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SRP170668
Rattus norvegicus
47 Downloadable Samples
NextSeq 500
Description
Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early response gene activated in the heart under beta-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by NR4A2 expression in cardiomyocytes, and their impact on the physiological response of those cells to sustained beta-adrenergic stimulation. Treatment of adult rat ventricular myocytes (ARVMs) with isoproterenol induced a rapid (< 4 hours) but transient (< 24 hours) increase in NR4A2 expression levels that was accompanied by increased nuclear localization of the transcription factor. Adenovirus-mediated overexpression of NR4A2 modulated the expression of genes linked to adrenoceptor signaling, calcium signaling, cell growth and proliferation, and counteracted the increase in protein synthesis rate and cell surface area mediated by chronic isoproterenol stimulation. In consistence with those findings, NR4A2 overexpression also blocked the phosphorylative activation of ERK1/2, Akt, and of their downstream effector in protein synthesis p70S6K. Prominent among the transcriptional changes induced by NR4A2 was the > 7-fold up-regulation of the dual-specificity phosphatases DUSP2 and DUSP14, two known inhibitors of ERK1/2. Pre-treatment of NR4A2-overexpressing cardiomyocytes with the DUSPs inhibitor BCI prevented the inhibition of ERK1/2 and p70S6K following isoproterenol stimulation. In conclusion, our results suggest that NR4A2 acts as a novel negative feedback regulator of the beta-adrenergic receptor-mediated growth response in cardiomyocytes, and this at least partly through DUSP-mediated inhibition of ERK1/2 signaling. Overall design: Isolated adult rat ventricular myocytes (ARVMs) were transduced at 50 m.o.i. with a recombinant adenovirus containing the full-length cDNA of human NR4A2 under the transcriptional control of the CMV promoter (Vector Biolabs Ad-h-NR4A2; Cat. No: ADV-217057). ARVMs transduced with a recombinant eGFP adenovirus (Vector Biolabs Ad-GFP; Cat. No. 1060) were used as the cell transduction control. At 48 hours post transduction, total RNA was etracted. A total of six independent experiments were performed using ARVMs isolated from different Sprague Dawley rats.
Publication Title
Nuclear receptor subfamily 4 group A member 2 inhibits activation of ERK signaling and cell growth in response to β-adrenergic stimulation in adult rat cardiomyocytes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 16 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Mid-shaft fracture stimulates bone lengthening by increasing linear growth at the growthplate. This project studied changes in mRNA in the proximal growthplate after a mid-shaft fracture in a rat model.
Publication Title
Evidence for overgrowth after midfemoral fracture via increased RNA for mitosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Members of rhinovirus C (RV-C) species are more likely to cause wheezing illnesses and asthma exacerbations compared to other rhinoviruses. The cellular receptor for these viruses was heretofore unknown. We measured gene expression (Human Gene 1.0 ST Array, Affymetrix) in two series of experiments involving cells that were either susceptible or not susceptible to RV-C infection. In one experimental series, susceptible cells included whole sinus mucosal tissue specimens (n = 5), epithelial cell suspension from sinus tissue, and nasal epithelium obtained via brushing, while non-susceptible cells included monolayers of primary undifferentiated epithelial cells and transformed cell lines (n = 5). In a second experimental series, we compared three pairs of undifferentiated and fully differentiated (ALI) sinus epithelial cell cultures. We identified a total of 12 genes upregulated in RV-C susceptible cells (represented by 14 probe sets) encoding proteins localized to plasma membrane, and/or with predicted or functionally demonstrated receptor activity, including members of the Human MHC class II, stomatin, guanine nucleotide-binding, type I cytokine and atypical chemokine receptor and cadherin protein families.
Publication Title
Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profiles of normal kidney (3 technical replicates) and a renal tumor (3 technical replicates) from a hereditary leiomyomatosis and renal cell cancer (HLRCC) patient carrying a germline mutation in the fumarate hydratase (FH) gene.
Publication Title
Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Despite significant advances in our understanding of the biology determining systemic energy homeostasis, the treatment of obesity remains a medical challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for the treatment of obesity and its complications. AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine kinase whose short-term activation has multiple beneficial metabolic effects. Whether these translate into long-term benefits for obesity and its complications is unknown. Here, we observe that mice with chronic AMPK activation, resulting from mutation of the AMPK ?2 subunit, exhibit ghrelin signalling-dependent hyperphagia, obesity and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. Our studies highlight that long-term AMPK activation can have adverse metabolic consequences with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease. Overall design: Transcriptomic profiling of the hypothalamic arcuate nucleus from AMPK ?2 R299Q knock-in mice
Publication Title
Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Caenorhabditis elegans
- 20 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 20 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Analysis of the transcriptional response to viral infection in C.elegans.
Publication Title
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Attempt to identify small non-coding RNAs that change in levels as a result of viral infection of C.elegans Overall design: Small non-coding RNA (18-30nt) was extracted from animals either infected with Orsay virus or uninfected as indicated.
Publication Title
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
Sample Metadata Fields
Cell line, Subject
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Illumina Genome Analyzer II
Description
The transition in developmental control from maternal to zygotic gene products marks a critical step in early embryogenesis. Here, we use GRO-seq analysis to map the genome-wide RNA polymerase distribution during the Drosophila maternal to zygotic transition. This analysis unambiguously identifies the zygotic transcriptome, and provides insight into its mechanisms of regulation. Overall design: Two replicates of GRO-seq at each time point.
Publication Title
Extensive polymerase pausing during Drosophila axis patterning enables high-level and pliable transcription.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Saccharomyces cerevisiae
- 24 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Yeast cells were grown up in SD media containing all required amino acids. Each strain set was performed in triplicate. One set had no changes, the second set had 1mM methionine supplenting the media for the duration of growth and the third set was exposed to 0.5mM hydrogen peroxide for 15 minutes prior to harvesting
Publication Title
Gcn4 is required for the response to peroxide stress in the yeast Saccharomyces cerevisiae.
Sample Metadata Fields
Compound
View Samples