retinal ganglion cells die after optic nerve injury, either crush or transection. The molecular causesunderlying this degeneration are largely unkwon
Time course profiling of the retinal transcriptome after optic nerve transection and optic nerve crush.
No sample metadata fields
View SamplesAlthough protein acetylation is widely observed, it has been associated with few specific regulatory functions making it poorly understood. To interrogate its functionality, we analyzed the acetylome in Escherichia coli knockout mutants of cobB, the only known sirtuin-like deacetylase, and patZ, the best-known protein acetyltransferase. For four growth conditions, more than 2,000 unique acetylated peptides, belonging to 809 proteins, were identified and differentially quantified. Nearly 65% of these proteins are related to metabolism. The global activity of CobB contributes to the deacetylation of a large number of substrates and has a major impact on physiology. Apart from the regulation of acetyl-CoA synthetase, we found that CobB-controlled acetylation of isocitrate lyase contributes to the fine-tuning of the glyoxylate shunt. Acetylation of the transcription factor RcsB prevents DNA binding, activating flagella biosynthesis and motility, and increases acid stress susceptibility. Surprisingly, deletion of patZ increased acetylation in acetate cultures, which suggests that it regulates the levels of acetylating agents. The results presented offer new insights into functional roles of protein acetylation in metabolic fitness and global cell regulation.
Protein acetylation affects acetate metabolism, motility and acid stress response in Escherichia coli.
No sample metadata fields
View SamplesEffects of betalains in C. elegans gene expression is studied, as our previous results showed a lifespan extension effect produced by theses molecules
Betalain health-promoting effects after ingestion in Caenorhabditis elegans are mediated by DAF-16/FOXO and SKN-1/Nrf2 transcription factors.
Age, Specimen part, Treatment
View SamplescAMP receptor protein (CRP, also known as the catabolite activator protein [CAP]) is arguably the best-studied of the global transcription factors of E coli. CRP alone is responsible for regulating at least 283 operons. Upon binding cAMP, the CRP dimer binds DNA and directly interacts with RNA polymerase (RNAP). At Class II promoters, CRP binds near position -41,5 relative to the transcription start site and contacts the amino-terminal domain of the RNAP subunit (RNAP-NTD). This interaction requires AR2, a patch of primarily positively charged residues (H19, H21, E96, and K101) that interact with negatively charged residues on RNAP-NTD. Acetylome analyses consistently detect lysine 100 (K100) of CRP as acetylated. Since K100 is adjacent to the positively charged AR2, we hypothesized that the K100 positive charge may also play a role in CRP function. We further hypothesized that acetylation of K100 would neutralize this positive charge, leading to a potential regulatory mechanism
Influence of Glucose Availability and CRP Acetylation on the Genome-Wide Transcriptional Response of <i>Escherichia coli</i>: Assessment by an Optimized Factorial Microarray Analysis.
No sample metadata fields
View SamplesConsider the problem of designing a panel of complex biomarkers to predict a patient's health or disease state when one can pair his or her current test sample, called a target sample, with the patient's previously acquired healthy sample, called a reference sample. As contrasted to a population averaged reference, this reference sample is individualized. Automated predictor algorithms that compare and contrast the paired samples to each other could result in a new generation of test panels that compare to a person's healthy reference to enhance predictive accuracy. This study develops such an individualized predictor and illustrates the added value of including the healthy reference for design of predictive gene expression panels. The objective is to predict each subject's state of infection, e.g., neither exposed nor infected, exposed but not infected, pre-acute phase of infection, acute phase of infection, post-acute phase of infection. Using gene microarray data collected in a large-scale serially sampled respiratory virus challenge study, we quantify the diagnostic advantage of pairing a person's baseline reference with his or her target sample.
An individualized predictor of health and disease using paired reference and target samples.
Specimen part, Subject, Time
View SamplesAfrican-American individuals of the GENOA cohort
Genetic Architecture of Gene Expression in European and African Americans: An eQTL Mapping Study in GENOA.
Sex, Age, Specimen part
View SamplesThe NIH Roadmap Epigenomics Mapping Consortium aims to produce a public resource of epigenomic maps for stem cells and primary ex vivo tissues selected to represent the normal counterparts of tissues and organ systems frequently involved in human disease.
The NIH Roadmap Epigenomics Mapping Consortium.
Sex, Specimen part, Disease, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility.
Sex, Specimen part
View SamplesA cardinal symptom of Major Depressive Disorder (MDD) is the disruption of circadian patterns. Yet, to date, there is no direct evidence of circadian clock dysregulation in the brains of MDD patients. Circadian rhythmicity of gene expression has been observed in animals and peripheral human tissues, but its presence and variability in the human brain was difficult to characterize. Here we applied time-of-death analysis to gene expression data from high-quality postmortem brains, examining 24-hour cyclic patterns in six cortical and limbic regions of 55 subjects with no history of psychiatric or neurological illnesses ('Controls') and 34 MDD patients. Our dataset covered ~12,000 transcripts in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (AnCg), hippocampus (HC), amygdala (AMY), nucleus accumbens (NAcc) and cerebellum (CB). Several hundred transcripts in each region showed 24-hour cyclic patterns in Controls, and >100 transcripts exhibited consistent rhythmicity and phase-synchrony across regions. Among the top ranked rhythmic genes were the canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERB), DBP, BHLHE40(DEC1), and BHLHE41(DEC2). The phasing of known circadian genes was consistent with data derived from other diurnal mammals. Cyclic patterns were much weaker in MDD brains, due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes. This is the first transcriptome-wide analysis of cyclic patterns in the human brain and demonstrates a rhythmic rise and fall of gene expression in regions outside of the suprachiasmatic nucleus in control subjects. The description of its breakdown in MDD suggest novel molecular targets for treatment of mood disorders.
Circadian patterns of gene expression in the human brain and disruption in major depressive disorder.
Subject
View SamplesWith aging, significant changes in circadian rhythms occur, including a shift in phase toward a morning chronotype and a loss of rhythmicity in circulating hormones. However, the effects of aging on molecular rhythms in the human brain have remained elusive. Here we employed a previously-described time-of-death analyses to identify transcripts throughout the genome that have a significant circadian rhythm in expression in the human prefrontal cortex (Brodmanns areas (BA) 11 and 47). Expression levels were determined by microarray analysis in 146 individuals. Rhythmicity in expression was found in ~10% of detected transcripts (p<0.05). Using a meta-analysis across the two brain areas, we identified a core set of 235 genes (q<0.05) with significant circadian rhythms of expression. These 235 genes showed 92% concordance in the phase of expression between the two areas. In addition to the canonical core circadian genes, a number of other genes were found to exhibit rhythmic expression in the brain. Notably, we identified more than one thousand genes (1186 in BA11; 1591 in BA47) that exhibited age-dependent rhythmicity or alterations in rhythmicity patterns with aging. Interestingly, a set of transcripts gained rhythmicity in older individuals, which may represent a compensatory mechanism due to a loss of canonical clock function. Thus, we confirm that rhythmic gene expression can be reliably measured in human brain and identified for the first time significant changes in molecular rhythms with aging that may contribute to altered cognition, sleep and mood in later life.
Effects of aging on circadian patterns of gene expression in the human prefrontal cortex.
Sex, Age, Specimen part, Race
View Samples