We used microarray analyses in adult female zebrafish (Danio rerio) to identify metabolic pathways regulated by starvation in two key organs that 1) serve biosynthetic and energy mobilizing functions (liver) and 2) consume energy and direct behavioral responses (brain). Starvation affected the expression of 574 transcripts in the liver, indicating an overall decrease in metabolic activity, reduced lipid metabolism, protein biosynthesis and proteolysis, and cellular respiration, and increased gluconeogenesis. Starvation also regulated expression of many components of the Unfolded Protein Response, the first such report in a species other than yeast (Saccharomyces cerevisiae) and mice (Mus musculus). The response of the zebrafish hepatic transcriptome to starvation was strikingly similar to that of rainbow trout (Oncorhynchus mykiss), but very different from common carp (Cyprinus carpio) and mouse. The transcriptome of zebrafish whole brain was much less affected than the liver, with only two differentially expressed genes, both down-regulated. Down-regulation of one of these genes, matrix metalloproteinase 9 (mmp9), suggests increased inhibition of apoptosis (neuroprotection) and decreased restructuring of the extracellular matrix in the brain of starved zebrafish. The low level of response in the transcriptome of whole zebrafish brain agrees with observations that the brain is metabolically protected compared to the rest of the body.
Effect of starvation on transcriptomes of brain and liver in adult female zebrafish (Danio rerio).
No sample metadata fields
View SamplesThe possible benefits of selenium (Se) supplementation are currently under investigation for prevention of certain cancers and treatment of neurological disorders. Little is known concerning the response of the brain to increased dietary Se under conditions of Se sufficiency, despite the majority of Se supplementation trials occurring in healthy subjects considered Se sufficient. We evaluated the transcriptional response of the zebrafish (Danio rerio) brain to supplementation with nutritionally relevant levels of dietary Se (sodium selenite) during conditions of assumed Se sufficiency.
Sex-specific transcriptional responses of the zebrafish (Danio rerio) brain selenoproteome to acute sodium selenite supplementation.
Sex, Age, Specimen part, Treatment
View SamplesEthanol is a well-known teratogen. While this teratogenic potential is well-characterized clinically, the mechanisms through which ethanol exposure results in developmental defects remain unclear. Here we use the zebrafish model to elucidate eye-specific mechanisms that may underlie ethanol-mediated microphthalmia (reduced eye size), using time-series microarray analysis of gene expression of eye tissues of embryos exposed to 1.5% ethanol vs. untreated embryos. We identified 62 genes differentially expressed in ethanol-treated as compared to control zebrafish eyes from all sampling times over the period of retinal neurogenesis (24-48 hours post-fertilization). Application of the EDGE (extraction of differential gene expression) algorithm identified over 3000 genes differentially expressed over developmental time in ethanol-treated embryo eyes as compared to untreated embryo eyes. These lists included several genes indicating a mis-regulated cellular stress response (heat shock response) due to ethanol exposure. Combined treatment with sub-threshold levels of ethanol and a morpholino (MO) targeting heat shock factor 1 (hsf-1) mRNA resulted in a microphthalmic phenotype, suggesting convergent molecular pathways. Manipulation of the heat shock response by thermal preconditioning partially prevented ethanol-mediated microphthalmia while maintaining Hsf-1 expression. Together these data are consistent with roles for reduced Hsf-1 in mediating microphthalmic effects of embryonic ethanol exposure in zebrafish.
Eye-specific gene expression following embryonic ethanol exposure in zebrafish: roles for heat shock factor 1.
Specimen part, Treatment
View SamplesThe signaling molecule retinoic acid (RA) regulates rod and cone photoreceptor fate, differentiation, and survival. The purpose of this study was to identify eye-specific genes controlled by RA during photoreceptor differentiation in the zebrafish.
Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish.
Specimen part
View SamplesAltered mRNA levels of HBT1 were observed in S. cerevisiae cells expressing hsc82-W296A compared to WT HSC82. We conducted microarray analysis to determine the extent of other changes in that strain.
Identification of an Hsp90 mutation that selectively disrupts cAMP/PKA signaling in Saccharomyces cerevisiae.
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 Samples