Objectives were to determine the effect of supplying butyrate post-ruminally on gene expression in the duodenum of growing polled Dorset lambs.
No associated publication
Specimen part
View SamplesThe ability to mature oocytes in vitro provides a tool for creating embryos by parthenogenesis, fertilization and cloning. Unfortunately the quality of oocytes matured in vitro falls behind that of in vivo matured oocytes. To address this difference transcriptional profiling by deep sequencing was conducted on pig oocytes that were either matured in vitro or in vivo. Alignment of over 18 million reads identified 1,316 transcripts that were differentially represented. One pathway that was overrepresented in the oocytes matured in vitro was for Wingless-type MMTV integration site (WNT) signaling. In an attempt to inhibit the WNT pathway Dickkopf-related protein 1 was added to the in vitro maturation medium. Addition of Dickkopf-related protein 1 improved the percentage of oocytes that matured to the metaphase II stage, increased the number of nuclei in the resulting blastocyst stage embryos, and in oocytes reduced the amount of disheveled segment polarity protein 1 protein. It is concluded that transcriptional profiling is a powerful method for detecting differences between in vitro and in vivo matured oocytes, and that the WNT signaling pathway is important for proper oocyte maturation.
No associated publication
Sex, Age, Specimen part, Disease, Disease stage, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
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.
No sample metadata fields
View SamplesU.S. Service Members and civilians are at risk of exposure to a variety of environmental health hazards throughout their normal duty activities and in industrial occupations. Metals are widely used in large quantities in a number of industrial processes and are a common environmental toxicant, which increases the possibility of being exposed at toxic levels. While metal toxicity has been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify candidate biomarkers, rats were exposed via a single intraperitoneal injection to three concentrations of CdCl2 and Na2Cr2O7, with livers harvested at 1, 3, or 7 days after exposure. Cd and Cr accumulated in the liver at 1 day post exposure. Cd levels remained elevated over the length of the experiment, while Cr levels declined. Metal exposures induced ROS, including hydroxyl radical (OH), resulting in DNA strand breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. Differentially expressed genes were identified via microarray analysis. Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers.
Temporal changes in rat liver gene expression after acute cadmium and chromium exposure.
Specimen part, Treatment
View SamplesCobalt is a transition group metal present in trace amounts in the human diet, but in larger doses it can be acutely toxic or cause adverse health effects in chronic, long term exposures. Its use in many industrial processes and alloys worldwide presents opportunities for occupational exposures, as well as exposures to military personnel. While the toxic effects of cobalt have been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify potential biomarkers of exposure or effect, we exposed two rat liver-derived cell lines, H4-II-E-C3 and MH1C1, to two concentrations of cobalt chloride. We examined changes in gene expression using DNA microarrays in both cell lines and examined changes in cytoplasmic protein abundance in MH1C1 cells using mass spectrometry. We chose to closely examine differentially expressed genes and proteins changing in abundance in both cells lines in order to remove cell line specific effects. We identified enriched pathways, networks, and biological functions using commercial bioinformatic tools and manual annotation. Many of the genes, proteins, and pathways modulated by exposure to cobalt appear to be due to an induction of a hypoxic-like response and oxidative stress. Genes that may be differentially expressed due to a hypoxic-like response are involved in Hif-1 signaling, glycolysis, gluconeogenesis, and other energy metabolism related processes. Gene expression changes linked to oxidative stress are also known to be involved in the NRF2-mediated response, protein degradation, and glutathione production. Using microarray and mass spectrometry analysis, we were able to identify modulated genes and proteins, further elucidate the mechanisms of toxicity of cobalt, and identify biomarkers of exposure and effect in vitro, providing targets for focused in vitro studies.
Exposure to cobalt causes transcriptomic and proteomic changes in two rat liver derived cell lines.
Cell line
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
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