Seven novel and potent Raf small molecule kinase inhibitors were evaluated in 7-day oral repeat-dose rat toxicity studies. All compounds tested induced hyperplasia in multiple tissues. Microarrays were used to investigate transciptional changes associated by treatment with a single compound to gain insight into the cellular changes that may contribute to the tissue hyperplasia.
Raf inhibition causes extensive multiple tissue hyperplasia and urinary bladder neoplasia in the rat.
Sex, Specimen part, Treatment
View SamplesI hypothesized that social interactions, such as those involved in reproductive behaviors, would lead to immediate and assayable changes in gene expression that may have important effects on individual reproductive success and fitness through alterations in physiology or via short-term or long-term changes in nervous system function.
A rapid genome-wide response to Drosophila melanogaster social interactions.
Sex, Age
View SamplesDetermination of the genes regulated by ERRalpha nuclear receptor in MDA-MB231 cells Overall design: MDA-MB231 cells were inactivated for ERRalpha using siRNA. Three different siRNAs were used (siE1, siE2, siE3). Cells treated with a control siRNA (siC samples) were used for comparison. Duplicate samples were analyzed. Transcriptomic analysis was performed by RNA-Seq
ERRα induces H3K9 demethylation by LSD1 to promote cell invasion.
Cell line, Subject
View SamplesDetermination of the genes regulated by LSD1 in MDA-MB231 cells Overall design: MDA-MB231 cells were inactivated for LSD1 using siRNA. Two different siRNAs were used (siL1, siL2). Cells treated with a control siRNA (siC samples) were used for comparison. Duplicate samples were analyzed. Transcriptomic analysis was performed by RNA-Seq
ERRα induces H3K9 demethylation by LSD1 to promote cell invasion.
No sample metadata fields
View SamplesWe hypothesized that social interactions, such as those involved in courtship and mating, would lead to assayable changes in gene expression that may have important effects on individual reproductive success and fitness through alterations in physiology or changes in nervous system function.
Mating alters gene expression patterns in Drosophila melanogaster male heads.
Sex, Age, Specimen part, Treatment
View SamplesWe hypothesized that social interactions, such as those involved in reproductive behaviors, would lead to immediate and assayable changes in gene expression that may have important effects on individual reproductive success and fitness through alterations in physiology or via short-term or long-term changes in nervous system function.
Socially-responsive gene expression in male Drosophila melanogaster is influenced by the sex of the interacting partner.
Sex, Age, Specimen part, Treatment
View SamplesRetinoic acid (RA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin activate distinct ligand-dependent transcription factors, and both cause cardiac malformation and heart failure in zebrafish embryos. We hypothesized that they cause this response by hyperactivating a common set of genes critical for heart development. To test this, we used microarrays to measure transcripts changes in hearts isolated from zebrafish embryos 1,2,4 and 12 h after exposure to 1M RA. We used hierarchical clustering to compare the transcriptional responses produced in the embryonic heart by RA and TCDD. We could identify no early responses in common between the two agents. However, at 12 h both treatments produced a dramatic downregulation of a common cluster of cell cycle progression genes, which we term the Cell Cycle Gene Cluster (CCGC). This was associated with a halt in heart growth. These results suggest that RA and TCDD ultimately trigger a common transcriptional response associated with heart failure, but not through the direct activation of a common set of genes. Among the genes rapidly induced by RA was Nr2F5, a member of the COUP-TF family of transcription repressors. We found that induction of Nr2F5 was both necessary and sufficient for the cardiotoxic response to RA.
Comparative genomics identifies genes mediating cardiotoxicity in the embryonic zebrafish heart.
No sample metadata fields
View SamplesA microarray study of sex- and gonad-biased gene expression was conducted to determine whether zebrafish demonstrate male-specific patterns consistent with those observed in other animals. We identified a large number of genes (5899) demonstrating statistical differences in transcript abundance between male and female Danio rerio. All sex-biases in gene expression were due to differences between testis and ovary, although differences between male and female body likely went undetected due to constraints imposed by study design and statistical criteria. Male-enriched genes were more abundant than female-enriched genes, and the magnitude of expression bias for male-enriched genes was greater than that for female-enriched genes. We also identified a large number of candidate reproductive genes based on elevated transcript abundance in testes and ovaries, relative to male body and female body, respectively. Gene expression patterns in adult zebrafish from this study are consistent with the male-biased patterns typical of most animal taxa studied to date. Recent zebrafish studies designed to address more specific questions have not reported the same findings, but major methodological and analytical differences across these studies could explain discrepancies.
A microarray analysis of sex- and gonad-biased gene expression in the zebrafish: evidence for masculinization of the transcriptome.
Sex
View SamplesInadequate dietary protein intake causes adverse changes in the morphology and function of skeletal muscle. These changes may be reflected in early alterations in muscle mRNA levels.
Inadequate protein intake affects skeletal muscle transcript profiles in older humans.
Sex
View SamplesWe report the effects of exposure to the endocrine disurptor (2-ethylhexyl) phthalate (DEHP) on transcriptome modification in the livers of in vivo Zebrafish. Our data indicate changes in fatty acid metabolism and insulin resistance, pathways associated with the development of Non-Alcoholic Fatty Liver Disease (NAFLD). Overall design: Examination of transcriptome changes in an in vivo model organism exposed to a common, environmental compound.
Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP).
No sample metadata fields
View Samples