Mutational burden in oesophagus nanoseq
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PROVIDER: EGAS00001007695 | EGA |
REPOSITORIES: EGA
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Project description:We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice. We identified similar patterns of transcriptional changes in brain and liver among three different alcohol consumption tests and lipopolysaccharide injection. We also demonstrated distinct genomic consequences of different types of alcohol consumption.
2013-04-01 | GSE42789 | GEO
Project description:In this study, to better understand the mechanisms of the profound impact of alcohol consumption on drug pharmacokinetics, efficacy, and toxicity, we characterized the alcohol-induced changes in the ensemble of drug-metabolizing enzymes and transporters (DMETs) in the human liver by performing global proteomic analysis of human liver microsomes from 94 donors. DMET protein levels were analyzed concerning alcohol consumption, smoking history, and sex using non-parametric tests, which were further strengthened by correlational analysis. To this end, we used a provisional index of alcohol exposure formulated based on the relative abundances of four marker proteins best correlating with the level of alcohol consumption. Alcohol-induced changes in the cytochrome P450 pool include significant increases in CYP2E1, CYP2B6, CYP2J2, and NADPH-cytochrome P450 reductase levels and the lowering of CYP1A2, CYP2C8, CYP2C9, CYP4A11, and cytochrome b5. Changes in UDP-glucuronosyltransferase (UGT) abundances comprise elevated UGT1A6, UGT1A9, and UGT2A1, and reduced UGT1A3, UGT1A4, UGT2B7, UGT2B10, and UGT2B15 levels. Tobacco smokers showed elevated CYP1A2, UGT1A6, and UGT2B4 and reduced FMO3, FMO4, and FMO5 levels, while in females, CYP1A2, UGT2B17, and UGT2B15 levels were lower, and UGT2A3 and STS were higher compared to males. The alcohol-induced changes in the DMET ensemble at the protein level reported herein provide deep insights into how alcohol impacts drug and xenobiotic metabolism.
2025-02-11 | PXD060653 | Pride
Project description:We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice. We identified similar patterns of transcriptional changes in brain and liver among three different alcohol consumption tests and lipopolysaccharide injection. We also demonstrated distinct genomic consequences of different types of alcohol consumption. The microarray experiment was performed to compare gene expression changes induced by three separate paradigms of alcohol consumption and immune activation by lipopolysaccharide injection. The three tests of alcohol consumption were the continuous chronic two bottle choice (Chronic), two bottle choice available every other day (Chronic Intermittent) and limited access to one bottle of ethanol (Drinking in the Dark). All alcohol studies utilized 20% ethanol and each treatment group had it's own control group which received only water. The immune activation test consisted of 2 lipopolysaccharide injections (1 mg/kg i.p.) spaced one week apart, with animals being sacrificed one week after the last injection. Control animals received saline injections. All studies used female, adult mice.
2013-04-01 | E-GEOD-42789 | biostudies-arrayexpress
Project description:Background: The most important risk factors for head and neck squamous carcinoma (HNSCC) are tobacco smoking and alcohol consumption, while subgroups are caused by infection with human papillomaviruses (HPV) or Epstein-Barr virus (EBV). Here, we studied alterations of somatic copy-number in whole genome, p16 protein and TP53 mutations by alcohol drinking, smoking and viral infections. Methods: We conducted a prospective cohort study. DNA obtained from tumors and margin samples as well as peripheral blood was assayed by array comparative genomic hybridization using Agilent Whole Human Genome 180K. Mutations of p53 gene by direct sequencing, detection of HPV by polymerase-chain-reaction (PCR), quantification of EBV by reverse transcription-PCR and p16 immunohistochemical (IHC) staining were also performed. prospective cohort study: 225 tumor samples were analyzed by Agilent-022060 SurePrint G3 Human CGH miroarray 4x180K. Log2 Ratio (tumor sample DNA/normal DNA) were compared among none alcohol drinkers, moderate alcohol drinkers, heavy alcohol drinkers, none smokers, moderate smokers, heavy smokers and both. Sample characteristics weres scored as following; Human Papilloma Virus Infection (gene detected by PCR in tumor sample): positive=1; negative=0 p16 protein immunohistochemistry: positive=1; negative=0 tumor grade: matured=0; moderate=1; immature=2 Radiotherapy with or without chemotherapy after operation: performed =1; not performed =0 Recurrence/relapse: rec =1; not rec =0 suvival status:death=1; survive=0 smoking status (Pack year of smoking): none smoker=0; pack-year <20 = 1 (moderate smoker); pack-year <=20 = 2 (heavy smoker) alcohol drinking: Alcohol drinkers were divided into non-drinker or less than one drink per day =0: one and more but less than two drinks per day = moderate drinker 1: two and more drinks per day=heavy drinker 2: during the 20 years preceding their treatment for HNSCC. One drink was defined as containing approximately 10g of alcohol, which is considered equal to 30 ml of hard liquor, 100 ml of wine containing 12% alcohol, or 360 ml of beer.
2013-07-01 | E-GEOD-47443 | biostudies-arrayexpress
Project description:PrEC cells treated with either 50uM alanine or 50uM sarcosine (N-methylglycine). Gene expression is measured after 6 hours. We wish to look at the effects of sarcosine addition in relation to alanine addition. Keywords: Amino acid addition response
2009-12-31 | GSE10164 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE31695: Comparison of Differences in Gene Expression in the Ventral Tegmental Area of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption GSE31705: Comparison of Differences in Gene Expression in the Nucleus Accumbens Shell of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption GSE31708: Comparison of Differences in Gene Expression in the Central Nucleus of the Amygdala (CeA) of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption Refer to individual Series
2012-07-31 | E-GEOD-31709 | biostudies-arrayexpress
Project description:Prenatal alcohol exposure can cause long-lasting changes in functional and genetic programs of the brain, which may underlie behavioral alterations found in FASD. Here, we demonstrated that maternal binge alcohol consumption alters the expression of genes involved in nervous system development. Maternal binge alcohol consumption alters several important genes that are involved in nervous system development in the mouse hippocampus at embryonic day 18 (ED18)
2014-09-04 | E-GEOD-61049 | biostudies-arrayexpress
Project description:We recently established ACSS2 as a potential candidate for therapeutic interventions in alcohol use disorders (AUD), in which memory of alcohol-associated environmental cues is a primary driver of craving and relapse. Prior research, however, has been limited to passive exposure to ethanol and the importance of this pathway in models of voluntary drinking that better approximate human alcohol consumption remains unknown. Therefore, we assessed the effect of genetic ACSS2 inhibition on voluntary alcohol intake and simultaneously assayed the epigenetic and transcriptional changes that accompany alcohol consumption.
2024-10-31 | GSE249119 | GEO
Project description:LncRNAs are important regulators of quantitative and qualitative features of the transcriptome. We have used QTL and other statistical analyses to identify a gene coexpression module associated with the phenotype of alcohol consumption. The “hub gene” of this module, Lrap (Long non-coding RNA for alcohol preference), was an unannotated transcript resembling a lncRNA. We used partial correlation analyses to establish that Lrap is a major contributor to the integrity of the coexpression module. Using CRISPR/Cas9 technology, we disrupted an exon of Lrap in Wistar rats. The genetically modified rats were assessed for alcohol consumption and brain RNA expression levels were evaluated using RNASeq. Measures of alcohol consumption in wild type, heterozygous and knockout rats demonstrated that disruption of Lrap produced increases in alcohol consumption/alcohol preference. The disruption of Lrap also produced changes in expression of over 700 other transcripts. Furthermore, it became apparent that Lrap may have a function in alternative splicing of the affected transcripts. More than 20% of the differentially expressed isoforms exhibited evidence for novel alternative splicing between Lrap+/+ and Lrap-/- rats. The GO category of “Response to Ethanol” emerged as one of the top candidates in an enrichment analysis of the differentially expressed transcripts. We validate the role of Lrap as a mediator of alcohol consumption by rats, and also implicate Lrap as a modifier of the expression and splicing of a large number of brain transcripts. A defined subset of these transcripts significantly impacts alcohol consumption by rats (and possibly humans).
2020-08-19 | GSE155709 | GEO
Project description:Purpose: Alcohol abuse induces changes in microglia morphology and immune function, but whether microglia initiate or simply amplify the harmful effects of alcohol exposure is still a matter of debate. Here we determined microglia function in acute and voluntary drinking behaviors using a colony stimulating factor 1 receptor inhibitor (PLX5622) and 3’UTR biased-sequencing. Therefore, The purpose of this study was to provide insight regarding microglia depletion and voluntary alcohol consumption. Methods: We performed 3’UTR biased transcriptome sequencing (3’Tag-seq) on total homogenate isolated from the prefrontal cortex (PFC) of C57BL6/J mice following microglia depletion and chronic every-other-day alcohol consumption. Results: Differential expression analysis and WGCNA network analysis revealed that although many immune genes have been implicated in alcohol abuse, downregulation of microglia genes does not necessitate changes in alcohol intake. Finally, we show that microglia depletion and chronic alcohol result in compensatory upregulation of ethanol-responsive, reactive astrocyte genes, indicating astrocytes may play a critical role in regulation of these alcohol behaviors. Conclusion:Taken together our behavioral and transcriptional data indicate that microglia are not the primary effector cell responsible for regulation of acute and voluntary alcohol behaviors. In addition, our data represents a novel resource for groups interested in transcriptional effects of microglia depletion after alcohol consumption.
2020-06-01 | GSE132516 | GEO