavior. Furthermore, anatase TiO2 NPs did not affect the worm's body length; however, we determined that a concentration of 500 g/ml anatase TiO2 NPs reduced a worm population by 50% within 72 hours. Notably, rutile TiO2 NPs negatively affect both body size and worm population. Worms unable to enter the L4 larval stage explain a severe reduction in the worm population at TiO2 NPs LC50/3d. To obtain a better understanding of the cellular mechanisms involved in TiO2 NPs intoxication, DNA microarray assays were employed to determine changes in gene expression in the presence or absence of TiO2 NPs exposure. Our data reveal three genes (with significant changes in expression levels) were related to metal binding or metal detoxification (mtl-2, C45B2.2 and nhr-247), six genes involved in fertility and reproduction (mtl-2, F26F2.3, ZK970.7, clec-70, K08C9.7 and C38C3.7), four genes involved in worm growth and body morphogenesis (mtl-2, F26F2.3, C38C3.7 and nhr-247), and five genes involved in neuronal function (C41G6.13, C45B2.2, srr-6, K08C9.7 and C38C3.7).	2	17637	Hu CC	Hu CC, Wu GH, Hua TE, Wagner OI, Yen TJ	Uptake of TiO2 Nanoparticles into C. elegans Neurons Negatively Affects Axonal Growth and Worm Locomotion Behavior.	ACS Appl Mater Interfaces	2018	WBPaper00053737:Control_rep3~WBPaper00053737:anatase-TiO2_rep3	Method: microarray|Species: Caenorhabditis elegans
196	29532717	WBPaper00053827.ce.mr.paper	GSE95510	GPL200	1	Pyoverdine, a siderophore from Pseudomonas aeruginosa, translocates into C. elegans, removes iron, and activates a distinct host response.	Pseudomonas aeruginosa, a re-emerging, opportunistic human pathogen, encodes a variety of virulence determinants. Pyoverdine, a siderophore produced by this bacterium, is essential for pathogenesis in mammalian infections. This observation is generally attributed to its roles in acquiring iron and/or regulating other virulence factors. Here we report that pyoverdine translocates into the host, where it binds and extracts iron from the host prior to its eventual exit. Pyoverdine-mediated iron extraction damages host mitochondria, disrupting their function and triggering mitochondrial turnover via autophagy. The host detects this damage via a conserved mitochondrial surveillance pathway mediated by the ESRE network. Our findings illuminate the pathogenic mechanisms of pyoverdine and highlight the importance of this bacterial product in host-pathogen interactions.	9	17638	Kang D	Kang D, Kirienko DR, Webster P, Fisher AL, Kirienko NV	Pyoverdine, a siderophore from Pseudomonas aeruginosa, translocates into C. elegans, removes iron, and activates a distinct host response.	Virulence	2018	WBPaper00053827:glp-4_NGM_repA~WBPaper00053827:glp-4_NGM_repB~WBPaper00053827:glp-4_NGM_repC~WBPaper00053827:glp-4_Basal_repA~WBPaper00053827:glp-4_Basal_repB~WBPaper00053827:glp-4_Basal_repC~WBPaper00053827:glp-4_PVD_repA~WBPaper00053827:glp-4_PVD_repB~WBPaper00053827:glp-4_PVD_repC	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism
197	29526616	WBPaper00053833.ce.mr.paper	GSE66680	GPL200	1	N-acetylcysteine and vitamin E rescue animal longevity and cellular oxidative stress in pre-clinical models of mitochondrial complex I disease.	Oxidative stress is a known contributing factor in mitochondrial respiratory chain (RC) disease pathogenesis. Yet, no efficient means exists to objectively evaluate the comparative therapeutic efficacy or toxicity of different antioxidant compounds empirically used in human RC disease. We postulated that pre-clinical comparative analysis of diverse antioxidant drugs having suggested utility in primary RC disease using animal and cellular models of RC dysfunction may improve understanding of their integrated effects and physiologic mechanisms, and enable prioritization of lead antioxidant molecules to pursue in human clinical trials. Here, lifespan effects of N-acetylcysteine (NAC), vitamin E, vitamin C, coenzyme Q10 (CoQ10), mitochondrial-targeted CoQ10 (MS010), lipoate, and orotate were evaluated as the primary outcome in a well-established, short-lived C. elegans gas-1(fc21) animal model of RC complex I disease. Healthspan effects were interrogated to assess potential reversal of their globally disrupted in vivo mitochondrial physiology, transcriptome profiles, and intermediary metabolic flux. NAC or vitamin E fully rescued, and coenzyme Q, lipoic acid, orotic acid, and vitamin C partially rescued gas-1(fc21) lifespan toward that of wild-type N2 Bristol worms. MS010 and CoQ10 largely reversed biochemical pathway expression changes in gas-1(fc21) worms. While nearly all drugs normalized the upregulated expression of the &quot;cellular antioxidant pathway&quot;, they failed to rescue the mutant worms' increased in vivo mitochondrial oxidant burden. NAC and vitamin E therapeutic efficacy were validated in human fibroblast and/or zebrafish complex I disease models. Remarkably, rotenone-induced zebrafish brain death was preventable partially with NAC and fully with vitamin E. Overall, these pre-clinical model animal data demonstrate that several classical antioxidant drugs do yield significant benefit on viability and survival in primary mitochondrial disease, where their major therapeutic benefit appears to result from targeting global cellular, rather than intramitochondria-specific, oxidative stress. Clinical trials are needed to evaluate whether the two antioxidants, NAC and vitamin E, that show greatest efficacy in translational model animals significantly improve the survival, function, and feeling of human subjects with primary mitochondrial RC disease.	75	9977	Polyak E	Polyak E, Ostrovsky J, Peng M, Dingley SD, Tsukikawa M, Kwon YJ, McCormack SE, Bennett M, Xiao R, Seiler C, Zhang Z, Falk MJ	N-acetylcysteine and vitamin E rescue animal longevity and cellular oxidative stress in pre-clinical models of mitochondrial complex I disease.	Mol Genet Metab	2018	WBPaper00053833:01_N2_untreated_adult_rep1~WBPaper00053833:02_N2_untreated_adult_rep2~WBPaper00053833:03_N2_untreated_adult_rep3~WBPaper00053833:04_N2_untreated_adult_rep4~WBPaper00053833:05_N2_untreated_adult_rep5~WBPaper00053833:06_N2_untreated_adult_rep6~WBPaper00053833:07_gas-1(fc21)_untreated_adult_rep7~WBPaper00053833:08_gas-1(fc21)_VitaminC_adult_rep8~WBPaper00053833:09_gas-1(fc21)_OroticAcid_adult_rep9~WBPaper00053833:10_gas-1(fc21)_LipoicAcid_adult_rep10~WBPaper00053833:11_gas-1(fc21)_N-Acetylcysteine_adult_rep11~WBPaper00053833:12_gas-1(fc21)_MS010_adult_rep12~WBPaper00053833:13_gas-1(fc21)_CoenzymeQ10_adult_rep13~WBPaper00053833:14_gas-1(fc21)_Decyl-TPP_adult_rep14~WBPaper00053833:15_gas-1(fc21)_untreated_adult_rep15~WBPaper00053833:16_gas-1(fc21)_VitaminC_adult_rep16~WBPaper00053833:17_gas-1(fc21)_OroticAcid_adult_rep17~WBPaper00053833:18_gas-1(fc21)_LipoicAcid_adult_rep18~WBPaper00053833:19_gas-1(fc21)_N-Acetylcysteine_adult_rep19~WBPaper00053833:20_gas-1(fc21)_MS010_adult_rep20~WBPaper00053833:21_gas-1(fc21)_CoenzymeQ10_adult_rep21~WBPaper00053833:22_gas-1(fc21)_Decyl-TPP_adult_rep22~WBPaper00053833:23_gas-1(fc21)_untreated_adult_rep23~WBPaper00053833:24_gas-1(fc21)_VitaminC_adult_rep24~WBPaper00053833:25_gas-1(fc21)_OroticAcid_adult_rep25~WBPaper00053833:26_gas-1(fc21)_LipoicAcid_adult_rep26~WBPaper00053833:27_gas-1(fc21)_N-Acetylcysteine_adult_rep27~WBPaper00053833:28_gas-1(fc21)_MS010_adult_rep28~WBPaper00053833:29_gas-1(fc21)_CoenzymeQ10_adult_rep29~WBPaper00053833:30_gas-1(fc21)_Decyl-TPP_adult_rep30~WBPaper00053833:31_gas-1(fc21)_untreated_adult_rep31~WBPaper00053833:32_gas-1(fc21)_VitaminC_adult_rep32~WBPaper00053833:33_gas-1(fc21)_OroticAcid_adult_rep33~WBPaper00053833:34_gas-1(fc21)_LipoicAcid_adult_rep34~WBPaper00053833:35_gas-1(fc21)_N-Acetylcysteine_adult_rep35~WBPaper00053833:36_gas-1(fc21)_MS010_adult_rep36~WBPaper00053833:37_gas-1(fc21)_CoenzymeQ10_adult_rep37~WBPaper00053833:38_gas-1(fc21)_Decyl-TPP_adult_rep38~WBPaper00053833:39_N2_untreated_L1_rep39~WBPaper00053833:40_N2_untreated_L1_rep40~WBPaper00053833:41_N2_untreated_L1_rep41~WBPaper00053833:42_N2_untreated_L1_rep42~WBPaper00053833:43_N2_untreated_L1_rep43~WBPaper00053833:44_gas-1(fc21)_untreated_L1_rep44~WBPaper00053833:45_gas-1(fc21)_VitaminC_L1_rep45~WBPaper00053833:46_gas-1(fc21)_OroticAcid_L1_rep46~WBPaper00053833:47_gas-1(fc21)_LipoicAcid_L1_rep47~WBPaper00053833:48_gas-1(fc21)_N-Acetylcysteine_L1_rep48~WBPaper00053833:49_gas-1(fc21)_MS010_L1_rep49~WBPaper00053833:50_gas-1(fc21)_CoenzymeQ10_L1_rep50~WBPaper00053833:51_gas-1(fc21)_Decyl-TPP_L1_rep51~WBPaper00053833:52_gas-1(fc21)_untreated_L1_rep52~WBPaper00053833:53_gas-1(fc21)_VitaminC_L1_rep53~WBPaper00053833:54_gas-1(fc21)_OroticAcid_L1_rep54~WBPaper00053833:55_gas-1(fc21)_LipoicAcid_L1_rep55~WBPaper00053833:56_gas-1(fc21)_N-Acetylcysteine_L1_rep56~WBPaper00053833:57_gas-1(fc21)_MS010_L1_rep57~WBPaper00053833:58_gas-1(fc21)_CoenzymeQ10_L1_rep58~WBPaper00053833:59_gas-1(fc21)_Decyl-TPP_L1_rep59~WBPaper00053833:60_gas-1(fc21)_untreated_L1_rep60~WBPaper00053833:61_gas-1(fc21)_VitaminC_L1_rep61~WBPaper00053833:62_gas-1(fc21)_OroticAcid_L1_rep62~WBPaper00053833:63_gas-1(fc21)_LipoicAcid_L1_rep63~WBPaper00053833:64_gas-1(fc21)_N-Acetylcysteine_L1_rep64~WBPaper00053833:65_gas-1(fc21)_MS010_L1_rep65~WBPaper00053833:66_gas-1(fc21)_CoenzymeQ10_L1_rep66~WBPaper00053833:67_gas-1(fc21)_Decyl-TPP_L1_rep67~WBPaper00053833:68_gas-1(fc21)_untreated_L1_rep68~WBPaper00053833:69_gas-1(fc21)_VitaminC_L1_rep69~WBPaper00053833:70_gas-1(fc21)_OroticAcid_L1_rep70~WBPaper00053833:71_gas-1(fc21)_LipoicAcid_L1_rep71~WBPaper00053833:72_gas-1(fc21)_N-Acetylcysteine_L1_rep72~WBPaper00053833:73_gas-1(fc21)_MS010_L1_rep73~WBPaper00053833:74_gas-1(fc21)_CoenzymeQ10_L1_rep74~WBPaper00053833:75_gas-1(fc21)_Decyl-TPP_L1_rep75	Method: microarray|Species: Caenorhabditis elegans
198	30333136	WBPaper00055482.ce.mr.paper	GSE99763	GPL19230	1	Lipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress.	Metabolic disorders such as nonalcoholic fatty liver disease (NAFLD) are emerging epidemics that affect the global population. One facet of these disorders is attributed to the disturbance of membrane lipid composition. Perturbation of endoplasmic reticulum (ER) homeostasis through alteration in membrane phospholipids activates the unfolded protein response (UPR) and causes dramatic transcriptional and translational changes in the cell. To restore cellular homeostasis, the three highly conserved UPR transducers ATF6, IRE1, and PERK mediate adaptive responses upon ER stress. The homeostatic UPR cascade is well characterised under conditions of proteotoxic stress, but much less so under lipid bilayer stress induced-UPR. Disrupted phosphatidylcholine (PC) synthesis in <i>C. elegans</i> causes lipid bilayer stress, lipid droplet accumulation and ER stress induction. Transcriptional profiling of PC-deficient worms shows a unique subset of genes regulated in a UPR-dependent manner that is independent from proteotoxic stress. Among these, we show that autophagy is modulated through the conserved IRE-1/XBP-1 axis, strongly suggesting of the importance of autophagy in maintaining cellular homeostasis during lipid bilayer induced-UPR.	30	26351	Koh JH	Koh JH, Wang L, Beaudoin-Chabot C, Thibault G	Lipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress.	J Cell Sci	2018	WBPaper00055482:N2_VectorControl_rep1~WBPaper00055482:N2_VectorControl_rep2~WBPaper00055482:N2_VectorControl_rep3~WBPaper00055482:N2_pmt-2(RNAi)_rep1~WBPaper00055482:N2_pmt-2(RNAi)_rep2~WBPaper00055482:N2_pmt-2(RNAi)_rep3~WBPaper00055482:N2_Tunicamycin_rep1~WBPaper00055482:N2_Tunicamycin_rep2~WBPaper00055482:N2_Tunicamycin_rep3~WBPaper00055482:atf-6(ok551)_VectorControl_rep1~WBPaper00055482:atf-6(ok551)_VectorControl_rep2~WBPaper00055482:atf-6(ok551)_VectorControl_rep3~WBPaper00055482:atf-6(ok551)_pmt-2(RNAi)_rep1~WBPaper00055482:atf-6(ok551)_pmt-2(RNAi)_rep2~WBPaper00055482:atf-6(ok551)_pmt-2(RNAi)_rep3~WBPaper00055482:ire-1(ok799)_VectorControl_rep1~WBPaper00055482:ire-1(ok799)_VectorControl_rep2~WBPaper00055482:ire-1(ok799)_VectorControl_rep3~WBPaper00055482:ire-1(ok799)_pmt-2(RNAi)_rep1~WBPaper00055482:ire-1(ok799)_pmt-2(RNAi)_rep2~WBPaper00055482:ire-1(ok799)_pmt-2(RNAi)_rep3~WBPaper00055482:pek-1(ok275)_VectorControl_rep1~WBPaper00055482:pek-1(ok275)_VectorControl_rep2~WBPaper00055482:pek-1(ok275)_VectorControl_rep3~WBPaper00055482:pek-1(ok275)_pmt-2(RNAi)_rep1~WBPaper00055482:pek-1(ok275)_pmt-2(RNAi)_rep2~WBPaper00055482:pek-1(ok275)_pmt-2(RNAi)_rep3~WBPaper00055482:pmt-2(vc1952)_VectorControl_rep1~WBPaper00055482:pmt-2(vc1952)_VectorControl_rep2~WBPaper00055482:pmt-2(vc1952)_VectorControl_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: obsolete mRNA splicing via endonucleolytic cleavage and ligation involved in unfolded protein response|Topic: endoplasmic reticulum unfolded protein response|Topic: endoplasmic reticulum
199	30630824	WBPaper00056167_1.ce.mr.paper	GSE125131,GSE125132,GSE125133	GPL19230	1	The intestinal intermediate filament network responds to and protects against microbial insults and toxins.	The enrichment of intermediate filaments in the apical cytoplasm of intestinal cells is evolutionary conserved forming a sheath that is anchored to apical junctions and positioned below the microvillar brush border suggestive of a protective intracellular barrier function. To test this, we used <i>C. elegans</i>, whose intestinal cells are endowed with a particularly dense intermediate filament-rich layer that is referred to as the endotube. We find alterations in endotube structure and intermediate filament expression upon infection with nematicidal <i>Bacillus thuringiensis</i> or treatment with its major pore-forming toxin crystal protein Cry5B. Endotube impairment due to defined genetic mutations of intermediate filaments and their regulators results in increased Cry5B sensitivity as evidenced by elevated larval arrest, prolonged time of larval development and reduced survival. Phenotype severity reflects the severity of endotube alterations and correlates with reduced rescue upon toxin removal. The results provide <i>in vivo</i> evidence for a major protective role of a properly configured intermediate filament network as an intracellular barrier in intestinal cells. This notion is further supported by increased sensitivity of endotube mutants to oxidative and osmotic stress.	6	26351	Geisler F	Geisler F, Coch RA, Richardson C, Goldberg M, Denecke B, Bossinger O, Leube RE	The intestinal intermediate filament network responds to and protects against microbial insults and toxins.	Development	2019	WBPaper00056167:N2_Cry5B_WholeAnimal_rep1~WBPaper00056167:N2_Cry5B_WholeAnimal_rep2~WBPaper00056167:N2_Cry5B_WholeAnimal_rep3~WBPaper00056167:N2_JM103_WholeAnimal_rep1~WBPaper00056167:N2_JM103_WholeAnimal_rep2~WBPaper00056167:N2_JM103_WholeAnimal_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response|Tissue Specific
200	30630824	WBPaper00056167_2.ce.mr.paper	GSE125131,GSE125132,GSE125133	GPL19230	1	The intestinal intermediate filament network responds to and protects against microbial insults and toxins.	The enrichment of intermediate filaments in the apical cytoplasm of intestinal cells is evolutionary conserved forming a sheath that is anchored to apical junctions and positioned below the microvillar brush border suggestive of a protective intracellular barrier function. To test this, we used <i>C. elegans</i>, whose intestinal cells are endowed with a particularly dense intermediate filament-rich layer that is referred to as the endotube. We find alterations in endotube structure and intermediate filament expression upon infection with nematicidal <i>Bacillus thuringiensis</i> or treatment with its major pore-forming toxin crystal protein Cry5B. Endotube impairment due to defined genetic mutations of intermediate filaments and their regulators results in increased Cry5B sensitivity as evidenced by elevated larval arrest, prolonged time of larval development and reduced survival. Phenotype severity reflects the severity of endotube alterations and correlates with reduced rescue upon toxin removal. The results provide <i>in vivo</i> evidence for a major protective role of a properly configured intermediate filament network as an intracellular barrier in intestinal cells. This notion is further supported by increased sensitivity of endotube mutants to oxidative and osmotic stress.	6	26351	Geisler F	Geisler F, Coch RA, Richardson C, Goldberg M, Denecke B, Bossinger O, Leube RE	The intestinal intermediate filament network responds to and protects against microbial insults and toxins.	Development	2019	WBPaper00056167:N2_OP50_intestine_rep1~WBPaper00056167:N2_OP50_intestine_rep2~WBPaper00056167:N2_OP50_intestine_rep3~WBPaper00056167:ifo-1(kc2)_OP50_intestine_rep1~WBPaper00056167:ifo-1(kc2)_OP50_intestine_rep2~WBPaper00056167:ifo-1(kc2)_OP50_intestine_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response|Tissue Specific
201	30823346	WBPaper00056297.ce.mr.paper	GSE114881	GPL19230	1	Toxicogenomic responses of Caenorhabditis elegans to pristine and transformed zinc oxide nanoparticles.	Manufactured nanoparticles (MNPs) undergo transformation immediately after they enter wastewater treatment streams and during their partitioning to sewage sludge, which is applied to agricultural soils in form of biosolids. We examined toxicogenomic responses of the model nematode Caenorhabditis elegans to pristine and transformed ZnO-MNPs (phosphatized pZnO- and sulfidized sZnO-MNPs). To account for the toxicity due to dissolved Zn, a ZnSO<sub>4</sub> treatment was included<sub>.</sub> Transformation of ZnO-MNPs reduced their toxicity by nearly ten-fold, while there was almost no difference in the toxicity of pristine ZnO-MNPs and ZnSO<sub>4</sub>. This combined with the fact that far more dissolved Zn was released from ZnO- compared to pZnO- or sZnO-MNPs, suggests that dissolution of pristine ZnO-MNPs is one of the main drivers of their toxicity. Transcriptomic responses at the EC<sub>30</sub> for reproduction resulted in a total of 1161 differentially expressed genes. Fifty percent of the genes differentially expressed in the ZnSO<sub>4</sub> treatment, including the three metal responsive genes (mtl-1, mtl-2 and numr-1), were shared among all treatments, suggesting that responses to all forms of Zn could be partially attributed to dissolved Zn. However, the toxicity and transcriptomic responses in all MNP treatments cannot be fully explained by dissolved Zn. Two of the biological pathways identified, one essential for protein biosynthesis (Aminoacyl-tRNA biosynthesis) and another associated with detoxification (ABC transporters), were shared among pristine and one or both transformed ZnO-MNPs, but not ZnSO<sub>4</sub>. When comparing pristine and transformed ZnO-MNPs, 66% and 40% of genes were shared between ZnO-MNPs and sZnO-MNPs or pZnO-MNPs, respectively. This suggests greater similarity in transcriptomic responses between ZnO-MNPs and sZnO-MNPs, while toxicity mechanisms are more distinct for pZnO-MNPs, where 13 unique biological pathways were identified. Based on these pathways, the toxicity of pZnO-MNPs is likely to be associated with their adverse effect on digestion and metabolism.	15	26351	Starnes D	Starnes D, Unrine J, Chen C, Lichtenberg S, Starnes C, Svendsen C, Kille P, Morgan J, Baddar ZE, Spear A, Bertsch P, Chen KC, Tsyusko O	Toxicogenomic responses of Caenorhabditis elegans to pristine and transformed zinc oxide nanoparticles.	Environ Pollut	2019	WBPaper00056297:Control_repC1~WBPaper00056297:Control_repC4~WBPaper00056297:Control_repC5~WBPaper00056297:Zn-ions_repI3~WBPaper00056297:Zn-ions_repI4~WBPaper00056297:Zn-ions_repI5~WBPaper00056297:Phosphate-ZnO-MNP_repP1~WBPaper00056297:Phosphate-ZnO-MNP_repP4~WBPaper00056297:Phosphate-ZnO-MNP_repP5~WBPaper00056297:Sulfidized-ZnO-MNP_repS3~WBPaper00056297:Sulfidized-ZnO-MNP_repS4~WBPaper00056297:Sulfidized-ZnO-MNP_repS5~WBPaper00056297:Pristine-ZnO-MNP_repZ3~WBPaper00056297:Pristine-ZnO-MNP_repZ4~WBPaper00056297:Pristine-ZnO-MNP_repZ5	Method: microarray|Species: Caenorhabditis elegans
202	30865620	WBPaper00056391.ce.mr.paper	GSE97678	GPL200	1	Interplay between mitochondria and diet mediates pathogen and stress resistance in Caenorhabditis elegans.	Diet is a crucial determinant of organismal biology; interactions between the host, its diet, and its microbiota are critical to determining the health of an organism. A variety of genetic and biochemical means were used to assay stress sensitivity in C. elegans reared on two standard laboratory diets: E. coli OP50, the most commonly used food for C. elegans, or E. coli HT115, which is typically used for RNAi-mediated gene knockdown. We demonstrated that the relatively subtle shift to a diet of E. coli HT115 had a dramatic impact on C. elegans's survival after exposure to pathogenic or abiotic stresses. Interestingly, this was independent of canonical host defense pathways. Instead the change arises from improvements in mitochondrial health, likely due to alleviation of a vitamin B12 deficiency exhibited by worms reared on an E. coli OP50 diet. Increasing B12 availability, by feeding on E. coli HT115, supplementing E. coli OP50 with exogenous vitamin B12, or overexpression of the B12 transporter, improved mitochondrial homeostasis and increased resistance. Loss of the methylmalonyl-CoA mutase gene mmcm-1/MUT, which requires vitamin B12 as a cofactor, abolished these improvements, establishing a genetic basis for the E. coli OP50-incurred sensitivity. Our study forges a mechanistic link between a dietary deficiency (nutrition/microbiota) and a physiological consequence (host sensitivity), using the host-microbiota-diet framework.	6	17638	Revtovich AV	Revtovich AV, Lee R, Kirienko NV	Interplay between mitochondria and diet mediates pathogen and stress resistance in Caenorhabditis elegans.	PLoS Genet	2019	WBPaper00056391:glp-4_OP50_repA~WBPaper00056391:glp-4_OP50_repB~WBPaper00056391:glp-4_OP50_repC~WBPaper00056391:glp-4_HT115_repA~WBPaper00056391:glp-4_HT115_repB~WBPaper00056391:glp-4_HT115_repC	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
203	31138438	WBPaper00056823.ce.mr.paper	GSE118294	GPL200	1	MANF deletion abrogates early larval Caenorhabditis elegans stress response to tunicamycin and Pseudomonas aeruginosa.	Mesencephalic astrocyte-derived neurotrophic factor (MANF) is the only human neurotrophic factor with an evolutionarily-conserved C. elegans homolog, Y54G2A.23 or manf-1. MANF is a small, soluble, endoplasmic-reticulum (ER)-resident protein that is secreted upon ER stress and promotes survival of target cells such as neurons. However, the role of MANF in ER stress and its mechanism of cellular protection are not clear and the function of MANF in C. elegans is only beginning to emerge. In this study, we show that depletion of C. elegans manf-1 causes a slight decrease in lifespan and brood size; furthermore, combined depletion of manf-1 and the IRE-1/XBP-1 ER stress/UPR pathway resulted in sterile animals that did not produce viable progeny. We demonstrate upregulation of markers of ER stress in L1 larval nematodes, as measured by hsp-3 and hsp-4 transcription, upon depletion of manf-1 by RNAi or mutation; however, there was no difference in tunicamycin-induced expression of hsp-3 and hsp-4 between wild-type and MANF-deficient worms. Surprisingly, larval growth arrest observed in wild-type nematodes reared on tunicamycin is completely prevented in the manf-1 (tm3603) mutant. Transcriptional microarray analysis revealed that manf-1 mutant L1 larvae exhibit a novel modulation of innate immunity genes in response to tunicamycin. The hypothesis that manf-1 negatively regulates the innate immunity pathway is supported by our finding that the development of manf-1 mutant larvae compared to wild-type larvae is not inhibited by growth on P. aeruginosa. Together, our data represent the first characterization of C. elegans MANF as a key modulator of organismal ER stress and immunity.	12	17638	Hartman JH	Hartman JH, Richie CT, Gordon KL, Mello DF, Castillo P, Zhu A, Wang Y, Hoffer BJ, Sherwood DR, Meyer JN, Harvey BK	MANF deletion abrogates early larval Caenorhabditis elegans stress response to tunicamycin and Pseudomonas aeruginosa.	Eur J Cell Biol	2019	WBPaper00056823:N2_control_rep1~WBPaper00056823:N2_treated_rep1~WBPaper00056823:manf-1(tm3603)_control_rep1~WBPaper00056823:manf-1(tm3603)_treated_rep1~WBPaper00056823:N2_control_rep2~WBPaper00056823:N2_treated_rep2~WBPaper00056823:manf-1(tm3603)_control_rep2~WBPaper00056823:manf-1(tm3603)_treated_rep2~WBPaper00056823:N2_control_rep3~WBPaper00056823:N2_treated_rep3~WBPaper00056823:manf-1(tm3603)_control_rep3~WBPaper00056823:manf-1(tm3603)_treated_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response|Topic: obsolete mRNA splicing via endonucleolytic cleavage and ligation involved in unfolded protein response|Topic: endoplasmic reticulum unfolded protein response|Topic: endoplasmic reticulum
204	31300558	WBPaper00057029.ce.mr.paper	GSE115677	GPL19230	1	DOT1L complex suppresses transcription from enhancer elements and ectopic RNAi in <i>Caenorhabditis elegans</i>.	Methylation of histone H3 on lysine 79 (H3K79) by DOT1L is associated with actively transcribed genes. Earlier, we described that DOT-1.1, the Caenorhabditis elegans homologue of mammalian DOT1L, cooperates with the chromatin-binding protein ZFP-1 (AF10 homologue) to negatively modulate transcription of highly and widely expressed target genes. Also, reduction of ZFP-1 levels has consistently been associated with lower efficiency of RNA interference (RNAi) triggered by exogenous double-stranded RNA (dsRNA), but the reason for this is not clear. Here, we demonstrate that the DOT1L complex suppresses transcription originating from enhancer elements and antisense transcription, thus potentiating expression of enhancer-regulated genes. We also show that worms lacking H3K79 methylation do not survive and this lethality is suppressed by mutations in caspase-3, and Dicer complex components that initiate gene silencing response to exogenous dsRNA. Our results suggest that ectopic elevation of endogenous dsRNA directly or indirectly resulting from global misregulation of transcription in DOT1L complex mutants may engage the Dicer complex and, therefore, limit the efficiency of exogenous RNAi.	12	26351	Esse R	Esse R, Gushchanskaia ES, Lord A, Grishok A	DOT1L complex suppresses transcription from enhancer elements and ectopic RNAi in <i>Caenorhabditis elegans</i>.	RNA	2019	WBPaper00057029:N2_rep1~WBPaper00057029:N2_rep2~WBPaper00057029:N2_rep3~WBPaper00057029:zfp-1(ok554)_rep1~WBPaper00057029:zfp-1(ok554)_rep2~WBPaper00057029:zfp-1(ok554)_rep3~WBPaper00057029:dot-1.1(gk1050594)_rep1~WBPaper00057029:dot-1.1(gk1050594)_rep2~WBPaper00057029:dot-1.1(gk1050594)_rep3~WBPaper00057029:mml-1(gk402844)_rep1~WBPaper00057029:mml-1(gk402844)_rep2~WBPaper00057029:mml-1(gk402844)_rep3	Method: microarray|Species: Caenorhabditis elegans
205	31358532	WBPaper00057136.ce.mr.paper	GSE133667	GPL200	1	The Hippo Pathway Is Essential for Maintenance of Apicobasal Polarity in the Growing Intestine of <i>Caenorhabditis elegans</i>.	Although multiple determinants for establishing polarity in membranes of epithelial cells have been identified, the mechanism for maintaining the apicobasal polarity is not fully understood. Here, we show that the conserved Hippo kinase pathway plays a role in the maintenance of apicobasal polarity in the developing intestine of <i>Caenorhabditis elegans</i> We screened suppressors of the mutation in <i>wts-1</i>, the gene that encodes the LATS kinase homolog, the deficiency of which leads to disturbance of the apicobasal polarity of the intestinal cells and to eventual death of the organism. We identified several alleles of <i>yap-1</i> and <i>egl-44</i> that suppress the effects of this mutation. <i>yap-1</i> encodes a homolog of YAP/Yki, and <i>egl-44</i> encodes a homolog of TEAD/Sd. WTS-1 bound directly to YAP-1 and inhibited its nuclear accumulation in intestinal cells. We also found that NFM-1, which is a homolog of NF2/Merlin, functioned in the same genetic pathway as WTS-1 to regulate YAP-1 to maintain cellular polarity. Transcriptome analysis identified several target candidates of the YAP-1-EGL-44 complex including TAT-2, which encodes a putative P-type ATPase. In summary, we have delineated the conserved Hippo pathway in <i>C. elegans</i> consisting of NFM-1-WTS-1-YAP-1-EGL-44 and proved that the proper regulation of YAP-1 by upstream NFM-1 and WTS-1 is esssential for maintenance of apicobasal membrane identities of the growing intestine.	6	17638	Lee H	Lee H, Kang J, Ahn S, Lee J	The Hippo Pathway Is Essential for Maintenance of Apicobasal Polarity in the Growing Intestine of <i>Caenorhabditis elegans</i>.	Genetics	2019	WBPaper00057136:N2_rep1~WBPaper00057136:N2_rep2~WBPaper00057136:N2_rep3~WBPaper00057136:yap-1(ys38)_rep1~WBPaper00057136:yap-1(ys38)_rep2~WBPaper00057136:yap-1(ys38)_rep3	Method: microarray|Species: Caenorhabditis elegans
206	31535080	WBPaper00058595.ce.mr.paper	GSE124300	GPL19230	1	Olfaction regulates organismal proteostasis and longevity via microRNA-dependent signaling.	The maintenance of proteostasis is crucial for any organism to survive and reproduce in an ever-changing environment, but its efficiency declines with age<sup>1</sup>. Posttranscriptional regulators such as microRNAs control protein translation of target mRNAs with major consequences for development, physiology, and longevity<sup>2,3</sup>. Here we show that food odor stimulates organismal proteostasis and promotes longevity in <i>Caenorhabditis elegans</i> through <i>mir-71</i>-mediated inhibition of <i>tir-1</i> mRNA stability in olfactory AWC neurons. Screening a collection of microRNAs that control aging<sup>3</sup> we find that miRNA <i>mir-71</i> regulates lifespan and promotes ubiquitin-dependent protein turnover, particularly in the intestine. We show that <i>mir-71</i> directly inhibits the toll receptor domain protein TIR-1 in AWC olfactory neurons and that disruption of <i>mir-71/tir-1</i> or loss of AWC olfactory neurons eliminates the influence of food source on proteostasis. <i>mir-71</i>-mediated regulation of TIR-1 controls chemotactic behavior and is regulated by odor. Thus, odor perception influences cell-type specific miRNA-target interaction to regulate organismal proteostasis and longevity. We anticipate that the proposed mechanism of food perception will stimulate further research on neuroendocrine brain-to-gut communication and may open the possibility for therapeutic interventions to improve proteostasis and organismal health via the sense of smell, with potential implication for obesity, diabetes and aging.	8	26351	Finger F	Finger F, Ottens F, Springhorn A, Drexel T, Proksch L, Metz S, Cochella L, Hoppe T	Olfaction regulates organismal proteostasis and longevity via microRNA-dependent signaling.	Nat Metab	2019	WBPaper00058595:N2_rep1~WBPaper00058595:N2_rep2~WBPaper00058595:N2_rep3~WBPaper00058595:N2_rep4~WBPaper00058595:mir-71(n4115)_rep1~WBPaper00058595:mir-71(n4115)_rep2~WBPaper00058595:mir-71(n4115)_rep3~WBPaper00058595:mir-71(n4115)_rep4	Method: microarray|Species: Caenorhabditis elegans
207	31346165	WBPaper00059194.ce.mr.paper	GSE61771	GPL19230	1	KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants.	Most manipulations that extend lifespan also increase resistance to various stress factors and environmental cues in a range of animals from yeast to mammals. However, the underlying molecular mechanisms regulating stress resistance during aging are still largely unknown. Here we identify Kruppel-like factor 1 (KLF-1) as a mediator of a cytoprotective response that dictates longevity induced by reduced mitochondrial function. A redox-regulated KLF-1 activation and transfer to the nucleus coincides with the peak of somatic mitochondrial biogenesis that occurs around a transition from larval stage L3 to D1. We further show that KLF-1 activates genes involved in the xenobiotic detoxification programme and identified cytochrome P450 oxidases, the KLF-1 main effectors, as longevity-assurance factors of mitochondrial mutants. Collectively, these findings underline the importance of the xenobiotic detoxification in the mitohormetic, longevity assurance pathway and identify KLF-1 as a central factor in orchestrating this response.	12	26351	Herholz M	Herholz M, Cepeda E, Baumann L, Kukat A, Hermeling J, Maciej S, Szczepanowska K, Pavlenko V, Frommolt P, Trifunovic A	KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants.	Nat Commun	2019	WBPaper00059194:isp-1(qm150);ctb-1(qm189)_klf-1(RNAi)-post-L4_rep1~WBPaper00059194:isp-1(qm150);ctb-1(qm189)_klf-1(RNAi)-post-L4_rep2~WBPaper00059194:isp-1(qm150);ctb-1(qm189)_klf-1(RNAi)-post-L4_rep3~WBPaper00059194:isp-1(qm150);ctb-1(qm189)_klf-1(RNAi)-pre-L4_rep1~WBPaper00059194:isp-1(qm150);ctb-1(qm189)_klf-1(RNAi)-pre-L4_rep2~WBPaper00059194:isp-1(qm150);ctb-1(qm189)_klf-1(RNAi)-pre-L4_rep3~WBPaper00059194:isp-1(qm150);ctb-1(qm189)_control_rep1~WBPaper00059194:isp-1(qm150);ctb-1(qm189)_control_rep2~WBPaper00059194:isp-1(qm150);ctb-1(qm189)_control_rep3~WBPaper00059194:N2_control_rep1~WBPaper00059194:N2_control_rep2~WBPaper00059194:N2_control_rep3	Method: microarray|Species: Caenorhabditis elegans
208	32160530	WBPaper00059406.ce.mr.paper	GSE119917	GPL19230	1	Intestine-to-Germline Transmission of Epigenetic Information Intergenerationally Ensures Systemic Stress Resistance in C.elegans.	Changes in epigenetic states affect organismal homeostasis, including stress resistance. However, the mechanisms coordinating epigenetic states and systemic stress resistance remain largely unknown. Here, we identify the intestine-to-germline communication of epigenetic states, which intergenerationally enhances stress resistance in C.elegans. The alterations in epigenetic states by deficiency of the histone H3K4me3 modifier ASH-2 in the intestine or germline increase organismal stress resistance, which is abrogated by knockdown of the H3K4 demethylase RBR-2. Remarkably, the increase in stress resistance induced by ASH-2 deficiency in the intestine is abrogated by RBR-2 knockdown in the germline, suggesting the intestine-to-germline transmission of epigenetic information. This communication from intestine to germline in the parental generation increases stress resistance in the next generation. Moreover, the intertissue communication is mediated partly by transcriptional regulation of F08F1.3. These results reveal that intertissue communication of epigenetic information provides mechanisms forintergenerational regulation of systemic stress resistance.	8	26351	Nono M	Nono M, Kishimoto S, Sato-Carlton A, Carlton PM, Nishida E, Uno M	Intestine-to-Germline Transmission of Epigenetic Information Intergenerationally Ensures Systemic Stress Resistance in C.elegans.	Cell Rep	2020	WBPaper00059406:N2_control~WBPaper00059406:N2_ash-2(RNAi)~WBPaper00059406:VP303_control~WBPaper00059406:VP303_ash-2(RNAi)~WBPaper00059406:NR350_control~WBPaper00059406:NR350_ash-2(RNAi)~WBPaper00059406:TU3401_control~WBPaper00059406:TU3401_ash-2(RNAi)	Method: microarray|Species: Caenorhabditis elegans
209	32282804	WBPaper00059541.ce.mr.paper	GSE137355	GPL19230	1	C9orf72/ALFA-1 controls TFEB/HLH-30-dependent metabolism through dynamic regulation ofrag GTPases.	Nutrient utilization and energy metabolism are critical for the maintenance of cellular homeostasis. A mutation in the C9orf72 gene has been linked to the most common forms of neurodegenerative diseases that include amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we have identified an evolutionarily conserved function of C9orf72 in the regulation of the transcription factor EB (TFEB), a master regulator of autophagic and lysosomal genes that is negatively modulated by mTORC1. Loss of the C. elegans orthologue of C9orf72, ALFA-1, causes the nuclear translocation of HLH-30/TFEB, leading to activation of lipolysis and premature lethality during starvation-induced developmental arrest in C. elegans. A similar conserved pathway exists in human cells, in which C9orf72 regulates mTOR and TFEB signaling. C9orf72 interacts with and dynamically regulates the level of Rag GTPases, which are responsible for the recruitment of mTOR and TFEB on the lysosome upon amino acid signals. These results have revealed previously unknown functions of C9orf72 in nutrient sensing and metabolic pathways and suggest that dysregulation of C9orf72 functions could compromise cellular fitness under conditions of nutrient stress.	16	26351	Ji YJ	Ji YJ, Ugolino J, Zhang T, Lu J, Kim D, Wang J	C9orf72/ALFA-1 controls TFEB/HLH-30-dependent metabolism through dynamic regulation ofrag GTPases.	PLoS Genet	2020	WBPaper00059541:N2_control_rep1~WBPaper00059541:N2_control_rep2~WBPaper00059541:N2_control_rep3~WBPaper00059541:N2_control_rep4~WBPaper00059541:N2_starvation_rep1~WBPaper00059541:N2_starvation_rep2~WBPaper00059541:N2_starvation_rep3~WBPaper00059541:N2_starvation_rep4~WBPaper00059541:alfa-1(ok3062)_control_rep1~WBPaper00059541:alfa-1(ok3062)_control_rep2~WBPaper00059541:alfa-1(ok3062)_control_rep3~WBPaper00059541:alfa-1(ok3062)_control_rep4~WBPaper00059541:alfa-1(ok3062)_starvation_rep1~WBPaper00059541:alfa-1(ok3062)_starvation_rep2~WBPaper00059541:alfa-1(ok3062)_starvation_rep3~WBPaper00059541:alfa-1(ok3062)_starvation_rep4	Method: microarray|Species: Caenorhabditis elegans
210	33392613	WBPaper00060828.ce.mr.paper	GSE149596	GPL19230	1	Perchlorate detection <i>via</i> an invertebrate biosensor.	Improvised explosive devices (IEDs) are constructed from easily obtainable ingredients that are often unregulated and difficult to trace. Salts of the oxyhalide perchlorate are frequently used as oxidisers in IEDs and in commercially available munitions, thus a reliable detection is needed to aid forensic investigations and the tracing of environmental ground or surface water contamination. We introduce the nematode Caenorhabditis elegans as a biosensor for the presence of perchlorate, a promising alternative to the costly, technically challenging and time-consuming current perchlorate detection methods. Perchlorate uptake dynamics in C. elegans were first validated using ion exchange chromatography followed by assessing the effects of perchlorate on key life-point indices to verify the suitability of the nematodes as a forensic biosensor. Whole genome microarrays and qPCR analyses established that a set of immune and stress response genes were enriched during perchlorate exposure. A nematode strain (agIs219) containing an integrated copy of the significantly overexpressed t24b8.5 gene promoter followed by a GFP reporter gene was shown to fluoresce in a perchlorate dose dependent manner with a limit of detection (LOD) of 0.5 mg mL-1. Whilst chemicals commonly used in the construction of IEDs did not induce fluorescence, exposure to other oxyhalides did, highlighting the presence of possible shared stress response pathways. Burnt wire sparklers containing potassium perchlorate elicited fluorescence while other non-perchlorate containing post-blast explosion matrices did not. This demonstrates how C. elegans can be used to screen for perchlorate at environmental hotspots, an optimization, possibly with other target transgenes, is required to enable the detection of perchlorate at concentrations below 0.5 mg mL-1.	6	26351	Alsaleh SA	Alsaleh SA, Barron L, Sturzenbaum S	Perchlorate detection <i>via</i> an invertebrate biosensor.	Anal Methods	2021	WBPaper00060828:control_rep1~WBPaper00060828:control_rep2~WBPaper00060828:control_rep3~WBPaper00060828:Perchlorate_rep1~WBPaper00060828:Perchlorate_rep2~WBPaper00060828:Perchlorate_rep3	Method: microarray|Species: Caenorhabditis elegans
211	33408224	WBPaper00060876.ce.mr.paper	GSE137516	GPL200	1	Novel Immune Modulators Enhance <i>Caenorhabditis elegans</i> Resistance to Multiple Pathogens.	Traditionally, treatments for bacterial infection have focused on killing the microbe or preventing its growth. As antimicrobial resistance becomes more ubiquitous, the feasibility of this approach is beginning to wane and attention has begun to shift toward disrupting the host-pathogen interaction by improving the host defense. Using a high-throughput, fragment-based screen to identify compounds that alleviate <i>Pseudomonas aeruginosa</i>-mediated killing of <i>Caenorhabditis elegans</i>, we identified over 20 compounds that stimulated host defense gene expression. Five of these molecules were selected for further characterization. Four of five compounds showed little toxicity against mammalian cells or worms, consistent with their identification in a phenotypic, high-content screen. Each of the compounds activated several host defense pathways, but the pathways were generally dispensable for compound-mediated rescue in liquid killing, suggesting redundancy or that the activation of unknown pathway(s) may be driving compound effects. A genetic mechanism was identified for LK56, which required the Mediator subunit MDT-15/MED15 and NHR-49/HNF4 for its function. Interestingly, LK32, LK34, LK38, and LK56 also rescued <i>C. elegans</i> from <i>P. aeruginosa</i> in an agar-based assay, which uses different virulence factors and defense mechanisms. Rescue in an agar-based assay for LK38 entirely depended upon the PMK-1/p38 MAPK pathway. Three compounds-LK32, LK34, and LK56-also conferred resistance to <i>Enterococcus faecalis</i>, and the two lattermost, LK34 and LK56, also reduced pathogenesis from <i>Staphylococcus aureus</i> This study supports a growing role for MDT-15 and NHR-49 in immune response and identifies five molecules that have significant potential for use as tools in the investigation of innate immunity.<b>IMPORTANCE</b> Trends moving in opposite directions (increasing antimicrobial resistance and declining novel antimicrobial development) have precipitated a looming crisis: the nearly complete inability to safely and effectively treat bacterial infections. To avert this, new approaches are needed. One idea is to stimulate host defense pathways to improve the clearance of bacterial infection. Here, we describe five small molecules that promote resistance to infectious bacteria by activating <i>C. elegans</i>' innate immune pathways. Several are effective against both Gram-positive and Gram-negative pathogens. One of the compounds was mapped to the action of MDT-15/MED15 and NHR-49/HNF4, a pair of transcriptional regulators more generally associated with fatty acid metabolism, potentially highlighting a new link between these biological functions. These studies pave the way for future characterization of the anti-infective activity of the molecules in higher organisms and highlight the compounds' potential utility for further investigation of immune modulation as a novel therapeutic approach.	18	17638	Hummell NA	Hummell NA, Revtovich AV, Kirienko NV	Novel Immune Modulators Enhance <i>Caenorhabditis elegans</i> Resistance to Multiple Pathogens.	mSphere	2021	WBPaper00060876:DMSO_repA~WBPaper00060876:DMSO_repB~WBPaper00060876:DMSO_repC~WBPaper00060876:LK32_repA~WBPaper00060876:LK32_repB~WBPaper00060876:LK32_repC~WBPaper00060876:LK34_repA~WBPaper00060876:LK34_repB~WBPaper00060876:LK34_repC~WBPaper00060876:LK35_repA~WBPaper00060876:LK35_repB~WBPaper00060876:LK35_repC~WBPaper00060876:LK38_repA~WBPaper00060876:LK38_repB~WBPaper00060876:LK38_repC~WBPaper00060876:LK56_repA~WBPaper00060876:LK56_repB~WBPaper00060876:LK56_repC	Method: microarray|Species: Caenorhabditis elegans
212	33674585	WBPaper00061115.ce.mr.paper	GSE148325	GPL200	1	Trauma-induced regulation of VHP-1 modulates the cellular response to mechanical stress.	Mechanical stimuli initiate adaptive signal transduction pathways, yet exceeding the cellular capacity to withstand physical stress results in death. The molecular mechanisms underlying trauma-induced degeneration remain unclear. In the nematode C. elegans, we have developed a method to study cellular degeneration in response to mechanical stress caused by blunt force trauma. Herein, we report that physical injury activates the c-Jun kinase, KGB-1, which modulates response elements through the AP-1 transcriptional complex. Among these, we have identified a dual-specificity MAPK phosphatase, VHP-1, as a stress-inducible modulator of neurodegeneration. VHP-1 regulates the transcriptional response to mechanical stress and is itself attenuated by KGB-1-mediated inactivation of a deubiquitinase, MATH-33, and proteasomal degradation. Together, we describe an uncharacterized stress response pathway in C. elegans and identify transcriptional and post-translational components comprising a feedback loop on Jun kinase and phosphatase activity.	15	17638	Egge N	Egge N, Arneaud SLB, Fonseca RS, Zuurbier KR, McClendon J, Douglas PM	Trauma-induced regulation of VHP-1 modulates the cellular response to mechanical stress.	Nat Commun	2021	WBPaper00061115:Day1Adult_uninjured_rep1~WBPaper00061115:Day1Adult_uninjured_rep2~WBPaper00061115:Day1Adult_uninjured_rep3~WBPaper00061115:Day1Adult_injured_rep1~WBPaper00061115:Day1Adult_injured_rep2~WBPaper00061115:Day1Adult_injured_rep3~WBPaper00061115:Day4Adult_uninjured_rep1~WBPaper00061115:Day4Adult_uninjured_rep2~WBPaper00061115:Day4Adult_uninjured_rep3~WBPaper00061115:Day4Adult_injured_rep1~WBPaper00061115:Day4Adult_injured_rep2~WBPaper00061115:Day4Adult_injured_rep3~WBPaper00061115:Day4Adult_injured-4x_rep1~WBPaper00061115:Day4Adult_injured-4x_rep2~WBPaper00061115:Day4Adult_injured-4x_rep3	Method: microarray|Species: Caenorhabditis elegans
213	32957299	WBPaper00061519.ce.mr.paper	GSE145995	GPL19230	1	Ecotoxicogenomic analysis of stress induced on Caenorhabditis elegans in heavy metal contaminated soil after nZVI treatment.	Soil contamination by heavy metals (HMs) is an environmental problem, and nanoremediation by using zero-valent iron nanoparticles (nZVI) has attracted increasing interest. We used ecotoxicological test and global transcriptome analysis with DNA microarrays to assess the suitability of C.elegans as a useful bioindicator to evaluate such strategy of nanoremediation in a highly polluted soil with Pb, Cd and Zn. The HMs produced devastating effect on C.elegans. nZVI treatment reversed this deleterious effect up to day 30 after application, but the reduction in the relative toxicity of HMs was lower at day 120. We stablished gene expression profile in C.elegans exposed to the polluted soil, treated and untreated with nZVI. The percentage of differentially expressed genes after treatment decreases with exposure time. After application of nZVI we found decreased toxicity, but increased biosynthesis of defensive enzymes responsive to oxidative stress. At day 14, when a decrease in toxicity has occurred, genes related to specific heavy metal detoxification mechanisms or to response to metal stress, were down regulated: gst-genes, encoding for glutathione-S-transferase, htm-1 (heavy metal tolerance factor), and pgp-5 and pgp-7, related to stress response to metals. At day 120, we found increased HMs toxicity compared to day 14, whereas the transcriptional oxidative and metal-induced responses were attenuated. These findings indicate that the profiled gene expression in C.elegans may be considered as an indicator of stress response that allows a reliable evaluation of the nanoremediation strategy.	18	26351	Fajardo C	Fajardo C, Martin M, Nande M, Botias P, Garcia-Cantalejo J, Mengs G, Costa G	Ecotoxicogenomic analysis of stress induced on Caenorhabditis elegans in heavy metal contaminated soil after nZVI treatment.	Chemosphere	2020	WBPaper00061519:Control_0-day_rep1~WBPaper00061519:Control_0-day_rep2~WBPaper00061519:Control_0-day_rep3~WBPaper00061519:Control_14-days_rep1~WBPaper00061519:Control_14-days_rep2~WBPaper00061519:Control_14-days_rep3~WBPaper00061519:Control_4-months_rep1~WBPaper00061519:Control_4-months_rep2~WBPaper00061519:Control_4-months_rep3~WBPaper00061519:nZVI-treated-soil_0-day_rep1~WBPaper00061519:nZVI-treated-soil_0-day_rep2~WBPaper00061519:nZVI-treated-soil_0-day_rep3~WBPaper00061519:nZVI-treated-soil_14-days_rep1~WBPaper00061519:nZVI-treated-soil_14-days_rep2~WBPaper00061519:nZVI-treated-soil_14-days_rep3~WBPaper00061519:nZVI-treated-soil_4-months_rep1~WBPaper00061519:nZVI-treated-soil_4-months_rep2~WBPaper00061519:nZVI-treated-soil_4-months_rep3	Method: microarray|Species: Caenorhabditis elegans
214	35453298	WBPaper00064073.ce.mr.paper	GSE195769	GPL19230	1	Aryl Hydrocarbon Receptor-Dependent and -Independent Pathways Mediate Curcumin Anti-Aging Effects.	The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor whose activity can be modulated by polyphenols, such as curcumin. AhR and curcumin have evolutionarily conserved effects on aging. Here, we investigated whether and how the AhR mediates the anti-aging effects of curcumin across species. Using a combination of in vivo, in vitro, and in silico analyses, we demonstrated that curcumin has AhR-dependent or -independent effects in a context-specific manner. We found that in <i>Caenorhabditis elegans</i>, AhR mediates curcumin-induced lifespan extension, most likely through a ligand-independent inhibitory mechanism related to its antioxidant activity. Curcumin also showed AhR-independent anti-aging activities, such as protection against aggregation-prone proteins and oxidative stress in <i>C. elegans</i> and promotion of the migratory capacity of human primary endothelial cells. These AhR-independent effects are largely mediated by the Nrf2/SKN-1 pathway.	20	26351	Brinkmann V	Brinkmann V, Romeo M, Larigot L, Hemmers A, Tschage L, Kleinjohann J, Schiavi A, Steinwachs S, Esser C, Menzel R, Giani Tagliabue S, Bonati L, Cox F, Ale-Agha N, Jakobs P, Altschmied J, Haendeler J, Coumoul X, Ventura N	Aryl Hydrocarbon Receptor-Dependent and -Independent Pathways Mediate Curcumin Anti-Aging Effects.	Antioxidants (Basel)	2022	WBPaper00064073:N2_DMSO_rep1~WBPaper00064073:N2_DMSO_rep2~WBPaper00064073:N2_DMSO_rep3~WBPaper00064073:N2_DMSO_rep4~WBPaper00064073:N2_DMSO_rep5~WBPaper00064073:N2_curcumin_rep1~WBPaper00064073:N2_curcumin_rep2~WBPaper00064073:N2_curcumin_rep3~WBPaper00064073:N2_curcumin_rep4~WBPaper00064073:N2_curcumin_rep5~WBPaper00064073:ahr-1(ju145)_DMSO_rep1~WBPaper00064073:ahr-1(ju145)_DMSO_rep2~WBPaper00064073:ahr-1(ju145)_DMSO_rep3~WBPaper00064073:ahr-1(ju145)_DMSO_rep4~WBPaper00064073:ahr-1(ju145)_DMSO_rep5~WBPaper00064073:ahr-1(ju145)_curcumin_rep1~WBPaper00064073:ahr-1(ju145)_curcumin_rep2~WBPaper00064073:ahr-1(ju145)_curcumin_rep3~WBPaper00064073:ahr-1(ju145)_curcumin_rep4~WBPaper00064073:ahr-1(ju145)_curcumin_rep5	Method: microarray|Species: Caenorhabditis elegans
215	35551180	WBPaper00064182.ce.mr.paper	GSE144573,GSE144574	GPL19230	1	Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans.	Complex-I-deficiency represents the most frequent pathogenetic cause of human mitochondriopathies. Therapeutic options for these neurodevelopmental life-threating disorders do not exist, partly due to the scarcity of appropriate model systems to study them. Caenorhabditis elegans is a genetically tractable model organism widely used to investigate neuronal pathologies. Here, we generate C. elegans models for mitochondriopathies and show that depletion of complex I subunits recapitulates biochemical, cellular and neurodevelopmental aspects of the human diseases. We exploit two models, nuo-5/NDUFS1- and lpd-5/NDUFS4-depleted animals, for a suppressor screening that identifies lutein for its ability to rescue animals' neurodevelopmental deficits. We uncover overexpression of synaptic neuroligin as an evolutionarily conserved consequence of mitochondrial dysfunction, which we find to mediate an early cholinergic defect in C. elegans. We show lutein exerts its beneficial effects by restoring neuroligin expression independently from its antioxidant activity, thus pointing to a possible novel pathogenetic target for the human disease.	12	26351	Maglioni S	Maglioni S, Schiavi A, Melcher M, Brinkmann V, Luo Z, Laromaine A, Raimundo N, Meyer JN, Distelmaier F, Ventura N	Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans.	Nat Commun	2022	WBPaper00064182:N2_repI~WBPaper00064182:N2_repIII~WBPaper00064182:N2_repIV~WBPaper00064182:N2_repV~WBPaper00064182:nuo-5(RNAi)-mild_repI~WBPaper00064182:nuo-5(RNAi)-mild_repIII~WBPaper00064182:nuo-5(RNAi)-mild_repIV~WBPaper00064182:nuo-5(RNAi)-mild_repV~WBPaper00064182:nuo-5(RNAi)-strong_repI~WBPaper00064182:nuo-5(RNAi)-strong_repIII~WBPaper00064182:nuo-5(RNAi)-strong_repIV~WBPaper00064182:nuo-5(RNAi)-strong_repV	Method: microarray|Species: Caenorhabditis elegans
216	36198694	WBPaper00064565.ce.mr.paper	GSE142371	GPL19230	1	Thermosensation in Caenorhabditis elegans is linked to ubiquitin-dependent protein turnover via insulin and calcineurin signalling.	Organismal physiology and survival are influenced by environmental conditions and linked to protein quality control. Proteome integrity is achieved by maintaining an intricate balance between protein folding and degradation. In Caenorhabditis elegans, acute heat stress determines cell non-autonomous regulation of chaperone levels. However, how the perception of environmental changes, including physiological temperature, affects protein degradation remains largely unexplored. Here, we show that loss-of-function of dyf-1 in Caenorhabditis elegans associated with dysfunctional sensory neurons leads to defects in both temperature perception and thermal adaptation of the ubiquitin/proteasome system centered on thermosensory AFD neurons. Impaired perception of moderate temperature changes worsens ubiquitin-dependent proteolysis in intestinal cells. Brain-gut communication regulating protein turnover is mediated by upregulation of the insulin-like peptide INS-5 and inhibition of the calcineurin-regulated forkhead-box transcription factor DAF-16/FOXO. Our data indicate that perception of ambient temperature and its neuronal integration is important for the control of proteome integrity in complex organisms.	8	26351	Segref A	Segref A, Vakkayil KL, Padvitski T, Li Q, Kroef V, Lormann J, Korner L, Finger F, Hoppe T	Thermosensation in Caenorhabditis elegans is linked to ubiquitin-dependent protein turnover via insulin and calcineurin signalling.	Nat Commun	2022	WBPaper00064565:dyf-1(mn335)_rep1~WBPaper00064565:dyf-1(mn335)_rep2~WBPaper00064565:dyf-1(mn335)_rep3~WBPaper00064565:dyf-1(mn335)_rep4~WBPaper00064565:N2_rep1~WBPaper00064565:N2_rep2~WBPaper00064565:N2_rep3~WBPaper00064565:N2_rep4	Method: microarray|Species: Caenorhabditis elegans
217	36611979	WBPaper00064957.ce.mr.paper	GSE201599	GPL19230	1	Transcriptomic Analysis Reveals JAK2/MPL-Independent Effects of Calreticulin Mutations in a C. elegans Model.	There is growing evidence that Ph-negative myeloproliferative neoplasms (MPNs) are disorders in which multiple molecular mechanisms are significantly disturbed. Since their discovery, CALR driver mutations have been demonstrated to trigger pathogenic mechanisms apart from the well-documented activation of JAK2/MPL-related pathways, but the lack of experimental models harboring CALR mutations in a JAK2/MPL knockout background has hindered the research on these non-canonical mechanisms. In this study, CRISPR/Cas9 was performed to introduce homozygous patient-like calreticulin mutations in a C. elegans model that naturally lacks JAK2 and MPL orthologs. Whole-genome transcriptomic analysis of these worms was conducted, and some of the genes identified to be associated with processes involved in the pathogenesis of MPNs were further validated by qPCR. Some of the transcriptomic alterations corresponded to typically altered genes and processes in cancer and Ph-negative MPN patients that are known to be triggered by mutant calreticulin without the intervention of JAK2/MPL. However, interestingly, we have also found altered other processes described in these diseases that had not been directly attributed to calreticulin mutations without the intervention of JAK2 or MPL. Thus, these results point to a new experimental model for the study of the JAK2/MPL-independent mechanisms of mutant calreticulin that induce these biological alterations, which could be useful to study unknown non-canonical effects of the mutant protein. The comparison with a calreticulin null strain revealed that the alteration of all of these processes seems to be a consequence of a loss of function of mutant calreticulin in the worm, except for the dysregulation of Hedgehog signaling and flh-3. Further analysis of this model could help to delineate these mechanisms, and the verification of these results in mammalian models may unravel new potential therapeutic targets in MPNs. As far as we know, this is the first time that a C. elegans strain with patient-like mutations is proposed as a potential model for leukemia research.	10	26351	Guijarro-Hernandez A	Guijarro-Hernandez A, Eder-Azanza L, Hurtado C, Navarro-Herrera D, Ezcurra B, Novo FJ, Cabello J, Vizmanos JL	Transcriptomic Analysis Reveals JAK2/MPL-Independent Effects of Calreticulin Mutations in a C. elegans Model.	Cells	2023	WBPaper00064957:crt-1(knu358)_rep1~WBPaper00064957:crt-1(knu358)_rep2~WBPaper00064957:crt-1(jvp1)_rep1~WBPaper00064957:crt-1(jvp1)_rep2~WBPaper00064957:crt-1(jvp1)_rep3~WBPaper00064957:N2_rep1~WBPaper00064957:N2_rep2~WBPaper00064957:N2_rep3~WBPaper00064957:crt-1(jh101)_rep1~WBPaper00064957:crt-1(jh101)_rep2	Method: microarray|Species: Caenorhabditis elegans
218	37020951	WBPaper00065197.ce.mr.paper	GSE225776	GPL19230	1	Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players.	Excessive iron accumulation or deficiency leads to a variety of pathologies in humans and developmental arrest in the nematode Caenorhabditis elegans. Instead, sub-lethal iron depletion extends C. elegans lifespan. Hypoxia preconditioning protects against severe hypoxia-induced neuromuscular damage across species but it has low feasible application. In this study, we assessed the potential beneficial effects of genetic and chemical interventions acting via mild iron instead of oxygen depletion. We show that limiting iron availability in C. elegans through frataxin silencing or the iron chelator bipyridine, similar to hypoxia preconditioning, protects against hypoxia-, age-, and proteotoxicity-induced neuromuscular deficits. Mechanistically, our data suggest that the beneficial effects elicited by frataxin silencing are in part mediated by counteracting ferroptosis, a form of non-apoptotic cell death mediated by iron-induced lipid peroxidation. This is achieved by impacting on different key ferroptosis players and likely via gpx-independent redox systems. We thus point to ferroptosis inhibition as a novel potential strategy to promote healthy aging.	30	26351	Schiavi A	Schiavi A, Salveridou E, Brinkmann V, Shaik A, Menzel R, Kalyanasundaram S, Nygard S, Nilsen H, Ventura N	Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players.	iScience	2023	WBPaper00065197:N2_day4_rep1~WBPaper00065197:N2_day4_rep2~WBPaper00065197:N2_day4_rep3~WBPaper00065197:N2_day4_rep4~WBPaper00065197:N2_day4_rep5~WBPaper00065197:N2_day7_rep1~WBPaper00065197:N2_day7_rep2~WBPaper00065197:N2_day7_rep3~WBPaper00065197:N2_day7_rep4~WBPaper00065197:N2_day7_rep5~WBPaper00065197:N2_day14_rep1~WBPaper00065197:N2_day14_rep2~WBPaper00065197:N2_day14_rep3~WBPaper00065197:N2_day14_rep4~WBPaper00065197:N2_day14_rep5~WBPaper00065197:frh-1(RNAi)_day4_rep1~WBPaper00065197:frh-1(RNAi)_day4_rep2~WBPaper00065197:frh-1(RNAi)_day4_rep3~WBPaper00065197:frh-1(RNAi)_day4_rep4~WBPaper00065197:frh-1(RNAi)_day4_rep5~WBPaper00065197:frh-1(RNAi)_day7_rep1~WBPaper00065197:frh-1(RNAi)_day7_rep2~WBPaper00065197:frh-1(RNAi)_day7_rep3~WBPaper00065197:frh-1(RNAi)_day7_rep4~WBPaper00065197:frh-1(RNAi)_day7_rep5~WBPaper00065197:frh-1(RNAi)_day14_rep1~WBPaper00065197:frh-1(RNAi)_day14_rep2~WBPaper00065197:frh-1(RNAi)_day14_rep3~WBPaper00065197:frh-1(RNAi)_day14_rep4~WBPaper00065197:frh-1(RNAi)_day14_rep5	Method: microarray|Species: Caenorhabditis elegans
219	37440595	WBPaper00065732.ce.mr.paper	GSE163072	GPL19230	1	Aminopeptidase MNP-1 triggers intestine protease production by activating daf-16 nuclear location to degrade pore-forming toxins in Caenorhabditis elegans.	Pore-forming toxins (PFTs) are effective tools for pathogens infection. By disrupting epithelial barriers and killing immune cells, PFTs promotes the colonization and reproduction of pathogenic microorganisms in their host. In turn, the host triggers defense responses, such as endocytosis, exocytosis, or autophagy. Bacillus thuringiensis (Bt) bacteria produce PFT, known as crystal proteins (Cry) which damage the intestinal cells of insects or nematodes, eventually killing them. In insects, aminopeptidase N (APN) has been shown to act as an important receptor for Cry toxins. Here, using the nematode Caenorhabditis elegans as model, an extensive screening of APN gene family was performed to analyze the potential role of these proteins in the mode of action of Cry5Ba against the nematode. We found that one APN, MNP-1, participate in the toxin defense response, since the mnp-1(ok2434) mutant showed a Cry5Ba hypersensitive phenotype. Gene expression analysis in mnp-1(ok2434) mutant revealed the involvement of two protease genes, F19C6.4 and R03G8.6, that participate in Cry5Ba degradation. Finally, analysis of the transduction pathway involved in F19C6.4 and R03G8.6 expression revealed that upon Cry5Ba exposure, the worms up regulated both protease genes through the activation of the FOXO transcription factor DAF-16, which was translocated into the nucleus. The nuclear location of DAF-16 was found to be dependent on mnp-1 under Cry5Ba treatment. Our work provides evidence of new host responses against PFTs produced by an enteric pathogenic bacterium, resulting in activation of host intestinal proteases that degrade the PFT in the intestine.	8	26351	Chen F	Chen F, Pang C, Zheng Z, Zhou W, Guo Z, Xiao D, Du H, Bravo A, Soberon M, Sun M, Peng D	Aminopeptidase MNP-1 triggers intestine protease production by activating daf-16 nuclear location to degrade pore-forming toxins in Caenorhabditis elegans.	PLoS Pathog	2023	WBPaper00065732:BL21-N2_rep1~WBPaper00065732:BL21-N2_rep2~WBPaper00065732:BL21-mnp-1(ok2434)_rep1~WBPaper00065732:BL21-mnp-1(ok2434)_rep2~WBPaper00065732:Cry5Ba_BL21-N2_rep1~WBPaper00065732:Cry5Ba_BL21-N2_rep2~WBPaper00065732:Cry5Ba_BL21-mnp-1(ok2434)_rep1~WBPaper00065732:Cry5Ba_BL21-mnp-1(ok2434)_rep2	Method: microarray|Species: Caenorhabditis elegans
220	38743782	WBPaper00066920.ce.mr.paper	GSE228851	GPL200	1	Whole genome profiling of short-term hypoxia induced genes and identification of HIF-1 binding sites provide insights into HIF-1 function in Caenorhabditis elegans.	Oxygen is essential to all the aerobic organisms. However, during normal development, disease and homeostasis, organisms are often challenged by hypoxia (oxygen deprivation). Hypoxia-inducible transcription factors (HIFs) are master regulators of hypoxia response and are evolutionarily conserved in metazoans. The homolog of HIF in the genetic model organism C. elegans is HIF-1. In this study, we aimed to understand short-term hypoxia response to identify HIF-1 downstream genes and identify HIF-1 direct targets in C. elegans. The central research questions were: (1) which genes are differentially expressed in response to short-term hypoxia? (2) Which of these changes in gene expression are dependent upon HIF-1 function? (3) Are any of these hif-1-dependent genes essential to survival in hypoxia? (4) Which genes are the direct targets of HIF-1? We combine whole genome gene expression analyses and chromatin immunoprecipitation sequencing (ChIP-seq) experiments to address these questions. In agreement with other published studies, we report that HIF-1-dependent hypoxia-responsive genes are involved in metabolism and stress response. Some HIF-1-dependent hypoxia-responsive genes like efk-1 and phy-2 dramatically impact survival in hypoxic conditions. Genes regulated by HIF-1 and hypoxia overlap with genes responsive to hydrogen sulfide, also overlap with genes regulated by DAF-16. The genomic regions that co-immunoprecipitate with HIF-1 are strongly enriched for genes involved in stress response. Further, some of these potential HIF-1 direct targets are differentially expressed under short-term hypoxia or are differentially regulated by mutations that enhance HIF-1 activity.	24	17638	Feng D	Feng D, Qu L, Powell-Coffman JA	Whole genome profiling of short-term hypoxia induced genes and identification of HIF-1 binding sites provide insights into HIF-1 function in Caenorhabditis elegans.	PLoS One	2024	WBPaper00066920:JAPC01_N2_BioRep1~WBPaper00066920:JAPC02_N2_BioRep2~WBPaper00066920:JAPC03_N2_BioRep3~WBPaper00066920:JAPC04_N2_hypoxia_BioRep1~WBPaper00066920:JAPC05_N2_hypoxia_BioRep2~WBPaper00066920:JAPC06_N2_hypoxia_BioRep3~WBPaper00066920:JAPC07_hif-1(ia04)_BioRep1~WBPaper00066920:JAPC08_hif-1(ia04)_BioRep2~WBPaper00066920:JAPC09_hif-1(ia04)_BioRep3~WBPaper00066920:JAPC10_hif-1(ia04)_hypoxia_BioRep1~WBPaper00066920:JAPC11_hif-1(ia04)_hypoxia_BioRep2~WBPaper00066920:JAPC12_hif-1(ia04)_hypoxia_BioRep3~WBPaper00066920:JAPC13_vhl-1(ok161)_BioRep1~WBPaper00066920:JAPC14_vhl-1(ok161)_BioRep2~WBPaper00066920:JAPC15_vhl-1(ok161)_BioRep3~WBPaper00066920:JAPC16_rhy-1(ok1402)_BioRep1~WBPaper00066920:JAPC17_rhy-1(ok1402)_BioRep2~WBPaper00066920:JAPC18_rhy-1(ok1402)_BioRep3~WBPaper00066920:JAPC19_egl-9(sa307)_BioRep1~WBPaper00066920:JAPC20_egl-9(sa307)_BioRep2~WBPaper00066920:JAPC21_egl-9(sa307)_BioRep3~WBPaper00066920:JAPC22_swan-1(ok267);vhl-1(ok161)_BioRep1~WBPaper00066920:JAPC23_swan-1(ok267);vhl-1(ok161)_BioRep2~WBPaper00066920:JAPC24_swan-1(ok267);vhl-1(ok161)_BioRep3	Method: microarray|Species: Caenorhabditis elegans
221	19416714	WBPaper00033126.ce.mr.paper	GSE15656	GPL7272	2	IRE-1 and HSP-4 contribute to energy homeostasis via fasting-induced lipases in C. elegans.	The endoplasmic reticulum (ER) is an organelle associated with lipid metabolism. However, the involvement of the ER in nutritional status-dependent energy homeostasis is largely unknown. We demonstrate that IRE-1, an ER protein known to be involved in the unfolded protein response, and HSP-4, an ER chaperone, regulate expression of the novel fasting-induced lipases FIL-1 and FIL-2, which induce fat granule hydrolysis upon fasting in C. elegans. RNAi and ectopic expression experiments demonstrated that FIL-1 and FIL-2 are both necessary and sufficient for fasting-induced fat granule breakdown. Failure of ire-1 and hsp-4 mutant animals to hydrolyze fat granules during starvation impaired their motility, which was rescued by glucose supplementation, implicating the importance of ire-1/hsp-4-dependent lipolysis for energy supply from stored fat during fasting. These data suggest that the ER-resident proteins IRE-1 and HSP-4 are key nutritional sensors that modulate expression of inducible lipases to maintain whole-body energy homeostasis in C. elegans.	1	17563	Jo H	Jo H, Shim J, Lee JH, Lee J, Kim JB	IRE-1 and HSP-4 contribute to energy homeostasis via fasting-induced lipases in C. elegans.	Cell Metab	2009	WBPaper00033126:synchronized_L4_fasted	Method: microarray|Species: Caenorhabditis elegans|Topic: obsolete mRNA splicing via endonucleolytic cleavage and ligation involved in unfolded protein response|Topic: endoplasmic reticulum unfolded protein response|Topic: endoplasmic reticulum|Topic: response to unfolded protein|Topic: mitochondrion|Topic: cytosol
222	19460346	WBPaper00033206.ce.mr.paper	GSE14913	GPL8209	1	The polycomb complex protein mes-2/E(z) promotes the transition from developmental plasticity to differentiation in C. elegans embryos.	We have used expression profiling and in vivo imaging to characterize Caenorhabditis elegans embryos as they transit from a developmentally plastic state to the onset of differentiation. Normally, this transition is accompanied by activation of developmental regulators and differentiation genes, downregulation of early-expressed genes, and large-scale reorganization of chromatin. We find that loss of plasticity and differentiation onset depends on the Polycomb complex protein mes-2/E(Z). mes-2 mutants display prolonged developmental plasticity in response to heterologous developmental regulators. Early-expressed genes remain active, differentiation genes fail to reach wild-type levels, and chromatin retains a decompacted morphology in mes-2 mutants. By contrast, loss of the developmental regulators pha-4/FoxA or end-1/GATA does not prolong plasticity. This study establishes a model by which to analyze developmental plasticity within an intact embryo. mes-2 orchestrates large-scale changes in chromatin organization and gene expression to promote the timely loss of developmental plasticity. Our findings indicate that loss of plasticity can be uncoupled from cell fate specification.	21	17563	Yuzyuk T	Yuzyuk T, Fakhouri TH, Kiefer J, Mango SE	The polycomb complex protein mes-2/E(z) promotes the transition from developmental plasticity to differentiation in C. elegans embryos.	Dev Cell	2009	WBPaper00033206:WT_embryo_2-cell_1~WBPaper00033206:WT_embryo_2-cell_2~WBPaper00033206:WT_embryo_2-cell_3~WBPaper00033206:WT_embryo_2E_1~WBPaper00033206:WT_embryo_2E_2~WBPaper00033206:WT_embryo_2E_3~WBPaper00033206:WT_embryo_4E_1~WBPaper00033206:WT_embryo_4E_2~WBPaper00033206:WT_embryo_4E_3~WBPaper00033206:WT_embryo_8E_1~WBPaper00033206:WT_embryo_8E_2~WBPaper00033206:WT_embryo_8E_3~WBPaper00033206:mes-2_embryo_2E_1~WBPaper00033206:mes-2_embryo_2E_2~WBPaper00033206:mes-2_embryo_2E_3~WBPaper00033206:mes-2_embryo_4E_1~WBPaper00033206:mes-2_embryo_4E_2~WBPaper00033206:mes-2_embryo_4E_3~WBPaper00033206:mes-2_embryo_8E_1~WBPaper00033206:mes-2_embryo_8E_2~WBPaper00033206:mes-2_embryo_8E_3	Method: microarray|Species: Caenorhabditis elegans
223	19745112	WBPaper00035187.cbg.mr.paper	GSE15234,GSE15551	GPL8304,GPL8303	1	Comparison of diverse developmental transcriptomes reveals that coexpression of gene neighbors is not evolutionarily conserved.	Genomic analyses have shown that adjacent genes are often coexpressed. However, it remains unclear whether the observed coexpression is a result of functional organization or a consequence of adjacent active chromatin or transcriptional read-through, which may be free of selective biases. Here, we compare temporal expression profiles of one-to-one orthologs in conserved or divergent genomic positions in two genetically distant nematode species-Caenorhabditis elegans and C. briggsae-that share a near-identical developmental program. We find, for all major patterns of temporal expression, a substantive amount of gene expression divergence. However, this divergence is not random: Genes that function in essential developmental processes show less divergence than genes whose functions are not required for viability. Coexpression of gene neighbors in either species is highly divergent in the other, in particular when the neighborhood is not conserved. Interestingly, essential genes appear to maintain their expression profiles despite changes in neighborhoods suggesting exposure to stronger selection. Our results suggest that a significant fraction of the coexpression observed among gene neighbors may be accounted for by neutral processes, and further that these may be distinguished by comparative gene expression analyses.	13	17014	Yanai I	Yanai I, Hunter CP	Comparison of diverse developmental transcriptomes reveals that coexpression of gene neighbors is not evolutionarily conserved.	Genome Res	2009	WBPaper00035187:CB_4-cell_AF16_Rep_A~WBPaper00035187:CB_4-cell_AF16_Rep_B~WBPaper00035187:CB_28-cell_AF16_Rep_A~WBPaper00035187:CB_28-cell_AF16_Rep_B~WBPaper00035187:CB_55-cell_AF16_Rep_A~WBPaper00035187:CB_55-cell_AF16_Rep_B~WBPaper00035187:CB_95-cell_AF16_Rep_A~WBPaper00035187:CB_190-cell_AF16_Rep_A~WBPaper00035187:CB_190-cell_AF16_Rep_B~WBPaper00035187:CB_55-cell_AF16_Rep_C~WBPaper00035187:CB_190-cell_AF16_Rep_C~WBPaper00035187:CB_95-cell_AF16_Rep_B~WBPaper00035187:CB_28-cell_AF16_Rep_C	Method: microarray|Species: Caenorhabditis briggsae
224	19745112	WBPaper00035187.ce.mr.paper	GSE15234,GSE15551	GPL8304,GPL8303	1	Comparison of diverse developmental transcriptomes reveals that coexpression of gene neighbors is not evolutionarily conserved.	Genomic analyses have shown that adjacent genes are often coexpressed. However, it remains unclear whether the observed coexpression is a result of functional organization or a consequence of adjacent active chromatin or transcriptional read-through, which may be free of selective biases. Here, we compare temporal expression profiles of one-to-one orthologs in conserved or divergent genomic positions in two genetically distant nematode species-Caenorhabditis elegans and C. briggsae-that share a near-identical developmental program. We find, for all major patterns of temporal expression, a substantive amount of gene expression divergence. However, this divergence is not random: Genes that function in essential developmental processes show less divergence than genes whose functions are not required for viability. Coexpression of gene neighbors in either species is highly divergent in the other, in particular when the neighborhood is not conserved. Interestingly, essential genes appear to maintain their expression profiles despite changes in neighborhoods suggesting exposure to stronger selection. Our results suggest that a significant fraction of the coexpression observed among gene neighbors may be accounted for by neutral processes, and further that these may be distinguished by comparative gene expression analyses.	16	18782	Yanai I	Yanai I, Hunter CP	Comparison of diverse developmental transcriptomes reveals that coexpression of gene neighbors is not evolutionarily conserved.	Genome Res	2009	WBPaper00035187:CE_95-cell_N2_Rep_A~WBPaper00035187:CE_55-cell_N2_Rep_A~WBPaper00035187:CE_28-cell_N2_Rep_A~WBPaper00035187:CE_4-cell_N2_Rep_A~WBPaper00035187:CE_4-cell_N2_Rep_B~WBPaper00035187:CE_4-cell_CB4856_Rep_A~WBPaper00035187:CE_190-cell_N2_Rep_A~WBPaper00035187:CE_190-cell_N2_Rep_B~WBPaper00035187:CE_95-cell_N2_Rep_B~WBPaper00035187:CE_55-cell_N2_Rep_B~WBPaper00035187:CE_28-cell_N2_Rep_B~WBPaper00035187:CE_28-cell_N2_Rep_C~WBPaper00035187:CE_4-cell_N2_Rep_C~WBPaper00035187:CE_4-cell_CB4856_Rep_B~WBPaper00035187:CE_4-cell_CB4856_Rep_C~WBPaper00035187:CE_95-cell_N2_Rep_C	Method: microarray|Species: Caenorhabditis elegans
225	19804759	WBPaper00035269.ce.mr.paper	GSE18202	GPL2875	2	CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs.	We have studied the function of a conserved germline-specific nucleotidyltransferase protein, CDE-1, in RNAi and chromosome segregation in C. elegans. CDE-1 localizes specifically to mitotic chromosomes in embryos. This localization requires the RdRP EGO-1, which physically interacts with CDE-1, and the Argonaute protein CSR-1. We found that CDE-1 is required for the uridylation of CSR-1 bound siRNAs, and that in the absence of CDE-1 these siRNAs accumulate to inappropriate levels, accompanied by defects in both meiotic and mitotic chromosome segregation. Elevated siRNA levels are associated with erroneous gene silencing, most likely through the inappropriate loading of CSR-1 siRNAs into other Argonaute proteins. We propose a model in which CDE-1 restricts specific EGO-1-generated siRNAs to the CSR-1 mediated, chromosome associated RNAi pathway, thus separating it from other endogenous RNAi pathways. The conserved nature of CDE-1 suggests that similar sorting mechanisms may operate in other animals, including mammals.	4	5940	van Wolfswinkel JC	van Wolfswinkel JC, Claycomb JM, Batista PJ, Mello CC, Berezikov E, Ketting RF	CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs.	Cell	2009	WBPaper00035269:N2_vs_cde-1_young_adults~WBPaper00035269:cde-1_vs_N2_young_adults~WBPaper00035269:N2_vs_cde-1_aged_adults~WBPaper00035269:cde-1_vs_N2_aged_adults	Method: microarray|Species: Caenorhabditis elegans
226	20386745	WBPaper00036130.ce.mr.paper	GSE20558	GPL8209	2	MicroRNA-directed siRNA biogenesis in Caenorhabditis elegans.	RNA interference (RNAi) is a post-transcriptional silencing process, triggered by double-stranded RNA (dsRNA), leading to the destabilization of homologous mRNAs. A distinction has been made between endogenous RNAi-related pathways and the exogenous RNAi pathway, the latter being essential for the experimental use of RNAi. Previous studies have shown that, in Caenorhabditis elegans, a complex containing the enzymes Dicer and the Argonaute RDE-1 process dsRNA. Dicer is responsible for cleaving dsRNA into short interfering RNAs (siRNAs) while RDE-1 acts as the siRNA acceptor. RDE-1 then guides a multi-protein complex to homologous targets to trigger mRNA destabilization. However, endogenous role(s) for RDE-1, if any, have remained unexplored. We here show that RDE-1 functions as a scavenger protein, taking up small RNA molecules from many different sources, including the microRNA (miRNA) pathway. This is in striking contrast to Argonaute proteins functioning directly in the miRNA pathway, ALG-1 and ALG-2: these proteins exclusively bind miRNAs. While playing no significant role in the biogenesis of the main pool of miRNAs, RDE-1 binds endogenous miRNAs and triggers RdRP activity on at least one perfectly matching, endogenous miRNA target. The resulting secondary siRNAs are taken up by a set of Argonaute proteins known to act as siRNA acceptors in exogenous RNAi, resulting in strong mRNA destabilization. Our results show that RDE-1 in an endogenous setting is actively screening the transcriptome using many different small RNAs, including miRNAs, as a guide, with implications for the evolution of transcripts with a potential to be recognized by Dicer.	6	17563	Correa RL	Correa RL, Steiner FA, Berezikov E, Ketting RF	MicroRNA-directed siRNA biogenesis in Caenorhabditis elegans.	PLoS Genet	2010	WBPaper00036130:mir-243_vs_N2_Rep1~WBPaper00036130:N2_vs_mir-243_Rep1~WBPaper00036130:mir-243_vs_N2_Rep2~WBPaper00036130:N2_vs_mir-243_Rep2~WBPaper00036130:mir-243_vs_N2_Rep3~WBPaper00036130:N2_vs_mir-243_Rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: regulation of pre-miRNA processing|Topic: regulation of primary miRNA processing|Topic: miRNA processing
227	20460307	WBPaper00036256.ce.mr.paper	GSE20148	GPL8209	2	Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity.	When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.	8	17446	Henis-Korenblit S	Henis-Korenblit S, Zhang P, Hansen M, McCormick M, Lee SJ, Cary M, Kenyon C	Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity.	Proc Natl Acad Sci U S A	2010	WBPaper00036256:daf-2(e1368)_xbp-1_vs_daf-2(e1368)_rep1~WBPaper00036256:daf-2(e1368)_xbp-1_vs_daf-2(e1368)_rep2~WBPaper00036256:daf-2(e1368)_xbp-1_vs_daf-2(e1368)_rep3~WBPaper00036256:daf-2(e1368)_xbp-1_vs_daf-2(e1368)_rep4~WBPaper00036256:daf-2(e1370)_xbp-1_vs_daf-2(e1370)_rep1~WBPaper00036256:daf-2(e1370)_xbp-1_vs_daf-2(e1370)_rep2~WBPaper00036256:daf-2(e1370)_xbp-1_vs_daf-2(e1370)_rep3~WBPaper00036256:daf-2(e1370)_xbp-1_vs_daf-2(e1370)_rep4	Method: microarray|Species: Caenorhabditis elegans|Topic: obsolete mRNA splicing via endonucleolytic cleavage and ligation involved in unfolded protein response|Topic: endoplasmic reticulum unfolded protein response|Topic: endoplasmic reticulum
228	20862312	WBPaper00037624.ce.mr.paper	GSE21851	GPL7272	2	ETS-4 is a transcriptional regulator of life span in Caenorhabditis elegans.	Aging is a complex phenotype responsive to a plethora of environmental inputs; yet only a limited number of transcriptional regulators are known to influence life span. How the downstream expression programs mediated by these factors (or others) are coordinated into common or distinct set of aging effectors is an addressable question in model organisms, such as C. elegans. Here, we establish the transcription factor ETS-4, an ortholog of vertebrate SPDEF, as a longevity determinant. Adult worms with ets-4 mutations had a significant extension of mean life span. Restoring ETS-4 activity in the intestine, but not neurons, of ets-4 mutant worms rescued life span to wild-type levels. Using RNAi, we demonstrated that ets-4 is required post-developmentally to regulate adult life span; thus uncoupling the role of ETS-4 in aging from potential functions in worm intestinal development. Seventy ETS-4-regulated genes, identified by gene expression profiling of two distinct ets-4 alleles and analyzed by bioinformatics, were enriched for known longevity effectors that function in lipid transport, lipid metabolism, and innate immunity. Putative target genes were enriched for ones that change expression during normal aging, the majority of which are controlled by the GATA factors. Also, some ETS-4-regulated genes function downstream of the FOXO factor, DAF-16 and the insulin/IGF-1 signaling pathway. However, epistasis and phenotypic analyses indicate that ets-4 functioned in parallel to the insulin/IGF-1 receptor, daf-2 and akt-1/2 kinases. Furthermore, ets-4 required daf-16 to modulate aging, suggesting overlap in function at the level of common targets that affect life span. In conclusion, ETS-4 is a new transcriptional regulator of aging, which shares transcriptional targets with GATA and FOXO factors, suggesting that overlapping pathways direct common sets of lifespan-related genes.	6	17563	Thyagarajan B	Thyagarajan B, Blaszczak AG, Chandler KJ, Watts JL, Johnson WE, Graves BJ	ETS-4 is a transcriptional regulator of life span in Caenorhabditis elegans.	PLoS Genet	2010	WBPaper00037624:N2_vs_ok165_rep1~WBPaper00037624:N2_vs_uz1_rep1~WBPaper00037624:N2_vs_ok165_rep2~WBPaper00037624:N2_vs_uz1_rep2~WBPaper00037624:N2_vs_ok165_rep3~WBPaper00037624:N2_vs_uz1_rep3	Method: microarray|Species: Caenorhabditis elegans
229	20947766	WBPaper00037680.ce.mr.paper	GSE23857	GPL7727	2	Selection at linked sites shapes heritable phenotypic variation in C. elegans.	Mutation generates the heritable variation that genetic drift and natural selection shape. In classical quantitative genetic models, drift is a function of the effective population size and acts uniformly across traits, whereas mutation and selection act trait-specifically. We identified thousands of quantitative trait loci (QTLs) influencing transcript abundance traits in a cross of two Caenorhabditis elegans strains; although trait-specific mutation and selection explained some of the observed pattern of QTL distribution, the pattern was better explained by trait-independent variation in the intensity of selection on linked sites. Our results suggest that traits in C. elegans exhibit different levels of variation less because of their own attributes than because of differences in the effective population sizes of the genomic regions harboring their underlying loci.	208	17321	Rockman MV	Rockman MV, Skrovanek SS, KRUGLYAK L	Selection at linked sites shapes heritable phenotypic variation in C. elegans.	Science	2010	WBPaper00037680:Strain_QX1_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX194_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX195_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX197_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX199_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX200_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX202_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX203_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX204_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX209_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX20_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX21_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX212_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX213_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX216_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX217_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX220_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX222_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX223_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX224_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX226_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX227_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX228_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX233_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX235_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX25_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX26_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX28_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX29_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX30_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX31_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX32_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX33_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX37_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX3_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX41_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX44_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX45_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX47_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX48_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX51_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX52_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX53_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX56_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX4_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX58_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX60_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX64_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX65_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX66_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX67_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX68_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX69_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX70_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX72_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX74_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX6_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX81_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX82_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX83_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX85_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX86_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX87_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX88_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX90_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX91_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX93_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX94_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX98_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX103_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX107_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX108_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX111_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX113_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX115_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX11_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX119_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX120_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX121_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX128_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX132_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX134_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX13_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX135_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX136_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX140_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX141_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX142_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX144_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX145_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX148_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX150_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX151_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX154_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX15_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX158_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX159_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX161_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX162_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX164_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX165_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX166_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX167_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX168_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX169_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX170_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX172_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX174_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX16_Cy5_vs_CommonReference_Cy3~WBPaper00037680:Strain_QX19_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX196_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX198_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX205_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX206_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX207_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX208_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX210_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX211_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX214_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX215_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX218_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX221_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX22_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX225_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX229_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX230_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX231_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX232_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX234_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX236_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX24_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX237_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX27_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX34_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX38_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX2_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX39_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX40_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX42_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX43_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX49_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX54_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX55_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX5_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX59_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX61_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX62_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX63_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX71_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX73_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX76_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX77_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX7_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX78_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX79_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX80_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX84_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX92_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX95_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX8_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX9_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX96_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX97_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX99_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX100_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX101_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX102_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX104_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX106_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX109_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX112_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX114_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX10_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX117_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX124_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX125_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX127_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX129_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX131_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX133_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX12_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX137_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX138_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX139_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX143_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX147_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX149_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX153_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX14_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX156_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX157_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX160_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX163_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX171_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX173_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX177_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX178_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX179_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX180_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX181_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX182_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX183_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX184_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX185_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX187_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX189_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX192_Cy3_vs_CommonReference_Cy5~WBPaper00037680:Strain_QX193_Cy3_vs_CommonReference_Cy5	Method: microarray|Species: Caenorhabditis elegans
230	20946987	WBPaper00037682.ce.mr.paper	GSE23446,GSE23447,GSE23448,GSE23509	GPL7727	2	TGF- and insulin signaling regulate reproductive aging via oocyte and germline quality maintenance.	Reproductive cessation is perhaps the earliest aging phenotype that humans experience. Similarly, reproduction of Caenorhabditis elegans ceases in mid-adulthood. Although somatic aging has been studied in both worms and humans, mechanisms regulating reproductive aging are not yet understood. Here, we show that TGF- Sma/Mab and Insulin/IGF-1 signaling regulate C. elegans reproductive aging by modulating multiple aspects of the reproductive process, including embryo integrity, oocyte fertilizability, chromosome segregation fidelity, DNA damage resistance, and oocyte and germline morphology. TGF- activity regulates reproductive span and germline/oocyte quality noncell-autonomously and is temporally and transcriptionally separable from its regulation of growth. Chromosome segregation, cell cycle, and DNA damage response genes are upregulated in TGF- mutant oocytes, decline in aged mammalian oocytes, and are critical for oocyte quality maintenance. Our data suggest that C. elegans and humans share many aspects of reproductive aging, including the correlation between reproductive aging and declining oocyte quality and mechanisms determining oocyte quality.	17	17321	Luo S	Luo S, Kleemann GA, Ashraf JM, Shaw WM, Murphy CT	TGF- and insulin signaling regulate reproductive aging via oocyte and germline quality maintenance.	Cell	2010	WBPaper00037682:sma-2;fem-1_oocyte_D8_vs_fem-1_oocyte_D8_rep1_SL2.6.09~WBPaper00037682:sma-2;fem-1_oocyte_D8_vs_fem-1_oocyte_D8_rep2_SL2.6.09~WBPaper00037682:sma-2;fem-1_oocyte_D8_vs_fem-1_oocyte_D8_rep3_SL2.6.09~WBPaper00037682:sma-2;fem-1_oocyte_D8_vs_fem-1_oocyte_D8_rep4_SL2.6.09~WBPaper00037682:sma-2;fem-1_oocyte_D8_vs_fem-1_oocyte_D8_rep5_SL2.6.09~WBPaper00037682:sma-2;fem-1_oocyte_D8_vs_fem-1_oocyte_D8_rep6_SL2.6.09~WBPaper00037682:sma-2;fem-1_oocyte_D8_vs_fem-1_oocyte_D8_rep8_SL2.6.09~WBPaper00037682:sma-2;fem-1_oocyte_D8_vs_fem-1_oocyte_D8_rep9_SL2.6.09~WBPaper00037682:sma-2x3_L4_vs_N2_L4_rep1_WS_4.6.07~WBPaper00037682:N2_L4_vs_sma-2x3_L4_rep2_DF_WS_4.6.07~WBPaper00037682:sma-2x3_L4_vs_N2_L4_rep3_WS_4.6.07~WBPaper00037682:sma-4(e729)_L4_vs_N2_L4_rep1_WS_4.10.7~WBPaper00037682:fem-1_oocyte_D3_vs_fem-1_oocyte_D8_rep3_SL9.13.08~WBPaper00037682:fem-1_oocyte_D3_vs_fem-1_oocyte_D8_rep5_SL12.02.08~WBPaper00037682:fem-1_oocyte_D3_vs_fem-1_oocyte_D8_rep6_SL12.02.08~WBPaper00037682:fem-1_oocyte_D3_vs_fem-1_oocyte_D8_rep7_SL12.02.08~WBPaper00037682:fem-1_oocyte_D3_vs_fem-1_oocyte_D8_rep8_SL12.02.08	Method: microarray|Species: Caenorhabditis elegans|Topic: programmed cell death|Topic: apoptotic DNA fragmentation|Topic: apoptotic process|Topic: engulfment of apoptotic cell|Tissue Specific
231	21408062	WBPaper00038237.ce.mr.paper	GSE18200	GPL2875	2	Co-regulation of the DAF-16 target gene, cyp-35B1/dod-13, by HSF-1 in C. elegans dauer larvae and daf-2 insulin pathway mutants.	Insulin/IGF-I-like signaling (IIS) has both cell autonomous and non-autonomous functions. In some cases, targets through which IIS regulates cell-autonomous functions, such as cell growth and metabolism, have been identified. In contrast, targets for many non-autonomous IIS functions, such as C. elegans dauer morphogenesis, remain elusive. Here, we report the use of genomic and genetic approaches to identify potential non-autonomous targets of C. elegans IIS. First, we used transcriptional microarrays to identify target genes regulated non-autonomously by IIS in the intestine or in neurons. C. elegans IIS controls expression of a number of stress response genes, which were differentially regulated by tissue-restricted IIS. In particular, expression of sod-3, a MnSOD enzyme, was not regulated by tissue-restricted IIS on the microarrays, while expression of hsp-16 genes was rescued back to wildtype by tissue restricted IIS. One IIS target regulated non-autonomously by age-1 was cyp-35B1/dod-13, encoding a cytochrome P450. Genetic analysis of the cyp-35B1 promoter showed both DAF-16 and HSF-1 are direct regulators. Based on these findings, we propose that hsf-1 may participate in the pathways mediating non-autonomous activities of age-1 in C. elegans.	8	4864	Iser WB	Iser WB, Wilson MA, Wood WH, Becker K, Wolkow CA	Co-regulation of the DAF-16 target gene, cyp-35B1/dod-13, by HSF-1 in C. elegans dauer larvae and daf-2 insulin pathway mutants.	PLoS One	2011	WBPaper00038237:age-1(mg44)_rep1~WBPaper00038237:intestine_age-1_rep1~WBPaper00038237:neuron_age-1_rep1~WBPaper00038237:age-1(mg44)_rep2~WBPaper00038237:intestine_age-1_rep2~WBPaper00038237:neuron_age-1_rep2~WBPaper00038237:intestine_age-1_rep3~WBPaper00038237:neuron_age-1_rep3	Method: microarray|Species: Caenorhabditis elegans
232	21673804	WBPaper00038519.ce.mr.paper	GSE27288	GPL13164	1	The effectiveness of RNAi in Caenorhabditis elegans is maintained during spaceflight.	BACKGROUND: Overcoming spaceflight-induced (patho)physiologic adaptations is a major challenge preventing long-term deep space exploration. RNA interference (RNAi) has emerged as a promising therapeutic for combating diseases on Earth; however the efficacy of RNAi in space is currently unknown. METHODS: Caenorhabditis elegans were prepared in liquid media on Earth using standard techniques and treated acutely with RNAi or a vector control upon arrival in Low Earth Orbit. After culturing during 4 and 8 d spaceflight, experiments were stopped by freezing at -80C until analysis by mRNA and microRNA array chips, microscopy and Western blot on return to Earth. Ground controls (GC) on Earth were simultaneously grown under identical conditions. RESULTS: After 8 d spaceflight, mRNA expression levels of components of the RNAi machinery were not different from that in GC (e.g., Dicer, Argonaute, Piwi; P&gt;0.05). The expression of 228 microRNAs, of the 232 analysed, were also unaffected during 4 and 8 d spaceflight (P&gt;0.05). In spaceflight, RNAi against green fluorescent protein (gfp) reduced chromosomal gfp expression in gonad tissue, which was not different from GC. RNAi against rbx-1 also induced abnormal chromosome segregation in the gonad during spaceflight as on Earth. Finally, culture in RNAi against lysosomal cathepsins prevented degradation of the muscle-specific -actin protein in both spaceflight and GC conditions. CONCLUSIONS: Treatment with RNAi works as effectively in the space environment as on Earth within multiple tissues, suggesting RNAi may provide an effective tool for combating spaceflight-induced pathologies aboard future long-duration space missions. Furthermore, this is the first demonstration that RNAi can be utilised to block muscle protein degradation, both on Earth and in space.	18	16257	Etheridge T	Etheridge T, Nemoto K, Hashizume T, Mori C, Sugimoto T, Suzuki H, Fukui K, Yamazaki T, Higashibata A, Szewczyk NJ, Higashitani A	The effectiveness of RNAi in Caenorhabditis elegans is maintained during spaceflight.	PLoS One	2011	WBPaper00038519:C.elegans_8days_1G_rep1-2~WBPaper00038519:C.elegans_8days_1G_rep2-2~WBPaper00038519:C.elegans_8days_1G_rep3-2~WBPaper00038519:C.elegans_8days_microG_rep1-2~WBPaper00038519:C.elegans_8days_microG_rep2-2~WBPaper00038519:C.elegans_8days_microG_rep3-2~WBPaper00038519:C.elegans_8days_GC_rep1-2~WBPaper00038519:C.elegans_8days_GC_rep2-2~WBPaper00038519:C.elegans_8days_GC_rep3-2~WBPaper00038519:C.elegans_8days_1G_rep1-1~WBPaper00038519:C.elegans_8days_1G_rep2-1~WBPaper00038519:C.elegans_8days_1G_rep3-1~WBPaper00038519:C.elegans_8days_microG_rep1-1~WBPaper00038519:C.elegans_8days_microG_rep2-1~WBPaper00038519:C.elegans_8days_microG_rep3-1~WBPaper00038519:C.elegans_8days_GC_rep1-1~WBPaper00038519:C.elegans_8days_GC_rep2-1~WBPaper00038519:C.elegans_8days_GC_rep3-1	Method: microarray|Species: Caenorhabditis elegans|Topic: regulatory ncRNA-mediated post-transcriptional gene silencing
233	21765926	WBPaper00039878.ce.mr.paper	GSE28301	GPL7727	1	Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms.	Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C. elegans cap'n'collar (CNC) transcription factor, SKN-1, mediates protective responses to oxidative stress. Genetic analysis showed that skn-1 activity is required for lifespan extension by low-dose plumbagin in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway.	8	17321	Hunt PR	Hunt PR, Son TG, Wilson MA, Yu QS, Wood WH, Zhang Y, Becker KG, Greig NH, Mattson MP, Camandola S, Wolkow CA	Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms.	PLoS One	2011	WBPaper00039878:DMSO_rep1~WBPaper00039878:PLB_rep1~WBPaper00039878:DMSO_rep2~WBPaper00039878:PLB_rep2~WBPaper00039878:DMSO_rep3~WBPaper00039878:PLB_rep3~WBPaper00039878:DMSO_rep4~WBPaper00039878:PLB_rep4	Method: microarray|Species: Caenorhabditis elegans
234	21858156	WBPaper00040116.ce.mr.paper	GSE26094	GPL11346	1	Lifespan-extending effects of royal jelly and its related substances on the nematode Caenorhabditis elegans.	BACKGROUND: One of the most important challenges in the study of aging is to discover compounds with longevity-promoting activities and to unravel their underlying mechanisms. Royal jelly (RJ) has been reported to possess diverse beneficial properties. Furthermore, protease-treated RJ (pRJ) has additional pharmacological activities. Exactly how RJ and pRJ exert these effects and which of their components are responsible for these effects are largely unknown. The evolutionarily conserved mechanisms that control longevity have been indicated. The purpose of the present study was to determine whether RJ and its related substances exert a lifespan-extending function in the nematode Caenorhabditis elegans and to gain insights into the active agents in RJ and their mechanism of action. PRINCIPAL FINDINGS: We found that both RJ and pRJ extended the lifespan of C. elegans. The lifespan-extending activity of pRJ was enhanced by Octadecyl-silica column chromatography (pRJ-Fraction 5). pRJ-Fr.5 increased the animals' lifespan in part by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS). pRJ-Fr.5 reduced the expression of ins-9, one of the insulin-like peptide genes. Moreover, pRJ-Fr.5 and reduced IIS shared some common features in terms of their effects on gene expression, such as the up-regulation of dod-3 and the down-regulation of dod-19, dao-4 and fkb-4. 10-Hydroxy-2-decenoic acid (10-HDA), which was present at high concentrations in pRJ-Fr.5, increased lifespan independently of DAF-16 activity. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that RJ and its related substances extend lifespan in C. elegans, suggesting that RJ may contain longevity-promoting factors. Further analysis and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network involved in longevity regulation in diverse species and may lead to the development of nutraceutical interventions in the aging process.	6	19636	Honda Y	Honda Y, Fujita Y, Maruyama H, Araki Y, Ichihara K, Sato A, Kojima T, Tanaka M, Nozawa Y, Ito M, Honda S	Lifespan-extending effects of royal jelly and its related substances on the nematode Caenorhabditis elegans.	PLoS One	2011	WBPaper00040116:Control_rep1~WBPaper00040116:Control_rep2~WBPaper00040116:Control_rep3~WBPaper00040116:pRJ-FR.5_fed_rep1~WBPaper00040116:pRJ-FR.5_fed_rep2~WBPaper00040116:pRJ-FR.5_fed_rep3	Method: microarray|Species: Caenorhabditis elegans
235	21909281	WBPaper00040184.ce.mr.paper	GSE30725	GPL13922	2	The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO.	The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.	28	314	Rizki G	Rizki G, Iwata TN, Li J, Riedel CG, Picard CL, Jan M, Murphy CT, Lee SS	The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO.	PLoS Genet	2011	WBPaper00040184:M2-S1(0.005):daf-16(RX5);hcf-1(pk924)(YA)_vs_hcf-1(pk924)(YA)~WBPaper00040184:M2-S1(0.1):daf-16(RX5);hcf-1(pk924)(YA)_vs_hcf-1(pk924)(YA)~WBPaper00040184:M2-S1(1):daf-16(RX5);hcf-1(pk924)(YA)_vs_hcf-1(pk924)(YA)~WBPaper00040184:M2-S2(0.005):daf-16(RX5);hcf-1(pk924)(YA)_vs_hcf-1(pk924)(YA)~WBPaper00040184:M2-S2(0.1):daf-16(RX5);hcf-1(pk924)(YA)_vs_hcf-1(pk924)(YA)~WBPaper00040184:M2-S2(1):daf-16(RX5);hcf-1(pk924)(YA)_vs_hcf-1(pk924)(YA)~WBPaper00040184:M2-S3(0.005):hcf-1(pk924)(YA)_vs_daf-16(RX5);hcf-1(pk924)(YA)~WBPaper00040184:M2-S3(0.1):hcf-1(pk924)(YA)_vs_daf-16(RX5);hcf-1(pk924)(YA)~WBPaper00040184:M2-S3(1):hcf-1(pk924)(YA)_vs_daf-16(RX5);hcf-1(pk924)(YA)~WBPaper00040184:M2-S4(0.005):hcf-1(pk924)(YA)_vs_daf-16(RX5);hcf-1(pk924)(YA)~WBPaper00040184:M2-S4(0.1):hcf-1(pk924)(YA)_vs_daf-16(RX5);hcf-1(pk924)(YA)~WBPaper00040184:M2-S4(1):hcf-1(pk924)(YA)_vs_daf-16(RX5);hcf-1(pk924)(YA)~WBPaper00040184:M3-S1(0.005):N2(YA)_vs_hcf-1(pk924)(YA)~WBPaper00040184:M3-S1(0.1):N2(YA)_vs_hcf-1(pk924)(YA)~WBPaper00040184:M3-S1(0.5):N2(YA)_vs_hcf-1(pk924)(YA)~WBPaper00040184:M3-S1(1):N2(YA)_vs_hcf-1(pk924)(YA)~WBPaper00040184:M3-S2(0.005):hcf-1(pk924)(YA)_vs_N2(YA)~WBPaper00040184:M3-S2(0.1):hcf-1(pk924)(YA)_vs_N2(YA)~WBPaper00040184:M3-S2(0.5):hcf-1(pk924)(YA)_vs_N2(YA)~WBPaper00040184:M3-S2(1):hcf-1(pk924)(YA)_vs_N2(YA)~WBPaper00040184:M3-S3(0.005):daf-16(RX5);hcf-1(pk924)(L4)_vs_hcf-1(pk924)(L4)~WBPaper00040184:M3-S3(0.1):daf-16(RX5);hcf-1(pk924)(L4)_vs_hcf-1(pk924)(L4)~WBPaper00040184:M3-S3(0.5):daf-16(RX5);hcf-1(pk924)(L4)_vs_hcf-1(pk924)(L4)~WBPaper00040184:M3-S3(1):daf-16(RX5);hcf-1(pk924)(L4)_vs_hcf-1(pk924)(L4)~WBPaper00040184:M3-S4(0.005):hcf-1(pk924)(L4)_vs_daf-16(RX5);hcf-1(pk924)(L4)~WBPaper00040184:M3-S4(0.1):hcf-1(pk924)(L4)_vs_daf-16(RX5);hcf-1(pk924)(L4)~WBPaper00040184:M3-S4(0.5):hcf-1(pk924)(L4)_vs_daf-16(RX5);hcf-1(pk924)(L4)~WBPaper00040184:M3-S4(1):hcf-1(pk924)(L4)_vs_daf-16(RX5);hcf-1(pk924)(L4)	Method: microarray|Species: Caenorhabditis elegans
236	22083954	WBPaper00040410.ce.mr.paper	GSE25714	GPL7727	1	Novel roles of Caenorhabditis elegans heterochromatin protein HP1 and linker histone in the regulation of innate immune gene expression.	Linker histone (H1) and heterochromatin protein 1 (HP1) are essential components of heterochromatin which contribute to the transcriptional repression of genes. It has been shown that the methylation mark of vertebrate histone H1 is specifically recognized by the chromodomain of HP1. However, the exact biological role of linker histone binding to HP1 has not been determined. Here, we investigate the function of the Caenorhabditis elegans H1 variant HIS-24 and the HP1-like proteins HPL-1 and HPL-2 in the cooperative transcriptional regulation of immune-relevant genes. We provide the first evidence that HPL-1 interacts with HIS-24 monomethylated at lysine 14 (HIS-24K14me1) and associates in vivo with promoters of genes involved in antimicrobial response. We also report an increase in overall cellular levels and alterations in the distribution of HIS-24K14me1 after infection with pathogenic bacteria. HIS-24K14me1 localization changes from being mostly nuclear to both nuclear and cytoplasmic in the intestinal cells of infected animals. Our results highlight an antimicrobial role of HIS-24K14me1 and suggest a functional link between epigenetic regulation by an HP1/H1 complex and the innate immune system in C. elegans.	10	17321	Studencka M	Studencka M, Konzer A, Moneron G, Wenzel D, Opitz L, Salinas-Riester G, Bedet C, Kruger M, Hell SW, Wisniewski JR, Schmidt H, Palladino F, Schulze E, Jedrusik-Bode M	Novel roles of Caenorhabditis elegans heterochromatin protein HP1 and linker histone in the regulation of innate immune gene expression.	Mol Cell Biol	2012	WBPaper00040410:Hpl1_KO_Mutant_Replicate1~WBPaper00040410:Hpl1_KO_Mutant_Replicate2~WBPaper00040410:Hpl2_KO_Mutant_Replicate1~WBPaper00040410:Hpl2_KO_Mutant_Replicate2~WBPaper00040410:His24_KO_Mutant_Replicate1~WBPaper00040410:His24_KO_Mutant_Replicate2~WBPaper00040410:WildType_Replicate1~WBPaper00040410:WildType_Replicate2~WBPaper00040410:WildType_Replicate3~WBPaper00040410:WildType_Replicate4	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
237	22102824	WBPaper00040426.ce.mr.paper	N.A.	N.A.	2	Caenorhabditis elegans cyclin D/CDK4 and cyclin E/CDK2 induce distinct cell cycle re-entry programs in differentiated muscle cells.	Cell proliferation and differentiation are regulated in a highly coordinated and inverse manner during development and tissue homeostasis. Terminal differentiation usually coincides with cell cycle exit and is thought to engage stable transcriptional repression of cell cycle genes. Here, we examine the robustness of the post-mitotic state, using Caenorhabditis elegans muscle cells as a model. We found that expression of a G1 Cyclin and CDK initiates cell cycle re-entry in muscle cells without interfering with the differentiated state. Cyclin D/CDK4 (CYD-1/CDK-4) expression was sufficient to induce DNA synthesis in muscle cells, in contrast to Cyclin E/CDK2 (CYE-1/CDK-2), which triggered mitotic events. Tissue-specific gene-expression profiling and single molecule FISH experiments revealed that Cyclin D and E kinases activate an extensive and overlapping set of cell cycle genes in muscle, yet failed to induce some key activators of G1/S progression. Surprisingly, CYD-1/CDK-4 also induced an additional set of genes primarily associated with growth and metabolism, which were not activated by CYE-1/CDK-2. Moreover, CYD-1/CDK-4 expression also down-regulated a large number of genes enriched for catabolic functions. These results highlight distinct functions for the two G1 Cyclin/CDK complexes and reveal a previously unknown activity of Cyclin D/CDK-4 in regulating metabolic gene expression. Furthermore, our data demonstrate that many cell cycle genes can still be transcriptionally induced in post-mitotic muscle cells, while maintenance of the post-mitotic state might depend on stable repression of a limited number of critical cell cycle regulators.	15	17478	Korzelius J	Korzelius J, The I, Ruijtenberg S, Prinsen MB, Portegijs V, Middelkoop TC, Groot Koerkamp MJ, Holstege FC, Boxem M, van den Heuvel S	Caenorhabditis elegans cyclin D/CDK4 and cyclin E/CDK2 induce distinct cell cycle re-entry programs in differentiated muscle cells.	PLoS Genet	2011	WBPaper00040426:IT004-totalRNA_vs_SV912#3~WBPaper00040426:SV912-s2_vs_IT003-refpool~WBPaper00040426:IT003-refpool_vs_SV911-s5~WBPaper00040426:SV911-s6_vs_IT003-refpool~WBPaper00040426:IT004-totalRNA_vs_SV985#3~WBPaper00040426:SV911-s3_vs_IT003-refpool~WBPaper00040426:SV985#4_vs_IT004-totalRNA~WBPaper00040426:IT004-totalRNA_vs_SV985#1~WBPaper00040426:IT003-refpool_vs_SV911-s1~WBPaper00040426:SV912#2_vs_IT004-totalRNA~WBPaper00040426:IT003-refpool_vs_SV912-s3~WBPaper00040426:SV985#2_vs_IT004-totalRNA~WBPaper00040426:IT003-refpool_vs_SV912-s1~WBPaper00040426:IT004-totalRNA_vs_SV912#1~WBPaper00040426:SV912-s4_vs_IT003-refpool	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
238	22370633	WBPaper00040823.ce.mr.paper	N.A.	N.A.	2	The microRNA pathway controls germ cell proliferation and differentiation in C. elegans.	The discovery of the miRNA pathway revealed a new layer of molecular control of biological processes. To uncover new functions of this gene regulatory pathway, we undertook the characterization of the two miRNA-specific Argonaute proteins in Caenorhabditis elegans, ALG-1 and ALG-2. We first observed that the loss-of-function of alg-1 and alg-2 genes resulted in reduced progeny number. An extensive analysis of the germline of these mutants revealed a reduced mitotic region, indicating fewer proliferating germ cells. We also observed an early entry into meiosis in alg-1 and alg-2 mutant animals. We detected ALG-1 and ALG-2 protein expressions in the distal tip cell (DTC), a specialized cell located at the tip of both C. elegans gonadal arms that regulates mitosis-meiosis transition. Re-establishing the expression of alg-1 specifically in the DTC of mutant animals partially rescued the observed germline defects. Further analyses also support the implication of the miRNA pathway in gametogenesis. Interestingly, we observed that disruption of five miRNAs expressed in the DTC led to similar phenotypes. Finally, gene expression analysis of alg-1 mutant gonads suggests that the miRNA pathway is involved in the regulation of different pathways important for germline proliferation and differentiation. Collectively, our data indicate that the miRNA pathway plays a crucial role in the control of germ cell biogenesis in C. elegans.	4	19636	Bukhari SI	Bukhari SI, Vasquez-Rifo A, Gagne D, Paquet ER, Zetka M, Robert C, Masson JY, Simard MJ	The microRNA pathway controls germ cell proliferation and differentiation in C. elegans.	Cell Res	2012	WBPaper00040823:alg-1(gk214)_vs_N2_rep1~WBPaper00040823:alg-1(gk214)_vs_N2_rep2~WBPaper00040823:N2_vs_alg-1(gk214)_rep1~WBPaper00040823:N2_vs_alg-1(gk214)_rep2	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
239	22669615	WBPaper00041174.ce.mr.paper	GSE34650	GPL13394	1	A genomic bias for genotype-environment interactions in C. elegans.	The phenotype of an organism is determined by its genotype and environment. An interaction between these two arises from the differential effect of the environment on gene expression in distinct genotypes; however, the genomic properties identifying these are not well understood. Here we analyze the transcriptomes of five C. elegans strains (genotype) cultivated in five growth conditions (environment), and find that highly regulated genes, as distinguished by intergenic lengths, motif concentration, and expression levels, are particularly biased toward genotype-environment interactions. Sequencing these strains, we find that genes with expression variation across genotypes are enriched for promoter single-nucleotide polymorphisms (SNPs), as expected. However, genes with genotype-environment interactions do not significantly differ from background in terms of their promoter SNPs. Collectively, these results indicate that the highly regulated nature of particular genes predispose them for exhibiting genotype-environment interaction as a consequence of changes to upstream regulators. This observation may provide a deeper understanding into the origin of the extraordinary gene expression diversity present in even closely related species.	90	14759	Grishkevich V	Grishkevich V, Ben-Elazar S, Hashimshony T, Schott DH, Hunter CP, Yanai I	A genomic bias for genotype-environment interactions in C. elegans.	Mol Syst Biol	2012	WBPaper00041174:AB2_Control_1~WBPaper00041174:CB4856_Control_1~WBPaper00041174:RC301_Control_1~WBPaper00041174:CB4857_Control_1~WBPaper00041174:N2_Control_1~WBPaper00041174:HC445_Control_1~WBPaper00041174:AB2_25C_1~WBPaper00041174:CB4856_25C_1~WBPaper00041174:RC301_25C_1~WBPaper00041174:CB4857_25C_1~WBPaper00041174:N2_25C_1~WBPaper00041174:HC445_25C_1~WBPaper00041174:AB2_High-pH-Salt_1~WBPaper00041174:CB4856_High-pH-Salt_1~WBPaper00041174:RC301_High-pH-Salt_1~WBPaper00041174:CB4857_High-pH-Salt_1~WBPaper00041174:N2_High-pH-Salt_1~WBPaper00041174:HC445_High-pH-Salt_1~WBPaper00041174:AB2_Liquid_1~WBPaper00041174:CB4856_Liquid_1~WBPaper00041174:RC301_Liquid_1~WBPaper00041174:CB4857_Liquid_1~WBPaper00041174:N2_Liquid_1~WBPaper00041174:HC445_Liquid_1~WBPaper00041174:AB2_infection_1~WBPaper00041174:CB4856_infection_1~WBPaper00041174:RC301_infection_1~WBPaper00041174:CB4857_infection_1~WBPaper00041174:N2_infection_1~WBPaper00041174:HC445_infection_1~WBPaper00041174:AB2_Control_2~WBPaper00041174:CB4856_Control_2~WBPaper00041174:RC301_Control_2~WBPaper00041174:CB4857_Control_2~WBPaper00041174:N2_Control_2~WBPaper00041174:HC445_Control_2~WBPaper00041174:AB2_25C_2~WBPaper00041174:CB4856_25C_2~WBPaper00041174:RC301_25C_2~WBPaper00041174:CB4857_25C_2~WBPaper00041174:N2_25C_2~WBPaper00041174:HC445_25C_2~WBPaper00041174:AB2_High-pH-Salt_2~WBPaper00041174:CB4856_High-pH-Salt_2~WBPaper00041174:RC301_High-pH-Salt_2~WBPaper00041174:CB4857_High-pH-Salt_2~WBPaper00041174:N2_High-pH-Salt_2~WBPaper00041174:HC445_High-pH-Salt_2~WBPaper00041174:AB2_Liquid_2~WBPaper00041174:CB4856_Liquid_2~WBPaper00041174:RC301_Liquid_2~WBPaper00041174:CB4857_Liquid_2~WBPaper00041174:N2_Liquid_2~WBPaper00041174:HC445_Liquid_2~WBPaper00041174:AB2_infection_2~WBPaper00041174:CB4856_infection_2~WBPaper00041174:RC301_infection_2~WBPaper00041174:CB4857_infection_2~WBPaper00041174:N2_infection_2~WBPaper00041174:HC445_infection_2~WBPaper00041174:AB2_Control_3~WBPaper00041174:CB4856_Control_3~WBPaper00041174:RC301_Control_3~WBPaper00041174:CB4857_Control_3~WBPaper00041174:N2_Control_3~WBPaper00041174:HC445_Control_3~WBPaper00041174:AB2_25C_3~WBPaper00041174:CB4856_25C_3~WBPaper00041174:RC301_25C_3~WBPaper00041174:CB4857_25C_3~WBPaper00041174:N2_25C_3~WBPaper00041174:HC445_25C_3~WBPaper00041174:AB2_High-pH-Salt_3~WBPaper00041174:CB4856_High-pH-Salt_3~WBPaper00041174:RC301_High-pH-Salt_3~WBPaper00041174:CB4857_High-pH-Salt_3~WBPaper00041174:N2_High-pH-Salt_3~WBPaper00041174:HC445_High-pH-Salt_3~WBPaper00041174:AB2_Liquid_3~WBPaper00041174:CB4856_Liquid_3~WBPaper00041174:RC301_Liquid_3~WBPaper00041174:CB4857_Liquid_3~WBPaper00041174:N2_Liquid_3~WBPaper00041174:HC445_Liquid_3~WBPaper00041174:AB2_infection_3~WBPaper00041174:CB4856_infection_3~WBPaper00041174:RC301_infection_3~WBPaper00041174:CB4857_infection_3~WBPaper00041174:N2_infection_3~WBPaper00041174:HC445_infection_3	Method: microarray|Species: Caenorhabditis elegans
240	22560298	WBPaper00041190.cbg.mr.paper	GSE31422	GPL14144	1	Developmental milestones punctuate gene expression in the Caenorhabditis embryo.	A fundamental question in developmental biology relates to the connection between morphological stages and their underlying molecular activity. Here we demonstrate that, at the molecular level, embryonic development in five Caenorhabditis species proceeds through two distinct milestones in which the transcriptome is resistant to differences in species-specific developmental timings. By comparing the complete protein-coding transcriptomes of individually timed embryos across ten morphological markers, we found that developmental milestones can be characterized by their expression dynamics and activation of key developmental regulators. This approach led us to discover the nematode phylotypic stage and to show that in chordates and arthropods it is represented as two distinct stages, suggesting that animal body plans might evolve by uncoupling and elaboration on formerly synchronous processes.	30	18270	Levin M	Levin M, Hashimshony T, Wagner F, Yanai I	Developmental milestones punctuate gene expression in the Caenorhabditis embryo.	Dev Cell	2012	WBPaper00041190:C.briggsae_rep1_stage1~WBPaper00041190:C.briggsae_rep1_stage2~WBPaper00041190:C.briggsae_rep1_stage3~WBPaper00041190:C.briggsae_rep1_stage4~WBPaper00041190:C.briggsae_rep1_stage5~WBPaper00041190:C.briggsae_rep1_stage6~WBPaper00041190:C.briggsae_rep1_stage7~WBPaper00041190:C.briggsae_rep1_stage8~WBPaper00041190:C.briggsae_rep1_stage9~WBPaper00041190:C.briggsae_rep1_stage10~WBPaper00041190:C.briggsae_rep2_stage1~WBPaper00041190:C.briggsae_rep2_stage2~WBPaper00041190:C.briggsae_rep2_stage3~WBPaper00041190:C.briggsae_rep2_stage4~WBPaper00041190:C.briggsae_rep2_stage5~WBPaper00041190:C.briggsae_rep2_stage6~WBPaper00041190:C.briggsae_rep2_stage7~WBPaper00041190:C.briggsae_rep2_stage8~WBPaper00041190:C.briggsae_rep2_stage9~WBPaper00041190:C.briggsae_rep2_stage10~WBPaper00041190:C.briggsae_rep3_stage1~WBPaper00041190:C.briggsae_rep3_stage2~WBPaper00041190:C.briggsae_rep3_stage3~WBPaper00041190:C.briggsae_rep3_stage4~WBPaper00041190:C.briggsae_rep3_stage5~WBPaper00041190:C.briggsae_rep3_stage6~WBPaper00041190:C.briggsae_rep3_stage7~WBPaper00041190:C.briggsae_rep3_stage8~WBPaper00041190:C.briggsae_rep3_stage9~WBPaper00041190:C.briggsae_rep3_stage10	Method: microarray|Species: Caenorhabditis briggsae
241	22560298	WBPaper00041190.cbn.mr.paper	GSE31422	GPL14144	1	Developmental milestones punctuate gene expression in the Caenorhabditis embryo.	A fundamental question in developmental biology relates to the connection between morphological stages and their underlying molecular activity. Here we demonstrate that, at the molecular level, embryonic development in five Caenorhabditis species proceeds through two distinct milestones in which the transcriptome is resistant to differences in species-specific developmental timings. By comparing the complete protein-coding transcriptomes of individually timed embryos across ten morphological markers, we found that developmental milestones can be characterized by their expression dynamics and activation of key developmental regulators. This approach led us to discover the nematode phylotypic stage and to show that in chordates and arthropods it is represented as two distinct stages, suggesting that animal body plans might evolve by uncoupling and elaboration on formerly synchronous processes.	30	24456	Levin M	Levin M, Hashimshony T, Wagner F, Yanai I	Developmental milestones punctuate gene expression in the Caenorhabditis embryo.	Dev Cell	2012	WBPaper00041190:C.brenneri_rep1_stage1~WBPaper00041190:C.brenneri_rep1_stage2~WBPaper00041190:C.brenneri_rep1_stage3~WBPaper00041190:C.brenneri_rep1_stage4~WBPaper00041190:C.brenneri_rep1_stage5~WBPaper00041190:C.brenneri_rep1_stage6~WBPaper00041190:C.brenneri_rep1_stage7~WBPaper00041190:C.brenneri_rep1_stage8~WBPaper00041190:C.brenneri_rep1_stage9~WBPaper00041190:C.brenneri_rep1_stage10~WBPaper00041190:C.brenneri_rep2_stage1~WBPaper00041190:C.brenneri_rep2_stage2~WBPaper00041190:C.brenneri_rep2_stage3~WBPaper00041190:C.brenneri_rep2_stage4~WBPaper00041190:C.brenneri_rep2_stage5~WBPaper00041190:C.brenneri_rep2_stage6~WBPaper00041190:C.brenneri_rep2_stage7~WBPaper00041190:C.brenneri_rep2_stage8~WBPaper00041190:C.brenneri_rep2_stage9~WBPaper00041190:C.brenneri_rep2_stage10~WBPaper00041190:C.brenneri_rep3_stage1~WBPaper00041190:C.brenneri_rep3_stage2~WBPaper00041190:C.brenneri_rep3_stage3~WBPaper00041190:C.brenneri_rep3_stage4~WBPaper00041190:C.brenneri_rep3_stage5~WBPaper00041190:C.brenneri_rep3_stage6~WBPaper00041190:C.brenneri_rep3_stage7~WBPaper00041190:C.brenneri_rep3_stage8~WBPaper00041190:C.brenneri_rep3_stage9~WBPaper00041190:C.brenneri_rep3_stage10	Method: microarray|Species: Caenorhabditis brenneri
242	22560298	WBPaper00041190.cja.mr.paper	GSE31422	GPL14144	1	Developmental milestones punctuate gene expression in the Caenorhabditis embryo.	A fundamental question in developmental biology relates to the connection between morphological stages and their underlying molecular activity. Here we demonstrate that, at the molecular level, embryonic development in five Caenorhabditis species proceeds through two distinct milestones in which the transcriptome is resistant to differences in species-specific developmental timings. By comparing the complete protein-coding transcriptomes of individually timed embryos across ten morphological markers, we found that developmental milestones can be characterized by their expression dynamics and activation of key developmental regulators. This approach led us to discover the nematode phylotypic stage and to show that in chordates and arthropods it is represented as two distinct stages, suggesting that animal body plans might evolve by uncoupling and elaboration on formerly synchronous processes.	30	14785	Levin M	Levin M, Hashimshony T, Wagner F, Yanai I	Developmental milestones punctuate gene expression in the Caenorhabditis embryo.	Dev Cell	2012	WBPaper00041190:C.japonica_rep1_stage1~WBPaper00041190:C.japonica_rep1_stage2~WBPaper00041190:C.japonica_rep1_stage3~WBPaper00041190:C.japonica_rep1_stage4~WBPaper00041190:C.japonica_rep1_stage5~WBPaper00041190:C.japonica_rep1_stage6~WBPaper00041190:C.japonica_rep1_stage7~WBPaper00041190:C.japonica_rep1_stage8~WBPaper00041190:C.japonica_rep1_stage9~WBPaper00041190:C.japonica_rep1_stage10~WBPaper00041190:C.japonica_rep2_stage1~WBPaper00041190:C.japonica_rep2_stage2~WBPaper00041190:C.japonica_rep2_stage3~WBPaper00041190:C.japonica_rep2_stage4~WBPaper00041190:C.japonica_rep2_stage5~WBPaper00041190:C.japonica_rep2_stage6~WBPaper00041190:C.japonica_rep2_stage7~WBPaper00041190:C.japonica_rep2_stage8~WBPaper00041190:C.japonica_rep2_stage9~WBPaper00041190:C.japonica_rep2_stage10~WBPaper00041190:C.japonica_rep3_stage1~WBPaper00041190:C.japonica_rep3_stage2~WBPaper00041190:C.japonica_rep3_stage3~WBPaper00041190:C.japonica_rep3_stage4~WBPaper00041190:C.japonica_rep3_stage5~WBPaper00041190:C.japonica_rep3_stage6~WBPaper00041190:C.japonica_rep3_stage7~WBPaper00041190:C.japonica_rep3_stage8~WBPaper00041190:C.japonica_rep3_stage9~WBPaper00041190:C.japonica_rep3_stage10	Method: microarray|Species: Caenorhabditis japonica
243	22560298	WBPaper00041190.cre.mr.paper	GSE31422	GPL14144	1	Developmental milestones punctuate gene expression in the Caenorhabditis embryo.	A fundamental question in developmental biology relates to the connection between morphological stages and their underlying molecular activity. Here we demonstrate that, at the molecular level, embryonic development in five Caenorhabditis species proceeds through two distinct milestones in which the transcriptome is resistant to differences in species-specific developmental timings. By comparing the complete protein-coding transcriptomes of individually timed embryos across ten morphological markers, we found that developmental milestones can be characterized by their expression dynamics and activation of key developmental regulators. This approach led us to discover the nematode phylotypic stage and to show that in chordates and arthropods it is represented as two distinct stages, suggesting that animal body plans might evolve by uncoupling and elaboration on formerly synchronous processes.	30	25399	Levin M	Levin M, Hashimshony T, Wagner F, Yanai I	Developmental milestones punctuate gene expression in the Caenorhabditis embryo.	Dev Cell	2012	WBPaper00041190:C.remanei_rep1_stage1~WBPaper00041190:C.remanei_rep1_stage2~WBPaper00041190:C.remanei_rep1_stage3~WBPaper00041190:C.remanei_rep1_stage4~WBPaper00041190:C.remanei_rep1_stage5~WBPaper00041190:C.remanei_rep1_stage6~WBPaper00041190:C.remanei_rep1_stage7~WBPaper00041190:C.remanei_rep1_stage8~WBPaper00041190:C.remanei_rep1_stage9~WBPaper00041190:C.remanei_rep1_stage10~WBPaper00041190:C.remanei_rep2_stage1~WBPaper00041190:C.remanei_rep2_stage2~WBPaper00041190:C.remanei_rep2_stage3~WBPaper00041190:C.remanei_rep2_stage4~WBPaper00041190:C.remanei_rep2_stage5~WBPaper00041190:C.remanei_rep2_stage6~WBPaper00041190:C.remanei_rep2_stage7~WBPaper00041190:C.remanei_rep2_stage8~WBPaper00041190:C.remanei_rep2_stage9~WBPaper00041190:C.remanei_rep2_stage10~WBPaper00041190:C.remanei_rep3_stage1~WBPaper00041190:C.remanei_rep3_stage2~WBPaper00041190:C.remanei_rep3_stage3~WBPaper00041190:C.remanei_rep3_stage4~WBPaper00041190:C.remanei_rep3_stage5~WBPaper00041190:C.remanei_rep3_stage6~WBPaper00041190:C.remanei_rep3_stage7~WBPaper00041190:C.remanei_rep3_stage8~WBPaper00041190:C.remanei_rep3_stage9~WBPaper00041190:C.remanei_rep3_stage10	Method: microarray|Species: Caenorhabditis remanei
244	22560298	WBPaper00041190.ce.mr.paper	GSE31422	GPL14144	1	Developmental milestones punctuate gene expression in the Caenorhabditis embryo.	A fundamental question in developmental biology relates to the connection between morphological stages and their underlying molecular activity. Here we demonstrate that, at the molecular level, embryonic development in five Caenorhabditis species proceeds through two distinct milestones in which the transcriptome is resistant to differences in species-specific developmental timings. By comparing the complete protein-coding transcriptomes of individually timed embryos across ten morphological markers, we found that developmental milestones can be characterized by their expression dynamics and activation of key developmental regulators. This approach led us to discover the nematode phylotypic stage and to show that in chordates and arthropods it is represented as two distinct stages, suggesting that animal body plans might evolve by uncoupling and elaboration on formerly synchronous processes.	30	18457	Levin M	Levin M, Hashimshony T, Wagner F, Yanai I	Developmental milestones punctuate gene expression in the Caenorhabditis embryo.	Dev Cell	2012	WBPaper00041190:C.elegans_rep1_stage1~WBPaper00041190:C.elegans_rep1_stage2~WBPaper00041190:C.elegans_rep1_stage3~WBPaper00041190:C.elegans_rep1_stage4~WBPaper00041190:C.elegans_rep1_stage5~WBPaper00041190:C.elegans_rep1_stage6~WBPaper00041190:C.elegans_rep1_stage7~WBPaper00041190:C.elegans_rep1_stage8~WBPaper00041190:C.elegans_rep1_stage9~WBPaper00041190:C.elegans_rep1_stage10~WBPaper00041190:C.elegans_rep2_stage1~WBPaper00041190:C.elegans_rep2_stage2~WBPaper00041190:C.elegans_rep2_stage3~WBPaper00041190:C.elegans_rep2_stage4~WBPaper00041190:C.elegans_rep2_stage5~WBPaper00041190:C.elegans_rep2_stage6~WBPaper00041190:C.elegans_rep2_stage7~WBPaper00041190:C.elegans_rep2_stage8~WBPaper00041190:C.elegans_rep2_stage9~WBPaper00041190:C.elegans_rep2_stage10~WBPaper00041190:C.elegans_rep3_stage1~WBPaper00041190:C.elegans_rep3_stage2~WBPaper00041190:C.elegans_rep3_stage3~WBPaper00041190:C.elegans_rep3_stage4~WBPaper00041190:C.elegans_rep3_stage5~WBPaper00041190:C.elegans_rep3_stage6~WBPaper00041190:C.elegans_rep3_stage7~WBPaper00041190:C.elegans_rep3_stage8~WBPaper00041190:C.elegans_rep3_stage9~WBPaper00041190:C.elegans_rep3_stage10	Method: microarray|Species: Caenorhabditis elegans
245	22712530	WBPaper00041207.ce.mr.paper	GSE31861,GSE36644	GPL14372	2	Divergent gene expression in the conserved dauer stage of the nematodes Pristionchus pacificus and Caenorhabditis elegans.	BACKGROUND: An organism can respond to changing environmental conditions by adjusting gene regulation and by forming alternative phenotypes. In nematodes, these mechanisms are coupled because many species will form dauer larvae, a stress-resistant and non-aging developmental stage, when exposed to unfavorable environmental conditions, and execute gene expression programs that have been selected for the survival of the animal in the wild. These dauer larvae represent an environmentally induced, homologous developmental stage across many nematode species, sharing conserved morphological and physiological properties. Hence it can be expected that some core components of the associated transcriptional program would be conserved across species, while others might diverge over the course of evolution. However, transcriptional and metabolic analysis of dauer development has been largely restricted to Caenorhabditis elegans. Here, we use a transcriptomic approach to compare the dauer stage in the evolutionary model system Pristionchus pacificus with the dauer stage in C. elegans. RESULTS: We have employed Agilent microarrays, which represent 20,446 P. pacificus and 20,143 C. elegans genes to show an unexpected divergence in the expression profiles of these two nematodes in dauer and dauer exit samples. P. pacificus and C. elegans differ in the dynamics and function of genes that are differentially expressed. We find that only a small number of orthologous gene pairs show similar expression pattern in the dauers of the two species, while the non-orthologous fraction of genes is a major contributor to the active transcriptome in dauers. Interestingly, many of the genes acquired by horizontal gene transfer and orphan genes in P. pacificus, are differentially expressed suggesting that these genes are of evolutionary and functional importance. CONCLUSION: Our data set provides a catalog for future functional investigations and indicates novel insight into evolutionary mechanisms. We discuss the limited conservation of core developmental and transcriptional programs as a common aspect of animal evolution.	8	19636	Sinha A	Sinha A, Sommer RJ, Dieterich C	Divergent gene expression in the conserved dauer stage of the nematodes Pristionchus pacificus and Caenorhabditis elegans.	BMC Genomics	2012	WBPaper00041207:CE_Dauers_vs_Mix-Stage_rep1~WBPaper00041207:CE_Dauers_vs_Mix-Stage_rep2~WBPaper00041207:CE_Dauers_vs_Mix-Stage_rep3~WBPaper00041207:CE_Dauers_vs_Mix-Stage_rep4~WBPaper00041207:CE_Dauer-Exit(12hrs)_vs_Mix-Stage_rep1~WBPaper00041207:CE_Dauer-Exit(12hrs)_vs_Mix-Stage_rep2~WBPaper00041207:CE_Dauer-Exit(12hrs)_vs_Mix-Stage_rep3~WBPaper00041207:CE_Dauer-Exit(12hrs)_vs_Mix-Stage_rep4	Method: microarray|Species: Caenorhabditis elegans
246	22712530	WBPaper00041207.ppa.mr.paper	GSE31861,GSE36644	GPL14372	2	Divergent gene expression in the conserved dauer stage of the nematodes Pristionchus pacificus and Caenorhabditis elegans.	BACKGROUND: An organism can respond to changing environmental conditions by adjusting gene regulation and by forming alternative phenotypes. In nematodes, these mechanisms are coupled because many species will form dauer larvae, a stress-resistant and non-aging developmental stage, when exposed to unfavorable environmental conditions, and execute gene expression programs that have been selected for the survival of the animal in the wild. These dauer larvae represent an environmentally induced, homologous developmental stage across many nematode species, sharing conserved morphological and physiological properties. Hence it can be expected that some core components of the associated transcriptional program would be conserved across species, while others might diverge over the course of evolution. However, transcriptional and metabolic analysis of dauer development has been largely restricted to Caenorhabditis elegans. Here, we use a transcriptomic approach to compare the dauer stage in the evolutionary model system Pristionchus pacificus with the dauer stage in C. elegans. RESULTS: We have employed Agilent microarrays, which represent 20,446 P. pacificus and 20,143 C. elegans genes to show an unexpected divergence in the expression profiles of these two nematodes in dauer and dauer exit samples. P. pacificus and C. elegans differ in the dynamics and function of genes that are differentially expressed. We find that only a small number of orthologous gene pairs show similar expression pattern in the dauers of the two species, while the non-orthologous fraction of genes is a major contributor to the active transcriptome in dauers. Interestingly, many of the genes acquired by horizontal gene transfer and orphan genes in P. pacificus, are differentially expressed suggesting that these genes are of evolutionary and functional importance. CONCLUSION: Our data set provides a catalog for future functional investigations and indicates novel insight into evolutionary mechanisms. We discuss the limited conservation of core developmental and transcriptional programs as a common aspect of animal evolution.	7	15992	Sinha A	Sinha A, Sommer RJ, Dieterich C	Divergent gene expression in the conserved dauer stage of the nematodes Pristionchus pacificus and Caenorhabditis elegans.	BMC Genomics	2012	WBPaper00041207:PP_Dauers_vs_Mix-Stage_rep1~WBPaper00041207:PP_Dauers_vs_Mix-Stage_rep2~WBPaper00041207:PP_Dauers_vs_Mix-Stage_rep3~WBPaper00041207:PP_Dauers_vs_Mix-Stage_rep4~WBPaper00041207:PP_Dauer-Exit(12hrs)_vs_Mix-Stage_rep1~WBPaper00041207:PP_Dauer-Exit(12hrs)_vs_Mix-Stage_rep2~WBPaper00041207:PP_Dauer-Exit(12hrs)_vs_Mix-Stage_rep3	Method: microarray|Species: Pristionchus pacificus
247	22912581	WBPaper00041466.ppa.mr.paper	GSE37331,GSE37337	GPL14372	2	Genome-wide analysis of germline signaling genes regulating longevity and innate immunity in the nematode Pristionchus pacificus.	Removal of the reproductive system of many animals including fish, flies, nematodes, mice and humans can increase lifespan through mechanisms largely unknown. The abrogation of the germline in Caenorhabditis elegans increases longevity by 60% due to a signal emitted from the somatic gonad. Apart from increased longevity, germline-less C. elegans is also resistant to other environmental stressors such as feeding on bacterial pathogens. However, the evolutionary conservation of this pathogen resistance, its genetic basis and an understanding of genes involved in producing this extraordinary survival phenotype are currently unknown. To study these evolutionary aspects we used the necromenic nematode Pristionchus pacificus, which is a genetic model system used in comparison to C. elegans. By ablation of germline precursor cells and subsequent feeding on the pathogen Serratia marcescens we discovered that P. pacificus shows remarkable resistance to bacterial pathogens and that this response is evolutionarily conserved across the Genus Pristionchus. To gain a mechanistic understanding of the increased resistance to bacterial pathogens and longevity in germline-ablated P. pacificus we used whole genome microarrays to profile the transcriptional response comparing germline ablated versus un-ablated animals when fed S. marcescens. We show that lipid metabolism, maintenance of the proteasome, insulin signaling and nuclear pore complexes are essential for germline deficient phenotypes with more than 3,300 genes being differentially expressed. In contrast, gene expression of germline-less P. pacificus on E. coli (longevity) and S. marcescens (immunity) is very similar with only 244 genes differentially expressed indicating that longevity is due to abundant gene expression also involved in immunity. By testing existing mutants of Ppa-DAF-16/FOXO and the nuclear hormone receptor Ppa-DAF-12 we show a conserved function of both genes in resistance to bacterial pathogens and longevity. This is the first study to show that the influence of the reproductive system on extending lifespan and innate immunity is conserved in evolution.	7	15992	Rae R	Rae R, Sinha A, Sommer RJ	Genome-wide analysis of germline signaling genes regulating longevity and innate immunity in the nematode Pristionchus pacificus.	PLoS Pathog	2012	WBPaper00041466:PP_germline-ablated_vs_PP_unablated_rep1~WBPaper00041466:PP_germline-ablated_vs_PP_unablated_rep2-Dye-flip.~WBPaper00041466:PP_germline-ablated_vs_PP_unablated_rep3-Dye-flip.~WBPaper00041466:PP_germline-ablated_S.marcescens_vs_PP_germline-ablated_rep1~WBPaper00041466:PP_germline-ablated_S.marcescens_vs_PP_germline-ablated_rep2~WBPaper00041466:PP_germline-ablated_S.marcescens_vs_PP_germline-ablated_rep3-Dye-swap.~WBPaper00041466:PP_germline-ablated_S.marcescens_vs_PP_germline-ablated_rep4-Dye-swap.	Method: microarray|Species: Pristionchus pacificus
248	23028509	WBPaper00041606.ce.mr.paper	GSE36517,GSE36519,GSE36521,GSE36523,GSE36636	GPL14372	2	System wide analysis of the evolution of innate immunity in the nematode model species Caenorhabditis elegans and Pristionchus pacificus.	The evolution of genetic mechanisms used to combat bacterial infections is critical for the survival of animals and plants, yet how these genes evolved to produce a robust defense system is poorly understood. Studies of the nematode Caenorhabditis elegans have uncovered a plethora of genetic regulators and effectors responsible for surviving pathogens. However, comparative studies utilizing other free-living nematodes and therefore providing an insight into the evolution of innate immunity have been lacking. Here, we take a systems biology approach and use whole genome microarrays to profile the transcriptional response of C. elegans and the necromenic nematode Pristionchus pacificus after exposure to the four different pathogens Serratia marcescens, Xenorhabdus nematophila, Staphylococcus aureus and Bacillus thuringiensis DB27. C. elegans is susceptible to all four pathogens whilst P. pacificus is only susceptible to S. marcescens and X. nematophila. We show an unexpected level of specificity in host responses to distinct pathogens within and across species, revealing an enormous complexity of effectors of innate immunity. Functional domains enriched in the transcriptomes on different pathogens are similar within a nematode species but different across them, suggesting differences in pathogen sensing and response networks. We find translation inhibition to be a potentially conserved response to gram-negative pathogens in both the nematodes. Further computational analysis indicates that both nematodes when fed on pathogens up-regulate genes known to be involved in other stress responses like heat shock, oxidative and osmotic stress, and genes regulated by DAF-16/FOXO and TGF-beta pathways. This study presents a platform for comparative systems analysis of two nematode model species, and a catalog of genes involved in the evolution of nematode immunity and identifies both pathogen specific and pan-pathogen responses. We discuss the potential effects of ecology on evolution of downstream effectors and upstream regulators on evolution of nematode innate immunity.	15	19636	Sinha A	Sinha A, Rae R, Iatsenko I, Sommer RJ	System wide analysis of the evolution of innate immunity in the nematode model species Caenorhabditis elegans and Pristionchus pacificus.	PLoS One	2012	WBPaper00041606:CE_B.thuringiensis-DB27_vs_OP50_4h_rep1~WBPaper00041606:CE_B.thuringiensis-DB27_vs_OP50_4h_rep2~WBPaper00041606:CE_B.thuringiensis-DB27_vs_OP50_4h_rep3~WBPaper00041606:CE_S.aureus_vs_OP50_4h_rep1~WBPaper00041606:CE_S.aureus_vs_OP50_4h_rep2~WBPaper00041606:CE_S.aureus_vs_OP50_4h_rep3_Dye-swap~WBPaper00041606:CE_S.aureus_vs_OP50_4h_rep4_Dye-swap~WBPaper00041606:CE_S.marcescens_vs_OP50_4h_rep1_Dye-swap~WBPaper00041606:CE_S.marcescens_vs_OP50_4h_rep2_Dye-swap~WBPaper00041606:CE_S.marcescens_vs_OP50_4h_rep3~WBPaper00041606:CE_S.marcescens_vs_OP50_4h_rep4~WBPaper00041606:CE_X.nematophila_vs_OP50_4h_rep1~WBPaper00041606:CE_X.nematophila_vs_OP50_4h_rep2~WBPaper00041606:CE_X.nematophila_vs_OP50_4h_rep3~WBPaper00041606:CE_X.nematophila_vs_OP50_4h_rep4	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response
249	23028509	WBPaper00041606.ppa.mr.paper	GSE36517,GSE36519,GSE36521,GSE36523,GSE36636	GPL14372	2	System wide analysis of the evolution of innate immunity in the nematode model species Caenorhabditis elegans and Pristionchus pacificus.	The evolution of genetic mechanisms used to combat bacterial infections is critical for the survival of animals and plants, yet how these genes evolved to produce a robust defense system is poorly understood. Studies of the nematode Caenorhabditis elegans have uncovered a plethora of genetic regulators and effectors responsible for surviving pathogens. However, comparative studies utilizing other free-living nematodes and therefore providing an insight into the evolution of innate immunity have been lacking. Here, we take a systems biology approach and use whole genome microarrays to profile the transcriptional response of C. elegans and the necromenic nematode Pristionchus pacificus after exposure to the four different pathogens Serratia marcescens, Xenorhabdus nematophila, Staphylococcus aureus and Bacillus thuringiensis DB27. C. elegans is susceptible to all four pathogens whilst P. pacificus is only susceptible to S. marcescens and X. nematophila. We show an unexpected level of specificity in host responses to distinct pathogens within and across species, revealing an enormous complexity of effectors of innate immunity. Functional domains enriched in the transcriptomes on different pathogens are similar within a nematode species but different across them, suggesting differences in pathogen sensing and response networks. We find translation inhibition to be a potentially conserved response to gram-negative pathogens in both the nematodes. Further computational analysis indicates that both nematodes when fed on pathogens up-regulate genes known to be involved in other stress responses like heat shock, oxidative and osmotic stress, and genes regulated by DAF-16/FOXO and TGF-beta pathways. This study presents a platform for comparative systems analysis of two nematode model species, and a catalog of genes involved in the evolution of nematode immunity and identifies both pathogen specific and pan-pathogen responses. We discuss the potential effects of ecology on evolution of downstream effectors and upstream regulators on evolution of nematode innate immunity.	15	15992	Sinha A	Sinha A, Rae R, Iatsenko I, Sommer RJ	System wide analysis of the evolution of innate immunity in the nematode model species Caenorhabditis elegans and Pristionchus pacificus.	PLoS One	2012	WBPaper00041606:PP_B.thuringiensis-DB27_vs_OP50_4h_rep1~WBPaper00041606:PP_B.thuringiensis-DB27_vs_OP50_4h_rep2~WBPaper00041606:PP_B.thuringiensis-DB27_vs_OP50_4h_rep3_Dye-swap~WBPaper00041606:PP_B.thuringiensis-DB27_vs_OP50_4h_rep4_Dye-swap~WBPaper00041606:PP_S.aureus_vs_OP50_4h_rep1~WBPaper00041606:PP_S.aureus_vs_OP50_4h_rep2_Dye-swap~WBPaper00041606:PP_S.aureus_vs_OP50_4h_rep3_Dye-swap~WBPaper00041606:PP_S.marcescens_vs_OP50_4h_rep1~WBPaper00041606:PP_S.marcescens_vs_OP50_4h_rep2~WBPaper00041606:PP_S.marcescens_vs_OP50_4h_rep3_Dye-swap.~WBPaper00041606:PP_S.marcescens_vs_OP50_4h_rep4_Dye-swap.~WBPaper00041606:PP_X.nematophila_vs_OP50_4h_rep1~WBPaper00041606:PP_X.nematophila_vs_OP50_4h_rep2~WBPaper00041606:PP_X.nematophila_vs_OP50_4h_rep3_Dye-swap~WBPaper00041606:PP_X.nematophila_vs_OP50_4h_rep4_Dye-swap	Method: microarray|Species: Pristionchus pacificus|Topic: innate immune response
250	23028351	WBPaper00041609.ce.mr.paper	GSE33339	GPL7727	1	Transcriptional repression of Hox genes by C. elegans HP1/HPL and H1/HIS-24.	Elucidation of the biological role of linker histone (H1) and heterochromatin protein 1 (HP1) in mammals has been difficult owing to the existence of a least 11 distinct H1 and three HP1 subtypes in mice. Caenorhabditis elegans possesses two HP1 homologues (HPL-1 and HPL-2) and eight H1 variants. Remarkably, one of eight H1 variants, HIS-24, is important for C. elegans development. Therefore we decided to analyse in parallel the transcriptional profiles of HIS-24, HPL-1/-2 deficient animals, and their phenotype, since hpl-1, hpl-2, and his-24 deficient nematodes are viable. Global transcriptional analysis of the double and triple mutants revealed that HPL proteins and HIS-24 play gene-specific roles, rather than a general repressive function. We showed that HIS-24 acts synergistically with HPL to allow normal reproduction, somatic gonad development, and vulval cell fate decision. Furthermore, the hpl-2; his-24 double mutant animals displayed abnormal development of the male tail and ectopic expression of C. elegans HOM-C/Hox genes (egl-5 and mab-5), which are involved in the developmental patterning of male mating structures. We found that HPL-2 and the methylated form of HIS-24 specifically interact with the histone H3 K27 region in the trimethylated state, and HIS-24 associates with the egl-5 and mab-5 genes. Our results establish the interplay between HPL-1/-2 and HIS-24 proteins in the regulation of positional identity in C. elegans males.	8	314	Studencka M	Studencka M, Wesolowski R, Opitz L, Salinas-Riester G, Wisniewski JR, Jedrusik-Bode M	Transcriptional repression of Hox genes by C. elegans HP1/HPL and H1/HIS-24.	PLoS Genet	2012	WBPaper00041609:Hpl2_His24_rep1~WBPaper00041609:Hpl2_His24_rep2~WBPaper00041609:Hpl1_His24_rep1~WBPaper00041609:Hpl1_His24_rep2~WBPaper00041609:Hpl1_Hpl2_rep1~WBPaper00041609:Hpl1_Hpl2_rep2~WBPaper00041609:Hpl1_Hpl2_His24_rep1~WBPaper00041609:Hpl1_Hpl2_His24_rep2	Method: microarray|Species: Caenorhabditis elegans
251	23566034	WBPaper00042236.ce.mr.paper	GSE43207	GPL11346	1	Loss of the Birt-Hogg-Dube gene product folliculin induces longevity in a hypoxia-inducible factor-dependent manner.	Signaling through the hypoxia-inducible factor hif-1 controls longevity, metabolism, and stress resistance in Caenorhabditis elegans. Hypoxia-inducible factor (HIF) protein levels are regulated through an evolutionarily conserved ubiquitin ligase complex. Mutations in the VHL gene, encoding a core component of this complex, cause a multitumor syndrome and renal cell carcinoma in humans. In the nematode, deficiency in vhl-1 promotes longevity mediated through HIF-1 stabilization. However, this longevity assurance pathway is not yet understood. Here, we identify folliculin (FLCN) as a novel interactor of the hif-1/vhl-1 longevity pathway. FLCN mutations cause Birt-Hogg-Dube syndrome in humans, another tumor syndrome with renal tumorigenesis reminiscent of the VHL disease. Loss of the C. elegans ortholog of FLCN F22D3.2 significantly increased lifespan and enhanced stress resistance in a hif-1-dependent manner. F22D3.2, vhl-1, and hif-1 control longevity by a mechanism distinct from insulin-like signaling. Daf-16 deficiency did not abrogate the increase in lifespan mediated by flcn-1. These findings define FLCN as a player in HIF-dependent longevity signaling and connect organismal aging, stress resistance, and regulation of longevity with the formation of renal cell carcinoma.	6	19636	Gharbi H	Gharbi H, Fabretti F, Bharill P, Rinschen M, Brinkkotter S, Frommolt P, Burst V, Schermer B, Benzing T, Muller RU	Loss of the Birt-Hogg-Dube gene product folliculin induces longevity in a hypoxia-inducible factor-dependent manner.	Aging Cell	2013	WBPaper00042236:N2_rep1~WBPaper00042236:flcn-1(ok975)_rep1~WBPaper00042236:flcn-1(ok975)_rep2~WBPaper00042236:flcn-1(ok975)_rep3~WBPaper00042236:N2_rep2~WBPaper00042236:N2_rep3	Method: microarray|Species: Caenorhabditis elegans
252	23818874	WBPaper00042548.ce.mr.paper	GSE45871	GPL5883	2	Functional analysis of neuronal microRNAs in Caenorhabditis elegans dauer formation by combinational genetics and Neuronal miRISC immunoprecipitation.	Identifying the physiological functions of microRNAs (miRNAs) is often challenging because miRNAs commonly impact gene expression under specific physiological conditions through complex miRNA::mRNA interaction networks and in coordination with other means of gene regulation, such as transcriptional regulation and protein degradation. Such complexity creates difficulties in dissecting miRNA functions through traditional genetic methods using individual miRNA mutations. To investigate the physiological functions of miRNAs in neurons, we combined a genetic &quot;enhancer&quot; approach complemented by biochemical analysis of neuronal miRNA-induced silencing complexes (miRISCs) in C. elegans. Total miRNA function can be compromised by mutating one of the two GW182 proteins (AIN-1), an important component of miRISC. We found that combining an ain-1 mutation with a mutation in unc-3, a neuronal transcription factor, resulted in an inappropriate entrance into the stress-induced, alternative larval stage known as dauer, indicating a role of miRNAs in preventing aberrant dauer formation. Analysis of this genetic interaction suggests that neuronal miRNAs perform such a role partly by regulating endogenous cyclic guanosine monophosphate (cGMP) signaling, potentially influencing two other dauer-regulating pathways. Through tissue-specific immunoprecipitations of miRISC, we identified miRNAs and their likely target mRNAs within neuronal tissue. We verified the biological relevance of several of these miRNAs and found that many miRNAs likely regulate dauer formation through multiple dauer-related targets. Further analysis of target mRNAs suggests potential miRNA involvement in various neuronal processes, but the importance of these miRNA::mRNA interactions remains unclear. Finally, we found that neuronal genes may be more highly regulated by miRNAs than intestinal genes. Overall, our study identifies miRNAs and their targets, and a physiological function of these miRNAs in neurons. It also suggests that compromising other aspects of gene expression, along with miRISC, can be an effective approach to reveal miRNA functions in specific tissues under specific physiological conditions.	4	17230	Than MT	Than MT, Kudlow BA, Han M	Functional analysis of neuronal microRNAs in Caenorhabditis elegans dauer formation by combinational genetics and Neuronal miRISC immunoprecipitation.	PLoS Genet	2013	WBPaper00042548:Neuronal-miRISC-IP_vs_Total-RNA_repB~WBPaper00042548:Neuronal-miRISC-IP_vs_Total-RNA_repC~WBPaper00042548:Neuronal-miRISC-IP_vs_Total-RNA_repD~WBPaper00042548:Neuronal-miRISC-IP_vs_Total-RNA_repE	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
253	23911329	WBPaper00044005.ce.mr.paper	N.A.	N.A.	2	PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity.	Reduced insulin/IGF-1-like signaling (IIS) extends C.elegans lifespan by upregulating stress response (class I) and downregulating other (class II) genes through a mechanism that depends on the conserved transcription factor DAF-16/FOXO. By integrating genome-wide mRNA expression responsiveness to DAF-16 with genome-wide invivo binding data for a compendium of transcription factors, we discovered that PQM-1 is the elusive transcriptional activator that directly controls development (class II) genes by binding to the DAF-16-associated element (DAE). DAF-16 directly regulates class I genes only, through the DAF-16-binding element (DBE). Loss of PQM-1 suppresses daf-2 longevity and further slows development. Surprisingly, the nuclear localization of PQM-1 and DAF-16 is controlled by IIS in opposite ways and was also found to be mutually antagonistic. We observe progressive loss of nuclear PQM-1 with age, explaining declining expression of PQM-1 targets. Together, our data suggest an elegant mechanism for balancing stress response and development.	1	19636	Tepper RG	Tepper RG, Ashraf J, Kaletsky R, Kleemann G, Murphy CT, Bussemaker HJ	PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity.	Cell	2013	WBPaper00044005:pqm-1(ok485)_vs_N2	Method: microarray|Species: Caenorhabditis elegans
254	23918784	WBPaper00044013.ce.mr.paper	GSE43905	GPL10094	2	New role for DCR-1/dicer in Caenorhabditis elegans innate immunity against the highly virulent bacterium Bacillus thuringiensis DB27.	Bacillus thuringiensis produces toxins that target invertebrates, including Caenorhabditis elegans. Virulence of Bacillus strains is often highly specific, such that B. thuringiensis strain DB27 is highly pathogenic to C. elegans but shows no virulence for another model nematode, Pristionchus pacificus. To uncover the underlying mechanisms of the differential responses of the two nematodes to B. thuringiensis DB27 and to reveal the C. elegans defense mechanisms against this pathogen, we conducted a genetic screen for C. elegans mutants resistant to B. thuringiensis DB27. Here, we describe a B. thuringiensis DB27-resistant C. elegans mutant that is identical to nasp-1, which encodes the C. elegans homolog of the nuclear-autoantigenic-sperm protein. Gene expression analysis indicated a substantial overlap between the genes downregulated in the nasp-1 mutant and targets of C. elegans dcr-1/Dicer, suggesting that dcr-1 is repressed in nasp-1 mutants, which was confirmed by quantitative PCR. Consistent with this, the nasp-1 mutant exhibits RNA interference (RNAi) deficiency and reduced longevity similar to those of a dcr-1 mutant. Building on these surprising findings, we further explored a potential role for dcr-1 in C. elegans innate immunity. We show that dcr-1 mutant alleles deficient in microRNA (miRNA) processing, but not those deficient only in RNAi, are resistant to B. thuringiensis DB27. Furthermore, dcr-1 overexpression rescues the nasp-1 mutant's resistance, suggesting that repression of dcr-1 determines the nasp-1 mutant's resistance. Additionally, we identified the collagen-encoding gene col-92 as one of the downstream effectors of nasp-1 that play an important role in resistance to DB27. Taken together, these results uncover a previously unknown role for DCR-1/Dicer in C. elegans antibacterial immunity that is largely associated with miRNA processing.	3	19636	Iatsenko I	Iatsenko I, Sinha A, ROdelsperger C, Sommer RJ	New role for DCR-1/dicer in Caenorhabditis elegans innate immunity against the highly virulent bacterium Bacillus thuringiensis DB27.	Infect Immun	2013	WBPaper00044013:nasp-1_vs_N2_rep1~WBPaper00044013:nasp-1_vs_N2_rep2~WBPaper00044013:N2_vs_nasp-1_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response
255	23931753	WBPaper00044030.ce.mr.paper	GSE48675	GPL7727	1	The NHR-8 nuclear receptor regulates cholesterol and bile acid homeostasis in C. elegans.	Hormone-gated nuclear receptors (NRs) are conserved transcriptional regulators of metabolism, reproduction, and homeostasis. Here we show that C. elegans NHR-8 NR, a homolog of vertebrate liver X and vitamin D receptors, regulates nematode cholesterol balance, fatty acid desaturation, apolipoprotein production, and bile acid metabolism. Loss of nhr-8 results in a deficiency in bile acid-like steroids, called the dafachronic acids, which regulate the related DAF-12/NR, thus controlling entry into the long-lived dauer stage through cholesterol availability. Cholesterol supplementation rescues various nhr-8 phenotypes, including developmental arrest, unsaturated fatty acid deficiency, reduced fertility, and shortened life span. Notably, nhr-8 also interacts with daf-16/FOXO to regulate steady-state cholesterol levels and is synthetically lethal in combination with insulin signaling mutants that promote unregulated growth. Our studies provide important insights into nuclear receptor control of cholesterol balance and metabolism and their impact on development, reproduction, and aging in the context of larger endocrine networks.	14	12880	Magner DB	Magner DB, Wollam J, Shen Y, Hoppe C, Li D, Latza C, Rottiers V, Hutter H, Antebi A	The NHR-8 nuclear receptor regulates cholesterol and bile acid homeostasis in C. elegans.	Cell Metab	2013	WBPaper00044030:N2_rep1~WBPaper00044030:N2_rep2~WBPaper00044030:nhr-8(hd117)_rep1~WBPaper00044030:N2_rep3~WBPaper00044030:nhr-8(hd117)_rep2~WBPaper00044030:nhr-8(hd117)_rep3~WBPaper00044030:N2_rep4~WBPaper00044030:nhr-8(hd117)_rep4~WBPaper00044030:N2_rep5~WBPaper00044030:nhr-8(hd117)_rep5~WBPaper00044030:N2_rep6~WBPaper00044030:nhr-8(hd117)_rep6~WBPaper00044030:N2_rep7~WBPaper00044030:nhr-8(hd117)_rep7	Method: microarray|Species: Caenorhabditis elegans
256	24118919	WBPaper00044316.ce.mr.paper	GSE28915	GPL7727	1	Comparative toxicogenomic responses of mercuric and methyl-mercury.	BACKGROUND: Mercury is a ubiquitous environmental toxicant that exists in multiple chemical forms. A paucity of information exists regarding the differences or similarities by which different mercurials act at the molecular level. RESULTS: Transcriptomes of mixed-stage C. elegans following equitoxic sub-, low- and high-toxicity exposures to inorganic mercuric chloride (HgCl2) and organic methylmercury chloride (MeHgCl) were analyzed. In C. elegans, the mercurials had highly different effects on transcription, with MeHgCl affecting the expression of significantly more genes than HgCl2. Bioinformatics analysis indicated that inorganic and organic mercurials affected different biological processes. RNAi identified 18 genes that were important in C. elegans response to mercurial exposure, although only two of these genes responded to both mercurials. To determine if the responses observed in C. elegans were evolutionarily conserved, the two mercurials were investigated in human neuroblastoma (SK-N-SH), hepatocellular carcinoma (HepG2) and embryonic kidney (HEK293) cells. The human homologs of the affected C. elegans genes were then used to test the effects on gene expression and cell viability after using siRNA during HgCl2 and MeHgCl exposure. As was observed with C. elegans, exposure to the HgCl2 and MeHgCl had different effects on gene expression, and different genes were important in the cellular response to the two mercurials. CONCLUSIONS: These results suggest that, contrary to previous reports, inorganic and organic mercurials have different mechanisms of toxicity. The two mercurials induced disparate effects on gene expression, and different genes were important in protecting the organism from mercurial toxicity.	24	17563	McElwee MK	McElwee MK, Ho LA, Chou JW, Smith MV, Freedman JH	Comparative toxicogenomic responses of mercuric and methyl-mercury.	BMC Genomics	2013	WBPaper00044316:HgCl2_0uM_rep1~WBPaper00044316:HgCl2_0uM_rep2~WBPaper00044316:HgCl2_0uM_rep3~WBPaper00044316:HgCl2_2uM_rep1~WBPaper00044316:HgCl2_2uM_rep2~WBPaper00044316:HgCl2_2uM_rep3~WBPaper00044316:HgCl2_7.5uM_rep1~WBPaper00044316:HgCl2_7.5uM_rep2~WBPaper00044316:HgCl2_7.5uM_rep3~WBPaper00044316:HgCl2_20uM_rep1~WBPaper00044316:HgCl2_20uM_rep2~WBPaper00044316:HgCl2_20uM_rep3~WBPaper00044316:CH3HgCl_0uM_rep1~WBPaper00044316:CH3HgCl_0uM_rep2~WBPaper00044316:CH3HgCl_0uM_rep3~WBPaper00044316:CH3HgCl_0.75uM_rep1~WBPaper00044316:CH3HgCl_0.75uM_rep2~WBPaper00044316:CH3HgCl_0.75uM_rep3~WBPaper00044316:CH3HgCl_2uM_rep1~WBPaper00044316:CH3HgCl_2uM_rep2~WBPaper00044316:CH3HgCl_2uM_rep3~WBPaper00044316:CH3HgCl_7.5uM_rep1~WBPaper00044316:CH3HgCl_7.5uM_rep2~WBPaper00044316:CH3HgCl_7.5uM_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: stress response to metal ion
257	24324795	WBPaper00044578.ce.mr.paper	N.A.	N.A.	1	Molecular strategies of the Caenorhabditis elegans dauer larva to survive extreme desiccation.	Massive water loss is a serious challenge for terrestrial animals, which usually has fatal consequences. However, some organisms have developed means to survive this stress by entering an ametabolic state called anhydrobiosis. The molecular and cellular mechanisms underlying this phenomenon are poorly understood. We recently showed that Caenorhabditis elegans dauer larva, an arrested stage specialized for survival in adverse conditions, is resistant to severe desiccation. However, this requires a preconditioning step at a mild desiccative environment to prepare the organism for harsher desiccation conditions. A systems approach was used to identify factors that are activated during this preconditioning. Using microarray analysis, proteomics, and bioinformatics, genes, proteins, and biochemical pathways that are upregulated during this process were identified. These pathways were validated via reverse genetics by testing the desiccation tolerances of mutants. These data show that the desiccation response is activated by hygrosensation (sensing the desiccative environment) via head neurons. This leads to elimination of reactive oxygen species and xenobiotics, expression of heat shock and intrinsically disordered proteins, polyamine utilization, and induction of fatty acid desaturation pathway. Remarkably, this response is specific and involves a small number of functional pathways, which represent the generic toolkit for anhydrobiosis in plants and animals.	8	19636	Erkut C	Erkut C, Vasilj A, Boland S, Habermann B, Shevchenko A, Kurzchalia TV	Molecular strategies of the Caenorhabditis elegans dauer larva to survive extreme desiccation.	PLoS One	2013	WBPaper00044578:reduced-humidity_repA~WBPaper00044578:reduced-humidity_repB~WBPaper00044578:reduced-humidity_repC~WBPaper00044578:reduced-humidity_repD~WBPaper00044578:control_repA~WBPaper00044578:control_repB~WBPaper00044578:control_repC~WBPaper00044578:control_repD	Method: microarray|Species: Caenorhabditis elegans
258	24586193	WBPaper00044939.ce.mr.paper	GSE49307	GPL8209	2	A variant in the neuropeptide receptor npr-1 is a major determinant of Caenorhabditis elegans growth and physiology.	The mechanistic basis for how genetic variants cause differences in phenotypic traits is often elusive. We identified a quantitative trait locus in Caenorhabditis elegans that affects three seemingly unrelated phenotypic traits: lifetime fecundity, adult body size, and susceptibility to the human pathogen Staphyloccus aureus. We found a QTL for all three traits arises from variation in the neuropeptide receptor gene npr-1. Moreover, we found that variation in npr-1 is also responsible for differences in 247 gene expression traits. Variation in npr-1 is known to determine whether animals disperse throughout a bacterial lawn or aggregate at the edges of the lawn. We found that the allele that leads to aggregation is associated with reduced growth and reproductive output. The altered gene expression pattern caused by this allele suggests that the aggregation behavior might cause a weak starvation state, which is known to reduce growth rate and fecundity. Importantly, we show that variation in npr-1 causes each of these phenotypic differences through behavioral avoidance of ambient oxygen concentrations. These results suggest that variation in npr-1 has broad pleiotropic effects mediated by altered exposure to bacterial food.	15	17563	Andersen EC	Andersen EC, Bloom JS, Gerke JP, KRUGLYAK L	A variant in the neuropeptide receptor npr-1 is a major determinant of Caenorhabditis elegans growth and physiology.	PLoS Genet	2014	WBPaper00044939:npr-1(ad609)_rep1~WBPaper00044939:kyIR9_rep1~WBPaper00044939:npr-1(ky13)_rep1~WBPaper00044939:CB4856_rep1~WBPaper00044939:CB4856_rep2~WBPaper00044939:qgIR1_rep1~WBPaper00044939:npr-1(ky13)_rep2~WBPaper00044939:N2_rep1~WBPaper00044939:npr-1(ad609)_rep2~WBPaper00044939:qgIR1_rep2~WBPaper00044939:kyIR9_rep2~WBPaper00044939:kyIR9_rep3~WBPaper00044939:npr-1(ky13)_rep3~WBPaper00044939:qgIR1_rep3~WBPaper00044939:N2_rep2	Method: microarray|Species: Caenorhabditis elegans
259	24655420	WBPaper00045036.ce.mr.paper	GSE40252	GPL11346	1	A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans.	Although dietary restriction (DR) is known to extend lifespan across species, from yeast to mammals, the signalling events downstream of food/nutrient perception are not well understood. In Caenorhabditis elegans, DR is typically attained either by using the eat-2 mutants that have reduced pharyngeal pumping leading to lower food intake or by feeding diluted bacterial food to the worms. In this study, we show that knocking down a mammalian MEKK3-like kinase gene, mekk-3 in C.elegans, initiates a process similar to DR without compromising food intake. This DR-like state results in upregulation of beta-oxidation genes through the nuclear hormone receptor NHR-49, a HNF-4 homolog, resulting in depletion of stored fat. This metabolic shift leads to low levels of reactive oxygen species (ROS), potent oxidizing agents that damage macromolecules. Increased beta-oxidation, in turn, induces the phase I and II xenobiotic detoxification genes, through PHA-4/FOXA, NHR-8 and aryl hydrocarbon receptor AHR-1, possibly to purge lipophilic endotoxins generated during fatty acid catabolism. The coupling of a metabolic shift with endotoxin detoxification results in extreme longevity following mekk-3 knock-down. Thus, MEKK-3 may function as an important nutrient sensor and signalling component within the organism that controls metabolism. Knocking down mekk-3 may signal an imminent nutrient crisis that results in initiation of a DR-like state, even when food is plentiful.	4	19636	Chamoli M	Chamoli M, Singh A, Malik Y, Mukhopadhyay A	A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans.	Aging Cell	2014	WBPaper00045036:control(RNAi)_rep1~WBPaper00045036:control(RNAi)_rep2~WBPaper00045036:drl-1(RNAi)_rep1~WBPaper00045036:drl-1(RNAi)_rep2	Method: microarray|Species: Caenorhabditis elegans
260	24960609	WBPaper00045417.ce.mr.paper	GSE35939	GPL2875	2	The Wnt receptor Ryk reduces neuronal and cell survival capacity by repressing FOXO activity during the early phases of mutant huntingtin pathogenicity.	The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including -secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD). Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT) in several models of Huntington's disease (HD). Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor -catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished -catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing -secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD.	6	5940	Tourette C	Tourette C, Farina F, Vazquez-Manrique RP, Orfila AM, Voisin J, Hernandez S, Offner N, Parker JA, Menet S, Kim J, Lyu J, Choi SH, Cormier K, Edgerly CK, Bordiuk OL, Smith K, Louise A, Halford M, Stacker S, Vert JP, Ferrante RJ, Lu W, Neri C	The Wnt receptor Ryk reduces neuronal and cell survival capacity by repressing FOXO activity during the early phases of mutant huntingtin pathogenicity.	PLoS Biol	2014	WBPaper00045417:128Q_vs_19Q_rep1~WBPaper00045417:128Q_vs_19Q_rep2~WBPaper00045417:128Q_vs_19Q_rep3~WBPaper00045417:19Q_vs_GFP-only_rep1~WBPaper00045417:19Q_vs_GFP-only_rep2~WBPaper00045417:19Q_vs_GFP-only_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: Wnt signaling pathway|Topic: canonical Wnt signaling pathway|Tissue Specific
261	25093668	WBPaper00045571.ce.mr.paper	GSE44703	GPL10094	2	A functional genomic screen for evolutionarily conserved genes required for lifespan and immunity in germline-deficient C. elegans.	The reproductive system regulates lifespan in insects, nematodes and vertebrates. In Caenorhabditis elegans removal of germline increases lifespan by 60% which is dependent upon insulin signaling, nuclear hormone signaling, autophagy and fat metabolism and their microRNA-regulators. Germline-deficient C. elegans are also more resistant to various bacterial pathogens but the underlying molecular mechanisms are largely unknown. Firstly, we demonstrate that previously identified genes that regulate the extended lifespan of germline-deficient C. elegans (daf-2, daf-16, daf-12, tcer-1, mir-7.1 and nhr-80) are also essential for resistance to the pathogenic bacterium Xenorhabdus nematophila. We then use a novel unbiased approach combining laser cell ablation, whole genome microarrays, RNAi screening and exposure to X. nematophila to generate a comprehensive genome-wide catalog of genes potentially required for increased lifespan and innate immunity in germline-deficient C. elegans. We find 3,440 genes to be upregulated in C. elegans germline-deficient animals in a gonad dependent manner, which are significantly enriched for genes involved in insulin signaling, fatty acid desaturation, translation elongation and proteasome complex function. Using RNAi against a subset of 150 candidate genes selected from the microarray results, we show that the upregulated genes such as transcription factor DAF-16/FOXO, the PTEN homolog lipid phosphatase DAF-18 and several components of the proteasome complex (rpn-6.1, rpn-7, rpn-9, rpn-10, rpt-6, pbs-3 and pbs-6) are essential for both lifespan and immunity of germline deficient animals. We also identify a novel role for genes including par-5 and T12G3.6 in both lifespan-extension and increased survival on X. nematophila. From an evolutionary perspective, most of the genes differentially expressed in germline deficient C. elegans also show a conserved expression pattern in germline deficient Pristionchus pacificus, a nematode species that diverged from C. elegans 250-400 MYA.	3	19636	Sinha A	Sinha A, Rae R	A functional genomic screen for evolutionarily conserved genes required for lifespan and immunity in germline-deficient C. elegans.	PLoS One	2014	WBPaper00045571:germline-ablated_vs_un-ablated_Rep1~WBPaper00045571:gonad-ablated_vs_un-ablated_Rep1~WBPaper00045571:gonad-ablated_vs_un-ablated_Rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response|Tissue Specific
262	25310986	WBPaper00045861.ce.mr.paper	GSE61094	GPL10094	1	The SET-2/SET1 histone H3K4 methyltransferase maintains pluripotency in the Caenorhabditis elegans germline.	Histone H3 Lys 4 methylation (H3K4me) is deposited by the conserved SET1/MLL methyltransferases acting in multiprotein complexes, including Ash2 and Wdr5. Although individual subunits contribute to complex activity, how they influence gene expression in specific tissues remains largely unknown. InCaenorhabditis elegans, SET-2/SET1, WDR-5.1, and ASH-2 are differentially required for germline H3K4 methylation. Using expression profiling on germlines from animals lacking set-2, ash-2, or wdr-5.1, we show that these subunits play unique as well as redundant functions in order to promote expression of germline genes and repress somatic genes. Furthermore, we show that in set-2- and wdr-5.1-deficient germlines, somatic gene misexpression is associated with conversion of germ cellsinto somatic cells and that nuclear RNAi acts in parallel with SET-2 and WDR-5.1 to maintain germline identity. These findings uncover a unique role forSET-2 and WDR-5.1 in preserving germline pluripotency and underline the complexity of the cellular network regulating this process.	12	19636	Robert VJ	Robert VJ, Mercier MG, Bedet C, Janczarski S, Merlet J, Garvis S, Ciosk R, Palladino F	The SET-2/SET1 histone H3K4 methyltransferase maintains pluripotency in the Caenorhabditis elegans germline.	Cell Rep	2014	WBPaper00045861:ash-2(tm1095)_gonads_rep1~WBPaper00045861:ash-2(tm1095)_gonads_rep2~WBPaper00045861:ash-2(lf)_gonads_rep3~WBPaper00045861:N2_gonads_rep1~WBPaper00045861:N2_gonads_rep2~WBPaper00045861:N2_gonads_rep3~WBPaper00045861:set-2(ok952)_gonads_rep1~WBPaper00045861:set-2(ok952)_gonads_rep2~WBPaper00045861:set-2(ok952)_gonads_rep3~WBPaper00045861:wdr-5.1(ok1417)_gonads_rep1~WBPaper00045861:wdr-5.1(ok1417)_gonads_rep2~WBPaper00045861:wdr-5.1(ok1417)_gonads_rep3	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
263	25340560	WBPaper00045918.ce.mr.paper	GSE54212	GPL11346	1	Recovery from an acute infection in C. elegans requires the GATA transcription factor ELT-2.	The mechanisms involved in the recognition of microbial pathogens and activation of the immune system have been extensively studied. However, the mechanisms involved in the recovery phase of an infection are incompletely characterized at both the cellular and physiological levels. Here, we establish a Caenorhabditis elegans-Salmonella enterica model of acute infection and antibiotic treatment for studying biological changes during the resolution phase of an infection. Using whole genome expression profiles of acutely infected animals, we found that genes that are markers of innate immunity are down-regulated upon recovery, while genes involved in xenobiotic detoxification, redox regulation, and cellular homeostasis are up-regulated. In silico analyses demonstrated that genes altered during recovery from infection were transcriptionally regulated by conserved transcription factors, including GATA/ELT-2, FOXO/DAF-16, and Nrf/SKN-1. Finally, we found that recovery from an acute bacterial infection is dependent on ELT-2 activity.	14	19636	Head B	Head B, Aballay A	Recovery from an acute infection in C. elegans requires the GATA transcription factor ELT-2.	PLoS Genet	2014	WBPaper00045918:fer-1_36h_E.coli-OP50_rep1~WBPaper00045918:fer-1_36h_E.coli-OP50_rep2~WBPaper00045918:fer-1_36h_S.enterica-SL1344_rep1~WBPaper00045918:fer-1_36h_S.enterica-SL1344_rep2~WBPaper00045918:fer-1_72h_S.enterica-SL1344_rep1~WBPaper00045918:fer-1_72h_S.enterica-SL1344_rep2~WBPaper00045918:fer-1_96h_S.enterica-SL1344_rep1~WBPaper00045918:fer-1_96h_S.enterica-SL1344_rep2~WBPaper00045918:fer-1_120h_S.enterica-SL1344_rep1~WBPaper00045918:fer-1_120h_S.enterica-SL1344_rep2~WBPaper00045918:fer-1_96h_E.coli-HT115+Tet_rep1~WBPaper00045918:fer-1_96h_E.coli-HT115+Tet_rep2~WBPaper00045918:fer-1_120h_E.coli-HT115+Tet_rep1~WBPaper00045918:fer-1_120h_E.coli-HT115+Tet_rep2	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
264	25552271	WBPaper00046212.ce.mr.paper	GSE30666	GPL13914	1	Natural RNA interference directs a heritable response to the environment.	RNA interference can induce heritable gene silencing, but it remains unexplored whether similar mechanisms play a general role in responses to cues that occur in the wild. We show that transient, mild heat stress in the nematode Caenorhabditis elegans results in changes in messenger RNA levels that last for more than one generation. The affected transcripts are enriched for genes targeted by germline siRNAs downstream of the piRNA pathway, and worms defective for germline RNAi are defective for these heritable effects. Our results demonstrate that a specific siRNA pathway transmits information about variable environmental conditions between generations.	24	14759	Schott D	Schott D, Yanai I, Hunter CP	Natural RNA interference directs a heritable response to the environment.	Sci Rep	2014	WBPaper00046212:N2_20C-G2_rep1~WBPaper00046212:N2_20C-G2_rep2~WBPaper00046212:N2_20C-G2_rep3~WBPaper00046212:N2_25C-G2_rep1~WBPaper00046212:N2_25C-G2_rep2~WBPaper00046212:N2_25C-G2_rep3~WBPaper00046212:HC445_20C-G2_rep1~WBPaper00046212:HC445_20C-G2_rep2~WBPaper00046212:HC445_20C-G2_rep3~WBPaper00046212:HC445_25C-G2_rep1~WBPaper00046212:HC445_25C-G2_rep2~WBPaper00046212:HC445_25C-G2_rep3~WBPaper00046212:N2_20C-G2-20C-G3_rep1~WBPaper00046212:N2_20C-G2-20C-G3_rep2~WBPaper00046212:N2_20C-G2-20C-G3_rep3~WBPaper00046212:N2_25C-G2-20C-G3_rep1~WBPaper00046212:N2_25C-G2-20C-G3_rep2~WBPaper00046212:N2_25C-G2-20C-G3_rep3~WBPaper00046212:HC445_20C-G2-20C-G3_rep1~WBPaper00046212:HC445_20C-G2-20C-G3_rep2~WBPaper00046212:HC445_20C-G2-20C-G3_rep3~WBPaper00046212:HC445_25C-G2-20C-G3_rep1~WBPaper00046212:HC445_25C-G2-20C-G3_rep2~WBPaper00046212:HC445_25C-G2-20C-G3_rep3	Method: microarray|Species: Caenorhabditis elegans
265	25859040	WBPaper00046643.ce.mr.paper	GSE63928	GPL19516	2	The principle of antagonism ensures protein targeting specificity at the endoplasmic reticulum.	The sorting of proteins to the appropriate compartment is one of the most fundamental cellular processes. We found that in the model organism Caenorhabditis elegans, correct cotranslational endoplasmic reticulum (ER) transport required the suppressor activity of the nascent polypeptide-associated complex (NAC). NAC did not affect the accurate targeting of ribosomes to ER translocons mediated by the signal recognition particle (SRP) pathway but inhibited additional unspecific contacts between ribosomes and translocons by blocking their autonomous binding affinity. NAC depletion shortened the life span of Caenorhabditis elegans, caused global mistargeting of translating ribosomes to the ER, and provoked incorrect import of mitochondrial proteins into the ER lumen, resulting in a strong impairment of protein homeostasis in both compartments. Thus, the antagonistic targeting activity of NAC is important in vivo to preserve the robustness and specificity of cellular protein-sorting routes.	8	40843	Gamerdinger M	Gamerdinger M, Hanebuth MA, Frickey T, Deuerling E	The principle of antagonism ensures protein targeting specificity at the endoplasmic reticulum.	Science	2015	WBPaper00046643:control_rep1~WBPaper00046643:icd-1(RNAi)-icd-2(RNAi)_rep1~WBPaper00046643:control_rep2~WBPaper00046643:icd-1(RNAi)-icd-2(RNAi)_rep2~WBPaper00046643:control_rep3~WBPaper00046643:icd-1(RNAi)-icd-2(RNAi)_rep3~WBPaper00046643:control_rep4~WBPaper00046643:icd-1(RNAi)-icd-2(RNAi)_rep4	Method: microarray|Species: Caenorhabditis elegans|Topic: obsolete mRNA splicing via endonucleolytic cleavage and ligation involved in unfolded protein response|Topic: endoplasmic reticulum unfolded protein response|Topic: endoplasmic reticulum|Topic: mitochondrial unfolded protein response|Topic: mitochondrion
266	26455306	WBPaper00048657.ce.mr.paper	GSE68351	GPL10094	2	Natural Variation in plep-1 Causes Male-Male Copulatory Behavior in C.elegans.	In sexual species, gametes have to find and recognize one another. Signaling is thus central to sexual reproduction and involves a rapidly evolving interplay of shared and divergent interests [1-4]. Among Caenorhabditis nematodes, three species have evolved self-fertilization, changing the balance of intersexual relations [5]. Males in these androdioecious species are rare, and the evolutionary interests of hermaphrodites dominate. Signaling has shifted accordingly, with females losing behavioral responses to males [6, 7] and males losing competitive abilities [8, 9]. Males in these species also show variable same-sex and autocopulatory mating behaviors [6, 10]. These behaviors could have evolved by relaxed selection on male function, accumulation of sexually antagonistic alleles that benefit hermaphrodites and harm males [5, 11], or neither of these, because androdioecy also reduces the ability of populations to respond to selection [12-14]. We have identified the genetic cause of a male-male mating behavior exhibited by geographically dispersed C.elegans isolates, wherein males mate with and deposit copulatory plugs on one another's excretory pores. We find a single locus of major effect that is explained by segregation of a loss-of-function mutation in an uncharacterized gene, plep-1, expressed in the excretory cell in both sexes. Males homozygous for the plep-1 mutation have excretory pores that are attractive or receptive to copulatory behavior of other males. Excretory pore plugs are injurious and hermaphrodite activity is compromised in plep-1 mutants, so the allele might be unconditionally deleterious, persisting in the population because the species' androdioecious mating system limits the reach of selection.	24	19636	Noble LM	Noble LM, Chang AS, McNelis D, Kramer M, Yen M, Nicodemus JP, Riccardi DD, Ammerman P, Phillips M, Islam T, Rockman MV	Natural Variation in plep-1 Causes Male-Male Copulatory Behavior in C.elegans.	Curr Biol	2015	WBPaper00048657:N2_vs_reference_rep1-hyb1~WBPaper00048657:plep-1(ttTi53821)_vs_reference_rep1-hyb1~WBPaper00048657:N2_vs_reference_rep2-hyb1~WBPaper00048657:plep-1(ttTi53821)_vs_reference_rep2-hyb1~WBPaper00048657:N2_vs_reference_rep3-hyb1~WBPaper00048657:plep-1(ttTi53821)_vs_reference_rep3-hyb1~WBPaper00048657:N2_vs_reference_rep4-hyb1~WBPaper00048657:plep-1(ttTi53821)_vs_reference_rep4-hyb1~WBPaper00048657:N2_vs_reference_rep1-hyb2~WBPaper00048657:plep-1(ttTi53821)_vs_reference_rep1-hyb2~WBPaper00048657:N2_vs_reference_rep2-hyb2~WBPaper00048657:plep-1(ttTi53821)_vs_reference_rep2-hyb2~WBPaper00048657:N2_vs_reference_rep3-hyb2~WBPaper00048657:plep-1(ttTi53821)_vs_reference_rep3-hyb2~WBPaper00048657:N2_vs_reference_rep4-hyb2~WBPaper00048657:plep-1(ttTi53821)_vs_reference_rep4-hyb2~WBPaper00048657:N2_vs_reference_rep1-hyb3~WBPaper00048657:plep-1(ttTi53821)_vs_reference_rep1-hyb3~WBPaper00048657:N2_vs_reference_rep2-hyb3~WBPaper00048657:plep-1(ttTi53821)_vs_reference_rep2-hyb3~WBPaper00048657:N2_vs_reference_rep3-hyb3~WBPaper00048657:plep-1(ttTi53821)_vs_reference_rep3-hyb3~WBPaper00048657:N2_vs_reference_rep4-hyb3~WBPaper00048657:plep-1(ttTi53821)_vs_reference_rep4-hyb3	Method: microarray|Species: Caenorhabditis elegans
267	26715664	WBPaper00048990.ce.mr.paper	GSE68520	GPL11346	1	The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in Caenorhabditis elegans.	Cell signaling pathways that control proliferation and determine cell fates are tightly regulated to prevent developmental anomalies and cancer. Transcription factors and coregulators are important effectors of signaling pathway output, as they regulate downstream gene programs. In Caenorhabditis elegans, several subunits of the Mediator transcriptional coregulator complex promote or inhibit vulva development, but pertinent mechanisms are poorly defined. Here, we show that Mediator's dissociable Cyclin Dependent Kinase 8 (CDK8) Module (CKM), consisting of cdk-8, cic-1/Cyclin C, mdt-12/dpy-22, and mdt-13/let-19, is required to inhibit ectopic vulval cell fates downstream of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. cdk-8 inhibits ectopic vulva formation by acting downstream of mpk-1/ERK, cell autonomously in vulval cells, and in a kinase-dependent manner. We also provide evidence that the CKM acts as a corepressor for the Ets-family transcription factor LIN-1, as cdk-8 promotes transcriptional repression by LIN-1. In addition, we find that CKM mutation alters Mediator subunit requirements in vulva development: the mdt-23/sur-2 subunit, which is required for vulva development in wild-type worms, is dispensable for ectopic vulva formation in CKM mutants, which instead display hallmarks of unrestrained Mediator tail module activity. We propose a model whereby the CKM controls EGFR-Ras-ERK transcriptional output by corepressing LIN-1 and by fine-tuning Mediator specificity, thus balancing transcriptional repression vs. activation in a critical developmental signaling pathway. Collectively, these data offer an explanation for CKM repression of EGFR signaling output and ectopic vulva formation and provide the first evidence of Mediator CKM-tail module subunit crosstalk in animals.	8	19636	Grants JM	Grants JM, Ying LT, Yoda A, You CC, Okano H, Sawa H, Taubert S	The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in Caenorhabditis elegans.	Genetics	2015	WBPaper00048990:N2_rep1~WBPaper00048990:N2_rep2~WBPaper00048990:N2_rep3~WBPaper00048990:N2_rep4~WBPaper00048990:cdk-8(tm1238)_rep1~WBPaper00048990:cdk-8(tm1238)_rep2~WBPaper00048990:cdk-8(tm1238)_rep3~WBPaper00048990:cdk-8(tm1238)_rep4	Method: microarray|Species: Caenorhabditis elegans
268	26949257	WBPaper00049336.ce.mr.paper	GSE73282,GSE73283	GPL11346	1	Sleep-active neuron specification and sleep induction require FLP-11 neuropeptides to systemically induce sleep.	Sleep is an essential behavioral state. It is induced by conserved sleep-active neurons that express GABA. However, little is known about how sleep neuron function is determined and how sleep neurons change physiology and behavior systemically. Here, we investigated sleep in C. elegans, which is induced by the single sleep-active neuron RIS. We found that the transcription factor LIM-6, which specifies GABAergic function, in parallel determines sleep neuron function through the expression of APTF-1, which specifies the expression of FLP-11 neuropeptides. Surprisingly FLP-11, and not GABA, is the major component that determines the sleep-promoting function of RIS. FLP-11 is constantly expressed in RIS. At sleep onset RIS depolarizes and releases FLP-11 to induce a systemic sleep state.	16	19636	Turek M	Turek M, Besseling J, Spies JP, Konig S, Bringmann H	Sleep-active neuron specification and sleep induction require FLP-11 neuropeptides to systemically induce sleep.	Elife	2016	WBPaper00049336:aptf-1(gk794)_L4_rep1~WBPaper00049336:aptf-1(gk794)_L4_rep2~WBPaper00049336:aptf-1(gk794)_L4_rep3~WBPaper00049336:aptf-1(gk794)_L4_rep4~WBPaper00049336:N2_L4_rep1~WBPaper00049336:N2_L4_rep2~WBPaper00049336:N2_L4_rep3~WBPaper00049336:N2_L4_rep4~WBPaper00049336:aptf-1(gk794)_3-fold-embryo_rep1~WBPaper00049336:aptf-1(gk794)_3-fold-embryo_rep2~WBPaper00049336:aptf-1(gk794)_3-fold-embryo_rep3~WBPaper00049336:aptf-1(gk794)_3-fold-embryo_rep4~WBPaper00049336:N2_3-fold-embryo_rep1~WBPaper00049336:N2_3-fold-embryo_rep2~WBPaper00049336:N2_3-fold-embryo_rep3~WBPaper00049336:N2_3-fold-embryo_rep4	Method: microarray|Species: Caenorhabditis elegans
269	26985669	WBPaper00049380.ce.mr.paper	GSE77905	GPL10094	1	Natural Genetic Variation Influences Protein Abundances in C. elegans Developmental Signalling Pathways.	Complex traits, including common disease-related traits, are affected by many different genes that function in multiple pathways and networks. The apoptosis, MAPK, Notch, and Wnt signalling pathways play important roles in development and disease progression. At the moment we have a poor understanding of how allelic variation affects gene expression in these pathways at the level of translation. Here we report the effect of natural genetic variation on transcript and protein abundance involved in developmental signalling pathways in Caenorhabditis elegans. We used selected reaction monitoring to analyse proteins from the abovementioned four pathways in a set of recombinant inbred lines (RILs) generated from the wild-type strains N2 (Bristol) and CB4856 (Hawaii) to enable quantitative trait locus (QTL) mapping. About half of the cases from the 44 genes tested showed a statistically significant change in protein abundance between various strains, most of these were however very weak (below 1.3-fold change). We detected a distant QTL on the left arm of chromosome II that affected protein abundance of the phosphatidylserine receptor protein PSR-1, and two separate QTLs that influenced embryonic and ionizing radiation-induced apoptosis on chromosome IV. Our results demonstrate that natural variation in C. elegans is sufficient to cause significant changes in signalling pathways both at the gene expression (transcript and protein abundance) and phenotypic levels.	78	19636	Singh KD	Singh KD, Roschitzki B, Snoek LB, Grossmann J, Zheng X, Elvin M, Kamkina P, Schrimpf SP, Poulin GB, Kammenga JE, Hengartner MO	Natural Genetic Variation Influences Protein Abundances in C. elegans Developmental Signalling Pathways.	PLoS One	2016	WBPaper00049380:WN190_Array01_Cy3~WBPaper00049380:WN124_Array02_Cy3~WBPaper00049380:WN116_Array03_Cy3~WBPaper00049380:WN110_Array04_Cy3~WBPaper00049380:control_Array05_Cy3~WBPaper00049380:control_Array06_Cy3~WBPaper00049380:WN021_Array07_Cy3~WBPaper00049380:control_Array08_Cy3~WBPaper00049380:WN174_Array09_Cy3~WBPaper00049380:WN153_Array10_Cy3~WBPaper00049380:WN072_Array11_Cy3~WBPaper00049380:N2_Array12_Cy3~WBPaper00049380:WN128_Array13_Cy3~WBPaper00049380:WN162_Array14_Cy3~WBPaper00049380:WN034_Array15_Cy3~WBPaper00049380:control_Array16_Cy3~WBPaper00049380:control_Array17_Cy3~WBPaper00049380:WN158_Array18_Cy3~WBPaper00049380:control_Array19_Cy3~WBPaper00049380:WN176_Array20_Cy3~WBPaper00049380:WN177_Array21_Cy3~WBPaper00049380:WN152_Array22_Cy3~WBPaper00049380:control_Array23_Cy3~WBPaper00049380:control_Array24_Cy3~WBPaper00049380:WN140_Array25_Cy3~WBPaper00049380:control_Array26_Cy3~WBPaper00049380:WN186_Array27_Cy3~WBPaper00049380:control_Array28_Cy3~WBPaper00049380:control_Array29_Cy3~WBPaper00049380:control_Array30_Cy3~WBPaper00049380:control_Array31_Cy3~WBPaper00049380:CB4856_Array32_Cy3~WBPaper00049380:control_Array33_Cy3~WBPaper00049380:WN076_Array34_Cy3~WBPaper00049380:WN106_Array35_Cy3~WBPaper00049380:WN109_Array36_Cy3~WBPaper00049380:WN142_Array37_Cy3~WBPaper00049380:WN135_Array38_Cy3~WBPaper00049380:control_Array39_Cy3~WBPaper00049380:control_Array01_Cy5~WBPaper00049380:WN098_Array02_Cy5~WBPaper00049380:control_Array03_Cy5~WBPaper00049380:control_Array04_Cy5~WBPaper00049380:WN020_Array05_Cy5~WBPaper00049380:WN038_Array06_Cy5~WBPaper00049380:CB4856_Array07_Cy5~WBPaper00049380:WN071_Array08_Cy5~WBPaper00049380:control_Array09_Cy5~WBPaper00049380:WN048_Array10_Cy5~WBPaper00049380:WN161_Array11_Cy5~WBPaper00049380:control_Array12_Cy5~WBPaper00049380:control_Array13_Cy5~WBPaper00049380:WN146_Array14_Cy5~WBPaper00049380:control_Array15_Cy5~WBPaper00049380:WN058_Array16_Cy5~WBPaper00049380:WN185_Array17_Cy5~WBPaper00049380:control_Array18_Cy5~WBPaper00049380:WN129_Array19_Cy5~WBPaper00049380:N2_Array20_Cy5~WBPaper00049380:WN113_Array21_Cy5~WBPaper00049380:control_Array22_Cy5~WBPaper00049380:WN159_Array23_Cy5~WBPaper00049380:WN057_Array24_Cy5~WBPaper00049380:control_Array25_Cy5~WBPaper00049380:WN134_Array26_Cy5~WBPaper00049380:control_Array27_Cy5~WBPaper00049380:WN041_Array28_Cy5~WBPaper00049380:WN098_Array29_Cy5~WBPaper00049380:WN046_Array30_Cy5~WBPaper00049380:N2_Array31_Cy5~WBPaper00049380:control_Array32_Cy5~WBPaper00049380:CB4856_Array33_Cy5~WBPaper00049380:control_Array34_Cy5~WBPaper00049380:control_Array35_Cy5~WBPaper00049380:control_Array36_Cy5~WBPaper00049380:control_Array37_Cy5~WBPaper00049380:control_Array38_Cy5~WBPaper00049380:WN075_Array39_Cy5	Method: microarray|Species: Caenorhabditis elegans|Topic: programmed cell death|Topic: apoptotic DNA fragmentation|Topic: apoptotic process|Topic: engulfment of apoptotic cell|Topic: Wnt signaling pathway|Topic: canonical Wnt signaling pathway
270	27320929	WBPaper00049736.ce.mr.paper	GSE81409	GPL10094	1	Sperm Affects Head Sensory Neuron in Temperature Tolerance of Caenorhabditis elegans.	Tolerance to environmental temperature change is essential for the survival and proliferation of animals. The process is controlled by various body tissues, but the orchestration of activity within the tissue network has not been elucidated in detail. Here, we show that sperm affects the activity of temperature-sensing neurons (ASJ) that control cold tolerance in Caenorhabditis elegans. Genetic impairment of sperm caused abnormal cold tolerance, which was unexpectedly restored by impairment of temperature signaling in ASJ neurons. Calcium imaging revealed that ASJ neuronal activity in response to temperature was decreased in sperm mutant gsp-4 with impaired protein phosphatase 1 and rescued by expressing gsp-4 in sperm. Genetic analysis revealed a feedback network in which ASJ neuronal activity regulates the intestine through insulin and a steroid hormone, which then affects sperm and, in turn, controls ASJ neuronal activity. Thus, we propose that feedback between sperm and a sensory neuron mediating temperature tolerance.	12	16707	Sonoda S	Sonoda S, Ohta A, Maruo A, Ujisawa T, Kuhara A	Sperm Affects Head Sensory Neuron in Temperature Tolerance of Caenorhabditis elegans.	Cell Rep	2016	WBPaper00049736:N2_15deg_repA~WBPaper00049736:N2_15deg-then-25deg(3hr)_repA~WBPaper00049736:N2_15deg-then-25deg(12hr)_repA~WBPaper00049736:daf-2(e1370)_15deg-then-25deg(12hr)_repA~WBPaper00049736:N2_15deg_repB~WBPaper00049736:N2_15deg-then-25deg(3hr)_repB~WBPaper00049736:N2_15deg-then-25deg(12hr)_repB~WBPaper00049736:daf-2(e1370)_15deg-then-25deg(12hr)_repB~WBPaper00049736:N2_15deg_rep1~WBPaper00049736:N2_15deg-then-25deg(3hr)_rep1~WBPaper00049736:N2_15deg-then-25deg(12hr)_rep1~WBPaper00049736:daf-2(e1370)_15deg-then-25deg(12hr)_rep1	Method: microarray|Species: Caenorhabditis elegans
271	27600703	WBPaper00050096.ce.mr.paper	GSE81592	GPL11346	1	Role of GATA transcription factor ELT-2 and p38 MAPK PMK-1 in recovery from acute P. aeruginosa infection in C. elegans.	Infectious diseases caused by bacterial pathogens reduce the fitness of their associated host but are generally limited in duration. In order for the diseased host to regain any lost fitness upon recovery, a variety of molecular, cellular, and physiological processes must be employed. To better understand mechanisms underlying the recovery process, we have modeled an acute Pseudomonas aeruginosa infection in C. elegans using brief exposures to this pathogen and subsequent antibiotic treatment. To identify host genes altered during recovery from P. aeruginosa infection, we performed whole genome expression profiling. The analysis of this dataset indicated that the activity of the host immune system is down-regulated upon recovery and revealed shared and pathogen-specific host responses during recovery. We determined that the GATA transcription factor ELT-2 and the p38 MAP kinase PMK-1 are necessary for animals to successfully recover from an acute P. aeruginosa infection. In addition, we found that ELT-2 plays a more prominent and earlier role than PMK-1 during recovery. Our data sheds further light on the molecular mechanisms and transcriptional programs involved in recovery from an acute bacterial infection, which provides a better understanding of the entire infectious disease process.	20	19636	Head BP	Head BP, Olaitan AO, Aballay A	Role of GATA transcription factor ELT-2 and p38 MAPK PMK-1 in recovery from acute P. aeruginosa infection in C. elegans.	Virulence	2016	WBPaper00050096:fer-1_72h_OP50_rep1~WBPaper00050096:fer-1_72h_OP50_rep2~WBPaper00050096:fer-1_72h_OP50_rep3~WBPaper00050096:fer-1_76h_PA14_rep1~WBPaper00050096:fer-1_76h_PA14_rep2~WBPaper00050096:fer-1_76h_PA14_rep3~WBPaper00050096:fer-1_82h_PA14_6h-recovery_rep1~WBPaper00050096:fer-1_82h_PA14_6h-recovery_rep2~WBPaper00050096:fer-1_82h_PA14_6h-recovery_rep3~WBPaper00050096:fer-1_88h_PA14_12h-recovery_rep1~WBPaper00050096:fer-1_88h_PA14_12h-recovery_rep2~WBPaper00050096:fer-1_88h_PA14_12h-recovery_rep3~WBPaper00050096:fer-1_100h_PA14_24h-recovery_rep1~WBPaper00050096:fer-1_100h_PA14_24h-recovery_rep2~WBPaper00050096:fer-1_100h_PA14_24h-recovery_rep3~WBPaper00050096:fer-1_82h_OP50_rep1~WBPaper00050096:fer-1_82h_OP50_rep2~WBPaper00050096:fer-1_82h_OP50_6h-recovery_rep1~WBPaper00050096:fer-1_82h_OP50_6h-recovery_rep2~WBPaper00050096:fer-1_82h_OP50_6h-recovery_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism
272	27905558	WBPaper00050488.ce.mr.paper	GSE76413	GPL10094	1	MicroRNA mir-34 provides robustness to environmental stress response via the DAF-16 network in C. elegans.	Diverse stresses and aging alter expression levels of microRNAs, suggesting a role for these posttranscriptional regulators of gene expression in stress modulation and longevity. Earlier studies demonstrated a central role for the miR-34 family in promoting cell cycle arrest and cell death following stress in human cells. However, the biological significance of this response was unclear. Here we show that in C. elegans mir-34 upregulation is necessary for developmental arrest, correct morphogenesis, and adaptation to a lower metabolic state to protect animals against stress-related damage. Either deletion or overexpression of mir-34 lead to an impaired stress response, which can largely be explained by perturbations in DAF-16/FOXO target gene expression. We demonstrate that mir-34 expression is regulated by the insulin signaling pathway via a negative feedback loop between miR-34 and DAF-16/FOXO. We propose that mir-34 provides robustness to stress response programs by controlling noise in the DAF-16/FOXO-regulated gene network.	30	19636	Isik M	Isik M, Blackwell TK, Berezikov E	MicroRNA mir-34 provides robustness to environmental stress response via the DAF-16 network in C. elegans.	Sci Rep	2016	WBPaper00050488:N2_adult_20C_rep1~WBPaper00050488:N2_adult_20C_rep2~WBPaper00050488:N2_adult_20C_rep3~WBPaper00050488:N2_adult_25C_rep1~WBPaper00050488:N2_adult_25C_rep2~WBPaper00050488:N2_adult_25C_rep3~WBPaper00050488:mir-34(gk437)_adult_20C_rep1~WBPaper00050488:mir-34(gk437)_adult_20C_rep2~WBPaper00050488:mir-34(gk437)_adult_20C_rep3~WBPaper00050488:mir-34(gk437)_adult_25C_rep1~WBPaper00050488:mir-34(gk437)_adult_25C_rep2~WBPaper00050488:mir-34(gk437)_adult_25C_rep3~WBPaper00050488:mir-34(OverExpression)_adult_20C_rep1~WBPaper00050488:mir-34(OverExpression)_adult_20C_rep2~WBPaper00050488:mir-34(OverExpression)_adult_25C_rep1~WBPaper00050488:mir-34(OverExpression)_adult_25C_rep2~WBPaper00050488:mir-34(OverExpression)_adult_25C_rep3~WBPaper00050488:N2_dauer_20C_rep1~WBPaper00050488:N2_dauer_20C_rep2~WBPaper00050488:mir-34(gk437)_dauer_20C_rep1~WBPaper00050488:mir-34(gk437)_dauer_20C_rep2~WBPaper00050488:mir-34(OverExpression)_dauer_20C_rep1~WBPaper00050488:daf-2(e1370)_dauer_25C_rep1~WBPaper00050488:daf-2(e1370)_dauer_25C_rep2~WBPaper00050488:daf-2(e1370);mir-34(gk437)_dauer_25C_rep1~WBPaper00050488:daf-2(e1370);mir-34(gk437)_dauer_25C_rep2~WBPaper00050488:mir-34(gk437)_dauer_20C_rep3~WBPaper00050488:mir-34(OverExpression)_dauer_20C_rep2~WBPaper00050488:mir-34(OverExpression)_dauer_20C_rep3~WBPaper00050488:daf-2(e1370);mir-34(gk437)_dauer_25C_rep3	Method: microarray|Species: Caenorhabditis elegans
273	28179390	WBPaper00050712.ce.mr.paper	GSE86431	GPL10094	1	Natural Genetic Variation in the Caenorhabditis elegans Response to Pseudomonas aeruginosa.	Caenorhabditis elegans responds to pathogenic microorganisms by activating its innate immune system, which consists of physical barriers, behavioral responses, and microbial killing mechanisms. We examined whether natural variation plays a role in the response of C. elegans to Pseudomonas aeruginosa using two C. elegans strains that carry the same allele of npr-1, a gene that encodes a G-protein-coupled receptor related to mammalian neuropeptide Y receptors, but that differ in their genetic backgrounds. Strains carrying an allele for the NPR-1 215F isoform have been shown to exhibit lack of pathogen avoidance behavior and deficient immune response towards P. aeruginosa relative to the wild-type (N2) strain. We found that the wild isolate from Germany RC301, which carries the allele for NPR-1 215F, shows an enhanced resistance to P. aeruginosa infection when compared with strain DA650, which also carries NPR-1 215F but in an N2 background. Using a whole-genome sequencing single-nucleotide polymorphism (WGS-SNP) mapping strategy, we determined that the resistance to P. aeruginosa infection maps to a region on chromosome V. Furthermore, we demonstrated that the mechanism for the enhanced resistance to P. aeruginosa infection relies exclusively on strong P. aeruginosa avoidance behavior and does not involve the main immune, stress and lifespan extension pathways in C. elegans Our findings underscore the importance of pathogen-specific behavioral immune defense in the wild, which seems to be favored over the more energy-costly mechanism of activation of physiological cellular defenses.	6	19636	Martin N	Martin N, Singh J, Aballay A	Natural Genetic Variation in the Caenorhabditis elegans Response to Pseudomonas aeruginosa.	G3 (Bethesda)	2017	WBPaper00050712:DA650_4h_PA14_rep1~WBPaper00050712:DA650_4h_PA14_rep2~WBPaper00050712:DA650_4h_PA14_rep3~WBPaper00050712:RC301_4h_PA14_rep1~WBPaper00050712:RC301_4h_PA14_rep2~WBPaper00050712:RC301_4h_PA14_rep3	Method: microarray|Species: Caenorhabditis elegans
274	28182654	WBPaper00050743.ce.mr.paper	GSE82322	GPL21109	1	ELLI-1, a novel germline protein, modulates RNAi activity and P-granule accumulation in Caenorhabditis elegans.	Germ cells contain non-membrane bound cytoplasmic organelles that help maintain germline integrity. In C. elegans they are called P granules; without them, the germline undergoes partial masculinization and aberrant differentiation. One key P-granule component is the Argonaute CSR-1, a small-RNA binding protein that antagonizes accumulation of sperm-specific transcripts in developing oocytes and fine-tunes expression of proteins critical to early embryogenesis. Loss of CSR-1 complex components results in a very specific, enlarged P-granule phenotype. In a forward screen to identify mutants with abnormal P granules, ten alleles were recovered with a csr-1 P-granule phenotype, eight of which contain mutations in known components of the CSR-1 complex (csr-1, ego-1, ekl-1, and drh-3). The remaining two alleles are in a novel gene now called elli-1 (enlarged germline granules). ELLI-1 is first expressed in primordial germ cells during mid-embryogenesis, and continues to be expressed in the adult germline. While ELLI-1 forms cytoplasmic aggregates, they occasionally dock, but do not co-localize with P granules. Instead, the majority of ELLI-1 aggregates accumulate in the shared germline cytoplasm. In elli-1 mutants, several genes that promote RNAi and P-granule accumulation are upregulated, and embryonic lethality, sterility, and RNAi resistance in a hypomorphic drh-3 allele is enhanced, suggesting that ELLI-1 functions with CSR-1 to modulate RNAi activity, P-granule accumulation, and post-transcriptional expression in the germline.	8	20441	Andralojc KM	Andralojc KM, Campbell AC, Kelly AL, Terrey M, Tanner PC, Gans IM, Senter-Zapata MJ, Khokhar ES, Updike DL	ELLI-1, a novel germline protein, modulates RNAi activity and P-granule accumulation in Caenorhabditis elegans.	PLoS Genet	2017	WBPaper00050743:elli-1(sam3)_rep1~WBPaper00050743:elli-1(sam3)_rep2~WBPaper00050743:elli-1(sam3)_rep3~WBPaper00050743:elli-1(sam3)_rep4~WBPaper00050743:control_rep1~WBPaper00050743:control_rep2~WBPaper00050743:control_rep3~WBPaper00050743:control_rep4	Method: microarray|Species: Caenorhabditis elegans
275	28397803	WBPaper00051079.ce.mr.paper	GSE85237	GPL10094	1	Tomatidine enhances lifespan and healthspan in C. elegans through mitophagy induction via the SKN-1/Nrf2 pathway.	Aging is a major international concern that brings formidable socioeconomic and healthcare challenges. Small molecules capable of improving the health of older individuals are being explored. Small molecules that enhance cellular stress resistance are a promising avenue to alleviate declines seen in human aging. Tomatidine, a natural compound abundant in unripe tomatoes, inhibits age-related skeletal muscle atrophy in mice. Here we show that tomatidine extends lifespan and healthspan in C. elegans, an animal model of aging which shares many major longevity pathways with mammals. Tomatidine improves many C. elegans behaviors related to healthspan and muscle health, including increased pharyngeal pumping, swimming movement, and reduced percentage of severely damaged muscle cells. Microarray, imaging, and behavioral analyses reveal that tomatidine maintains mitochondrial homeostasis by modulating mitochondrial biogenesis and PINK-1/DCT-1-dependent mitophagy. Mechanistically, tomatidine induces mitochondrial hormesis by mildly inducing ROS production, which in turn activates the SKN-1/Nrf2 pathway and possibly other cellular antioxidant response pathways, followed by increased mitophagy. This mechanism occurs in C. elegans, primary rat neurons, and human cells. Our data suggest that tomatidine may delay some physiological aspects of aging, and points to new approaches for pharmacological interventions for diseases of aging.	7	19636	Fang EF	Fang EF, Waltz TB, Kassahun H, Lu Q, Kerr JS, Morevati M, Fivenson EM, Wollman BN, Marosi K, Wilson MA, Iser WB, Eckley DM, Zhang Y, Lehrmann E, Goldberg IG, Scheibye-Knudsen M, Mattson MP, Nilsen H, Bohr VA, Becker KG	Tomatidine enhances lifespan and healthspan in C. elegans through mitophagy induction via the SKN-1/Nrf2 pathway.	Sci Rep	2017	WBPaper00051079:Control_rep1~WBPaper00051079:Control_rep2~WBPaper00051079:Control_rep3~WBPaper00051079:Control_rep4~WBPaper00051079:Tomatidine_rep1~WBPaper00051079:Tomatidine_rep2~WBPaper00051079:Tomatidine_rep3	Method: microarray|Species: Caenorhabditis elegans
276	28495447	WBPaper00051223.ce.mr.paper	N.A.	N.A.	2	Characterization of gene expression associated with the adaptation of the nematode C. elegans to hypoxia and reoxygenation stress reveals an unexpected function of the neuroglobin GLB-5 in innate immunity.	Oxygen (O2) is a double-edged sword to cells, for while it is vital for energy production in all aerobic animals and insufficient O2 (hypoxia) can lead to cell death, the reoxygenation of hypoxic tissues may trigger the generation of reactive oxygen species (ROS) that can destroy any biological molecule. Indeed, both hypoxia and hypoxia-reoxygenation (H/R) stress are harmful, and may play a critical role in the pathophysiology of many human diseases, such as myocardial ischemia and stroke. Therefore, understanding how animals adapt to hypoxia and H/R stress is critical for developing better treatments for these diseases. Previous studies showed that the neuroglobin GLB-5(Haw) is essential for the fast recovery of the nematode Caenorhabditis elegans (C. elegans) from H/R stress. Here, we characterize the changes in neuronal gene expression during the adaptation of worms to hypoxia and recovery from H/R stress. Our analysis shows that innate immunity genes are differentially expressed during both adaptation to hypoxia and recovery from H/R stress. Moreover, we reveal that the prolyl hydroxylase EGL-9, a known regulator of both adaptation to hypoxia and the innate immune response, inhibits the fast recovery from H/R stress through its activity in the O2-sensing neurons AQR, PQR, and URX. Finally, we show that GLB-5(Haw) acts in AQR, PQR, and URX to increase the tolerance of worms to Pseudomonas aeruginosa pathogenesis. Together, our studies suggest that innate immunity and recovery from H/R stress are regulated by overlapping signaling pathways.	16	10762	Zuckerman B	Zuckerman B, Abergel Z, Zelmanovich V, Romero L, Abergel R, Livshits L, Smith Y, Gross E	Characterization of gene expression associated with the adaptation of the nematode C. elegans to hypoxia and reoxygenation stress reveals an unexpected function of the neuroglobin GLB-5 in innate immunity.	Free Radic Biol Med	2017	WBPaper00051223:glb-5(Haw);npr-1(ad609)_neurons_0hr_vs_glb-5(Haw);npr-1(ad609)_neurons_3hr~WBPaper00051223:glb-5(Haw);npr-1(ad609)_neurons_3hr_vs_glb-5(Haw);npr-1(ad609)_neurons_6hr~WBPaper00051223:glb-5(Haw);npr-1(ad609)_neurons_6hr_vs_glb-5(Haw);npr-1(ad609)_neurons_24.5hr~WBPaper00051223:glb-5(Haw);npr-1(ad609)_neurons_24.5hr_vs_glb-5(Haw);npr-1(ad609)_neurons_28hr~WBPaper00051223:npr-1(ad609)_neurons_0hr_vs_npr-1(ad609)_neurons_3hr~WBPaper00051223:npr-1(ad609)_neurons_3hr_vs_npr-1(ad609)_neurons_6hr~WBPaper00051223:npr-1(ad609)_neurons_6hr_vs_npr-1(ad609)_neurons_24.5hr~WBPaper00051223:npr-1(ad609)_neurons_24.5hr_vs_npr-1(ad609)_neurons_28hr~WBPaper00051223:glb-5(Haw);npr-1(ad609)_gut_0hr_vs_glb-5(Haw);npr-1(ad609)_gut_3hr~WBPaper00051223:glb-5(Haw);npr-1(ad609)_gut_3hr_vs_glb-5(Haw);npr-1(ad609)_gut_6hr~WBPaper00051223:glb-5(Haw);npr-1(ad609)_gut_6hr_vs_glb-5(Haw);npr-1(ad609)_gut_24.5hr~WBPaper00051223:glb-5(Haw);npr-1(ad609)_gut_24.5hr_vs_glb-5(Haw);npr-1(ad609)_gut_28hr~WBPaper00051223:glb-5(Haw);npr-1(ad609)_neurons_3hr_vs_glb-5(Haw);npr-1(ad609)_gut_3hr~WBPaper00051223:glb-5(Haw);npr-1(ad609)_neurons_3hr_vs_npr-1(ad609)_neurons_3hr~WBPaper00051223:glb-5(Haw);npr-1(ad609)_neurons_24.5hr_vs_glb-5(Haw);npr-1(ad609)_gut_24.5hr~WBPaper00051223:glb-5(Haw);npr-1(ad609)_neurons_24.5hr_vs_npr-1(ad609)_neurons_24.5hr	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response|Tissue Specific
277	28560849	WBPaper00051304.ce.mr.paper	GSE67754	GPL10094	2	Transcription factors CEP-1/p53 and CEH-23 collaborate with AAK-2/AMPK to modulate longevity in Caenorhabditis elegans.	A decline in mitochondrial electron transport chain (ETC) function has long been implicated in aging and various diseases. Recently, moderate mitochondrial ETC dysfunction has been found to prolong lifespan in diverse organisms, suggesting a conserved and complex role of mitochondria in longevity determination. Several nuclear transcription factors have been demonstrated to mediate the lifespan extension effect associated with partial impairment of the ETC, suggesting that compensatory transcriptional response to be crucial. In this study, we showed that the transcription factors CEP-1/p53 and CEH-23 act through a similar mechanism to modulate longevity in response to defective ETC in Caenorhabditis elegans. Genomewide gene expression profiling comparison revealed a new link between these two transcription factors and AAK-2/AMP kinase (AMPK) signaling. Further functional analyses suggested that CEP-1/p53 and CEH-23 act downstream of AAK-2/AMPK signaling and CRTC-1 transcriptional coactivator to promote stress resistance and lifespan. As AAK-2, CEP-1, and CEH-23 are all highly conserved, our findings likely provide important insights for understanding the organismal adaptive response to mitochondrial dysfunction in diverse organisms and will be relevant to aging and pathologies with a mitochondrial etiology in human.	4	19636	Chang HW	Chang HW, Pisano S, Chaturbedi A, Chen J, Gordon S, Baruah A, Lee SS	Transcription factors CEP-1/p53 and CEH-23 collaborate with AAK-2/AMPK to modulate longevity in Caenorhabditis elegans.	Aging Cell	2017	WBPaper00051304:isp-1(qm150);ceh-23(ms23)_vs_isp-1(qm150)_rep1~WBPaper00051304:isp-1(qm150)_vs_isp-1(qm150);ceh-23(ms23)_rep1~WBPaper00051304:isp-1(qm150)_vs_isp-1(qm150);ceh-23(ms23)_rep2~WBPaper00051304:isp-1(qm150)_vs_isp-1(qm150);ceh-23(ms23)_rep3	Method: microarray|Species: Caenorhabditis elegans
278	28725724	WBPaper00051537.ce.mr.paper	GSE71770	GPL11346	1	Fluid dynamics alter Caenorhabditis elegans body length via TGF-/DBL-1 neuromuscular signaling.	Skeletal muscle wasting is a major obstacle for long-term space exploration. Similar to astronauts, the nematode Caenorhabditis elegans displays negative muscular and physical effects when in microgravity in space. It remains unclear what signaling molecules and behavior(s) cause these negative alterations. Here we studied key signaling molecules involved in alterations of C. elegans physique in response to fluid dynamics in ground-based experiments. Placing worms in space on a 1G accelerator increased a myosin heavy chain, myo-3, and a transforming growth factor- (TGF-), dbl-1, gene expression. These changes also occurred when the fluid dynamic parameters viscosity/drag resistance or depth of liquid culture were increased on the ground. In addition, body length increased in wild type and body wall cuticle collagen mutants, rol-6 and dpy-5, grown in liquid culture. In contrast, body length did not increase in TGF-, dbl-1, or downstream signaling pathway, sma-4/Smad, mutants. Similarly, a D1-like dopamine receptor, DOP-4, and a mechanosensory channel, UNC-8, were required for increased dbl-1 expression and altered physique in liquid culture. As C. elegans contraction rates are much higher when swimming in liquid than when crawling on an agar surface, we also examined the relationship between body length enhancement and rate of contraction. Mutants with significantly reduced contraction rates were typically smaller. However, in dop-4, dbl-1, and sma-4 mutants, contraction rates still increased in liquid. These results suggest that neuromuscular signaling via TGF-/DBL-1 acts to alter body physique in response to environmental conditions including fluid dynamics.	9	16911	Harada S	Harada S, Hashizume T, Nemoto K, Shao Z, Higashitani N, Etheridge T, Szewczyk NJ, Fukui K, Higashibata A, Higashitani A	Fluid dynamics alter Caenorhabditis elegans body length via TGF-/DBL-1 neuromuscular signaling.	NPJ Microgravity	2016	WBPaper00051537:microG_4days_rep1~WBPaper00051537:microG_4days_rep2~WBPaper00051537:microG_4days_rep3~WBPaper00051537:1G-control_4days_rep1~WBPaper00051537:1G-control_4days_rep2~WBPaper00051537:1G-control_4days_rep3~WBPaper00051537:ground-control_4days_rep1~WBPaper00051537:ground-control_4days_rep2~WBPaper00051537:ground-control_4days_rep3	Method: microarray|Species: Caenorhabditis elegans
279	28725720	WBPaper00051538.ce.mr.paper	GSE71771	GPL11346	1	Microgravity elicits reproducible alterations in cytoskeletal and metabolic gene and protein expression in space-flown Caenorhabditis elegans.	Although muscle atrophy is a serious problem during spaceflight, little is known about the sequence of molecular events leading to atrophy in response to microgravity. We carried out a spaceflight experiment using Caenorhabditis elegans onboard the Japanese Experiment Module of the International Space Station. Worms were synchronously cultured in liquid media with bacterial food for 4 days under microgravity or on a 1-G centrifuge. Worms were visually observed for health and movement and then frozen. Upon return, we analyzed global gene and protein expression using DNA microarrays and mass spectrometry. Body length and fat accumulation were also analyzed. We found that in worms grown from the L1 larval stage to adulthood under microgravity, both gene and protein expression levels for muscular thick filaments, cytoskeletal elements, and mitochondrial metabolic enzymes decreased relative to parallel cultures on the 1-G centrifuge (95% confidence interval (P0.05)). In addition, altered movement and decreased body length and fat accumulation were observed in the microgravity-cultured worms relative to the 1-G cultured worms. These results suggest protein expression changes that may account for the progressive muscular atrophy observed in astronauts.	6	16779	Higashibata A	Higashibata A, Hashizume T, Nemoto K, Higashitani N, Etheridge T, Mori C, Harada S, Sugimoto T, Szewczyk NJ, Baba SA, Mogami Y, Fukui K, Higashitani A	Microgravity elicits reproducible alterations in cytoskeletal and metabolic gene and protein expression in space-flown Caenorhabditis elegans.	NPJ Microgravity	2016	WBPaper00051538:Ground_rep1~WBPaper00051538:Ground_rep2~WBPaper00051538:Ground_rep3~WBPaper00051538:Flight_rep1~WBPaper00051538:Flight_rep2~WBPaper00051538:Flight_rep3	Method: microarray|Species: Caenorhabditis elegans
280	27732836	WBPaper00051555.ce.mr.paper	N.A.	N.A.	1	NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair.	Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive neurodegeneration and cerebellar ataxia. A-T is causally linked to defects in ATM, a master regulator of the response to and repair of DNA double-strand breaks. The molecular basis of cerebellar atrophy and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD(+), and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD(+) reduce the severity of A-T neuropathology, normalize neuromuscular function, delay memory loss, and extend lifespan inboth animal models. Mechanistically, treatments that increase intracellular NAD(+) also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy. This work links two major theories on aging, DNA damage accumulation, and mitochondrial dysfunction through nuclear DNA damage-induced nuclear-mitochondrial signaling, and demonstrates that they are important pathophysiological determinants in premature aging of A-T, pointing to therapeutic interventions.	48	19636	Fang EF	Fang EF, Kassahun H, Croteau DL, Scheibye-Knudsen M, Marosi K, Lu H, Shamanna RA, Kalyanasundaram S, Bollineni RC, Wilson MA, Iser WB, Wollman BN, Morevati M, Li J, Kerr JS, Lu Q, Waltz TB, Tian J, Sinclair DA, Mattson MP, Nilsen H, Bohr VA	NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair.	Cell Metab	2016	WBPaper00051555:N2_Control_Day1_Rep1~WBPaper00051555:N2_Control_Day1_Rep2~WBPaper00051555:N2_Control_Day1_Rep3~WBPaper00051555:N2_Nicotinamide-Riboside_Day1_Rep1~WBPaper00051555:N2_Nicotinamide-Riboside_Day1_Rep2~WBPaper00051555:N2_Nicotinamide-Riboside_Day1_Rep3~WBPaper00051555:N2_Sirtuin1720_Day1_Rep1~WBPaper00051555:N2_Sirtuin1720_Day1_Rep2~WBPaper00051555:N2_Sirtuin1720_Day1_Rep3~WBPaper00051555:N2_Olaparib_Day1_Rep1~WBPaper00051555:N2_Olaparib_Day1_Rep2~WBPaper00051555:N2_Olaparib_Day1_Rep3~WBPaper00051555:atm-1(gk186)_Control_Day1_Rep1~WBPaper00051555:atm-1(gk186)_Control_Day1_Rep2~WBPaper00051555:atm-1(gk186)_Control_Day1_Rep3~WBPaper00051555:atm-1(gk186)_Nicotinamide-Riboside_Day1_Rep1~WBPaper00051555:atm-1(gk186)_Nicotinamide-Riboside_Day1_Rep2~WBPaper00051555:atm-1(gk186)_Nicotinamide-Riboside_Day1_Rep3~WBPaper00051555:atm-1(gk186)_Sirtuin1720_Day1_Rep1~WBPaper00051555:atm-1(gk186)_Sirtuin1720_Day1_Rep2~WBPaper00051555:atm-1(gk186)_Sirtuin1720_Day1_Rep3~WBPaper00051555:atm-1(gk186)_Olaparib_Day1_Rep1~WBPaper00051555:atm-1(gk186)_Olaparib_Day1_Rep2~WBPaper00051555:atm-1(gk186)_Olaparib_Day1_Rep3~WBPaper00051555:N2_Control_Day10_Rep1~WBPaper00051555:N2_Control_Day10_Rep2~WBPaper00051555:N2_Control_Day10_Rep3~WBPaper00051555:N2_Nicotinamide-Riboside_Day10_Rep1~WBPaper00051555:N2_Nicotinamide-Riboside_Day10_Rep2~WBPaper00051555:N2_Nicotinamide-Riboside_Day10_Rep3~WBPaper00051555:N2_Sirtuin1720_Day10_Rep1~WBPaper00051555:N2_Sirtuin1720_Day10_Rep2~WBPaper00051555:N2_Sirtuin1720_Day10_Rep3~WBPaper00051555:N2_Olaparib_Day10_Rep1~WBPaper00051555:N2_Olaparib_Day10_Rep2~WBPaper00051555:N2_Olaparib_Day10_Rep3~WBPaper00051555:atm-1(gk186)_Control_Day10_Rep1~WBPaper00051555:atm-1(gk186)_Control_Day10_Rep2~WBPaper00051555:atm-1(gk186)_Control_Day10_Rep3~WBPaper00051555:atm-1(gk186)_Nicotinamide-Riboside_Day10_Rep1~WBPaper00051555:atm-1(gk186)_Nicotinamide-Riboside_Day10_Rep2~WBPaper00051555:atm-1(gk186)_Nicotinamide-Riboside_Day10_Rep3~WBPaper00051555:atm-1(gk186)_Sirtuin1720_Day10_Rep1~WBPaper00051555:atm-1(gk186)_Sirtuin1720_Day10_Rep2~WBPaper00051555:atm-1(gk186)_Sirtuin1720_Day10_Rep3~WBPaper00051555:atm-1(gk186)_Olaparib_Day10_Rep1~WBPaper00051555:atm-1(gk186)_Olaparib_Day10_Rep2~WBPaper00051555:atm-1(gk186)_Olaparib_Day10_Rep3	Method: microarray|Species: Caenorhabditis elegans
281	28958206	WBPaper00053137.ce.mr.paper	GSE86342	GPL11346	1	PKA/KIN-1 mediates innate immune responses to bacterial pathogens in Caenorhabditis elegans.	The genetically tractable organism Caenorhabditis elegans is a powerful model animal for the study of host innate immunity. Although the intestine and the epidermis of C. elegans that is in contact with pathogens are likely to function as sites for the immune function, recent studies indicate that the nervous system could control innate immunity in C. elegans. In this report, we demonstrated that protein kinase A (PKA)/KIN-1 in the neurons contributes to resistance against Salmonella enterica infection in C. elegans. Microarray analysis revealed that PKA/KIN-1 regulates the expression of a set of antimicrobial effectors in the non-neuron tissues, which are required for innate immune responses to S. enterica. Furthermore, PKA/KIN-1 regulated the expression of lysosomal genes during S. enterica infection. Our results suggest that the lysosomal signaling molecules are involved in autophagy by controlling autophagic flux, rather than formation of autophagosomes. As autophagy is crucial for host defense against S. enterica infection in a metazoan, the lysosomal pathway also acts as a downstream effector of the PKA/KIN-1 signaling for innate immunity. Our data indicate that the PKA pathway contributes to innate immunity in C. elegans by signaling from the nervous system to periphery tissues to protect the host against pathogens.	3	18700	Xiao Y	Xiao Y, Liu F, Zhao PJ, Zou CG, Zhang KQ	PKA/KIN-1 mediates innate immune responses to bacterial pathogens in Caenorhabditis elegans.	Innate Immun	2017	WBPaper00053137:N2_control~WBPaper00053137:N2_S.enterica~WBPaper00053137:kin-1(ok338)_S.enterica	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
282	29216338	WBPaper00053427.ce.mr.paper	GSE92588	GPL10094	1	Transcriptome States Reflect Imaging of Aging States.	In this study, we describe a morphological biomarker that detects multiple discrete sub-populations (or &quot;age states&quot;) at several chronological ages in a population of nematodes (C. elegans). We determined the frequencies of three healthy adult states and the timing of the transitions between them across the lifespan. We used short-lived and long-lived strains to confirm the general applicability of the state classifier and to monitor state progression. This exploration revealed healthy and unhealthy states, the former being favored in long-lived strains and the latter showing delayed onset. Short-lived strains rapidly transitioned through the putative healthy state. We previously found that age-matched animals in different age states have distinct transcriptome profiles. We isolated animals at the beginning and end of each identified state and performed microarray analysis (Principal component analysis, relative sample to sample distance measurements and gene set enrichment analysis). In some comparisons, chronologically identical individuals were farther apart than morphologically identical individuals isolated on different days. The age state biomarker allowed assessment of aging in a novel manner, complementary to chronological age progression. We found hsp70 and some small heat shock protein genes are expressed later in adulthood, consistent with the proteostasis collapse model.	24	19636	Eckley DM	Eckley DM, Coletta CE, Orlov NV, Wilson MA, Iser W, Bastian P, Lehrmann E, Zhang Y, Becker KG, Goldberg IG	Transcriptome States Reflect Imaging of Aging States.	J Gerontol A Biol Sci Med Sci	2017	WBPaper00053427:agestate1_early_rep1~WBPaper00053427:agestate1_early_rep2~WBPaper00053427:agestate1_early_rep3~WBPaper00053427:agestate1_late_rep1~WBPaper00053427:agestate1_late_rep2~WBPaper00053427:agestate1_late_rep3~WBPaper00053427:agestate1_late_rep4~WBPaper00053427:agestate2_early_rep1~WBPaper00053427:agestate2_early_rep2~WBPaper00053427:agestate2_early_rep3~WBPaper00053427:agestate2_early_rep4~WBPaper00053427:agestate2_late_rep1~WBPaper00053427:agestate2_late_rep2~WBPaper00053427:agestate2_late_rep3~WBPaper00053427:agestate2_late_rep4~WBPaper00053427:agestate3_early_rep1~WBPaper00053427:agestate3_early_rep2~WBPaper00053427:agestate3_early_rep3~WBPaper00053427:agestate3_early_rep4~WBPaper00053427:agestate3_early_rep5~WBPaper00053427:agestate3_early_rep6~WBPaper00053427:agestate3_late_rep1~WBPaper00053427:agestate3_late_rep2~WBPaper00053427:agestate3_late_rep3	Method: microarray|Species: Caenorhabditis elegans
283	30300667	WBPaper00055386.ce.mr.paper	GSE106672	GPL21109	1	Identification of key pathways and metabolic fingerprints of longevity in C. elegans.	Impaired insulin/IGF-1 signaling (IIS) and caloric restriction (CR) prolong lifespan in the nematode C. elegans. However, a cross comparison of these longevity pathways using a multi-omics integration approach is lacking. In this study, we aimed to identify key pathways and metabolite fingerprints of longevity that are shared between IIS and CR worm models using multi-omics integration. We generated transcriptomics and metabolomics data from long-lived worm strains, i.e. daf-2 (impaired IIS) and eat-2 (CR model) and compared them with the wild-type strain N2. Transcriptional profiling identified shared longevity signatures, such as an upregulation of lipid storage and defense responses, and downregulation of macromolecule synthesis and developmental processes. Metabolomics profiling identified an increase in the levels of glycerol3P, adenine, xanthine, and AMP, and a decrease in the levels of the amino acid pool, as well as the C18:0, C17:1, C19:1, C20:0 and C22:0 fatty acids. After we integrated transcriptomics and metabolomics data based on the annotations in KEGG, our results highlighted increased amino acid metabolism and an upregulation of purine metabolism as a commonality between the two long-lived mutants. Overall, our findings point towards the existence of shared metabolic pathways that are likely important for lifespan extension and provide novel insights into potential regulators and metabolic fingerprints for longevity.	12	20441	Gao AW	Gao AW, Smith RL, van Weeghel M, Kamble R, Janssens GE, Houtkooper RH	Identification of key pathways and metabolic fingerprints of longevity in C. elegans.	Exp Gerontol	2018	WBPaper00055386:N2_rep1~WBPaper00055386:N2_rep2~WBPaper00055386:N2_rep3~WBPaper00055386:N2_rep4~WBPaper00055386:daf-2(e1370)_rep1~WBPaper00055386:daf-2(e1370)_rep2~WBPaper00055386:daf-2(e1370)_rep3~WBPaper00055386:daf-2(e1370)_rep4~WBPaper00055386:eat-2(ad465)_rep1~WBPaper00055386:eat-2(ad465)_rep2~WBPaper00055386:eat-2(ad465)_rep3~WBPaper00055386:eat-2(ad465)_rep4	Method: microarray|Species: Caenorhabditis elegans
284	30547801	WBPaper00055899.ce.mr.paper	GSE92365	GPL22795	1	Comparative toxicogenomics of three insensitive munitions constituents 2,4-dinitroanisole, nitroguanidine and nitrotriazolone in the soil nematode Caenorhabditis elegans.	BACKGROUND: Ecotoxicological studies on the insensitive munitions formulation IMX-101 and its components 2,4-dinitroanisole (DNAN), nitroguanidine (NQ) and nitrotriazolone (NTO) in various organisms showed that DNAN was the main contributor to the overall toxicity of IMX-101 and suggested that the three compounds acted independently. These results motivated this toxicogenomics study to discern toxicological mechanisms for these compounds at the molecular level. METHODS: Here we used the soil nematode Caenorhabditis elegans, a well-characterized genomics model, as the test organism and a species-specific, transcriptome-wide 44K-oligo probe microarray for gene expression analysis. In addition to the control treatment, C. elegans were exposed for 24h to 6 concentrations of DNAN (1.95-62.5ppm) or NQ (83-2667ppm) or 5 concentrations of NTO (187-3000ppm) with ten replicates per treatment. The nematodes were transferred to a clean environment after exposure. Reproduction endpoints (egg and larvae counts) were measured at three time points (i.e., 24-, 48- and 72-h). Gene expression profiling was performed immediately after 24-h exposure to each chemical at the lowest, medium and highest concentrations plus the control with four replicates per treatment. RESULTS: Statistical analyses indicated that chemical treatment did not significantly affect nematode reproduction but did induce 2175, 378, and 118 differentially expressed genes (DEGs) in NQ-, DNAN-, and NTO-treated nematodes, respectively. Bioinformatic analysis indicated that the three compounds shared both DEGs and DEG-mapped Reactome pathways. Gene set enrichment analysis further demonstrated that DNAN and NTO significantly altered 12 and 6 KEGG pathways, separately, with three pathways in common. NTO mainly affected carbohydrate, amino acid and xenobiotics metabolism while DNAN disrupted protein processing, ABC transporters and several signal transduction pathways. NQ-induced DEGs were mapped to a wide variety of metabolism, cell cycle, immune system and extracellular matrix organization pathways. CONCLUSION: Despite the absence of significant effects on apical reproduction endpoints, DNAN, NTO and NQ caused significant alterations in gene expression and pathways at 1.95ppm, 187ppm and 83ppm, respectively. This study provided supporting evidence that the three chemicals may exert independent toxicity by acting on distinct molecular targets and pathways.	48	19475	Gong P	Gong P, Donohue KB, Mayo AM, Wang Y, Hong H, Wilbanks MS, Barker ND, Guan X, Gust KA	Comparative toxicogenomics of three insensitive munitions constituents 2,4-dinitroanisole, nitroguanidine and nitrotriazolone in the soil nematode Caenorhabditis elegans.	BMC Syst Biol	2018	WBPaper00055899:NTO_Control_rep5~WBPaper00055899:NTO_187ppm_rep5~WBPaper00055899:DNAN_Control_rep3~WBPaper00055899:DNAN_15.5ppm_rep1~WBPaper00055899:DNAN_1.9ppm_rep1~WBPaper00055899:DNAN_62.5ppm_rep3~WBPaper00055899:NTO_3000ppm_rep4~WBPaper00055899:NQ_Control_rep1~WBPaper00055899:NQ_83ppm_rep2~WBPaper00055899:NTO_750ppm_rep3~WBPaper00055899:NTO_3000ppm_rep5~WBPaper00055899:DNAN_62.5ppm_rep1~WBPaper00055899:DNAN_1.9ppm_rep5~WBPaper00055899:NQ_666ppm_rep4~WBPaper00055899:NQ_83ppm_rep1~WBPaper00055899:DNAN_15.5ppm_rep2~WBPaper00055899:NQ_666ppm_rep1~WBPaper00055899:NTO_3000ppm_rep1~WBPaper00055899:NQ_2667ppm_rep4~WBPaper00055899:DNAN_15.5ppm_rep4~WBPaper00055899:DNAN_15.5ppm_rep5~WBPaper00055899:NTO_187ppm_rep3~WBPaper00055899:NQ_666ppm_rep5~WBPaper00055899:NQ_2667ppm_rep3~WBPaper00055899:NQ_83ppm_rep5~WBPaper00055899:DNAN_62.5ppm_rep4~WBPaper00055899:NQ_2667ppm_rep2~WBPaper00055899:NTO_750ppm_rep5~WBPaper00055899:DNAN_Control_rep1~WBPaper00055899:NTO_Control_rep1~WBPaper00055899:DNAN_Control_rep2~WBPaper00055899:NQ_666ppm_rep2~WBPaper00055899:DNAN_1.9ppm_rep2~WBPaper00055899:DNAN_62.5ppm_rep5~WBPaper00055899:DNAN_Control_rep4~WBPaper00055899:DNAN_1.9ppm_rep3~WBPaper00055899:NQ_Control_rep3~WBPaper00055899:NTO_Control_rep3~WBPaper00055899:NQ_83ppm_rep4~WBPaper00055899:NTO_750ppm_rep1~WBPaper00055899:NQ_Control_rep2~WBPaper00055899:NTO_187ppm_rep1~WBPaper00055899:NTO_3000ppm_rep2~WBPaper00055899:NQ_2667ppm_rep1~WBPaper00055899:NTO_187ppm_rep4~WBPaper00055899:NTO_Control_rep2~WBPaper00055899:NTO_750ppm_rep4~WBPaper00055899:NQ_Control_rep4	Method: microarray|Species: Caenorhabditis elegans
285	30845140	WBPaper00056330.ce.mr.paper	GSE117581	GPL21109	1	Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion.	The deregulation of metabolism is a hallmark of aging. As such, changes in the expression of metabolic genes and the profiles of amino acid levels are features associated with aging animals. We previously reported that the levels of most amino acids decline with age in Caenorhabditis elegans (C. elegans). Glycine, in contrast, substantially accumulates in aging C. elegans. In this study we show that this is coupled to a decrease in gene expression of enzymes important for glycine catabolism. We further show that supplementation of glycine significantly prolongs C. elegans lifespan, and early adulthood is important for its salutary effects. Moreover, supplementation of glycine ameliorates specific transcriptional changes that are associated with aging. Glycine feeds into the methionine cycle. We find that mutations in components of this cycle, methionine synthase (metr-1) and S-adenosylmethionine synthetase (sams-1), completely abrogate glycine-induced lifespan extension. Strikingly, the beneficial effects of glycine supplementation are conserved when we supplement with serine, which also feeds into the methionine cycle. RNA-sequencing reveals a similar transcriptional landscape in serine- and glycine-supplemented worms both demarked by widespread gene repression. Taken together, these data uncover a novel role of glycine in the deceleration of aging through its function in the methionine cycle.	8	20441	Liu YJ	Liu YJ, Janssens GE, McIntyre RL, Molenaars M, Kamble R, Gao AW, Jongejan A, Weeghel MV, MacInnes AW, Houtkooper RH	Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion.	PLoS Genet	2019	WBPaper00056330:control_rep1~WBPaper00056330:control_rep2~WBPaper00056330:control_rep3~WBPaper00056330:control_rep4~WBPaper00056330:mrps-5(RNAi)_rep1~WBPaper00056330:mrps-5(RNAi)_rep2~WBPaper00056330:mrps-5(RNAi)_rep3~WBPaper00056330:mrps-5(RNAi)_rep4	Method: microarray|Species: Caenorhabditis elegans
286	30917316	WBPaper00056471.ce.mr.paper	GSE128029	GPL11346	1	The Transcription Factors TFEB and TFE3 Link the FLCN-AMPK Signaling Axis to Innate Immune Response and Pathogen Resistance.	TFEB and TFE3 are transcriptional regulators of the innate immune response, but the mechanisms regulating their activation upon pathogen infection are poorly elucidated. Using C.elegans and mammalian models, we report that the master metabolic modulator 5'-AMP-activated protein kinase (AMPK) and its negative regulator Folliculin (FLCN) act upstream of TFEB/TFE3 in the innate immune response, independently of the mTORC1 signaling pathway. In nematodes, loss of FLCN or overexpression of AMPK confers pathogen resistance via activation ofTFEB/TFE3-dependent antimicrobial genes, whereas ablation of total AMPK activity abolishes this phenotype. Similarly, in mammalian cells, loss of FLCN or pharmacological activation of AMPK induces TFEB/TFE3-dependent pro-inflammatory cytokine expression. Importantly, a rapid reduction in cellular ATP levels in murine macrophages is observed upon lipopolysaccharide (LPS) treatment accompanied by an acute AMPK activation and TFEB nuclear localization. These results uncover an ancient, highly conserved, and pharmacologically actionable mechanism coupling energy status with innate immunity.	8	19636	El-Houjeiri L	El-Houjeiri L, Possik E, Vijayaraghavan T, Paquette M, Martina JA, Kazan JM, Ma EH, Jones R, Blanchette P, Puertollano R, Pause A	The Transcription Factors TFEB and TFE3 Link the FLCN-AMPK Signaling Axis to Innate Immune Response and Pathogen Resistance.	Cell Rep	2019	WBPaper00056471:N2_rep4~WBPaper00056471:N2_rep3~WBPaper00056471:N2_rep2~WBPaper00056471:N2_rep1~WBPaper00056471:flcn-1(ok975)_rep4~WBPaper00056471:flcn-1(ok975)_rep3~WBPaper00056471:flcn-1(ok975)_rep2~WBPaper00056471:flcn-1(ok975)_rep1	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
287	31754102	WBPaper00058882.ce.mr.paper	GSE108968	GPL10094	1	NAD<sup>+</sup> augmentation restores mitophagy and limits accelerated aging in Werner syndrome.	Metabolic dysfunction is a primary feature of Werner syndrome (WS), a human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. WS patients exhibit severe metabolic phenotypes, but the underlying mechanisms are not understood, and whether the metabolic deficit can be targeted for therapeutic intervention has not been determined. Here we report impaired mitophagy and depletion of NAD<sup>+</sup>, a fundamental ubiquitous molecule, in WS patient samples and WS invertebrate models. WRN regulates transcription of a key NAD<sup>+</sup> biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1). NAD<sup>+</sup> repletion restores NAD<sup>+</sup> metabolic profiles and improves mitochondrial quality through DCT-1 and ULK-1-dependent mitophagy. At the organismal level, NAD<sup>+</sup> repletion remarkably extends lifespan and delays accelerated aging, including stem cell dysfunction, in Caenorhabditis elegans and Drosophila melanogaster models of WS. Our findings suggest that accelerated aging in WS is mediated by impaired mitochondrial function and mitophagy, and that bolstering cellular NAD<sup>+</sup> levels counteracts WS phenotypes.	32	19636	Fang EF	Fang EF, Hou Y, Lautrup S, Jensen MB, Yang B, SenGupta T, Caponio D, Khezri R, Demarest TG, Aman Y, Figueroa D, Morevati M, Lee HJ, Kato H, Kassahun H, Lee JH, Filippelli D, Okur MN, Mangerich A, Croteau DL, Maezawa Y, Lyssiotis CA, Tao J, Yokote K, Rusten TE, Mattson MP, Jasper H, Nilsen H, Bohr VA	NAD<sup>+</sup> augmentation restores mitophagy and limits accelerated aging in Werner syndrome.	Nat Commun	2019	WBPaper00058882:N2_control_rep1~WBPaper00058882:N2_control_rep2~WBPaper00058882:N2_control_rep3~WBPaper00058882:N2_control_rep4~WBPaper00058882:N2_NR_rep1~WBPaper00058882:N2_NR_rep2~WBPaper00058882:N2_NR_rep3~WBPaper00058882:N2_NR_rep4~WBPaper00058882:N2_SRIT1_rep1~WBPaper00058882:N2_SRIT1_rep2~WBPaper00058882:N2_SRIT1_rep3~WBPaper00058882:N2_SRIT1_rep4~WBPaper00058882:N2_Ola_rep1~WBPaper00058882:N2_Ola_rep2~WBPaper00058882:N2_Ola_rep3~WBPaper00058882:N2_Ola_rep4~WBPaper00058882:wrn-1(gk99)_control_rep1~WBPaper00058882:wrn-1(gk99)_control_rep2~WBPaper00058882:wrn-1(gk99)_control_rep3~WBPaper00058882:wrn-1(gk99)_control_rep4~WBPaper00058882:wrn-1(gk99)_NR_rep1~WBPaper00058882:wrn-1(gk99)_NR_rep2~WBPaper00058882:wrn-1(gk99)_NR_rep3~WBPaper00058882:wrn-1(gk99)_NR_rep4~WBPaper00058882:wrn-1(gk99)_SRIT1_rep1~WBPaper00058882:wrn-1(gk99)_SRIT1_rep2~WBPaper00058882:wrn-1(gk99)_SRIT1_rep3~WBPaper00058882:wrn-1(gk99)_SRIT1_rep4~WBPaper00058882:wrn-1(gk99)_Ola_rep1~WBPaper00058882:wrn-1(gk99)_Ola_rep2~WBPaper00058882:wrn-1(gk99)_Ola_rep3~WBPaper00058882:wrn-1(gk99)_Ola_rep4	Method: microarray|Species: Caenorhabditis elegans
288	32350153	WBPaper00059610.ce.mr.paper	GSE99020	GPL10094	1	A cellular surveillance and defense system that delays aging phenotypes in <i>C. elegans</i>.	Physiological stresses, such as pathogen infection, are detected by &quot;cellular Surveillance Activated Detoxification and Defenses&quot; (cSADD) systems that trigger host defense responses. Aging is associated with physiological stress, including impaired mitochondrial function. Here, we investigated whether an endogenous cSADD pathway is activated during aging in <i>C. elegans</i>. We provide evidence that the transcription factor ZIP-2, a well-known immune response effector in <i>C. elegans</i>, is activated in response to age-associated mitochondrial dysfunction. ZIP-2 mitigates multiple aging phenotypes, including mitochondrial disintegration and reduced motility of the pharynx and intestine. Importantly, our data suggest that ZIP-2 is activated during aging independently of bacterial infection and of the transcription factors ATFS-1 and CEBP-2. Thus, ZIP-2 is a key component of an endogenous pathway that delays aging phenotypes in <i>C. elegans</i>. Our data suggest that aging coopted a compensatory strategy for regulation of aging process as a guarded process rather than a simple passive deterioration process.	4	19636	Hahm JH	Hahm JH, Jeong C, Lee W, Koo HJ, Kim S, Hwang D, Nam HG	A cellular surveillance and defense system that delays aging phenotypes in <i>C. elegans</i>.	Aging (Albany NY)	2020	WBPaper00059610:Low-maximum-velocity_rep1~WBPaper00059610:Low-maximum-velocity_rep2~WBPaper00059610:High-maximum-velocity_rep1~WBPaper00059610:High-maximum-velocity_rep2	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging|Topic: defense response|Topic: defense response to other organism
289	32820022	WBPaper00060122.ce.mr.paper	GSE157800	GPL11346	1	Loss of the seipin gene perturbs eggshell formation in <i>C. elegans</i>.	SEIPIN, an evolutionary conserved protein, plays pivotal roles during lipid droplet (LD) biogenesis and is associated with various human diseases with unclear mechanisms. Here, we analyzed <i>C. elegans</i> mutants deleted of the sole SEIPIN gene, <i>seip-1</i> Homozygous <i>seip-1</i> mutants displayed penetrant embryonic lethality, which is caused by the disruption of the lipid-rich permeability barrier, the innermost layer of the <i>C. elegans</i> embryonic eggshell. In <i>C. elegans</i> oocytes and embryos, SEIP-1 is associated with LDs and crucial for controlling LD size and lipid homeostasis. The <i>seip-1</i> deletion mutants reduced the ratio of polyunsaturated fatty acids (PUFAs) in their embryonic fatty acid pool. Interestingly, dietary supplementation of selected n-6 PUFAs rescued the embryonic lethality and defective permeability barrier. Accordingly, we propose that SEIP-1 may maternally regulate LD biogenesis and lipid homeostasis to orchestrate the formation of the permeability barrier for eggshell synthesis during embryogenesis. A lipodystrophy allele of <i>seip-1</i> resulted in embryonic lethality as well and could be rescued by PUFA supplementation; these experiments support a great potential of using <i>C. elegans</i> to model SEIPIN-associated human diseases.	8	19636	Bai X	Bai X, Huang LJ, Chen SW, Nebenfuhr B, Wysolmerski B, Wu JC, Olson SK, Golden A, Wang CW	Loss of the seipin gene perturbs eggshell formation in <i>C. elegans</i>.	Development	2020	WBPaper00060122:N2_embryo_rep1~WBPaper00060122:N2_embryo_rep2~WBPaper00060122:seip-1(av109)_embryo_rep1~WBPaper00060122:seip-1(av109)_embryo_rep2~WBPaper00060122:N2_adult_worm_rep1~WBPaper00060122:N2_adult_worm_rep2~WBPaper00060122:seip-1(av109)_adult_worm_rep1~WBPaper00060122:seip-1(av109)_adult_worm_rep2	Method: microarray|Species: Caenorhabditis elegans
290	33009389	WBPaper00060399.ce.mr.paper	GSE139562	GPL10094	2	PQM-1 controls hypoxic survival via regulation of lipid metabolism.	Animals have evolved responses to low oxygen conditions to ensure their survival. Here, we have identified the C. elegans zinc finger transcription factor PQM-1 as a regulator of the hypoxic stress response. PQM-1 is required for the longevity of insulin signaling mutants, but surprisingly, loss of PQM-1 increases survival under hypoxic conditions. PQM-1 functions as a metabolic regulator by controlling oxygen consumption rates, suppressing hypoxic glycogen levels, and inhibiting the expression of the sorbitol dehydrogenase-1 SODH-1, a crucial sugar metabolism enzyme. PQM-1 promotes hypoxic fat metabolism by maintaining the expression of the stearoyl-CoA desaturase FAT-7, an oxygen consuming, rate-limiting enzyme in fatty acid biosynthesis. PQM-1 activity positively regulates fat transport to developing oocytes through vitellogenins under hypoxic conditions, thereby increasing survival rates of arrested progeny during hypoxia. Thus, while pqm-1 mutants increase survival of mothers, ultimately this loss is detrimental to progeny survival. Our data support a model in which PQM-1 controls a trade-off between lipid metabolic activity in the mother and her progeny to promote the survival of the species under hypoxic conditions.	24	19636	Heimbucher T	Heimbucher T, Hog J, Gupta P, Murphy CT	PQM-1 controls hypoxic survival via regulation of lipid metabolism.	Nat Commun	2020	WBPaper00060399:N2_CoCl2_6hr_vs_N2_control_6hr_rep1~WBPaper00060399:N2_CoCl2_6hr_vs_N2_control_6hr_rep2~WBPaper00060399:N2_CoCl2_6hr_vs_N2_control_6hr_rep3~WBPaper00060399:pqm-1(ok485)_CoCl2_6hr_vs_pqm-1(ok485)_control_6hr_rep1b~WBPaper00060399:pqm-1(ok485)_CoCl2_6hr_vs_pqm-1(ok485)_control_6hr_rep2~WBPaper00060399:pqm-1(ok485)_CoCl2_6hr_vs_pqm-1(ok485)_control_6hr_rep3~WBPaper00060399:pqm-1(ok485)_control_6hr_vs_N2_control_6hr_rep1b~WBPaper00060399:pqm-1(ok485)_control_6hr_vs_N2_control_6hr_rep2~WBPaper00060399:pqm-1(ok485)_control_6hr_vs_N2_control_6hr_rep3~WBPaper00060399:pqm-1(ok485)_CoCl2_6hr_vs_N2_CoCl2_6hr_rep1~WBPaper00060399:pqm-1(ok485)_CoCl2_6hr_vs_N2_CoCl2_6hr_rep2~WBPaper00060399:pqm-1(ok485)_CoCl2_6hr_vs_N2_CoCl2_6hr_rep3~WBPaper00060399:N2_CoCl2_20hr_vs_N2_control_20hr_rep1b~WBPaper00060399:N2_CoCl2_20hr_vs_N2_control_20hr_rep2~WBPaper00060399:N2_CoCl2_20hr_vs_N2_control_20hr_rep3~WBPaper00060399:pqm-1(ok485)_CoCl2_20hr_vs_pqm-1(ok485)_control_20hr_rep1~WBPaper00060399:pqm-1(ok485)_CoCl2_20hr_vs_pqm-1(ok485)_control_20hr_rep2~WBPaper00060399:pqm-1(ok485)_CoCl2_20hr_vs_pqm-1(ok485)_control_20hr_rep3~WBPaper00060399:pqm-1(ok485)_control_20hr_vs_N2_control_20hr_rep1~WBPaper00060399:pqm-1(ok485)_control_20hr_vs_N2_control_20hr_rep2~WBPaper00060399:pqm-1(ok485)_control_20hr_vs_N2_control_20hr_rep3~WBPaper00060399:pqm-1(ok485)_CoCl2_20hr_vs_N2_CoCl2_20hr_rep1~WBPaper00060399:pqm-1(ok485)_CoCl2_20hr_vs_N2_CoCl2_20hr_rep2~WBPaper00060399:pqm-1(ok485)_CoCl2_20hr_vs_N2_CoCl2_20hr_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: response to hypoxia
291	34040055	WBPaper00061443.ce.mr.paper	N.A.	N.A.	1	Transcriptional analysis of the response of C. elegans to ethanol exposure.	Ethanol-induced transcriptional changes underlie important physiological responses to ethanol that are likely to contribute to the addictive properties of the drug. We examined the transcriptional responses of Caenorhabditis elegans across a timecourse of ethanol exposure, between 30 min and 8 h, to determine what genes and genetic pathways are regulated in response to ethanol in this model. We found that short exposures to ethanol (up to 2 h) induced expression of metabolic enzymes involved in metabolizing ethanol and retinol, while longer exposure (8 h) had much more profound effects on the transcriptome. Several genes that are known to be involved in the physiological response to ethanol, including direct ethanol targets, were regulated at 8 h of exposure. This longer exposure to ethanol also resulted in the regulation of genes involved in cilia function, which is consistent with an important role for the effects of ethanol on cilia in the deleterious effects of chronic ethanol consumption in humans. Finally, we found that food deprivation for an 8-h period induced gene expression changes that were somewhat ameliorated by the presence of ethanol, supporting previous observations that worms can use ethanol as a calorie source.	40	51	Sterken MG	Sterken MG, van Wijk MH, Quamme EC, Riksen JAG, Carnell L, Mathies LD, Davies AG, Kammenga JE, Bettinger JC	Transcriptional analysis of the response of C. elegans to ethanol exposure.	Sci Rep	2021	WBPaper00061443:0.4mM-ethanol_120min_Sample1~WBPaper00061443:0.4mM-ethanol_480min_Sample2~WBPaper00061443:0.4mM-ethanol_120min_Sample3~WBPaper00061443:0.4mM-ethanol_0min_Sample4~WBPaper00061443:0.4mM-ethanol_60min_Sample5~WBPaper00061443:0.4mM-ethanol_30min_Sample6~WBPaper00061443:0.4mM-ethanol_30min_Sample7~WBPaper00061443:0.4mM-ethanol_60min_Sample8~WBPaper00061443:control_0min_Sample9~WBPaper00061443:control_0min_Sample10~WBPaper00061443:control_480min_Sample11~WBPaper00061443:control_30min_Sample12~WBPaper00061443:control_60min_Sample13~WBPaper00061443:0.4mM-ethanol_480min_Sample14~WBPaper00061443:control_480min_Sample15~WBPaper00061443:0.4mM-ethanol_0min_Sample16~WBPaper00061443:control_60min_Sample17~WBPaper00061443:control_120min_Sample18~WBPaper00061443:control_30min_Sample19~WBPaper00061443:control_120min_Sample20~WBPaper00061443:0.4mM-ethanol_480min_Sample21~WBPaper00061443:0.4mM-ethanol_60min_Sample22~WBPaper00061443:control_60min_Sample23~WBPaper00061443:0.4mM-ethanol_30min_Sample24~WBPaper00061443:0.4mM-ethanol_480min_Sample25~WBPaper00061443:control_120min_Sample26~WBPaper00061443:0.4mM-ethanol_0min_Sample27~WBPaper00061443:control_60min_Sample28~WBPaper00061443:control_120min_Sample29~WBPaper00061443:0.4mM-ethanol_30min_Sample30~WBPaper00061443:control_0min_Sample31~WBPaper00061443:0.4mM-ethanol_60min_Sample32~WBPaper00061443:0.4mM-ethanol_0min_Sample33~WBPaper00061443:control_480min_Sample34~WBPaper00061443:0.4mM-ethanol_120min_Sample35~WBPaper00061443:0.4mM-ethanol_120min_Sample36~WBPaper00061443:control_30min_Sample37~WBPaper00061443:control_0min_Sample38~WBPaper00061443:control_30min_Sample39~WBPaper00061443:control_480min_Sample40	Method: microarray|Species: Caenorhabditis elegans
292	34440335	WBPaper00061877.ce.mr.paper	N.A.	N.A.	1	Heat Stress Reduces the Susceptibility of Caenorhabditis elegans to Orsay Virus Infection.	The nematode Caenorhabditis elegans has been a versatile model for understanding the molecular responses to abiotic stress and pathogens. In particular, the response to heat stress and virus infection has been studied in detail. The Orsay virus (OrV) is a natural virus of C. elegans and infection leads to intracellular infection and proteostatic stress, which activates the intracellular pathogen response (IPR). IPR related gene expression is regulated by the genes pals-22 and pals-25, which also control thermotolerance and immunity against other natural pathogens. So far, we have a limited understanding of the molecular responses upon the combined exposure to heat stress and virus infection. We test the hypothesis that the response of C. elegans to OrV infection and heat stress are co-regulated and may affect each other. We conducted a combined heat-stress-virus infection assay and found that after applying heat stress, the susceptibility of C. elegans to OrV was decreased. This difference was found across different wild types of C. elegans. Transcriptome analysis revealed a list of potential candidate genes associated with heat stress and OrV infection. Subsequent mutant screens suggest that pals-22 provides a link between viral response and heat stress, leading to enhanced OrV tolerance of C. elegans after heat stress.	8	19636	Huang Y	Huang Y, Sterken MG, van Zwet K, van Sluijs L, Pijlman GP, Kammenga JE	Heat Stress Reduces the Susceptibility of Caenorhabditis elegans to Orsay Virus Infection.	Genes (Basel)	2021	WBPaper00061877:HeatStress_N2_OrsayVirus~WBPaper00061877:HeatStress_CB4856_noInfection~WBPaper00061877:HeatStress_N2_noInfection~WBPaper00061877:HeatStress_CB4856_OrsayVirus~WBPaper00061877:noStress_CB4856_noInfection~WBPaper00061877:noStress_N2_OrsayVirus~WBPaper00061877:noStress_CB4856_OrsayVirus~WBPaper00061877:noStress_N2_noInfection	Method: microarray|Species: Caenorhabditis elegans
293	34534386	WBPaper00061936.ce.mr.paper	N.A.	N.A.	1	Virus infection modulates male sexual behavior in Caenorhabditis elegans.	Mating dynamics follow from natural selection on mate choice and individuals maximizing their reproductive success. Mate discrimination reveals itself by a plethora of behaviors and morphological characteristics, each of which can be affected by pathogens. A key question is how pathogens affect mate choice and outcrossing behavior. Here we investigated the effect of Orsay virus on the mating dynamics of the androdiecious (male and hermaphrodite) nematode Caenorhabditis elegans. We tested genetically distinct strains and found that viral susceptibility differed between sexes in a genotype-dependent manner with males of reference strain N2 being more resistant than hermaphrodites. Males displayed a constitutively higher expression of Intracellular Pathogen Response (IPR) genes, whereas the antiviral RNAi response did not have increased activity in males. Subsequent monitoring of sex ratios over ten generations revealed that viral presence can change mating dynamics in isogenic populations. Sexual attraction assays showed that males preferred mating with uninfected rather than infected hermaphrodites. Together our results illustrate for the first time that viral infection can significantly affect male mating choice and suggest altered mating dynamics as a novel cause benefitting outcrossing under pathogenic stress conditions in C. elegans.	32	19636	van Sluijs L	van Sluijs L, Liu J, Schrama M, van Hamond S, Vromans SPJM, Scholten MH, Zibrat N, Riksen JAG, Pijlman GP, Sterken MG, Kammenga JE	Virus infection modulates male sexual behavior in Caenorhabditis elegans.	Mol Ecol	2021	WBPaper00061936:male_noInfection_rep1~WBPaper00061936:male_noInfection_rep12~WBPaper00061936:hermaphrodite_noInfection_rep14~WBPaper00061936:hermaphrodite_noInfection_rep15~WBPaper00061936:hermaphrodite_noInfection_rep16~WBPaper00061936:hermaphrodite_noInfection_rep18~WBPaper00061936:hermaphrodite_noInfection_rep2~WBPaper00061936:male_noInfection_rep28~WBPaper00061936:male_noInfection_rep3~WBPaper00061936:hermaphrodite_noInfection_rep31~WBPaper00061936:male_noInfection_rep32~WBPaper00061936:hermaphrodite_noInfection_rep4~WBPaper00061936:male_noInfection_rep5~WBPaper00061936:hermaphrodite_noInfection_rep6~WBPaper00061936:male_noInfection_rep7~WBPaper00061936:male_noInfection_rep9~WBPaper00061936:hermaphrodite_OrsayVirus_rep10~WBPaper00061936:male_OrsayVirus_rep11~WBPaper00061936:hermaphrodite_OrsayVirus_rep13~WBPaper00061936:male_OrsayVirus_rep17~WBPaper00061936:hermaphrodite_OrsayVirus_rep19~WBPaper00061936:male_OrsayVirus_rep20~WBPaper00061936:hermaphrodite_OrsayVirus_rep21~WBPaper00061936:male_OrsayVirus_rep22~WBPaper00061936:hermaphrodite_OrsayVirus_rep23~WBPaper00061936:male_OrsayVirus_rep24~WBPaper00061936:hermaphrodite_OrsayVirus_rep25~WBPaper00061936:male_OrsayVirus_rep26~WBPaper00061936:hermaphrodite_OrsayVirus_rep27~WBPaper00061936:male_OrsayVirus_rep29~WBPaper00061936:hermaphrodite_OrsayVirus_rep30~WBPaper00061936:male_OrsayVirus_rep8	Method: microarray|Species: Caenorhabditis elegans
294	35602005	WBPaper00064061.ce.mr.paper	GSE196891	GPL10094	1	Assessment of the effects of organic vs. inorganic arsenic and mercury in <i>Caenorhabditis elegans</i>.	Exposures to mercury and arsenic are known to pose significant threats to human health. Effects specific to organic vs. inorganic forms of these toxic elements are less understood however, especially for organic dimethylarsinic acid (DMA), which has recently been detected in pups of rodent dams orally exposed to inorganic sodium (meta)arsenite (NaAsO2). Caenorhabditis elegans is a small animal alternative toxicity model. To fill data gaps on the effects of DMA relative to NaAsO2, C. elegans were exposed to these two compounds alongside more thoroughly researched inorganic mercury chloride (HgCl2) and organic methylmercury chloride (meHgCl). For timing of developmental milestone acquisition in C. elegans, meHgCl was 2 to 4-fold more toxic than HgCl2, and NaAsO2 was 20-fold more toxic than DMA, ranking the four compounds meHgCl > HgCl2 > NaAsO2 &#8811; DMA for developmental toxicity. Methylmercury induced significant decreases in population locomotor activity levels in developing C. elegans. DMA was also associated with developmental hypoactivity, but at >100-fold higher concentrations than meHgCl. Transcriptional alterations in native genes were observed in wild type C. elegans adults exposed to concentrations equitoxic for developmental delay in juveniles. Both forms of arsenic induced genes involved in immune defense and oxidative stress response, while the two mercury species induced proportionally more genes involved in transcriptional regulation. A transgenic bioreporter for activation of conserved proteosome specific unfolded protein response was strongly activated by NaAsO2, but not DMA at tested concentrations. HgCl2 and meHgCl had opposite effects on a bioreporter for unfolded protein response in the endoplasmic reticulum. Presented experiments indicating low toxicity for DMA in C. elegans are consistent with human epidemiologic data correlating higher arsenic methylation capacity with resistance to arsenic toxicity. This work contributes to the understanding of the accuracy and fit-for-use categories for C. elegans toxicity screening and its usefulness to prioritize compounds of concern for further testing.	16	19636	Camacho J	Camacho J, de Conti A, Pogribny IP, Sprando RL, Hunt PR	Assessment of the effects of organic vs. inorganic arsenic and mercury in <i>Caenorhabditis elegans</i>.	Curr Res Toxicol	2022	WBPaper00064061:Water_rep2G~WBPaper00064061:NaAsO2_rep2H~WBPaper00064061:DMA_rep2I~WBPaper00064061:HgCl2_rep2J~WBPaper00064061:meHgCl_rep2L~WBPaper00064061:Water_rep3F~WBPaper00064061:NaAsO2_rep3G~WBPaper00064061:DMA_rep3H~WBPaper00064061:HgCl2_rep3I~WBPaper00064061:meHgCl_rep3J~WBPaper00064061:Water_rep4F~WBPaper00064061:NaAsO2_rep5G~WBPaper00064061:DMA_rep5H~WBPaper00064061:HgCl2_rep5I~WBPaper00064061:meHgCl_rep5J~WBPaper00064061:Water_rep5F	Method: microarray|Species: Caenorhabditis elegans
295	35504961	WBPaper00064093.ce.mr.paper	GSE144059	GPL11346	1	Remofuscin induces xenobiotic detoxification via a lysosome-to-nucleus signaling pathway to extend the Caenorhabditis elegans lifespan.	Lipofuscin is a representative biomarker of aging that is generated naturally over time. Remofuscin (soraprazan) improves age-related eye diseases by removing lipofuscin from retinal pigment epithelium (RPE) cells. In this study, the effect of remofuscin on longevity in Caenorhabditis elegans and the underlying mechanism were investigated. The results showed that remofuscin significantly (p < 0.05) extended the lifespan of C. elegans (N2) compared with the negative control. Aging biomarkers were improved in remofuscin-treated worms. The expression levels of genes related to lysosomes (lipl-1 and lbp-8), a nuclear hormone receptor (nhr-234), fatty acid beta-oxidation (ech-9), and xenobiotic detoxification (cyp-34A1, cyp-35A1, cyp-35A2, cyp-35A3, cyp-35A4, cyp-35A5, cyp-35C1, gst-28, and gst-5) were increased in remofuscin-treated worms. Moreover, remofuscin failed to extend the lives of C. elegans with loss-of-function mutations (lipl-1, lbp-8, nhr-234, nhr-49, nhr-8, cyp-35A1, cyp-35A2, cyp-35A3, cyp-35A5, and gst-5), suggesting that these genes are associated with lifespan extension in remofuscin-treated C. elegans. In conclusion, remofuscin activates the lysosome-to-nucleus pathway in C. elegans, thereby increasing the expression levels of xenobiotic detoxification genes resulted in extending their lifespan.	4	19636	Oh M	Oh M, Yeom J, Schraermeyer U, Julien-Schraermeyer S, Lim YH	Remofuscin induces xenobiotic detoxification via a lysosome-to-nucleus signaling pathway to extend the Caenorhabditis elegans lifespan.	Sci Rep	2022	WBPaper00064093:control_rep0731~WBPaper00064093:control_rep0801~WBPaper00064093:200uM-soraprazan_rep0731~WBPaper00064093:200uM-soraprazan_rep0801	Method: microarray|Species: Caenorhabditis elegans
296	33166073	WBPaper00064098.ce.mr.paper	GSE144556,GSE144558	GPL10094	1	Cockayne syndrome proteins CSA and CSB maintain mitochondrial homeostasis through NAD<sup>+</sup> signaling.	Cockayne syndrome (CS) is a rare premature aging disease, most commonly caused by mutations of the genes encoding the CSA or CSB proteins. CS patients display cachectic dwarfism and severe neurological manifestations and have an average life expectancy of 12years. The CS proteins are involved in transcription and DNA repair, with the latter including transcription-coupled nucleotide excision repair (TC-NER). However, there is also evidence for mitochondrial dysfunction in CS, which likely contributes to the severe premature aging phenotype of this disease. While damaged mitochondria and impaired mitophagy were characterized in mice with CSB deficiency, such changes in the CS nematode model and CS patients are not fully known. Our cross-species transcriptomic analysis in CS postmortem brain tissue, CS mouse, and nematode models shows that mitochondrial dysfunction is indeed a common feature in CS. Restoration of mitochondrial dysfunction through NAD<sup>+</sup> supplementation significantly improved lifespan and healthspan in the CS nematodes, highlighting mitochondrial dysfunction as a major driver of the aging features of CS. In cerebellar samples from CS patients, we found molecular signatures of dysfunctional mitochondrial dynamics and impaired mitophagy/autophagy. In primary cells depleted for CSA or CSB, this dysfunction can be corrected with supplementation of NAD<sup>+</sup> precursors. Our study provides support for the interconnection between major causative aging theories, DNA damage accumulation, mitochondrial dysfunction, and compromised mitophagy/autophagy. Together, these three agents contribute to an accelerated aging program that can be averted by cellular NAD<sup>+</sup> restoration.	32	19636	Okur MN	Okur MN, Fang EF, Fivenson EM, Tiwari V, Croteau DL, Bohr VA	Cockayne syndrome proteins CSA and CSB maintain mitochondrial homeostasis through NAD<sup>+</sup> signaling.	Aging Cell	2020	WBPaper00064098:N2_control_rep1~WBPaper00064098:N2_control_rep2~WBPaper00064098:N2_control_rep3~WBPaper00064098:N2_control_rep4~WBPaper00064098:N2_NAD+Precursor_rep1~WBPaper00064098:N2_NAD+Precursor_rep2~WBPaper00064098:N2_NAD+Precursor_rep3~WBPaper00064098:N2_NAD+Precursor_rep4~WBPaper00064098:csa-1(tm4539)_control_rep1~WBPaper00064098:csa-1(tm4539)_control_rep2~WBPaper00064098:csa-1(tm4539)_control_rep3~WBPaper00064098:csa-1(tm4539)_control_rep4~WBPaper00064098:csa-1(tm4539)_NAD+Precursor_rep1~WBPaper00064098:csa-1(tm4539)_NAD+Precursor_rep2~WBPaper00064098:csa-1(tm4539)_NAD+Precursor_rep3~WBPaper00064098:csa-1(tm4539)_NAD+Precursor_rep4~WBPaper00064098:csb-1(ok2335)_control_rep1~WBPaper00064098:csb-1(ok2335)_control_rep2~WBPaper00064098:csb-1(ok2335)_control_rep3~WBPaper00064098:csb-1(ok2335)_control_rep4~WBPaper00064098:csb-1(ok2335)_NAD+Precursor_rep1~WBPaper00064098:csb-1(ok2335)_NAD+Precursor_rep2~WBPaper00064098:csb-1(ok2335)_NAD+Precursor_rep3~WBPaper00064098:csb-1(ok2335)_NAD+Precursor_rep4~WBPaper00064098:csa-1(tm4539);csb-1(ok2335)_control_rep1~WBPaper00064098:csa-1(tm4539);csb-1(ok2335)_control_rep2~WBPaper00064098:csa-1(tm4539);csb-1(ok2335)_control_rep3~WBPaper00064098:csa-1(tm4539);csb-1(ok2335)_control_rep4~WBPaper00064098:csa-1(tm4539);csb-1(ok2335)_NAD+Precursor_rep1~WBPaper00064098:csa-1(tm4539);csb-1(ok2335)_NAD+Precursor_rep2~WBPaper00064098:csa-1(tm4539);csb-1(ok2335)_NAD+Precursor_rep3~WBPaper00064098:csa-1(tm4539);csb-1(ok2335)_NAD+Precursor_rep4	Method: microarray|Species: Caenorhabditis elegans
297	36190544	WBPaper00064552.ce.mr.paper	N.A.	N.A.	1	Determining Toxic Potencies of Water-Soluble Contaminants in Wastewater Influents and Effluent Using Gene Expression Profiling in C. elegans as a Bioanalytical Tool.	With chemical analysis, it is impossible to qualify and quantify the toxic potency of especially hydrophilic bioactive contaminants. In this study, we applied the nematode C. elegans as a model organism for detecting the toxic potency of whole influent wastewater samples. Gene expression in the nematode was used as bioanalytical tool to reveal the presence, type and potency of molecular pathways induced by 24-h exposure to wastewater from a hospital (H), nursing home (N), community (C), and influent (I) and treated effluent (E) from a local wastewater treatment plant. Exposure to influent water significantly altered expression of 464 genes, while only two genes were differentially expressed in nematodes treated with effluent. This indicates a significant decrease in bioactive pollutant-load after wastewater treatment. Surface water receiving the effluent did not induce any genes in exposed nematodes. A subset of 209 genes was differentially expressed in all untreated wastewaters, including cytochromes P450 and C-type lectins related to the nematode's xenobiotic metabolism and immune response, respectively. Different subsets of genes responded to particular waste streams making them candidates to fingerprint-specific wastewater sources. This study shows that gene expression profiling in C. elegans can be used for mechanism-based identification of hydrophilic bioactive compounds and fingerprinting of specific wastewaters. More comprehensive than with chemical analysis, it can demonstrate the effective overall removal of bioactive compounds through wastewater treatment. This bioanalytical tool can also be applied in the process of identification of the bioactive compounds via a process of toxicity identification evaluation.	24	19636	Karengera A	Karengera A, Verburg I, Sterken MG, Riksen JAG, Murk AJ, Dinkla IJT	Determining Toxic Potencies of Water-Soluble Contaminants in Wastewater Influents and Effluent Using Gene Expression Profiling in C. elegans as a Bioanalytical Tool.	Arch Environ Contam Toxicol	2022	WBPaper00064552:Community_Sample16~WBPaper00064552:Community_Sample17~WBPaper00064552:Community_Sample3~WBPaper00064552:Hospital_Sample13~WBPaper00064552:Hospital_Sample5~WBPaper00064552:Hospital_Sample7~WBPaper00064552:NursingHome_Sample2~WBPaper00064552:NursingHome_Sample21~WBPaper00064552:NursingHome_Sample4~WBPaper00064552:Surface_Sample1~WBPaper00064552:Surface_Sample11~WBPaper00064552:Surface_Sample15~WBPaper00064552:Surface_Sample18~WBPaper00064552:Surface_Sample20~WBPaper00064552:Surface_Sample22~WBPaper00064552:Surface_Sample24~WBPaper00064552:Surface_Sample6~WBPaper00064552:Surface_Sample9~WBPaper00064552:WasteEffluent_Sample12~WBPaper00064552:WasteEffluent_Sample14~WBPaper00064552:WasteEffluent_Sample19~WBPaper00064552:WasteInfluent_Sample10~WBPaper00064552:WasteInfluent_Sample23~WBPaper00064552:WasteInfluent_Sample8	Method: microarray|Species: Caenorhabditis elegans
298	36861370	WBPaper00065209.ce.mr.paper	N.A.	N.A.	1	Cryptic genetic variation of eQTL architecture revealed by genetic perturbation in C. elegans.	Genetic perturbation in different genetic backgrounds can cause a range of phenotypes within a species. These phenotypic differences can be the result of the interaction between the genetic background and the perturbation. Previously we reported that perturbation of gld-1, an important player in developmental control of C. elegans, released cryptic genetic variation affecting fitness in different genetic backgrounds. Here we investigated the change in transcriptional architecture. We found 414 genes with a cis-eQTL and 991 genes with a trans-eQTL that were specifically found in the gld-1 RNAi treatment. In total, we detected 16 eQTL-hotspots, of which 7 were only found in the gld-1 RNAi treatment. Enrichment analysis of those 7 hotspots showed that the regulated genes were associated with neurons and the pharynx. Furthermore, we found evidence of accelerated transcriptional aging in the gld-1 RNAi treated nematodes. Overall, our results illustrate that studying CGV leads to the discovery of hidden polymorphic regulators.	94	19636	van Wijk MH	van Wijk MH, Riksen JAG, Elvin M, Poulin GB, Maulana MI, Kammenga JE, Snoek BL, Sterken MG	Cryptic genetic variation of eQTL architecture revealed by genetic perturbation in C. elegans.	G3 (Bethesda)	2023	WBPaper00065209:Sample_1_WN129_gld-1(RNAi)~WBPaper00065209:Sample_2_WN134_gld-1(RNAi)~WBPaper00065209:Sample_3_WN057_gld-1(RNAi)~WBPaper00065209:Sample_4_WN135_gld-1(RNAi)~WBPaper00065209:Sample_5_WN098_gld-1(RNAi)~WBPaper00065209:Sample_6_WN185_gld-1(RNAi)~WBPaper00065209:Sample_7_WN111_gld-1(RNAi)~WBPaper00065209:Sample_8_WN067_gld-1(RNAi)~WBPaper00065209:Sample_9_WN174_gld-1(RNAi)~WBPaper00065209:Sample_10_WN076_gld-1(RNAi)~WBPaper00065209:Sample_11_WN036_gld-1(RNAi)~WBPaper00065209:Sample_12_WN054_gld-1(RNAi)~WBPaper00065209:Sample_13_WN058_gld-1(RNAi)~WBPaper00065209:Sample_14_WN146_gld-1(RNAi)~WBPaper00065209:Sample_15_WN124_gld-1(RNAi)~WBPaper00065209:Sample_16_WN049_gld-1(RNAi)~WBPaper00065209:Sample_17_WN038_empty-vector~WBPaper00065209:Sample_18_WN161_gld-1(RNAi)~WBPaper00065209:Sample_19_WN190_empty-vector~WBPaper00065209:Sample_20_WN071_empty-vector~WBPaper00065209:Sample_21_WN109_gld-1(RNAi)~WBPaper00065209:Sample_22_WN105_empty-vector~WBPaper00065209:Sample_23_WN116_empty-vector~WBPaper00065209:Sample_24_WN152_empty-vector~WBPaper00065209:Sample_25_WN048_gld-1(RNAi)~WBPaper00065209:Sample_26_WN176_gld-1(RNAi)~WBPaper00065209:Sample_27_WN020_empty-vector~WBPaper00065209:Sample_28_WN171_empty-vector~WBPaper00065209:Sample_29_CB4856_empty-vector~WBPaper00065209:Sample_30_WN158_empty-vector~WBPaper00065209:Sample_31_WN196_gld-1(RNAi)~WBPaper00065209:Sample_32_WN159_empty-vector~WBPaper00065209:Sample_33_WN177_empty-vector~WBPaper00065209:Sample_34_WN113_empty-vector~WBPaper00065209:Sample_35_WN013_empty-vector~WBPaper00065209:Sample_36_N2_gld-1(RNAi)~WBPaper00065209:Sample_37_WN162_empty-vector~WBPaper00065209:Sample_38_WN186_gld-1(RNAi)~WBPaper00065209:Sample_39_CB4856_empty-vector~WBPaper00065209:Sample_40_WN142_gld-1(RNAi)~WBPaper00065209:Sample_41_WN140_empty-vector~WBPaper00065209:Sample_42_WN106_empty-vector~WBPaper00065209:Sample_43_WN128_empty-vector~WBPaper00065209:Sample_44_CB4856_gld-1(RNAi)~WBPaper00065209:Sample_45_WN153_empty-vector~WBPaper00065209:Sample_46_WN034_gld-1(RNAi)~WBPaper00065209:Sample_47_WN021_empty-vector~WBPaper00065209:Sample_48_WN071_gld-1(RNAi)~WBPaper00065209:Sample_49_WN080_gld-1(RNAi)~WBPaper00065209:Sample_50_WN021_gld-1(RNAi)~WBPaper00065209:Sample_51_WN020_gld-1(RNAi)~WBPaper00065209:Sample_52_WN177_gld-1(RNAi)~WBPaper00065209:Sample_53_WN158_gld-1(RNAi)~WBPaper00065209:Sample_54_WN162_gld-1(RNAi)~WBPaper00065209:Sample_55_WN105_gld-1(RNAi)~WBPaper00065209:Sample_56_WN040_gld-1(RNAi)~WBPaper00065209:Sample_57_WN072_empty-vector~WBPaper00065209:Sample_58_WN031_gld-1(RNAi)~WBPaper00065209:Sample_59_WN038_gld-1(RNAi)~WBPaper00065209:Sample_60_WN113_gld-1(RNAi)~WBPaper00065209:Sample_61_WN190_gld-1(RNAi)~WBPaper00065209:Sample_62_WN041_gld-1(RNAi)~WBPaper00065209:Sample_63_WN153_gld-1(RNAi)~WBPaper00065209:Sample_64_WN054_empty-vector~WBPaper00065209:Sample_65_WN171_gld-1(RNAi)~WBPaper00065209:Sample_66_WN146_empty-vector~WBPaper00065209:Sample_67_WN129_empty-vector~WBPaper00065209:Sample_68_WN116_gld-1(RNAi)~WBPaper00065209:Sample_69_WN067_empty-vector~WBPaper00065209:Sample_70_WN109_empty-vector~WBPaper00065209:Sample_71_WN196_empty-vector~WBPaper00065209:Sample_72_WN013_empty-vector~WBPaper00065209:Sample_73_WN159_gld-1(RNAi)~WBPaper00065209:Sample_74_WN135_empty-vector~WBPaper00065209:Sample_75_WN161_empty-vector~WBPaper00065209:Sample_76_N2_empty-vector~WBPaper00065209:Sample_77_WN185_empty-vector~WBPaper00065209:Sample_78_WN152_gld-1(RNAi)~WBPaper00065209:Sample_79_WN176_empty-vector~WBPaper00065209:Sample_80_WN098_empty-vector~WBPaper00065209:Sample_81_WN058_empty-vector~WBPaper00065209:Sample_82_WN048_empty-vector~WBPaper00065209:Sample_83_N2_empty-vector~WBPaper00065209:Sample_84_WN111_empty-vector~WBPaper00065209:Sample_85_WN140_gld-1(RNAi)~WBPaper00065209:Sample_86_CB4856_gld-1(RNAi)~WBPaper00065209:Sample_87_WN128_gld-1(RNAi)~WBPaper00065209:Sample_88_WN186_empty-vector~WBPaper00065209:Sample_89_WN034_empty-vector~WBPaper00065209:Sample_90_WN142_empty-vector~WBPaper00065209:Sample_91_N2_gld-1(RNAi)~WBPaper00065209:Sample_92_WN049_empty-vector~WBPaper00065209:Sample_93_WN106_gld-1(RNAi)~WBPaper00065209:Sample_94_WN057_empty-vector	Method: microarray|Species: Caenorhabditis elegans
299	37075089	WBPaper00065288.ce.mr.paper	GSE220955	GPL11346	1	Mediator subunit MDT-15 promotes expression of propionic acid breakdown genes to prevent embryonic lethality in Caenorhabditis elegans.	The micronutrient vitamin B12 is an essential cofactor for two enzymes: methionine synthase, which plays a key role in the one-carbon cycle; and methylmalonyl-CoA mutase, an enzyme in a pathway that breaks down branched-chain amino acids and odd-chain fatty acids. A second, vitamin B12-independent pathway that degrades propionic acid was recently described in Caenorhabditis elegans, the propionate shunt pathway. Activation of five shunt pathway genes in response to low vitamin B12 availability or high propionic acid levels is accomplished by a transcriptional regulatory mechanism involving two nuclear hormone receptors, NHR-10 and NHR-68. Here, we report that the C. elegans Mediator subunit mdt-15 is also essential for the activation of the propionate shunt pathway genes, likely by acting as a transcriptional coregulator for NHR-10. C. elegans mdt-15 mutants fed a low vitamin B12 diet have transcriptomes resembling those of wild-type worms fed a high vitamin B12 diet, with low expression of the shunt genes. Phenotypically, the embryonic lethality of mdt-15 mutants is specifically rescued by diets high in vitamin B12, but not by dietary polyunsaturated fatty acids, which rescue many other phenotypes of the mdt-15 mutants. Finally, NHR-10 binds to MDT-15 in yeast-two-hybrid assays, and the transcriptomes of nhr-10 mutants share overlap with those of mdt-15 mutants. Our data show that MDT-15 is a key coregulator for an NHR regulating propionic acid detoxification, adding to roles played by NHR:MDT-15 partnerships in metabolic regulation and pinpointing vitamin B12 availability as a requirement for mdt-15 dependent embryonic development.	8	19636	Goh GYS	Goh GYS, Beigi A, Yan J, Doering KRS, Taubert S	Mediator subunit MDT-15 promotes expression of propionic acid breakdown genes to prevent embryonic lethality in Caenorhabditis elegans.	G3 (Bethesda)	2023	WBPaper00065288:N2_rep1~WBPaper00065288:N2_rep2~WBPaper00065288:N2_rep3~WBPaper00065288:N2_rep4~WBPaper00065288:mdt-15(tm2182)_rep1~WBPaper00065288:mdt-15(tm2182)_rep2~WBPaper00065288:mdt-15(tm2182)_rep3~WBPaper00065288:mdt-15(tm2182)_rep4	Method: microarray|Species: Caenorhabditis elegans
300	20091141	WBPaper00035654.ce.mr.paper	GSE14899	GPL8200	2	Global microRNA expression profiling of Caenorhabditis elegans Parkinson's disease models.	MicroRNAs (miRNAs) play an important role in human brain development and maintenance. To search for miRNAs that may be involved in the pathogenesis of Parkinsons disease (PD), we utilized miRNA microarrays to identify potential gene expression changes in 115 annotated miRNAs in PD-associated Caenorhabditis elegans models that either overexpress human A53T alpha-synuclein or have mutations within the vesicular catecholamine transporter (cat-1) or parkin (pdr-1) ortholog. Here, we show that 12 specific miRNAs are differentially regulated in the animals overexpressing alpha-synuclein, five in cat-1, and three in the pdr-1 mutants. The family of miR-64 and miR-65 are co-underexpressed in the alpha-synuclein transgenic and cat-1 strains, and members of let-7 family co-underexpressed in the alpha-synuclein and pdr-1 strains; mdl-1 and ptc-1 genes are target candidates for miR-64 and miR-65 and are overexpressed in alpha-synuclein transgenic as well as miR-64/65 (tm3711) knockout animals. These results indicate that miRNAs are differentially expressed in C. elegans PD models and suggest a role for these molecules in disease pathogenesis.	12	69	Asikainen S	Asikainen S, Rudgalvyte M, Heikkinen L, Louhiranta K, Lakso M, Wong G, Nass R	Global microRNA expression profiling of Caenorhabditis elegans Parkinson's disease models.	J Mol Neurosci	2010	WBPaper00035654:alpha-synuclein-Is10_vs_N2_rep1~WBPaper00035654:alpha-synuclein-Is10_vs_N2_rep2~WBPaper00035654:alpha-synuclein-Is10_vs_N2_rep3~WBPaper00035654:alpha-synuclein-Is10_vs_N2_rep4~WBPaper00035654:cat-1(e1111)_vs_N2_rep1~WBPaper00035654:cat-1(e1111)_vs_N2_rep2~WBPaper00035654:cat-1(e1111)_vs_N2_rep3~WBPaper00035654:cat-1(e1111)_vs_N2_rep4~WBPaper00035654:pdr-1(gk448)_vs_N2_rep1~WBPaper00035654:pdr-1(gk448)_vs_N2_rep2~WBPaper00035654:pdr-1(gk448)_vs_N2_rep3~WBPaper00035654:pdr-1(gk448)_vs_N2_rep4	Method: microarray|Species: Caenorhabditis elegans
301	20096582	WBPaper00035664.ce.mr.paper	GSE19557	GPL9815	1	Many families of C. elegans microRNAs are not essential for development or viability.	MicroRNAs (miRNAs) are approximately 23 nt regulatory RNAs that posttranscriptionally inhibit the functions of protein-coding mRNAs. We previously found that most C. elegans miRNAs are individually not essential for development or viability and proposed that paralogous miRNAs might often function redundantly. To test this hypothesis, we generated mutant C. elegans strains that each lack multiple or all members of one of 15 miRNA families. Mutants for 12 of these families did not display strong synthetic abnormalities, suggesting that these miRNA families have subtle roles during development. By contrast, mutants deleted for all members of the mir-35 or mir-51 families died as embryos or early larvae, and mutants deleted for four members of the mir-58 family showed defects in locomotion, body size, and egg laying and an inability to form dauer larvae. Our findings indicate that the regulatory functions of most individual miRNAs and most individual families of miRNAs related in sequence are not critical for development or viability. Conversely, because in some cases miRNA family members act redundantly, our findings emphasize the importance of determining miRNA function in the absence of miRNAs related in sequence.	6	106	Alvarez-Saavedra E	Alvarez-Saavedra E, Horvitz HR	Many families of C. elegans microRNAs are not essential for development or viability.	Curr Biol	2010	WBPaper00035664:fem-2(b245ts)_Rep1-biolrep1~WBPaper00035664:fem-2(b245ts)_Rep2-biolrep1~WBPaper00035664:fem-2(b245ts)_Rep1-biolrep2~WBPaper00035664:fem-3(q20ts)_Rep1-biolrep1~WBPaper00035664:fem-3(q20ts)_Rep2-biolrep1~WBPaper00035664:fem-3(q20ts)_Rep1-biolrep2	Method: microarray|Species: Caenorhabditis elegans
302	21673804	WBPaper00038519_2.ce.mr.paper	GSE27288	GPL13164	1	The effectiveness of RNAi in Caenorhabditis elegans is maintained during spaceflight.	BACKGROUND: Overcoming spaceflight-induced (patho)physiologic adaptations is a major challenge preventing long-term deep space exploration. RNA interference (RNAi) has emerged as a promising therapeutic for combating diseases on Earth; however the efficacy of RNAi in space is currently unknown. METHODS: Caenorhabditis elegans were prepared in liquid media on Earth using standard techniques and treated acutely with RNAi or a vector control upon arrival in Low Earth Orbit. After culturing during 4 and 8 d spaceflight, experiments were stopped by freezing at -80C until analysis by mRNA and microRNA array chips, microscopy and Western blot on return to Earth. Ground controls (GC) on Earth were simultaneously grown under identical conditions. RESULTS: After 8 d spaceflight, mRNA expression levels of components of the RNAi machinery were not different from that in GC (e.g., Dicer, Argonaute, Piwi; P&gt;0.05). The expression of 228 microRNAs, of the 232 analysed, were also unaffected during 4 and 8 d spaceflight (P&gt;0.05). In spaceflight, RNAi against green fluorescent protein (gfp) reduced chromosomal gfp expression in gonad tissue, which was not different from GC. RNAi against rbx-1 also induced abnormal chromosome segregation in the gonad during spaceflight as on Earth. Finally, culture in RNAi against lysosomal cathepsins prevented degradation of the muscle-specific -actin protein in both spaceflight and GC conditions. CONCLUSIONS: Treatment with RNAi works as effectively in the space environment as on Earth within multiple tissues, suggesting RNAi may provide an effective tool for combating spaceflight-induced pathologies aboard future long-duration space missions. Furthermore, this is the first demonstration that RNAi can be utilised to block muscle protein degradation, both on Earth and in space.	6	172	Etheridge T	Etheridge T, Nemoto K, Hashizume T, Mori C, Sugimoto T, Suzuki H, Fukui K, Yamazaki T, Higashibata A, Szewczyk NJ, Higashitani A	The effectiveness of RNAi in Caenorhabditis elegans is maintained during spaceflight.	PLoS One	2011	WBPaper00038519:miRNA_micro-gravity_4d~WBPaper00038519:miRNA_micro-gravity_8d~WBPaper00038519:miRNA_1G-flight-control_4d~WBPaper00038519:miRNA_1G-flight-control_8d~WBPaper00038519:miRNA_ground-control_4d~WBPaper00038519:miRNA_ground-control_8d	Method: microarray|Species: Caenorhabditis elegans|Topic: regulatory ncRNA-mediated post-transcriptional gene silencing
303	22448270	WBPaper00040911.ce.mr.paper	GSE35505	GPL15181	1	Developmental characterization of the microRNA-specific C. elegans Argonautes alg-1 and alg-2.	The genes alg-1 and alg-2 (referred to as &quot;alg-1/2&quot;) encode the Argonaute proteins affiliated to the microRNA (miRNA) pathway in C. elegans. Bound to miRNAs they form the effector complex that effects post-transcriptional gene silencing. In order to define biological features important to understand the mode of action of these Argonautes, we characterize aspects of these genes during development. We establish that alg-1/2 display an overlapping spatio-temporal expression profile and shared association to a miRNAs set, but with gene-specific predominant expression in various cells and increased relative association to defined miRNAs. Congruent with their spatio-temporal coincidence and regardless of alg-1/2 drastic post-embryonic differences, only loss of both genes leads to embryonic lethality. Embryos without zygotic alg-1/2 predominantly arrest during the morphogenetic process of elongation with defects in the epidermal-muscle attachment structures. Altogether our results highlight similarities and specificities of the alg-1/2 likely to be explained at different cellular and molecular levels.	16	94	Vasquez-Rifo A	Vasquez-Rifo A, Jannot G, Armisen J, Labouesse M, Bukhari SI, Rondeau EL, Miska EA, Simard MJ	Developmental characterization of the microRNA-specific C. elegans Argonautes alg-1 and alg-2.	PLoS One	2012	WBPaper00040911:L4_ALG-1_IP~WBPaper00040911:L4_ALG-2-TAG_IP~WBPaper00040911:L4_ALG-1_control_IP~WBPaper00040911:L4_ALG-2-TAG_control_IP~WBPaper00040911:L3_ALG-1_IP~WBPaper00040911:L3_ALG-2-TAG_IP~WBPaper00040911:L3_ALG-1_control_IP~WBPaper00040911:L3_ALG-2-TAG_control_IP~WBPaper00040911:L2_ALG-1_IP~WBPaper00040911:L2_ALG-2-TAG_IP~WBPaper00040911:L2_ALG-1_control_IP~WBPaper00040911:L2_ALG-2-TAG_control_IP~WBPaper00040911:L1_ALG-1_IP~WBPaper00040911:L1_ALG-2-TAG_IP~WBPaper00040911:L1_ALG-1_control_IP~WBPaper00040911:L1_ALG-2-TAG_control_IP	Method: microarray|Species: Caenorhabditis elegans|Topic: regulation of pre-miRNA processing|Topic: regulation of primary miRNA processing|Topic: miRNA processing
304	22457637	WBPaper00040932.ce.mr.paper	GSE35634	GPL15202	2	lin-28 controls the succession of cell fate choices via two distinct activities.	lin-28 is a conserved regulator of cell fate succession in animals. In Caenorhabditis elegans, it is a component of the heterochronic gene pathway that governs larval developmental timing, while its vertebrate homologs promote pluripotency and control differentiation in diverse tissues. The RNA binding protein encoded by lin-28 can directly inhibit let-7 microRNA processing by a novel mechanism that is conserved from worms to humans. We found that C. elegans LIN-28 protein can interact with four distinct let-7 family pre-microRNAs, but in vivo inhibits the premature accumulation of only let-7. Surprisingly, however, lin-28 does not require let-7 or its relatives for its characteristic promotion of second larval stage cell fates. In other words, we find that the premature accumulation of mature let-7 does not account for lin-28's precocious phenotype. To explain let-7's role in lin-28 activity, we provide evidence that lin-28 acts in two steps: first, the let-7-independent positive regulation of hbl-1 through its 3'UTR to control L2 stage-specific cell fates; and second, a let-7-dependent step that controls subsequent fates via repression of lin-41. Our evidence also indicates that let-7 functions one stage earlier in C. elegans development than previously thought. Importantly, lin-28's two-step mechanism resembles that of the heterochronic gene lin-14, and the overlap of their activities suggests a clockwork mechanism for developmental timing. Furthermore, this model explains the previous observation that mammalian Lin28 has two genetically separable activities. Thus, lin-28's two-step mechanism may be an essential feature of its evolutionarily conserved role in cell fate succession.	6	101	Vadla B	Vadla B, Kemper K, Alaimo J, Heine C, Moss EG	lin-28 controls the succession of cell fate choices via two distinct activities.	PLoS Genet	2012	WBPaper00040932:lin-28(n719)_lin-46(ma164)_rep1~WBPaper00040932:N2_rep1~WBPaper00040932:lin-28(n719)_lin-46(ma164)_rep2~WBPaper00040932:lin-28(n719)_lin-46(ma164)_rep3~WBPaper00040932:N2_rep2~WBPaper00040932:N2_rep3	Method: microarray|Species: Caenorhabditis elegans
305	25257166	WBPaper00045807_2.ce.mr.paper	N.A.	N.A.	1	Neurotoxic action of microcystin-LR is reflected in the transcriptional stress response of Caenorhabditis elegans.	Cyanobacterial blooms in aquatic environments are frequently characterized by elevated levels of microcystins, a potent hepatotoxin. Here we exposed the nematode Caenorhabditis elegans with environmentally realistic concentrations of MC-LR to explore its non-hepatic toxicity. Lifespan, reproduction and growth assays confirmed the toxic potential of 100 g/L MC-LR even in this liver-lacking invertebrate. Whole-genome microarray analysis revealed that a neuromodulating action was the dominant response in nematodes challenged with 100 g/L MC-LR. Indeed, most of the 201 differentially expressed genes were associated with neurobehavior, neurogenesis, and signaling associated pathways. In addition, a whole-genome miRNA-microarray highlighted that, in particular, members of the let-7 family were differentially regulated. These miRNAs are involved in the developmental timing of cell fates, including neurons, and are probably also part of the stress response system. To conclude, neurological modulation is the main transcriptional stress response in C. elegans exposed to MC-LR.	6	218	Saul N	Saul N, Chakrabarti S, Sturzenbaum SR, Menzel R, Steinberg CE	Neurotoxic action of microcystin-LR is reflected in the transcriptional stress response of Caenorhabditis elegans.	Chem Biol Interact	2014	WBPaper00045807:Control-miRNA_Rep1~WBPaper00045807:Control-miRNA_Rep2~WBPaper00045807:Control-miRNA_Rep3~WBPaper00045807:microcystin-LR-miRNA_Rep1~WBPaper00045807:microcystin-LR-miRNA_Rep2~WBPaper00045807:microcystin-LR-miRNA_Rep3	Method: microarray|Species: Caenorhabditis elegans
306	15048112	WBPaper00006488.ce.mr.paper	N.A.	N.A.	1	TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM.	Both plants and animals respond to infection by synthesizing compounds that directly inhibit or kill invading pathogens. We report here the identification of infection-inducible antimicrobial peptides in Caenorhabditis elegans. Expression of two of these peptides, NLP-29 and NLP-31, was differentially regulated by fungal and bacterial infection and was controlled in part by tir-1, which encodes an ortholog of SARM, a Toll-interleukin 1 receptor (TIR) domain protein. Inactivation of tir-1 by RNA interference caused increased susceptibility to infection. We identify protein partners for TIR-1 and show that the small GTPase Rab1 and the f subunit of ATP synthase participate specifically in the control of antimicrobial peptide gene expression. As the activity of tir-1 was independent of the single nematode Toll-like receptor, TIR-1 may represent a component of a previously uncharacterized, but conserved, innate immune	16	5	Couillault C	Couillault C, Pujol N, Reboul J, Sabatier L, Guichou JF, Kohara Y, Ewbank J	TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM.	Nat Immunol	2004	WBPaper00006488:fer-15(b26ts)_12h_DConiospora_rep3~WBPaper00006488:fer-15(b26ts)_12h_DConiospora_rep2~WBPaper00006488:fer-15(b26ts)_12h_DConiospora_rep1~WBPaper00006488:fer-15(b26ts)_12h_DConiospora_rep4~WBPaper00006488:fer-15(b26ts)_12h_control_rep1~WBPaper00006488:fer-15(b26ts)_12h_control_rep2~WBPaper00006488:fer-15(b26ts)_12h_control_rep4~WBPaper00006488:fer-15(b26ts)_12h_control_rep3~WBPaper00006488:fer-15(b26ts)_24h_DConiospora_rep3~WBPaper00006488:fer-15(b26ts)_24h_DConiospora_rep2~WBPaper00006488:fer-15(b26ts)_24h_DConiospora_rep4~WBPaper00006488:fer-15(b26ts)_24h_control_rep1~WBPaper00006488:fer-15(b26ts)_24h_control_rep2~WBPaper00006488:fer-15(b26ts)_24h_control_rep4~WBPaper00006488:fer-15(b26ts)_24h_control_rep3~WBPaper00006488:fer-15(b26ts)_24h_DConiospora_rep1	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
307	17499272	WBPaper00029387.ce.mr.paper	GSE7125	GPL4469	2	Cytochrome P450s and short-chain dehydrogenases mediate the toxicogenomic response of PCB52 in the nematode Caenorhabditis elegans.	Although non-coplanar PCBs are ubiquitous organic chemicals known to induce numerous biological responses and thus are toxic to man and wildlife, little is known about the toxic mode of action. Using PCB52, an ortho-substituted, 2,2'',5,5''-tetrachlorobiphenyl, it was possible to pinpoint the relationship between induced gene expression and observed toxicity in the model nematode Caenorhabditis elegans. On the basis of the calculated EC20 for brood size (5 mg/l), whole genome DNA microarray experiments were performed to identify differentially expressed genes. Gene knockdown by RNAi was used to determine the consequences in reproductive fitness in the presence and in the absence of PCB52. On the basis of altered phenotype, several gene classes were identified to have a pivotal role in PCB52 toxicogenesis, most notably cytochrome P450s, short-chain dehydrogenases and lipases. In addition to this, four of six selected cytochrome P450s were shown to be involved in fat storage, with PCB52 exposure increasing the fat content in N2 wild-type as indicated by staining with Nile red. Furthermore, exposure to PCB52 induces a general detoxification response via small heat-shock proteins and caspases. Our data provide strong evidence of the molecular mechanisms that underlie the toxicity of non-coplanar PCBs, and confirms that, despite the ability to metabolize PCB, alterations in lipid metabolism and storage are major factors that drive the toxic effect of PCB52.	8	12003	Menzel R	Menzel R, Yeo HL, Rienau S, Li S, Steinberg CE, Sturzenbaum SR	Cytochrome P450s and short-chain dehydrogenases mediate the toxicogenomic response of PCB52 in the nematode Caenorhabditis elegans.	J Mol Biol	2007	WBPaper00029387:control_rep1~WBPaper00029387:control_rep2~WBPaper00029387:control_rep3~WBPaper00029387:control_rep4~WBPaper00029387:PCB52-exposed_rep1~WBPaper00029387:PCB52-exposed_rep2~WBPaper00029387:PCB52-exposed_rep3~WBPaper00029387:PCB52-exposed_rep4	Method: microarray|Species: Caenorhabditis elegans
308	18636113	WBPaper00032031_2.ce.mr.paper	N.A.	N.A.	1	Anti-fungal innate immunity in C. elegans is enhanced by evolutionary diversification of antimicrobial peptides.	Encounters with pathogens provoke changes in gene transcription that are an integral part of host innate immune responses. In recent years, studies with invertebrate model organisms have given insights into the origin, function, and evolution of innate immunity. Here, we use genome-wide transcriptome analysis to characterize the consequence of natural fungal infection in Caenorhabditis elegans. We identify several families of genes encoding putative antimicrobial peptides (AMPs) and proteins that are transcriptionally up-regulated upon infection. Many are located in small genomic clusters. We focus on the nlp-29 cluster of six AMP genes and show that it enhances pathogen resistance in vivo. The same cluster has a different structure in two other Caenorhabditis species. A phylogenetic analysis indicates that the evolutionary diversification of this cluster, especially in cases of intra-genomic gene duplications, is driven by natural selection. We further show that upon osmotic stress, two genes of the nlp-29 cluster are strongly induced. In contrast to fungus-induced nlp expression, this response is independent of the p38 MAP kinase cascade. At the same time, both involve the epidermal GATA factor ELT-3. Our results suggest that selective pressure from pathogens influences intra-genomic diversification of AMPs and reveal an unexpected complexity in AMP regulation as part of the invertebrate innate immune response.	12	6534	Pujol N	Pujol N, Zugasti O, Wong D, Couillault C, Kurz CL, Schulenburg H, Ewbank JJ	Anti-fungal innate immunity in C. elegans is enhanced by evolutionary diversification of antimicrobial peptides.	PLoS Pathog	2008	WBPaper00032031:N2_12h_control_rep1~WBPaper00032031:N2_12h_DConiospora_rep1~WBPaper00032031:N2_24h_control_rep1~WBPaper00032031:N2_24h_DConiospora_rep1~WBPaper00032031:N2_12h_control_rep2~WBPaper00032031:N2_12h_DConiospora_rep2~WBPaper00032031:N2_24h_control_rep2~WBPaper00032031:N2_24h_DConiospora_rep2~WBPaper00032031:N2_12h_control_rep3~WBPaper00032031:N2_12h_DConiospora_rep3~WBPaper00032031:N2_24h_control_rep3~WBPaper00032031:N2_24h_DConiospora_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
309	19366437	WBPaper00033070.ce.mr.paper	GSE11837	GPL6965	2	Gene expression profiling to characterize sediment toxicity--a pilot study using Caenorhabditis elegans whole genome microarrays.	BACKGROUND: Traditionally, toxicity of river sediments is assessed using whole sediment tests with benthic organisms. The challenge, however, is the differentiation between multiple effects caused by complex contaminant mixtures and the unspecific toxicity endpoints such as survival, growth or reproduction. The use of gene expression profiling facilitates the identification of transcriptional changes at the molecular level that are specific to the bio-available fraction of pollutants. RESULTS: In this pilot study, we exposed the nematode Caenorhabditis elegans to three sediments of German rivers with varying (low, medium and high) levels of heavy metal and organic contamination. Beside chemical analysis, three standard bioassays were performed: reproduction of C. elegans, genotoxicity (Comet assay) and endocrine disruption (YES test). Gene expression was profiled using a whole genome DNA-microarray approach to identify overrepresented functional gene categories and derived cellular processes. Disaccharide and glycogen metabolism were found to be affected, whereas further functional pathways, such as oxidative phosphorylation, ribosome biogenesis, metabolism of xenobiotics, aging and several developmental processes were found to be differentially regulated only in response to the most contaminated sediment. CONCLUSION: This study demonstrates how ecotoxicogenomics can identify transcriptional responses in complex mixture scenarios to distinguish different samples of river sediments.	15	16195	Menzel R	Menzel R, Swain SC, Hoess S, Claus E, Menzel S, Steinberg CE, Reifferscheid G, Sturzenbaum SR	Gene expression profiling to characterize sediment toxicity--a pilot study using Caenorhabditis elegans whole genome microarrays.	BMC Genomics	2009	WBPaper00033070:Danube_rep1~WBPaper00033070:Danube_rep2~WBPaper00033070:Danube_rep3~WBPaper00033070:Danube_rep4~WBPaper00033070:Danube_rep5~WBPaper00033070:Elbe_rep1~WBPaper00033070:Elbe_rep2~WBPaper00033070:Elbe_rep3~WBPaper00033070:Elbe_rep4~WBPaper00033070:Elbe_rep5~WBPaper00033070:Rhine_rep1~WBPaper00033070:Rhine_rep2~WBPaper00033070:Rhine_rep3~WBPaper00033070:Rhine_rep4~WBPaper00033070:Rhine_rep5	Method: microarray|Species: Caenorhabditis elegans|Topic: stress response to metal ion
310	19853451	WBPaper00035408.ce.mr.paper	GSE16621	GPL8673	1	The C. elegans dosage compensation complex propagates dynamically and independently of X chromosome sequence.	BACKGROUND: The C. elegans dosage compensation complex (DCC) associates with both X chromosomes of XX animals to reduce X-linked transcript levels. Five DCC members are homologous to subunits of the evolutionarily conserved condensin complex, and two noncondensin subunits are required for DCC recruitment to X. RESULTS: We investigated the molecular mechanism of DCC recruitment and spreading along X by examining gene expression and the binding patterns of DCC subunits in different stages of development, and in strains harboring X;autosome (X;A) fusions. We show that DCC binding is dynamically specified according to gene activity during development and that the mechanism of DCC spreading is independent of X chromosome DNA sequence. Accordingly, in X;A fusion strains, DCC binding propagates from X-linked recruitment sites onto autosomal promoters as a function of distance. Quantitative analysis of spreading suggests that the condensin-like subunits spread from recruitment sites to promoters more readily than subunits involved in initial X targeting. CONCLUSIONS: A highly conserved chromatin complex is appropriated to accomplish domain-scale transcriptional regulation during C. elegans development. Unlike X recognition, which is specified partly by DNA sequence, spreading is sequence independent and coupled to transcriptional activity. Similarities to the X recognition and spreading strategies used by the Drosophila DCC suggest mechanisms fundamental to chromosome-scale gene regulation.	9	19348	Ercan S	Ercan S, Dick LL, Lieb JD	The C. elegans dosage compensation complex propagates dynamically and independently of X chromosome sequence.	Curr Biol	2009	WBPaper00035408:N2_totalRNA_rep1~WBPaper00035408:N2_totalRNA_rep2~WBPaper00035408:N2_totalRNA_rep3~WBPaper00035408:YPT41_totalRNA_rep1~WBPaper00035408:YPT41_totalRNA_rep2~WBPaper00035408:YPT41_totalRNA_rep3~WBPaper00035408:YPT47_totalRNA_rep1~WBPaper00035408:YPT47_totalRNA_rep2~WBPaper00035408:YPT47_totalRNA_rep3	Method: microarray|Species: Caenorhabditis elegans
311	19883616	WBPaper00035479.ce.mr.paper	GSE18561,GSE18562,GSE18563	GPL9450	2	Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression.	Many studies have addressed the effect of dietary glycemic index on obesity and diabetes, but little is known about its effect on life span itself. We found that adding a small amount of glucose to the medium (2%) shortened the life span of C. elegans by inhibiting the activities of life span-extending transcription factors that are also inhibited by insulin signaling: the FOXO family member DAF-16 and the heat shock factor HSF-1. This effect involved the downregulation of an aquaporin glycerol channel, aqp-1. We show that changes in glycerol metabolism are likely to underlie the life span-shortening effect of glucose and that aqp-1 may act cell nonautonomously as a feedback regulator in the insulin/IGF-1-signaling pathway. Insulin downregulates similar glycerol channels in mammals, suggesting that this glucose-responsive pathway might be conserved evolutionarily. Together, these findings raise the possibility that a low-sugar diet might have beneficial effects on life span in higher organisms.	14	16850	Lee SJ	Lee SJ, Murphy CT, Kenyon C	Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression.	Cell Metab	2009	WBPaper00035479:daf-2(e1370)_daf-16(RNAi)_vs_daf-2(e1370)_control_rep1~WBPaper00035479:daf-2(e1370)_daf-16(RNAi)_vs_daf-2(e1370)_control_rep2~WBPaper00035479:daf-2(e1370)_daf-16(RNAi)_vs_daf-2(e1370)_control_rep3~WBPaper00035479:daf-2(e1370)_daf-16(RNAi)_vs_daf-2(e1370)_control_rep4~WBPaper00035479:daf-2(e1370)_daf-16(RNAi)_vs_daf-2(e1370)_control_rep5~WBPaper00035479:daf-2(e1370)_daf-16(RNAi)_vs_daf-2(e1370)_control_rep6~WBPaper00035479:daf-2(e1370)_daf-16(RNAi)_vs_daf-2(e1370)_control_rep7~WBPaper00035479:daf-2(e1370)_daf-16(RNAi)_vs_daf-2(e1370)_control_rep8~WBPaper00035479:N2_glucose_vs_N2_control_rep1~WBPaper00035479:N2_glucose_vs_N2_control_rep2~WBPaper00035479:N2_glucose_vs_N2_control_rep3~WBPaper00035479:N2_glucose_vs_N2_control_rep4~WBPaper00035479:N2_glucose_vs_N2_control_rep5~WBPaper00035479:N2_glucose_vs_N2_control_rep6	Method: microarray|Species: Caenorhabditis elegans
312	20331876	WBPaper00036123.ce.mr.paper	GSE21008,GSE21010,GSE21011,GSE21012	GPL10238	1	Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans.	BACKGROUND: Physiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used in Caenorhabditis elegans to identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to three toxic chemicals: cadmium, fluoranthene (FA) and atrazine (AZ). RESULTS: For Cd, the physiological mode of action as indicated by DEBtox model fitting was an effect on energy assimilation from food, suggesting that the transcriptional response to exposure should be dominated by changes in the expression of transcripts associated with energy metabolism and the mitochondria. While evidence for effect on genes associated with energy production were seen, an ontological analysis also indicated an effect of Cd exposure on DNA integrity and transcriptional activity. DEBtox modelling showed an effect of FA on costs for growth and reproduction (i.e. for production of new and differentiated biomass). The microarray analysis supported this effect, showing an effect of FA on protein integrity and turnover that would be expected to have consequences for rates of somatic growth. For AZ, the physiological mode of action predicted by DEBtox was increased cost for maintenance. The transcriptional analysis demonstrated that this increase resulted from effects on DNA integrity as indicated by changes in the expression of genes chromosomal repair. CONCLUSIONS: Our results have established that outputs from process based models and transcriptomics analyses can help to link mechanisms of action of toxic chemicals with resulting demographic effects. Such complimentary analyses can assist in the categorisation of chemicals for risk assessment purposes.	72	13107	Swain S	Swain S, Wren JF, Sturzenbaum SR, Kille P, Morgan AJ, Jager T, Jonker MJ, Hankard PK, Svendsen C, Owen J, Hedley BA, Blaxter M, Spurgeon DJ	Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans.	BMC Syst Biol	2010	WBPaper00036123:GE31_0mg_Atrazine_rep4~WBPaper00036123:GE31_0mg_Atrazine_rep5~WBPaper00036123:GE31_0mg_Atrazine_rep6~WBPaper00036123:GE31_0mg_Atrazine_rep7~WBPaper00036123:GE31_0mg_Atrazine_rep8~WBPaper00036123:GE31_5mg_Atrazine_rep1~WBPaper00036123:GE31_5mg_Atrazine_rep2~WBPaper00036123:GE31_5mg_Atrazine_rep3~WBPaper00036123:GE31_5mg_Atrazine_rep4~WBPaper00036123:GE31_5mg_Atrazine_rep5~WBPaper00036123:GE31_25mg_Atrazine_rep1~WBPaper00036123:GE31_25mg_Atrazine_rep2~WBPaper00036123:GE31_25mg_Atrazine_rep3~WBPaper00036123:GE31_25mg_Atrazine_rep4~WBPaper00036123:GE31_25mg_Atrazine_rep5~WBPaper00036123:GE31_75mg_Atrazine_rep1~WBPaper00036123:GE31_75mg_Atrazine_rep2~WBPaper00036123:GE31_75mg_Atrazine_rep5~WBPaper00036123:GE31_150mg_Atrazine_rep1~WBPaper00036123:GE31_150mg_Atrazine_rep2~WBPaper00036123:GE31_150mg_Atrazine_rep3~WBPaper00036123:GE31_150mg_Atrazine_rep4~WBPaper00036123:GE31_150mg_Atrazine_rep5~WBPaper00036123:GE31_0mg_Cadmium_rep1~WBPaper00036123:GE31_0mg_Cadmium_rep2~WBPaper00036123:GE31_0mg_Cadmium_rep3~WBPaper00036123:GE31_0mg_Cadmium_rep4b~WBPaper00036123:GE31_0mg_Cadmium_rep5b~WBPaper00036123:GE31_10mg_Cadmium_rep1~WBPaper00036123:GE31_10mg_Cadmium_rep2~WBPaper00036123:GE31_10mg_Cadmium_rep3~WBPaper00036123:GE31_10mg_Cadmium_rep4~WBPaper00036123:GE31_20mg_Cadmium_rep1~WBPaper00036123:GE31_20mg_Cadmium_rep2~WBPaper00036123:GE31_20mg_Cadmium_rep3~WBPaper00036123:GE31_20mg_Cadmium_rep4~WBPaper00036123:GE31_40mg_Cadmium_rep1~WBPaper00036123:GE31_40mg_Cadmium_rep2~WBPaper00036123:GE31_40mg_Cadmium_rep3~WBPaper00036123:GE31_40mg_Cadmium_rep4~WBPaper00036123:GE31_40mg_Cadmium_rep5~WBPaper00036123:GE31_60mg_Cadmium_rep1~WBPaper00036123:GE31_60mg_Cadmium_rep2~WBPaper00036123:GE31_60mg_Cadmium_rep3~WBPaper00036123:GE31_60mg_Cadmium_rep4~WBPaper00036123:GE31_60mg_Cadmium_rep5~WBPaper00036123:GE31_0mg_Fluoranthene_rep2b~WBPaper00036123:GE31_0mg_Fluoranthene_rep3b~WBPaper00036123:GE31_0mg_Fluoranthene_rep4c~WBPaper00036123:GE31_0mg_Fluoranthene_rep5c~WBPaper00036123:GE31_0mg_Fluoranthene_rep6b~WBPaper00036123:GE31_0mg_Fluoranthene_rep7b~WBPaper00036123:GE31_0mg_Fluoranthene_rep8b~WBPaper00036123:GE31_100mg_Fluoranthene_rep1~WBPaper00036123:GE31_100mg_Fluoranthene_rep2~WBPaper00036123:GE31_100mg_Fluoranthene_rep3~WBPaper00036123:GE31_100mg_Fluoranthene_rep4~WBPaper00036123:GE31_250mg_Fluoranthene_rep1~WBPaper00036123:GE31_250mg_Fluoranthene_rep2~WBPaper00036123:GE31_250mg_Fluoranthene_rep3~WBPaper00036123:GE31_250mg_Fluoranthene_rep4~WBPaper00036123:GE31_250mg_Fluoranthene_rep5~WBPaper00036123:GE31_500mg_Fluoranthene_rep1~WBPaper00036123:GE31_500mg_Fluoranthene_rep2~WBPaper00036123:GE31_500mg_Fluoranthene_rep3~WBPaper00036123:GE31_500mg_Fluoranthene_rep4~WBPaper00036123:GE31_500mg_Fluoranthene_rep5~WBPaper00036123:GE31_1000mg_Fluoranthene_rep1~WBPaper00036123:GE31_1000mg_Fluoranthene_rep2~WBPaper00036123:GE31_1000mg_Fluoranthene_rep3~WBPaper00036123:GE31_1000mg_Fluoranthene_rep4~WBPaper00036123:GE31_1000mg_Fluoranthene_rep5	Method: microarray|Species: Caenorhabditis elegans|Topic: stress response to metal ion
313	20824077	WBPaper00037131.ce.mr.paper	GSE58759	GPL18856	1	The histone H3K36 methyltransferase MES-4 acts epigenetically to transmit the memory of germline gene expression to progeny.	Methylation of histone H3K36 in higher eukaryotes is mediated by multiple methyltransferases. Set2-related H3K36 methyltransferases are targeted to genes by association with RNA Polymerase II and are involved in preventing aberrant transcription initiation within the body of genes. The targeting and roles of the NSD family of mammalian H3K36 methyltransferases, known to be involved in human developmental disorders and oncogenesis, are not known. We used genome-wide chromatin immunoprecipitation (ChIP) to investigate the targeting and roles of the Caenorhabditis elegans NSD homolog MES-4, which is maternally provided to progeny and is required for the survival of nascent germ cells. ChIP analysis in early C. elegans embryos revealed that, consistent with immunostaining results, MES-4 binding sites are concentrated on the autosomes and the leftmost approximately 2% (300 kb) of the X chromosome. MES-4 overlies the coding regions of approximately 5,000 genes, with a modest elevation in the 5' regions of gene bodies. Although MES-4 is generally found over Pol II-bound genes, analysis of gene sets with different temporal-spatial patterns of expression revealed that Pol II association with genes is neither necessary nor sufficient to recruit MES-4. In early embryos, MES-4 associates with genes that were previously expressed in the maternal germ line, an interaction that does not require continued association of Pol II with those loci. Conversely, Pol II association with genes newly expressed in embryos does not lead to recruitment of MES-4 to those genes. These and other findings suggest that MES-4, and perhaps the related mammalian NSD proteins, provide an epigenetic function for H3K36 methylation that is novel and likely to be unrelated to ongoing transcription. We propose that MES-4 transmits the memory of gene expression in the parental germ line to offspring and that this memory role is critical for the PGCs to execute a proper germline program.	4	19348	Rechtsteiner A	Rechtsteiner A, Ercan S, Takasaki T, Phippen TM, Egelhofer TA, Wang W, Kimura H, Lieb JD, Strome S	The histone H3K36 methyltransferase MES-4 acts epigenetically to transmit the memory of germline gene expression to progeny.	PLoS Genet	2010	WBPaper00037131:N2_early-embryo_rep1~WBPaper00037131:N2_early-embryo_rep2~WBPaper00037131:N2_early-embryo_rep3~WBPaper00037131:N2_early-embryo_rep4	Method: microarray|Species: Caenorhabditis elegans
314	21177966	WBPaper00037949.ce.mr.paper	GSE20136	GPL8673	1	High nucleosome occupancy is encoded at X-linked gene promoters in C. elegans.	We mapped nucleosome occupancy by paired-end Illumina sequencing in C. elegans embryonic cells, adult somatic cells, and a mix of adult somatic and germ cells. In all three samples, the nucleosome occupancy of gene promoters on the X chromosome differed from autosomal promoters. While both X and autosomal promoters exhibit a typical nucleosome-depleted region upstream of transcript start sites and a well-positioned +1 nucleosome, X-linked gene promoters on average exhibit higher nucleosome occupancy relative to autosomal promoters. We show that the difference between X and autosomes does not depend on the somatic dosage compensation machinery. Instead, the chromatin difference at promoters is partly encoded by DNA sequence, because a model trained on nucleosome sequence preferences from S. cerevisiae in vitro data recapitulate nearly completely the experimentally observed difference between X and autosomal promoters. The model predictions also correlate very well with experimentally determined occupancy values genome-wide. The nucleosome occupancy differences observed on X promoters may bear on mechanisms of X chromosome dosage compensation in the soma, and chromosome-wide repression of X in the germline.	7	19348	Ercan S	Ercan S, Lubling Y, Segal E, Lieb JD	High nucleosome occupancy is encoded at X-linked gene promoters in C. elegans.	Genome Res	2011	WBPaper00037949:GermlineContaining_adult_rep1~WBPaper00037949:GermlineContaining_adult_rep2~WBPaper00037949:Germlineless_adult_rep1~WBPaper00037949:Germlineless_adult_rep2~WBPaper00037949:N2_embryo_rep1~WBPaper00037949:N2_embryo_rep2~WBPaper00037949:XO-hermaphrodite_L3_rep1	Method: microarray|Species: Caenorhabditis elegans
315	23284299	WBPaper00041876.ce.mr.paper	GSE41943	GPL9450	2	Genes that act downstream of sensory neurons to influence longevity, dauer formation, and pathogen responses in Caenorhabditis elegans.	The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems.	3	16090	Gaglia MM	Gaglia MM, Jeong DE, Ryu EA, Lee D, Kenyon C, Lee SJ	Genes that act downstream of sensory neurons to influence longevity, dauer formation, and pathogen responses in Caenorhabditis elegans.	PLoS Genet	2012	WBPaper00041876:daf-10(m79)_vs_N2_rep1~WBPaper00041876:daf-10(m79)_vs_N2_rep2~WBPaper00041876:daf-10(m79)_vs_N2_rep3	Method: microarray|Species: Caenorhabditis elegans
316	24332851	WBPaper00044638.ce.mr.paper	GSE52340	GPL17925	1	Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans.	Inhibition of DAF-2 (insulin-like growth factor 1 [IGF-1] receptor) or RSKS-1 (S6K), key molecules in the insulin/IGF-1 signaling (IIS) and target of rapamycin (TOR) pathways, respectively, extend lifespan in Caenorhabditis elegans. However, it has not been clear how and in which tissues they interact with each other to modulate longevity. Here, we demonstrate that a combination of mutations in daf-2 and rsks-1 produces a nearly 5-fold increase in longevity that is much greater than the sum of single mutations. This synergistic lifespan extension requires positive feedback regulation of DAF-16 (FOXO) via the AMP-activated protein kinase (AMPK) complex. Furthermore, we identify germline as the key tissue for this synergistic longevity. Moreover, germline-specific inhibition of rsks-1 activates DAF-16 in the intestine. Together, our findings highlight the importance of the germline in the significantly increased longevity produced by daf-2 rsks-1, which has important implications for interactions between the two major conserved longevity pathways in more complex organisms.	47	11226	Chen D	Chen D, Li PW, Goldstein BA, Cai W, Thomas EL, Chen F, Hubbard AE, Melov S, Kapahi P	Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans.	Cell Rep	2013	WBPaper00044638:N2_rep1~WBPaper00044638:N2_rep2~WBPaper00044638:N2_rep8~WBPaper00044638:N2_rep3~WBPaper00044638:N2_rep4~WBPaper00044638:N2_rep5~WBPaper00044638:N2_rep6~WBPaper00044638:N2_rep7~WBPaper00044638:N2_rep10~WBPaper00044638:rsks-1(ok1255)_rep1~WBPaper00044638:rsks-1(ok1255)_rep2~WBPaper00044638:rsks-1(ok1255)_rep3~WBPaper00044638:rsks-1(ok1255)_rep4~WBPaper00044638:rsks-1(ok1255)_rep6~WBPaper00044638:rsks-1(ok1255)_rep7~WBPaper00044638:rsks-1(ok1255)_rep8~WBPaper00044638:rsks-1(ok1255)_rep9~WBPaper00044638:rsks-1(ok1255)_rep10~WBPaper00044638:daf-2(e1370)_rep1~WBPaper00044638:daf-2(e1370)_rep2~WBPaper00044638:daf-2(e1370)_rep3~WBPaper00044638:daf-2(e1370)_rep5~WBPaper00044638:daf-2(e1370)_rep6~WBPaper00044638:daf-2(e1370)_rep7~WBPaper00044638:daf-2(e1370)_rep8~WBPaper00044638:daf-2(e1370)_rep9~WBPaper00044638:daf-2(e1370)_rep10~WBPaper00044638:daf-2(e1370)rsks-1(ok1255)_rep1~WBPaper00044638:daf-2(e1370)rsks-1(ok1255)_rep2~WBPaper00044638:daf-2(e1370)rsks-1(ok1255)_rep3~WBPaper00044638:daf-2(e1370)rsks-1(ok1255)_rep4~WBPaper00044638:daf-2(e1370)rsks-1(ok1255)_rep5~WBPaper00044638:daf-2(e1370)rsks-1(ok1255)_rep6~WBPaper00044638:daf-2(e1370)rsks-1(ok1255)_rep7~WBPaper00044638:daf-2(e1370)rsks-1(ok1255)_rep8~WBPaper00044638:daf-2(e1370)rsks-1(ok1255)_rep9~WBPaper00044638:daf-2(e1370)rsks-1(ok1255)_rep10~WBPaper00044638:daf-16(mgDf47);daf-2(e1370)rsks-1(ok1255)_rep1~WBPaper00044638:daf-16(mgDf47);daf-2(e1370)rsks-1(ok1255)_rep2~WBPaper00044638:daf-16(mgDf47);daf-2(e1370)rsks-1(ok1255)_rep3~WBPaper00044638:daf-16(mgDf47);daf-2(e1370)rsks-1(ok1255)_rep4~WBPaper00044638:daf-16(mgDf47);daf-2(e1370)rsks-1(ok1255)_rep5~WBPaper00044638:daf-16(mgDf47);daf-2(e1370)rsks-1(ok1255)_rep6~WBPaper00044638:daf-16(mgDf47);daf-2(e1370)rsks-1(ok1255)_rep7~WBPaper00044638:daf-16(mgDf47);daf-2(e1370)rsks-1(ok1255)_rep8~WBPaper00044638:daf-16(mgDf47);daf-2(e1370)rsks-1(ok1255)_rep9~WBPaper00044638:daf-16(mgDf47);daf-2(e1370)rsks-1(ok1255)_rep10	Method: microarray|Species: Caenorhabditis elegans
317	25467431	WBPaper00046104.ce.mr.paper	GSE58760,GSE58764	GPL18855	1	Defining heterochromatin in C. elegans through genome-wide analysis of the heterochromatin protein 1 homolog HPL-2.	Formation of heterochromatin serves a critical role in organizing the genome and regulating gene expression. In most organisms, heterochromatin flanks centromeres and telomeres. To identify heterochromatic regions in the heavily studied model C. elegans, which possesses holocentric chromosomes with dispersed centromeres, we analyzed the genome-wide distribution of the heterochromatin protein 1 (HP1) ortholog HPL-2 and compared its distribution to other features commonly associated with heterochromatin. HPL-2 binding highly correlates with histone H3 mono- and dimethylated at lysine 9 (H3K9me1 and H3K9me2) and forms broad domains on autosomal arms. Although HPL-2, like other HP1 orthologs, binds H3K9me peptides in vitro, the distribution of HPL-2 in vivo appears relatively normal in mutant embryos that lack H3K9me, demonstrating that the chromosomal distribution of HPL-2 can be achieved in an H3K9me-independent manner. Consistent with HPL-2 serving roles independent of H3K9me, hpl-2 mutant worms display more severe defects than mutant worms lacking H3K9me. HPL-2 binding is enriched for repetitive sequences, and on chromosome arms is anticorrelated with centromeres. At the genic level, HPL-2 preferentially associates with well-expressed genes, and loss of HPL-2 results in up-regulation of some binding targets and down-regulation of others. Our work defines heterochromatin in an important model organism and uncovers both shared and distinctive properties of heterochromatin relative to other systems.	4	19348	Garrigues JM	Garrigues JM, Sidoli S, Garcia BA, Strome S	Defining heterochromatin in C. elegans through genome-wide analysis of the heterochromatin protein 1 homolog HPL-2.	Genome Res	2015	WBPaper00046104:hpl-2(tm1489)_early-embryo_rep1~WBPaper00046104:hpl-2(tm1489)_early-embryo_rep2~WBPaper00046104:hpl-2(tm1489)_early-embryo_rep3~WBPaper00046104:hpl-2(tm1489)_early-embryo_rep4	Method: microarray|Species: Caenorhabditis elegans
318	0	WBPaper00038011.ce.mr.paper	GSE21526	GPL8673	1	Few gene expression differences between C. elegans grown in liquid versus on plates	N.A.	6	19348	Reinke, Valerie	Reinke, Valerie, Mann, Frederick G., Whittle, Christina M., Lieb, Jason D.	Few gene expression differences between C. elegans grown in liquid versus on plates	Worm Breeder's Gazette	2010	WBPaper00038011:N2_adult_liquid_rep2~WBPaper00038011:N2_adult_plate_rep2~WBPaper00038011:N2_adult_plate_rep1~WBPaper00038011:N2_adult_plate_rep3~WBPaper00038011:N2_adult_liquid_rep3~WBPaper00038011:N2_adult_liquid_rep1	Method: microarray|Species: Caenorhabditis elegans
319	11795393	WBPaper00005124.ce.mr.paper	GSE2970	GPL2652,GPL2653	2	Caenorhabditis elegans as an environmental monitor using DNA microarray analysis.	In order to assist in the identification of possible endocrine disrupting chemicals (EDC) in groundwater, we are developing Caenorhabditis elegans as a high throughput bioassay system in which responses to EDC may be detected by gene expression using DNA microarray analysis. As a first step we examined gene expression patterns and vitellogenin responses of this organism to vertebrate steroid, in liquid culture. Western blotting showed the expected number and size of vitellogenin translation products after estrogen exposure. At 10(-9) M, vitellogenin decreased, but at 10(-7) and 10(-5), vitellogenin was increased. Testosterone (10(-5) M) increased the synthesis of vitellogenin, but progesterone-treated cultures (10(-5) M) had less vitellogenin. Using DNA microarray analysis, we examined the pattern of gene expression after progesterone (10(-5), 10(-7), and 10(-9) M), estrogen (10(-5) M) and testosterone (10(-9) M) exposure, with special attention to the traditional biomarker genes used in environmental studies [vitellogenin, cytochrome P450 (CYP), glutathione s-transferase (GST), metallothionein (MT), and heat shock proteins (HSP).] GST and P450 genes were affected by estrogen (10(-5) M) and progesterone (10(-5) and 10(-7) M) treatments. For vitellogenin genes, estrogen treatment (10(-5) M) caused overexpression of the vit-2 and vit-6 genes (2.68 and 3.25 times, respectively). After progesterone treatment (10(-7) M), the vit-5 and vit-6 were down-regulated and vit-1 up-regulated (3.59-fold). Concentrations of testosterone and progesterone at 10(-9) M did not influence the expression of the vit, CYP, or GST genes. Although the analysis is incomplete, and low doses and combinations of EDC need to be tested, these preliminary results indicate C. elegans may be a useful	6	16720	Custodia N	Custodia N, Won SJ, Novilla A, Li C, Callard IP, Novillo A, Wieland M	Caenorhabditis elegans as an environmental monitor using DNA microarray analysis.	Ann N Y Acad Sci	2001	[cgc5124]:testosterone_10-9M~[cgc5124]:progesterone_10-9M~[cgc5124]:progesterone_10-7M~[cgc5124]:estrogen_10-5M~[cgc5124]:cholesterol_10-9M~[cgc5124]:progesterone_10-5M	Method: microarray|Species: Caenorhabditis elegans
320	12214599	WBPaper00005428.ce.mr.paper	GSE2971	GPL2653	2	Chromosomal clustering of muscle-expressed genes in Caenorhabditis elegans.	Chromosomes are divided into domains of open chromatin, where genes have the potential to be expressed, and domains of closed chromatin, where genes are not expressed1. Classic examples of open chromatin domains include puffs on polytene chromosomes in Drosophila and extended loops from lampbrush chromosomes2,3. If multiple genes were typically expressed together from a single open chromatin domain, the position of co-expressed genes along the chromosomes would appear clustered. To investigate whether co-expressed genes are clustered, we examined the chromosomal positions of the genes expressed in muscle of Caenorhabditis elegans at the first larval stage. Here we show that co-expressed genes in C. elegans are clustered in groups of 25 along the chromosomes, suggesting that expression from a chromatin domain can extend over several genes. These observations reveal a higher-order organization of the structure of the genome, in which the order of genes along the chromosome is correlated with their expression in specific tissues.	6	16663	Roy PJ	Roy PJ, Stuart JM, Lund J, Kim SK	Chromosomal clustering of muscle-expressed genes in Caenorhabditis elegans.	Nature	2002	WBPaper00005428:myo-3p-IP_vs_totalRNA_Rep2~WBPaper00005428:myo-3p-IP_vs_totalRNA_Rep3~WBPaper00005428:myo-3p-IP_vs_totalRNA_Rep4~WBPaper00005428:myo-3p-IP_vs_totalRNA_Rep5~WBPaper00005428:myo-3p-IP_vs_totalRNA_Rep6~WBPaper00005428:myo-3p-IP_vs_totalRNA_Rep1	Method: microarray|Species: Caenorhabditis elegans|Topic: gene expression|Topic: somatic muscle development|Tissue Specific
321	12600716	WBPaper00005751.ce.mr.paper	N.A.	N.A.	2	Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer's disease model.	We have engineered transgenic Caenorhabditis elegans animals to inducibly express the human beta amyloid peptide (Abeta). Gene expression changes resulting from Abeta induction have been monitored by cDNA hybridization to glass slide microarrays containing probes for almost all known or predicted C. elegans genes. Using statistical criteria, we have identified 67 up-regulated and 240 down-regulated genes. Subsets of these regulated genes have been tested and confirmed by quantitative RT-PCR. To investigate whether genes identified in this model system also show gene expression changes in Alzheimer's disease (AD) brain, we have also used quantitative RT-PCR to examine in post-mortem AD brain tissue transcript levels of alphaB-crystallin (CRYAB) and tumor necrosis factor-induced protein 1 (TNFAIP1), human homologs of genes found to be robustly induced in the transgenic C. elegans model. Both CRYAB and TNFAIP1 show increased transcript levels in AD brains, supporting the validity of this approach.	3	15333	Link CD	Link CD, Taft A, Kapulkin V, Duke K, Kim S, Fei Q, Wood DE, Sahagan BG	Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer's disease model.	Neurobiol Aging	2003	[cgc5751]:induced_22hr~[cgc5751]:induced_29hr~[cgc5751]:uninduced	Method: microarray|Species: Caenorhabditis elegans
322	15893731	WBPaper00025192.ce.mr.paper	N.A.	N.A.	2	Regulation of tissue-specific and extracellular matrix-related genes by a class I histone deacetylase.	Class I histone deacetylases (HDACs) repress transcription by deacetylating histones and have been shown to play crucial roles in mouse, Xenopus, zebrafish, and C. elegans development. To identify the molecular networks regulated by a class I HDAC in a multicellular organism, we carried out a global gene expression profiling study using C. elegans embryos, and identified tissue-specific and extracellular matrix (ECM)-related genes as major HDA-1 targets. Ectopic expression of HDA-1 or C. elegans cystatin, an HDA-1 target identified from the microarray, significantly perturbed mammalian cell invasion. Similarly, RNAi depletion or overexpression of human HDAC-1 also affected cell migration. These findings suggest that HDA-1/HDAC-1 may play a critical, evolutionarily conserved role in regulating the extracellular microenvironment. Because human HDACs are targets for cancer therapy, these findings have significant implications in cancer treatment.	3	15604	Whetstine JR	Whetstine JR, Ceron J, Ladd B, Dufourcq P, Reinke V, Shi Y	Regulation of tissue-specific and extracellular matrix-related genes by a class I histone deacetylase.	Mol Cell	2005	WBPaper00025192:hda-1(RNAi)_vs_control_Rep2~WBPaper00025192:hda-1(RNAi)_vs_control_Rep3~WBPaper00025192:hda-1(RNAi)_vs_control_Rep1	Method: microarray|Species: Caenorhabditis elegans
323	15781453	WBPaper00026596.ce.mr.paper	GSE2836	GPL2569	2	Roles of the HIF-1 hypoxia-inducible factor during hypoxia response in Caenorhabditis elegans.	The human hypoxia inducible transcription factor HIF-1 is a critical regulator of cellular and systemic responses to low oxygen levels. When oxygen levels are high, the HIF-1 alpha subunit is hydroxylated and is targeted for degradation by the von Hippel-Lindau tumor suppressor protein (VHL). This regulatory pathway is evolutionarily conserved, and the C. elegans hif-1 and vhl-1 genes encode homologs of the HIF alpha subunit and VHL. To more fully understand and describe the molecular basis for hypoxia response in this important genetic model system, we compared hypoxia-induced changes in mRNA expression in wild-type, hif-1-deficient, and vhl-1-deficient C. elegans using whole-genome microarrays. These studies identify 110 hypoxia-regulated gene expression changes, 63 of which require hif-1 function. Mutation of vhl-1 abrogates most hif-1-dependent changes in mRNA expression. Genes regulated by C. elegans hif-1 have predicted functions in signal transduction, metabolism, transport, and extra cellular matrix remodeling. We examined the in vivo requirement for 16 HIF-1 target genes and discovered that the phy-2 prolyl 4-hydroxylase alpha subunit is critical for survival in hypoxic conditions. Some HIF-1 target genes negatively regulate formation of stress-resistant dauer larvae. The microarray data presented herein also provide clear evidence for a HIF-1-independent pathway for hypoxia response, and this pathway regulates the expression of multiple heat shock proteins and several transcription factors.	9	16657	Shen C	Shen C, Nettleton D, Jiang M, Kim SK, Powell-Coffman JA	Roles of the HIF-1 hypoxia-inducible factor during hypoxia response in Caenorhabditis elegans.	J Biol Chem	2005	WBPaper00026596:N2_normoxia_vs_N2_hypoxia_Rep1~WBPaper00026596:vhl-1(ok161)_normoxia_vs_vhl-1(ok161)_hypoxia_Rep1~WBPaper00026596:vhl-1(ok161)_normoxia_vs_vhl-1(ok161)_hypoxia_Rep2~WBPaper00026596:hif-1(ia4)_normoxia_vs_hif-1(ia4)_hypoxia_Rep1~WBPaper00026596:vhl-1(ok161)_normoxia_vs_vhl-1(ok161)_hypoxia_Rep3~WBPaper00026596:N2_normoxia_vs_N2_hypoxia_Rep2~WBPaper00026596:N2_normoxia_vs_N2_hypoxia_Rep3~WBPaper00026596:hif-1(ia4)_normoxia_vs_hif-1(ia4)_hypoxia_Rep2~WBPaper00026596:hif-1(ia4)_normoxia_vs_hif-1(ia4)_hypoxia_Rep3	Method: microarray|Species: Caenorhabditis elegans
324	16256736	WBPaper00026929.ce.mr.paper	GSE4402,GSE4093,GSE4094,GSE4095	GPL3390,GPL3391	2	A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span.	C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in endoplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span.	12	16663	Viswanathan M	Viswanathan M, Kim SK, Berdichevsky A, Guarente L	A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span.	Dev Cell	2005	WBPaper00026929:Resveratrol_daf-16_Rep1~WBPaper00026929:Resveratrol_daf-16_Rep2~WBPaper00026929:Resveratrol_daf-16_Rep3~WBPaper00026929:Resveratrol_daf-16_Rep4~WBPaper00026929:Resveratrol_N2_Rep1~WBPaper00026929:Resveratrol_N2_Rep2~WBPaper00026929:Resveratrol_N2_Rep3~WBPaper00026929:Resveratrol_N2_Rep4~WBPaper00026929:sir-2.1_overexpression_Rep1~WBPaper00026929:sir-2.1_overexpression_Rep2~WBPaper00026929:sir-2.1_overexpression_Rep3~WBPaper00026929:sir-2.1_overexpression_Rep4	Method: microarray|Species: Caenorhabditis elegans|Topic: obsolete mRNA splicing via endonucleolytic cleavage and ligation involved in unfolded protein response|Topic: endoplasmic reticulum unfolded protein response|Topic: endoplasmic reticulum|Topic: response to unfolded protein|Topic: mitochondrion|Topic: cytosol
325	17186023	WBPaper00028948.ce.mr.paper	N.A.	N.A.	2	Regulation of developmental rate and germ cell proliferation in Caenorhabditis elegans by the p53 gene network.	Caenorhabditis elegans CEP-1 activates germline apoptosis in response to genotoxic stress, similar to its mammalian counterpart, tumor suppressor p53. In mammals, there are three p53 family members (p53, p63, and p73) that activate and repress many distinct and overlapping sets of genes, revealing a complex transcriptional regulatory network. Because CEP-1 is the sole p53 family member in C. elegans, analysis of this network is greatly simplified in this organism. We found that CEP-1 functions during normal development in the absence of stress to repress many (331) genes and activate only a few (28) genes. In response to genotoxic stress, 1394 genes are activated and 942 are repressed, many of which contain p53-binding sites. Comparison of the CEP-1 transcriptional network with transcriptional targets of the human p53 family reveals considerable overlap between CEP-1-regulated genes and homologues regulated by human p63 and p53, suggesting a composite p53/p63 action for CEP-1. We found that phg-1, the C. elegans Gas1 (growth arrest-specific 1) homologue, is activated by CEP-1 and is a negative regulator of cell proliferation in the germline in response to genotoxic stress. Further, we find that CEP-1 and PHG-1 mediate the decreased developmental rate and embryonic viability of mutations in the clk-2/TEL2 gene, which regulates lifespan and checkpoint responses.Cell Death and Differentiation advance online publication, 22 December 2006; doi:10.1038/sj.cdd.4402075.	6	15776	Derry WB	Derry WB, Bierings R, van Iersel M, Satkunendran T, Reinke V, Rothman JH	Regulation of developmental rate and germ cell proliferation in Caenorhabditis elegans by the p53 gene network.	Cell Death Differ	2007	WBPaper00028948:N2_vs_cep-1(gk138)_repA~WBPaper00028948:N2_vs_cep-1(gk138)_repB~WBPaper00028948:N2_vs_cep-1(gk138)_repC~WBPaper00028948:N2+UV_vs_cep-1(gk138)+UV_repA~WBPaper00028948:N2+UV_vs_cep-1(gk138)+UV_repB~WBPaper00028948:N2+UV_vs_cep-1(gk138)+UV_repC	Method: microarray|Species: Caenorhabditis elegans|Topic: cell death|Topic: programmed cell death|Topic: apoptotic DNA fragmentation|Topic: apoptotic process|Topic: engulfment of apoptotic cell
326	17277379	WBPaper00029087.ce.mr.paper	N.A.	N.A.	2	Differential gene expression of Caenorhabditis elegans grown on unmethylated sterols or 4alpha-methylsterols.	Transcriptional profiles of Caenorhabditis elegans grown on unmethylated sterols (desMSs) or on 4a-methylsterols (4MSs) were compared using microarrays. Thirty-four genes were up-regulated and two down-regulated &gt;2-fold by growth on 4MSs, including 13 cuticle collagen (col) genes, 1 cuticlin gene (cut-1), 2 groundhog-like (grl) genes and 1 groundhog gene (grd-4); col-36 and grl-20 were 12- and 19-fold elevated, respectively. 15 of these 17 genes are assigned by Kim et al. (2001) to metabolic mountain 17, suggesting coordinate 4MS-mediated regulation of expression. Quantitative RT-PCR was performed on 27-51 h old animals, grown on cholesterol (a desMS) or lophenol (a 4MS). col-36 and grl-20 showed similar cyclic peaks of expression in cholesterol, and similar alterations in lophenol, suggesting co-regulation. Of 6 additional grl genes, only grl-3 was up-regulated on lophenol, the rest down-regulated; cyclic expression was lost or altered in all six. Nuclear receptor genes nhr-23, nhr-25, nhr-41, and daf-12 all showed cyclic expression in cholesterol and significant down-regulation in lophenol by RT-PCR. Expression of the insulin-like receptor daf-2 was lower in lophenol, while that of its major downstream target daf-16 was higher. Thus, major changes in gene expression accompany growth on 4MSs, but with surprisingly little effect on normal growth and development.	12	7655	Merris M	Merris M, Wang T, Soteropoulos P, Lenard J	Differential gene expression of Caenorhabditis elegans grown on unmethylated sterols or 4alpha-methylsterols.	J Lipid Res	2007	WBPaper00029087:cholesterol_vs_lophenol_1~WBPaper00029087:cholesterol_vs_delta_8(14)_sterol_1~WBPaper00029087:lathosterol_vs_lophenol_1~WBPaper00029087:lathosterol_vs_delta_8(14)_sterol_1~WBPaper00029087:cholesterol_vs_lophenol_2~WBPaper00029087:cholesterol_vs_delta_8(14)_sterol_2~WBPaper00029087:lathosterol_vs_lophenol_2~WBPaper00029087:lathosterol_vs_delta_8(14)_sterol_2~WBPaper00029087:cholesterol_vs_lophenol_3~WBPaper00029087:cholesterol_vs_delta_8(14)_sterol_3~WBPaper00029087:lathosterol_vs_lophenol_3~WBPaper00029087:lathosterol_vs_delta_8(14)_sterol_3	Method: microarray|Species: Caenorhabditis elegans
327	17875205	WBPaper00030985.ce.mr.paper	N.A.	N.A.	2	Genome-wide investigation reveals pathogen-specific and shared signatures in the response of Caenorhabditis elegans to infection.	ABSTRACT: BACKGROUND: There are striking similarities between the innate immune systems of invertebrates and vertebrates. Caenorhabditis elegans is increasingly used as a model for the study of innate immunity. Evidence is accumulating that C. elegans mounts distinct responses to different pathogens, but the true extent of this specificity is unclear. Here, we employ direct comparative genomic analyses to explore the nature of the host immune response. RESULTS: Using whole-genome microarrays representing 20334 genes, we analysed the transcriptional response of C. elegans to four bacterial pathogens. Different bacteria provoke pathogen-specific signatures within the host, involving differential regulation of 3.5-5% of all genes. These include genes that encode potential pathogen-recognition and antimicrobial proteins. Additionally, variance analysis revealed a robust pathogen-shared signature, involving 22 genes associated with proteolysis, cell death and stress responses. The expression of these genes, including those that mediate necrosis, is similarly altered following infection with three bacterial pathogens. We show that necrosis aggravates pathogenesis and accelerates the death of the host. CONCLUSION: Our results suggest that in C. elegans, different infections trigger both specific and pathogen-shared responses involving immune defence genes. The pathogen-shared response involves necrotic cell death, which has been associated with infection in humans. Our results are the first indication that necrosis is important for disease susceptibility in C. elegans. This opens the way for detailed study of the means by which certain bacteria exploit conserved elements of host cell death machinery to increase their effective virulence.	34	16781	Wong D	Wong D, Bazopoulou D, Pujol N, Tavernarakis N, Ewbank JJ	Genome-wide investigation reveals pathogen-specific and shared signatures in the response of Caenorhabditis elegans to infection.	Genome Biol	2007	WBPaper00030985:Aeromonas_hydrophila_rep1~WBPaper00030985:Aeromonas_hydrophila_rep2~WBPaper00030985:Aeromonas_hydrophila_rep3~WBPaper00030985:Aeromonas_hydrophila_rep4~WBPaper00030985:Aeromonas_hydrophila_rep5~WBPaper00030985:Aeromonas_hydrophila_rep6~WBPaper00030985:Serratia_marcesens_rep1~WBPaper00030985:Serratia_marcesens_rep2~WBPaper00030985:Serratia_marcesens_rep3~WBPaper00030985:Serratia_marcesens_rep4~WBPaper00030985:Serratia_marcesens_rep5~WBPaper00030985:Serratia_marcesens_rep6~WBPaper00030985:Serratia_marcesens_rep7~WBPaper00030985:Serratia_marcesens_rep8~WBPaper00030985:Serratia_marcesens_rep9~WBPaper00030985:Serratia_marcesens_rep10~WBPaper00030985:Enterococcus_faecalis_rep1~WBPaper00030985:Enterococcus_faecalis_rep2~WBPaper00030985:Enterococcus_faecalis_rep3~WBPaper00030985:Enterococcus_faecalis_rep4~WBPaper00030985:Enterococcus_faecalis_rep5~WBPaper00030985:Enterococcus_faecalis_rep6~WBPaper00030985:Erwinia_carotovora_rep1~WBPaper00030985:Erwinia_carotovora_rep2~WBPaper00030985:Erwinia_carotovora_rep3~WBPaper00030985:Erwinia_carotovora_rep4~WBPaper00030985:Erwinia_carotovora_rep5~WBPaper00030985:Erwinia_carotovora_rep6~WBPaper00030985:Photorhabdus_luminescens_rep1~WBPaper00030985:Photorhabdus_luminescens_rep2~WBPaper00030985:Photorhabdus_luminescens_rep3~WBPaper00030985:Photorhabdus_luminescens_rep4~WBPaper00030985:Photorhabdus_luminescens_rep5~WBPaper00030985:Photorhabdus_luminescens_rep6	Method: microarray|Species: Caenorhabditis elegans
328	18454197	WBPaper00031850.ce.mr.paper	GSE9720	GPL5859	2	The Mediator subunit MDT-15 confers metabolic adaptation to ingested material.	In eukaryotes, RNA polymerase II (Pol(II)) dependent gene expression requires accessory factors termed transcriptional coregulators. One coregulator that universally contributes to Pol(II)-dependent transcription is the Mediator, a multisubunit complex that is targeted by many transcriptional regulatory factors. For example, the Caenorhabditis elegans Mediator subunit MDT-15 confers the regulatory actions of the sterol response element binding protein SBP-1 and the nuclear hormone receptor NHR-49 on fatty acid metabolism. Here, we demonstrate that MDT-15 displays a broader spectrum of activities, and that it integrates metabolic responses to materials ingested by C. elegans. Depletion of MDT-15 protein or mutation of the mdt-15 gene abrogated induction of specific detoxification genes in response to certain xenobiotics or heavy metals, rendering these animals hypersensitive to toxin exposure. Intriguingly, MDT-15 appeared to selectively affect stress responses related to ingestion, as MDT-15 functional defects did not abrogate other stress responses, e.g., thermotolerance. Together with our previous finding that MDT-15:NHR-49 regulatory complexes coordinate a sector of the fasting response, we propose a model whereby MDT-15 integrates several transcriptional regulatory pathways to monitor both the availability and quality of ingested materials, including nutrients and xenobiotic compounds.	5	16997	Taubert S	Taubert S, Hansen M, van Gilst MR, Cooper SB, Yamamoto KR	The Mediator subunit MDT-15 confers metabolic adaptation to ingested material.	PLoS Genet	2008	WBPaper00031850:mdt-15(RNAi)_vs_control_rep1~WBPaper00031850:mdt-15(RNAi)_vs_control_rep2~WBPaper00031850:mdt-15(RNAi)_vs_control_rep3~WBPaper00031850:mdt-15(RNAi)_vs_control_rep4~WBPaper00031850:mdt-15(RNAi)_vs_control_rep5	Method: microarray|Species: Caenorhabditis elegans|Topic: stress response to metal ion
329	11697852	WBPaper00004966.ce.mr.paper	GSE3680	GPL2646,GPL2655,GPL3097	2	A systematic gene expression screen of Caenorhabditis elegans cytochrome P450 genes reveals CYP35 as strongly xenobiotic inducible.	The soil nematode Caenorhabditis elegans is one of the simplest animals having the status of a laboratory model. Its genome contains 80 cytochrome P450 genes (CYP). In order to study CYP gene expression in C. elegans mixed stages and synchronized hermaphrodites were exposed to 18 known xenobiotic cytochrome P450 inducers. Messenger RNA expression was detected by DNA arrays and semiquantitative RTPCR. Using subfamily-specific primers, a pooled set of exon-rich CYP fragments could be amplified. In this way it was possible to systematically check the influence of different inducers on CYP expression at the same time. The well-known CYP1A inducers beta -naphthoflavone, PCB52, and lansoprazol were the most active and in particular they strongly induced almost all CYP35 isoforms. A few number of further CYP forms were found to be inducible by other xenobiotics like phenobarbital, atrazine, and clofibrate. In addition, a transgenic C. elegans line expressing CYP under control of the CYP35A2 promoter showed a strong induction of the fusion by beta -naphthoflavone in the intestine.	3	16720	Menzel R	Menzel R, Bogaert T, Achazi R	A systematic gene expression screen of Caenorhabditis elegans cytochrome P450 genes reveals CYP35 as strongly xenobiotic inducible.	Arch Biochem Biophys	2001	WBPaper00004966:7a_DMSO_vs_7b_naph~WBPaper00004966:4a_DMSO_vs_4b_naph~WBPaper00004966:8a_DMSO_vs_8b_naph	Method: microarray|Species: Caenorhabditis elegans
330	12882324	WBPaper00005896.ce.mr.paper	GSE3089	GPL2653	2	Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16.	In Caenorhabditis elegans, the forkhead protein DAF-16 transduces insulin-like signals that regulate larval development and adult lifespan. To identify DAF-16-dependent transcriptional alterations that occur in a long-lived C. elegans strain, we used cDNA microarrays and genomic analysis to identify putative direct and indirect DAF-16 transcriptional target genes. Our analysis suggests that DAF-16 action regulates a wide range of physiological responses by altering the expression of genes involved in metabolism, energy generation and cellular stress responses. Furthermore, we observed a large overlap between DAF-16-dependent transcription and genes normally expressed in the long-lived dauer larval stage. Finally, we examined the in vivo role of 35 of these target genes by RNA-mediated interference and identified one gene encoding a putative protease that is necessary for the daf-2 Age phenotype.	4	16663	McElwee J	McElwee J, Bubb K, Thomas JH	Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16.	Aging Cell	2003	WBPaper00005896:daf-2_4-1_vs_daf-16_4-1~WBPaper00005896:daf-2_3-1_vs_daf-16_3-1~WBPaper00005896:daf-2_1-1_vs_daf-16_1-1~WBPaper00005896:daf-2_2-1_vs_daf-16_2-1	Method: microarray|Species: Caenorhabditis elegans
331	15028283	WBPaper00006465.ce.mr.paper	GSE3727	GPL2646,GPL2653,GPL3097	2	Ethanol-response genes and their regulation analyzed by a microarray and comparative genomic approach in the nematode Caenorhabditis elegans.	The nematode shows responses to acute ethanol exposure that are similar to those observed in humans, mice, and Drosophila, namely hyperactivity followed by uncoordination and sedation. We used in this report the nematode Caenorhabditis elegans as a model system to identify and characterize the genes that are affected by ethanol exposure and to link those genes functionally into an ethanol-induced gene network. By analyzing the expression profiles of all C. elegans ORTs using microarrays, we identified 230 genes affected by ethanol. While the ethanol response of some of the identified genes was significant at early time points, that of the majority was at late time points, indicating that the genes in the latter case might represent the physiological consequence of the ethanol exposure. We further characterized the early response genes that may represent those involved directly in the ethanol response. These genes included many heat shock protein genes, indicating that high concentration of ethanol acts as a strong stress to the animal. Interestingly, we identified two non-heat-shock protein genes that were specifically responsive to ethanol. glr-2 was the only glutamate receptor gene to be induced by ethanol. T28C12.4, which encodes a protein with limited homology to human neuroligin, was also specific to ethanol stress. Finally, by analyzing the promoter regions of the early response genes, we identified a regulatory element, TCTGCGTCTCT, that was necessary for the expression of subsets of ethanol	7	16720	Kwon JY	Kwon JY, Hong M, Choi MS, Kang S, Duke K, Kim S, Lee S, Lee J	Ethanol-response genes and their regulation analyzed by a microarray and comparative genomic approach in the nematode Caenorhabditis elegans.	Genomics	2004	WBPaper00006465:EtOH_treated_6hr-7~WBPaper00006465:EtOH_treated_6hr-5~WBPaper00006465:EtOH_treated_6hr-3~WBPaper00006465:EtOH_treated_15min-2~WBPaper00006465:EtOH_treated_15min-1~WBPaper00006465:EtOH_treated_30min~WBPaper00006465:EtOH_treated_6hr-4	Method: microarray|Species: Caenorhabditis elegans
332	15183729	WBPaper00013489.ce.mr.paper	GSE3979	GPL2646,GPL3308,GPL3309	2	Identification of C. elegans sensory ray genes using whole-genome expression profiling.	The three cells that comprise each C. elegans sensory ray (two sensory neurons and a structural cell) descend from a single neuroblast precursor cell. The atonal ortholog lin-32 and the E/daughterless ortholog hlh-2 act to confer neural competence during ray development, but additional regulatory factors that control specific aspects of cell fate are largely unknown. Here, we use full-genome DNA microarrays to compare gene expression profiles in adult males of two mutant strains to identify new components of the regulatory network that controls ray development and function. This approach identified a large set of candidate ray genes. Using reporter genes, we confirmed ray expression for 13 of these, including a beta-tubulin, a TWK-family channel, a putative chemoreceptor and four novel genes (the cwp genes) with a potential role in sensory signaling through the C. elegans polycystins lov-1 and pkd-2. Additionally, we have found several ray-expressed transcription factors, including the Zn-finger factor egl-46 and the bHLH gene hlh-10. The expression of many of these genes requires lin-32 function, though this requirement may not reflect direct activation by lin-32. Our strategy provides a complementary foundation for modeling the genetic network that controls the development of a simple sensory organ.	1	16572	Portman DS	Portman DS, Emmons SW	Identification of C. elegans sensory ray genes using whole-genome expression profiling.	Dev Biol	2004	WBPaper00013489:Ray_vs_noRay	Method: microarray|Species: Caenorhabditis elegans|Topic: sensory organ development
333	15361934	WBPaper00024375.ce.mr.paper	GSE2963	GPL2646,GPL2647	2	Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegans.	The von Hippel-Lindau (VHL) tumor suppressor functions as a ubiquitin ligase that mediates proteolytic inactivation of hydroxylated alpha subunits of hypoxia-inducible factor (HIF). Although studies of VHL-defective renal carcinoma cells suggest the existence of other VHL tumor suppressor pathways, dysregulation of the HIF transcriptional cascade has extensive effects that make it difficult to distinguish whether, and to what extent, observed abnormalities in these cells represent effects on pathways that are distinct from HIF. Here, we report on a genetic analysis of HIF-dependent and -independent effects of VHL inactivation by studying gene expression patterns in Caenorhabditis elegans. We show tight conservation of the HIF-1/VHL-1/EGL-9 hydroxylase pathway. However, persisting differential gene expression in hif-1 versus hif-1; vhl-1 double mutant worms clearly distinguished HIF-1-independent effects of VHL-1 inactivation. Genomic clustering, predicted functional similarities, and a common pattern of dysregulation in both vhl-1 worms and a set of mutants (dpy-18, let-268, gon-1, mig-17, and unc-6), with different defects in extracellular matrix formation, suggest that dysregulation of these genes reflects a discrete HIF-1-independent function of VHL-1 that is connected with extracellular matrix function.	2	16600	Bishop T	Bishop T, Lau KW, Epstein AC, Kim SK, Jiang M, O'Rourke D, Pugh CW, Gleadle JM, Taylor MS, Hodgkin J, Ratcliffe PJ	Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegans.	PLoS Biol	2004	WBPaper00024375:N2_vs_vhl-1~WBPaper00024375:hif-1_vs_hif-1_vhl-1	Method: microarray|Species: Caenorhabditis elegans
334	15852004	WBPaper00025099.ce.mr.paper	GSE4123	GPL2646,GPL2766,GPL3096,GPL3097,GPL3098,GPL3178,GPL3399	2	The transcriptional consequences of mutation and natural selection in Caenorhabditis elegans.	The evolutionary importance of gene-expression divergence is unclear: some studies suggest that it is an important mechanism for evolution by natural selection, whereas others claim that most between-species regulatory changes are neutral or nearly neutral. We examined global transcriptional divergence patterns in a set of Caenorhabditis elegans mutation-accumulation lines and natural isolate lines to provide insights into the evolutionary importance of transcriptional variation and to discriminate between the forces of mutation and natural selection in shaping the evolution of gene expression. We detected the effects of selection on transcriptional divergence patterns and characterized them with respect to coexpressed gene sets, chromosomal clustering of expression changes and functional gene categories. We directly compared observed transcriptional variation patterns in the mutation-accumulation and natural isolate lines to a neutral model of transcriptome evolution to show that strong stabilizing selection dominates the evolution of transcriptional change for thousands of C. elegans expressed sequences.	49	16720	Denver DR	Denver DR, Morris K, Streelman JT, Kim SK, Lynch M, Thomas WK	The transcriptional consequences of mutation and natural selection in Caenorhabditis elegans.	Nat Genet	2005	WBPaper00025099:N2-II_starting_line_vs_MA96-II_no_selection~WBPaper00025099:N2-I_starting_line_vs_PB306-I_with_selection~WBPaper00025099:N2-III_starting_line_vs_MA59-III_no_selection~WBPaper00025099:N2-II_starting_line_vs_MA59-II_no_selection~WBPaper00025099:MA41-4_A_no_selection_vs_MA24-4_B_no_selection~WBPaper00025099:MA41-3_A_no_selection_vs_MA24-3_B_no_selection~WBPaper00025099:CB4856-3_A_vs_AB1-3_B~WBPaper00025099:CB4856-4_A_vs_AB1-4_B~WBPaper00025099:N2-I_starting_line_vs_MA96-I_no_selection~WBPaper00025099:N2_vs_MA24_rep1~WBPaper00025099:N2_vs_MA24_rep2~WBPaper00025099:N2_vs_MA24_rep3~WBPaper00025099:N2_vs_MA99_rep1~WBPaper00025099:MA24-3_A_vs_N2-3_B~WBPaper00025099:N2-II_starting_line_vs_PB306-II_with_selection~WBPaper00025099:N2-III_starting_line_vs_PB306-III_with_selection~WBPaper00025099:MA24-2_B_no_selection_vs_MA41-2_A_no_selection~WBPaper00025099:MA24-1_B_no_selection_vs_MA41-1_A_no_selection~WBPaper00025099:N2-I_starting_line_vs_MA59-I_no_selection~WBPaper00025099:PB303-3_A_vs_N2-3_B~WBPaper00025099:AB1-3_A_vs_PB306-3_B~WBPaper00025099:MA83-2_B_vs_MA99-2_A~WBPaper00025099:AB1-1_B_vs_CB4856-1_A~WBPaper00025099:MA83-1_B_vs_MA99-1_A~WBPaper00025099:CB4856-2_B_vs_N2-2_A~WBPaper00025099:MA99-4_A_vs_MA83-4_B~WBPaper00025099:MA99-3_A_vs_MA83-3_B~WBPaper00025099:N2-3_A_vs_CB4856-3_B~WBPaper00025099:PB303-4_A_vs_N2-4_B~WBPaper00025099:N2_vs_MA99_rep2~WBPaper00025099:MA41-1_B_vs_MA83-1_A~WBPaper00025099:N2-4_A_vs_CB4856-4_B~WBPaper00025099:PB303-1_B_vs_PB306-1_A~WBPaper00025099:MA99_vs_N2_rep1~WBPaper00025099:MA83-4_A_vs_MA41-4_B~WBPaper00025099:AB1-2_B_vs_CB4856-2_A~WBPaper00025099:PB303-2_B_vs_PB306-2_A~WBPaper00025099:MA99_vs_N2_rep2~WBPaper00025099:MA83-3_A_vs_MA41-3_B~WBPaper00025099:PB306-4_A_vs_PB303-4_B~WBPaper00025099:N2_vs_PB303~WBPaper00025099:N2-1_B_vs_PB303-1_A~WBPaper00025099:PB306-1_B_vs_AB1-1_A~WBPaper00025099:AB1_vs_PB306-1~WBPaper00025099:MA24-4_A_vs_N2-4_B~WBPaper00025099:PB306-2_B_vs_AB1-2_A~WBPaper00025099:PB303_vs_PB306-2~WBPaper00025099:CB4856_vs_N2~WBPaper00025099:MA41_vs_MA83	Method: microarray|Species: Caenorhabditis elegans
335	16314527	WBPaper00026952.ce.mr.paper	GSE8520	GPL2646,GPL14	2	The Caenorhabditis elegans heterochronic regulator LIN-14 is a novel transcription factor that controls the developmental timing of transcription from the insulin/insulin-like growth factor gene ins-33 by direct DNA binding.	A temporal gradient of the novel nuclear protein LIN-14 specifies the timing and sequence of stage-specific developmental events in Caenorhabditis elegans. The profound effects of lin-14 mutations on worm development suggest that LIN-14 directly or indirectly regulates stage-specific gene expression. We show that LIN-14 can associate with chromatin in vivo and has in vitro DNA binding activity. A bacterially expressed C-terminal domain of LIN-14 was used to select DNA sequences that contain a putative consensus binding site from a pool of randomized double-stranded oligonucleotides. To identify candidates for genes directly regulated by lin-14, we employed DNA microarray hybridization to compare the mRNA abundance of C. elegans genes in wild-type animals to that in mutants with reduced or elevated lin-14 activity. Five of the candidate LIN-14 target genes identified by microarrays, including the insulin/insulin-like growth factor family gene ins-33, contain putative LIN-14 consensus sites in their upstream DNA sequences. Genetic analysis indicates that the developmental regulation of ins-33 mRNA involves the stage-specific repression of ins-33 transcription by LIN-14 via sequence-specific DNA binding. These results reinforce the conclusion that lin-14 encodes a novel class of transcription factor.	5	16663	Hristova M	Hristova M, Birse D, Hong Y, Ambros V	The Caenorhabditis elegans heterochronic regulator LIN-14 is a novel transcription factor that controls the developmental timing of transcription from the insulin/insulin-like growth factor gene ins-33 by direct DNA binding.	Mol Cell Biol	2005	WBPaper00026952:N2b_vs_lin-4b~WBPaper00026952:N2_vs_lin-14(n179ts)~WBPaper00026952:N2c_vs_lin-4c~WBPaper00026952:N2_vs_lin-14(n179ts)_rep2~WBPaper00026952:N2a_vs_lin-4a	Method: microarray|Species: Caenorhabditis elegans
336	16968818	WBPaper00028483.ce.mr.paper	GSE5454	GPL3860	2	MES-4: an autosome-associated histone methyltransferase that participates in silencing the X chromosomes in the C. elegans germ line.	Germ cell development in C. elegans requires that the X chromosomes be globally silenced during mitosis and early meiosis. We previously found that the nuclear proteins MES-2, MES-3, MES-4 and MES-6 regulate the different chromatin states of autosomes versus X chromosomes and are required for germline viability. Strikingly, the SET-domain protein MES-4 is concentrated on autosomes and excluded from the X chromosomes. Here, we show that MES-4 has histone H3 methyltransferase (HMT) activity in vitro, and is required for histone H3K36 dimethylation in mitotic and early meiotic germline nuclei and early embryos. MES-4 appears unlinked to transcription elongation, thus distinguishing it from other known H3K36 HMTs. Based on microarray analysis, loss of MES-4 leads to derepression of X-linked genes in the germ line. We discuss how an autosomally associated HMT may participate in silencing genes on the X chromosome, in coordination with the direct silencing effects of the other MES proteins.	4	16737	Bender LB	Bender LB, Suh J, Carroll CR, Fong Y, Fingerman IM, Briggs SD, Cao R, Zhang Y, Reinke V, Strome S	MES-4: an autosome-associated histone methyltransferase that participates in silencing the X chromosomes in the C. elegans germ line.	Development	2006	WBPaper00028483:N2_vs_mes-4_1~WBPaper00028483:N2_vs_mes-4_2~WBPaper00028483:mes-4_vs_N2_1~WBPaper00028483:mes-4_vs_N2_2	Method: microarray|Species: Caenorhabditis elegans|Topic: gene expression|Tissue Specific
337	17096596	WBPaper00028788.ce.mr.paper	GSE5069	GPL446,GPL539,GPL540,GPL3859,GPL3860,GPL3861	2	Expression profiling of MAP kinase-mediated meiotic progression in Caenorhabditis elegans.	The LET-60 (Ras)/LIN-45 (Raf)/MPK-1 (MAP kinase) signaling pathway plays a key role in the development of multiple tissues in Caenorhabditis elegans. For the most part, the identities of the downstream genes that act as the ultimate effectors of MPK-1 signaling have remained elusive. A unique allele of mpk-1, ga111, displays a reversible, temperature-sensitive, tissue-specific defect in progression through meiotic prophase I. We performed gene expression profiling on mpk-1(ga111) animals to identify candidate downstream effectors of MPK-1 signaling in the germ line. This analysis delineated a cohort of genes whose expression requires MPK-1 signaling in germ cells in the pachytene stage of meiosis I. RNA in situ hybridization analysis shows that these genes are expressed in the germ line in an MPK-1-dependent manner and have a spatial expression pattern consistent with the location of activated MPK-1. We found that one MPK-1 signaling-responsive gene encoding a C2H2 zinc finger protein plays a role in meiotic chromosome segregation downstream of MPK-1. Additionally, discovery of genes responsive to MPK-1 signaling permitted us to order MPK-1 signaling relative to several events occurring in pachytene, including EFL-1/DPL-1 gene regulation and X chromosome reactivation. This study highlights the utility of applying global gene expression methods to investigate genes downstream of commonly used signaling pathways in vivo.	24	16670	Leacock SW	Leacock SW, Reinke V	Expression profiling of MAP kinase-mediated meiotic progression in Caenorhabditis elegans.	PLoS Genet	2006	WBPaper00028788:0_hr_unc-79_fem-1_vs_ref_1~WBPaper00028788:0_hr_unc-79_fem-1_vs_ref_2~WBPaper00028788:0_hr_unc-79_fem-1_vs_ref_3~WBPaper00028788:0_hr_unc-79_mpk-1_fem-1_vs_ref_1~WBPaper00028788:0_hr_unc-79_mpk-1_fem-1_vs_ref_2~WBPaper00028788:0_hr_unc-79_mpk-1_fem-1_vs_ref_3~WBPaper00028788:3_hr_unc-79_mpk-1_fem-1_vs_ref_1~WBPaper00028788:3_hr_unc-79_mpk-1_fem-1_vs_ref_2~WBPaper00028788:3_hr_unc-79_mpk-1_fem-1_vs_ref_3~WBPaper00028788:6_hr_unc-79_mpk-1_fem-1_vs_ref_1~WBPaper00028788:6_hr_unc-79_mpk-1_fem-1_vs_ref_2~WBPaper00028788:6_hr_unc-79_mpk-1_fem-1_vs_ref_3~WBPaper00028788:9_hr_unc-79_mpk-1_fem-1_vs_ref_1~WBPaper00028788:9_hr_unc-79_mpk-1_fem-1_vs_ref_2~WBPaper00028788:12_hr_unc-79_mpk-1_fem-1_vs_ref_1~WBPaper00028788:12_hr_unc-79_mpk-1_fem-1_vs_ref_2~WBPaper00028788:12_hr_unc-79_mpk-1_fem-1_vs_ref_3~WBPaper00028788:15_hr_unc-79_mpk-1_fem-1_vs_ref_1~WBPaper00028788:15_hr_unc-79_mpk-1_fem-1_vs_ref_2~WBPaper00028788:15_hr_unc-79_mpk-1_fem-1_vs_ref_3~WBPaper00028788:15_hr_unc-79_fem-1_vs_ref_1~WBPaper00028788:15_hr_unc-79_fem-1_vs_ref_2~WBPaper00028788:15_hr_unc-79_fem-1_vs_ref_3~WBPaper00028788:9_hr_unc-79_mpk-1_fem-1_vs_ref_3	Method: microarray|Species: Caenorhabditis elegans|Topic: meiosis I|Topic: meiosis II
338	18234720	WBPaper00031477.ce.mr.paper	GSE9993	GPL3860	2	DEPS-1 promotes P-granule assembly and RNA interference in C. elegans germ cells.	P granules are germ-cell-specific cytoplasmic structures containing RNA and protein, and required for proper germ cell development in C. elegans. PGL-1 and GLH-1 were previously identified as critical components of P granules. We have identified a new P-granule-associated protein, DEPS-1, the loss of which disrupts P-granule structure and function. DEPS-1 is required for the proper localization of PGL-1 to P granules, the accumulation of glh-1 mRNA and protein, and germ cell proliferation and fertility at elevated temperatures. In addition, DEPS-1 is required for RNA interference (RNAi) of germline-expressed genes, possibly because DEPS-1 promotes the accumulation of RDE-4, a dsRNA-binding protein required for RNAi. A genome wide analysis of gene expression in deps-1 mutant germ lines identified additional targets of DEPS-1 regulation, many of which are also regulated by the RNAi factor RDE-3. Our studies suggest that DEPS-1 is a key component of the P-granule assembly pathway and that its roles include promoting accumulation of some mRNAs, such as glh-1 and rde-4, and reducing accumulation of other mRNAs, perhaps by collaborating with RDE-3 to generate endogenous short interfering RNAs (endo-siRNAs).	4	16701	Spike CA	Spike CA, Bader J, Reinke V, Strome S	DEPS-1 promotes P-granule assembly and RNA interference in C. elegans germ cells.	Development	2008	WBPaper00031477:deps-1_vs_N2_1~WBPaper00031477:deps-1_vs_N2_2~WBPaper00031477:N2_vs_deps-1_1~WBPaper00031477:N2_vs_deps-1_2	Method: microarray|Species: Caenorhabditis elegans|Topic: P granule organization|Topic: regulatory ncRNA-mediated post-transcriptional gene silencing|Tissue Specific
339	18927620	WBPaper00032276.ce.mr.paper	GSE13473	GPL7559,GPL7560,GPL7561,GPL7562	2	Pseudomonas aeruginosa suppresses host immunity by activating the DAF-2 insulin-like signaling pathway in Caenorhabditis elegans.	Some pathogens have evolved mechanisms to overcome host immune defenses by inhibiting host defense signaling pathways and suppressing the expression of host defense effectors. We present evidence that Pseudomonas aeruginosa is able to suppress the expression of a subset of immune defense genes in the animal host Caenorhabditis elegans by activating the DAF-2/DAF-16 insulin-like signaling pathway. The DAF-2/DAF-16 pathway is important for the regulation of many aspects of organismal physiology, including metabolism, stress response, longevity, and immune function. We show that intestinal expression of DAF-16 is required for resistance to P. aeruginosa and that the suppression of immune defense genes is dependent on the insulin-like receptor DAF-2 and the FOXO transcription factor DAF-16. By visualizing the subcellular localization of DAF-16::GFP fusion protein in live animals during infection, we show that P. aeruginosa-mediated downregulation of a subset of immune genes is associated with the ability to translocate DAF-16 from the nuclei of intestinal cells. Suppression of DAF-16 is mediated by an insulin-like peptide, INS-7, which functions upstream of DAF-2. Both the inhibition of DAF-16 and downregulation of DAF-16-regulated genes, such as thn-2, lys-7, and spp-1, require the P. aeruginosa two-component response regulator GacA and the quorum-sensing regulators LasR and RhlR and are not observed during infection with Salmonella typhimurium or Enterococcus faecalis. Our results reveal a new mechanism by which P. aeruginosa suppresses host immune defense.	26	16718	Evans EA	Evans EA, Kawli T, Tan MW	Pseudomonas aeruginosa suppresses host immunity by activating the DAF-2 insulin-like signaling pathway in Caenorhabditis elegans.	PLoS Pathog	2008	WBPaper00032276:op50_0421_N2_24h~WBPaper00032276:daf-2_OP50_1~WBPaper00032276:op50_0529_N2_4h~WBPaper00032276:pa14_0421_N2_24h~WBPaper00032276:daf-2_PA14_4~WBPaper00032276:pa14_sma6_0730_4h~WBPaper00032276:pa14_0422_N2_24h~WBPaper00032276:daf-2_PA14_2~WBPaper00032276:pa14_0629_4hr~WBPaper00032276:pa14_0423_N2_24h~WBPaper00032276:pa14_sma6_0702_4h~WBPaper00032276:op50_0507_N2_4h~WBPaper00032276:op50_0422_N2_24h~WBPaper00032276:daf-2_OP50_3~WBPaper00032276:daf-2_PA14_3~WBPaper00032276:op50_0629_N2_4h~WBPaper00032276:op50_0429_sma6_4h~WBPaper00032276:pa14_0507_N2_4h~WBPaper00032276:daf-2_PA14_1~WBPaper00032276:daf-2_OP50_4~WBPaper00032276:op50_sma6_0702_4h~WBPaper00032276:pa14_0429_sma6_4h~WBPaper00032276:op50_sma6_0730_4h~WBPaper00032276:pa14_0529_N2_4h~WBPaper00032276:op50_N2_1119_24h~WBPaper00032276:daf-2_OP50_2	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
340	20599896	WBPaper00036429.ce.mr.paper	GSE21531	GPL540	2	Genome-wide analysis of germ cell proliferation in C.elegans identifies VRK-1 as a key regulator of CEP-1/p53.	Proliferating germ cells in Caenorhabditiselegans provide a useful model system for deciphering fundamental mechanisms underlying the balance between proliferation and differentiation. Using gene expression profiling, we identified approximately 200 genes upregulated in the proliferating germ cells of C. elegans. Functional characterization using RNA-mediated interference demonstrated that over forty of these factors are required for normal germline proliferation and development. Detailed analysis of two of these factors defined an important regulatory relationship controlling germ cell proliferation. We established that the kinase VRK-1 is required for normal germ cell proliferation, and that it acts in part to regulate CEP-1(p53) activity. Loss of cep-1 significantly rescued the proliferation defects of vrk-1 mutants. We suggest that VRK-1 prevents CEP-1 from triggering an inappropriate cell cycle arrest, thereby promoting germ cell proliferation. This finding reveals a previously unsuspected mechanism for negative regulation of p53 activity in germ cells to control proliferation.	4	15314	Waters K	Waters K, Yang AZ, Reinke V	Genome-wide analysis of germ cell proliferation in C.elegans identifies VRK-1 as a key regulator of CEP-1/p53.	Dev Biol	2010	WBPaper00036429:excess_prolif_ya_rep1~WBPaper00036429:excess_prolif_ya_rep2~WBPaper00036429:excess_prolif_ya_rep3~WBPaper00036429:excess_prolif_ya_rep4	Method: microarray|Species: Caenorhabditis elegans
341	23980181	WBPaper00044091.ce.mr.paper	N.A.	N.A.	2	Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific degradation of a GATA transcription factor.	Burkholderia pseudomallei is a Gram-negative soil bacterium that infects both humans and animals. Although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. To gain insights into the host defense responses to B. pseudomallei infection within an intact host, we analyzed the genome-wide transcriptome of infected Caenorhabditis elegans and identified 6% of the nematode genes that were significantly altered over a 12-h course of infection. An unexpected feature of the transcriptional response to B. pseudomallei was a progressive increase in the proportion of down-regulated genes, of which ELT-2 transcriptional targets were significantly enriched. ELT-2 is an intestinal GATA transcription factor with a conserved role in immune responses. We demonstrate that B. pseudomallei down-regulation of ELT-2 targets is associated with degradation of ELT-2 protein by the host ubiquitin-proteasome system. Degradation of ELT-2 requires the B. pseudomallei type III secretion system. Together, our studies using an intact host provide evidence for pathogen-mediated host immune suppression through the destruction of a host transcription factor.	27	16460	Lee SH	Lee SH, Wong RR, Chin CY, Lim TY, Eng SA, Kong C, Ijap NA, Lau MS, Lim MP, Gan YH, He FL, Tan MW, Nathan S	Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific degradation of a GATA transcription factor.	Proc Natl Acad Sci U S A	2013	WBPaper00044091:OP50_0h_rep2~WBPaper00044091:OP50_0h_rep3~WBPaper00044091:OP50_2h_rep1~WBPaper00044091:OP50_2h_rep2~WBPaper00044091:OP50_2h_rep3~WBPaper00044091:OP50_4h_rep1~WBPaper00044091:OP50_4h_rep2~WBPaper00044091:OP50_4h_rep3~WBPaper00044091:OP50_8h_rep1~WBPaper00044091:OP50_8h_rep2~WBPaper00044091:OP50_8h_rep3~WBPaper00044091:OP50_12h_rep1~WBPaper00044091:OP50_12h_rep2~WBPaper00044091:OP50_12h_rep3~WBPaper00044091:BpR15_2h_rep1~WBPaper00044091:BpR15_2h_rep2~WBPaper00044091:BpR15_2h_rep3~WBPaper00044091:BpR15_4h_rep1~WBPaper00044091:BpR15_4h_rep2~WBPaper00044091:BpR15_4h_rep3~WBPaper00044091:BpR15_8h_rep1~WBPaper00044091:BpR15_8h_rep2~WBPaper00044091:BpR15_8h_rep3~WBPaper00044091:BpR15_12h_rep1~WBPaper00044091:BpR15_12h_rep2~WBPaper00044091:BpR15_12h_rep3~WBPaper00044091:OP50_0h_rep1	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
342	14730301	WBPaper00006365.ce.mr.paper	GSE832,GSE946	GPL576,GPL924	2	Comparing genomic expression patterns across species identifies shared transcriptional profile in aging.	We developed a method for systematically comparing gene expression patterns across organisms using genome-wide comparative analysis of DNA microarray experiments. We identified analogous gene expression programs comprising shared patterns of regulation across orthologous genes. Biological features of these patterns could be identified as highly conserved subpatterns that correspond to Gene Ontology categories. Here, we demonstrate these methods by analyzing a specific biological process, aging, and show that similar analysis can be applied to a range of biological processes. We found that two highly diverged animals, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, implement a shared adult-onset expression program of genes involved in mitochondrial metabolism, DNA repair, catabolism, peptidolysis and cellular transport. Most of these changes were implemented early in adulthood. Using this approach to search databases of gene expression data, we found conserved transcriptional signatures in larval development, embryogenesis, gametogenesis and mRNA degradation.	14	16735	McCarroll SA	McCarroll SA, Murphy CT, Zou S, Pletcher SD, Chin CS, Jan YN, Kenyon C, Bargmann CI, Li H	Comparing genomic expression patterns across species identifies shared transcriptional profile in aging.	Nat Genet	2004	WBPaper00006365:Adult_0_hr~WBPaper00006365:Adult_8_hr~WBPaper00006365:Adult_16_hr~WBPaper00006365:Adult_28_hr~WBPaper00006365:Adult_52_hr~WBPaper00006365:Adult_96_hr~WBPaper00006365:Adult_144_hr~WBPaper00006365:HeatShock_0_hr~WBPaper00006365:HeatShock_2_hr~WBPaper00006365:HeatShock_4_hr~WBPaper00006365:HeatShock_6_hr~WBPaper00006365:HeatShock_8_hr~WBPaper00006365:HeatShock_10_hr~WBPaper00006365:HeatShock_12_hr	Method: microarray|Species: Caenorhabditis elegans
343	16626392	WBPaper00027339.ce.mr.paper	N.A.	N.A.	2	The nuclear hormone receptor DAF-12 has opposing effects on Caenorhabditis elegans lifespan and regulates genes repressed in multiple long-lived worms.	The orphan nuclear hormone receptor gene daf-12 in Caenorhabditis elegans plays a key role in the regulation of development and determination of adult longevity. To understand the effects of daf-12 on aging we characterized the lifespan of loss-of-function and gain-of-function daf-12 alleles that have been identified on the basis of their effects on dauer development. We find that these mutations have opposing effects on longevity and resistance to oxidative and thermal stress which makes daf-12 the first gene with alleles that can extend or shorten lifespan. We find that the shortened lifespan of the loss-of-function mutation is due to accelerated aging in young adulthood rather than an adverse effect of the mutation on development. Microarray analysis of worms carrying the two alleles revealed a relatively small number of genes differentially expressed between the two genotypes. Comparison of the expression profiles with the profiles associated with dauer formation and long-lived daf-2 mutants revealed that while the profiles are largely different, there is significant overlap among the genes down-regulated, but not up-regulated, in all profiles. Several of these genes down-regulated in multiple long-lived worms have known effects on lifespan, and many of the genes belong to a family of poorly characterized genes that are strongly down-regulated in dauers, daf-2 mutants, and long-lived daf-12 mutants. Our results point to daf-12 modulating aging and stress responses in part through the repression of specific genes, and emphasize the role that the repression of genes that curtail maximal lifespan plays in lifespan determination.	16	16997	Fisher AL	Fisher AL, Lithgow GJ	The nuclear hormone receptor DAF-12 has opposing effects on Caenorhabditis elegans lifespan and regulates genes repressed in multiple long-lived worms.	Aging Cell	2006	WBPaper00027339:daf-12(rh61rh411)_vs_N2_rep1~WBPaper00027339:daf-12(rh61rh411)_vs_N2_rep2~WBPaper00027339:daf-12(rh61rh411)_vs_N2_rep3~WBPaper00027339:daf-12(rh61rh411)_vs_N2_rep4~WBPaper00027339:daf-12(rh61rh411)_vs_N2_rep1(DyeSwap)~WBPaper00027339:daf-12(rh61rh411)_vs_N2_rep2(DyeSwap)~WBPaper00027339:daf-12(rh61rh411)_vs_N2_rep3(DyeSwap)~WBPaper00027339:daf-12(rh61rh411)_vs_N2_rep4(DyeSwap)~WBPaper00027339:daf-12(rh273)_vs_N2_rep1~WBPaper00027339:daf-12(rh273)_vs_N2_rep2~WBPaper00027339:daf-12(rh273)_vs_N2_rep3~WBPaper00027339:daf-12(rh273)_vs_N2_rep4~WBPaper00027339:daf-12(rh273)_vs_N2_rep1(DyeSwap)~WBPaper00027339:daf-12(rh273)_vs_N2_rep2(DyeSwap)~WBPaper00027339:daf-12(rh273)_vs_N2_rep3(DyeSwap)~WBPaper00027339:daf-12(rh273)_vs_N2_rep4(DyeSwap)	Method: microarray|Species: Caenorhabditis elegans
344	18042455	WBPaper00031252.ce.mr.paper	GSE9073	GPL5883	1	Systematic identification of C. elegans miRISC proteins, miRNAs, and mRNA targets by their interactions with GW182 proteins AIN-1 and AIN-2.	MicroRNAs (miRNAs) regulate gene expression for diverse functions, but only a limited number of mRNA targets have been experimentally identified. We show that GW182 family proteins AIN-1 and AIN-2 act redundantly to regulate the expression of miRNA targets, but not miRNA biogenesis. Immunoprecipitation (IP) and mass spectrometry indicate that AIN-1 and AIN-2 interact only with miRNA-specific Argonaute proteins ALG-1 and ALG-2 and with components of the core translational initiation complex. Known miRNA targets are enriched in AIN-2 complexes, correlating with the expression of corresponding miRNAs. Combining IP with pyrosequencing and microarray analysis of RNAs associated with AIN-1/AIN-2, we identified 106 previously annotated miRNAs plus nine new candidate miRNAs, but nearly no siRNAs, and more than 3500 potential miRNA targets, including nearly all known ones. Our results demonstrate an effective biochemical approach to systematically identify miRNA targets and provide valuable insights regarding the properties of miRNA effector complexes.	20	16997	Zhang L	Zhang L, Ding L, Cheung TH, Dong MQ, Chen J, Sewell AK, Liu X, Yates JR, Han M	Systematic identification of C. elegans miRISC proteins, miRNAs, and mRNA targets by their interactions with GW182 proteins AIN-1 and AIN-2.	Mol Cell	2007	WBPaper00031252:AIN-1_IP_rep1~WBPaper00031252:AIN-1_IP_rep2~WBPaper00031252:AIN-1_IP_rep3~WBPaper00031252:Preimmune_IP_rep1~WBPaper00031252:Preimmune_IP_rep2~WBPaper00031252:Preimmune_IP_rep3~WBPaper00031252:AIN-2-GFP_IP_rep1~WBPaper00031252:AIN-2-GFP_IP_rep2~WBPaper00031252:AIN-2-GFP_IP_rep3~WBPaper00031252:GFP_IP_rep1~WBPaper00031252:GFP_IP_rep2~WBPaper00031252:GFP_IP_rep3~WBPaper00031252:N2_totalRNA_rep1~WBPaper00031252:N2_totalRNA_rep2~WBPaper00031252:AIN-2-GFP_totalRNA_rep1~WBPaper00031252:AIN-2-GFP_totalRNA_rep2~WBPaper00031252:AIN-2-GFP_totalRNA_rep3~WBPaper00031252:AIN-2_promoter_GFP_totalRNA_rep1~WBPaper00031252:AIN-2_promoter_GFP_totalRNA_rep2~WBPaper00031252:AIN-2_promoter_GFP_totalRNA_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: regulation of pre-miRNA processing|Topic: regulation of primary miRNA processing|Topic: miRNA processing
345	18636113	WBPaper00032031.ce.mr.paper	N.A.	N.A.	2	Anti-fungal innate immunity in C. elegans is enhanced by evolutionary diversification of antimicrobial peptides.	Encounters with pathogens provoke changes in gene transcription that are an integral part of host innate immune responses. In recent years, studies with invertebrate model organisms have given insights into the origin, function, and evolution of innate immunity. Here, we use genome-wide transcriptome analysis to characterize the consequence of natural fungal infection in Caenorhabditis elegans. We identify several families of genes encoding putative antimicrobial peptides (AMPs) and proteins that are transcriptionally up-regulated upon infection. Many are located in small genomic clusters. We focus on the nlp-29 cluster of six AMP genes and show that it enhances pathogen resistance in vivo. The same cluster has a different structure in two other Caenorhabditis species. A phylogenetic analysis indicates that the evolutionary diversification of this cluster, especially in cases of intra-genomic gene duplications, is driven by natural selection. We further show that upon osmotic stress, two genes of the nlp-29 cluster are strongly induced. In contrast to fungus-induced nlp expression, this response is independent of the p38 MAP kinase cascade. At the same time, both involve the epidermal GATA factor ELT-3. Our results suggest that selective pressure from pathogens influences intra-genomic diversification of AMPs and reveal an unexpected complexity in AMP regulation as part of the invertebrate innate immune response.	32	16997	Pujol N	Pujol N, Zugasti O, Wong D, Couillault C, Kurz CL, Schulenburg H, Ewbank JJ	Anti-fungal innate immunity in C. elegans is enhanced by evolutionary diversification of antimicrobial peptides.	PLoS Pathog	2008	WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM0~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM1~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM2~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM3~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM4~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM5~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM6~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM7~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM8~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM9~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM10~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM11~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM12~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM13~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM14~WBPaper00032031:N2_12h_DConiospora_vs_N2_12h_control_GEM15~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM16~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM17~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM18~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM19~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM20~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM21~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM22~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM23~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM24~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM25~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM26~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM27~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM28~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM29~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM30~WBPaper00032031:N2_24h_DConiospora_vs_N2_24h_control_GEM31	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
346	19380113	WBPaper00033094.ce.mr.paper	N.A.	N.A.	2	Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and a conserved p38 MAPK cascade.	Like other multicellular organisms, the model nematode C. elegans responds to infection by inducing the expression of defense genes. Among the genes upregulated in response to a natural fungal pathogen is nlp-29, encoding an antimicrobial peptide. In a screen for mutants that fail to express nlp-29 following fungal infection, we isolated alleles of tpa-1, homologous to the mammalian protein kinase C (PKC) delta. Through epistasis analyses, we demonstrate that C. elegans PKC acts through the p38 MAPK pathway to regulate nlp-29. This involves G protein signaling and specific C-type phospholipases acting upstream of PKCdelta. Unexpectedly and unlike in mammals, tpa-1 does not act via D-type protein kinases, but another C. elegans PKC gene, pkc-3, functions nonredundantly with tpa-1 to control nlp-29 expression. Finally, the tribbles-like kinase nipi-3 acts upstream of PKCdelta in this antifungal immune signaling cascade. These findings greatly expand our understanding of the pathways involved in C. elegans innate immunity.	8	16830	Ziegler K	Ziegler K, Kurz CL, Cypowyj S, Couillault C, Pophillat M, Pujol N, Ewbank JJ	Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and a conserved p38 MAPK cascade.	Cell Host Microbe	2009	WBPaper00033094:tpa-1_DConiospora_vs_tpa-1_control_rep1~WBPaper00033094:tpa-1_DConiospora_vs_tpa-1_control_rep2~WBPaper00033094:tpa-1_DConiospora_vs_tpa-1_control_rep3~WBPaper00033094:tpa-1_DConiospora_vs_tpa-1_control_rep4~WBPaper00033094:WT_DConiospora_vs_WT_control_rep1~WBPaper00033094:WT_DConiospora_vs_WT_control_rep2~WBPaper00033094:WT_DConiospora_vs_WT_control_rep3~WBPaper00033094:WT_DConiospora_vs_WT_control_rep4	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
347	19379696	WBPaper00033101.ce.mr.paper	GSE14432	GPL5859	2	A C. elegans LSD1 demethylase contributes to germline immortality by reprogramming epigenetic memory.	Epigenetic information undergoes extensive reprogramming in the germline between generations. This reprogramming may be essential to establish a developmental ground state in the zygote. We show that mutants in spr-5, the Caenorhabditis elegans ortholog of the H3K4me2 demethylase LSD1/KDM1, exhibit progressive sterility over many generations. This sterility correlates with the misregulation of spermatogenesis-expressed genes and transgenerational accumulation of the histone modification dimethylation of histone H3 on lysine 4 (H3K4me2). This suggests that H3K4me2 can serve as a stable epigenetic memory, and that erasure of H3K4me2 by LSD/KDM1 in the germline prevents the inappropriate transmission of this epigenetic memory from one generation to the next. Thus, our results provide direct mechanistic insights into the processes that are required for epigenetic reprogramming between generations.	12	16997	Katz DJ	Katz DJ, Edwards TM, Reinke V, Kelly WG	A C. elegans LSD1 demethylase contributes to germline immortality by reprogramming epigenetic memory.	Cell	2009	WBPaper00033101:f1_v_f13~WBPaper00033101:f1_v_f26~WBPaper00033101:f13_v_f1~WBPaper00033101:f1_v_N2~WBPaper00033101:f13_v_f26~WBPaper00033101:f13_v_N2~WBPaper00033101:f26_v_f1~WBPaper00033101:f26_v_f13~WBPaper00033101:f26_v_N2~WBPaper00033101:N2_v_f1~WBPaper00033101:N2_v_f13~WBPaper00033101:N2_v_f26	Method: microarray|Species: Caenorhabditis elegans|Topic: germ-line stem cell population maintenance|Topic: germ-line stem-cell niche homeostasis|Topic: germ-line stem cell division
348	19503598	WBPaper00033444.ce.mr.paper	GSE15923	GPL5883	2	Caenorhabditis elegans genomic response to soil bacteria predicts environment-specific genetic effects on life history traits.	With the post-genomic era came a dramatic increase in high-throughput technologies, of which transcriptional profiling by microarrays was one of the most popular. One application of this technology is to identify genes that are differentially expressed in response to different environmental conditions. These experiments are constructed under the assumption that the differentially expressed genes are functionally important in the environment where they are induced. However, whether differential expression is predictive of functional importance has yet to be tested. Here we have addressed this expectation by employing Caenorhabditis elegans as a model for the interaction of native soil nematode taxa and soil bacteria. Using transcriptional profiling, we identified candidate genes regulated in response to different bacteria isolated in association with grassland nematodes or from grassland soils. Many of the regulated candidate genes are predicted to affect metabolism and innate immunity suggesting similar genes could influence nematode community dynamics in natural systems. Using mutations that inactivate 21 of the identified genes, we showed that most contribute to lifespan and/or fitness in a given bacterial environment. Although these bacteria may not be natural food sources for C. elegans, we show that changes in food source, as can occur in environmental disturbance, can have a large effect on gene expression, with important consequences for fitness. Moreover, we used regression analysis to demonstrate that for many genes the degree of differential gene expression between two bacterial environments predicted the magnitude of the effect of the loss of gene function on life history traits in those environments.	36	16997	Coolon JD	Coolon JD, Jones KL, Todd TC, Carr BC, Herman MA	Caenorhabditis elegans genomic response to soil bacteria predicts environment-specific genetic effects on life history traits.	PLoS Genet	2009	WBPaper00033444:105_rep2_P_vs_M~WBPaper00033444:111_rep2_P_vs_B~WBPaper00033444:112_rep2_M_vs_B~WBPaper00033444:114_rep2_E_vs_P~WBPaper00033444:13228210_rep2_E_vs_M~WBPaper00033444:13228212_rep2_B_vs_E~WBPaper00033444:1319585_rep3_M_vs_E~WBPaper00033444:13198581_rep3_E_vs_B~WBPaper00033444:13201463_rep3_M_vs_P~WBPaper00033444:13201466_rep3_B_vs_P~WBPaper00033444:13228207_rep3_B_vs_M~WBPaper00033444:13228208_rep3_P_vs_E~WBPaper00033444:13201460_rep3_M_vs_B~WBPaper00033444:13201473_rep4_B_vs_E~WBPaper00033444:13201474_rep4_P_vs_M~WBPaper00033444:13201475_rep4_P_vs_B~WBPaper00033444:13201476_rep4_E_vs_M~WBPaper00033444:13228201_rep4_E_vs_P~WBPaper00033444:13201477_rep5_M_vs_E~WBPaper00033444:13201478_rep5_P_vs_E~WBPaper00033444:13201479_rep5_M_vs_P~WBPaper00033444:13201481_rep5_E_vs_B~WBPaper00033444:13201482_rep5_B_vs_M~WBPaper00033444:13228209_rep5_B_vs_P~WBPaper00033444:13228202_rep6_E_vs_P~WBPaper00033444:13228204_rep6_B_vs_E~WBPaper00033444:13228206_rep6_M_vs_B~WBPaper00033444:13288434_rep6_P_vs_M~WBPaper00033444:13288436_rep6_M_vs_E~WBPaper00033444:13288437_rep6_B_vs_P~WBPaper00033444:13228205_rep7_B_vs_M~WBPaper00033444:13288438_rep7_P_vs_E~WBPaper00033444:13288439_rep7_E_vs_B~WBPaper00033444:13288440_rep7_M_vs_P~WBPaper00033444:13288441_rep7_E_vs_M~WBPaper00033444:13288442_rep7_P_vs_B	Method: microarray|Species: Caenorhabditis elegans
349	19675127	WBPaper00035084.ce.mr.paper	GSE16208	GPL5883	1	Systematic analysis of dynamic miRNA-target interactions during C. elegans development.	Although microRNA (miRNA)-mediated functions have been implicated in many aspects of animal development, the majority of miRNA::mRNA regulatory interactions remain to be characterized experimentally. We used an AIN/GW182 protein immunoprecipitation approach to systematically analyze miRNA::mRNA interactions during C. elegans development. We characterized the composition of miRNAs in functional miRNA-induced silencing complexes (miRISCs) at each developmental stage and identified three sets of miRNAs with distinct stage-specificity of function. We then identified thousands of miRNA targets in each developmental stage, including a significant portion that is subject to differential miRNA regulation during development. By identifying thousands of miRNA family-mRNA pairs with temporally correlated patterns of AIN-2 association, we gained valuable information on the principles of physiological miRNA::target recognition and predicted 1589 high-confidence miRNA family::mRNA interactions. Our data support the idea that miRNAs preferentially target genes involved in signaling processes and avoid genes with housekeeping functions, and that miRNAs orchestrate temporal developmental programs by coordinately targeting or avoiding genes involved in particular biological functions.	36	16997	Zhang L	Zhang L, Hammell M, Kudlow BA, Ambros V, Han M	Systematic analysis of dynamic miRNA-target interactions during C. elegans development.	Development	2009	WBPaper00035084:1_Egg_IP~WBPaper00035084:1_Egg_tot~WBPaper00035084:2_Egg_IP~WBPaper00035084:2_Egg_tot~WBPaper00035084:4_Egg_IP~WBPaper00035084:4_Egg_tot~WBPaper00035084:5_Egg_IP~WBPaper00035084:5_Egg_tot~WBPaper00035084:2_L1_IP~WBPaper00035084:2_L1_tot~WBPaper00035084:5_L1_IP~WBPaper00035084:5_L1_tot~WBPaper00035084:10_L1_IP~WBPaper00035084:10_L1_tot~WBPaper00035084:11_L1_IP~WBPaper00035084:11_L1_tot~WBPaper00035084:1_L2_IP~WBPaper00035084:1_L2_tot~WBPaper00035084:2_L2_IP~WBPaper00035084:2_L2_tot~WBPaper00035084:3_L2_IP~WBPaper00035084:3_L2_tot~WBPaper00035084:1_L3_IP~WBPaper00035084:1_L3_tot~WBPaper00035084:2_L3_IP~WBPaper00035084:2_L3_tot~WBPaper00035084:3_L3_IP~WBPaper00035084:3_L3_tot~WBPaper00035084:5_L3_IP~WBPaper00035084:5_L3_tot~WBPaper00035084:1_L4_IP~WBPaper00035084:1_L4_tot~WBPaper00035084:3_L4_IP~WBPaper00035084:3_L4_tot~WBPaper00035084:10_L4_IP~WBPaper00035084:10_L4_tot	Method: microarray|Species: Caenorhabditis elegans
350	19875417	WBPaper00035424.ce.mr.paper	N.A.	N.A.	2	Single-cell transcriptional analysis of taste sensory neuron pair in Caenorhabditis elegans.	The nervous system is composed of a wide variety of neurons. A description of the transcriptional profiles of each neuron would yield enormous information about the molecular mechanisms that define morphological or functional characteristics. Here we show that RNA isolation from single neurons is feasible by using an optimized mRNA tagging method. This method extracts transcripts in the target cells by co-immunoprecipitation of the complexes of RNA and epitope-tagged poly(A) binding protein expressed specifically in the cells. With this method and genome-wide microarray, we compared the transcriptional profiles of two functionally different neurons in the main C. elegans gustatory neuron class ASE. Eight of the 13 known subtype-specific genes were successfully detected. Additionally, we identified nine novel genes including a receptor guanylyl cyclase, secreted proteins, a TRPC channel and uncharacterized genes conserved among nematodes, suggesting the two neurons are substantially different than previously thought. The expression of these novel genes was controlled by the previously known regulatory network for subtype differentiation. We also describe unique motif organization within individual gene groups classified by the expression patterns in ASE. Our study paves the way to the complete catalog of the expression profiles of individual C. elegans neurons.	6	16997	Takayama J	Takayama J, Faumont S, Kunitomo H, Lockery SR, Iino Y	Single-cell transcriptional analysis of taste sensory neuron pair in Caenorhabditis elegans.	Nucleic Acids Res	2010	WBPaper00035424:ASEL_vs_ASER_rep1~WBPaper00035424:ASER_vs_ASEL_rep1~WBPaper00035424:ASER_vs_ASEL_rep2~WBPaper00035424:ASER_vs_ASEL_rep3~WBPaper00035424:ASEL_vs_ASER_rep2~WBPaper00035424:ASEL_vs_ASER_rep3	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
351	19936206	WBPaper00035504.ce.mr.paper	GSE18601	GPL9458	1	Divergent mechanisms controlling hypoxic sensitivity and lifespan by the DAF-2/insulin/IGF-receptor pathway.	Organisms and their cells vary greatly in their tolerance of low oxygen environments (hypoxia). A delineation of the determinants of hypoxia tolerance is incomplete, despite intense interest for its implications in diseases such as stroke and myocardial infarction. The insulin/IGF-1 receptor (IGFR) signaling pathway controls survival of Caenorhabditis elegans from a variety of stressors including aging, hyperthermia, and hypoxia. daf-2 encodes a C. elegans IGFR homolog whose primary signaling pathway modulates the activity of the FOXO transcription factor DAF-16. DAF-16 regulates the transcription of a large number of genes, some of which have been shown to control aging. To identify genes that selectively regulate hypoxic sensitivity, we compared the whole-organismal transcriptomes of three daf-2 reduction-of-function alleles, all of which are hypoxia resistant, thermotolerant, and long lived, but differ in their rank of severities for these phenotypes. The transcript levels of 172 genes were increased in the most hypoxia resistant daf-2 allele, e1370, relative to the other alleles whereas transcripts from only 10 genes were decreased in abundance. RNAi knockdown of 6 of the 10 genes produced a significant increase in organismal survival after hypoxic exposure as would be expected if down regulation of these genes by the e1370 mutation was responsible for hypoxia resistance. However, RNAi knockdown of these genes did not prolong lifespan. These genes definitively separate the mechanisms of hypoxic sensitivity and lifespan and identify biological strategies to survive hypoxic injury.	18	16997	Mabon ME	Mabon ME, Scott BA, Crowder CM	Divergent mechanisms controlling hypoxic sensitivity and lifespan by the DAF-2/insulin/IGF-receptor pathway.	PLoS One	2009	WBPaper00035504:m596_1~WBPaper00035504:m596_2~WBPaper00035504:m596_3~WBPaper00035504:e1368_1~WBPaper00035504:e1368_2~WBPaper00035504:e1368_3~WBPaper00035504:m596_4~WBPaper00035504:m596_5~WBPaper00035504:m596_6~WBPaper00035504:e1370_1~WBPaper00035504:e1370_2~WBPaper00035504:e1370_3~WBPaper00035504:e1370_4~WBPaper00035504:e1370_5~WBPaper00035504:e1370_6~WBPaper00035504:e1368_4~WBPaper00035504:e1368_5~WBPaper00035504:e1368_6	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging
352	20045492	WBPaper00035560.ce.mr.paper	GSE16036	GPL5883	1	Fatty acid composition and gene expression profiles are altered in aryl hydrocarbon receptor-1 mutant Caenorhabditis elegans.	The aryl hydrocarbon receptor (AHR) is a eukaryotic transcription factor that plays an essential role in neuronal, immune, vascular, hepatic and hematopoietic development. In mammals, AHR induces metabolism-associated genes in response to xenobiotics. AHR is evolutionarily conserved, and the C. elegans AHR ortholog likely shares many physiologic functions with the mammalian version. While the role of AHR in development is known, the molecular basis of AHR action is less well understood. To understand the physiologic role of AHR in C. elegans, a combination of fatty acid profiling, transcriptomics, and phenotyping approaches was used. Fatty acid profiles from L4 larval stage whole animals indicated that C17isoA, C18:1n9t, C20:3n6 and C20:4n6 were significantly increased in an ahr-1 mutant compared to wild-type. Consistent with these changes, we observed a significant 5.8 fold increase in fat-7, and 1.7-1.9 fold increases in elo-5, nhr-49, and mdt-15 gene expression during the L4 stage. The ahr-1(ju145) mutant displayed deficits in growth and development including a reduced number of eggs laid, a higher proportion of dead embryos, delay in time to reach L4 stage, and movement deficits including a fewer number of body bends and a longer defecation cycle. To understand global effects of AHR-1 on transcription, microarray analysis was performed on L1 stage animals. Expression changes (324 under- and 238 over-expressed) were found in genes associated with metabolism, growth, and development. These results indicate a role for C. elegans AHR in regulating fatty acid composition and in contributing to some aspects of development. Since the transcriptional control of AHR targets may be evolutionarily conserved, these results provide a deeper understanding of the molecular actions of AHR in a model invertebrate system that may be informative for higher organisms.	7	1115	Aarnio V	Aarnio V, Storvik M, Lehtonen M, Asikainen S, Reisner K, Callaway J, Rudgalvyte M, Lakso M, Wong G	Fatty acid composition and gene expression profiles are altered in aryl hydrocarbon receptor-1 mutant Caenorhabditis elegans.	Comp Biochem Physiol C Toxicol Pharmacol	2010	WBPaper00035560:ahr-1_L1_sample56~WBPaper00035560:ahr-1_L1_sample60~WBPaper00035560:ahr-1_L1_sample62~WBPaper00035560:ahr-1_L1_sample54~WBPaper00035560:N2_L1_sample59~WBPaper00035560:N2_L1_sample61~WBPaper00035560:N2_L1_sample63	Method: microarray|Species: Caenorhabditis elegans
353	20488933	WBPaper00036286.ce.mr.paper	GSE17071	GPL4038	2	Genome-wide gene expression regulation as a function of genotype and age in C. elegans.	Gene expression becomes more variable with age, and it is widely assumed that this is due to a decrease in expression regulation. But currently there is no understanding how gene expression regulatory patterns progress with age. Here we explored genome-wide gene expression variation and regulatory loci (eQTL) in a population of developing and aging C. elegans recombinant inbred worms. We found almost 900 genes with an eQTL, of which almost half were found to have a genotype-by-age effect ((gxa)eQTL). The total number of eQTL decreased with age, whereas the variation in expression increased. In developing worms, the number of genes with increased expression variation (1282) was similar to the ones with decreased expression variation (1328). In aging worms, the number of genes with increased variation (1772) was nearly five times higher than the number of genes with a decreased expression variation (373). The number of cis-acting eQTL in juveniles decreased by almost 50% in old worms, whereas the number of trans-acting loci decreased by approximately 27%, indicating that cis-regulation becomes relatively less frequent than trans-regulation in aging worms. Of the 373 genes with decreased expression level variation in aging worms, approximately 39% had an eQTL compared with approximately 14% in developing worms. (gxa)eQTL were found for approximately 21% of these genes in aging worms compared with only approximately 6% in developing worms. We highlight three examples of linkages: in young worms (pgp-6), in old worms (daf-16), and throughout life (lips-16). Our findings demonstrate that eQTL patterns are strongly affected by age, and suggest that gene network integrity declines with age.	54	16997	Vinuela A	Vinuela A, Snoek LB, Riksen JA, Kammenga JE	Genome-wide gene expression regulation as a function of genotype and age in C. elegans.	Genome Res	2010	WBPaper00036286:WN8_vs_WN41_T1~WBPaper00036286:WN60_vs_WN77_T1~WBPaper00036286:WN9_vs_WN62_T1~WBPaper00036286:WN71_vs_WN79_T1~WBPaper00036286:WN27_vs_WN56_T1~WBPaper00036286:WN46_vs_WN69_T1~WBPaper00036286:WN68_vs_WN37_T1~WBPaper00036286:WN13_vs_WN21_T1~WBPaper00036286:WN20_vs_WN53_T1~WBPaper00036286:WN57_vs_WN32_T1~WBPaper00036286:WN19_vs_WN39_T1~WBPaper00036286:WN76_vs_WN59_T1~WBPaper00036286:WN28_vs_WN50_T1~WBPaper00036286:WN44_vs_WN2_T1~WBPaper00036286:WN24_vs_WN16_T1~WBPaper00036286:WN11_vs_WN25_T1~WBPaper00036286:WN19_vs_WN1_T1~WBPaper00036286:WN33_vs_WN3_T1~WBPaper00036286:WN8_vs_WN41_T2~WBPaper00036286:WN60_vs_WN77_T2~WBPaper00036286:WN9_vs_WN62_T2~WBPaper00036286:WN71_vs_WN79_T2~WBPaper00036286:WN27_vs_WN56_T2~WBPaper00036286:WN46_vs_WN69_T2~WBPaper00036286:WN68_vs_WN37_T2~WBPaper00036286:WN13_vs_WN21_T2~WBPaper00036286:WN20_vs_WN53_T2~WBPaper00036286:WN57_vs_WN32_T2~WBPaper00036286:WN19_vs_WN39_T2~WBPaper00036286:WN76_vs_WN59_T2~WBPaper00036286:WN28_vs_WN50_T2~WBPaper00036286:WN44_vs_WN2_T2~WBPaper00036286:WN24_vs_WN16_T2~WBPaper00036286:WN11_vs_WN25_T2~WBPaper00036286:WN19_vs_WN1_T2~WBPaper00036286:WN33_vs_WN3_T2~WBPaper00036286:WN8_vs_WN41_T3~WBPaper00036286:WN60_vs_WN77_T3~WBPaper00036286:WN9_vs_WN62_T3~WBPaper00036286:WN71_vs_WN79_T3~WBPaper00036286:WN27_vs_WN56_T3~WBPaper00036286:WN46_vs_WN69_T3~WBPaper00036286:WN68_vs_WN37_T3~WBPaper00036286:WN13_vs_WN21_T3~WBPaper00036286:WN20_vs_WN53_T3~WBPaper00036286:WN57_vs_WN32_T3~WBPaper00036286:WN19_vs_WN39_T3~WBPaper00036286:WN76_vs_WN59_T3~WBPaper00036286:WN28_vs_WN50_T3~WBPaper00036286:WN44_vs_WN2_T3~WBPaper00036286:WN24_vs_WN16_T3~WBPaper00036286:WN11_vs_WN25_T3~WBPaper00036286:WN19_vs_WN1_T3~WBPaper00036286:WN33_vs_WN3_T3	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging
354	20808445	WBPaper00037113.ce.mr.paper	GSE16686,GSE16688,GSE16698,GSE16719	GPL4038	2	Genome-wide gene expression analysis in response to organophosphorus pesticide chlorpyrifos and diazinon in C. elegans.	Organophosphorus pesticides (OPs) were originally designed to affect the nervous system by inhibiting the enzyme acetylcholinesterase, an important regulator of the neurotransmitter acetylcholine. Over the past years evidence is mounting that these compounds affect many other processes. Little is known, however, about gene expression responses against OPs in the nematode Caenorhabditis elegans. This is surprising because C. elegans is extensively used as a model species in toxicity studies. To address this question we performed a microarray study in C. elegans which was exposed for 72 hrs to two widely used Ops, chlorpyrifos and diazinon, and a low dose mixture of these two compounds. Our analysis revealed transcriptional responses related to detoxification, stress, innate immunity, and transport and metabolism of lipids in all treatments. We found that for both compounds as well as in the mixture, these processes were regulated by different gene transcripts. Our results illustrate intense, and unexpected crosstalk between gene pathways in response to chlorpyrifos and diazinon in C. elegans.	18	16997	Vinuela A	Vinuela A, Snoek LB, Riksen JA, Kammenga JE	Genome-wide gene expression analysis in response to organophosphorus pesticide chlorpyrifos and diazinon in C. elegans.	PLoS One	2010	WBPaper00037113:Control_vs_DZN-(1)_Rep1~WBPaper00037113:Control_vs_DZN-(1)_Rep2~WBPaper00037113:Control_vs_DZN-(1)_Rep3~WBPaper00037113:DZN-(1)_vs_Control_Rep1~WBPaper00037113:DZN-(1)_vs_Control_Rep2~WBPaper00037113:DZN-(1)_vs_Control_Rep3~WBPaper00037113:Control_vs_CPF-(0.5)_Rep1~WBPaper00037113:Control_vs_CPF-(0.5)_Rep2~WBPaper00037113:Control_vs_CPF-(0.5)_Rep3~WBPaper00037113:CPF-(0.5)_vs_Control_Rep1~WBPaper00037113:CPF-(0.5)_vs_Control_Rep2~WBPaper00037113:CPF-(0.5)_vs_Control_Rep3~WBPaper00037113:Control_vs_CPF-(0.5)_DZN-(1)_Rep1~WBPaper00037113:Control_vs_CPF-(0.5)_DZN-(1)_Rep2~WBPaper00037113:Control_vs_CPF-(0.5)_DZN-(1)_Rep3~WBPaper00037113:CPF-(0.5)_DZN-(1)_vs_Control_Rep1~WBPaper00037113:CPF-(0.5)_DZN-(1)_vs_Control_Rep2~WBPaper00037113:CPF-(0.5)_DZN-(1)_vs_Control_Rep3	Method: microarray|Species: Caenorhabditis elegans
355	20816092	WBPaper00037147.ce.mr.paper	GSE22383	GPL9458	2	Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans.	The insulin-like signaling (ILS) pathway regulates metabolism and is known to modulate adult life span in C. elegans. Altered stress responses and resistance to a wide range of stressors are also associated with changes in ILS and contribute to enhanced longevity. The transcription factors DAF-16 and HSF-1 are key effectors of the longevity phenotype. We demonstrate that increased intrinsic thermotolerance, due to lower ILS, is not dependent on stress-induced transcriptional responses but instead requires active protein translation. Translation profiling experiments reveal genes that are posttranscriptionally regulated in response to altered ILS during heat shock in a DAF-16-dependent manner. Furthermore, several novel proteins are specifically required for ILS effects on thermotolerance. We propose that lowered ILS results in metabolic and physiological changes. These DAF-16-induced changes precondition a translational response under acute stress to modulate survival.	72	16983	McColl G	McColl G, Rogers AN, Alavez S, Hubbard AE, Melov S, Link CD, Bush AI, Kapahi P, Lithgow GJ	Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans.	Cell Metab	2010	WBPaper00037147:N2_control_Fraction1_group1~WBPaper00037147:N2_control_Fraction2_group1~WBPaper00037147:N2_control_Fraction3_group1~WBPaper00037147:N2_HeatShocked_Fraction1_group1~WBPaper00037147:N2_HeatShocked_Fraction2_group1~WBPaper00037147:N2_HeatShocked_Fraction3_group1~WBPaper00037147:N2_control_Fraction1_group2~WBPaper00037147:N2_control_Fraction2_group2~WBPaper00037147:N2_control_Fraction3_group2~WBPaper00037147:N2_HeatShocked_Fraction1_group2~WBPaper00037147:N2_HeatShocked_Fraction2_group2~WBPaper00037147:N2_HeatShocked_Fraction3_group2~WBPaper00037147:N2_control_Fraction1_group3~WBPaper00037147:N2_control_Fraction2_group3~WBPaper00037147:N2_control_Fraction3_group3~WBPaper00037147:N2_HeatShocked_Fraction1_group3~WBPaper00037147:N2_HeatShocked_Fraction2_group3~WBPaper00037147:N2_HeatShocked_Fraction3_group3~WBPaper00037147:N2_control_Fraction1_group4~WBPaper00037147:N2_control_Fraction2_group4~WBPaper00037147:N2_control_Fraction3_group4~WBPaper00037147:N2_HeatShocked_Fraction1_group4~WBPaper00037147:N2_HeatShocked_Fraction2_group4~WBPaper00037147:N2_HeatShocked_Fraction3_group4~WBPaper00037147:daf-2(e1370)_control_Fraction1_group1~WBPaper00037147:daf-2(e1370)_control_Fraction2_group1~WBPaper00037147:daf-2(e1370)_control_Fraction3_group1~WBPaper00037147:daf-2(e1370)_HeatShocked_Fraction1_group1~WBPaper00037147:daf-2(e1370)_HeatShocked_Fraction2_group1~WBPaper00037147:daf-2(e1370)_HeatShocked_Fraction3_group1~WBPaper00037147:daf-2(e1370)_control_Fraction1_group2~WBPaper00037147:daf-2(e1370)_control_Fraction2_group2~WBPaper00037147:daf-2(e1370)_control_Fraction3_group2~WBPaper00037147:daf-2(e1370)_HeatShocked_Fraction1_group2~WBPaper00037147:daf-2(e1370)_HeatShocked_Fraction2_group2~WBPaper00037147:daf-2(e1370)_HeatShocked_Fraction3_group2~WBPaper00037147:daf-2(e1370)_control_Fraction1_group3~WBPaper00037147:daf-2(e1370)_control_Fraction2_group3~WBPaper00037147:daf-2(e1370)_control_Fraction3_group3~WBPaper00037147:daf-2(e1370)_HeatShocked_Fraction1_group3~WBPaper00037147:daf-2(e1370)_HeatShocked_Fraction2_group3~WBPaper00037147:daf-2(e1370)_HeatShocked_Fraction3_group3~WBPaper00037147:daf-2(e1370)_control_Fraction1_group4~WBPaper00037147:daf-2(e1370)_control_Fraction2_group4~WBPaper00037147:daf-2(e1370)_control_Fraction3_group4~WBPaper00037147:daf-2(e1370)_HeatShocked_Fraction1_group4~WBPaper00037147:daf-2(e1370)_HeatShocked_Fraction2_group4~WBPaper00037147:daf-2(e1370)_HeatShocked_Fraction3_group4~WBPaper00037147:daf16(M26);daf-2(e1370)_control_Fraction1_group1~WBPaper00037147:daf16(M26);daf-2(e1370)_control_Fraction2_group1~WBPaper00037147:daf16(M26);daf-2(e1370)_control_Fraction3_group1~WBPaper00037147:daf16(M26);daf-2(e1370)_HeatShocked_Fraction1_group1~WBPaper00037147:daf16(M26);daf-2(e1370)_HeatShocked_Fraction2_group1~WBPaper00037147:daf16(M26);daf-2(e1370)_HeatShocked_Fraction3_group1~WBPaper00037147:daf16(M26);daf-2(e1370)_control_Fraction1_group2~WBPaper00037147:daf16(M26);daf-2(e1370)_control_Fraction2_group2~WBPaper00037147:daf16(M26);daf-2(e1370)_control_Fraction3_group2~WBPaper00037147:daf16(M26);daf-2(e1370)_HeatShocked_Fraction1_group2~WBPaper00037147:daf16(M26);daf-2(e1370)_HeatShocked_Fraction2_group2~WBPaper00037147:daf16(M26);daf-2(e1370)_HeatShocked_Fraction3_group2~WBPaper00037147:daf16(M26);daf-2(e1370)_control_Fraction1_group3~WBPaper00037147:daf16(M26);daf-2(e1370)_control_Fraction2_group3~WBPaper00037147:daf16(M26);daf-2(e1370)_control_Fraction3_group3~WBPaper00037147:daf16(M26);daf-2(e1370)_HeatShocked_Fraction1_group3~WBPaper00037147:daf16(M26);daf-2(e1370)_HeatShocked_Fraction2_group3~WBPaper00037147:daf16(M26);daf-2(e1370)_HeatShocked_Fraction3_group3~WBPaper00037147:daf16(M26);daf-2(e1370)_control_Fraction1_group4~WBPaper00037147:daf16(M26);daf-2(e1370)_control_Fraction2_group4~WBPaper00037147:daf16(M26);daf-2(e1370)_control_Fraction3_group4~WBPaper00037147:daf16(M26);daf-2(e1370)_HeatShocked_Fraction1_group4~WBPaper00037147:daf16(M26);daf-2(e1370)_HeatShocked_Fraction2_group4~WBPaper00037147:daf16(M26);daf-2(e1370)_HeatShocked_Fraction3_group4	Method: microarray|Species: Caenorhabditis elegans
356	21115607	WBPaper00037849.ce.mr.paper	GSE25285	GPL5859	2	Regulation of C. elegans presynaptic differentiation and neurite branching via a novel signaling pathway initiated by SAM-10.	Little is known about transcriptional control of neurite branching or presynaptic differentiation, events that occur relatively late in neuronal development. Using the Caenorhabditis elegans mechanosensory circuit as an in vivo model, we show that SAM-10, an ortholog of mammalian single-stranded DNA-binding protein (SSDP), functions cell-autonomously in the nucleus to regulate synaptic differentiation, as well as positioning of, a single neurite branch. PLM mechanosensory neurons in sam-10 mutants exhibit abnormal placement of the neurite branch point, and defective synaptogenesis, characterized by an overextended synaptic varicosity, underdeveloped synaptic morphology and disrupted colocalization of active zone and synaptic vesicles. SAM-10 functions coordinately with Lim domain-binding protein 1 (LDB-1), demonstrated by our observations that: (1) mutations in either gene show similar defects in PLM neurons; and (2) LDB-1 is required for SAM-10 nuclear localization. SAM-10 regulates PLM synaptic differentiation by suppressing transcription of prk-2, which encodes an ortholog of the mammalian Pim kinase family. PRK-2-mediated activities of SAM-10 are specifically involved in PLM synaptic differentiation, but not other sam-10 phenotypes such as neurite branching. Thus, these data reveal a novel transcriptional signaling pathway that regulates neuronal specification of neurite branching and presynaptic differentiation.	8	9346	Zheng Q	Zheng Q, Schaefer AM, Nonet ML	Regulation of C. elegans presynaptic differentiation and neurite branching via a novel signaling pathway initiated by SAM-10.	Development	2011	WBPaper00037849:Cy3N2_vs_Cy5sam-10_rep1~WBPaper00037849:Cy3sam-10_vs_Cy5N2_rep1~WBPaper00037849:Cy3N2_vs_Cy5sam-10_rep2~WBPaper00037849:Cy3sam-10_vs_Cy5N2_rep2~WBPaper00037849:Cy3N2_vs_Cy5sam-10_rep3~WBPaper00037849:Cy3sam-10_vs_Cy5N2_rep3~WBPaper00037849:Cy3N2_vs_Cy5sam-10_rep4~WBPaper00037849:Cy3sam-10_vs_Cy5N2_rep4	Method: microarray|Species: Caenorhabditis elegans
357	21343362	WBPaper00038168.ce.mr.paper	GSE26825,GSE26824,GSE26823	GPL5859	2	synMuv B proteins antagonize germline fate in the intestine and ensure C. elegans survival.	Previous studies demonstrated that a subset of synMuv B mutants ectopically misexpress germline-specific P-granule proteins in their somatic cells, suggesting a failure to properly orchestrate a soma/germline fate decision. Surprisingly, this fate confusion does not affect viability at low to ambient temperatures. Here, we show that, when grown at high temperature, a majority of synMuv B mutants irreversibly arrest at the L1 stage. High temperature arrest (HTA) is accompanied by upregulation of many genes characteristic of germ line, including genes encoding components of the synaptonemal complex and other meiosis proteins. HTA is suppressed by loss of global regulators of germline chromatin, including MES-4, MRG-1, ISW-1 and the MES-2/3/6 complex, revealing that arrest is caused by somatic cells possessing a germline-like chromatin state. Germline genes are preferentially misregulated in the intestine, and necessity and sufficiency tests demonstrate that the intestine is the tissue responsible for HTA. We propose that synMuv B mutants fail to erase or antagonize an inherited germline chromatin state in somatic cells during embryonic and early larval development. As a consequence, somatic cells gain a germline program of gene expression in addition to their somatic program, leading to a mixed fate. Somatic expression of germline genes is enhanced at elevated temperature, leading to developmentally compromised somatic cells and arrest of newly hatched larvae.	12	15935	Petrella LN	Petrella LN, Wang W, Spike CA, Rechtsteiner A, Reinke V, Strome S	synMuv B proteins antagonize germline fate in the intestine and ensure C. elegans survival.	Development	2011	WBPaper00038168:lin-15B_rep1~WBPaper00038168:lin-15B_rep2~WBPaper00038168:lin-15B_rep3~WBPaper00038168:lin-15B_rep4~WBPaper00038168:lin-35_rep1~WBPaper00038168:lin-35_rep2~WBPaper00038168:lin-35_rep3~WBPaper00038168:lin-35_rep4~WBPaper00038168:lin-35_mes-4(RNAi)_rep1~WBPaper00038168:lin-35_mes-4(RNAi)_rep2~WBPaper00038168:lin-35_mes-4(RNAi)_rep3~WBPaper00038168:lin-35_mes-4(RNAi)_rep4	Method: microarray|Species: Caenorhabditis elegans
358	21723504	WBPaper00039835.ce.mr.paper	GSE28665	GPL9458	2	Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans.	Reducing protein synthesis slows growth and development but can increase adult life span. We demonstrate that knockdown of eukaryotic translation initiation factor 4G (eIF4G), which is downregulated during starvation and dauer state, results in differential translation of genes important for growth and longevity in C.elegans. Genome-wide mRNA translation state analysis showed that inhibition of IFG-1, the C.elegans ortholog of eIF4G, results in a relative increase in ribosomal loading and translation of stress response genes. Some of these genes are required for life span extension when IFG-1 is inhibited. Furthermore, enhanced ribosomal loading of certain mRNAs upon IFG-1 inhibition was correlated with increased mRNA length. This association was supported by changes in the proteome assayed via quantitative mass spectrometry. Our results suggest that IFG-1 mediates the antagonistic effects on growth and somatic maintenance by regulating mRNA translation of particular mRNAs based, in part, on transcript length.	24	16983	Rogers AN	Rogers AN, Chen D, McColl G, Czerwieniec G, Felkey K, Gibson BW, Hubbard A, Melov S, Lithgow GJ, Kapahi P	Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans.	Cell Metab	2011	WBPaper00039835:N2_control_Fraction1_group1~WBPaper00039835:N2_control_Fraction2_group1~WBPaper00039835:N2_control_Fraction3_group1~WBPaper00039835:N2_control_Fraction1_group2~WBPaper00039835:N2_control_Fraction2_group2~WBPaper00039835:N2_control_Fraction3_group2~WBPaper00039835:N2_control_Fraction1_group3~WBPaper00039835:N2_control_Fraction2_group3~WBPaper00039835:N2_control_Fraction3_group3~WBPaper00039835:N2_control_Fraction1_group4~WBPaper00039835:N2_control_Fraction2_group4~WBPaper00039835:N2_control_Fraction3_group4~WBPaper00039835:N2_ifg-1_Fraction1_group1~WBPaper00039835:N2_ifg-1_Fraction2_group1~WBPaper00039835:N2_ifg-1_Fraction3_group1~WBPaper00039835:N2_ifg-1_Fraction1_group2~WBPaper00039835:N2_ifg-1_Fraction2_group2~WBPaper00039835:N2_ifg-1_Fraction3_group2~WBPaper00039835:N2_ifg-1_Fraction1_group3~WBPaper00039835:N2_ifg-1_Fraction2_group3~WBPaper00039835:N2_ifg-1_Fraction3_group3~WBPaper00039835:N2_ifg-1_Fraction1_group4~WBPaper00039835:N2_ifg-1_Fraction2_group4~WBPaper00039835:N2_ifg-1_Fraction3_group4	Method: microarray|Species: Caenorhabditis elegans|Topic: determination of adult lifespan|Topic: obsolete aging
359	21931806	WBPaper00040210.ce.mr.paper	GSE24229,GSE24230,GSE24254,GSE24257	GPL4038	2	Gene expression modifications by temperature-toxicants interactions in Caenorhabditis elegans.	Although organophosphorus pesticides (OP) share a common mode of action, there is increased awareness that they elicit a diverse range of gene expression responses. As yet however, there is no clear understanding of these responses and how they interact with ambient environmental conditions. In the present study, we investigated genome-wide gene expression profiles in the nematode Caenorhabditis elegans exposed to two OP, chlorpyrifos and diazinon, in single and combined treatments at different temperatures. Our results show that chlorpyrifos and diazinon induced expression of different genes and that temperature affected the response of detoxification genes to the pesticides. The analysis of transcriptional responses to a combination of chlorpyrifos and diazinon shows interactions between toxicants that affect gene expression. Furthermore, our combined analysis of the transcriptional responses to OP at different temperatures suggests that the combination of OP and high temperatures affect detoxification genes and modified the toxic levels of the pesticides.	18	16997	Vinuela A	Vinuela A, Snoek LB, Riksen JA, Kammenga JE	Gene expression modifications by temperature-toxicants interactions in Caenorhabditis elegans.	PLoS One	2011	WBPaper00040210:Control_vs_CPF-(0.5)_Rep1~WBPaper00040210:Control_vs_CPF-(0.5)_Rep2~WBPaper00040210:Control_vs_CPF-(0.5)_Rep3~WBPaper00040210:CPF-(0.5)_vs_Control_Rep1~WBPaper00040210:CPF-(0.5)_vs_Control_Rep2~WBPaper00040210:CPF-(0.5)_vs_Control_Rep3~WBPaper00040210:Control_vs_DZN-(0.5)_Rep1~WBPaper00040210:Control_vs_DZN-(0.5)_Rep2~WBPaper00040210:Control_vs_DZN-(0.5)_Rep3~WBPaper00040210:DZN-(0.5)_vs_Control_Rep1~WBPaper00040210:DZN-(0.5)_vs_Control_Rep2~WBPaper00040210:DZN-(0.5)_vs_Control_Rep3~WBPaper00040210:Control_vs_CPF-(0.5)_DZN-(1)_Rep1~WBPaper00040210:Control_vs_CPF-(0.5)_DZN-(1)_Rep2~WBPaper00040210:Control_vs_CPF-(0.5)_DZN-(1)_Rep3~WBPaper00040210:CPF-(0.5)_DZN-(1)_vs_Control_Rep1~WBPaper00040210:CPF-(0.5)_DZN-(1)_vs_Control_Rep2~WBPaper00040210:CPF-(0.5)_DZN-(1)_vs_Control_Rep3	Method: microarray|Species: Caenorhabditis elegans
360	22670229	WBPaper00040858.ce.mr.paper	GSE22887	GPL4038	2	Aging Uncouples Heritability and Expression-QTL in Caenorhabditis elegans	The number and distribution of gene expression QTL (eQTL) represent the genetic architecture of many complex traits, including common human diseases. We previously reported that the heritable eQTL patterns are highly dynamic with age in an N2 x CB4856 recombinant inbred population of the nematode Caenorhabditis elegans. In particular, we showed that the number of eQTL decreased with age. Here, we investigated the reason for this decrease by combining gene expression profiles at three ages in the wild types N2 and CB4856 with the reported expression profiles of the RIL population. We determined heritability and transgression (when gene expression levels in the RILs are more extreme than the parents) and investigated their relation with eQTL changes with age. Transgressive segregation was widespread but depended on physiological age. The percentage of genes with an eQTL increased with a higher heritability in young worms. However, for old worms this percentage hardly increased. Using a single marker approach, we found that almost 20% of genes with heritability >0.9 had an eQTL in developing worms. Surprisingly, only 10% was found in old worms. Using a multimarker approach, this percentage increased to almost 30% for both age groups. Comparison of the single marker to a multiple marker eQTL mapping indicated that heritable regulation of gene expression becomes more polygenic in aging worms due to multiple loci and possible epistatic interactions. We conclude that linkage studies should account for the relation between increased polygenic regulation and diminished effects at older ages.	14	16997	Vinuela A	Vinuela A, Snoek LB, Riksen JA, Kammenga JE	Aging Uncouples Heritability and Expression-QTL in Caenorhabditis elegans	G3 (Bethesda)	2012	WBPaper00040858:N2_vs_CB4856_T1_rep1~WBPaper00040858:CB4856_vs_N2_T1_rep1~WBPaper00040858:N2_vs_CB4856_T1_rep2~WBPaper00040858:CB4856_vs_N2_T1_rep2~WBPaper00040858:N2_vs_CB4856_T1_rep3~WBPaper00040858:N2_vs_CB4856_T2_rep1~WBPaper00040858:CB4856_vs_N2_T2_rep1~WBPaper00040858:N2_vs_CB4856_T2_rep2~WBPaper00040858:N2_vs_CB4856_T2_rep3~WBPaper00040858:N2_vs_CB4856_T3_rep1~WBPaper00040858:N2_vs_CB4856_T3_rep2~WBPaper00040858:CB4856_vs_N2_T3_rep1~WBPaper00040858:N2_vs_CB4856_T3_rep3~WBPaper00040858:CB4856_vs_N2_T3_rep2	Method: microarray|Species: Caenorhabditis elegans
361	22503424	WBPaper00040985.ce.mr.paper	GSE36419	GPL5883	2	Systematic analysis of tissue-restricted miRISCs reveals a broad role for microRNAs in suppressing basal activity of the C. elegans pathogen response.	Gene regulation by microRNAs (miRNAs) under specific physiological conditions often involves complex interactions between multiple miRNAs and a large number of their targets, as well as coordination with other regulatory mechanisms, limiting the effectiveness of classical genetic methods to identify miRNA functions. We took a systematic approach to analyze the miRNA-induced silencing complex (miRISC) in individual tissues of C. elegans and found that mRNAs encoded by pathogen-responsive genes were dramatically overrepresented in the intestinal miRISC, and that multiple miRNAs accumulated in the intestinal miRISCs upon infection. Inactivation of the miRISC or ablation of miRNAs from multiple families resulted in overexpression of several pathogen-responsive genes under basal conditions and, surprisingly, enhanced worm survival on pathogenic Pseudomonas aeruginosa. These results indicate that much of the miRNA activity in the gut is dedicated to attenuating the activity of the pathogen-response system, uncovering a complex physiological function of the miRNA network.	15	16997	Kudlow BA	Kudlow BA, Zhang L, Han M	Systematic analysis of tissue-restricted miRISCs reveals a broad role for microRNAs in suppressing basal activity of the C. elegans pathogen response.	Mol Cell	2012	WBPaper00040985:Asynch-Intestine_IP_vs_Total-Rep1~WBPaper00040985:Asynch-Intestine_IP_vs_Total-Rep2~WBPaper00040985:Asynch-Intestine_IP_vs_Total-Rep3~WBPaper00040985:Asynch-Intestine_IP_vs_Total-Rep4~WBPaper00040985:Asynch-Muscle_IP_vs_Total-Rep1~WBPaper00040985:Asynch-Muscle_IP_vs_Total-Rep2~WBPaper00040985:Asynch-Muscle_IP_vs_Total-Rep3~WBPaper00040985:Asynch-Muscle_IP_vs_Total-Rep4~WBPaper00040985:L4-Intestine_IP_vs_Total-Rep1~WBPaper00040985:L4-Intestine_IP_vs_Total-Rep2~WBPaper00040985:L4-Intestine_IP_vs_Total-Rep3~WBPaper00040985:L4-Intestine_IP_vs_Total-Rep4~WBPaper00040985:L4-Intestine_IP_vs_Total-Rep5~WBPaper00040985:GFP_IP_vs_Total-Rep1~WBPaper00040985:GFP_IP_vs_Total-Rep2	Method: microarray|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Tissue Specific
362	22514739	WBPaper00040990.ce.mr.paper	GSE39536	GPL9458	2	Dissociation of immune responses from pathogen colonization supports pattern recognition in C. elegans.	Caenorhabditis elegans has been used for over a decade to characterize signaling cascades controlling innate immune responses. However, what initiates these responses in the worm has remained elusive. To gain a better understanding of the initiating events we delineated genome-wide immune responses to the bacterial pathogen Pseudomonas aeruginosa in worms heavily-colonized by the pathogen versus worms visibly not colonized. We found that infection responses in both groups were identical, suggesting that immune responses were not correlated with colonization and its associated damage. Quantitative RT-PCR measurements further showed that pathogen secreted factors were not able to induce an immune response, but exposure to a non-pathogenic Pseudomonas species was. These findings raise the possibility that the C.elegans immune response is initiated by recognition of microbe-associated molecular patterns. In the absence of orthologs of known pattern recognition receptors, C. elegans may rely on novel mechanisms, thus holding the potential to advance our understanding of evolutionarily conserved strategies for pathogen recognition.	9	7963	Twumasi-Boateng K	Twumasi-Boateng K, Shapira M	Dissociation of immune responses from pathogen colonization supports pattern recognition in C. elegans.	PLoS One	2012	WBPaper00040990:OP50_HandPicked_rep1~WBPaper00040990:OP50_WormSorter_rep2~WBPaper00040990:OP50_WormSorter_rep3~WBPaper00040990:PA14_non-colonized_HandPicked_rep1~WBPaper00040990:PA14_non-colonized_WormSorter_rep2~WBPaper00040990:PA14_non-colonized_WormSorter_rep3~WBPaper00040990:PA14_colonized_HandPicked_rep1~WBPaper00040990:PA14_colonized_WormSorter_rep2~WBPaper00040990:PA14_colonized_WormSorter_rep3	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response
363	22511885	WBPaper00040998.ce.mr.paper	GSE34856	GPL9458	2	Coordinate regulation of lipid metabolism by novel nuclear receptor partnerships.	Mammalian nuclear receptors broadly influence metabolic fitness and serve as popular targets for developing drugs to treat cardiovascular disease, obesity, and diabetes. However, the molecular mechanisms and regulatory pathways that govern lipid metabolism remain poorly understood. We previously found that the Caenorhabditis elegans nuclear hormone receptor NHR-49 regulates multiple genes in the fatty acid beta-oxidation and desaturation pathways. Here, we identify additional NHR-49 targets that include sphingolipid processing and lipid remodeling genes. We show that NHR-49 regulates distinct subsets of its target genes by partnering with at least two other distinct nuclear receptors. Gene expression profiles suggest that NHR-49 partners with NHR-66 to regulate sphingolipid and lipid remodeling genes and with NHR-80 to regulate genes involved in fatty acid desaturation. In addition, although we did not detect a direct physical interaction between NHR-49 and NHR-13, we demonstrate that NHR-13 also regulates genes involved in the desaturase pathway. Consistent with this, gene knockouts of these receptors display a host of phenotypes that reflect their gene expression profile. Our data suggest that NHR-80 and NHR-13's modulation of NHR-49 regulated fatty acid desaturase genes contribute to the shortened lifespan phenotype of nhr-49 deletion mutant animals. In addition, we observed that nhr-49 animals had significantly altered mitochondrial morphology and function, and that distinct aspects of this phenotype can be ascribed to defects in NHR-66- and NHR-80-mediated activities. Identification of NHR-49's binding partners facilitates a fine-scale dissection of its myriad regulatory roles in C. elegans. Our findings also provide further insights into the functions of the mammalian lipid-sensing nuclear receptors HNF4 and PPAR.	9	16997	Pathare PP	Pathare PP, Lin A, Bornfeldt KE, Taubert S, van Gilst MR	Coordinate regulation of lipid metabolism by novel nuclear receptor partnerships.	PLoS Genet	2012	WBPaper00040998:nhr-49_vs_WT_rep1~WBPaper00040998:nhr-49_vs_WT_rep2~WBPaper00040998:nhr-66_vs_WT_rep1~WBPaper00040998:nhr-66_vs_WT_rep2~WBPaper00040998:nhr-66_vs_WT_rep3~WBPaper00040998:nhr-80_vs_WT_rep1~WBPaper00040998:nhr-80_vs_WT_rep2~WBPaper00040998:nhr-80_vs_WT_rep3~WBPaper00040998:nhr-80_vs_WT_rep4	Method: microarray|Species: Caenorhabditis elegans
364	22796420	WBPaper00041300.ce.mr.paper	GSE29979	GPL9458	1	Radiation-induced genomic instability in Caenorhabditis elegans.	Radiation-induced genomic instability has been well documented, particularly in vitro. However, the understanding of its mechanisms and their consequences in vivo is still limited. In this study, Caenorhabditis elegans (C. elegans; strain CB665) nematodes were exposed to X-rays at doses of 0.1, 1, 3 or 10Gy. The endpoints were measured several generations after exposure and included mutations in the movement-related gene unc-58, alterations in gene expression analysed with oligoarrays containing the entire C. elegans genome, and micro-satellite mutations measured by capillary electrophoresis. The progeny of the irradiated nematodes showed an increased mutation frequency in the unc-58 gene, with a maximum response observed at 1Gy. Significant differences were also found in gene expression between the irradiated (1Gy) and non-irradiated nematode lines. Differences in gene expression did not show clear clustering into certain gene categories, suggesting that the instability might be a chaotic process rather than a result of changes in the function of few specific genes such as, e.g., those responsible for DNA repair. Increased heterogeneity in gene expression, which has previously been described in irradiated cultured human lymphocytes, was also observed in the present study in C. elegans, the coefficient of variation of gene expression being higher in the progeny of irradiated nematodes than in control nematodes. To the best of our knowledge, this is the first publication reporting radiation-induced genomic instability in C. elegans.	8	16997	Huumonen K	Huumonen K, Immonen HK, Baverstock K, Hiltunen M, Korkalainen M, Lahtinen T, Parviainen J, Viluksela M, Wong G, Naarala J, Juutilainen J	Radiation-induced genomic instability in Caenorhabditis elegans.	Mutat Res	2012	WBPaper00041300:Control_rep1~WBPaper00041300:Control_rep7~WBPaper00041300:Control_rep9~WBPaper00041300:Control_rep10~WBPaper00041300:X_radiation_1_Gy_rep2~WBPaper00041300:X_radiation_1_Gy_rep3~WBPaper00041300:X_radiation_1_Gy_rep5~WBPaper00041300:X_radiation_1_Gy_rep15	Method: microarray|Species: Caenorhabditis elegans
365	23103171	WBPaper00041688.ce.mr.paper	GSE38158,GSE38160	GPL5883	1	Antagonism between MES-4 and Polycomb repressive complex 2 promotes appropriate gene expression in C. elegans germ cells.	The Caenorhabditis elegans MES proteins are key chromatin regulators of the germline. MES-2, MES-3, and MES-6 form the C.elegans Polycomb repressive complex 2 and generate repressive H3K27me3. MES-4 generates H3K36me3 on germline-expressed genes. Transcript profiling of dissected mutant germlines revealed that MES-2/3/6 and MES-4 cooperate to promote the expression of germline genes and repress the X chromosomes and somatic genes. Results from genome-wide chromatin immunoprecipitation showed that H3K27me3 and H3K36me3 occupy mutually exclusive domains on the autosomes and that H3K27me3 is enriched on the X. Loss of MES-4 from germline genes causes H3K27me3 to spread to germline genes, resulting in reduced H3K27me3 elsewhere on the autosomes and especially on the X. Our findings support a model in which H3K36me3 repels H3K27me3 from germline genes and concentrates it on other regions of the genome. This antagonism ensures proper patterns of gene expression for germ cells, which includes repression of somatic genes and the X chromosomes.	12	16829	Gaydos LJ	Gaydos LJ, Rechtsteiner A, Egelhofer TA, Carroll CR, Strome S	Antagonism between MES-4 and Polycomb repressive complex 2 promotes appropriate gene expression in C. elegans germ cells.	Cell Rep	2012	WBPaper00041688:mes-2_vs_wt_rep1~WBPaper00041688:mes-2_vs_wt_rep2~WBPaper00041688:mes-2_vs_wt_rep3~WBPaper00041688:mes-2_vs_wt_rep4~WBPaper00041688:mes-4_vs_wt_rep1~WBPaper00041688:mes-4_vs_wt_rep2~WBPaper00041688:mes-4_vs_wt_rep3~WBPaper00041688:mes-4_vs_wt_rep4~WBPaper00041688:mes-2_mes-4_vs_wt_rep1~WBPaper00041688:mes-2_mes-4_vs_wt_rep2~WBPaper00041688:mes-2_mes-4_vs_wt_rep3~WBPaper00041688:mes-2_mes-4_vs_wt_rep4	Method: microarray|Species: Caenorhabditis elegans|Tissue Specific
366	24651852	WBPaper00045015.ce.mr.paper	GSE48605	GPL5859	2	Defects in the C. elegans acyl-CoA synthase, acs-3, and nuclear hormone receptor, nhr-25, cause sensitivity to distinct, but overlapping stresses.	Metazoan transcription factors control distinct networks of genes in specific tissues, yet understanding how these networks are integrated into physiology, development, and homeostasis remains challenging. Inactivation of the nuclear hormone receptor nhr-25 ameliorates developmental and metabolic phenotypes associated with loss of function of an acyl-CoA synthetase gene, acs-3. ACS-3 activity prevents aberrantly high NHR-25 activity. Here, we investigated this relationship further by examining gene expression patterns following acs-3 and nhr-25 inactivation. Unexpectedly, we found that the acs-3 mutation or nhr-25 RNAi resulted in similar transcriptomes with enrichment in innate immunity and stress response gene expression. Mutants of either gene exhibited distinct sensitivities to pathogens and environmental stresses. Only nhr-25 was required for wild-type levels of resistance to the bacterial pathogen P. aeruginosa and only acs-3 was required for wild-type levels of resistance to osmotic stress and the oxidative stress generator, juglone. Inactivation of either acs-3 or nhr-25 compromised lifespan and resistance to the fungal pathogen D. coniospora. Double mutants exhibited more severe defects in the lifespan and P. aeruginosa assays, but were similar to the single mutants in other assays. Finally, acs-3 mutants displayed defects in their epidermal surface barrier, potentially accounting for the observed sensitivities. Together, these data indicate that inactivation of either acs-3 or nhr-25 causes stress sensitivity and increased expression of innate immunity/stress genes, most likely by different mechanisms. Elevated expression of these immune/stress genes appears to abrogate the transcriptional signatures relevant to metabolism and development.	6	16997	Ward JD	Ward JD, Mullaney B, Schiller BJ, He le D, Petnic SE, Couillault C, Pujol N, Bernal TU, van Gilst MR, Ashrafi K, Ewbank JJ, Yamamoto KR	Defects in the C. elegans acyl-CoA synthase, acs-3, and nuclear hormone receptor, nhr-25, cause sensitivity to distinct, but overlapping stresses.	PLoS One	2014	WBPaper00045015:nhr-25(RNAi)_vs_N2(control-RNAi)_rep1~WBPaper00045015:nhr-25(RNAi)_vs_N2(control-RNAi)_rep2~WBPaper00045015:nhr-25(RNAi)_vs_N2(control-RNAi)_rep3~WBPaper00045015:acs-3(ft5)_vs_N2_rep1~WBPaper00045015:acs-3(ft5)_vs_N2_rep2~WBPaper00045015:acs-3(ft5)_vs_N2_rep3	Method: microarray|Species: Caenorhabditis elegans
367	26016853	WBPaper00046858.ce.mr.paper	GSE63846	GPL9458	2	The Developmental Intestinal Regulator ELT-2 Controls p38-Dependent Immune Responses in Adult C. elegans.	GATA transcription factors play critical roles in cellular differentiation and development. However, their roles in mature tissues are less understood. In C. elegans larvae, the transcription factor ELT-2 regulates terminal differentiation of the intestine. It is also expressed in the adult intestine, where it was suggested to maintain intestinal structure and function, and where it was additionally shown to contribute to infection resistance. To study the function of elt-2 in adults we characterized elt-2-dependent gene expression following its knock-down specifically in adults. Microarray analysis identified two ELT-2-regulated gene subsets: one, enriched for hydrolytic enzymes, pointed at regulation of constitutive digestive functions as a dominant role of adult elt-2; the second was enriched for immune genes that are induced in response to Pseudomonas aeruginosa infection. Focusing on the latter, we used genetic analyses coupled to survival assays and quantitative RT-PCR to interrogate the mechanism(s) through which elt-2 contributes to immunity. We show that elt-2 controls p38-dependent gene induction, cooperating with two p38-activated transcription factors, ATF-7 and SKN-1. This demonstrates a mechanism through which the constitutively nuclear elt-2 can impact induced responses, and play a dominant role in C. elegans immunity.	14	7469	Block DH	Block DH, Twumasi-Boateng K, Kang HS, Carlisle JA, Hanganu A, Lai TY, Shapira M	The Developmental Intestinal Regulator ELT-2 Controls p38-Dependent Immune Responses in Adult C. elegans.	PLoS Genet	2015	WBPaper00046858:control-RNAi_OP50_hand-picked_rep1~WBPaper00046858:control-RNAi_OP50_worm-sorter_rep2~WBPaper00046858:control-RNAi_OP50_worm-sorter_rep3~WBPaper00046858:control-RNAi_PA14-non-colonized_hand-picked_rep1~WBPaper00046858:control-RNAi_PA14-non-colonized_worm-sorter_rep2~WBPaper00046858:control-RNAi_PA14-non-colonized_worm-sorter_rep3~WBPaper00046858:control-RNAi_PA14-colonized_hand-picked_rep1~WBPaper00046858:control-RNAi_PA14-colonized_worm-sorter_rep2~WBPaper00046858:control-RNAi_PA14-colonized_worm-sorter_rep3~WBPaper00046858:elt-2(RNAi)_OP50_hand-picked_rep1~WBPaper00046858:elt-2(RNAi)_OP50_wormsorter_rep2~WBPaper00046858:elt-2(RNAi)_PA14-non-colonized_hand-picked_rep1~WBPaper00046858:elt-2(RNAi)_PA14-non-colonized_worm-sorter_rep2~WBPaper00046858:elt-2(RNAi)_PA14-colonized_hand-picked_rep1	Method: microarray|Species: Caenorhabditis elegans|Topic: innate immune response
368	27864060	WBPaper00050448.ce.mr.paper	GSE82238	GPL9458	2	FOS-1 functions as a transcriptional activator downstream of the C. elegans JNK homolog KGB-1.	JNK proteins are conserved stress-activated MAP kinases. In C. elegans, the JNK-homolog KGB-1 plays essential roles in protection from heavy metals and protein folding stress. However, the contributions of KGB-1 are age-dependent, providing protection in larvae, but reducing stress resistance and shortening lifespan in adults. Attenuation of DAF-16 was linked to the detrimental contributions of KGB-1 in adults, but its involvement in KGB-1-dependent protection in larvae remains unclear. To characterize age-dependent contributions of KGB-1, we used microarray analysis to measure gene expression following KGB-1 activation either in developing larvae or in adults, achieved by knocking down its negative phosphatase regulator vhp-1. This revealed a robust KGB-1 regulon, most of which consisting of genes induced following KGB-1 activation regardless of age; a smaller number of genes was regulated in an age-dependent manner. We found that the bZIP transcription factor FOS-1 was essential for age-invariant KGB-1-dependent gene induction, but not for age-dependent expression. The latter was more affected by DAF-16, which was further found to be required for KGB-1-dependent cadmium resistance in larvae. Our results identify FOS-1 as a transcriptional activator mediating age-invariant contributions of KGB-1, including a regulatory loop of KGB-1 signaling, but also stress the importance of DAF-16 as a mediator of age-dependent contributions.	33	6513	Zhang Z	Zhang Z, Liu L, Twumasi-Boateng K, Block DH, Shapira M	FOS-1 functions as a transcriptional activator downstream of the C. elegans JNK homolog KGB-1.	Cell Signal	2016	WBPaper00050448:N2_control(RNAi)_development_rep1~WBPaper00050448:N2_control(RNAi)_development_rep2~WBPaper00050448:N2_control(RNAi)_development_rep3~WBPaper00050448:N2_vhp-1(RNAi)_development_rep1~WBPaper00050448:N2_vhp-1(RNAi)_development_rep2~WBPaper00050448:N2_vhp-1(RNAi)_development_rep3~WBPaper00050448:N2_control(RNAi)_adult_rep1~WBPaper00050448:N2_control(RNAi)_adult_rep2~WBPaper00050448:N2_control(RNAi)_adult_rep3~WBPaper00050448:N2_vhp-1(RNAi)_adult_rep1~WBPaper00050448:N2_vhp-1(RNAi)_adult_rep2~WBPaper00050448:N2_vhp-1(RNAi)_adult_rep3~WBPaper00050448:kgb-1(km21)_control(RNAi)_development_rep1~WBPaper00050448:kgb-1(km21)_control(RNAi)_development_rep2~WBPaper00050448:kgb-1(km21)_control(RNAi)_development_rep3~WBPaper00050448:kgb-1(km21)_vhp-1(RNAi)_development_rep1~WBPaper00050448:kgb-1(km21)_vhp-1(RNAi)_development_rep2~WBPaper00050448:kgb-1(km21)_vhp-1(RNAi)_development_rep3~WBPaper00050448:kgb-1(km21)_control(RNAi)_adult_rep1~WBPaper00050448:kgb-1(km21)_control(RNAi)_adult_rep2~WBPaper00050448:kgb-1(km21)_control(RNAi)_adult_rep3~WBPaper00050448:kgb-1(km21)_control(RNAi)_adult_rep4~WBPaper00050448:kgb-1(km21)_vhp-1(RNAi)_adult_rep1~WBPaper00050448:kgb-1(km21)_vhp-1(RNAi)_adult_rep2~WBPaper00050448:kgb-1(km21)_vhp-1(RNAi)_adult_rep3~WBPaper00050448:daf-16(mu86);pmk-1(km25)_control(RNAi)_development_rep1~WBPaper00050448:daf-16(mu86);pmk-1(km25)_control(RNAi)_development_rep2~WBPaper00050448:daf-16(mu86);pmk-1(km25)_vhp-1(RNAi)_development_rep1~WBPaper00050448:daf-16(mu86);pmk-1(km25)_vhp-1(RNAi)_development_rep2~WBPaper00050448:daf-16(mu86);pmk-1(km25)_control(RNAi)_adult_rep1~WBPaper00050448:daf-16(mu86);pmk-1(km25)_control(RNAi)_adult_rep2~WBPaper00050448:daf-16(mu86);pmk-1(km25)_vhp-1(RNAi)_adult_rep1~WBPaper00050448:daf-16(mu86);pmk-1(km25)_vhp-1(RNAi)_adult_rep2	Method: microarray|Species: Caenorhabditis elegans|Topic: stress response to metal ion
369	24002365	WBPaper00044128.ce.ms.paper	N.A.	N.A.	1	Reduced insulin/insulin-like growth factor-1 signaling and dietary restriction inhibit translation but preserve muscle mass in Caenorhabditis elegans.	Reduced signaling through the C. elegans insulin/insulin-like growth factor-1-like tyrosine kinase receptor daf-2 and dietary restriction via bacterial dilution are two well-characterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LC-MS/MS quantitative proteomics, we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction, as well as in the daf-2(e1370) insulin/insulin-like growth factor-1-receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that post-transcriptional regulation determines ribosome content. Proteomics also revealed the increased presence of many structural muscle cell components in long-lived worms, which appeared to result from the prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF-16, but not diet restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf-2-specific proteome changes include overexpression of aerobic metabolism enzymes and general activation of stress-responsive and immune defense systems, whereas the increased abundance of many protein subunits of the proteasome core complex is a dietary-restriction-specific characteristic.	15	787	Depuydt G	Depuydt G, Xie F, Petyuk VA, Shanmugam N, Smolders A, Dhondt I, Brewer HM, Camp DG, Smith RD, Braeckman BP	Reduced insulin/insulin-like growth factor-1 signaling and dietary restriction inhibit translation but preserve muscle mass in Caenorhabditis elegans.	Mol Cell Proteomics	2013	MassSpec_WBPaper00044128:control-FullyFed_rep1~MassSpec_WBPaper00044128:control-FullyFed_rep2~MassSpec_WBPaper00044128:control-FullyFed_rep3~MassSpec_WBPaper00044128:control-FullyFed_rep4~MassSpec_WBPaper00044128:control-FullyFed_rep5~MassSpec_WBPaper00044128:control-DietaryRestricted_rep1~MassSpec_WBPaper00044128:control-DietaryRestricted_rep2~MassSpec_WBPaper00044128:control-DietaryRestricted_rep3~MassSpec_WBPaper00044128:control-DietaryRestricted_rep4~MassSpec_WBPaper00044128:control-DietaryRestricted_rep5~MassSpec_WBPaper00044128:daf2-FullyFed_rep1~MassSpec_WBPaper00044128:daf2-FullyFed_rep2~MassSpec_WBPaper00044128:daf2-FullyFed_rep3~MassSpec_WBPaper00044128:daf2-FullyFed_rep4~MassSpec_WBPaper00044128:daf2-FullyFed_rep5	Method: proteomics|Species: Caenorhabditis elegans
370	24999909	WBPaper00045460.ce.ms.paper	N.A.	N.A.	1	Intestinal amino acid availability via PEPT-1 affects TORC1/2 signaling and the unfolded protein response.	The intestinal peptide transporter PEPT-1 plays an important role in development, growth, reproduction, and stress tolerance in Caenorhabditis elegans, as revealed by the severe phenotype of the pept-1-deficient strain. The reduced number of offspring and increased stress resistance were shown to result from changes in the insulin/IGF-signaling cascade. To further elucidate the regulatory network behind the phenotypic alterations in PEPT1-deficient animals, a quantitative proteome analysis combined with transcriptome profiling was applied. Various target genes of XBP-1, the major mediator of the unfolded protein response, were found to be downregulated at the mRNA and protein levels, accompanied by a reduction of spliced xbp-1 mRNA. Proteome analysis also revealed a markedly reduced content of numerous ribosomal proteins. This was associated with a reduction in the protein synthesis rate in pept-1 C. elegans, a process that is strictly regulated by the TOR (target of rapamycine) complex, the cellular sensor for free amino acids. These data argue for a central role of PEPT-1 in cellular amino acid homeostasis. In PEPT-1 deficiency, amino acid levels dropped systematically, leading to alterations in protein synthesis and in the IRE-1/XBP-1 pathway.	14	414	Geillinger KE	Geillinger KE, Kuhlmann K, Eisenacher M, Giesbertz P, Meyer HE, Daniel H, Spanier B	Intestinal amino acid availability via PEPT-1 affects TORC1/2 signaling and the unfolded protein response.	J Proteome Res	2014	MassSpec_WBPaper00045460:N2_20h_after_L1_rep1~MassSpec_WBPaper00045460:N2_40h_after_L1_rep1~MassSpec_WBPaper00045460:N2_60h_after_L1_rep1~MassSpec_WBPaper00045460:N2_20h_after_L1_rep2~MassSpec_WBPaper00045460:N2_40h_after_L1_rep2~MassSpec_WBPaper00045460:N2_60h_after_L1_rep2~MassSpec_WBPaper00045460:pept-1(lg601)_20h_after_L1_rep1~MassSpec_WBPaper00045460:pept-1(lg601)_20h_after_L1_rep2~MassSpec_WBPaper00045460:pept-1(lg601)_40h_after_L1_rep1~MassSpec_WBPaper00045460:pept-1(lg601)_40h_after_L1_rep2~MassSpec_WBPaper00045460:pept-1(lg601)_60h_after_L1_rep1~MassSpec_WBPaper00045460:pept-1(lg601)_60h_after_L1_rep2~MassSpec_WBPaper00045460:pept-1(lg601)_80h_after_L1_rep1~MassSpec_WBPaper00045460:pept-1(lg601)_80h_after_L1_rep2	Method: proteomics|Species: Caenorhabditis elegans|Topic: response to unfolded protein|Topic: endoplasmic reticulum|Topic: mitochondrion|Topic: cytosol
371	25530493	WBPaper00046217.ce.ms.paper	N.A.	N.A.	1	Comparison of proteomic and metabolomic profiles of mutants of the mitochondrial respiratory chain in Caenorhabditis elegans.	Single-gene mutations that disrupt mitochondrial respiratory chain function in Caenorhabditis elegans change patterns of protein expression and metabolites. Our goal was to develop useful molecular fingerprints employing adaptable techniques to recognize mitochondrial defects in the electron transport chain. We analyzed mutations affecting complex I, complex II, or ubiquinone synthesis and discovered overarching patterns in the response of C. elegans to mitochondrial dysfunction across all of the mutations studied. These patterns are in KEGG pathways conserved from C. elegans to mammals, verifying that the nematode can serve as a model for mammalian disease. In addition, specific differences exist between mutants that may be useful in diagnosing specific mitochondrial diseases in patients.	4	1458	Morgan PG	Morgan PG, Higdon R, Kolker N, Bauman AT, Ilkayeva O, Newgard CB, Kolker E, Steele LM, Sedensky MM	Comparison of proteomic and metabolomic profiles of mutants of the mitochondrial respiratory chain in Caenorhabditis elegans.	Mitochondrion	2015	MassSpec_WBPaper00046217:Clk1~MassSpec_WBPaper00046217:Gas1~MassSpec_WBPaper00046217:Mev1~MassSpec_WBPaper00046217:N2	Method: proteomics|Species: Caenorhabditis elegans
372	25963834	WBPaper00046795.ce.ms.paper	N.A.	N.A.	1	Global Proteomics Analysis of the Response to Starvation in C. elegans.	Periodic starvation of animals induces large shifts in metabolism but may also influence many other cellular systems and can lead to adaption to prolonged starvation conditions. To date, there is limited understanding of how starvation affects gene expression, particularly at the protein level. Here, we have used mass-spectrometry-based quantitative proteomics to identify global changes in the Caenorhabditis elegans proteome due to acute starvation of young adult animals. Measuring changes in the abundance of over 5,000 proteins, we show that acute starvation rapidly alters the levels of hundreds of proteins, many involved in central metabolic pathways, highlighting key regulatory responses. Surprisingly, we also detect changes in the abundance of chromatin-associated proteins, including specific linker histones, histone variants, and histone posttranslational modifications associated with the epigenetic control of gene expression. To maximize community access to these data, they are presented in an online searchable database, the Encyclopedia of Proteome Dynamics (http:\/\/www.peptracker.com/epd/).	5	4850	Larance M	Larance M, Pourkarimi E, Wang B, Murillo AB, Kent R, Lamond AI, Gartner A	Global Proteomics Analysis of the Response to Starvation in C. elegans.	Mol Cell Proteomics	2015	MassSpec_WBPaper00046795:0h_starvation~MassSpec_WBPaper00046795:4h_starvation~MassSpec_WBPaper00046795:8h_starvation~MassSpec_WBPaper00046795:16h_starvation~MassSpec_WBPaper00046795:32h_starvation	Method: proteomics|Species: Caenorhabditis elegans
373	26121959	WBPaper00046981.ce.ms.paper	N.A.	N.A.	1	Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein.	Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified Caenorhabditis elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols is rich in fatty acid species obtained from the dietary Escherichia coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type and high-fat daf-2 mutant strains shows a very similar proteome in both strains, except that the most abundant protein in the C. elegans lipid droplet proteome, MDT-28, is relatively less abundant in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans. Finally, we confirmed the localization of one of the newly identified lipid droplet proteins, ACS-4. We found that ACS-4 localizes to the surface of lipid droplets in the C. elegans intestine and skin. This study bolsters C. elegans as a model to study the dynamics and functions of lipid droplets in a multicellular organism.	2	312	Vrablik TL	Vrablik TL, Petyuk VA, Larson EM, Smith RD, Watts JL	Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein.	Biochim Biophys Acta	2015	MassSpec_WBPaper00046981:daf-2(e1370)_liplid-droplet~MassSpec_WBPaper00046981:N2_lipid-droplet	Method: proteomics|Species: Caenorhabditis elegans
374	26392051	WBPaper00048573.ce.ms.paper	N.A.	N.A.	1	NeuCode Labeling in Nematodes: Proteomic and Phosphoproteomic Impact of Ascaroside Treatment in Caenorhabditis elegans.	The nematode Caenorhabditis elegans is an important model organism for biomedical research. We previously described NeuCode stable isotope labeling by amino acids in cell culture (SILAC), a method for accurate proteome quantification with potential for multiplexing beyond the limits of traditional stable isotope labeling by amino acids in cell culture. Here we apply NeuCode SILAC to profile the proteomic and phosphoproteomic response of C. elegans to two potent members of the ascaroside family of nematode pheromones. By consuming labeled E. coli as part of their diet, C. elegans nematodes quickly and easily incorporate the NeuCode heavy lysine isotopologues by the young adult stage. Using this approach, we report, at high confidence, one of the largest proteomic and phosphoproteomic data sets to date in C. elegans: 6596 proteins at a false discovery rate  1% and 6620 phosphorylation isoforms with localization probability 75%. Our data reveal a post-translational signature of pheromone sensing that includes many conserved proteins implicated in longevity and response to stress.	9	6407	Rhoads TW	Rhoads TW, Prasad A, Kwiecien NW, Merrill AE, Zawack K, Westphall MS, Schroeder FC, Kimble J, Coon JJ	NeuCode Labeling in Nematodes: Proteomic and Phosphoproteomic Impact of Ascaroside Treatment in Caenorhabditis elegans.	Mol Cell Proteomics	2015	MassSpec_WBPaper00048573:Ascaroside-2_rep1~MassSpec_WBPaper00048573:Ascaroside-2_rep2~MassSpec_WBPaper00048573:Ascaroside-2_rep3~MassSpec_WBPaper00048573:Ascaroside-5_rep1~MassSpec_WBPaper00048573:Ascaroside-5_rep2~MassSpec_WBPaper00048573:Ascaroside-5_rep3~MassSpec_WBPaper00048573:Control_rep1~MassSpec_WBPaper00048573:Control_rep2~MassSpec_WBPaper00048573:Control_rep3	Method: proteomics|Species: Caenorhabditis elegans
375	26595419	WBPaper00048910.ce.ms.paper	N.A.	N.A.	1	Conserved mRNA-binding proteomes in eukaryotic organisms.	RNA-binding proteins (RBPs) are essential for post-transcriptional regulation of gene expression. Recent high-throughput screens have dramatically increased the number of experimentally identified RBPs; however, comprehensive identification of RBPs within living organisms is elusive. Here we describe the repertoire of 765 and 594 proteins that reproducibly interact with polyadenylated mRNAs in Saccharomyces cerevisiae and Caenorhabditis elegans, respectively. Furthermore, we report the differential association of mRNA-binding proteins (mRPBs) upon induction of apoptosis in C. elegans L4-stage larvae. Strikingly, most proteins composing mRBPomes, including components of early metabolic pathways and the proteasome, are evolutionarily conserved between yeast and C. elegans. We speculate, on the basis of our evidence that glycolytic enzymes bind distinct glycolytic mRNAs, that enzyme-mRNA interactions relate to an ancient mechanism for post-transcriptional coordination of metabolic pathways that perhaps was established during the transition from the early 'RNA world' to the 'protein world'.	9	626	Matia-Gonzalez AM	Matia-Gonzalez AM, Laing EE, Gerber AP	Conserved mRNA-binding proteomes in eukaryotic organisms.	Nat Struct Mol Biol	2015	MassSpec_WBPaper00048910:Mixed-stage_rep1~MassSpec_WBPaper00048910:Mixed-stage_rep2~MassSpec_WBPaper00048910:Mixed-stage_rep3~MassSpec_WBPaper00048910:L4_rep1~MassSpec_WBPaper00048910:L4_rep2~MassSpec_WBPaper00048910:L4_rep3~MassSpec_WBPaper00048910:L4-ENU_rep1~MassSpec_WBPaper00048910:L4-ENU_rep2~MassSpec_WBPaper00048910:L4-ENU_rep3	Method: proteomics|Species: Caenorhabditis elegans
376	27594427	WBPaper00050091.ce.ms.paper	N.A.	N.A.	1	Polar Positioning of Phase-Separated Liquid Compartments in Cells Regulated by an mRNA Competition Mechanism.	P granules are non-membrane-bound RNA-protein compartments that are involved in germline development in C.elegans. They are liquids that condense at one end of the embryo by localized phase separation, driven by gradients of polarity proteins such as the mRNA-binding protein MEX-5. To probe how polarity proteins regulate phase separation, we combined biochemistry and theoretical modeling. We reconstitute P granule-like droplets invitro using a single protein PGL-3. By combining invitro reconstitution with measurements of intracellular concentrations, we show that competition between PGL-3 andMEX-5 for mRNA can regulate the formation of PGL-3 droplets. Using theory, we show that, in a MEX-5 gradient, this mRNA competition mechanism can drive a gradient of P granule assembly with similar spatial and temporal characteristics to P granule assembly invivo. We conclude that gradients of polarity proteins can position RNP granules during development by using RNA competition to regulate local phase separation.	1	6136	Saha S	Saha S, Weber CA, Nousch M, Adame-Arana O, Hoege C, Hein MY, Osborne-Nishimura E, Mahamid J, Jahnel M, Jawerth L, Pozniakovski A, Eckmann CR, Julicher F, Hyman AA	Polar Positioning of Phase-Separated Liquid Compartments in Cells Regulated by an mRNA Competition Mechanism.	Cell	2016	MassSpec_WBPaper00050091:embryo	Method: proteomics|Species: Caenorhabditis elegans
377	26829753	WBPaper00050919.ce.ms.paper	N.A.	N.A.	1	The genomic basis of parasitism in the Strongyloides clade of nematodes.	Soil-transmitted nematodes, including the Strongyloides genus, cause one of the most prevalent neglected tropical diseases. Here we compare the genomes of four Strongyloides species, including the human pathogen Strongyloides stercoralis, and their close relatives that are facultatively parasitic (Parastrongyloides trichosuri) and free-living (Rhabditophanes sp. KR3021). A significant paralogous expansion of key gene families--families encoding astacin-like and SCP/TAPS proteins--is associated with the evolution of parasitism in this clade. Exploiting the unique Strongyloides life cycle, we compare the transcriptomes of the parasitic and free-living stages and find that these same gene families are upregulated in the parasitic stages, underscoring their role in nematode parasitism.	12	1266	Hunt VL	Hunt VL, Tsai IJ, Coghlan A, Reid AJ, Holroyd N, Foth BJ, Tracey A, Cotton JA, Stanley EJ, Beasley H, Bennett HM, Brooks K, Harsha B, Kajitani R, Kulkarni A, Harbecke D, Nagayasu E, Nichol S, Ogura Y, Quail MA, Randle N, Xia D, Brattig NW, Soblik H, Ribeiro DM, Sanchez-Flores A, Hayashi T, Itoh T, Denver DR, Grant W, Stoltzfus JD, Lok JB, Murayama H, Wastling J, Streit A, Kikuchi T, Viney M, Berriman M	The genomic basis of parasitism in the Strongyloides clade of nematodes.	Nat Genet	2016	MassSpec_WBPaper00050919:S.ratti_FreeLiving_rep1_01~MassSpec_WBPaper00050919:S.ratti_FreeLiving_rep1_02~MassSpec_WBPaper00050919:S.ratti_FreeLiving_rep1_03~MassSpec_WBPaper00050919:S.ratti_FreeLiving_rep2_01~MassSpec_WBPaper00050919:S.ratti_FreeLiving_rep2_02~MassSpec_WBPaper00050919:S.ratti_FreeLiving_rep2_03~MassSpec_WBPaper00050919:S.ratti_Parasitic_rep1_01~MassSpec_WBPaper00050919:S.ratti_Parasitic_rep1_02~MassSpec_WBPaper00050919:S.ratti_Parasitic_rep1_03~MassSpec_WBPaper00050919:S.ratti_Parasitic_rep2_01~MassSpec_WBPaper00050919:S.ratti_Parasitic_rep2_02~MassSpec_WBPaper00050919:S.ratti_Parasitic_rep2_03	Method: proteomics|Species: Caenorhabditis elegans
378	28734827	WBPaper00051532.ce.ms.paper	N.A.	N.A.	1	Multi-omics Analyses of Starvation Responses Reveal a Central Role for Lipoprotein Metabolism in Acute Starvation Survival in C.elegans.	Starvation causes comprehensive metabolic changes, which are still not fully understood. Here, we used quantitative proteomics and RNA sequencing to examine the temporal starvation responses in wild-type Caenorhabditis elegans and animals lacking the transcription factor HLH-30. Our findings show that starvation alters the abundance of hundreds of proteins and mRNAs in a temporal manner, many of which are involved in central metabolic pathways, including lipoprotein metabolism. We demonstrate that premature death of hlh-30 animals under starvation can be prevented by knockdown of either vit-1 or vit-5, encoding two different lipoproteins. We further show that the size and number of intestinal lipid droplets under starvation are altered in hlh-30 animals, which can be rescued by knockdown of vit-1. Taken together, this indicates that survival of hlh-30 animals under starvation is closely linked to regulation of intestinal lipid stores. We provide the most detailed poly-omic analysis of starvation responses to date, which serves as a resource for further mechanistic studies of starvation.	42	4154	Harvald EB	Harvald EB, Sprenger RR, Dall KB, Ejsing CS, Nielsen R, Mandrup S, Murillo AB, Larance M, Gartner A, Lamond AI, Faergeman NJ	Multi-omics Analyses of Starvation Responses Reveal a Central Role for Lipoprotein Metabolism in Acute Starvation Survival in C.elegans.	Cell Syst	2017	MassSpec_WBPaper00051532:N2_fed_RepA~MassSpec_WBPaper00051532:N2_fed_RepB~MassSpec_WBPaper00051532:N2_fed_RepC~MassSpec_WBPaper00051532:N2_1hr-starvation_RepA~MassSpec_WBPaper00051532:N2_1hr-starvation_RepB~MassSpec_WBPaper00051532:N2_1hr-starvation_RepC~MassSpec_WBPaper00051532:N2_2hr-starvation_RepA~MassSpec_WBPaper00051532:N2_2hr-starvation_RepB~MassSpec_WBPaper00051532:N2_2hr-starvation_RepC~MassSpec_WBPaper00051532:N2_3hr-starvation_RepA~MassSpec_WBPaper00051532:N2_3hr-starvation_RepB~MassSpec_WBPaper00051532:N2_3hr-starvation_RepC~MassSpec_WBPaper00051532:N2_4hr-starvation_RepA~MassSpec_WBPaper00051532:N2_4hr-starvation_RepB~MassSpec_WBPaper00051532:N2_4hr-starvation_RepC~MassSpec_WBPaper00051532:N2_6hr-starvation_RepA~MassSpec_WBPaper00051532:N2_6hr-starvation_RepB~MassSpec_WBPaper00051532:N2_6hr-starvation_RepC~MassSpec_WBPaper00051532:N2_16hr-starvation_RepA~MassSpec_WBPaper00051532:N2_16hr-starvation_RepB~MassSpec_WBPaper00051532:N2_16hr-starvation_RepC~MassSpec_WBPaper00051532:hlh-30(tm1978)_fed_RepA~MassSpec_WBPaper00051532:hlh-30(tm1978)_fed_RepB~MassSpec_WBPaper00051532:hlh-30(tm1978)_fed_RepC~MassSpec_WBPaper00051532:hlh-30(tm1978)_1hr-starvation_RepA~MassSpec_WBPaper00051532:hlh-30(tm1978)_1hr-starvation_RepB~MassSpec_WBPaper00051532:hlh-30(tm1978)_1hr-starvation_RepC~MassSpec_WBPaper00051532:hlh-30(tm1978)_2hr-starvation_RepA~MassSpec_WBPaper00051532:hlh-30(tm1978)_2hr-starvation_RepB~MassSpec_WBPaper00051532:hlh-30(tm1978)_2hr-starvation_RepC~MassSpec_WBPaper00051532:hlh-30(tm1978)_3hr-starvation_RepA~MassSpec_WBPaper00051532:hlh-30(tm1978)_3hr-starvation_RepB~MassSpec_WBPaper00051532:hlh-30(tm1978)_3hr-starvation_RepC~MassSpec_WBPaper00051532:hlh-30(tm1978)_4hr-starvation_RepA~MassSpec_WBPaper00051532:hlh-30(tm1978)_4hr-starvation_RepB~MassSpec_WBPaper00051532:hlh-30(tm1978)_4hr-starvation_RepC~MassSpec_WBPaper00051532:hlh-30(tm1978)_6hr-starvation_RepA~MassSpec_WBPaper00051532:hlh-30(tm1978)_6hr-starvation_RepB~MassSpec_WBPaper00051532:hlh-30(tm1978)_6hr-starvation_RepC~MassSpec_WBPaper00051532:hlh-30(tm1978)_16hr-starvation_RepA~MassSpec_WBPaper00051532:hlh-30(tm1978)_16hr-starvation_RepB~MassSpec_WBPaper00051532:hlh-30(tm1978)_16hr-starvation_RepC	Method: proteomics|Species: Caenorhabditis elegans
379	36939052	WBPaper00065132.ce.ms.paper	N.A.	N.A.	1	A proinsulin-dependent interaction between ENPL-1 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans.	Neuropeptides, including insulin, are important regulators of physiological functions of the organisms. Trafficking through the Golgi is crucial for the regulation of secretion of insulin-like peptides. ASNA-1 (TRC40) and ENPL-1 (GRP94) are conserved insulin secretion regulators in Caenorhabditis elegans (and mammals), and mouse Grp94 mutants display type 2 diabetes. ENPL-1/GRP94 binds proinsulin and regulates proinsulin levels in C. elegans and mammalian cells. Here, we have found that ASNA-1 and ENPL-1 cooperate to regulate insulin secretion in worms via a physical interaction that is independent of the insulin-binding site of ENPL-1. The interaction occurs in DAF-28/insulin-expressing neurons and is sensitive to changes in DAF-28 pro-peptide levels. Consistently, ASNA-1 acted in neurons to promote DAF-28/insulin secretion. The chaperone form of ASNA-1 was likely the interaction partner of ENPL-1. Loss of asna-1 disrupted Golgi trafficking pathways. ASNA-1 localization to the Golgi was affected in enpl-1 mutants and ENPL-1 overexpression partially bypassed the ASNA-1 requirement. Taken together, we find a functional interaction between ENPL-1 and ASNA-1 that is necessary to maintain proper insulin secretion in C. elegans and provides insights into how their loss might cause diabetes in mammals.	8	4602	Podraza-Farhanieh A	Podraza-Farhanieh A, Raj D, Kao G, Naredi P	A proinsulin-dependent interaction between ENPL-1 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans.	Development	2023	MassSpec_WBPaper00065132:asna-1(ok938)_rep1~MassSpec_WBPaper00065132:asna-1(ok938)_rep2~MassSpec_WBPaper00065132:asna-1(ok938)_rep3and4~MassSpec_WBPaper00065132:asna-1(ok938)_rep5~MassSpec_WBPaper00065132:N2_rep1~MassSpec_WBPaper00065132:N2_rep2~MassSpec_WBPaper00065132:N2_rep3~MassSpec_WBPaper00065132:N2_rep4	Method: proteomics|Species: Caenorhabditis elegans
380	37818754	WBPaper00066328.ce.ms.paper	N.A.	N.A.	1	<i>Cronobacter sakazakii</i> infection implicates multifaceted neuro-immune regulatory pathways of <i>Caenorhabditis elegans</i>.	The neural pathways of <i>Caenorhabditis elegans</i> play a crucial role in regulating host immunity and inflammation during pathogenic infections. To understand the major neuro-immune signaling pathways, this study aimed to identify the key regulatory proteins in the host <i>C. elegans</i> during <i>C. sakazakii</i> infection. We used high-throughput label-free quantitative proteomics and identified 69 differentially expressed proteins. KEGG analysis revealed that <i>C. sakazakii</i> elicited host immune signaling cascades primarily including mTOR signaling, axon regeneration, metabolic pathways (<i>let-363</i> and <i>acox-1.4</i>), calcium signaling <i>(mlck-1)</i>, and longevity regulating pathways (<i>ddl-2</i>), respectively. The abrogation in functional loss of mTOR-associated players deciphered that <i>C. sakazakii</i> infection negatively regulated the lifespan of mutant worms (<i>akt-1</i>, <i>let-363</i> and <i>dlk-1</i>), including physiological aberrations, such as reduced pharyngeal pumping and egg production. Additionally, the candidate pathway proteins were validated by transcriptional profiling of their corresponding genes. Furthermore, immunoblotting showed the downregulation of mTORC2/SGK-1 during the later hours of pathogen exposure. Overall, our findings profoundly provide an understanding of the specificity of proteome imbalance in affecting neuro-immune regulations during <i>C. sakazakii</i> infection.	18	803	VenkataKrishna LM	VenkataKrishna LM, Balasubramaniam B, Sushmitha TJ, Ravichandiran V, Balamurugan K	<i>Cronobacter sakazakii</i> infection implicates multifaceted neuro-immune regulatory pathways of <i>Caenorhabditis elegans</i>.	Mol Omics	2023	MassSpec_WBPaper00066328:OP50_24H_repA~MassSpec_WBPaper00066328:OP50_24H_repB~MassSpec_WBPaper00066328:OP50_24H_repC~MassSpec_WBPaper00066328:OP50_48H_repA~MassSpec_WBPaper00066328:OP50_48H_repB~MassSpec_WBPaper00066328:OP50_48H_repC~MassSpec_WBPaper00066328:OP50_72H_repA~MassSpec_WBPaper00066328:OP50_72H_repB~MassSpec_WBPaper00066328:OP50_72H_repC~MassSpec_WBPaper00066328:CS_24H_repA~MassSpec_WBPaper00066328:CS_24H_repB~MassSpec_WBPaper00066328:CS_24H_repC~MassSpec_WBPaper00066328:CS_48H_repA~MassSpec_WBPaper00066328:CS_48H_repB~MassSpec_WBPaper00066328:CS_48H_repC~MassSpec_WBPaper00066328:CS_72H_repA~MassSpec_WBPaper00066328:CS_72H_repB~MassSpec_WBPaper00066328:CS_72H_repC	Method: proteomics|Species: Caenorhabditis elegans
381	38267699	WBPaper00066417.ce.ms.paper	N.A.	N.A.	1	Mobilization of cholesterol induces the transition from quiescence to growth in Caenorhabditis elegans through steroid hormone and mTOR signaling.	Recovery from the quiescent developmental stage called dauer is an essential process in C. elegans and provides an excellent model to understand how metabolic transitions contribute to developmental plasticity. Here we show that cholesterol bound to the small secreted proteins SCL-12 or SCL-13 is sequestered in the gut lumen during the dauer state. Upon recovery from dauer, bound cholesterol undergoes endocytosis into lysosomes of intestinal cells, where SCL-12 and SCL-13 are degraded and cholesterol is released. Free cholesterol activates mTORC1 and is used for the production of dafachronic acids. This leads to promotion of protein synthesis and growth, and a metabolic switch at the transcriptional level. Thus, mobilization of sequestered cholesterol stores is the key event for transition from quiescence to growth, and cholesterol is the major signaling molecule in this process.	12	5114	Schmeisser K	Schmeisser K, Kaptan D, Raghuraman BK, Shevchenko A, Rodenfels J, Penkov S, Kurzchalia TV	Mobilization of cholesterol induces the transition from quiescence to growth in Caenorhabditis elegans through steroid hormone and mTOR signaling.	Commun Biol	2024	MassSpec_WBPaper00066417:Dauer_BR1_Rep1~MassSpec_WBPaper00066417:Dauer_BR1_Rep2~MassSpec_WBPaper00066417:Dauer_BR2_Rep1~MassSpec_WBPaper00066417:Dauer_BR2_Rep2~MassSpec_WBPaper00066417:Dauer_BR3_Rep1~MassSpec_WBPaper00066417:Dauer_BR3_Rep2~MassSpec_WBPaper00066417:L3_BR1_Rep1~MassSpec_WBPaper00066417:L3_BR1_Rep2~MassSpec_WBPaper00066417:L3_BR2_Rep1~MassSpec_WBPaper00066417:L3_BR2_Rep2~MassSpec_WBPaper00066417:L3_BR3_Rep1~MassSpec_WBPaper00066417:L3_BR3_Rep2	Method: proteomics|Species: Caenorhabditis elegans
382	38320757	WBPaper00066469.ce.ms.paper	N.A.	N.A.	1	The protein tyrosine phosphatase PPH-7 is required for fertility and embryonic development in C.&#x2009;elegans at elevated temperatures.	Post-translational modifications are key in the regulation of activity, structure, localization, and stability of most proteins in eukaryotes. Phosphorylation is potentially the most studied post-translational modification, also due to its reversibility and thereby the regulatory role this modification often plays. While most research attention was focused on kinases in the past, phosphatases remain understudied, most probably because the addition and presence of the modification is more easily studied than its removal and absence. Here, we report the identification of an uncharacterized protein tyrosine phosphatase PPH-7 in C.&#x2009;elegans, a member of the evolutionary conserved PTPN family of phosphatases. Lack of PPH-7 function led to reduction of fertility and embryonic lethality at elevated temperatures. Proteomics revealed changes in the regulation of targets of the von Hippel-Lindau (VHL) E3 ligase, suggesting a potential role for PPH-7 in the regulation of VHL.	8	2233	Franziscus CA	Franziscus CA, Ritz D, Kappel NC, Solinger JA, Schmidt A, Spang A	The protein tyrosine phosphatase PPH-7 is required for fertility and embryonic development in C.&#x2009;elegans at elevated temperatures.	FEBS Open Bio	2024	MassSpec_WBPaper00066469:N2_rep1~MassSpec_WBPaper00066469:N2_rep2~MassSpec_WBPaper00066469:N2_rep3~MassSpec_WBPaper00066469:pph-7(tm5332)_rep1~MassSpec_WBPaper00066469:pph-7(tm5332)_rep2~MassSpec_WBPaper00066469:pph-7(tm5332)_rep3~MassSpec_WBPaper00066469:pph-7(af5)_rep1~MassSpec_WBPaper00066469:pph-7(af5)_rep2	Method: proteomics|Species: Caenorhabditis elegans
383	38402241	WBPaper00066531.ce.ms.paper	N.A.	N.A.	1	Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans.	Ribosome biogenesis is initiated by RNA polymerase I (Pol I)-mediated synthesis of pre-ribosomal RNA (pre-rRNA). Pol I activity was previously linked to longevity, but the underlying mechanisms were not studied beyond effects on nucleolar structure and protein translation. Here we use multi-omics and functional tests to show that curtailment of Pol I activity remodels the lipidome and preserves mitochondrial function to promote longevity in Caenorhabditis elegans. Reduced pre-rRNA synthesis improves energy homeostasis and metabolic plasticity also in human primary cells. Conversely, the enhancement of pre-rRNA synthesis boosts growth and neuromuscular performance of young nematodes at the cost of accelerated metabolic decline, mitochondrial stress and premature aging. Moreover, restriction of Pol I activity extends lifespan more potently than direct repression of protein synthesis, and confers geroprotection even when initiated late in life, showcasing this intervention as an effective longevity and metabolic health treatment not limited by aging.	45	5486	Sharifi S	Sharifi S, Chaudhari P, Martirosyan A, Eberhardt AO, Witt F, Gollowitzer A, Lange L, Woitzat Y, Okoli EM, Li H, Rahnis N, Kirkpatrick J, Werz O, Ori A, Koeberle A, Bierhoff H, Ermolaeva M	Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans.	Nat Commun	2024	MassSpec_WBPaper00066531:EVD2_rep1_1~MassSpec_WBPaper00066531:EVD2_rep2_2~MassSpec_WBPaper00066531:EVD2_rep3_3~MassSpec_WBPaper00066531:EVD2_rep4_4~MassSpec_WBPaper00066531:EVD2_rep5_5~MassSpec_WBPaper00066531:EVD6_rep1_6~MassSpec_WBPaper00066531:EVD6_rep2_7~MassSpec_WBPaper00066531:EVD6_rep3_8~MassSpec_WBPaper00066531:EVD6_rep_4_9~MassSpec_WBPaper00066531:EVD6_rep5_10~MassSpec_WBPaper00066531:EVD12_rep2_12~MassSpec_WBPaper00066531:EVD12_rep1_11~MassSpec_WBPaper00066531:EVD12_rep3_13~MassSpec_WBPaper00066531:EVD12_rep4_14~MassSpec_WBPaper00066531:EVD12_rep5_15~MassSpec_WBPaper00066531:C36D2_rep1_16~MassSpec_WBPaper00066531:C36D2_rep2_17~MassSpec_WBPaper00066531:C36D2_rep3_18~MassSpec_WBPaper00066531:C36D2_rep4_19~MassSpec_WBPaper00066531:C36D2_rep5_20~MassSpec_WBPaper00066531:C36D6_rep1_21~MassSpec_WBPaper00066531:C36D6_rep2_22~MassSpec_WBPaper00066531:C36D6_rep3_23~MassSpec_WBPaper00066531:C36D6_rep4_24~MassSpec_WBPaper00066531:C36D6_rep5_25~MassSpec_WBPaper00066531:C36D12_rep1_26~MassSpec_WBPaper00066531:C36D12_rep2_27~MassSpec_WBPaper00066531:C36D12_rep3_28~MassSpec_WBPaper00066531:C36D12_rep4_29~MassSpec_WBPaper00066531:C36D12_rep5_30~MassSpec_WBPaper00066531:NCL1D2_rep1_31~MassSpec_WBPaper00066531:NCL1D2_rep2_32~MassSpec_WBPaper00066531:NCL1D2_rep_3_33~MassSpec_WBPaper00066531:NCL1D2_rep4_34~MassSpec_WBPaper00066531:NCL1D2_rep5_35~MassSpec_WBPaper00066531:NCL1D6_rep1_36~MassSpec_WBPaper00066531:NCL1D6_rep2_37~MassSpec_WBPaper00066531:NCL1D6_rep3_38~MassSpec_WBPaper00066531:NCL1D6_rep4_39~MassSpec_WBPaper00066531:NCL1D6_rep5_40~MassSpec_WBPaper00066531:NCL1D12_rep1_41~MassSpec_WBPaper00066531:NCL1D12_rep2_42~MassSpec_WBPaper00066531:NCL1D12_rep3_43~MassSpec_WBPaper00066531:NCL1D12_rep4_44~MassSpec_WBPaper00066531:NCL1D12_rep5_45	Method: proteomics|Species: Caenorhabditis elegans
384	38418585	WBPaper00066547.ce.ms.paper	N.A.	N.A.	1	Enhanced branched-chain amino acid metabolism improves age-related reproduction in C. elegans.	Reproductive ageing is one of the earliest human ageing phenotypes, and mitochondrial dysfunction has been linked to oocyte quality decline; however, it is not known which mitochondrial metabolic processes are critical for oocyte quality maintenance with age. To understand how mitochondrial processes contribute to Caenorhabditis&#x2009;elegans oocyte quality, we characterized the mitochondrial proteomes of young and aged wild-type and long-reproductive daf-2 mutants. Here we show that the mitochondrial proteomic profiles of young wild-type and daf-2 worms are similar and share upregulation of branched-chain amino acid (BCAA) metabolism pathway enzymes. Reduction of the BCAA catabolism enzyme BCAT-1 shortens reproduction, elevates mitochondrial reactive oxygen species levels, and shifts mitochondrial localization. Moreover, bcat-1 knockdown decreases oocyte quality in daf-2 worms and reduces reproductive capability, indicating the role of this pathway in the maintenance of oocyte quality with age. Notably, oocyte quality deterioration can be delayed, and reproduction can be extended in wild-type animals both by bcat-1 overexpression and by supplementing with vitamin B1, a cofactor needed for BCAA metabolism.	12	1547	Lesnik C	Lesnik C, Kaletsky R, Ashraf JM, Sohrabi S, Cota V, SenGupta T, Keyes W, Luo S, Murphy CT	Enhanced branched-chain amino acid metabolism improves age-related reproduction in C. elegans.	Nat Metab	2024	MassSpec_WBPaper00066547:daf-2(e1370)_day1_repI~MassSpec_WBPaper00066547:daf-2(e1370)_day1_repII~MassSpec_WBPaper00066547:daf-2(e1370)_day1_repIII~MassSpec_WBPaper00066547:daf-2(e1370)_day5_repI~MassSpec_WBPaper00066547:daf-2(e1370)_day5_repII~MassSpec_WBPaper00066547:daf-2(e1370)_day5_repIII~MassSpec_WBPaper00066547:N2_day1_repI~MassSpec_WBPaper00066547:N2_day1_repII~MassSpec_WBPaper00066547:N2_day1_repIII~MassSpec_WBPaper00066547:N2_day5_repI~MassSpec_WBPaper00066547:N2_day5_repII~MassSpec_WBPaper00066547:N2_day5_repIII	Method: proteomics|Species: Caenorhabditis elegans
385	38411078	WBPaper00066632.ce.ms.paper	N.A.	N.A.	1	The <i>Caenorhabditis elegans</i> proteome response to two protective <i>Pseudomonas</i> symbionts.	The <i>Caenorhabditis elegans</i> natural microbiota isolates <i>Pseudomonas lurida</i> MYb11 and <i>Pseudomonas fluorescens</i> MYb115 protect the host against pathogens through distinct mechanisms. While <i>P. lurida</i> produces an antimicrobial compound and directly inhibits pathogen growth, <i>P. fluorescens</i> MYb115 protects the host without affecting pathogen growth. It is unknown how these two protective microbes affect host biological processes. We used a proteomics approach to elucidate the <i>C. elegans</i> response to MYb11 and MYb115. We found that both <i>Pseudomonas</i> isolates increase vitellogenin protein production in young adults, which confirms previous findings on the effect of microbiota on <i>C. elegans</i> reproductive timing. Moreover, the <i>C. elegans</i> responses to MYb11 and MYb115 exhibit common signatures with the response to other vitamin B<sub>12</sub>-producing bacteria, emphasizing the importance of vitamin B<sub>12</sub> in <i>C. elegans</i>-microbe metabolic interactions. We further analyzed signatures in the <i>C. elegans</i> response specific to MYb11 or MYb115. We provide evidence for distinct modifications in lipid metabolism by both symbiotic microbes. We could identify the activation of host-pathogen defense responses as an MYb11-specific proteome signature and provide evidence that the intermediate filament protein IFB-2 is required for MYb115-mediated protection. These results indicate that MYb11 not only produces an antimicrobial compound but also activates host antimicrobial defenses, which together might increase resistance to infection. In contrast, MYb115 affects host processes such as lipid metabolism and cytoskeleton dynamics, which might increase host tolerance to infection. Overall, this study pinpoints proteins of interest that form the basis for additional exploration into the mechanisms underlying <i>C. elegans</i> microbiota-mediated protection from pathogen infection and other microbiota-mediated traits.IMPORTANCESymbiotic bacteria can defend their host against pathogen infection. While some protective symbionts directly interact with pathogenic bacteria, other protective symbionts elicit a response in the host that improves its own pathogen defenses. To better understand how a host responds to protective symbionts, we examined which host proteins are affected by two protective <i>Pseudomonas</i> bacteria in the model nematode <i>Caenorhabditis elegans</i>. We found that the <i>C. elegans</i> response to its protective symbionts is manifold, which was reflected in changes in proteins that are involved in metabolism, the immune system, and cell structure. This study provides a foundation for exploring the contribution of the host response to symbiont-mediated protection from pathogen infection.	12	3481	Pees B	Pees B, Peters L, Treitz C, Hamerich IK, Kissoyan KAB, Tholey A, Dierking K	The <i>Caenorhabditis elegans</i> proteome response to two protective <i>Pseudomonas</i> symbionts.	mBio	2024	MassSpec_WBPaper00066632:KK04_E.coli_OP50~MassSpec_WBPaper00066632:KK10_E.coli_OP50~MassSpec_WBPaper00066632:KK16_E.coli_OP50~MassSpec_WBPaper00066632:KK29_E.coli_OP50~MassSpec_WBPaper00066632:KK01_P.lurida_MYb11~MassSpec_WBPaper00066632:KK08_P.lurida_MYb11~MassSpec_WBPaper00066632:KK09_P.lurida_MYb11~MassSpec_WBPaper00066632:KK13avg_P.lurida_MYb11~MassSpec_WBPaper00066632:KK15_P.fluorescens_MYb115~MassSpec_WBPaper00066632:KK27_P.fluorescens_MYb115~MassSpec_WBPaper00066632:KK28_P.fluorescens_MYb115~MassSpec_WBPaper00066632:KK30_P.fluorescens_MYb115	Method: proteomics|Species: Caenorhabditis elegans
386	38753516	WBPaper00066799.ce.ms.paper	N.A.	N.A.	1	MACSPI enables tissue-selective proteomic and interactomic analyses in multicellular organisms.	Multicellular organisms are composed of many tissue types that have distinct morphologies and functions, which are largely driven by specialized proteomes and interactomes. To define the proteome and interactome of a specific type of tissue in an intact animal, we developed a localized proteomics approach called Methionine Analog-based Cell-Specific Proteomics and Interactomics (MACSPI). This method uses the tissue-specific expression of an engineered methionyl-tRNA synthetase to label proteins with a bifunctional amino acid 2-amino-5-diazirinylnonynoic acid in selected cells. We applied MACSPI in <i>Caenorhabditis elegans,</i> a model multicellular organism, to selectively label, capture, and profile the proteomes of the body wall muscle and the nervous system, which led to the identification of tissue-specific proteins. Using the photo-cross-linker, we successfully profiled HSP90 interactors in muscles and neurons and identified tissue-specific interactors and stress-related interactors. Our study demonstrates that MACSPI can be used to profile tissue-specific proteomes and interactomes in intact multicellular organisms.	4	885	Huang S	Huang S, Ran Q, Li XM, Bao X, Zheng C, Li XD	MACSPI enables tissue-selective proteomic and interactomic analyses in multicellular organisms.	Proc Natl Acad Sci U S A	2024	MassSpec_WBPaper00066799:body-wall-muscle_rep1~MassSpec_WBPaper00066799:body-wall-muscle_rep2~MassSpec_WBPaper00066799:neuron_rep1~MassSpec_WBPaper00066799:neuron_rep2	Method: proteomics|Species: Caenorhabditis elegans
387	38861598	WBPaper00066880.ce.ms.paper	N.A.	N.A.	1	Single-tissue proteomics in <i>Caenorhabditis elegans</i> reveals proteins resident in intestinal lysosome-related organelles.	The nematode intestine is the primary site for nutrient uptake and storage as well as the synthesis of biomolecules; lysosome-related organelles known as gut granules are important for many of these functions. Aspects of intestine biology are not well understood, including the export of the nutrients it imports and the molecules it synthesizes, as well as the complete functions and protein content of the gut granules. Here, we report a mass spectrometry (MS)-based proteomic analysis of the intestine of the <i>Caenorhabditis elegans</i> and of its gut granules. Overall, we identified approximately 5,000 proteins each in the intestine and the gonad and showed that most of these proteins can be detected in samples extracted from a single worm, suggesting the feasibility of individual-level genetic analysis using proteomes. Comparing proteomes and published transcriptomes of the intestine and the gonad, we identified proteins that appear to be synthesized in the intestine and then transferred to the gonad. To identify gut granule proteins, we compared the proteome of individual intestines deficient in gut granules to the wild type. The identified gut granule proteome includes proteins known to be exclusively localized to the granules and additional putative gut granule proteins. We selected two of these putative gut granule proteins for validation via immunohistochemistry, and our successful confirmation of both suggests that our strategy was effective in identifying the gut granule proteome. Our results demonstrate the practicability of single-tissue MS-based proteomic analysis in small organisms and in its future utility.	6	2007	Tan CH	Tan CH, Wang TY, Park H, Lomenick B, Chou TF, Sternberg PW	Single-tissue proteomics in <i>Caenorhabditis elegans</i> reveals proteins resident in intestinal lysosome-related organelles.	Proc Natl Acad Sci U S A	2024	MassSpec_WBPaper00066880:F10_WT-G~MassSpec_WBPaper00066880:F11_WT-G~MassSpec_WBPaper00066880:F12_WT-G~MassSpec_WBPaper00066880:F7_WT-I~MassSpec_WBPaper00066880:F8_WT-I~MassSpec_WBPaper00066880:F9_WT-I	Method: proteomics|Species: Caenorhabditis elegans|Tissue Specific
388	39173071	WBPaper00067175.ce.ms.paper	N.A.	N.A.	1	A conserved protein tyrosine phosphatase, PTPN-22, functions in diverse developmental processes in C. elegans.	Protein tyrosine phosphatases non-receptor type (PTPNs) have been studied extensively in the context of the adaptive immune system; however, their roles beyond immunoregulation are less well explored. Here we identify novel functions for the conserved C. elegans phosphatase PTPN-22, establishing its role in nematode molting, cell adhesion, and cytoskeletal regulation. Through a non-biased genetic screen, we found that loss of PTPN-22 phosphatase activity suppressed molting defects caused by loss-of-function mutations in the conserved NIMA-related kinases NEKL-2 (human NEK8/NEK9) and NEKL-3 (human NEK6/NEK7), which act at the interface of membrane trafficking and actin regulation. To better understand the functions of PTPN-22, we carried out proximity labeling studies to identify candidate interactors of PTPN-22 during development. Through this approach we identified the CDC42 guanine-nucleotide exchange factor DNBP-1 (human DNMBP) as an in vivo partner of PTPN-22. Consistent with this interaction, loss of DNBP-1 also suppressed nekl-associated molting defects. Genetic analysis, co-localization studies, and proximity labeling revealed roles for PTPN-22 in several epidermal adhesion complexes, including C. elegans hemidesmosomes, suggesting that PTPN-22 plays a broad role in maintaining the structural integrity of tissues. Localization and proximity labeling also implicated PTPN-22 in functions connected to nucleocytoplasmic transport and mRNA regulation, particularly within the germline, as nearly one-third of proteins identified by PTPN-22 proximity labeling are known P granule components. Collectively, these studies highlight the utility of combined genetic and proteomic approaches for identifying novel gene functions.	8	2263	Binti S	Binti S, Linder AG, Edeen PT, Fay DS	A conserved protein tyrosine phosphatase, PTPN-22, functions in diverse developmental processes in C. elegans.	PLoS Genet	2024	MassSpec_WBPaper00067175:N2_rep1~MassSpec_WBPaper00067175:N2_rep2~MassSpec_WBPaper00067175:N2_rep3~MassSpec_WBPaper00067175:N2_rep4~MassSpec_WBPaper00067175:PTPN-22-TurboID_rep1~MassSpec_WBPaper00067175:PTPN-22-TurboID_rep2~MassSpec_WBPaper00067175:PTPN-22-TurboID_rep3~MassSpec_WBPaper00067175:PTPN-22-TurboID_rep4	Method: proteomics|Species: Caenorhabditis elegans
389	39083540	WBPaper00067340.ce.ms.paper	N.A.	N.A.	1	Floxuridine supports UPS independent of germline signaling and proteostasis regulators via involvement of detoxification in C. elegans.	The ubiquitin-proteasome system (UPS) is critical for maintaining proteostasis, influencing stress resilience, lifespan, and thermal adaptability in organisms. In Caenorhabditis elegans, specific proteasome subunits and activators, such as RPN-6, PBS-6, and PSME-3, are associated with heat resistance, survival at cold (4&#xb0;C), and enhanced longevity at moderate temperatures (15&#xb0;C). Previously linked to improving proteostasis, we investigated the impact of sterility-inducing floxuridine (FUdR) on UPS functionality under proteasome dysfunction and its potential to improve cold survival. Our findings reveal that FUdR significantly enhances UPS activity and resilience during proteasome inhibition or subunit deficiency, supporting worms' normal lifespan and adaptation to cold. Importantly, FUdR effect on UPS activity occurs independently of major proteostasis regulators and does not rely on the germ cells proliferation or spermatogenesis. Instead, FUdR activates a distinct detoxification pathway that supports UPS function, with GST-24 appearing to be one of the factors contributing to the enhanced activity of the UPS upon knockdown of the SKN-1-mediated proteasome surveillance pathway. Our study highlights FUdR unique role in the UPS modulation and its crucial contribution to enhancing survival under low-temperature stress, providing new insights into its mechanisms of action and potential therapeutic applications.	8	5898	Dubey AA	Dubey AA, Sarkar A, Milcz K, Szulc NA, Thapa P, Piechota M, Serwa RA, Pokrzywa W	Floxuridine supports UPS independent of germline signaling and proteostasis regulators via involvement of detoxification in C. elegans.	PLoS Genet	2024	MassSpec_WBPaper00067340:N2_rep1~MassSpec_WBPaper00067340:N2_rep2~MassSpec_WBPaper00067340:N2_rep3~MassSpec_WBPaper00067340:N2_FUdR_rep1~MassSpec_WBPaper00067340:N2_FUdR_rep2~MassSpec_WBPaper00067340:N2_FUdR_rep3~MassSpec_WBPaper00067340:glp-1(e2144)_rep1~MassSpec_WBPaper00067340:glp-1(e2144)_rep2	Method: proteomics|Species: Caenorhabditis elegans
390	18204455	WBPaper00031443.ce.rs.paper	N.A.	N.A.	1	Whole-genome sequencing and variant discovery in C. elegans.	Massively parallel sequencing instruments enable rapid and inexpensive DNA sequence data production. Because these instruments are new, their data require characterization with respect to accuracy and utility. To address this, we sequenced a Caernohabditis elegans N2 Bristol strain isolate using the Solexa Sequence Analyzer, and compared the reads to the reference genome to characterize the data and to evaluate coverage and representation. Massively parallel sequencing facilitates strain-to-reference comparison for genome-wide sequence variant discovery. Owing to the short-read-length sequences produced, we developed a revised approach to determine the regions of the genome to which short reads could be uniquely mapped. We then aligned Solexa reads from C. elegans strain CB4858 to the reference, and screened for single-nucleotide polymorphisms (SNPs) and small indels. This study demonstrates the utility of massively parallel short read sequencing for whole genome resequencing and for accurate discovery of genome-wide polymorphisms.	5	46405	Hillier LW	Hillier LW, Marth GT, Quinlan AR, Dooling D, Fewell G, Barnett D, Fox P, Glasscock JI, Hickenbotham M, Huang W, Magrini VJ, Richt RJ, Sander SN, Stewart DA, Stromberg M, Tsung EF, Wylie T, Schedl T, Wilson RK, Mardis ER	Whole-genome sequencing and variant discovery in C. elegans.	Nat Methods	2008	RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP000244.SRX029428~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP000244.SRX029429~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP000244.SRX029430~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP000244.SRX029431~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP000244.SRX029432	Method: RNAseq|Species: Caenorhabditis elegans
391	18611272	WBPaper00032006.ce.rs.paper	N.A.	N.A.	1	Transcriptome analysis for Caenorhabditis elegans based on novel expressed sequence tags.	ABSTRACT: BACKGROUND: We have applied a high-throughput pyrosequencing technology for transcriptome profiling of Caenorhabditis elegans in its first larval stage. Using this approach, we have generated a large amount of data for expressed sequence tags, which provides an opportunity for the discovery of putative novel transcripts and alternative splice variants that could be developmentally specific to the first larval stage. This work also demonstrates the successful and efficient application of a next generation sequencing methodology. RESULTS: We have generated over 30 million bases of novel expressed sequence tags from first larval stage worms utilizing high-throughput sequencing technology. We have shown that approximately 14% of the newly sequenced expressed sequence tags map completely or partially to genomic regions where there are no annotated genes or splice variants and therefore, imply that these are novel genetic structures. Expressed sequence tags, which map to intergenic (around 1000) and intronic regions (around 580), may represent novel transcribed regions, such as unannotated or unrecognized small protein-coding or non-protein-coding genes or splice variants. Expressed sequence tags, which map across intron-exon boundaries (around 300), indicate possible alternative splice sites, while expressed sequence tags, which map near the ends of known transcripts (around 600), suggest extension of the coding or untranslated regions. We have also discovered that intergenic and intronic expressed sequence tags, which are well conserved across different nematode species, are likely to represent non-coding RNAs. Lastly, we have incorporated available serial analysis of gene expression data generated from first larval stage worms, in order to predict novel transcripts that might be specifically or predominantly expressed in the first larval stage. CONCLUSIONS: We have demonstrated the use of a high-throughput sequencing methodology to efficiently produce a snap-shot of transcriptional activities occurring in the first larval stage of C. elegans development. Such application of this new sequencing technique allows for high-throughput, genome-wide experimental verification of known and novel transcripts. This study provides a more complete C. elegans transcriptome profile and, furthermore, gives insight into the evolutionary and biological complexity of this organism.	1	47156	Shin H	Shin H, Hirst M, Bainbridge M, Magrini V, Mardis E, Moerman DG, Marra MA, Baillie DL, Jones SJ	Transcriptome analysis for Caenorhabditis elegans based on novel expressed sequence tags.	BMC Biol	2008	RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP000253.SRX017684	Method: RNAseq|Species: Caenorhabditis elegans
392	20980554	WBPaper00037732.ce.rs.paper	N.A.	N.A.	1	Scaffolding a Caenorhabditis nematode genome with RNA-seq.	Efficient sequencing of animal and plant genomes by next-generation technology should allow many neglected organisms of biological and medical importance to be better understood. As a test case, we have assembled a draft genome of Caenorhabditis sp. 3 PS1010 through a combination of direct sequencing and scaffolding with RNA-seq. We first sequenced genomic DNA and mixed-stage cDNA using paired 75-nt reads from an Illumina GAII. A set of 230 million genomic reads yielded an 80-Mb assembly, with a supercontig N50 of 5.0 kb, covering 90% of 429 kb from previously published genomic contigs. Mixed-stage poly(A)(+) cDNA gave 47.3 million mappable 75-mers (including 5.1 million spliced reads), which separately assembled into 17.8 Mb of cDNA, with an N50 of 1.06 kb. By further scaffolding our genomic supercontigs with cDNA, we increased their N50 to 9.4 kb, nearly double the average gene size in C. elegans. We predicted 22,851 protein-coding genes, and detected expression in 78% of them. Multigenome alignment and data filtering identified 2672 DNA elements conserved between PS1010 and C. elegans that are likely to encode regulatory sequences or previously unknown ncRNAs. Genomic and cDNA sequencing followed by joint assembly is a rapid and useful strategy for biological analysis.	2	47144	Mortazavi A	Mortazavi A, Schwarz EM, Williams B, Schaeffer L, Antoshechkin I, Wold BJ, Sternberg PW	Scaffolding a Caenorhabditis nematode genome with RNA-seq.	Genome Res	2010	RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP003492.SRX026728~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP003492.SRX026729	Method: RNAseq|Species: Caenorhabditis elegans
393	21177965	WBPaper00037948.ce.rs.paper	GSE22410	GPL9269	1	Multimodal RNA-seq using single-strand, double-strand, and CircLigase-based capture yields a refined and extended description of the C. elegans transcriptome.	We have used a combination of three high-throughput RNA capture and sequencing methods to refine and augment the transcriptome map of a well-studied genetic model, Caenorhabditis elegans. The three methods include a standard (non-directional) library preparation protocol relying on cDNA priming and foldback that has been used in several previous studies for transcriptome characterization in this species, and two directional protocols, one involving direct capture of single-stranded RNA fragments and one involving circular-template PCR (CircLigase). We find that each RNA-seq approach shows specific limitations and biases, with the application of multiple methods providing a more complete map than was obtained from any single method. Of particular note in the analysis were substantial advantages of CircLigase-based and ssRNA-based capture for defining sequences and structures of the precise 5' ends (which were lost using the double-strand cDNA capture method). Of the three methods, ssRNA capture was most effective in defining sequences to the poly(A) junction. Using data sets from a spectrum of C. elegans strains and stages and the UCSC Genome Browser, we provide a series of tools, which facilitate rapid visualization and assignment of gene structures.	15	47143	Lamm AT	Lamm AT, Stadler MR, Zhang H, Gent JI, Fire AZ	Multimodal RNA-seq using single-strand, double-strand, and CircLigase-based capture yields a refined and extended description of the C. elegans transcriptome.	Genome Res	2011	RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP003783.SRX028190~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP003783.SRX028191~RNASeq.elegans.WBStrain00022523.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP003783.SRX028192~RNASeq.elegans.WBStrain00000364.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP003783.SRX028193~RNASeq.elegans.WBStrain00030567.WBls:0000002.Male.WBbt:0007833.SRP003783.SRX028194~RNASeq.elegans.WBStrain00030567.WBls:0000002.Male.WBbt:0007833.SRP003783.SRX028195~RNASeq.elegans.WBStrain00030566.WBls:0000038.Male.WBbt:0007833.SRP003783.SRX028196~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP003783.SRX028197~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP003783.SRX028198~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP003783.SRX028199~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP003783.SRX028200~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP003783.SRX028201~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP003783.SRX028202~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP003783.SRX028203~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP003783.SRX028204	Method: RNAseq|Species: Caenorhabditis elegans
394	21177976	WBPaper00037953.ce.rs.paper	GSE25785,GSE25786,GSE25788,GSE25789,GSE25790,GSE25791,GSE25792,GSE25793,GSE25794,GSE25795,GSE25798,GSE25800,GSE25801,GSE25802,GSE25803,GSE25804,GSE25805,GSE25808,GSE25809,GSE25810,GSE25811	GPL9309	1	Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.	We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.	246	47109	Gerstein MB	Gerstein MB, Lu ZJ, Van Nostrand EL, Cheng C, Arshinoff BI, Liu T, Yip KY, Robilotto R, Rechtsteiner A, Ikegami K, Alves P, Chateigner A, Perry M, Morris M, Auerbach RK, Feng X, Leng J, Vielle A, Niu W, Rhrissorrakrai K, Agarwal A, Alexander RP, Barber G, Brdlik CM, Brennan J, Brouillet JJ, Carr A, Cheung MS, Clawson H, Contrino S, Dannenberg LO, Dernburg AF, Desai A, Dick L, Dose AC, Du J, Egelhofer T, Ercan S, Euskirchen G, Ewing B, Feingold EA, Gassmann R, Good PJ, Green P, Gullier F, Gutwein M, Guyer MS, Habegger L, Han T, Henikoff JG, Henz SR, Hinrichs A, Holster H, Hyman T, Iniguez AL, Janette J, Jensen M, Kato M, Kent WJ, Kephart E, Khivansara V, Khurana E, Kim JK, Kolasinska-Zwierz P, Lai EC, Latorre I, Leahey A, Lewis S, Lloyd P, Lochovsky L, Lowdon RF, Lubling Y, Lyne R, MacCoss M, Mackowiak SD, Mangone M, McKay S, Mecenas D, Merrihew G, Miller DM, Muroyama A, Murray JI, Ooi SL, Pham H, Phippen T, Preston EA, Rajewsky N, Ratsch G, Rosenbaum H, Rozowsky J, Rutherford K, Ruzanov P, Sarov M, Sasidharan R, Sboner A, Scheid P, Segal E, Shin H, Shou C, Slack FJ, Slightam C, Smith R, Spencer WC, Stinson EO, Taing S, Takasaki T, Vafeados D, Voronina K, Wang G, Washington NL, Whittle CM, Wu B, Yan KK, Zeller G, Zha Z, Zhong M, Zhou X, Ahringer J, Strome S, Gunsalus KC, Micklem G, Liu XS, Reinke V, Kim SK, Hillier LW, Henikoff S, Piano F, Snyder M, Stein L, Lieb JD, Waterston RH	Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.	Science	2010	RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP000401.SRX001872~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP000401.SRX001873~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP000401.SRX001874~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP000401.SRX001875~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX004863~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX004864~RNASeq.elegans.WBStrain00000001.WBls:0000021.Hermaphrodite.WBbt:0007833.SRP000401.SRX004865~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX004866~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP000401.SRX004867~RNASeq.elegans.WBStrain00004578.WBls:0000038.Male.WBbt:0007833.SRP000401.SRX004868~RNASeq.elegans.WBStrain00027375.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP000401.SRX004869~RNASeq.elegans.WBStrain00000377.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP000401.SRX008136~RNASeq.elegans.WBStrain00004309.WBls:0000032.Hermaphrodite.WBbt:0007833.SRP000401.SRX008138~RNASeq.elegans.WBStrain00004309.WBls:0000031.Hermaphrodite.WBbt:0007833.SRP000401.SRX008139~RNASeq.elegans.WBStrain00004309.WBls:0000052.Hermaphrodite.WBbt:0007833.SRP000401.SRX008140~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP000401.SRX008144~RNASeq.elegans.WBStrain00004346.WBls:0000003.Male.WBbt:0007833.SRP000401.SRX011569~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP000401.SRX014006~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP000401.SRX014007~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP000401.SRX014008~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP000401.SRX014009~RNASeq.elegans.WBStrain00022538.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP000401.SRX014010~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP000401.SRX035162~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP000401.SRX036881~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP000401.SRX036882~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP000401.SRX036967~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP000401.SRX036969~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP000401.SRX036970~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX037186~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX037197~RNASeq.elegans.WBStrain00004346.WBls:0000003.Male.WBbt:0007833.SRP000401.SRX037198~RNASeq.elegans.WBStrain00004309.WBls:0000052.Hermaphrodite.WBbt:0007833.SRP000401.SRX037199~RNASeq.elegans.WBStrain00022538.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP000401.SRX037200~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP000401.SRX037288~RNASeq.elegans.WBStrain00000001.WBls:0000021.Hermaphrodite.WBbt:0007833.SRP000401.SRX047446~RNASeq.elegans.WBStrain00000001.WBls:0000038.Male.WBbt:0007833.SRP000401.SRX047469~RNASeq.elegans.WBStrain00004309.WBls:0000031.Hermaphrodite.WBbt:0007833.SRP000401.SRX047470~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP000401.SRX047635~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP000401.SRX047653~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP000401.SRX047787~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP000401.SRX049268~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP000401.SRX049269~RNASeq.elegans.WBStrain00000001.WBls:0000021.Hermaphrodite.WBbt:0007833.SRP000401.SRX049270~RNASeq.elegans.WBStrain00027375.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP000401.SRX049744~RNASeq.elegans.WBStrain00000001.WBls:0000038.Male.WBbt:0007833.SRP000401.SRX049745~RNASeq.elegans.WBStrain00027375.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP000401.SRX050610~RNASeq.elegans.WBStrain00000001.WBls:0000038.Male.WBbt:0007833.SRP000401.SRX050630~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX085111~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX085112~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX085217~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX085218~RNASeq.elegans.WBStrain00000001.WBls:0000008.Hermaphrodite.WBbt:0007833.SRP000401.SRX085219~RNASeq.elegans.WBStrain00000001.WBls:0000008.Hermaphrodite.WBbt:0007833.SRP000401.SRX085220~RNASeq.elegans.WBStrain00000001.WBls:0000021.Hermaphrodite.WBbt:0005451.SRP000401.SRX085286~RNASeq.elegans.WBStrain00000001.WBls:0000021.Hermaphrodite.WBbt:0005451.SRP000401.SRX085287~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX092371~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX092372~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX092477~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX092478~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX092479~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX092480~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX099901~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX099902~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX099907~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX099908~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX099915~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX099973~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX099974~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX099975~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX099976~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX099977~RNASeq.elegans.WBStrain00000001.WBls:0000021.Hermaphrodite.WBbt:0007833.SRP000401.SRX099978~RNASeq.elegans.WBStrain00000001.WBls:0000021.Hermaphrodite.WBbt:0007833.SRP000401.SRX099979~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX099980~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX099981~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX099982~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX099983~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX099984~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX099985~RNASeq.elegans.WBStrain00000001.WBls:0000013.Hermaphrodite.WBbt:0007833.SRP000401.SRX099986~RNASeq.elegans.WBStrain00000001.WBls:0000013.Hermaphrodite.WBbt:0007833.SRP000401.SRX099987~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX099988~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX099989~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX099990~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX099991~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX099992~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX099993~RNASeq.elegans.WBStrain00000001.WBls:0000021.Hermaphrodite.WBbt:0007833.SRP000401.SRX099994~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX099995~RNASeq.elegans.WBStrain00000001.WBls:0000013.Hermaphrodite.WBbt:0007833.SRP000401.SRX099996~RNASeq.elegans.WBStrain00000001.WBls:0000013.Hermaphrodite.WBbt:0007833.SRP000401.SRX099997~RNASeq.elegans.WBStrain00000001.WBls:0000013.Hermaphrodite.WBbt:0007833.SRP000401.SRX099998~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX099999~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX100000~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX100001~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX100002~RNASeq.elegans.WBStrain00004309.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX100003~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX100004~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX100005~RNASeq.elegans.WBStrain00000001.WBls:0000021.Hermaphrodite.WBbt:0007833.SRP000401.SRX100006~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP000401.SRX100631~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP000401.SRX100633~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX100819~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX1020630~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX1020631~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX1020633~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1020634~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1020635~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1020636~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1020637~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1020638~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1020639~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1020640~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1020641~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022568~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022569~RNASeq.elegans.WBStrain00000001.WBls:0000013.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022570~RNASeq.elegans.WBStrain00000001.WBls:0000013.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022571~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022572~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022573~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022575~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022576~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022578~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022579~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022580~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022581~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022582~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022583~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022585~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022586~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022587~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022588~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022589~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022592~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022593~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022596~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022597~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022598~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022599~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022600~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022601~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022602~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022603~RNASeq.elegans.WBStrain00000001.WBls:0000013.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022604~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022605~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022607~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022608~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022609~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022610~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022611~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022645~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022646~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022647~RNASeq.elegans.WBStrain00000001.WBls:0000013.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022648~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022649~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022651~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022652~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022653~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX1022654~RNASeq.elegans.WBStrain00004309.WBls:0000052.Hermaphrodite.WBbt:0007833.SRP000401.SRX103269~RNASeq.elegans.WBStrain00004309.WBls:0000052.Hermaphrodite.WBbt:0007833.SRP000401.SRX103270~RNASeq.elegans.WBStrain00004309.WBls:0000052.Hermaphrodite.WBbt:0007833.SRP000401.SRX103271~RNASeq.elegans.WBStrain00004309.WBls:0000052.Hermaphrodite.WBbt:0007833.SRP000401.SRX103272~RNASeq.elegans.WBStrain00004309.WBls:0000031.Hermaphrodite.WBbt:0007833.SRP000401.SRX103273~RNASeq.elegans.WBStrain00004309.WBls:0000031.Hermaphrodite.WBbt:0007833.SRP000401.SRX103274~RNASeq.elegans.WBStrain00004309.WBls:0000031.Hermaphrodite.WBbt:0007833.SRP000401.SRX103275~RNASeq.elegans.WBStrain00004309.WBls:0000031.Hermaphrodite.WBbt:0007833.SRP000401.SRX103276~RNASeq.elegans.WBStrain00004309.WBls:0000031.Hermaphrodite.WBbt:0007833.SRP000401.SRX103277~RNASeq.elegans.WBStrain00004309.WBls:0000052.Hermaphrodite.WBbt:0007833.SRP000401.SRX103278~RNASeq.elegans.WBStrain00004309.WBls:0000052.Hermaphrodite.WBbt:0007833.SRP000401.SRX103279~RNASeq.elegans.WBStrain00004309.WBls:0000052.Hermaphrodite.WBbt:0007833.SRP000401.SRX103280~RNASeq.elegans.WBStrain00004309.WBls:0000052.Hermaphrodite.WBbt:0007833.SRP000401.SRX103281~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX103649~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX103650~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX103651~RNASeq.elegans.WBStrain00000001.WBls:0000013.Hermaphrodite.WBbt:0007833.SRP000401.SRX103652~RNASeq.elegans.WBStrain00000001.WBls:0000013.Hermaphrodite.WBbt:0007833.SRP000401.SRX103653~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX103669~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX103670~RNASeq.elegans.WBStrain00000001.WBls:0000020.Hermaphrodite.WBbt:0007833.SRP000401.SRX103671~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX103672~RNASeq.elegans.WBStrain00000001.WBls:0000015.Hermaphrodite.WBbt:0007833.SRP000401.SRX103673~RNASeq.elegans.WBStrain00000001.WBls:0000014.Hermaphrodite.WBbt:0007833.SRP000401.SRX103677~RNASeq.elegans.WBStrain00004030.WBls:0000004.Hermaphrodite.WBbt:0006746.SRP000401.SRX1037996~RNASeq.elegans.WBStrain00006127.WBls:0000021.Hermaphrodite.WBbt:0005733.SRP000401.SRX1037998~RNASeq.elegans.WBStrain00006127.WBls:0000021.Hermaphrodite.WBbt:0005733.SRP000401.SRX1038000~RNASeq.elegans.WBStrain00006127.WBls:0000021.Hermaphrodite.WBbt:0005733.SRP000401.SRX1038001~RNASeq.elegans.WBStrain00004309.WBls:0000032.Hermaphrodite.WBbt:0007833.SRP000401.SRX103983~RNASeq.elegans.WBStrain00004309.WBls:0000032.Hermaphrodite.WBbt:0007833.SRP000401.SRX103984~RNASeq.elegans.WBStrain00004309.WBls:0000032.Hermaphrodite.WBbt:0007833.SRP000401.SRX103985~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP000401.SRX103986~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP000401.SRX103987~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP000401.SRX103988~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP000401.SRX103989~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP000401.SRX103990~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP000401.SRX103991~RNASeq.elegans.WBStrain00034458.WBls:0000004.Hermaphrodite.WBbt:0006849.SRP000401.SRX1041553~RNASeq.elegans.WBStrain00034458.WBls:0000004.Hermaphrodite.WBbt:0006849.SRP000401.SRX1041554~RNASeq.elegans.WBStrain00027573.WBls:0000004.Hermaphrodite.WBbt:0006825.SRP000401.SRX1041557~RNASeq.elegans.WBStrain00028689.WBls:0000021.Hermaphrodite.WBbt:0005840.SRP000401.SRX1041558~RNASeq.elegans.WBStrain00028689.WBls:0000021.Hermaphrodite.WBbt:0005840.SRP000401.SRX1041559~RNASeq.elegans.WBStrain00034458.WBls:0000004.Hermaphrodite.WBbt:0006849.SRP000401.SRX1041561~RNASeq.elegans.WBStrain00034458.WBls:0000004.Hermaphrodite.WBbt:0006849.SRP000401.SRX1041562~RNASeq.elegans.WBStrain00027573.WBls:0000004.Hermaphrodite.WBbt:0006825.SRP000401.SRX1041564~RNASeq.elegans.WBStrain00028689.WBls:0000021.Hermaphrodite.WBbt:0005840.SRP000401.SRX1041571~RNASeq.elegans.WBStrain00028689.WBls:0000021.Hermaphrodite.WBbt:0005840.SRP000401.SRX1041572~RNASeq.elegans.WBStrain00028688.WBls:0000038.Hermaphrodite.WBbt:0003670.SRP000401.SRX1041641~RNASeq.elegans.WBStrain00028685.WBls:0000021.Hermaphrodite.WBbt:0006819.SRP000401.SRX1041642~RNASeq.elegans.WBStrain00028685.WBls:0000021.Hermaphrodite.WBbt:0006819.SRP000401.SRX1041643~RNASeq.elegans.WBStrain00028688.WBls:0000038.Hermaphrodite.WBbt:0003670.SRP000401.SRX1041644~RNASeq.elegans.WBStrain00028685.WBls:0000021.Hermaphrodite.WBbt:0006819.SRP000401.SRX1041646~RNASeq.elegans.WBStrain00028685.WBls:0000021.Hermaphrodite.WBbt:0006819.SRP000401.SRX1041647~RNASeq.elegans.WBStrain00007725.WBls:0000004.Hermaphrodite.WBbt:0003670.SRP000401.SRX1041666~RNASeq.elegans.WBStrain00028688.WBls:0000038.Hermaphrodite.WBbt:0003670.SRP000401.SRX1041748~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP000401.SRX139566~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0005409.SRP000401.SRX139567~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP000401.SRX139591~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0005409.SRP000401.SRX139592~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0003666.SRP000401.SRX139602~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0005409.SRP000401.SRX139603~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0003679.SRP000401.SRX145443~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP000401.SRX145444~RNASeq.elegans.WBStrain00026383.WBls:0000024.Hermaphrodite.WBbt:0003666.SRP000401.SRX145445~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0003679.SRP000401.SRX145446~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP000401.SRX145447~RNASeq.elegans.WBStrain00000001.WBls:0000008.Hermaphrodite.WBbt:0007833.SRP000401.SRX145480~RNASeq.elegans.WBStrain00000001.WBls:0000010.Hermaphrodite.WBbt:0005772.SRP000401.SRX145482~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX145486~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX145660~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP000401.SRX145661~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX151597~RNASeq.elegans.WBStrain00006450.WBls:0000003.Hermaphrodite.WBbt:0008378.SRP000401.SRX151598~RNASeq.elegans.WBStrain00029126.WBls:0000024.Hermaphrodite.WBbt:0003679.SRP000401.SRX151599~RNASeq.elegans.WBStrain00029126.WBls:0000024.Hermaphrodite.WBbt:0003679.SRP000401.SRX151602~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP000401.SRX151607~RNASeq.elegans.WBStrain00026383.WBls:0000024.Hermaphrodite.WBbt:0003666.SRP000401.SRX151617~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0005175.SRP000401.SRX151618~RNASeq.elegans.WBStrain00006450.WBls:0000003.Hermaphrodite.WBbt:0008378.SRP000401.SRX190363~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX190364~RNASeq.elegans.WBStrain00029126.WBls:0000024.Hermaphrodite.WBbt:0003679.SRP000401.SRX190365~RNASeq.elegans.WBStrain00029126.WBls:0000024.Hermaphrodite.WBbt:0003679.SRP000401.SRX190366~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0005175.SRP000401.SRX190367~RNASeq.elegans.WBStrain00026383.WBls:0000024.Hermaphrodite.WBbt:0003666.SRP000401.SRX190368~RNASeq.elegans.WBStrain00000001.WBls:0000004.Hermaphrodite.WBbt:0007833.SRP000401.SRX190369~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP000401.SRX190370~RNASeq.elegans.WBStrain00026383.WBls:0000024.Hermaphrodite.WBbt:0003666.SRP000401.SRX732432	Method: RNAseq|Species: Caenorhabditis elegans|Tissue Specific
395	21396820	WBPaper00038226.ce.rs.paper	N.A.	N.A.	1	EGO-1, a C. elegans RdRP, modulates gene expression via production of mRNA-templated short antisense RNAs.	BACKGROUND: The development of the germline in Caenorhabditis elegans is a complex process involving the regulation of thousands of genes in a coordinated manner. Several genes required for small RNA biogenesis and function are among those required for the proper organization of the germline. EGO-1 is a putative RNA-directed RNA polymerase (RdRP) that is required for multiple aspects of C. elegans germline development and efficient RNA interference (RNAi) of germline-expressed genes. RdRPs have been proposed to act through a variety of mechanisms, including the posttranscriptional targeting of specific mRNAs, as well as through a direct interaction with chromatin. Despite extensive investigation, the molecular role of EGO-1 has remained enigmatic. RESULTS: Here we use high-throughput small RNA and messenger RNA sequencing to investigate EGO-1 function. We found that EGO-1 is required to produce a distinct pool of small RNAs antisense to a number of germline-expressed mRNAs through several developmental stages. These potential mRNA targets fall into distinct classes, including genes required for kinetochore and nuclear pore assembly, histone-modifying activities, and centromeric proteins. We also found several RNAi-related genes to be targets of EGO-1. Finally, we show a strong association between the loss of small RNAs and the rise of mRNA levels in ego-1(-) animals. CONCLUSIONS: Our data support the conclusion that EGO-1 produces triphosphorylated small RNAs derived from mRNA templates and that these small RNAs modulate gene expression through the targeting of their cognate mRNAs.	16	47156	Maniar JM	Maniar JM, Fire AZ	EGO-1, a C. elegans RdRP, modulates gene expression via production of mRNA-templated short antisense RNAs.	Curr Biol	2011	RNASeq.elegans.WBStrain00030624.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP005562.SRX040314~RNASeq.elegans.WBStrain00030624.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP005562.SRX040315~RNASeq.elegans.WBStrain00030625.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP005562.SRX040316~RNASeq.elegans.WBStrain00030625.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP005562.SRX040317~RNASeq.elegans.WBStrain00030624.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP005562.SRX040318~RNASeq.elegans.WBStrain00030624.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP005562.SRX040319~RNASeq.elegans.WBStrain00030625.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP005562.SRX040320~RNASeq.elegans.WBStrain00030625.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP005562.SRX040321~RNASeq.elegans.WBStrain00030624.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP005562.SRX040322~RNASeq.elegans.WBStrain00030624.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP005562.SRX040323~RNASeq.elegans.WBStrain00030624.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP005562.SRX040324~RNASeq.elegans.WBStrain00030624.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP005562.SRX040325~RNASeq.elegans.WBStrain00030625.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP005562.SRX040326~RNASeq.elegans.WBStrain00030625.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP005562.SRX040327~RNASeq.elegans.WBStrain00030625.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP005562.SRX040328~RNASeq.elegans.WBStrain00030625.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP005562.SRX040329	Method: RNAseq|Species: Caenorhabditis elegans
396	22045228	WBPaper00040379.ce.rs.paper	N.A.	N.A.	1	Wobble base-pairing slows in vivo translation elongation in metazoans.	In the universal genetic code, most amino acids can be encoded by multiple trinucleotide codons, and the choice among available codons can influence position-specific translation elongation rates. By using sequence-based ribosome profiling, we obtained transcriptome-wide profiles of in vivo ribosome occupancy as a function of codon identity in Caenorhabditis elegans and human cells. Particularly striking in these profiles was a universal trend of higher ribosome occupancy for codons translated via G:U wobble base-pairing compared with synonymous codons that pair with the same tRNA family using G:C base-pairing. These data support a model in which ribosomal translocation is slowed at wobble codon positions.	16	47152	Stadler M	Stadler M, Fire A	Wobble base-pairing slows in vivo translation elongation in metazoans.	RNA	2011	RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP010374.SRX116361~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP010374.SRX116363~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP010374.SRX118116~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP010374.SRX118117~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP010374.SRX118118~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP010374.SRX118119~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP010374.SRX118120~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP010374.SRX118124~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP010374.SRX118125~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP010374.SRX118126~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP010374.SRX118127~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP010374.SRX118128~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP010374.SRX118139~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP010374.SRX118140~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP010374.SRX118143~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP010374.SRX118144	Method: RNAseq|Species: Caenorhabditis elegans
397	22482728	WBPaper00040959.ce.rs.paper	GSE36041	GPL13776	1	Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal.	Impaired insulin and IGF-1 signaling (iIIS) in C.elegans daf-2 mutants extends life span more than 2-fold. Constitutively, iIIS increases mitochondrial activity and reduces reactive oxygen species (ROS) levels. By contrast, acute impairment of daf-2 in adult C.elegans reduces glucose uptake and transiently increases ROS. Consistent with the concept ofmitohormesis, this ROS signal causes an adaptive response by inducing ROS defense enzymes (SOD, catalase), culminating in ultimately reduced ROS levels despite increased mitochondrial activity. Inhibition of this ROS signal by antioxidants reduces iIIS-mediated longevity by up to 60%. Induction of the ROS signal requires AAK-2 (AMPK), while PMK-1 (p38) and SKN-1 (NRF-2) are needed for the retrograde response. IIIS upregulates mitochondrial L-proline catabolism, and impairment of the latter impairs the life span-extending capacity of iIIS while L-proline supplementation extends C.elegans life span. Taken together, iIIS promotes L-proline metabolism to generate a ROS signal for the adaptive induction of endogenous stress defense to extend life span.	6	47121	Zarse K	Zarse K, Schmeisser S, Groth M, Priebe S, Beuster G, Kuhlow D, Guthke R, Platzer M, Kahn CR, Ristow M	Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal.	Cell Metab	2012	RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP011038.SRX121891~RNASeq.elegans.WBStrain00012787.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP011038.SRX121892~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP011038.SRX121893~RNASeq.elegans.WBStrain00012787.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP011038.SRX121894~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP011038.SRX121895~RNASeq.elegans.WBStrain00012787.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP011038.SRX121896	Method: RNAseq|Species: Caenorhabditis elegans
398	22539650	WBPaper00041010.ce.rs.paper	GSE33023	GPL14752	1	Nutritional control of mRNA isoform expression during developmental arrest and recovery in C. elegans.	Nutrient availability profoundly influences gene expression. Many animal genes encode multiple transcript isoforms, yet the effect of nutrient availability on transcript isoform expression has not been studied in genome-wide fashion. When Caenorhabditis elegans larvae hatch without food, they arrest development in the first larval stage (L1 arrest). Starved larvae can survive L1 arrest for weeks, but growth and post-embryonic development are rapidly initiated in response to feeding. We used RNA-seq to characterize the transcriptome during L1 arrest and over time after feeding. Twenty-seven percent of detectable protein-coding genes were differentially expressed during recovery from L1 arrest, with the majority of changes initiating within the first hour, demonstrating widespread, acute effects of nutrient availability on gene expression. We used two independent approaches to track expression of individual exons and mRNA isoforms, and we connected changes in expression to functional consequences by mining a variety of databases. These two approaches identified an overlapping set of genes with alternative isoform expression, and they converged on common functional patterns. Genes affecting mRNA splicing and translation are regulated by alternative isoform expression, revealing post-transcriptional consequences of nutrient availability on gene regulation. We also found that phosphorylation sites are often alternatively expressed, revealing a common mode by which alternative isoform expression modifies protein function and signal transduction. Our results detail rich changes in C. elegans gene expression as larvae initiate growth and post-embryonic development, and they provide an excellent resource for ongoing investigation of transcriptional regulation and developmental physiology.	10	47150	Maxwell C	Maxwell C, Antoshechkin I, Kurhanewicz N, Belsky J, Baugh LR	Nutritional control of mRNA isoform expression during developmental arrest and recovery in C. elegans.	Genome Res	2012	RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP008969.SRX101381~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP008969.SRX101382~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP008969.SRX101383~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP008969.SRX101384~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP008969.SRX101385~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP008969.SRX101386~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP008969.SRX101387~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP008969.SRX101388~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP008969.SRX101389~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP008969.SRX101390	Method: RNAseq|Species: Caenorhabditis elegans
399	22614838	WBPaper00041119.ce.rs.paper	GSE40507	GPL13776	1	Multiple insert size paired-end sequencing for deconvolution of complex transcriptomes.	Deep sequencing of transcriptomes allows quantitative and qualitative analysis of many RNA species in a sample, with parallel comparison of expression levels, splicing variants, natural antisense transcripts, RNA editing and transcriptional start and stop sites the ideal goal. By computational modeling, we show how libraries of multiple insert sizes combined with strand-specific, paired-end (SS-PE) sequencing can increase the information gained on alternative splicing, especially in higher eukaryotes. Despite the benefits of gaining SS-PE data with paired ends of varying distance, the standard Illumina protocol allows only non-strand-specific, paired-end sequencing with a single insert size. Here, we modify the Illumina RNA ligation protocol to allow SS-PE sequencing by using a custom pre-adenylated 3' adaptor. We generate parallel libraries with differing insert sizes to aid deconvolution of alternative splicing events and to characterize the extent and distribution of natural antisense transcription in C. elegans. Despite stringent requirements for detection of alternative splicing, our data increases the number of intron retention and exon skipping events annotated in the Wormbase genome annotations by 127% and 121%, respectively. We show that parallel libraries with a range of insert sizes increase transcriptomic information gained by sequencing and that by current established benchmarks our protocol gives competitive results with respect to library quality.	4	47153	Smith LM	Smith LM, Hartmann L, Drewe P, Bohnert R, Kahles A, Lanz C, Ratsch G	Multiple insert size paired-end sequencing for deconvolution of complex transcriptomes.	RNA Biol	2012	RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP015332.SRX181515~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP015332.SRX181516~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP015332.SRX181517~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP015332.SRX181518	Method: RNAseq|Species: Caenorhabditis elegans
400	22855835	WBPaper00041361.ce.rs.paper	N.A.	N.A.	1	Contributions of mRNA abundance, ribosome loading, and post- or peri-translational effects to temporal repression of C. elegans heterochronic miRNA targets.	miRNAs are post-transcriptional regulators of gene activity that reduce protein accumulation from target mRNAs. Elucidating precise molecular effects that animal miRNAs have on target transcripts has proven complex, with varied evidence indicating that miRNA regulation may produce different molecular outcomes in different species, systems, and/or physiological conditions. Here we use high-throughput ribosome profiling to analyze detailed translational parameters for five well-studied targets of miRNAs that regulate C. elegans developmental timing. For two targets of the miRNA lin-4 (lin-14 and lin-28), functional down-regulation was associated with decreases in both overall mRNA abundance and ribosome loading; however, these changes were of substantially smaller magnitude than corresponding changes observed in protein abundance. For three functional targets of the let-7 miRNA family for which down-regulation is critical in temporal progression of the animal (daf-12, hbl-1, and lin-41), we observed only modest changes in mRNA abundance and ribosome loading. lin-41 provides a striking example in that populations of ribosome-protected fragments from this gene remained essentially unchanged during the L3-L4 time interval when lin-41 activity is substantially down-regulated by let-7. Spectra of ribosomal positions were also examined for the five lin-4 and let-7 target mRNAs as a function of developmental time, with no indication of miRNA-induced ribosomal drop-off or significant pauses in translation. These data are consistent with models in which physiological regulation by this set of C. elegans miRNAs derives from combinatorial effects including suppressed recruitment/activation of translational machinery, compromised stability of target messages, and post- or peri-translational effects on lifetimes of polypeptide products.	17	46403	Stadler M	Stadler M, Artiles K, Pak J, Fire A	Contributions of mRNA abundance, ribosome loading, and post- or peri-translational effects to temporal repression of C. elegans heterochronic miRNA targets.	Genome Res	2012	RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP014427.SRX160147~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP014427.SRX160148~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP014427.SRX160149~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP014427.SRX160157~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP014427.SRX160290~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP014427.SRX160291~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP014427.SRX160292~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP014427.SRX160293~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP014427.SRX160510~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP014427.SRX160511~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP014427.SRX160512~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP014427.SRX160513~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP014427.SRX160514~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP014427.SRX160515~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP014427.SRX160516~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP014427.SRX160517~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP014427.SRX160518	Method: RNAseq|Species: Caenorhabditis elegans
401	22991463	WBPaper00041549.ce.rs.paper	N.A.	N.A.	1	Functional transcriptomics of a migrating cell in Caenorhabditis elegans.	In both metazoan development and metastatic cancer, migrating cells must carry out a detailed, complex program of sensing cues, binding substrates, and moving their cytoskeletons. The linker cell in Caenorhabditis elegans males undergoes a stereotyped migration that guides gonad organogenesis, occurs with precise timing, and requires the nuclear hormone receptor NHR-67. To better understand how this occurs, we performed RNA-seq of individually staged and dissected linker cells, comparing transcriptomes from linker cells of third-stage (L3) larvae, fourth-stage (L4) larvae, and nhr-67-RNAi-treated L4 larvae. We observed expression of 8,000-10,000 genes in the linker cell, 22-25% of which were up- or down-regulated 20-fold during development by NHR-67. Of genes that we tested by RNAi, 22% (45 of 204) were required for normal shape and migration, suggesting that many NHR-67-dependent, linker cell-enriched genes play roles in this migration. One unexpected class of genes up-regulated by NHR-67 was tandem pore potassium channels, which are required for normal linker-cell migration. We also found phenotypes for genes with human orthologs but no previously described migratory function. Our results provide an extensive catalog of genes that act in a migrating cell, identify unique molecular functions involved in nematode cell migration, and suggest similar functions in humans.	20	47155	Schwarz EM	Schwarz EM, Kato M, Sternberg PW	Functional transcriptomics of a migrating cell in Caenorhabditis elegans.	Proc Natl Acad Sci U S A	2012	RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP015688.SRX185637~RNASeq.elegans.WBStrain00030950.WBls:0000038.Male.WBbt:0005062.SRP015688.SRX185638~RNASeq.elegans.WBStrain00000001.WBls:0000023.Hermaphrodite.WBbt:0007833.SRP015688.SRX185639~RNASeq.elegans.WBStrain00030950.WBls:0000035.Male.WBbt:0005062.SRP015688.SRX185660~RNASeq.elegans.WBStrain00030950.WBls:0000038.Male.WBbt:0005062.SRP015688.SRX185661~RNASeq.elegans.WBStrain00030950.WBls:0000038.Male.WBbt:0005062.SRP015688.SRX185662~RNASeq.elegans.WBStrain00030950.WBls:0000038.Male.WBbt:0005062.SRP015688.SRX185663~RNASeq.elegans.WBStrain00030950.WBls:0000038.Male.WBbt:0005062.SRP015688.SRX185664~RNASeq.elegans.WBStrain00030950.WBls:0000038.Male.WBbt:0005062.SRP015688.SRX185665~RNASeq.elegans.WBStrain00030950.WBls:0000038.Male.WBbt:0005062.SRP015688.SRX185666~RNASeq.elegans.WBStrain00030950.WBls:0000035.Male.WBbt:0005062.SRP015688.SRX185667~RNASeq.elegans.WBStrain00030950.WBls:0000035.Male.WBbt:0005062.SRP015688.SRX185668~RNASeq.elegans.WBStrain00030950.WBls:0000035.Male.WBbt:0005062.SRP015688.SRX185669~RNASeq.elegans.WBStrain00030950.WBls:0000035.Male.WBbt:0005062.SRP015688.SRX185670~RNASeq.elegans.WBStrain00030950.WBls:0000035.Male.WBbt:0005062.SRP015688.SRX185672~RNASeq.elegans.WBStrain00030950.WBls:0000038.Male.WBbt:0005062.SRP015688.SRX185674~RNASeq.elegans.WBStrain00030950.WBls:0000038.Male.WBbt:0005062.SRP015688.SRX185676~RNASeq.elegans.WBStrain00030950.WBls:0000038.Male.WBbt:0005062.SRP015688.SRX185678~RNASeq.elegans.WBStrain00030950.WBls:0000038.Male.WBbt:0005062.SRP015688.SRX185680~RNASeq.elegans.WBStrain00030950.WBls:0000038.Male.WBbt:0005062.SRP015688.SRX185681	Method: RNAseq|Species: Caenorhabditis elegans|Tissue Specific
402	23103191	WBPaper00041689.ce.rs.paper	GSE41367	GPL13776,GPL13657,GPL13776,GPL16135,GPL16136,GPL16137,GPL16138,GPL16139,GPL16140,GPL16141	1	Simplification and desexualization of gene expression in self-fertile nematodes.	Evolutionary transitions between sexual modes could be potent forces in genome evolution. Several Caenorhabditis nematode species have evolved self-fertile hermaphrodites from the obligately outcrossing females of their ancestors. We explored the relationship between sexual mode and global gene expression by comparing two selfing species, C. elegans and C. briggsae, with three phylogenetically informative outcrossing relatives, C. remanei, C. brenneri, and C. japonica. Adult transcriptome assemblies from the selfing species are consistently and strikingly smaller than those of the outcrossing species. Against this background of overall simplification, genes conserved in multiple outcrossing species with strong sex-biased expression are even more likely to be missing from the genomes of the selfing species. In addition, the sexual regulation of remaining transcripts has diverged markedly from the ancestral pattern in both selfing lineages, though in distinct ways. Thus, both the complexity and the sexual specialization of transciptomes are rapidly altered in response to the evolution of self-fertility. These changes may result from the combination of relaxed sexual selection and a recently reported genetic mechanism favoring genome shrinkage in partial selfers.	6	47125	Thomas CG	Thomas CG, Li R, Smith HE, Woodruff GC, Oliver B, Haag ES	Simplification and desexualization of gene expression in self-fertile nematodes.	Curr Biol	2012	RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP016006.SRX191947~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP016006.SRX191948~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP016006.SRX191949~RNASeq.elegans.WBStrain00000001.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191950~RNASeq.elegans.WBStrain00000001.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191951~RNASeq.elegans.WBStrain00000001.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191952	Method: RNAseq|Species: Caenorhabditis elegans
403	23117578	WBPaper00041697.ce.rs.paper	GSE41205	GPL13657	1	The p38 MAPK PMK-1 shows heat-induced nuclear translocation, supports chaperone expression, and affects the heat tolerance of Caenorhabditis elegans.	The p38 mitogen-activated protein kinase PMK-1 of Caenorhabditis elegans has been associated with heavy metal, oxidative and pathogen stress. Pmk-1 is part of an operon comprising three p38 homologues, with pmk-1 expression suggested to be regulated by the operon promoter. There are contradictory reports about the cellular localization of PMK-1. We were interested to study principles of pmk-1 expression and to analyze the role of PMK-1 under heat stress. Using a translational GFP reporter, we found pmk-1 expression to be driven by a promoter in front of pmk-1. PMK-1 was detected in intestinal cells and neurons, with a cytoplasmic localization at moderate temperature. Increasing temperature above 32 C, however, induced a nuclear translocation of PMK-1 as well as PMK-1 accumulation near to apical membranes. Testing survival rates revealed 34-35 C as critical temperature range, where short-term survival severely decreased. Mutants of the PMK-1 pathway (pmk-1, sek-1, mek-1) as well as a mutant of JNK pathway (jnk-1) showed significantly lower survival rates than wild-type or mutants of other pathways (kgb-1, daf-2). Rescue and overexpression experiments verified the negative effects of pmk-1 on heat tolerance. Studying gene expression by RNA-seq and semi-quantitative reverse transcriptase polymerase chain reaction revealed positive effects of the PMK-1 pathway on the expression of genes for chaperones, protein biosynthesis, protein degradation, and other functional categories. Thus, the PMK-1 pathway is involved in the heat stress responses of C. elegans, possibly by a PMK-1-mediated activation of the transcription factor SKN-1 and/or an indirect or direct PMK-1-dependent activation (hyperphosphorylation) of heat-shock factor 1.	2	47152	Mertenskotter A	Mertenskotter A, Keshet A, Gerke P, Paul RJ	The p38 MAPK PMK-1 shows heat-induced nuclear translocation, supports chaperone expression, and affects the heat tolerance of Caenorhabditis elegans.	Cell Stress Chaperones	2013	RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP015918.SRX189885~RNASeq.elegans.WBStrain00024040.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP015918.SRX189886	Method: RNAseq|Species: Caenorhabditis elegans
404	23415229	WBPaper00042034.ce.rs.paper	N.A.	N.A.	1	Bacterial nitric oxide extends the lifespan of C. elegans.	Nitric oxide (NO) is an important signaling molecule in multicellular organisms. Most animals produce NO from L-arginine via a family of dedicated enzymes known as NO synthases (NOSes). A rare exception is the roundworm Caenorhabditis elegans, which lacks its own NOS. However, in its natural environment, C. elegans feeds on Bacilli that possess functional NOS. Here, we demonstrate that bacterially derived NO enhances C. elegans longevity and stress resistance via a defined group of genes that function under the dual control of HSF-1 and DAF-16 transcription factors. Our work provides an example of interspecies signaling by a small molecule and illustrates the lifelong value of commensal bacteria to their host.	4	47148	Gusarov I	Gusarov I, Gautier L, Smolentseva O, Shamovsky I, Eremina S, Mironov A, Nudler E	Bacterial nitric oxide extends the lifespan of C. elegans.	Cell	2013	RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP018033.SRX218380~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP018033.SRX218381~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP018033.SRX218382~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP018033.SRX218383	Method: RNAseq|Species: Caenorhabditis elegans
405	23534459	WBPaper00042179.ce.rs.paper	GSE46257	GPL13776	1	Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension.	Arsenite is one of the most toxic chemical substances known and is assumed to exert detrimental effects on viability even at lowest concentrations. By contrast and unlike higher concentrations, we here find that exposure to low-dose arsenite promotes growth of cultured mammalian cells. In the nematode C. elegans, low-dose arsenite promotes resistance against thermal and chemical stressors and extends lifespan of this metazoan, whereas higher concentrations reduce longevity. While arsenite causes a transient increase in reactive oxygen species (ROS) levels in C. elegans, co-exposure to ROS scavengers prevents the lifespan-extending capabilities of arsenite, indicating that transiently increased ROS levels act as transducers of arsenite effects on lifespan, a process known as mitohormesis. This requires two transcription factors, namely DAF-16 and SKN-1, which employ the metallothionein MTL-2 as well as the mitochondrial transporter TIN-9.1 to extend lifespan. Taken together, low-dose arsenite extends lifespan, providing evidence for nonlinear dose-response characteristics of toxin-mediated stress resistance and longevity in a multicellular organism.	4	47109	Schmeisser S	Schmeisser S, Schmeisser K, Weimer S, Groth M, Priebe S, Fazius E, Kuhlow D, Pick D, Einax JW, Guthke R, Platzer M, Zarse K, Ristow M	Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension.	Aging Cell	2013	RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP021462.SRX270953~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP021462.SRX270954~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP021462.SRX270955~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP021462.SRX270956	Method: RNAseq|Species: Caenorhabditis elegans
406	23604319	WBPaper00042296.ce.rs.paper	N.A.	N.A.	1	DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity.	Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The forkhead boxO (FOXO) transcription factor DAF-16 (hereafter referred to as DAF-16/FOXO) is a central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO-binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF. DAF-16/FOXO and SWI/SNF form a complex and globally co-localize at DAF-16/FOXO target promoters. We show that specifically for gene activation, DAF-16/FOXO depends on SWI/SNF, facilitating SWI/SNF recruitment to target promoters, to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role for SWI/SNF in DAF-16/FOXO-mediated processes, in particular dauer formation, stress resistance and the promotion of longevity. Thus, we give insight into the mechanisms of DAF-16/FOXO-mediated transcriptional regulation and establish a critical link between ATP-dependent chromatin remodelling and lifespan regulation.	8	47140	Riedel CG	Riedel CG, Dowen RH, Lourenco GF, Kirienko NV, Heimbucher T, West JA, Bowman SK, Kingston RE, Dillin A, Asara JM, Ruvkun G	DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity.	Nat Cell Biol	2013	RNASeq.elegans.WBStrain00004309.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP017908.SRX216722~RNASeq.elegans.WBStrain00004309.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP017908.SRX216723~RNASeq.elegans.WBStrain00007897.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP017908.SRX216724~RNASeq.elegans.WBStrain00007897.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP017908.SRX216725~RNASeq.elegans.WBStrain00007952.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP017908.SRX216726~RNASeq.elegans.WBStrain00007952.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP017908.SRX216727~RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP017908.SRX218153~RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP017908.SRX218190	Method: RNAseq|Species: Caenorhabditis elegans
407	23642123	WBPaper00042361.ce.rs.paper	N.A.	N.A.	1	Functional transcriptomic analysis of the role of MAB-5/Hox in Q neuroblast migration in Caenorhabditis elegans.	BACKGROUND: Directed cell migration is a fundamental process in normal development and in tumor metastasis. In C. elegans the MAB-5/Hox transcription factor is a determinant of posterior migration of the Q neuroblast descendants. In this work, mab-5 transcriptional targets that control Q descendant migration are identified by comparing RNA-seq profiles in wild type and mab-5 mutant backgrounds. RESULTS: Transcriptome profiling is a widely-used and potent tool to identify genes involved in developmental and pathological processes, and is most informative when RNA can be isolated from individual cell or tissue types. Cell-specific RNA samples can be difficult to obtain from invertebrate model organisms such as Drosophila and C. elegans. Here we test the utility of combining a whole organism RNA-seq approach with mab-5 loss and gain-of-function mutants and functional validation using RNAi to identify genes regulated by MAB-5 to control Q descendant migration. We identified 22 genes whose expression was controlled by mab-5 and that controlled Q descendant migration. Genes regulated by mab-5 were enriched for secreted and transmembrane molecules involved in basement membrane interaction and modification, and some affected Q descendant migration. CONCLUSIONS: Our results indicate that a whole-organism RNA-seq approach, when combined with mutant analysis and functional validation, can be a powerful method to identify genes involved in a specific developmental process, in this case Q descendant posterior migration. These genes could act either autonomously in the Q cells, or non-autonomously in other cells that express MAB-5. The identities of the genes regulated by MAB-5 indicate that MAB-5 acts by modifying interactions with the basement membrane, resulting in posterior versus anterior migration.	26	47150	Tamayo JV	Tamayo JV, Gujar M, Macdonald SJ, Lundquist EA	Functional transcriptomic analysis of the role of MAB-5/Hox in Q neuroblast migration in Caenorhabditis elegans.	BMC Genomics	2013	RNASeq.elegans.WBStrain00024162.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212092~RNASeq.elegans.WBStrain00024162.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212095~RNASeq.elegans.WBStrain00024162.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212097~RNASeq.elegans.WBStrain00024162.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212098~RNASeq.elegans.WBStrain00024162.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212099~RNASeq.elegans.WBStrain00024162.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212100~RNASeq.elegans.WBStrain00024162.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212101~RNASeq.elegans.WBStrain00024162.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212102~RNASeq.elegans.WBStrain00024165.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212103~RNASeq.elegans.WBStrain00024165.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212104~RNASeq.elegans.WBStrain00024165.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212105~RNASeq.elegans.WBStrain00024165.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212106~RNASeq.elegans.WBStrain00024165.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212107~RNASeq.elegans.WBStrain00024165.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212109~RNASeq.elegans.WBStrain00024166.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212110~RNASeq.elegans.WBStrain00024166.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212111~RNASeq.elegans.WBStrain00024166.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212112~RNASeq.elegans.WBStrain00024166.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212113~RNASeq.elegans.WBStrain00024166.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212114~RNASeq.elegans.WBStrain00024166.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212115~RNASeq.elegans.WBStrain00024167.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212116~RNASeq.elegans.WBStrain00024167.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212118~RNASeq.elegans.WBStrain00024167.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212119~RNASeq.elegans.WBStrain00024167.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212120~RNASeq.elegans.WBStrain00024167.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212121~RNASeq.elegans.WBStrain00024167.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP017621.SRX212122	Method: RNAseq|Species: Caenorhabditis elegans
408	23935515	WBPaper00044037.ce.rs.paper	N.A.	N.A.	1	Dietary restriction induced longevity is mediated by nuclear receptor NHR-62 in Caenorhabditis elegans.	Dietary restriction (DR) extends lifespan in a wide variety of species, yet the underlying mechanisms are not well understood. Here we show that the Caenorhabditis elegans HNF4-related nuclear hormone receptor NHR-62 is required for metabolic and physiologic responses associated with DR-induced longevity. nhr-62 mediates the longevity of eat-2 mutants, a genetic mimetic of dietary restriction, and blunts the longevity response of DR induced by bacterial food dilution at low nutrient levels. Metabolic changes associated with DR, including decreased Oil Red O staining, decreased triglyceride levels, and increased autophagy are partly reversed by mutation of nhr-62. Additionally, the DR fatty acid profile is altered in nhr-62 mutants. Expression profiles reveal that several hundred genes induced by DR depend on the activity of NHR-62, including a putative lipase required for the DR response. This study provides critical evidence of nuclear hormone receptor regulation of the DR longevity response, suggesting hormonal and metabolic control of life span.	12	47111	Heestand BN	Heestand BN, Shen Y, Liu W, Magner DB, Storm N, Meharg C, Habermann B, Antebi A	Dietary restriction induced longevity is mediated by nuclear receptor NHR-62 in Caenorhabditis elegans.	PLoS Genet	2013	RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP040269.SRX494547~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP040269.SRX494548~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP040269.SRX494549~RNASeq.elegans.WBStrain00000029.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP040269.SRX494550~RNASeq.elegans.WBStrain00000029.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP040269.SRX494551~RNASeq.elegans.WBStrain00000029.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP040269.SRX494552~RNASeq.elegans.WBStrain00000031.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP040269.SRX494553~RNASeq.elegans.WBStrain00000031.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP040269.SRX494554~RNASeq.elegans.WBStrain00000031.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP040269.SRX494555~RNASeq.elegans.WBStrain00000030.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP040269.SRX494556~RNASeq.elegans.WBStrain00000030.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP040269.SRX494557~RNASeq.elegans.WBStrain00000030.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP040269.SRX494558	Method: RNAseq|Species: Caenorhabditis elegans
409	24077178	WBPaper00044260.ce.rs.paper	N.A.	N.A.	1	Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide.	Sirtuins, a family of histone deacetylases, have a fiercely debated role in regulating lifespan. In contrast with recent observations, here we find that overexpression of sir-2.1, the ortholog of mammalian SirT1, does extend Caenorhabditis elegans lifespan. Sirtuins mandatorily convert NAD(+) into nicotinamide (NAM). We here find that NAM and its metabolite, 1-methylnicotinamide (MNA), extend C. elegans lifespan, even in the absence of sir-2.1. We identify a previously unknown C. elegans nicotinamide-N-methyltransferase, encoded by a gene now named anmt-1, to generate MNA from NAM. Disruption and overexpression of anmt-1 have opposing effects on lifespan independent of sirtuins, with loss of anmt-1 fully inhibiting sir-2.1-mediated lifespan extension. MNA serves as a substrate for a newly identified aldehyde oxidase, GAD-3, to generate hydrogen peroxide, which acts as a mitohormetic reactive oxygen species signal to promote C. elegans longevity. Taken together, sirtuin-mediated lifespan extension depends on methylation of NAM, providing an unexpected mechanistic role for sirtuins beyond histone deacetylation.	9	47143	Schmeisser K	Schmeisser K, Mansfeld J, Kuhlow D, Weimer S, Priebe S, Heiland I, Birringer M, Groth M, Segref A, Kanfi Y, Price NL, Schmeisser S, Schuster S, Pfeiffer AF, Guthke R, Platzer M, Hoppe T, Cohen HY, Zarse K, Sinclair DA, Ristow M	Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide.	Nat Chem Biol	2013	RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP028602.SRX332740~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP028602.SRX332741~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP028602.SRX332742~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP028602.SRX332743~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP028602.SRX332744~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP028602.SRX332745~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP028602.SRX332746~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP028602.SRX332747~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP028602.SRX332748	Method: RNAseq|Species: Caenorhabditis elegans
410	24167253	WBPaper00044391.ce.rs.paper	N.A.	N.A.	1	Large-scale detection of in vivo transcription errors.	Accurate transmission and expression of genetic information are crucial for the survival of all living organisms. Recently, the coupling of mutation accumulation experiments and next-generation sequencing has greatly expanded our knowledge of the genomic mutation rate in both prokaryotes and eukaryotes. However, because of their transient nature, transcription errors have proven extremely difficult to quantify, and current estimates of transcription fidelity are derived from artificial constructs applied to just a few organisms. Here we report a unique cDNA library preparation technique that allows error detection in natural transcripts at the transcriptome-wide level. Application of this method to the model organism Caenorhabditis elegans revealed a base misincorporation rate in mRNAs of ~4 x 10(-6) per site, with a very biased molecular spectrum. Because the proposed method is readily applicable to other organisms, this innovation provides unique opportunities for studying the incidence of transcription errors across the tree of life.	9	47156	Gout JF	Gout JF, Kelley Thomas W, Smith Z, Okamoto K, Lynch M	Large-scale detection of in vivo transcription errors.	Proc Natl Acad Sci U S A	2013	RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP030526.SRX360655~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP030526.SRX360860~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP030526.SRX362654~RNASeq.elegans.WBStrain00031599.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP030526.SRX362655~RNASeq.elegans.WBStrain00031599.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP030526.SRX362686~RNASeq.elegans.WBStrain00031599.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP030526.SRX362687~RNASeq.elegans.WBStrain00036497.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP030526.SRX362860~RNASeq.elegans.WBStrain00036497.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP030526.SRX362868~RNASeq.elegans.WBStrain00036497.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP030526.SRX362869	Method: RNAseq|Species: Caenorhabditis elegans
411	24199155	WBPaper00044426.ce.rs.paper	N.A.	N.A.	1	Neuronal ROS signaling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension.	Dietary restriction (DR) extends lifespan and promotes metabolic health in evolutionary distinct species. DR is widely believed to promote longevity by causing an energy deficit leading to increased mitochondrial respiration. We here show that inhibitors of mitochondrial complex I promote physical activity, stress resistance as well as lifespan of Caenorhabditis elegans despite normal food uptake, i.e. in the absence of DR. However, complex I inhibition does not further extend lifespan in dietarily restricted nematodes, indicating that impaired complex I activity mimics DR. Promotion of longevity due to complex I inhibition occurs independently of known energy sensors, including DAF-16/FoxO, as well as AAK-2/AMPK and SIR-2.1/sirtuins, or both. Consistent with the concept of mitohormesis, complex I inhibition transiently increases mitochondrial formation of reactive oxygen species (ROS) that activate PMK-1/p38 MAP kinase and SKN-1/NRF-2. Interference with this retrograde redox signal as well as ablation of two redox-sensitive neurons in the head of the worm similarly prevents extension of lifespan. These findings unexpectedly indicate that DR extends organismal lifespan through transient neuronal ROS signaling rather than sensing of energy depletion, providing unexpected pharmacological options to promote exercise capacity and healthspan despite unaltered eating habits.	22	47124	Schmeisser S	Schmeisser S, Priebe S, Groth M, Monajembashi S, Hemmerich P, Guthke R, Platzer M, Ristow M	Neuronal ROS signaling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension.	Mol Metab	2013	RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP021083.SRX265354~RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP021083.SRX265355~RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP021083.SRX265356~RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP021083.SRX265357~RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP021083.SRX265358~RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP021083.SRX265359~RNASeq.elegans.WBStrain00000001.WBls:0000068.Hermaphrodite.WBbt:0007833.SRP021083.SRX265360~RNASeq.elegans.WBStrain00000001.WBls:0000068.Hermaphrodite.WBbt:0007833.SRP021083.SRX265361~RNASeq.elegans.WBStrain00000001.WBls:0000068.Hermaphrodite.WBbt:0007833.SRP021083.SRX265362~RNASeq.elegans.WBStrain00000001.WBls:0000068.Hermaphrodite.WBbt:0007833.SRP021083.SRX265363~RNASeq.elegans.WBStrain00000001.WBls:0000068.Hermaphrodite.WBbt:0007833.SRP021083.SRX265364~RNASeq.elegans.WBStrain00000001.WBls:0000068.Hermaphrodite.WBbt:0007833.SRP021083.SRX265365~RNASeq.elegans.WBStrain00000001.WBls:0000674.Hermaphrodite.WBbt:0007833.SRP021083.SRX265366~RNASeq.elegans.WBStrain00000001.WBls:0000674.Hermaphrodite.WBbt:0007833.SRP021083.SRX265367~RNASeq.elegans.WBStrain00000001.WBls:0000674.Hermaphrodite.WBbt:0007833.SRP021083.SRX265368~RNASeq.elegans.WBStrain00000001.WBls:0000674.Hermaphrodite.WBbt:0007833.SRP021083.SRX265369~RNASeq.elegans.WBStrain00000001.WBls:0000674.Hermaphrodite.WBbt:0007833.SRP021083.SRX265370~RNASeq.elegans.WBStrain00000001.WBls:0000674.Hermaphrodite.WBbt:0007833.SRP021083.SRX265371~RNASeq.elegans.WBStrain00000001.WBls:0000676.Hermaphrodite.WBbt:0007833.SRP021083.SRX265372~RNASeq.elegans.WBStrain00000001.WBls:0000676.Hermaphrodite.WBbt:0007833.SRP021083.SRX265373~RNASeq.elegans.WBStrain00000001.WBls:0000676.Hermaphrodite.WBbt:0007833.SRP021083.SRX265374~RNASeq.elegans.WBStrain00000001.WBls:0000676.Hermaphrodite.WBbt:0007833.SRP021083.SRX265375	Method: RNAseq|Species: Caenorhabditis elegans
412	24360276	WBPaper00044616.ce.rs.paper	GSE49672	GPL13776	1	Argonautes promote male fertility and provide a paternal memory of germline gene expression in C. elegans.	During each life cycle, germ cells preserve and pass on both genetic and epigenetic information. In C.elegans, the ALG-3/4 Argonaute proteins are expressed during male gametogenesis and promote male fertility. Here, we show that the CSR-1 Argonaute functions with ALG-3/4 to positively regulate target genes required for spermiogenesis. Our findings suggest that ALG-3/4 functions during spermatogenesis to amplify a small RNA signal that represents an epigenetic memory of male-specific gene expression. CSR-1, which is abundant in mature sperm, appears to transmit this memory to offspring. Surprisingly, in addition to small RNAs targeting male-specific genes, we show that males also harbor an extensive repertoire of CSR-1 smallRNAs targeting oogenesis-specific mRNAs. Together, these findings suggest that C.elegans sperm transmit not only the genome but also epigenetic binary signals in the form of Argonaute/small RNA complexes that constitute a memory of gene expression in preceding generations.	4	46405	Conine CC	Conine CC, Moresco JJ, Gu W, Shirayama M, Conte D, Yates JR, Mello CC	Argonautes promote male fertility and provide a paternal memory of germline gene expression in C. elegans.	Cell	2013	RNASeq.elegans.WBStrain00000001.WBls:0000041.Male.WBbt:0005784.SRP028611.SRX333008~RNASeq.elegans.WBStrain00000001.WBls:0000041.Male.WBbt:0005784.SRP028611.SRX333009~RNASeq.elegans.WBStrain00040479.WBls:0000041.Male.WBbt:0005784.SRP028611.SRX333010~RNASeq.elegans.WBStrain00040479.WBls:0000041.Male.WBbt:0005784.SRP028611.SRX333011	Method: RNAseq|Species: Caenorhabditis elegans|Tissue Specific
413	24462290	WBPaper00044760.ce.rs.paper	GSE53359	GPL13776	1	Conservation of mRNA and protein expression during development of C. elegans.	Spatiotemporal control of gene expression is crucial for development and subject to evolutionary changes. Although proteins are the final product of most genes, the developmental proteome of an animal has not yet been comprehensively defined, and the correlation between mRNA and protein abundance during development is largely unknown. Here, we globally measured and compared protein and mRNA expression changes during the life cycle of the nematodes C. elegans and C. briggsae, separated by ~30 million years of evolution. We observed that developmental mRNA and protein changes were highly conserved to a surprisingly similar degree but were poorly correlated within a species, suggesting important and widespread posttranscriptional regulation. Posttranscriptional control was particularly well conserved if mRNA fold changes were buffered on the protein level, indicating a predominant repressive function. Finally, among divergently expressed genes, we identified insulin signaling, a pathway involved in lifespan determination, as a putative target of adaptive evolution.	13	47150	Grun D	Grun D, Kirchner M, Thierfelder N, Stoeckius M, Selbach M, Rajewsky N	Conservation of mRNA and protein expression during development of C. elegans.	Cell Rep	2014	RNASeq.elegans.WBStrain00000001.WBls:0000003.Hermaphrodite.WBbt:0007833.SRP034522.SRX392693~RNASeq.elegans.WBStrain00000001.WBls:0000003.Hermaphrodite.WBbt:0007833.SRP034522.SRX392694~RNASeq.elegans.WBStrain00000001.WBls:0000003.Hermaphrodite.WBbt:0007833.SRP034522.SRX392695~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP034522.SRX392696~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP034522.SRX392697~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP034522.SRX392698~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP034522.SRX392699~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP034522.SRX392700~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP034522.SRX392701~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP034522.SRX392702~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP034522.SRX392703~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP034522.SRX392704~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP034522.SRX392705	Method: RNAseq|Species: Caenorhabditis elegans
414	24490688	WBPaper00044786.ce.rs.paper	GSE44682	GPL13776	1	Genome-wide analysis links emerin to neuromuscular junction activity in Caenorhabditis elegans.	BACKGROUND: Laminopathies are diseases characterized by defects in nuclear envelope structure. A well-known example is Emery-Dreifuss muscular dystrophy, which is caused by mutations in the human lamin A/C and emerin genes. While most nuclear envelope proteins are ubiquitously expressed, laminopathies often affect only a subset of tissues. The molecular mechanisms underlying these tissue-specific manifestations remain elusive. We hypothesize that different functional subclasses of genes might be differentially affected by defects in specific nuclear envelope components. RESULTS: Here we determine genome-wide DNA association profiles of two nuclear envelope components, lamin/LMN-1 and emerin/EMR-1 in adult Caenorhabditis elegans. Although both proteins bind to transcriptionally inactive regions of the genome, EMR-1 is enriched at genes involved in muscle and neuronal function. Deletion of either EMR-1 or LEM-2, another integral envelope protein, causes local changes in nuclear architecture as evidenced by altered association between DNA and LMN-1. Transcriptome analyses reveal that EMR-1 and LEM-2 are associated with gene repression, particularly of genes implicated in muscle and nervous system function. We demonstrate that emr-1, but not lem-2, mutants are sensitive to the cholinesterase inhibitor aldicarb, indicating altered activity at neuromuscular junctions. CONCLUSIONS: We identify a class of elements that bind EMR-1 but do not associate with LMN-1, and these are enriched for muscle and neuronal genes. Our data support a redundant function of EMR-1 and LEM-2 in chromatin anchoring to the nuclear envelope and gene repression. We demonstrate a specific role of EMR-1 in neuromuscular junction activity that may contribute to Emery-Dreifuss muscular dystrophy in humans.	9	47153	Gonzalez-Aguilera C	Gonzalez-Aguilera C, Ikegami K, Ayuso C, de Luis A, Iniguez M, Cabello J, Lieb JD, Askjaer P	Genome-wide analysis links emerin to neuromuscular junction activity in Caenorhabditis elegans.	Genome Biol	2014	RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP018867.SRX245821~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP018867.SRX245822~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP018867.SRX245823~RNASeq.elegans.WBStrain00003835.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP018867.SRX245824~RNASeq.elegans.WBStrain00003835.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP018867.SRX245825~RNASeq.elegans.WBStrain00003834.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP018867.SRX245826~RNASeq.elegans.WBStrain00003834.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP018867.SRX245827~RNASeq.elegans.WBStrain00003834.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP018867.SRX245828~RNASeq.elegans.WBStrain00003834.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP018867.SRX245829	Method: RNAseq|Species: Caenorhabditis elegans
415	24508457	WBPaper00044827.ce.rs.paper	N.A.	N.A.	1	The dsRBP and inactive editor ADR-1 utilizes dsRNA binding to regulate A-to-I RNA editing across the C. elegans transcriptome.	Inadequate adenosine-to-inosine editing of noncoding regions occurs in disease but is often uncorrelated with ADAR levels, underscoring the need tostudy deaminase-independent control of editing. C.elegans have two ADAR proteins, ADR-2 and thetheoretically catalytically inactive ADR-1. Using high-throughput RNA sequencing of wild-type and adr mutant worms, we expand the repertoire of C.elegans edited transcripts over 5-fold and confirm that ADR-2 is the only active deaminase invivo. Despite lacking deaminase function, ADR-1 affects editing of over 60 adenosines within the 3' UTRs of 16 different mRNAs. Furthermore, ADR-1 interacts directly with ADR-2 substrates, even in the absence of ADR-2, and mutations within its double-stranded RNA (dsRNA) binding domains abolish both binding and editing regulation. We conclude that ADR-1 acts as a major regulator of editing by binding ADR-2 substrates invivo. These results raise the possibility that other dsRNA binding proteins, including the inactive human ADARs, regulate RNA editing through deaminase-independent mechanisms.	8	47146	Washburn MC	Washburn MC, Kakaradov B, Sundararaman B, Wheeler E, Hoon S, Yeo GW, Hundley HA	The dsRBP and inactive editor ADR-1 utilizes dsRNA binding to regulate A-to-I RNA editing across the C. elegans transcriptome.	Cell Rep	2014	RNASeq.elegans.WBStrain00000439.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP031831.SRX366861~RNASeq.elegans.WBStrain00000437.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP031831.SRX366862~RNASeq.elegans.WBStrain00000438.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP031831.SRX366863~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP031831.SRX366864~RNASeq.elegans.WBStrain00000439.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP031831.SRX366865~RNASeq.elegans.WBStrain00000439.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP031831.SRX366866~RNASeq.elegans.WBStrain00000439.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP031831.SRX366867~RNASeq.elegans.WBStrain00000439.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP031831.SRX366868	Method: RNAseq|Species: Caenorhabditis elegans
416	24581041	WBPaper00044954.ce.rs.paper	N.A.	N.A.	1	Characterisation of Caenorhabditis elegans sperm transcriptome and proteome.	BACKGROUND: Although sperm is transcriptionally and translationally quiescent, complex populations of RNAs, including mRNAs and non-coding RNAs, exist in sperm. Previous microarray analysis of germ cell mutants identified hundreds of sperm genes in Caenorhabditis elegans. To take a more comprehensive view on C. elegans sperm genes, here, we isolate highly pure sperm cells and employ high-throughput technologies to obtain sperm transcriptome and proteome. RESULTS: First, sperm transcriptome consists of considerable amounts of non-coding RNAs, many of which have not been annotated and may play functional roles during spermatogenesis. Second, apart from kinases/phosphatases as previously reported, ion binding proteins are also enriched in sperm, underlying the crucial roles of intracellular ions in post-translational regulation in sperm. Third, while the majority of sperm genes/proteins have low abundance, a small number of sperm genes/proteins are hugely enriched in sperm, implying that sperm only rely on a small set of proteins for post-translational regulation. Lastly, by extensive RNAi screening of sperm enriched genes, we identified a few genes that control fertility. Our further analysis reveals a tight correlation between sperm transcriptome and sperm small RNAome, suggesting that the endogenous siRNAs strongly repress sperm genes. This leads to an idea that the inefficient RNAi screening of sperm genes, a phenomenon currently with unknown causes, might result from the competition between the endogenous RNAi pathway and the exogenous RNAi pathway. CONCLUSIONS: Together, the obtained sperm transcriptome and proteome serve as valuable resources to systematically study spermatogenesis in C. elegans.	1	47156	Ma X	Ma X, Zhu Y, Li C, Xue P, Zhao Y, Chen S, Yang F, Miao L	Characterisation of Caenorhabditis elegans sperm transcriptome and proteome.	BMC Genomics	2014	RNASeq.elegans.WBStrain00006269.WBls:0000041.Male.WBbt:0006798.SRP014581.SRX170940	Method: RNAseq|Species: Caenorhabditis elegans|Tissue Specific
417	24613396	WBPaper00045017.ce.rs.paper	N.A.	N.A.	1	DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation.	Developmental timing genes catalyze stem cell progression and animal maturation programs across taxa. Caenorhabditis elegans DRE-1/FBXO11 functions in an SCF E3-ubiquitin ligase complex to regulate the transition to adult programs, but its cognate proteolytic substrates are unknown. Here, we identify the conserved transcription factor BLMP-1 as a substrate of the SCF(DRE-1/FBXO11) complex. blmp-1 deletion suppressed dre-1 mutant phenotypes and exhibited developmental timing defects opposite to dre-1. blmp-1 also opposed dre-1 for other life history traits, including entry into the dauer diapause and longevity. BLMP-1 protein was strikingly elevated upon dre-1 depletion and dysregulated in a stage- and tissue-specific manner. The role of DRE-1 in regulating BLMP-1 stability is evolutionary conserved, aswe observed direct protein interaction and degradation function for worm and human counterparts. Taken together, posttranslational regulation ofBLMP-1/BLIMP-1 by DRE-1/FBXO11 coordinates C.elegans developmental timing and other life history traits, suggesting that this two-protein module mediates metazoan maturation processes.	6	47145	Horn M	Horn M, Geisen C, Cermak L, Becker B, Nakamura S, Klein C, Pagano M, Antebi A	DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation.	Dev Cell	2014	RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP038704.SRX474206~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP038704.SRX474207~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP038704.SRX474208~RNASeq.elegans.WBStrain00047070.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP038704.SRX474209~RNASeq.elegans.WBStrain00047070.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP038704.SRX474210~RNASeq.elegans.WBStrain00047070.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP038704.SRX474211	Method: RNAseq|Species: Caenorhabditis elegans
418	24714520	WBPaper00045095.ce.rs.paper	N.A.	N.A.	1	D-Glucosamine supplementation extends life span of nematodes and of ageing mice.	D-Glucosamine (GlcN) is a freely available and commonly used dietary supplement potentially promoting cartilage health in humans, which also acts as an inhibitor of glycolysis. Here we show that GlcN, independent of the hexosamine pathway, extends Caenorhabditis elegans life span by impairing glucose metabolism that activates AMP-activated protein kinase (AMPK/AAK-2) and increases mitochondrial biogenesis. Consistent with the concept of mitohormesis, GlcN promotes increased formation of mitochondrial reactive oxygen species (ROS) culminating in increased expression of the nematodal amino acid-transporter 1 (aat-1) gene. Ameliorating mitochondrial ROS formation or impairment of aat-1-expression abolishes GlcN-mediated life span extension in an NRF2/SKN-1-dependent fashion. Unlike other calorie restriction mimetics, such as 2-deoxyglucose, GlcN extends life span of ageing C57BL/6 mice, which show an induction of mitochondrial biogenesis, lowered blood glucose levels, enhanced expression of several murine amino-acid transporters, as well as increased amino-acid catabolism. Taken together, we provide evidence that GlcN extends life span in evolutionary distinct species by mimicking a low-carbohydrate diet.	12	47119	Weimer S	Weimer S, Priebs J, Kuhlow D, Groth M, Priebe S, Mansfeld J, Merry TL, Dubuis S, Laube B, Pfeiffer AF, Schulz TJ, Guthke R, Platzer M, Zamboni N, Zarse K, Ristow M	D-Glucosamine supplementation extends life span of nematodes and of ageing mice.	Nat Commun	2014	RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP037555.SRX469110~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP037555.SRX469111~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP037555.SRX469112~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP037555.SRX469113~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP037555.SRX469114~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP037555.SRX469115~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP037555.SRX469116~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP037555.SRX469117~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP037555.SRX469118~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP037555.SRX469119~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP037555.SRX469120~RNASeq.elegans.WBStrain00000001.WBls:0000065.Hermaphrodite.WBbt:0007833.SRP037555.SRX469121	Method: RNAseq|Species: Caenorhabditis elegans
419	24793291	WBPaper00045232.ce.rs.paper	N.A.	N.A.	1	Sex-biased gene expression and evolution of the x chromosome in nematodes.	Studies of X chromosome evolution in various organisms have indicated that sex-biased genes are nonrandomly distributed between the X and autosomes. Here, to extend these studies to nematodes, we annotated and analyzed X chromosome gene content in four Caenorhabditis species and in Pristionchus pacificus. Our gene expression analyses comparing young adult male and female mRNA-seq data indicate that, in general, nematode X chromosomes are enriched for genes with high female-biased expression and depleted of genes with high male-biased expression. Genes with low sex-biased expression do not show the same trend of X chromosome enrichment and depletion. Combined with the observation that highly sex-biased genes are primarily expressed in the gonad, differential distribution of sex-biased genes reflects differences in evolutionary pressures linked to tissue-specific regulation of X chromosome transcription. Our data also indicate that X dosage imbalance between males (XO) and females (XX) is influential in shaping both expression and gene content of the X chromosome. Predicted upregulation of the single male X to match autosomal transcription (Ohno's hypothesis) is supported by our observation that overall transcript levels from the X and autosomes are similar for highly expressed genes. However, comparison of differentially located one-to-one orthologs between C. elegans and P. pacificus indicates lower expression of X-linked orthologs, arguing against X upregulation. These contradicting observations may be reconciled if X upregulation is not a global mechanism but instead acts locally on a subset of tissues and X-linked genes that are dosage sensitive.	8	47156	Albritton SE	Albritton SE, Kranz AL, Rao P, Kramer M, Dieterich C, Ercan S	Sex-biased gene expression and evolution of the x chromosome in nematodes.	Genetics	2014	RNASeq.elegans.WBStrain00000001.WBls:0000063.Male.WBbt:0007833.SRP034667.SRX397084~RNASeq.elegans.WBStrain00000001.WBls:0000063.Male.WBbt:0007833.SRP034667.SRX397085~RNASeq.elegans.WBStrain00000001.WBls:0000063.Male.WBbt:0007833.SRP034667.SRX397086~RNASeq.elegans.WBStrain00000001.WBls:0000063.Male.WBbt:0007833.SRP034667.SRX397087~RNASeq.elegans.WBStrain00000001.WBls:0000063.Female.WBbt:0007833.SRP034667.SRX397088~RNASeq.elegans.WBStrain00000001.WBls:0000063.Female.WBbt:0007833.SRP034667.SRX397089~RNASeq.elegans.WBStrain00000001.WBls:0000063.Female.WBbt:0007833.SRP034667.SRX397090~RNASeq.elegans.WBStrain00000001.WBls:0000063.Female.WBbt:0007833.SRP034667.SRX397091	Method: RNAseq|Species: Caenorhabditis elegans
420	24884413	WBPaper00045316.ce.rs.paper	N.A.	N.A.	1	The influences of PRG-1 on the expression of small RNAs and mRNAs.	BACKGROUND: In metazoans, Piwi-related Argonaute proteins play important roles in maintaining germline integrity and fertility and have been linked to a class of germline-enriched small RNAs termed piRNAs. Caenorhabditis elegans encodes two Piwi family proteins called PRG-1 and PRG-2, and PRG-1 interacts with the C. elegans piRNAs (21U-RNAs). Previous studies found that mutation of prg-1 causes a marked reduction in the expression of 21U-RNAs, temperature-sensitive defects in fertility and other phenotypic defects. RESULTS: In this study, we wanted to systematically demonstrate the function of PRG-1 in the regulation of small RNAs and their targets. By analyzing small RNAs and mRNAs with and without a mutation in prg-1 during C. elegans development, we demonstrated that (1) mutation of prg-1 leads to a decrease in the expression of 21U-RNAs, and causes 35 ~ 40% of miRNAs to be down-regulated; (2) in C. elegans, approximately 3% (6% in L4) of protein-coding genes are differentially expressed after mutating prg-1, and 60 ~ 70% of these substantially altered protein-coding genes are up-regulated; (3) the target genes of the down-regulated miRNAs and the candidate target genes of the down-regulated 21U-RNAs are enriched in the up-regulated protein-coding genes; and (4) PRG-1 regulates protein-coding genes by down-regulating small RNAs (miRNAs and 21U-RNAs) that target genes that participate in the development of C. elegans. CONCLUSIONS: In prg-1-mutated C. elegans, the expression of miRNAs and 21U-RNAs was reduced, and the protein-coding targets, which were associated with the development of C. elegans, were up-regulated. This may be the mechanism underlying PRG-1 function.	4	47154	Wang JJ	Wang JJ, Cui DY, Xiao T, Sun X, Zhang P, Chen R, He S, Huang DW	The influences of PRG-1 on the expression of small RNAs and mRNAs.	BMC Genomics	2014	RNASeq.elegans.WBStrain00040453.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP040623.SRX501864~RNASeq.elegans.WBStrain00040453.WBls:0000027.Hermaphrodite.WBbt:0007833.SRP040623.SRX501865~RNASeq.elegans.WBStrain00040453.WBls:0000035.Hermaphrodite.WBbt:0007833.SRP040623.SRX501866~RNASeq.elegans.WBStrain00040453.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP040623.SRX501867	Method: RNAseq|Species: Caenorhabditis elegans
421	24910101	WBPaper00045350.ce.rs.paper	N.A.	N.A.	1	A pair of RNA-binding proteins controls networks of splicing events contributing to specialization of neural cell types.	Alternative splicing is important for the development and function of the nervous system, but little is known about the differences in alternative splicing between distinct types of neurons. Furthermore, the factors that control cell-type-specific splicing and the physiological roles of these alternative isoforms are unclear. By monitoring alternative splicing at single-cell resolution in Caenorhabditis elegans, we demonstrate that splicing patterns in different neurons are often distinct and highly regulated. We identify two conserved RNA-binding proteins, UNC-75/CELF and EXC-7/Hu/ELAV, which regulate overlapping networks of splicing events in GABAergic and cholinergic neurons. We use the UNC-75 exon network to discover regulators of synaptic transmission and to identify unique roles for isoforms of UNC-64/Syntaxin, a protein required for synaptic vesicle fusion. Our results indicate that combinatorial regulation of alternative splicing in distinct neurons provides a mechanism to specialize metazoan nervous systems.	1	47130	Norris AD	Norris AD, Gao S, Norris ML, Ray D, Ramani AK, Fraser AG, Morris Q, Hughes TR, Zhen M, Calarco JA	A pair of RNA-binding proteins controls networks of splicing events contributing to specialization of neural cell types.	Mol Cell	2014	RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP041095.SRX514835	Method: RNAseq|Species: Caenorhabditis elegans
422	24894551	WBPaper00045359.ce.rs.paper	GSE57351	GPL13776	1	Paternal RNA contributions in the Caenorhabditis elegans zygote.	Development of the early embryo is thought to be mainly driven by maternal gene products and post-transcriptional gene regulation. Here, we used metabolic labeling to show that RNA can be transferred by sperm into the oocyte upon fertilization. To identify genes with paternal expression in the embryo, we performed crosses of males and females from divergent Caenorhabditis elegans strains. RNA sequencing of mRNAs and small RNAs in the 1-cell hybrid embryo revealed that about one hundred sixty paternal mRNAs are reproducibly expressed in the embryo and that about half of all assayed endogenous siRNAs and piRNAs are also of paternal origin. Together, our results suggest an unexplored paternal contribution to early development.	15	46383	Stoeckius M	Stoeckius M, Grun D, Rajewsky N	Paternal RNA contributions in the Caenorhabditis elegans zygote.	EMBO J	2014	RNASeq.elegans.WBStrain00000001.WBls:0000006.Hermaphrodite.WBbt:0007833.SRP041708.SRX533796~RNASeq.elegans.WBStrain00000001.WBls:0000006.Hermaphrodite.WBbt:0007833.SRP041708.SRX533797~RNASeq.elegans.WBStrain00000001.WBls:0000006.Hermaphrodite.WBbt:0007833.SRP041708.SRX533798~RNASeq.elegans.WBStrain00000001.WBls:0000006.Hermaphrodite.WBbt:0007833.SRP041708.SRX533799~RNASeq.elegans.WBStrain00000001.WBls:0000006.Hermaphrodite.WBbt:0007833.SRP041708.SRX533800~RNASeq.elegans.WBStrain00000001.WBls:0000006.Hermaphrodite.WBbt:0007833.SRP041708.SRX533801~RNASeq.elegans.WBStrain00004602.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP041708.SRX533802~RNASeq.elegans.WBStrain00004602.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP041708.SRX533803~RNASeq.elegans.WBStrain00004602.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP041708.SRX533804~RNASeq.elegans.WBStrain00004602.WBls:0000041.Male.WBbt:0006798.SRP041708.SRX533805~RNASeq.elegans.WBStrain00004602.WBls:0000041.Male.WBbt:0006798.SRP041708.SRX533806~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP041708.SRX533807~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP041708.SRX533808~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP041708.SRX533809~RNASeq.elegans.WBStrain00000001.WBls:0000041.Male.WBbt:0006798.SRP041708.SRX533810	Method: RNAseq|Species: Caenorhabditis elegans|Tissue Specific
423	24957527	WBPaper00045420.ce.rs.paper	GSE58141	GPL13776	1	Global characterization of the oocyte-to-embryo transition in Caenorhabditis elegans uncovers a novel mRNA clearance mechanism.	The oocyte-to-embryo transition (OET) is thought to be mainly driven by post-transcriptional gene regulation. However, expression of both RNAs and proteins during the OET has not been comprehensively assayed. Furthermore, specific molecular mechanisms that regulate gene expression during OET are largely unknown. Here, we quantify and analyze transcriptome-wide, expression of mRNAs and thousands of proteins in Caenorhabditis elegans oocytes, 1-cell, and 2-cell embryos. This represents a first comprehensive gene expression atlas during the OET in animals. We discovered a first wave of degradation in which thousands of mRNAs are cleared shortly after fertilization. Sequence analysis revealed a statistically highly significant presence of a polyC motif in the 3' untranslated regions of most of these degraded mRNAs. Transgenic reporter assays demonstrated that this polyC motif is required and sufficient for mRNA degradation after fertilization. We show that orthologs of human polyC-binding protein specifically bind this motif. Our data suggest a mechanism in which the polyC motif and binding partners direct degradation of maternal mRNAs. Our data also indicate that endogenous siRNAs but not miRNAs promote mRNA clearance during the OET.	8	47143	Stoeckius M	Stoeckius M, Grun D, Kirchner M, Ayoub S, Torti F, Piano F, Herzog M, Selbach M, Rajewsky N	Global characterization of the oocyte-to-embryo transition in Caenorhabditis elegans uncovers a novel mRNA clearance mechanism.	EMBO J	2014	RNASeq.elegans.WBStrain00000001.WBls:0000006.Hermaphrodite.WBbt:0007833.SRP042619.SRX559705~RNASeq.elegans.WBStrain00000001.WBls:0000006.Hermaphrodite.WBbt:0007833.SRP042619.SRX559706~RNASeq.elegans.WBStrain00000001.WBls:0000007.Hermaphrodite.WBbt:0007833.SRP042619.SRX559707~RNASeq.elegans.WBStrain00000001.WBls:0000007.Hermaphrodite.WBbt:0007833.SRP042619.SRX559708~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0006797.SRP042619.SRX559709~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0006797.SRP042619.SRX559710~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0006798.SRP042619.SRX559711~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0006798.SRP042619.SRX559712	Method: RNAseq|Species: Caenorhabditis elegans|Tissue Specific
424	24185836	WBPaper00045464.ce.rs.paper	N.A.	N.A.	1	Systematic evaluation of spliced alignment programs for RNA-seq data.	High-throughput RNA sequencing is an increasingly accessible method for studying gene structure and activity on a genome-wide scale. A critical step in RNA-seq data analysis is the alignment of partial transcript reads to a reference genome sequence. To assess the performance of current mapping software, we invited developers of RNA-seq aligners to process four large human and mouse RNA-seq data sets. In total, we compared 26 mapping protocols based on 11 programs and pipelines and found major performance differences between methods on numerous benchmarks, including alignment yield, basewise accuracy, mismatch and gap placement, exon junction discovery and suitability of alignments for transcript reconstruction. We observed concordant results on real and simulated RNA-seq data, confirming the relevance of the metrics employed. Future developments in RNA-seq alignment methods would benefit from improved placement of multimapped reads, balanced utilization of existing gene annotation and a reduced false discovery rate for splice junctions.	3	47153	Engstrom PG	Engstrom PG, Steijger T, Sipos B, Grant GR, Kahles A, Ratsch G, Goldman N, Hubbard TJ, Harrow J, Guigo R, Bertone P	Systematic evaluation of spliced alignment programs for RNA-seq data.	Nat Methods	2013	RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.ERP003471.ERX278737~RNASeq.elegans.WBStrain00000001.WBls:0000027.Hermaphrodite.WBbt:0007833.ERP003471.ERX278739~RNASeq.elegans.WBStrain00000001.WBls:0000035.Hermaphrodite.WBbt:0007833.ERP003471.ERX278740	Method: RNAseq|Species: Caenorhabditis elegans
425	24098135	WBPaper00045465.ce.rs.paper	N.A.	N.A.	1	Conserved translatome remodeling in nematode species executing a shared developmental transition.	Nematodes of the genus Caenorhabditis enter a developmental diapause state after hatching in the absence of food. To better understand the relative contributions of distinct regulatory modalities to gene expression changes associated with this developmental transition, we characterized genome-wide changes in mRNA abundance and translational efficiency associated with L1 diapause exit in four species using ribosome profiling and mRNA-seq. We found a strong tendency for translational regulation and mRNA abundance processes to act synergistically, together effecting a dramatic remodeling of the gene expression program. While gene-specific differences were observed between species, overall translational dynamics were broadly and functionally conserved. A striking, conserved feature of the response was strong translational suppression of ribosomal protein production during L1 diapause, followed by activation upon resumed development. On a global scale, ribosome footprint abundance changes showed greater similarity between species than changes in mRNA abundance, illustrating a substantial and genome-wide contribution of translational regulation to evolutionary maintenance of stable gene expression.	6	46402	Stadler M	Stadler M, Fire A	Conserved translatome remodeling in nematode species executing a shared developmental transition.	PLoS Genet	2013	RNASeq.elegans.WBStrain00000001.WBls:0000802.Hermaphrodite.WBbt:0007833.SRP026198.SRX311774~RNASeq.elegans.WBStrain00000001.WBls:0000802.Hermaphrodite.WBbt:0007833.SRP026198.SRX311775~RNASeq.elegans.WBStrain00000001.WBls:0000802.Hermaphrodite.WBbt:0007833.SRP026198.SRX311776~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP026198.SRX311777~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP026198.SRX311778~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP026198.SRX311779	Method: RNAseq|Species: Caenorhabditis elegans
426	25060624	WBPaper00045521.ce.rs.paper	N.A.	N.A.	1	A new dataset of spermatogenic vs. oogenic transcriptomes in the nematode Caenorhabditis elegans.	The nematode Caenorhabditis elegans is an important model for studies of germ cell biology, including the meiotic cell cycle, gamete specification as sperm or oocyte, and gamete development. Fundamental to those studies is a genome-level knowledge of the germline transcriptome. Here, we use RNA-Seq to identify genes expressed in isolated XX gonads, which are approximately 95% germline and 5% somatic gonadal tissue. We generate data from mutants making either sperm [fem-3(q96)] or oocytes [fog-2(q71)], both grown at 22. Our dataset identifies a total of 10,754 mRNAs in the polyadenylated transcriptome of XX gonads, with 2748 enriched in spermatogenic gonads, 1732 enriched in oogenic gonads, and the remaining 6274 not enriched in either. These spermatogenic, oogenic, and gender-neutral gene datasets compare well with those of previous studies, but double the number of genes identified. A comparison of the additional genes found in our study with in situ hybridization patterns in the Kohara database suggests that most are expressed in the germline. We also query our RNA-Seq data for differential exon usage and find 351 mRNAs with sex-enriched isoforms. We suggest that this new dataset will prove useful for studies focusing on C. elegans germ cell biology.	16	47140	Ortiz MA	Ortiz MA, Noble D, Sorokin EP, Kimble J	A new dataset of spermatogenic vs. oogenic transcriptomes in the nematode Caenorhabditis elegans.	G3 (Bethesda)	2014	RNASeq.elegans.WBStrain00004538.WBls:0000002.Hermaphrodite.WBbt:0006798.SRP041461.SRX527951~RNASeq.elegans.WBStrain00004538.WBls:0000002.Hermaphrodite.WBbt:0006798.SRP041461.SRX527952~RNASeq.elegans.WBStrain00004538.WBls:0000002.Hermaphrodite.WBbt:0006798.SRP041461.SRX527953~RNASeq.elegans.WBStrain00004538.WBls:0000002.Hermaphrodite.WBbt:0006798.SRP041461.SRX527954~RNASeq.elegans.WBStrain00004538.WBls:0000002.Hermaphrodite.WBbt:0006798.SRP041461.SRX527955~RNASeq.elegans.WBStrain00004538.WBls:0000002.Hermaphrodite.WBbt:0006798.SRP041461.SRX527956~RNASeq.elegans.WBStrain00004538.WBls:0000002.Hermaphrodite.WBbt:0006798.SRP041461.SRX527957~RNASeq.elegans.WBStrain00004538.WBls:0000002.Hermaphrodite.WBbt:0006798.SRP041461.SRX527958~RNASeq.elegans.WBStrain00022571.WBls:0000002.Hermaphrodite.WBbt:0006797.SRP041461.SRX527959~RNASeq.elegans.WBStrain00022571.WBls:0000002.Hermaphrodite.WBbt:0006797.SRP041461.SRX527960~RNASeq.elegans.WBStrain00022571.WBls:0000002.Hermaphrodite.WBbt:0006797.SRP041461.SRX527961~RNASeq.elegans.WBStrain00022571.WBls:0000002.Hermaphrodite.WBbt:0006797.SRP041461.SRX527962~RNASeq.elegans.WBStrain00022571.WBls:0000002.Hermaphrodite.WBbt:0006797.SRP041461.SRX527963~RNASeq.elegans.WBStrain00022571.WBls:0000002.Hermaphrodite.WBbt:0006797.SRP041461.SRX527964~RNASeq.elegans.WBStrain00022571.WBls:0000002.Hermaphrodite.WBbt:0006797.SRP041461.SRX527965~RNASeq.elegans.WBStrain00022571.WBls:0000002.Hermaphrodite.WBbt:0006797.SRP041461.SRX527966	Method: RNAseq|Species: Caenorhabditis elegans|Topic: oogenesis|Topic: spermatogenesis|Tissue Specific
427	25146970	WBPaper00045618.ce.rs.paper	GSE54030	GPL13776	1	Competence for chemical reprogramming of sexual fate correlates with an intersexual molecular signature in Caenorhabditis elegans.	In multicellular organisms, genetic programs guide cells to adopt cell fates as tissues are formed during development, maintained in adults, and repaired after injury. Here we explore how a small molecule in the environment can switch a genetic program from one fate to another. Wild-type Caenorhabditis elegans XX adult hermaphrodites make oocytes continuously, but certain mutant XX adults make sperm instead in an otherwise hermaphrodite soma. Thus, puf-8; lip-1 XX adults make only sperm, but they can be switched from sperm to oocyte production by treatment with a small-molecule MEK inhibitor. To ask whether this chemical reprogramming is common, we tested six XX sperm-only mutants, but found only one other capable of cell fate switching, fbf-1; lip-1. Therefore, reprogramming competence relies on genotype, with only certain mutants capable of responding to the MEK inhibitor with a cell fate change. To gain insight into the molecular basis of competence for chemical reprogramming, we compared polyadenylated transcriptomes of competent and noncompetent XX sperm-only mutants in the absence of the MEK inhibitor and hence in the absence of cell fate reprogramming. Despite their cellular production of sperm, competent mutants were enriched for oogenic messenger RNAs relative to mutants lacking competence for chemical reprogramming. In addition, competent mutants expressed the oocyte-specific protein RME-2, whereas those lacking competence did not. Therefore, mutants competent for reprogramming possess an intersexual molecular profile at both RNA and protein levels. We suggest that this intersexual molecular signature is diagnostic of an intermediate network state that poises the germline tissue for changing its cellular fate in response to environmental cues.	52	47139	Sorokin EP	Sorokin EP, Gasch AP, Kimble J	Competence for chemical reprogramming of sexual fate correlates with an intersexual molecular signature in Caenorhabditis elegans.	Genetics	2014	RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426002~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426003~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426004~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426005~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426006~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426007~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426008~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426009~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426010~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426011~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426012~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426013~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426014~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426015~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426016~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426017~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426018~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426019~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426020~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426021~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426022~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426023~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426024~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426025~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426026~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426027~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426028~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426029~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426030~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426031~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426032~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426033~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426034~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426035~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426036~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426037~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426038~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426039~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426040~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426041~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426042~RNASeq.elegans.WBStrain00022651.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426043~RNASeq.elegans.WBStrain00022618.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426044~RNASeq.elegans.WBStrain00022618.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426045~RNASeq.elegans.WBStrain00022618.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426046~RNASeq.elegans.WBStrain00022618.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426047~RNASeq.elegans.WBStrain00022618.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426048~RNASeq.elegans.WBStrain00022618.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426049~RNASeq.elegans.WBStrain00022618.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426050~RNASeq.elegans.WBStrain00022618.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426051~RNASeq.elegans.WBStrain00022618.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426052~RNASeq.elegans.WBStrain00022618.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP035359.SRX426053	Method: RNAseq|Species: Caenorhabditis elegans
428	25199833	WBPaper00045705.ce.rs.paper	GSE59705	GPL13776	1	Alternative 3' UTR selection controls PAR-5 homeostasis and cell polarity in C. elegans embryos.	Cell polarity in one-cell C. elegans embryos guides asymmetric cell division and cell-fate specification. Shortly after fertilization, embryos establish two antagonistic cortical domains of PAR proteins. Here, we find that the conserved polarity factor PAR-5 regulates PAR domain size in a dose-dependent manner. Using quantitative imaging and controlled genetic manipulation, we find that PAR-5 protein levels reflect the cumulative output of three mRNA isoforms with different translational efficiencies mediated by their 3' UTRs. 3' UTR selection is regulated, influencing PAR-5 protein abundance. Alternative splicing underlies the selection of par-5 3' UTR isoforms. 3' UTR splicing is enhanced by the SR protein kinase SPK-1, and accordingly, SPK-1 is required for wild-type PAR-5 levels and PAR domain size. Precise regulation of par-5 isoform selection is essential for polarization when the posterior PAR network is compromised. Together, strict control of PAR-5 protein levels and feedback from polarity to par-5 3' UTR selection confer robustness to embryo polarization.	8	47153	Mikl M	Mikl M, Cowan CR	Alternative 3' UTR selection controls PAR-5 homeostasis and cell polarity in C. elegans embryos.	Cell Rep	2014	RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP044752.SRX659943~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP044752.SRX659944~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP044752.SRX659945~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP044752.SRX659946~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP044752.SRX659947~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP044752.SRX659948~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP044752.SRX659949~RNASeq.elegans.WBStrain00000001.WBls:0000002.Hermaphrodite.WBbt:0007833.SRP044752.SRX659950	Method: RNAseq|Species: Caenorhabditis elegans
429	25217583	WBPaper00045729.ce.rs.paper	N.A.	N.A.	1	The cytoplasmic poly(A) polymerases GLD-2 and GLD-4 promote general gene expression via distinct mechanisms.	Post-transcriptional gene regulation mechanisms decide on cellular mRNA activities. Essential gatekeepers of post-transcriptional mRNA regulation are broadly conserved mRNA-modifying enzymes, such as cytoplasmic poly(A) polymerases (cytoPAPs). Although these non-canonical nucleotidyltransferases efficiently elongate mRNA poly(A) tails in artificial tethering assays, we still know little about their global impact on poly(A) metabolism and their individual molecular roles in promoting protein production in organisms. Here, we use the animal model Caenorhabditis elegans to investigate the global mechanisms of two germline-enriched cytoPAPs, GLD-2 and GLD-4, by combining polysome profiling with RNA sequencing. Our analyses suggest that GLD-2 activity mediates mRNA stability of many translationally repressed mRNAs. This correlates with a general shortening of long poly(A) tails in gld-2-compromised animals, suggesting that most if not all targets are stabilized via robust GLD-2-mediated polyadenylation. By contrast, only mild polyadenylation defects are found in gld-4-compromised animals and few mRNAs change in abundance. Interestingly, we detect a reduced number of polysomes in gld-4 mutants and GLD-4 protein co-sediments with polysomes, which together suggest that GLD-4 might stimulate or maintain translation directly. Our combined data show that distinct cytoPAPs employ different RNA-regulatory mechanisms to promote gene expression, offering new insights into translational activation of mRNAs.	9	47149	Nousch M	Nousch M, Yeroslaviz A, Habermann B, Eckmann CR	The cytoplasmic poly(A) polymerases GLD-2 and GLD-4 promote general gene expression via distinct mechanisms.	Nucleic Acids Res	2014	RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP043990.SRX643418~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP043990.SRX643419~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP043990.SRX643420~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP043990.SRX643421~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP043990.SRX643422~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP043990.SRX643423~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP043990.SRX643424~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP043990.SRX643425~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0007833.SRP043990.SRX643426	Method: RNAseq|Species: Caenorhabditis elegans
430	25346348	WBPaper00045934.ce.rs.paper	N.A.	N.A.	1	Expression profile of Caenorhabditis elegans mutant for the Werner syndrome gene ortholog reveals the impact of vitamin C on development to increase life span.	BACKGROUND: Werner Syndrome (WS) is a rare disorder characterized by the premature onset of a number of age-related diseases. The gene responsible for WS encodes a DNA helicase/exonuclease protein believed to affect different aspects of transcription, replication, and DNA repair. Caenorhabditis elegans (C. elegans) with a nonfunctional wrn-1 DNA helicase ortholog also exhibits a shorter life span, which can be rescued by vitamin C. In this study, we analyzed the impact of a mutation in the wrn-1 gene and the dietary supplementation of vitamin C on the global mRNA expression of the whole C. elegans by the RNA-seq technology. RESULTS: Vitamin C increased the mean life span of the wrn-1(gk99) mutant and the N2 wild type strains at 25C. However, the alteration of gene expression by vitamin C is different between wrn-1(gk99) and wild type strains. We observed alteration in the expression of 1522 genes in wrn-1(gk99) worms compared to wild type animals. Such genes significantly affected the metabolism of lipid, cellular ketone, organic acid, and carboxylic acids. Vitamin C, in return, altered the expression of genes in wrn-1(gk99) worms involved in locomotion and anatomical structure development. Proteolysis was the only biological process significantly affected by vitamin C in wild type worms. CONCLUSIONS: Expression profiling of wrn-1(gk99) worms revealed a very different response to the addition of vitamin C compared to wild type worms. Finally, vitamin C extended the life span of wrn-1(gk99) animals by altering biological processes involved mainly in locomotion and anatomical structure development.	12	47154	Dallaire A	Dallaire A, Proulx S, Simard MJ, Lebel M	Expression profile of Caenorhabditis elegans mutant for the Werner syndrome gene ortholog reveals the impact of vitamin C on development to increase life span.	BMC Genomics	2014	RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP035479.SRX435689~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP035479.SRX435690~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP035479.SRX435691~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP035479.SRX435692~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP035479.SRX435693~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP035479.SRX435694~RNASeq.elegans.WBStrain00035559.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP035479.SRX435695~RNASeq.elegans.WBStrain00035559.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP035479.SRX435696~RNASeq.elegans.WBStrain00035559.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP035479.SRX435697~RNASeq.elegans.WBStrain00035559.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP035479.SRX435698~RNASeq.elegans.WBStrain00035559.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP035479.SRX435699~RNASeq.elegans.WBStrain00035559.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP035479.SRX435700	Method: RNAseq|Species: Caenorhabditis elegans
431	25366321	WBPaper00045971.ce.rs.paper	N.A.	N.A.	1	The RtcB RNA ligase is an essential component of the metazoan unfolded protein response.	RNA ligation can regulate RNA function by altering RNA sequence, structure and coding potential. For example, the function of XBP1 in mediating the unfolded protein response requires RNA ligation, as does the maturation of some tRNAs. Here, we describe a novel in vivo model in Caenorhabditis elegans for the conserved RNA ligase RtcB and show that RtcB ligates the xbp-1 mRNA during the IRE-1 branch of the unfolded protein response. Without RtcB, protein stress results in the accumulation of unligated xbp-1 mRNA fragments, defects in the unfolded protein response, and decreased lifespan. RtcB also ligates endogenous pre-tRNA halves, and RtcB mutants have defects in growth and lifespan that can be bypassed by expression of pre-spliced tRNAs. In addition, animals that lack RtcB have defects that are independent of tRNA maturation and the unfolded protein response. Thus, RNA ligation by RtcB is required for the function of multiple endogenous target RNAs including both xbp-1 and tRNAs. RtcB is uniquely capable of performing these ligation functions, and RNA ligation by RtcB mediates multiple essential processes in vivo.	4	47145	Kosmaczewski SG	Kosmaczewski SG, Edwards TJ, Han SM, Eckwahl MJ, Meyer BI, Peach S, Hesselberth JR, Wolin SL, Hammarlund M	The RtcB RNA ligase is an essential component of the metazoan unfolded protein response.	EMBO Rep	2014	RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP047464.SRX709649~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP047464.SRX709650~RNASeq.elegans.WBStrain00006736.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP047464.SRX709651~RNASeq.elegans.WBStrain00006736.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP047464.SRX709652	Method: RNAseq|Species: Caenorhabditis elegans|Topic: obsolete mRNA splicing via endonucleolytic cleavage and ligation involved in unfolded protein response|Topic: endoplasmic reticulum unfolded protein response|Topic: endoplasmic reticulum
432	25378320	WBPaper00045985.ce.rs.paper	N.A.	N.A.	1	Functional characterization of C. elegans Y-box-binding proteins reveals tissue-specific functions and a critical role in the formation of polysomes.	The cold shock domain is one of the most highly conserved motifs between bacteria and higher eukaryotes. Y-box-binding proteins represent a subfamily of cold shock domain proteins with pleiotropic functions, ranging from transcription in the nucleus to translation in the cytoplasm. These proteins have been investigated in all major model organisms except Caenorhabditis elegans. In this study, we set out to fill this gap and present a functional characterization of CEYs, the C. elegans Y-box-binding proteins. We find that, similar to other organisms, CEYs are essential for proper gametogenesis. However, we also report a novel function of these proteins in the formation of large polysomes in the soma. In the absence of the somatic CEYs, polysomes are dramatically reduced with a simultaneous increase in monosomes and disomes, which, unexpectedly, has no obvious impact on animal biology. Because transcripts that are enriched in polysomes in wild-type animals tend to be less abundant in the absence of CEYs, our findings suggest that large polysomes might depend on transcript stabilization mediated by CEY proteins.	4	47142	Arnold A	Arnold A, Rahman MM, Lee MC, Muehlhaeusser S, Katic I, Gaidatzis D, Hess D, Scheckel C, Wright JE, Stetak A, Boag PR, Ciosk R	Functional characterization of C. elegans Y-box-binding proteins reveals tissue-specific functions and a critical role in the formation of polysomes.	Nucleic Acids Res	2014	RNASeq.elegans.WBStrain00034434.WBls:0000063.Hermaphrodite.WBbt:0005175.SRP049412.SRX747677~RNASeq.elegans.WBStrain00034434.WBls:0000063.Hermaphrodite.WBbt:0005175.SRP049412.SRX747678~RNASeq.elegans.WBStrain00034434.WBls:0000063.Hermaphrodite.WBbt:0005784.SRP049412.SRX747679~RNASeq.elegans.WBStrain00034434.WBls:0000063.Hermaphrodite.WBbt:0005784.SRP049412.SRX747680	Method: RNAseq|Species: Caenorhabditis elegans|Tissue Specific
433	25487147	WBPaper00046121.ce.rs.paper	N.A.	N.A.	1	Spatiotemporal transcriptomics reveals the evolutionary history of the endoderm germ layer.	The concept of germ layers has been one of the foremost organizing principles in developmental biology, classification, systematics and evolution for 150 years (refs 1 - 3). Of the three germ layers, the mesoderm is found in bilaterian animals but is absent in species in the phyla Cnidaria and Ctenophora, which has been taken as evidence that the mesoderm was the final germ layer to evolve. The origin of the ectoderm and endoderm germ layers, however, remains unclear, with models supporting the antecedence of each as well as a simultaneous origin. Here we determine the temporal and spatial components of gene expression spanning embryonic development for all Caenorhabditis elegans genes and use it to determine the evolutionary ages of the germ layers. The gene expression program of the mesoderm is induced after those of the ectoderm and endoderm, thus making it the last germ layer both to evolve and to develop. Strikingly, the C. elegans endoderm and ectoderm expression programs do not co-induce; rather the endoderm activates earlier, and this is also observed in the expression of endoderm orthologues during the embryology of the frog Xenopus tropicalis, the sea anemone Nematostella vectensis and the sponge Amphimedon queenslandica. Querying the phylogenetic ages of specifically expressed genes reveals that the endoderm comprises older genes. Taken together, we propose that the endoderm program dates back to the origin of multicellularity, whereas the ectoderm originated as a secondary germ layer freed from ancestral feeding functions.	154	47156	Hashimshony T	Hashimshony T, Feder M, Levin M, Hall BK, Yanai I	Spatiotemporal transcriptomics reveals the evolutionary history of the endoderm germ layer.	Nature	2015	RNASeq.elegans.WBStrain00000001.WBls:0000141.Hermaphrodite.WBbt:0007833.SRP029448.SRX343161~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0007833.SRP029448.SRX343162~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0007833.SRP029448.SRX343163~RNASeq.elegans.WBStrain00000001.WBls:0000181.Hermaphrodite.WBbt:0007833.SRP029448.SRX343164~RNASeq.elegans.WBStrain00000001.WBls:0000191.Hermaphrodite.WBbt:0007833.SRP029448.SRX343165~RNASeq.elegans.WBStrain00000001.WBls:0000231.Hermaphrodite.WBbt:0007833.SRP029448.SRX343167~RNASeq.elegans.WBStrain00000001.WBls:0000251.Hermaphrodite.WBbt:0007833.SRP029448.SRX343168~RNASeq.elegans.WBStrain00000001.WBls:0000261.Hermaphrodite.WBbt:0007833.SRP029448.SRX343169~RNASeq.elegans.WBStrain00000001.WBls:0000281.Hermaphrodite.WBbt:0007833.SRP029448.SRX343170~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0007833.SRP029448.SRX343171~RNASeq.elegans.WBStrain00000001.WBls:0000301.Hermaphrodite.WBbt:0007833.SRP029448.SRX343172~RNASeq.elegans.WBStrain00000001.WBls:0000311.Hermaphrodite.WBbt:0007833.SRP029448.SRX343173~RNASeq.elegans.WBStrain00000001.WBls:0000321.Hermaphrodite.WBbt:0007833.SRP029448.SRX343174~RNASeq.elegans.WBStrain00000001.WBls:0000331.Hermaphrodite.WBbt:0007833.SRP029448.SRX343175~RNASeq.elegans.WBStrain00000001.WBls:0000331.Hermaphrodite.WBbt:0007833.SRP029448.SRX343176~RNASeq.elegans.WBStrain00000001.WBls:0000351.Hermaphrodite.WBbt:0007833.SRP029448.SRX343178~RNASeq.elegans.WBStrain00000001.WBls:0000351.Hermaphrodite.WBbt:0007833.SRP029448.SRX343179~RNASeq.elegans.WBStrain00000001.WBls:0000361.Hermaphrodite.WBbt:0007833.SRP029448.SRX343180~RNASeq.elegans.WBStrain00000001.WBls:0000391.Hermaphrodite.WBbt:0007833.SRP029448.SRX343181~RNASeq.elegans.WBStrain00000001.WBls:0000401.Hermaphrodite.WBbt:0007833.SRP029448.SRX343182~RNASeq.elegans.WBStrain00000001.WBls:0000421.Hermaphrodite.WBbt:0007833.SRP029448.SRX343184~RNASeq.elegans.WBStrain00000001.WBls:0000431.Hermaphrodite.WBbt:0007833.SRP029448.SRX343185~RNASeq.elegans.WBStrain00000001.WBls:0000451.Hermaphrodite.WBbt:0007833.SRP029448.SRX343186~RNASeq.elegans.WBStrain00000001.WBls:0000461.Hermaphrodite.WBbt:0007833.SRP029448.SRX343187~RNASeq.elegans.WBStrain00000001.WBls:0000471.Hermaphrodite.WBbt:0007833.SRP029448.SRX343189~RNASeq.elegans.WBStrain00000001.WBls:0000491.Hermaphrodite.WBbt:0007833.SRP029448.SRX343191~RNASeq.elegans.WBStrain00000001.WBls:0000501.Hermaphrodite.WBbt:0007833.SRP029448.SRX343192~RNASeq.elegans.WBStrain00000001.WBls:0000511.Hermaphrodite.WBbt:0007833.SRP029448.SRX343194~RNASeq.elegans.WBStrain00000001.WBls:0000521.Hermaphrodite.WBbt:0007833.SRP029448.SRX343195~RNASeq.elegans.WBStrain00000001.WBls:0000531.Hermaphrodite.WBbt:0007833.SRP029448.SRX343196~RNASeq.elegans.WBStrain00000001.WBls:0000531.Hermaphrodite.WBbt:0007833.SRP029448.SRX343197~RNASeq.elegans.WBStrain00000001.WBls:0000541.Hermaphrodite.WBbt:0007833.SRP029448.SRX343198~RNASeq.elegans.WBStrain00000001.WBls:0000541.Hermaphrodite.WBbt:0007833.SRP029448.SRX343199~RNASeq.elegans.WBStrain00000001.WBls:0000551.Hermaphrodite.WBbt:0007833.SRP029448.SRX343200~RNASeq.elegans.WBStrain00000001.WBls:0000561.Hermaphrodite.WBbt:0007833.SRP029448.SRX343201~RNASeq.elegans.WBStrain00000001.WBls:0000581.Hermaphrodite.WBbt:0007833.SRP029448.SRX343202~RNASeq.elegans.WBStrain00000001.WBls:0000621.Hermaphrodite.WBbt:0007833.SRP029448.SRX343203~RNASeq.elegans.WBStrain00000001.WBls:0000694.Hermaphrodite.WBbt:0007833.SRP029448.SRX343205~RNASeq.elegans.WBStrain00000001.WBls:0000695.Hermaphrodite.WBbt:0007833.SRP029448.SRX343206~RNASeq.elegans.WBStrain00000001.WBls:0000696.Hermaphrodite.WBbt:0007833.SRP029448.SRX343207~RNASeq.elegans.WBStrain00000001.WBls:0000697.Hermaphrodite.WBbt:0007833.SRP029448.SRX343208~RNASeq.elegans.WBStrain00000001.WBls:0000699.Hermaphrodite.WBbt:0007833.SRP029448.SRX343210~RNASeq.elegans.WBStrain00000001.WBls:0000700.Hermaphrodite.WBbt:0007833.SRP029448.SRX343211~RNASeq.elegans.WBStrain00000001.WBls:0000701.Hermaphrodite.WBbt:0007833.SRP029448.SRX343212~RNASeq.elegans.WBStrain00000001.WBls:0000702.Hermaphrodite.WBbt:0007833.SRP029448.SRX343213~RNASeq.elegans.WBStrain00000001.WBls:0000703.Hermaphrodite.WBbt:0007833.SRP029448.SRX343214~RNASeq.elegans.WBStrain00000001.WBls:0000007.Hermaphrodite.WBbt:0007833.SRP029448.SRX343215~RNASeq.elegans.WBStrain00000001.WBls:0000007.Hermaphrodite.WBbt:0007833.SRP029448.SRX343216~RNASeq.elegans.WBStrain00000001.WBls:0000007.Hermaphrodite.WBbt:0004015.SRP029448.SRX343218~RNASeq.elegans.WBStrain00000001.WBls:0000007.Hermaphrodite.WBbt:0004015.SRP029448.SRX343219~RNASeq.elegans.WBStrain00000001.WBls:0000131.Hermaphrodite.WBbt:0004015.SRP029448.SRX343220~RNASeq.elegans.WBStrain00000001.WBls:0000131.Hermaphrodite.WBbt:0006876.SRP029448.SRX343221~RNASeq.elegans.WBStrain00000001.WBls:0000131.Hermaphrodite.WBbt:0006876.SRP029448.SRX343222~RNASeq.elegans.WBStrain00000001.WBls:0000131.Hermaphrodite.WBbt:0006876.SRP029448.SRX343223~RNASeq.elegans.WBStrain00000001.WBls:0000131.Hermaphrodite.WBbt:0006771.SRP029448.SRX343225~RNASeq.elegans.WBStrain00000001.WBls:0000131.Hermaphrodite.WBbt:0006771.SRP029448.SRX343226~RNASeq.elegans.WBStrain00000001.WBls:0000131.Hermaphrodite.WBbt:0004015.SRP029448.SRX343227~RNASeq.elegans.WBStrain00000001.WBls:0000131.Hermaphrodite.WBbt:0004015.SRP029448.SRX343228~RNASeq.elegans.WBStrain00000001.WBls:0000131.Hermaphrodite.WBbt:0004015.SRP029448.SRX343229~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0004804.SRP029448.SRX343230~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0004804.SRP029448.SRX343231~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0004804.SRP029448.SRX343232~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0004804.SRP029448.SRX343233~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0004804.SRP029448.SRX343234~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0004804.SRP029448.SRX343235~RNASeq.elegans.WBStrain00000001.WBls:0000201.Hermaphrodite.WBbt:0004804.SRP029448.SRX343236~RNASeq.elegans.WBStrain00000001.WBls:0000201.Hermaphrodite.WBbt:0004804.SRP029448.SRX343237~RNASeq.elegans.WBStrain00000001.WBls:0000201.Hermaphrodite.WBbt:0004804.SRP029448.SRX343238~RNASeq.elegans.WBStrain00000001.WBls:0000221.Hermaphrodite.WBbt:0004804.SRP029448.SRX343241~RNASeq.elegans.WBStrain00000001.WBls:0000251.Hermaphrodite.WBbt:0004804.SRP029448.SRX343242~RNASeq.elegans.WBStrain00000001.WBls:0000251.Hermaphrodite.WBbt:0004804.SRP029448.SRX343243~RNASeq.elegans.WBStrain00000001.WBls:0000251.Hermaphrodite.WBbt:0004804.SRP029448.SRX343244~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0004804.SRP029448.SRX343245~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0004804.SRP029448.SRX343246~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0004804.SRP029448.SRX343247~RNASeq.elegans.WBStrain00000001.WBls:0000381.Hermaphrodite.WBbt:0004804.SRP029448.SRX343248~RNASeq.elegans.WBStrain00000001.WBls:0000381.Hermaphrodite.WBbt:0004804.SRP029448.SRX343249~RNASeq.elegans.WBStrain00000001.WBls:0000381.Hermaphrodite.WBbt:0004804.SRP029448.SRX343250~RNASeq.elegans.WBStrain00000001.WBls:0000471.Hermaphrodite.WBbt:0004804.SRP029448.SRX343251~RNASeq.elegans.WBStrain00000001.WBls:0000017.Hermaphrodite.WBbt:0004804.SRP029448.SRX343252~RNASeq.elegans.WBStrain00000001.WBls:0000017.Hermaphrodite.WBbt:0004804.SRP029448.SRX343253~RNASeq.elegans.WBStrain00000001.WBls:0000017.Hermaphrodite.WBbt:0004804.SRP029448.SRX343254~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0004458.SRP029448.SRX343255~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0004458.SRP029448.SRX343256~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0004458.SRP029448.SRX343257~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0004458.SRP029448.SRX343258~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0004458.SRP029448.SRX343259~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0004458.SRP029448.SRX343260~RNASeq.elegans.WBStrain00000001.WBls:0000201.Hermaphrodite.WBbt:0004458.SRP029448.SRX343261~RNASeq.elegans.WBStrain00000001.WBls:0000201.Hermaphrodite.WBbt:0004458.SRP029448.SRX343262~RNASeq.elegans.WBStrain00000001.WBls:0000201.Hermaphrodite.WBbt:0004458.SRP029448.SRX343263~RNASeq.elegans.WBStrain00000001.WBls:0000221.Hermaphrodite.WBbt:0004458.SRP029448.SRX343264~RNASeq.elegans.WBStrain00000001.WBls:0000221.Hermaphrodite.WBbt:0004458.SRP029448.SRX343265~RNASeq.elegans.WBStrain00000001.WBls:0000221.Hermaphrodite.WBbt:0004458.SRP029448.SRX343266~RNASeq.elegans.WBStrain00000001.WBls:0000251.Hermaphrodite.WBbt:0004458.SRP029448.SRX343268~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0004458.SRP029448.SRX343271~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0004458.SRP029448.SRX343272~RNASeq.elegans.WBStrain00000001.WBls:0000381.Hermaphrodite.WBbt:0004458.SRP029448.SRX343274~RNASeq.elegans.WBStrain00000001.WBls:0000381.Hermaphrodite.WBbt:0004458.SRP029448.SRX343275~RNASeq.elegans.WBStrain00000001.WBls:0000471.Hermaphrodite.WBbt:0004458.SRP029448.SRX343276~RNASeq.elegans.WBStrain00000001.WBls:0000017.Hermaphrodite.WBbt:0004458.SRP029448.SRX343277~RNASeq.elegans.WBStrain00000001.WBls:0000017.Hermaphrodite.WBbt:0004458.SRP029448.SRX343278~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0004015.SRP029448.SRX343280~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0004015.SRP029448.SRX343281~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0004015.SRP029448.SRX343282~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0004015.SRP029448.SRX343283~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0004015.SRP029448.SRX343284~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0004015.SRP029448.SRX343285~RNASeq.elegans.WBStrain00000001.WBls:0000201.Hermaphrodite.WBbt:0004015.SRP029448.SRX343287~RNASeq.elegans.WBStrain00000001.WBls:0000201.Hermaphrodite.WBbt:0004015.SRP029448.SRX343288~RNASeq.elegans.WBStrain00000001.WBls:0000221.Hermaphrodite.WBbt:0004015.SRP029448.SRX343290~RNASeq.elegans.WBStrain00000001.WBls:0000221.Hermaphrodite.WBbt:0004015.SRP029448.SRX343291~RNASeq.elegans.WBStrain00000001.WBls:0000251.Hermaphrodite.WBbt:0004015.SRP029448.SRX343292~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0004015.SRP029448.SRX343294~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0004015.SRP029448.SRX343295~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0004015.SRP029448.SRX343296~RNASeq.elegans.WBStrain00000001.WBls:0000381.Hermaphrodite.WBbt:0004015.SRP029448.SRX343297~RNASeq.elegans.WBStrain00000001.WBls:0000381.Hermaphrodite.WBbt:0004015.SRP029448.SRX343299~RNASeq.elegans.WBStrain00000001.WBls:0000471.Hermaphrodite.WBbt:0004015.SRP029448.SRX343300~RNASeq.elegans.WBStrain00000001.WBls:0000471.Hermaphrodite.WBbt:0004015.SRP029448.SRX343301~RNASeq.elegans.WBStrain00000001.WBls:0000471.Hermaphrodite.WBbt:0004015.SRP029448.SRX343302~RNASeq.elegans.WBStrain00000001.WBls:0000017.Hermaphrodite.WBbt:0004015.SRP029448.SRX343304~RNASeq.elegans.WBStrain00000001.WBls:0000017.Hermaphrodite.WBbt:0004015.SRP029448.SRX343305~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0003810.SRP029448.SRX343308~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0003810.SRP029448.SRX343309~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0003810.SRP029448.SRX343310~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0003810.SRP029448.SRX343311~RNASeq.elegans.WBStrain00000001.WBls:0000201.Hermaphrodite.WBbt:0003810.SRP029448.SRX343312~RNASeq.elegans.WBStrain00000001.WBls:0000201.Hermaphrodite.WBbt:0003810.SRP029448.SRX343313~RNASeq.elegans.WBStrain00000001.WBls:0000221.Hermaphrodite.WBbt:0003810.SRP029448.SRX343314~RNASeq.elegans.WBStrain00000001.WBls:0000221.Hermaphrodite.WBbt:0003810.SRP029448.SRX343315~RNASeq.elegans.WBStrain00000001.WBls:0000251.Hermaphrodite.WBbt:0003810.SRP029448.SRX343317~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0003810.SRP029448.SRX343318~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0003810.SRP029448.SRX343319~RNASeq.elegans.WBStrain00000001.WBls:0000381.Hermaphrodite.WBbt:0003810.SRP029448.SRX343320~RNASeq.elegans.WBStrain00000001.WBls:0000017.Hermaphrodite.WBbt:0003810.SRP029448.SRX343324~RNASeq.elegans.WBStrain00000001.WBls:0000017.Hermaphrodite.WBbt:0003810.SRP029448.SRX343325~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0008115.SRP029448.SRX343326~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0008115.SRP029448.SRX343327~RNASeq.elegans.WBStrain00000001.WBls:0000151.Hermaphrodite.WBbt:0008115.SRP029448.SRX343328~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0008115.SRP029448.SRX343329~RNASeq.elegans.WBStrain00000001.WBls:0000171.Hermaphrodite.WBbt:0008115.SRP029448.SRX343330~RNASeq.elegans.WBStrain00000001.WBls:0000201.Hermaphrodite.WBbt:0008115.SRP029448.SRX343331~RNASeq.elegans.WBStrain00000001.WBls:0000201.Hermaphrodite.WBbt:0008115.SRP029448.SRX343332~RNASeq.elegans.WBStrain00000001.WBls:0000221.Hermaphrodite.WBbt:0008115.SRP029448.SRX343333~RNASeq.elegans.WBStrain00000001.WBls:0000221.Hermaphrodite.WBbt:0008115.SRP029448.SRX343334~RNASeq.elegans.WBStrain00000001.WBls:0000251.Hermaphrodite.WBbt:0008115.SRP029448.SRX343335~RNASeq.elegans.WBStrain00000001.WBls:0000251.Hermaphrodite.WBbt:0008115.SRP029448.SRX343336~RNASeq.elegans.WBStrain00000001.WBls:0000251.Hermaphrodite.WBbt:0008115.SRP029448.SRX343337~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0008115.SRP029448.SRX343338~RNASeq.elegans.WBStrain00000001.WBls:0000291.Hermaphrodite.WBbt:0008115.SRP029448.SRX343339~RNASeq.elegans.WBStrain00000001.WBls:0000381.Hermaphrodite.WBbt:0008115.SRP029448.SRX343340~RNASeq.elegans.WBStrain00000001.WBls:0000471.Hermaphrodite.WBbt:0008115.SRP029448.SRX343341~RNASeq.elegans.WBStrain00000001.WBls:0000017.Hermaphrodite.WBbt:0008115.SRP029448.SRX343342	Method: RNAseq|Species: Caenorhabditis elegans|Tissue Specific
434	25720978	WBPaper00046497.ce.rs.paper	N.A.	N.A.	1	Overlapping and unique signatures in the proteomic and transcriptomic responses of the nematode Caenorhabditis elegans toward pathogenic Bacillus thuringiensis.	Pathogen infection can activate multiple signaling cascades that ultimately alter the abundance of molecules in cells. This change can be measured both at the transcript and protein level. Studies analyzing the immune response at both levels are, however, rare. Here, we compare transcriptome and proteome data generated after infection of the nematode and model organism Caenorhabditis elegans with the Gram-positive pathogen Bacillus thuringiensis. Our analysis revealed a high overlap between abundance changes of corresponding transcripts and gene products, especially for genes encoding C-type lectin domain-containing proteins, indicating their particular role in worm immunity. We additionally identified a unique signature at the proteome level, suggesting that the C. elegans response to infection is shaped by changes beyond transcription. Such effects appear to be influenced by AMP-activated protein kinases (AMPKs), which may thus represent previously unknown regulators of C. elegans immune defense.	24	47149	Yang W	Yang W, Dierking K, Esser D, Tholey A, Leippe M, Rosenstiel P, Schulenburg H	Overlapping and unique signatures in the proteomic and transcriptomic responses of the nematode Caenorhabditis elegans toward pathogenic Bacillus thuringiensis.	Dev Comp Immunol	2015	RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819627~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819628~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819629~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819630~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819631~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819632~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819633~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819634~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819635~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819636~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819637~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819638~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819639~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819640~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819641~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819642~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819643~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819644~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819645~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819646~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819647~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819648~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819649~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0007833.SRP051404.SRX819650	Method: RNAseq|Species: Caenorhabditis elegans|Topic: defense response|Topic: defense response to other organism|Topic: innate immune response
435	25730766	WBPaper00046511.ce.rs.paper	N.A.	N.A.	1	The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families.	Hookworms infect over 400 million people, stunting and impoverishing them. Sequencing hookworm genomes and finding which genes they express during infection should help in devising new drugs or vaccines against hookworms. Unlike other hookworms, Ancylostoma ceylanicum infects both humans and other mammals, providing a laboratory model for hookworm disease. We determined an A. ceylanicum genome sequence of 313 Mb, with transcriptomic data throughout infection showing expression of 30,738 genes. Approximately 900 genes were upregulated during early infection in vivo, including ASPRs, a cryptic subfamily of activation-associated secreted proteins (ASPs). Genes downregulated during early infection included ion channels and G protein-coupled receptors; this downregulation was observed in both parasitic and free-living nematodes. Later, at the onset of heavy blood feeding, C-lectin genes were upregulated along with genes for secreted clade V proteins (SCVPs), encoding a previously undescribed protein family. These findings provide new drug and vaccine targets and should help elucidate hookworm pathogenesis.	2	47140	Schwarz EM	Schwarz EM, Hu Y, Antoshechkin I, Miller MM, Sternberg PW, Aroian RV	The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families.	Nat Genet	2015	RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0003810.SRP035507.SRX437635~RNASeq.elegans.WBStrain00000001.WBls:0000038.Hermaphrodite.WBbt:0003810.SRP035507.SRX437640	Method: RNAseq|Species: Caenorhabditis elegans
436	25875092	WBPaper00046691.ce.rs.paper	N.A.	N.A.	1	Asymmetric transcript discovery by RNA-seq in C. elegans blastomeres identifies neg-1, a gene important for anterior morphogenesis.	After fertilization but prior to the onset of zygotic transcription, the C. elegans zygote cleaves asymmetrically to create the anterior AB and posterior P1 blastomeres, each of which goes on to generate distinct cell lineages. To understand how patterns of RNA inheritance and abundance arise after this first asymmetric cell division, we pooled hand-dissected AB and P1 blastomeres and performed RNA-seq. Our approach identified over 200 asymmetrically abundant mRNA transcripts. We confirmed symmetric or asymmetric abundance patterns for a subset of these transcripts using smFISH. smFISH also revealed heterogeneous subcellular patterning of the P1-enriched transcripts chs-1 and bpl-1. We screened transcripts enriched in a given blastomere for embryonic defects using RNAi. The gene neg-1 (F32D1.6) encoded an AB-enriched (anterior) transcript and was required for proper morphology of anterior tissues. In addition, analysis of the asymmetric transcripts yielded clues regarding the post-transcriptional mechanisms that control cellular mRNA abundance during asymmetric cell divisions, which are common in developing organisms.	6	47140	Osborne Nishimura E	Osborne Nishimura E, Zhang JC, Werts AD, Goldstein B, Lieb JD	Asymmetric transcript discovery by RNA-seq in C. elegans blastomeres identifies neg-1, a gene important for anterior morphogenesis.	PLoS Genet	2015	RNASeq.elegans.WBStrain00000001.WBls:0000007.Hermaphrodite.WBbt:0004015.SRP045110.SRX666563~RNASeq.elegans.WBStrain00000001.WBls:0000007.Hermaphrodite.WBbt:0006770.SRP045110.SRX666564~RNASeq.elegans.WBStrain00000001.WBls:0000007.Hermaphrodite.WBbt:0004015.SRP045110.SRX666565~RNASeq.elegans.WBStrain00000001.WBls:0000007.Hermaphrodite.WBbt:0006770.SRP045110.SRX666566~RNASeq.elegans.WBStrain00000001.WBls:0000007.Hermaphrodite.WBbt:0004015.SRP045110.SRX666567~RNASeq.elegans.WBStrain00000001.WBls:0000007.Hermaphrodite.WBbt:0006770.SRP045110.SRX666568	Method: RNAseq|Species: Caenorhabditis elegans|Tissue Specific
437	25968310	WBPaper00046805.ce.rs.paper	N.A.	N.A.	1	CSR-1 and P granules suppress sperm-specific transcription in the C. elegans germline.	Germ granules (P granules) in C. elegans are required for fertility and function to maintain germ cell identity and pluripotency. Sterility in the absence of P granules is often accompanied by the misexpression of soma-specific proteins and the initiation of somatic differentiation in germ cells. To investigate whether this is caused by the accumulation of somatic transcripts, we performed mRNA-seq on dissected germlines with and without P granules. Strikingly, we found that somatic transcripts do not increase in the young adult germline when P granules are impaired. Instead, we found that impairing P granules causes sperm-specific mRNAs to become highly overexpressed. This includes the accumulation of major sperm protein (MSP) transcripts in germ cells, a phenotype that is suppressed by feminization of the germline. A core component of P granules, the endo-siRNA-binding Argonaute protein CSR-1, has recently been ascribed with the ability to license transcripts for germline expression. However, impairing CSR-1 has very little effect on the accumulation of its mRNA targets. Instead, we found that CSR-1 functions with P granules to prevent MSP and sperm-specific mRNAs from being transcribed in the hermaphrodite germline. These findings suggest that P granules protect germline integrity through two different mechanisms, by (1) preventing the inappropriate expression of somatic proteins at the level of translational regulation, and by (2) functioning with CSR-1 to limit the domain of sperm-specific expression at the level of transcription.	2	47090	Campbell AC	Campbell AC, Updike DL	CSR-1 and P granules suppress sperm-specific transcription in the C. elegans germline.	Development	2015	RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0005784.SRP057263.SRX997493~RNASeq.elegans.WBStrain00000001.WBls:0000063.Hermaphrodite.WBbt:0005784.SRP057263.SRX997495	Method: RNAseq|Species: Caenorhabditis elegans|Tissue Specific
438	26392177	WBPaper00050230.ce.rs.paper	N.A.	N.A.	1	Comparative genomics of Steinernema reveals deeply conserved gene regulatory networks.	BACKGROUND: Parasitism is a major ecological niche for a variety of nematodes. Multiple nematode lineages have specialized as pathogens, including deadly parasites of insects that are used in biological control. We have sequenced and analyzed the draft genomes and transcriptomes of the entomopathogenic nematode Steinernema carpocapsae and four congeners (S. scapterisci, S. monticolum, S. feltiae, and S. glaseri). RESULTS: We used these genomes to establish phylogenetic relationships, explore gene conservation across species, and identify genes uniquely expanded in insect parasites. Protein domain analysis in Steinernema revealed a striking expansion of numerous putative parasitism genes, including certain protease and protease inhibitor families, as well as fatty acid- and retinol-binding proteins. Stage-specific gene expression of some of these expanded families further supports the notion that they are involved in insect parasitism by Steinernema. We show that sets of novel conserved non-coding regulatory motifs are associated with orthologous genes in Steinernema and Caenorhabditis. CONCLUSIONS: We have identified a set of expanded gene families that are likely to be involved in parasitism. We have also identified a set of non-coding motifs associated with groups of orthologous genes in Steinernema and Caenorhabditis involved in neurogenesis and embryonic development that are likely part of conserved protein-DNA relationships shared between these two genera.	8	47155	Dillman AR	Dillman AR, Macchietto M, Porter CF, Rogers A, Williams B, Antoshechkin I, Lee MM, Goodwin Z, Lu X, Lewis EE, Goodrich-Blair H, Stock SP, Adams BJ, Sternberg PW, Mortazavi A	Comparative genomics of Steinernema reveals deeply conserved gene regulatory networks.	Genome Biol	2015	RNASeq.elegans.WBStrain00000001.WBls:0000003.Hermaphrodite.WBbt:0007833.SRP058023.SRX1019174~RNASeq.elegans.WBStrain00000001.WBls:0000003.Hermaphrodite.WBbt:0007833.SRP058023.SRX1019175~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP058023.SRX1019176~RNASeq.elegans.WBStrain00000001.WBls:0000024.Hermaphrodite.WBbt:0007833.SRP058023.SRX1019177~RNASeq.elegans.WBStrain00000001.WBls:0000032.Hermaphrodite.WBbt:0007833.SRP058023.SRX1019178~RNASeq.elegans.WBStrain00000001.WBls:0000032.Hermaphrodite.WBbt:0007833.SRP058023.SRX1019179~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP058023.SRX1019180~RNASeq.elegans.WBStrain00000001.WBls:0000041.Hermaphrodite.WBbt:0007833.SRP058023.SRX1019181	Method: RNAseq|Species: Caenorhabditis elegans
439	27654945	WBPaper00050344.ce.rs.paper	N.A.	N.A.	1	The tubulin repertoire of C. elegans sensory neurons and its context-dependent role in process outgrowth.	Microtubules contribute to many cellular processes, including transport, signaling, and chromosome separation during cell division (Kapitein and Hoogenraad, 2015). They are comprised of -tubulin heterodimers arranged into linear protofilaments and assembled into tubes. Eukaryotes express multiple tubulin isoforms (Gogonea et al., 1999), and there has been a longstanding debate as to whether the isoforms are redundant or perform specialized roles as part of a tubulin code (Fulton and Simpson, 1976). Here, we use the well-characterized touch receptor neurons (TRNs) of Caenorhabditis elegans to investigate this question, through genetic dissection of process outgrowth both in vivo and in vitro With single-cell RNA-seq, we compare transcription profiles for TRNs with those of two other sensory neurons, and present evidence that each sensory neuron expresses a distinct palette of tubulin genes. In the TRNs, we analyze process outgrowth and show that four tubulins (tba-1, tba-2, tbb-1, and tbb-2) function partially or fully redundantly, while two others (mec-7 and mec-12) perform specialized, context-dependent roles. Our findings support a model in which sensory neurons express overlapping subsets of tubulin genes whose functional redundancy varies between cell types and in vivo and in vitro contexts.	3	47152	Lockhead D	Lockhead D, Schwarz EM, O'Hagan R, Bellotti S, Krieg M, Barr MM, Dunn AR, Sternberg PW, Goodman MB	The tubulin repertoire of C. elegans sensory neurons and its context-dependent role in process outgrowth.	Mol Biol Cell	2016	RNASeq.elegans.WBStrain00005555.WBls:0000002.Hermaphrodite.WBbt:0003903.SRP074511.SRX1746473~RNASeq.elegans.WBStrain00035051.WBls:0000038.Hermaphrodite.WBbt:0005490.SRP074511.SRX1746482~RNASeq.elegans.WBStrain00005557.WBls:0000002.Hermaphrodite.WBbt:0005662.SRP074511.SRX1746483	Method: RNAseq|Species: Caenorhabditis elegans|Tissue Specific
440	19181841	WBPaper00032529.cja.rs.paper	N.A.	N.A.	1	Massively parallel sequencing of the polyadenylated transcriptome of C. elegans.	Using massively parallel sequencing by synthesis methods, we have surveyed the poly-A+ transcripts from four stages of the nematode C. elegans to an unprecedented depth. Using novel statistical approaches, we evaluated the coverage of annotated features of the genome and of candidate processed transcripts, including splice junctions, trans-spliced leader sequences and poly-adenylation tracts. The data provide experimental support for more than 85% of the annotated protein coding transcripts in WormBase (WS170) and confirm additional details of processing. For example, the total number of confirmed splice junctions was raised from 70,911 to over 98,000. The data also suggest thousands of modifications to WormBase annotations, and identify new spliced junctions and genes not part of any WormBase annotation, including at least 80 putative genes not found in any of three predicted gene sets. The quantitative nature of the data also suggests that mRNA levels may be measured by this approach with unparalleled precision. Although most sequences align with protein coding genes, a small fraction fall in introns and intergenic regions. One notable region on the X chromosome encodes a noncoding transcript of greater than 10 kb localized to somatic nuclei.	6	32340	Hillier LW	Hillier LW, Reinke V, Green P, Hirst M, Marra MA, Waterston RH	Massively parallel sequencing of the polyadenylated transcriptome of C. elegans.	Genome Res	2009	RNASeq.japonica.WBStrain00041019.WBls:0000027.Unknown.WBbt:0007833.SRP006033.SRX100090~RNASeq.japonica.WBStrain00041019.WBls:0000038.Unknown.WBbt:0007833.SRP006033.SRX100091~RNASeq.japonica.WBStrain00041019.WBls:0000038.Unknown.WBbt:0007833.SRP006033.SRX100092~RNASeq.japonica.WBStrain00041019.WBls:0000041.Male.WBbt:0007833.SRP006033.SRX100093~RNASeq.japonica.WBStrain00041019.WBls:0000041.Female.WBbt:0007833.SRP006033.SRX100094~RNASeq.japonica.WBStrain00041019.WBls:0000004.Unknown.WBbt:0007833.SRP006033.SRX100095	Method: RNAseq|Species: Caenorhabditis japonica|Tissue Specific
441	23103191	WBPaper00041689.cja.rs.paper	GSE41367	GPL13776,GPL13657,GPL13776,GPL16135,GPL16136,GPL16137,GPL16138,GPL16139,GPL16140,GPL16141	1	Simplification and desexualization of gene expression in self-fertile nematodes.	Evolutionary transitions between sexual modes could be potent forces in genome evolution. Several Caenorhabditis nematode species have evolved self-fertile hermaphrodites from the obligately outcrossing females of their ancestors. We explored the relationship between sexual mode and global gene expression by comparing two selfing species, C. elegans and C. briggsae, with three phylogenetically informative outcrossing relatives, C. remanei, C. brenneri, and C. japonica. Adult transcriptome assemblies from the selfing species are consistently and strikingly smaller than those of the outcrossing species. Against this background of overall simplification, genes conserved in multiple outcrossing species with strong sex-biased expression are even more likely to be missing from the genomes of the selfing species. In addition, the sexual regulation of remaining transcripts has diverged markedly from the ancestral pattern in both selfing lineages, though in distinct ways. Thus, both the complexity and the sexual specialization of transciptomes are rapidly altered in response to the evolution of self-fertility. These changes may result from the combination of relaxed sexual selection and a recently reported genetic mechanism favoring genome shrinkage in partial selfers.	6	32339	Thomas CG	Thomas CG, Li R, Smith HE, Woodruff GC, Oliver B, Haag ES	Simplification and desexualization of gene expression in self-fertile nematodes.	Curr Biol	2012	RNASeq.japonica.WBStrain00041019.WBls:0000041.Female.WBbt:0007833.SRP016006.SRX191959~RNASeq.japonica.WBStrain00041019.WBls:0000041.Female.WBbt:0007833.SRP016006.SRX191960~RNASeq.japonica.WBStrain00041019.WBls:0000041.Female.WBbt:0007833.SRP016006.SRX191961~RNASeq.japonica.WBStrain00041019.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191962~RNASeq.japonica.WBStrain00041019.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191963~RNASeq.japonica.WBStrain00041019.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191964	Method: RNAseq|Species: Caenorhabditis japonica
442	19181841	WBPaper00032529.cre.rs.paper	N.A.	N.A.	1	Massively parallel sequencing of the polyadenylated transcriptome of C. elegans.	Using massively parallel sequencing by synthesis methods, we have surveyed the poly-A+ transcripts from four stages of the nematode C. elegans to an unprecedented depth. Using novel statistical approaches, we evaluated the coverage of annotated features of the genome and of candidate processed transcripts, including splice junctions, trans-spliced leader sequences and poly-adenylation tracts. The data provide experimental support for more than 85% of the annotated protein coding transcripts in WormBase (WS170) and confirm additional details of processing. For example, the total number of confirmed splice junctions was raised from 70,911 to over 98,000. The data also suggest thousands of modifications to WormBase annotations, and identify new spliced junctions and genes not part of any WormBase annotation, including at least 80 putative genes not found in any of three predicted gene sets. The quantitative nature of the data also suggests that mRNA levels may be measured by this approach with unparalleled precision. Although most sequences align with protein coding genes, a small fraction fall in introns and intergenic regions. One notable region on the X chromosome encodes a noncoding transcript of greater than 10 kb localized to somatic nuclei.	19	32932	Hillier LW	Hillier LW, Reinke V, Green P, Hirst M, Marra MA, Waterston RH	Massively parallel sequencing of the polyadenylated transcriptome of C. elegans.	Genome Res	2009	RNASeq.remanei.WBStrain00042077.WBls:0000027.Unknown.WBbt:0007833.SRP006033.SRX052082~RNASeq.remanei.WBStrain00042077.WBls:0000038.Unknown.WBbt:0007833.SRP006033.SRX052083~RNASeq.remanei.WBStrain00042077.WBls:0000038.Unknown.WBbt:0007833.SRP006033.SRX101879~RNASeq.remanei.WBStrain00042077.WBls:0000038.Unknown.WBbt:0007833.SRP006033.SRX101880~RNASeq.remanei.WBStrain00042077.WBls:0000004.Unknown.WBbt:0007833.SRP006033.SRX101881~RNASeq.remanei.WBStrain00042077.WBls:0000004.Unknown.WBbt:0007833.SRP006033.SRX101882~RNASeq.remanei.WBStrain00042077.WBls:0000027.Unknown.WBbt:0007833.SRP006033.SRX101883~RNASeq.remanei.WBStrain00042077.WBls:0000027.Unknown.WBbt:0007833.SRP006033.SRX101884~RNASeq.remanei.WBStrain00042077.WBls:0000027.Unknown.WBbt:0007833.SRP006033.SRX101885~RNASeq.remanei.WBStrain00042077.WBls:0000063.Female.WBbt:0007833.SRP006033.SRX101886~RNASeq.remanei.WBStrain00042077.WBls:0000063.Female.WBbt:0007833.SRP006033.SRX101887~RNASeq.remanei.WBStrain00042077.WBls:0000063.Female.WBbt:0007833.SRP006033.SRX101888~RNASeq.remanei.WBStrain00042077.WBls:0000063.Female.WBbt:0007833.SRP006033.SRX101889~RNASeq.remanei.WBStrain00042077.WBls:0000063.Female.WBbt:0007833.SRP006033.SRX101890~RNASeq.remanei.WBStrain00042077.WBls:0000063.Male.WBbt:0007833.SRP006033.SRX101891~RNASeq.remanei.WBStrain00042077.WBls:0000063.Male.WBbt:0007833.SRP006033.SRX101892~RNASeq.remanei.WBStrain00042077.WBls:0000063.Male.WBbt:0007833.SRP006033.SRX101893~RNASeq.remanei.WBStrain00042077.WBls:0000063.Male.WBbt:0007833.SRP006033.SRX101894~RNASeq.remanei.WBStrain00042077.WBls:0000063.Male.WBbt:0007833.SRP006033.SRX101895	Method: RNAseq|Species: Caenorhabditis remanei|Tissue Specific
443	23103191	WBPaper00041689.cre.rs.paper	GSE41367	GPL13776,GPL13657,GPL13776,GPL16135,GPL16136,GPL16137,GPL16138,GPL16139,GPL16140,GPL16141	1	Simplification and desexualization of gene expression in self-fertile nematodes.	Evolutionary transitions between sexual modes could be potent forces in genome evolution. Several Caenorhabditis nematode species have evolved self-fertile hermaphrodites from the obligately outcrossing females of their ancestors. We explored the relationship between sexual mode and global gene expression by comparing two selfing species, C. elegans and C. briggsae, with three phylogenetically informative outcrossing relatives, C. remanei, C. brenneri, and C. japonica. Adult transcriptome assemblies from the selfing species are consistently and strikingly smaller than those of the outcrossing species. Against this background of overall simplification, genes conserved in multiple outcrossing species with strong sex-biased expression are even more likely to be missing from the genomes of the selfing species. In addition, the sexual regulation of remaining transcripts has diverged markedly from the ancestral pattern in both selfing lineages, though in distinct ways. Thus, both the complexity and the sexual specialization of transciptomes are rapidly altered in response to the evolution of self-fertility. These changes may result from the combination of relaxed sexual selection and a recently reported genetic mechanism favoring genome shrinkage in partial selfers.	6	32932	Thomas CG	Thomas CG, Li R, Smith HE, Woodruff GC, Oliver B, Haag ES	Simplification and desexualization of gene expression in self-fertile nematodes.	Curr Biol	2012	RNASeq.remanei.WBStrain00042077.WBls:0000041.Female.WBbt:0007833.SRP016006.SRX191971~RNASeq.remanei.WBStrain00042077.WBls:0000041.Female.WBbt:0007833.SRP016006.SRX191972~RNASeq.remanei.WBStrain00042077.WBls:0000041.Female.WBbt:0007833.SRP016006.SRX191973~RNASeq.remanei.WBStrain00042077.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191974~RNASeq.remanei.WBStrain00042077.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191975~RNASeq.remanei.WBStrain00042077.WBls:0000041.Male.WBbt:0007833.SRP016006.SRX191976	Method: RNAseq|Species: Caenorhabditis remanei
444	24098135	WBPaper00045465.cre.rs.paper	N.A.	N.A.	1	Conserved translatome remodeling in nematode species executing a shared developmental transition.	Nematodes of the genus Caenorhabditis enter a developmental diapause state after hatching in the absence of food. To better understand the relative contributions of distinct regulatory modalities to gene expression changes associated with this developmental transition, we characterized genome-wide changes in mRNA abundance and translational efficiency associated with L1 diapause exit in four species using ribosome profiling and mRNA-seq. We found a strong tendency for translational regulation and mRNA abundance processes to act synergistically, together effecting a dramatic remodeling of the gene expression program. While gene-specific differences were observed between species, overall translational dynamics were broadly and functionally conserved. A striking, conserved feature of the response was strong translational suppression of ribosomal protein production during L1 diapause, followed by activation upon resumed development. On a global scale, ribosome footprint abundance changes showed greater similarity between species than changes in mRNA abundance, illustrating a substantial and genome-wide contribution of translational regulation to evolutionary maintenance of stable gene expression.	6	32932	Stadler M	Stadler M, Fire A	Conserved translatome remodeling in nematode species executing a shared developmental transition.	PLoS Genet	2013	RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP026198.SRX311798~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP026198.SRX311799~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP026198.SRX311800~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP026198.SRX311801~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP026198.SRX311802~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP026198.SRX311803	Method: RNAseq|Species: Caenorhabditis remanei
445	24727288	WBPaper00046092.cre.rs.paper	N.A.	N.A.	1	Rapid evolution of phenotypic plasticity and shifting thresholds of genetic assimilation in the nematode Caenorhabditis remanei.	Many organisms can acclimate to new environments through phenotypic plasticity, a complex trait that can be heritable, subject to selection, and evolve. However, the rate and genetic basis of plasticity evolution remain largely unknown. We experimentally evolved outbred populations of the nematode Caenorhabditis remanei under an acute heat shock during early larval development. When raised in a nonstressful environment, ancestral populations were highly sensitive to a 36.8 heat shock and exhibited high mortality. However, initial exposure to a nonlethal high temperature environment resulted in significantly reduced mortality during heat shock (hormesis). Lines selected for heat shock resistance rapidly evolved the capacity to withstand heat shock in the native environment without any initial exposure to high temperatures, and early exposure to high temperatures did not lead to further increases in heat resistance. This loss of plasticity would appear to have resulted from the genetic assimilation of the heat induction response in the noninducing environment. However, analyses of transcriptional variation via RNA-sequencing from the selected populations revealed no global changes in gene regulation correlated with the observed changes in heat stress resistance. Instead, assays of the phenotypic response across a broader range of temperatures revealed that the induced plasticity was not fixed across environments, but rather the threshold for the response was shifted to higher temperatures over evolutionary time. These results demonstrate that apparent genetic assimilation can result from shifting thresholds of induction across environments and that analysis of the broader environmental context is critically important for understanding the evolution of phenotypic plasticity.	36	32932	Sikkink KL	Sikkink KL, Reynolds RM, Ituarte CM, Cresko WA, Phillips PC	Rapid evolution of phenotypic plasticity and shifting thresholds of genetic assimilation in the nematode Caenorhabditis remanei.	G3 (Bethesda)	2014	RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510986~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510987~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510988~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510989~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510990~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510991~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510992~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510993~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510994~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510995~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510996~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510997~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510998~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX510999~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511000~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511001~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511002~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511003~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511004~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511005~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511006~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511007~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511008~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511009~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511010~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511011~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511012~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511013~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511014~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511015~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511016~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511017~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511018~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511019~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511020~RNASeq.remanei.WBStrain00042077.WBls:0000024.Unknown.WBbt:0007833.SRP040962.SRX511021	Method: RNAseq|Species: Caenorhabditis remanei
446	25283346	WBPaper00055069.cre.rs.paper	N.A.	N.A.	1	The transgenerational effects of heat stress in the nematode Caenorhabditis remanei are negative and rapidly eliminated under direct selection for increased stress resistance in larvae.	Parents encountering stress environments can influence the phenotype of their offspring in a form of transgenerational phenotypic plasticity that has the potential to be adaptive if offspring are thereby better able to deal with future stressors. Here, we test for the existence of anticipatory parental effects in the heat stress response in the highly polymorphic nematode Caenorhabditis remanei. Rather providing an anticipatory response, parents subject to a prior heat stress actually produce offspring that are less able to survive a severe heat shock. Selection on heat shock resistance within the larvae via experimental evolution leads to a loss of sensitivity (robustness) to environmental variation during both the parental and larval periods. Whole genome transcriptional analysis of both ancestor and selected lines shows that there is weak correspondence between genetic pathways induced via temperature shifts during parental and larval periods. Parental effects can evolve very rapidly via selection acting directly on offspring.	12	32932	Sikkink KL	Sikkink KL, Ituarte CM, Reynolds RM, Cresko WA, Phillips PC	The transgenerational effects of heat stress in the nematode Caenorhabditis remanei are negative and rapidly eliminated under direct selection for increased stress resistance in larvae.	Genomics	2014	RNASeq.remanei.WBStrain00031117.WBls:0000024.Unknown.WBbt:0007833.SRP049403.SRX747479~RNASeq.remanei.WBStrain00031117.WBls:0000024.Unknown.WBbt:0007833.SRP049403.SRX747480~RNASeq.remanei.WBStrain00031117.WBls:0000024.Unknown.WBbt:0007833.SRP049403.SRX747481~RNASeq.remanei.WBStrain00031117.WBls:0000024.Unknown.WBbt:0007833.SRP049403.SRX747482~RNASeq.remanei.WBStrain00031117.WBls:0000024.Unknown.WBbt:0007833.SRP049403.SRX747483~RNASeq.remanei.WBStrain00031117.WBls:0000024.Unknown.WBbt:0007833.SRP049403.SRX747484~RNASeq.remanei.WBStrain00031117.WBls:0000024.Unknown.WBbt:0007833.SRP049403.SRX747485~RNASeq.remanei.WBStrain00031117.WBls:0000024.Unknown.WBbt:0007833.SRP049403.SRX747486~RNASeq.remanei.WBStrain00031117.WBls:0000024.Unknown.WBbt:0007833.SRP049403.SRX747487~RNASeq.remanei.WBStrain00031117.WBls:0000024.Unknown.WBbt:0007833.SRP049403.SRX747488~RNASeq.remanei.WBStrain00031117.WBls:0000024.Unknown.WBbt:0007833.SRP049403.SRX747489~RNASeq.remanei.WBStrain00031117.WBls:0000024.Unknown.WBbt:0007833.SRP049403.SRX747490	Method: RNAseq|Species: Caenorhabditis remanei
447	24587458	WBPaper00048621.ovo.rs.paper	N.A.	N.A.	1	Immunoepidemiological profiling of onchocerciasis patients reveals associations with microfilaria loads and ivermectin intake on both individual and community levels.	Mass drug administration (MDA) programmes against Onchocerca volvulus use ivermectin (IVM) which targets microfilariae (MF), the worm's offspring. Most infected individuals are hyporesponsive and present regulated immune responses despite high parasite burden. Recently, with MDA programmes, the existence of amicrofilaridermic (a-MF) individuals has become apparent but little is known about their immune responses. Within this immunoepidemiological study, we compared parasitology, pathology and immune profiles in infection-free volunteers and infected individuals that were MF(+) or a-MF. The latter stemmed from villages in either Central or Ashanti regions of Ghana which, at the time of the study, had received up to eight or only one round of MDA respectively. Interestingly, a-MF patients had fewer nodules and decreased IL-10 responses to all tested stimuli. On the other hand, this patient group displayed contrary IL-5 profiles following in vitro stimulation or in plasma and the dampened response in the latter correlated to reduced eosinophils and associated factors but elevated neutrophils. Furthermore, multivariable regression analysis with covariates MF, IVM or the region (Central vs. Ashanti) revealed that immune responses were associated with different covariates: whereas O. volvulus-specific IL-5 responses were primarily associated with MF, IL-10 secretion had a negative correlation with times of individual IVM therapy (IIT). All plasma parameters (eosinophil cationic protein, IL-5, eosinophils and neutrophils) were highly associated with MF. With regards to IL-17 secretion, although no differences were observed between the groups to filarial-specific or bystander stimuli, these responses were highly associated with the region. These data indicate that immune responses are affected by both, IIT and the rounds of IVM MDA within the community. Consequently, it appears that a lowered infection pressure due to IVM MDA may affect the immune profile of community members even if they have not regularly participated in the programmes.	9	12603	Arndts K	Arndts K, Specht S, Debrah AY, Tamarozzi F, Klarmann Schulz U, Mand S, Batsa L, Kwarteng A, Taylor M, Adjei O, Martin C, Layland LE, Hoerauf A	Immunoepidemiological profiling of onchocerciasis patients reveals associations with microfilaria loads and ivermectin intake on both individual and community levels.	PLoS Negl Trop Dis	2014	RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.SRP056861.SRX978156~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.SRP056861.SRX978157~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.SRP056861.SRX978158~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.SRP056861.SRX978159~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.SRP056861.SRX978160~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.SRP056861.SRX978161~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Male.WBbt:0007833.SRP056861.SRX978162~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.SRP056861.SRX978163~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.SRP056861.SRX978164	Method: RNAseq|Species: Onchocerca volvulus
448	0	WBPaper01000000.ovo.rs.paper	N.A.	N.A.	1	N.A.	N.A.	12	12603	N.A.	N.A.	N.A.	N.A.	0	RNASeq.ovolvulus.WBStrain00041977.WBls:0000108.Unknown.WBbt:0007833.ERP001350.ERX200391~RNASeq.ovolvulus.WBStrain00041977.WBls:0000108.Unknown.WBbt:0007833.ERP001350.ERX200392~RNASeq.ovolvulus.WBStrain00041977.WBls:0000108.Unknown.WBbt:0007833.ERP001350.ERX200393~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Male.WBbt:0007833.ERP001350.ERX200394~RNASeq.ovolvulus.WBStrain00041977.WBls:0000107.Unknown.WBbt:0007833.ERP001350.ERX200395~RNASeq.ovolvulus.WBStrain00041977.WBls:0000664.Unknown.WBbt:0007833.ERP001350.ERX200396~RNASeq.ovolvulus.WBStrain00041977.WBls:0000664.Unknown.WBbt:0007833.ERP001350.ERX200397~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.ERP001350.ERX450840~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.ERP001350.ERX450841~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.ERP001350.ERX450842~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.ERP001350.ERX529044~RNASeq.ovolvulus.WBStrain00041977.WBls:0000104.Female.WBbt:0007833.ERP001350.ERX529045	Method: RNAseq|Species: Onchocerca volvulus
449	20237107	WBPaper00036038.ppa.rs.paper	N.A.	N.A.	1	Proteogenomics of Pristionchus pacificus reveals distinct proteome structure of nematode models.	Pristionchus pacificus is a nematode model organism whose genome has recently been sequenced. To refine the genome annotation we performed transcriptome and proteome analysis and gathered comprehensive experimental information on gene expression. Transcriptome analysis on a 454 Life Sciences (Roche) FLX platform generated &gt;700,000 expressed sequence tags (ESTs) from two normalized EST libraries, whereas proteome analysis on an LTQ-Orbitrap mass spectrometer detected &gt;27,000 nonredundant peptide sequences from more than 4000 proteins at sub-parts-per-million (ppm) mass accuracy and a false discovery rate of &lt;1%. Retraining of the SNAP gene prediction algorithm using the gene expression data led to a decrease in the number of previously predicted protein-coding genes from 29,000 to 24,000 and refinement of numerous gene models. The P. pacificus proteome contains a high proportion of small proteins with no known homologs in other species ("pioneer" proteins). Some of these proteins appear to be products of highly homologous genes, pointing to their common origin. We show that &gt;50% of all pioneer genes are transcribed under standard culture conditions and that pioneer proteins significantly contribute to a unimodal distribution of predicted protein sizes in P. pacificus, which has an unusually low median size of 240 amino acids (26.8 kDa). In contrast, the predicted proteome of Caenorhabditis elegans follows a distinct bimodal protein size distribution, with significant functional differences between small and large protein populations. Combined, these results provide the first catalog of the expressed genome of P. pacificus, refinement of its genome annotation, and the first comparison of related nematode models at the proteome level.	2	26342	Borchert N	Borchert N, Dieterich C, Krug K, Schutz W, Jung S, Nordheim A, Sommer RJ, Macek B	Proteogenomics of Pristionchus pacificus reveals distinct proteome structure of nematode models.	Genome Res	2010	RNASeq.pristionchus.WBStrain00042002.WBls:0000101.Unknown.WBbt:0007833.SRP001700.SRX015656~RNASeq.pristionchus.WBStrain00042002.WBls:0000032.Unknown.WBbt:0007833.SRP001700.SRX015659	Method: RNAseq|Species: Pristionchus pacificus
450	24793291	WBPaper00045232.ppa.rs.paper	N.A.	N.A.	1	Sex-biased gene expression and evolution of the x chromosome in nematodes.	Studies of X chromosome evolution in various organisms have indicated that sex-biased genes are nonrandomly distributed between the X and autosomes. Here, to extend these studies to nematodes, we annotated and analyzed X chromosome gene content in four Caenorhabditis species and in Pristionchus pacificus. Our gene expression analyses comparing young adult male and female mRNA-seq data indicate that, in general, nematode X chromosomes are enriched for genes with high female-biased expression and depleted of genes with high male-biased expression. Genes with low sex-biased expression do not show the same trend of X chromosome enrichment and depletion. Combined with the observation that highly sex-biased genes are primarily expressed in the gonad, differential distribution of sex-biased genes reflects differences in evolutionary pressures linked to tissue-specific regulation of X chromosome transcription. Our data also indicate that X dosage imbalance between males (XO) and females (XX) is influential in shaping both expression and gene content of the X chromosome. Predicted upregulation of the single male X to match autosomal transcription (Ohno's hypothesis) is supported by our observation that overall transcript levels from the X and autosomes are similar for highly expressed genes. However, comparison of differentially located one-to-one orthologs between C. elegans and P. pacificus indicates lower expression of X-linked orthologs, arguing against X upregulation. These contradicting observations may be reconciled if X upregulation is not a global mechanism but instead acts locally on a subset of tissues and X-linked genes that are dosage sensitive.	6	25516	Albritton SE	Albritton SE, Kranz AL, Rao P, Kramer M, Dieterich C, Ercan S	Sex-biased gene expression and evolution of the x chromosome in nematodes.	Genetics	2014	RNASeq.pristionchus.WBStrain00042002.WBls:0000101.Male.WBbt:0007833.SRP034667.SRX397078~RNASeq.pristionchus.WBStrain00042002.WBls:0000101.Male.WBbt:0007833.SRP034667.SRX397079~RNASeq.pristionchus.WBStrain00042002.WBls:0000101.Male.WBbt:0007833.SRP034667.SRX397080~RNASeq.pristionchus.WBStrain00042002.WBls:0000101.Female.WBbt:0007833.SRP034667.SRX397081~RNASeq.pristionchus.WBStrain00042002.WBls:0000101.Female.WBbt:0007833.SRP034667.SRX397082~RNASeq.pristionchus.WBStrain00042002.WBls:0000101.Female.WBbt:0007833.SRP034667.SRX397083	Method: RNAseq|Species: Pristionchus pacificus
451	26829753	WBPaper00050919.sra.rs.paper	N.A.	N.A.	1	The genomic basis of parasitism in the Strongyloides clade of nematodes.	Soil-transmitted nematodes, including the Strongyloides genus, cause one of the most prevalent neglected tropical diseases. Here we compare the genomes of four Strongyloides species, including the human pathogen Strongyloides stercoralis, and their close relatives that are facultatively parasitic (Parastrongyloides trichosuri) and free-living (Rhabditophanes sp. KR3021). A significant paralogous expansion of key gene families--families encoding astacin-like and SCP/TAPS proteins--is associated with the evolution of parasitism in this clade. Exploiting the unique Strongyloides life cycle, we compare the transcriptomes of the parasitic and free-living stages and find that these same gene families are upregulated in the parasitic stages, underscoring their role in nematode parasitism.	16	12972	Hunt VL	Hunt VL, Tsai IJ, Coghlan A, Reid AJ, Holroyd N, Foth BJ, Tracey A, Cotton JA, Stanley EJ, Beasley H, Bennett HM, Brooks K, Harsha B, Kajitani R, Kulkarni A, Harbecke D, Nagayasu E, Nichol S, Ogura Y, Quail MA, Randle N, Xia D, Brattig NW, Soblik H, Ribeiro DM, Sanchez-Flores A, Hayashi T, Itoh T, Denver DR, Grant W, Stoltzfus JD, Lok JB, Murayama H, Wastling J, Streit A, Kikuchi T, Viney M, Berriman M	The genomic basis of parasitism in the Strongyloides clade of nematodes.	Nat Genet	2016	RNASeq.sratti.WBStrain00041039.WBls:0000682.Unknown.WBbt:0007833.ERP001672.ERX200443~RNASeq.sratti.WBStrain00041039.WBls:0000680.Unknown.WBbt:0007833.ERP001672.ERX200444~RNASeq.sratti.WBStrain00041039.WBls:0000678.Female.WBbt:0007833.ERP002187.ERX272493~RNASeq.sratti.WBStrain00041039.WBls:0000678.Female.WBbt:0007833.ERP002187.ERX272494~RNASeq.sratti.WBStrain00041039.WBls:0000678.Female.WBbt:0007833.ERP002187.ERX272495~RNASeq.sratti.WBStrain00041039.WBls:0000677.Female.WBbt:0007833.ERP002187.ERX272496~RNASeq.sratti.WBStrain00041039.WBls:0000677.Female.WBbt:0007833.ERP002187.ERX272497~RNASeq.sratti.WBStrain00041039.WBls:0000677.Female.WBbt:0007833.ERP002187.ERX272498~RNASeq.sratti.WBStrain00041039.WBls:0000678.Female.WBbt:0007833.ERP002187.ERX272499~RNASeq.sratti.WBStrain00041039.WBls:0000678.Female.WBbt:0007833.ERP002187.ERX272500~RNASeq.sratti.WBStrain00041039.WBls:0000678.Female.WBbt:0007833.ERP002187.ERX272501~RNASeq.sratti.WBStrain00041039.WBls:0000677.Female.WBbt:0007833.ERP002187.ERX272502~RNASeq.sratti.WBStrain00041039.WBls:0000677.Female.WBbt:0007833.ERP002187.ERX272503~RNASeq.sratti.WBStrain00041039.WBls:0000677.Female.WBbt:0007833.ERP002187.ERX272504~RNASeq.sratti.WBStrain00041039.WBls:0000678.Female.WBbt:0007833.ERP002187.ERX322575~RNASeq.sratti.WBStrain00041039.WBls:0000678.Female.WBbt:0007833.ERP002187.ERX322576	Method: RNAseq|Species: Strongyloides ratti
452	21177967	WBPaper00037950.ce.tr.paper	GSE23245,GSE23246,GSE23247,GSE23248,GSE23249,GSE23250,GSE23251,GSE23252,GSE23253,GSE23254,GSE23255,GSE23256,GSE23257,GSE23258,GSE23259,GSE23260,GSE23261,GSE23262,GSE23263,GSE23264,GSE23265,GSE23266,GSE23267,GSE23268,GSE23269,GSE23270,GSE23271,GSE23272,GSE23273,GSE23274,GSE23275,GSE23276,GSE23277,GSE23278,GSE23279,GSE23280,GSE23281,GSE23282,GSE23283,GSE23284,GSE23285,GSE23286,GSE23287,GSE23770,GSE25350,GSE25351	GPL5634	1	TilingArray: A spatial and temporal map of C. elegans gene expression.	The C. elegans genome has been completely sequenced, and the developmental anatomy of this model organism is described at single-cell resolution. Here we utilize strategies that exploit this precisely defined architecture to link gene expression to cell type. We obtained RNAs from specific cells and from each developmental stage using tissue-specific promoters to mark cells for isolation by FACS or for mRNA extraction by the mRNA-tagging method. We then generated gene expression profiles of more than 30 different cells and developmental stages using tiling arrays. Machine-learning-based analysis detected transcripts corresponding to established gene models and revealed novel transcriptionally active regions (TARs) in noncoding domains that comprise at least 10% of the total C. elegans genome. Our results show that about 75% of transcripts with detectable expression are differentially expressed among developmental stages and across cell types. Examination of known tissue- and cell-specific transcripts validates these data sets and suggests that newly identified TARs may exercise cell-specific functions. Additionally, we used self-organizing maps to define groups of coregulated transcripts and applied regulatory element analysis to identify known transcription factor- and miRNA-binding sites, as well as novel motifs that likely function to control subsets of these genes. By using cell-specific, whole-genome profiling strategies, we have detected a large number of novel transcripts and produced high-resolution gene expression maps that provide a basis for establishing the roles of individual genes in cellular differentiation.	47	10491	Spencer WC	Spencer WC, Zeller G, Watson JD, Henz SR, Watkins KL, McWhirter RD, Petersen SC, Sreedharan VT, Widmer C, Jo J, Reinke V, Petrella L, Strome S, Von Stetina S, Katz M, Shaham S, Raetsch G, Miller DM	A spatial and temporal map of C. elegans gene expression.	Genome Res	2011	TAR_early_embryo_20dC_0_4hrs_post_fertilization_N2~TAR_EE_Z1_Z4_male~TAR_embryo_0hr_reference~TAR_embryo_A_class_motor_neurons~TAR_embryo_all_cells_reference~TAR_embryo_AVA_neurons~TAR_embryo_AVE_neurons~TAR_embryo_BAG_neurons~TAR_embryo_body_wall_muscle~TAR_embryo_coelomocytes~TAR_embryo_dopaminergic_neurons~TAR_embryo_GABA_motor_neurons~TAR_embryo_germline_precursor_cells~TAR_embryo_hypodermal_cells~TAR_embryo_intestine~TAR_embryo_panneural~TAR_embryo_pharyngeal_muscle~TAR_embryo_PVC_neurons~TAR_emb_Z1_Z4~TAR_gonad_from_young_adult_20dC_42hrs_post_L1_N2~TAR_L1_20dC_0hrs_post_L1_N2~TAR_L2_25dC_14hrs_post_L1_N2~TAR_L2_A_class_neuron~TAR_L2_AFD~TAR_L2_body_wall_muscle~TAR_L2_coelomocytes~TAR_L2_excretory_cell~TAR_L2_GABA_alr_1~TAR_L2_GABA_neurons~TAR_L2_glutamate_receptor_expressing_neurons~TAR_L2_intestine~TAR_L2_panneural~TAR_L2_polyA_enriched_20dC_14hrs_post_L1_N2~TAR_L2_reference__mockIP~TAR_L3_25dC_25hrs_post_L1_N2~TAR_L3_L4_dopaminergic_neuron~TAR_L3_L4_hypodermal_cells~TAR_L3_L4_PVD___OLL_neurons~TAR_L3_L4_rectal_epithelial_cells~TAR_L3_L4_reference__mockIP~TAR_L4_25dC_36hrs_post_L1_N2~TAR_late_embryo_20dC_6_12hrs_post_fertilization_N2~TAR_male_L4_25dC_36hrs_post_L1_CB4689~TAR_soma_only_mid_L4_25dC_36hrs_post_L1_JK1107~TAR_young_adult_25dC_42hrs_post_L1_N2~TAR_Young_Adult_Cephalic_sheath__CEPsh~TAR_Young_Adult_reference__mockIP	Method: tiling array|Species: Caenorhabditis elegans|Tissue Specific
453	21177976	WBPaper00037953.ce.tr.paper	GSE25785,GSE25786,GSE25788,GSE25789,GSE25790,GSE25791,GSE25792,GSE25793,GSE25794,GSE25795,GSE25798,GSE25800,GSE25801,GSE25802,GSE25803,GSE25804,GSE25805,GSE25808,GSE25809,GSE25810,GSE25811	GPL9309	1	TilingArray: Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.	We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.	6	10474	Gerstein MB	Gerstein MB, Lu ZJ, Van Nostrand EL, Cheng C, Arshinoff BI, Liu T, Yip KY, Robilotto R, Rechtsteiner A, Ikegami K, Alves P, Chateigner A, Perry M, Morris M, Auerbach RK, Feng X, Leng J, Vielle A, Niu W, Rhrissorrakrai K, Agarwal A, Alexander RP, Barber G, Brdlik CM, Brennan J, Brouillet JJ, Carr A, Cheung MS, Clawson H, Contrino S, Dannenberg LO, Dernburg AF, Desai A, Dick L, Dose AC, Du J, Egelhofer T, Ercan S, Euskirchen G, Ewing B, Feingold EA, Gassmann R, Good PJ, Green P, Gullier F, Gutwein M, Guyer MS, Habegger L, Han T, Henikoff JG, Henz SR, Hinrichs A, Holster H, Hyman T, Iniguez AL, Janette J, Jensen M, Kato M, Kent WJ, Kephart E, Khivansara V, Khurana E, Kim JK, Kolasinska-Zwierz P, Lai EC, Latorre I, Leahey A, Lewis S, Lloyd P, Lochovsky L, Lowdon RF, Lubling Y, Lyne R, MacCoss M, Mackowiak SD, Mangone M, McKay S, Mecenas D, Merrihew G, Miller DM, Muroyama A, Murray JI, Ooi SL, Pham H, Phippen T, Preston EA, Rajewsky N, Ratsch G, Rosenbaum H, Rozowsky J, Rutherford K, Ruzanov P, Sarov M, Sasidharan R, Sboner A, Scheid P, Segal E, Shin H, Shou C, Slack FJ, Slightam C, Smith R, Spencer WC, Stinson EO, Taing S, Takasaki T, Vafeados D, Voronina K, Wang G, Washington NL, Whittle CM, Wu B, Yan KK, Zeller G, Zha Z, Zhong M, Zhou X, Ahringer J, Strome S, Gunsalus KC, Micklem G, Liu XS, Reinke V, Kim SK, Hillier LW, Henikoff S, Piano F, Snyder M, Stein L, Lieb JD, Waterston RH	Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.	Science	2010	TAR_pathogen_control_OP50_25dC_24hr_exposure_post_adulthood_N2~TAR_pathogen_control_OP50_25dC_48hr_exposure_post_adulthood_N2~TAR_pathogen_Efaecalis_25dC_24hr_exposure_post_adulthood_N2~TAR_pathogen_Pluminscens_25dC_24hr_exposure_post_adulthood_N2~TAR_pathogen_Smarcescens_25dC_24hr_exposure_post_adulthood_N2~TAR_pathogen_Smarcescens_25dC_48hr_exposure_post_adulthood_N2	Method: tiling array|Species: Caenorhabditis elegans|Tissue Specific
