Genetic disruption of thioredoxin reductase 1 protects against acetaminophen (APAP) toxicity.
A Txnrd1-dependent metabolic switch alters hepatic lipogenesis, glycogen storage, and detoxification.
Sex, Specimen part
View SamplesWild-type laboratory strains of model organisms are typically kept in isolation for many years, with the action of genetic drift and selection on mutational variation causing lineages to diverge with time. Natural populations from which such strains are established, show that gender-specific interactions in particular drive many aspects of sequence level and transcriptional level variation. Here, our goal was to identify genes that display transcriptional variation between laboratory strains of Drosophila melanogaster, and to explore evidence of gender-biased interactions underlying that variability.
Variable sexually dimorphic gene expression in laboratory strains of Drosophila melanogaster.
Sex
View SamplesGender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex-chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences.
Gender-specific gene expression in post-mortem human brain: localization to sex chromosomes.
No sample metadata fields
View SamplesPseudomonas aeruginosa displays tremendous metabolic diversity, controlled in part by the abundance of transcription regulators in the genome. We have been investigating P. aeruginosas response to the host, particularly changes regulated by the host-derived quaternary amines choline and glycine betaine (GB). We previously identified GbdR as an AraC-family transcription factor that directly regulates choline acquisition from host phospholipids (via binding to plcH and pchP promoters), is required for catabolism of the choline metabolite GB, and is an activator that induces transcription in response to GB or dimethylglycine. Our goal was to characterize the GbdR regulon in P. aeruginosa using genetics and chemical biology in combination with transcriptomics and in vitro DNA-binding assays. Here we show that GbdR activation regulates transcription of 26 genes from 12 promoters; 11 of which have measureable binding to GbdR in vitro. The GbdR regulon includes the genes encoding GB, dimethylglycine, sarcosine, glycine, and serine catabolic enzymes, and the BetX and CbcXWV quaternary amine transport proteins. . Additionally, identification of two uncharacterized regulon members suggests roles for these proteins in response to choline metabolites.
Characterization of the GbdR regulon in Pseudomonas aeruginosa.
Treatment
View SamplesRNAseq analysis of caecal tissue from 14 C. jejuni-susceptible and 14 C. jejuni-resistant birds from a single population of infected chickens was conducted in order to identify gene expression associated with resistance to colonization. Significantly higher expression of genes involved in the innate immune response, cytokine signaling, B cell and T cell activation and immunoglobulin production, as well as the renin-angiotensin system was observed in resistant birds. Overall design: A population of 255 Barred Rock chickens were orally inoculated with C. jejuni and their caecal colonization levels estimated 48 hours post-inoculation. Caecal samples from 14 birds with no colonization and the 14 birds with the highest colonization were selected for mRNA sequencing.
Genome-wide association analysis of avian resistance to Campylobacter jejuni colonization identifies risk locus spanning the CDH13 gene.
Specimen part, Subject
View SamplesWhole genome microarrays were probed with total mRNA from PTD-DRBD GAPDH siRNA treated H1299 cells at 12 h and 24 h. Using a 1.6x fold increase/decrease filter of cellular mRNAs, we detected a dramatic reduction in the target GAPDH mRNA along with a limited number of both up and down regulated genes. The up regulated genes were reduced in numbers and to nearly background 1.6x levels at 24 h, while the down regulated genes increased slightly in numbers and maintained a similar magnitude at 24 h. In contrast, lipofection treated cells showed both a dramatic increase in both the total number of genes altered and the magnitude of the increase. In addition, the numbers of genes affected increased between 12 h and 24 h, suggesting that lipofection of siRNAs into cells results in a substantial alteration to the transcriptome and may thereby confound interpretation of experimental outcomes. Moreover, the GAPDH specific knockdown was significantly smaller than PTD-DRBD mediated knockdown.
Efficient siRNA delivery into primary cells by a peptide transduction domain-dsRNA binding domain fusion protein.
Cell line, Time
View SamplesHuman herpesvirus-8 (HHV-8) is the causative agent of Kaposis sarcoma and is associated with the angioproliferative disorders primary effusion lymphoma (PEL) and multicentric Castlemans disease (MCD). We have previously described evidence of HHV-8 infection within the pulmonary vasculature of patients with idiopathic pulmonary arterial hypertension (IPAH). We speculated that viral infection of the pulmonary microvascular endothelial cells could cause the angioproliferative phenotype characteristic of severe pulmonary arterial hypertension (PAH). We now demonstrate the ability of HHV-8 to infect human pulmonary microvascular endothelial cells (HPMVECs) in vitro, confirming both latent and lytic infection. HHV-8 infection of HPMVECs resulted in significant changes of gene expression including alterations of pathways integral to both cellular apoptosis and angiogenesis. This infection also results in alterations of genes integral to the bone morphogenic protein (BMP) pathway, including down regulation of bone morphogenic protein receptor 1a (BMPR1a) and bone morphogenic protein 4 (BMP4). Other genes previously implicated in the development of PAH are also altered in expression by HHV-8 infection. These include increased expression of Interleukin-6 (IL-6) and the matrix metalloproteinases (MMP)-1, MMP-2 and MMP-10. Lastly, cells infected with HHV-8 apoptosis resistant. Infection of pulmonary microvascular endothelial cells with human herepesvirus-8 results in alteration of the BMP pathway as well as an anti-apoptotic phenotype, consistent with the development of plexiform lesions characteristic of pulmonary arterial hypertension.
Human herpesvirus-8 infection of primary pulmonary microvascular endothelial cells.
No sample metadata fields
View SamplesThe regulation of endometrial inflammation has important consequences for the resumption of bovine fertility post-partum. All cows experience bacterial influx into the uterus after calving; however a significant proportion fail to clear infection leading to the development of cytological endometritis (CE) and compromised fertility. We hypothesised that early immunological changes could not only act as potential prognostic biomarkers for the subsequent development of disease but also shed light on the pathogenesis of endometritis in the post-partum dairy cow. Here, next-generation sequencing from endometrial biopsies taken at 7 days post-partum (DPP) identified significant expression of inflammatory genes in all cows. Despite the common inflammatory profile and enrichment of the Toll-like receptor, NF?B and TNF signalling pathways, 73 genes and 31 miRNAs differentiated between healthy cows (HC, n=9) and cows which subsequently developed CE at 7 DPP (n=6, FDR<0.1). In healthy cows, 4197 differentially expressed genes between 7 and 21 DPP whereas only 31 genes were differentially expressed in samples from cows with CE. At 21 DPP, a further 1167 genes were differentially expressed between HC cows and cows diagnosed with CE (FDR<0.1). These changes in host gene expression reflected culture-independent microbiological analysis which showed significant differences in uterine bacterial profiles between groups. Inflammatory activity was not confined to the uterus; decreased circulating granulocytes and increased Acute Phase Protein (SAA and HP) plasma expression levels were detected at 7 DPP in cows that developed CE. In conclusion, our data suggests that the major inflammatory cascade activated early post-partum is resolved thereby restoring homeostasis in healthy cows by 21 DPP, but this transition fails to occur in cows which develop CE. Despite a common inflammatory profile, differential expression of specific immune genes may identify cows at risk of prolonged inflammation and the development of CE post-partum. Overall design: Sixteen Holstein Friesian cows, of mixed parity, within the same university dairy herd were sampled 7 and 21 days postpartum (DPP) in the morning after milking, over an eight week period.
Integrated analysis of the local and systemic changes preceding the development of post-partum cytological endometritis.
Specimen part, Subject, Time
View SamplesTo identify potential biological targets of the TGFß pathway involved in AVM formation, we performed RNA-seq on endothelial cells (ECs) isolated from a Smad4 inducible, EC specific knockout (Smad4-iECKO; Smad4f/f;Cdh5-CreERT2) mouse model that develops retinal AVMs. Overall design: We sequenced a total of 6 samples. We used three wild type samples (Smad4f/f- samples names: Lit38s45, Lit38s6, Lit40s56) and three mutant samples (Smad4f/f;Cdh5-CreERT2- sample names: Lit38s12, Lit38s37, Lit40s12). For more detailed information please see supplemental document: GSE116230_Smad4ff_vs_Smad4iECKO.report.pdf
Angiopoietin-2 Inhibition Rescues Arteriovenous Malformation in a Smad4 Hereditary Hemorrhagic Telangiectasia Mouse Model.
Specimen part, Cell line, Subject
View SamplesRationale: Pulmonary arterial hypertension is a common and potentially fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. The ability to identify patients at risk for developing pulmonary hypertension would be clinically beneficial.
Altered immune phenotype in peripheral blood cells of patients with scleroderma-associated pulmonary hypertension.
Sex, Specimen part, Disease, Disease stage
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