Saccharomyces cerevisiae flocculation occurs when fermentable sugars are limiting and is therefore considered as a way to enhance the survival chance of Flo-expressing yeast cells. In this paper, the role of Flo1p in mating was demonstrated by showing that the mating efficiency, which contributes to the increased survival rate as well by generating genetic variability, is increased when cells flocculate. This was revealed by liquid growth experiments in a low shear environment and differential transcriptome analysis of FLO1 expressing cells compared to the non-flocculent wild-type cells. The results show that a floc provides a uniquely organized multicellular ultrastructure that provides a suitable microenvironment to induce and perform cell conjugation.
Molecular mechanism of flocculation self-recognition in yeast and its role in mating and survival.
No sample metadata fields
View SamplesAim of the study was to characterize the transcriptional response of human primary renal proximal tubule epithelial cells (RPTEC) to low oxygen stress.
The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesWe recently identified the nonreceptor tyrosine kinase syk as a tumor suppressor in pancreatic ductal adenocarcinoma cells. Reintroduction of syk into Panc1 cells promoted a more differentiated phenotype and retarded invasion and tumorigenic growth. Gene array analysis identified over 2,000 transcripts differentially expressed at FDR<0.01. Among these were members of the MMP2 axis, which were subsequently shown to regulate Panc1 invasion.
Syk tyrosine kinase acts as a pancreatic adenocarcinoma tumor suppressor by regulating cellular growth and invasion.
Cell line
View SamplesIntroduction: Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this study was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Methods: Left renal ischemia was induced in rats by clamping renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n=8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (Saline) intraperitoneally. Animals were sacrificed at 3h, 24h or 120h post- IR and blood, urine and kidney were collected. Results: Serum creatinine (mg/dL) at 24 h IR in VPA (2.71.8) and Dex (2.31.2) was reduced (P<0.05) compared to Vehicle (3.80.5). At 3h post-IR, urine albumin (mg/ml) was higher in Vehicle (1.470.10), VPA (0.840.62) and Dex (1.040.73) compared to uninjured/untreated control (0.140.26) group. At 24h post-IR urine Lipocalin-2 (g/ml) was significantly higher (P<0.05) in VPA, Dex and Vehicle groups (9.61-11.36) compared to uninjured/untreated control (0.67o.29); also, Kidney Injury Molecule-1 (KIM-1; ng/ml) was significantly higher in VPA, Dex and Vehicle groups (13.7-18.7) compared uninjured/untreated control (1.71.9). KIM-1 levels were significantly (P<0.05) higher in all groups compared to uninjured/untreated control levels. Histopathology at 3h post IR demonstrated (P<0.05) reduction in ischemic injury in the renal cortex in VPA (Grade 1.6 1.5) compared to Vehicle (Grade 2.91.1) group. Inflammatory cytokines IL1 and IL6 were down-regulated in VPA and Dex groups. BCL2 was higher in VPA group. DNA microarray analysis demonstrated reduced stress response and injury, and improved recovery related gene expression in the kidneys of VPA treated animals. Conclusions: VPA administration reduced kidney IR injury and improved regeneration. KIM-1 and Lipocalin-2 appear to be promising early urine biomarkers of acute ischemic kidney injury.
Effects of valproic acid and dexamethasone administration on early bio-markers and gene expression profile in acute kidney ischemia-reperfusion injury in the rat.
Sex, 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 SamplesDespite an abundance of evidence to the contrary from animal studies, large clinical trials on humans have shown that estrogen administered to post-menopausal women increases the risk of cardiovascular disease. However, timing may be everything, as estrogen is often administered immediately after ovariectomy (ovx) in animal studies, while estrogen administration in human studies occurred many years post-menopause. This study investigates the discrepancy by administering 17-estradiol (E2) in a slow-release capsule to Norway Brown rats both immediately following ovx and 9 weeks post-ovx (Late), and studying differences in gene expression between these 2 groups as compared to age-matched ovx and sham operated animals. Two different types of microarray were used to analyze the left ventricles from these groups: an Affymetrix array (2 samples/group, each sample contained total RNAs pooled from 3 rats) and an Inflammatory Cytokines and Receptors PCR array (N=4 /group). Key genes were analyzed by western blotting. Ovx without replacement led to an increase in caspase 3, caspase 9, calpain 2, MMP9, and TNF. Caspase 6, STAT3, and CD11b increased in the Late group, while TIMP2, MMP14, and collagen I 1 were decreased. MADD and fibronectin were increased in both Ovx and Late. TNF protein levels increased with Late replacement. Many of these changes were prevented by early E2 replacement. These findings suggest that increased TNF may be involved in some of the deleterious effects of delayed E2 administration seen in human studies.
Impact of aging vs. estrogen loss on cardiac gene expression: estrogen replacement and inflammation.
Sex, Specimen part, Treatment
View SamplesLow-dose epirubicin at non-cytotoxic doses down regulated NLRP3 inflammasome components and reduced the release of proinflammatory cytokines.
Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines.
Cell line
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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics.
No sample metadata fields
View SamplesTo model human cerebellar disease, we developed a novel, reproducible method to generate cerebellar Purkinje cells (PCs) from human pluripotent stem cells (hPSCs) that formed synapses when cultured with mouse granule cells and fired large calcium currents, measured with the genetically encoded calcium indicator jRGECO1a. Using translating ribosomal affinity purification (TRAP) to compare gene expression of differentiating hPSC-PCs to developing mouse PCs, we found hPSC-PCs to be most similar to late juvenile (P21) mouse PCs. Analysis of mouse PCs defined novel developmental expression patterns for mitochondria and autophagy associated genes, recapitulated in hPSC-PCs. We further identified species differences in gene expression and confirmed protein expression of CD40LG in native human, but not mouse PCs. This study provides a robust method for generating relatively mature hPSC-PCs with human specific gene expression and defines novel genetic features in comparison to the first comprehensive analysis of global gene expression patterns of postnatal mouse PC development.
Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics.
No sample metadata fields
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