This SuperSeries is composed of the SubSeries listed below.
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Specimen part, Cell line
View SamplesIn order to examine the long term effects of the OPs, murine liver cells (BNL CL.2, ATCC TIB-73) have been exposed to sub-lethal doses of three OPs: diisopropylfluorophosphate (DFP) representative of sarin and soman, O,S-diethyl methylphosphonothioate (OSD) serving as a simulant for VX, and paraoxon as an example of OP insecticides. Dosing levels of these compounds was set at 20% of the IV LD50 for each, with a 4 hour exposure time. Gene arrays and physiological tests were run at three time points following exposure; 2 hours, 2 days, and 2 weeks. The physiological results showed little to no effect upon exposure to sub-lethal dose of OPs. Gene expression and microRNA (miRNA) profiles using GeneChip Mouse Gene 1.0 ST arrays and miRNA arrays (Affymetrix, Santa Clara, CA) found that the OPs did alter expression of genes related to several systems previously implicated in OP exposure with no long term effects. In addition, a significant number of sRNA/snRNA and ribosomal RNA were found to be affected suggesting the need for further study of the changes in these regulators.
No associated publication
Specimen part, Cell line
View SamplesSeveral different mechanisms have been proposed to explain the possible role of cranberries, cranberry juice, and cranberry extracts in inhibiting bacterial growth. In this report, we showed that Escherichia coli showed slower growth rate in response to the presence of cranberry juice in the growth media. By compareing the global transcript profiles, significant modulation of several genes of E. coli grown in LB broth with 10% cranberry juice were identified and provided identification of the potential mechanisms involved in the inhibitory effects of cranberry juice. The results presented clearly demonstrate that the inhibitory effect on bacterial growth observed in the presence of cranberry juice/extracts is primarily a result of the iron chelation capacity of PACs and direct disruption of metabolic enzymes. The results are discussed with a focus on the genes associated with iron chelation capability.
Impact of cranberry on Escherichia coli cellular surface characteristics.
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View SamplesIn response to limited nitrogen and abundant carbon sources, diploid Saccharomyces cerevisiae strains undergo a filamentous transition in cell growth as part of pseudohyphal differentiation. Use of the disaccharide maltose as the principal carbon source, in contrast to the preferred nutrient monosaccharide glucose, has been shown to induce a hyper-filamentous growth phenotype in a strain deficient for GPA2 which codes for a Galpha protein component that interacts with the glucose-sensing receptor Gpr1p to regulate filamentous growth. In this report, we compare the global transcript and proteomic profiles of wild-type and Gpa2p deficient diploid yeast strains grown on both rich and nitrogen starved maltose media. We find that deletion of GPA2 results in significantly different transcript and protein profiles when switching from rich to nitrogen starvation media. The results are discussed with a focus on the genes associated with carbon utilization, or regulation thereof, and a model for the contribution of carbon sensing/metabolism-based signal transduction to pseudohyphal differentiation is proposed.
Transcript and proteomic analyses of wild-type and gpa2 mutant Saccharomyces cerevisiae strains suggest a role for glycolytic carbon source sensing in pseudohyphal differentiation.
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View SamplesHuanglongbing (HLB) (=citrus greening) is a destructive disease of citrus which is caused by a fastidious, phloem-inhabiting bacterium of the genus Candidatus Liberibacter. Large-scale analysis of gene expression changes in Valencia orange leaves were studied during the course of 19 weeks after inoculation with Ca. L. asiaticus using the Affymetrix GeneChip citrus genome array to provide new insights into the molecular basis of citrus response to this pathogen. Of the more than 33,000 probe sets on the microarray 21,067 were expressed in the leaves, of which 279 and 515 were differentially expressed (FDR 0.05) five to nine and 13-17 weeks after inoculation, respectively. Results from semi-quantitative RT-PCR analysis performed on 14 selected genes were highly correlated with those observed with the microarray. Gene expression changes involved a variety of different processes including cell defense, transport, cellular organization, photosynthesis, and carbohydrate metabolism. Notable was the pathogen-induced accumulation of transcripts for a phloem-specific lectin PP2-like protein. Transcriptional changes and their relation to disease symptom development are discussed. This is the first study of transcriptional profiling in citrus in response to liberibacter infection using microarray technology.
No associated publication
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Sex, Specimen part
View SamplesMale and female CD-1 mice were administered dietary Phenobarbital for 2 or 7 days. In-life, enzyme activity, cell proliferation, genomic analysis, and Bench-mark dose modeling was carried out.
Dose-response modeling of early molecular and cellular key events in the CAR-mediated hepatocarcinogenesis pathway.
Specimen part
View SamplesHigh-throughput transcriptomic (HTTr) technologies are increasingly being used to screen environmental chemicals in vitro to identify molecular targets and provide mechanistic context for regulatory testing. The androgen receptor (AR, NR3C4) regulates male sexual development, is involved in the pathogenesis of a number of cancers, and is often the target of endocrine disruptors. Here, we describe the development and validation of a novel gene expression biomarker to identify AR-modulating chemicals using a pattern matching method. AR biomarker genes were identified by their consistent expression after exposure to 4 AR agonists and opposite expression after exposure to 4 AR antagonists. A genetic filter was used to include only those genes that were regulated by AR. Most of the resulting 51 biomarker genes were shown to be directly regulated by AR as determined by ChIP-Seq analysis of AR-DNA interactions. The biomarker was evaluated as a predictive tool using the fold-change rank-based Running Fisher algorithm which compares the expression of AR biomarker genes under various treatment conditions. Using 163 comparisons from cells treated with 98 chemicals, the biomarker gave balanced accuracies for prediction of AR activation or AR suppression of 97% or 98%, respectively. The biomarker was able to correctly classify 16 out of 17 AR reference antagonists including those that are weak and very weak. Predictions based on comparisons from AR-positive LAPC-4 cells treated with 28 chemicals in antagonist mode were compared to those from an AR pathway model based on 11 in vitro high-throughput screening assays that queried different steps in AR signaling. The balanced accuracy was 93% for suppression. Using our approach, we identified conditions in which AR was modulated in a large collection of microarray profiles from prostate cancer cell lines including 1) AR constitutively active mutants or knockdown of AR, 2) depletion of androgens by castration or removal from media, and 3) modulators that work through indirect mechanisms including suppression of AR expression. These results demonstrate that the AR gene expression biomarker could be a useful tool in HTTr to identify AR modulators in large collections of microarray data derived from AR-positive prostate cancer cell lines.
Identification of Androgen Receptor Modulators in a Prostate Cancer Cell Line Microarray Compendium.
Specimen part, Cell line
View SamplesThe modes of triazole reproductive toxicity have been characterized by an observed increased in serum testosterone and reduced insemination and fertility indices. The key events involved in the disruption in testosterone homeostasis and reduced fertility remain unclear. Gene expression analysis was conducted on liver from Sprague Dawley rats dosed with myclobutanil (300 mg/kg/day) or triadimefon (175 mg/kg/day) for 6, 24 or 336 hours. Pathway-based analysis highlighted key biological processes affected by all three triazoles in the liver including fatty acid catabolism, steroid metabolism, and xenobiotic metabolism. Within the pathways identified in the liver, specific genes involved in phase I-III metabolism and fatty acid metabolism were affected by all three triazoles. These modulated genes are part of a network of lipid and testosterone homeostasis pathways regulated by the constitutive androstane (CAR) and pregnane X (PXR) receptors. Gene expression profiles from this study indicate triazoles activate CAR and PXR; increase fatty acid catabolism and steroid metabolism in the liver; constituting a plausible series of key events contributing to the observed disruption in testosterone homeostasis.
Toxicogenomic effects common to triazole antifungals and conserved between rats and humans.
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View SamplesThe triazole antifungals myclobutanil (MYC), propiconazole (PPZ) and triadimefon (TDF) [Propiconazole CASNR 60207-90-1; Triadimefon CASNR 43121-43-3; Myclobutanil CASNR 88671-89-0] all disrupt steroid hormone homeostasis and cause varying degrees of hepatic toxicity. To identify biological pathways consistently activated across various study designs, gene expression profiling was conducted on livers from rats following acute, repeated dose, or prenatal to adult exposures. To explore conservation of responses across species, gene expression from these rat in vivo studies were also compared to in vitro data from rat and human primary hepatocytes exposed to MYC, PPZ, or TDF. Pathway and gene level analyses across time of exposure, dose, and species identified patterns of expression common to all three triazoles, which were also conserved between rodents and humans. Pathways affected included androgen and estrogen metabolism, xenobiotic metabolism signaling through CAR and PXR, and CYP mediated metabolism. Many of the differentially expressed genes are regulated by the nuclear receptors CAR, PPAR alpha and PXR, including ABC transporter genes (Abcb1 and MDR1), genes significant to xenobiotic, fatty acid, sterol and steroid metabolism (Cyp2b2 and CYP2B6; Cyp3a1 and CYP3A4; Cyp4a22 and CYP4A11) and xxx (Ugt1a1 and UGT1A1). Modulation of hepatic sterol and steroid metabolism is a plausible mechanism for triazole induced increases in serum testosterone. The gene expression changes caused by all three triazoles appear to focus on pathways regulating lipid and testosterone homeostasis, identifying potential common mechanisms of triazole hepatotoxicity that are conserved between rodents and humans.
Toxicogenomic effects common to triazole antifungals and conserved between rats and humans.
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