Skeletal muscle adapts to exercise training of various modes, intensities and durations with a programmed gene expression response. This study dissects the independent and combined effects of exercise mode, intensity and duration to identify which exercise has the most positive effects on skeletal muscle health. Full details on exercise groups can be found in: Kraus et al Med Sci Sports Exerc. 2001 Oct;33(10):1774-84 and Bateman et al Am J Cardiol. 2011 Sep 15;108(6):838-44.
Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness.
Sex, Age, Specimen part, Race, Subject
View SamplesPGC-1 transcription factor was customized to limit its interations to ERRalpha. This mutant (2x9) was used to dissect the transcription activation patterns that are attributable to the PGC1-ERR interaction and PGC-1 actions that are independent of ERR. Inactive mutant with the deleted LLXXL motifs (L2L3) and wt PGC-1 were used as negative and positive controls respectively. BGAL-expressing construct was used to control for non-specific effects of adenoviral infection.
Receptor-selective coactivators as tools to define the biology of specific receptor-coactivator pairs.
No sample metadata fields
View SamplesCompelling evidence suggests that mitochondrial dysfunction contributes to the pathogenesis of heart failure, including defects in the substrate oxidation, and the electron transport chain (ETC) and oxidative phosphorylation (OXPHOS). However, whether such changes occur early in the development of heart failure, and are potentially involved in the pathologic events that lead to cardiac dysfunction is unknown. To address this question, we conducted transcriptomic/metabolomics profiling in hearts of mice with two progressive stages of pressure overload-induced cardiac hypetrophy: i) cardiac hypertrophy with preserved ventricular function achieved via transverse aortic constriction for 4 weeks (TAC) and ii) decompensated cardiac hypertrophy or heart failure (HF) caused by combining 4 wk TAC with a small apical myocardial infarction. Transcriptomic analyses revealed, as shown previously, downregulated expression of genes involved in mitochondrial fatty acid oxidation in both TAC and HF hearts compared to sham-operated control hearts. Surprisingly, however, there were very few changes in expression of genes involved in other mitochondrial energy transduction pathways, ETC, or OXPHOS. Metabolomic analyses demonstrated significant alterations in pathway metabolite levels in HF (but not in TAC), including elevations in acylcarnitines, a subset of amino acids, and the lactate/pyruvate ratio. In contrast, the majority of organic acids were lower than controls. This metabolite profile suggests bottlenecks in the carbon substrate input to the TCA cycle. This transcriptomic/metabolomic profile was markedly different from that of mice PGC-1a/b deficiency in which a global downregulation of genes involved in mitochondrial ETC and OXPHOS was noted. In addition, the transcriptomic/metabolomic signatures of HF differed markedly from that of the exercise-trained mouse heart. We conclude that in contrast to current dogma, alterations in mitochondrial metabolism that occur early in the development of heart failure reflect largely post-transcriptional mechanisms resulting in impedance to substrate flux into the TCA cycle, reflected by alterations in the metabolome.
Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes.
Sex, Age, Specimen part
View SamplesGene expression analyses in whole blood reveal a network of genes related to schizophrenia
A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes.
Sex, Age, Specimen part
View SamplesExpression quantitative trait loci (eQTL) analyses were conducted separately on the glomerular and tubular portions of healthy human kidney samples obtained from subjects of European descent. Overall design: We aimed to define genotype driven gene expression changes in the glomerular and tubular compartments of human kidneys, identifying genetic variants (eVariants) that influence the expression of genes (eGenes). Later, we integrated this information with genotype and phenotype association studies (GWAS) to identify genes for which expression in the kidney shows differences in patients with GWAS variants.
Mapping eGFR loci to the renal transcriptome and phenome in the VA Million Veteran Program.
Specimen part, Disease, Disease stage, Subject
View SamplesAT6.1 cells transfected to over-express Ndrg-1 were compared with AT6.1 vector control cells in a microarray analysis. The aim of the study was to identify differentially expressed genes between the two cell lines, as these may be modulated by Ndrg-1.
The iron-regulated metastasis suppressor, Ndrg-1: identification of novel molecular targets.
Cell line
View SamplesEnd stage renal disease (ESRD) is associated with hyperplastic-cystic remodelling of the kidneys (ARCD) and increased rate of kidney tumours. Using the Affymetrix oligoarray, we have established the gene expression signature of ESRD/ARCD kidneys and compared to those of normal kidneys and of distinct types of renal tumours.
Gene expression profiling of chromophobe renal cell carcinomas and renal oncocytomas by Affymetrix GeneChip using pooled and individual tumours.
No sample metadata fields
View SamplesTo understand the population genetics of structural variants (SVs), and their effects on phenotypes, we developed an approach to mapping SVs, particularly transpositions, segregating in a sequenced population, and which avoids calling SVs directly. The evidence for a potential SV at a locus is indicated by variation in the counts of short-reads that map anomalously to the locus. These SV traits are treated as quantitative traits and mapped genetically, analogously to a gene expression study. Association between an SV trait at one locus and genotypes at a distant locus indicate the origin and target of a transposition. Using ultra-low-coverage (0.3x) population sequence data from 488 recombinant inbred Arabidopsis genomes, we identified 6,502 segregating SVs. Remarkably, 25% of these were transpositions. Whilst many SVs cannot be delineated precisely, PCR validated 83% of 44 predicted transposition breakpoints. We show that specific SVs may be causative for quantitative trait loci for germination, fungal disease resistance and other phenotypes. Further we show that the phenotypic heritability attributable to sequence anomalies differs from, and in the case of time to germination and bolting, exceeds that due to standard genetic variation. Gene expression within SVs is also more likely to be silenced or dysregulated, as inferred from RNA-seq data collected from a subset of just over 200 of the MAGIC lines. This approach is generally applicable to large populations sequenced at low-coverage, and complements the prevalent strategy of SV discovery in fewer individuals sequenced at high coverage. Overall design: 209 samples consisting of different inbred lines from the Multiparent Advance Generation InterCross (MAGIC) population in the reference plant, Arabidopsis thaliana. For each sample, RNA was collected from the aerial shoot at the 4th true leaf stage, and Illumina mRNA-seq libraries were constructed (a single library was constructed with each line; that is, each MAGIC line is represented by one biological replicate). Using these libraries, which were non-stranded, paired-end 100 bp RNA-seq Illumina reads were generated for each sample, and used to quantify gene expresison in each MAGIC line. The resulting expression phenotypes are suitable for describing the impacts of genetic variation in the MAGIC line founders on the control of gene expression.
Genomic Rearrangements in <i>Arabidopsis</i> Considered as Quantitative Traits.
Subject
View SamplesParathyroid hormone (PTH) plays an essential role in regulating calcium and bone homeostasis in the adult, but whether PTH is required at all for regulating fetal-placental mineral homeostasis is uncertain. To address this we treated Pth-null mice in utero with 1 nmol PTH (1-84) or saline and examined placental calcium transfer 90 minutes later. It was found that placental calcium transfer increased in Pth-null fetuses treated with PTH as compared to Pth-null fetuses treated with saline. Subsequently, to determine the effect of PTH treatment on placental gene expression, in a separate experiment, 90 minutes after the fetal injections the placentas were removed for subsequent RNA extraction and microarray analysis.
Parathyroid hormone regulates fetal-placental mineral homeostasis.
Sex, Specimen part, Treatment
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