The Snf1 kinase plays a critical role in recalibrating cellular metabolism in response to glucose depletion. Hundreds of genes show changes in expression levels when the SNF1 gene is deleted. However, cells can adapt to the absence of a specific gene when grown in long term culture. Here we apply a chemical genetic method to rapidly and selectively inactivate a modified Snf1 kinase using a pyrazolopyrimidine inhibitor. By allowing cells to adjust to a change in carbon source prior to inhibition of the Snf1 kinase activity, we identified a set of genes whose expression increased when Snf1 was inhibited. Prominent in this set are genes that are activated by Gcn4, a transcriptional activator of amino acid biosynthetic genes. Deletion of Snf1 increased Gcn4 protein levels without affecting its mRNA levels. The increased Gcn4 protein levels required the Gcn2 kinase and Gcn20, regulators of GCN4 translation. These data indicate that Snf1 functions upstream of Gcn20 to regulate control of GCN4 translation.
A chemical genomics study identifies Snf1 as a repressor of GCN4 translation.
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View SamplesSplenocytes from lymphoreplete, unmanipulated mice were analyzed for basal mRNA levels. We hypothesized, based on previous data from our lab and others, that many cytokine/inflammatory response genes would show an increase from na誰ve CD5lo<CD5hi<Virtual memory. Overall design: mRNA was analyzed from mouse splenocytes separated into na誰ve CD5lo, na誰ve CD5hi, and virtual memory cells. Mice were lymphoreplete and unmanipulated.
Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner.
Cell line, Subject
View SamplesIn order to define the targets of two miRNA overexpressed in NK cells in CFS/ME paitents, miRNA precursors for hsa-miR-99b and hsa-miR-330-3p were transfected in to buffy coat derived Natural Killer cells isolated by negative magnetic selection.
MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME).
Specimen part, Disease, Disease stage
View SamplesMicroglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer's disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis. Unbiased RNA-Seq profiling was used to identify gene expression changes in isolated microglia in response to recurring bouts of voluntary alcohol drinking behavior. Gene coexpression analysis identified a coordinately regulated group of genes, unique to microglia, that collectively are associated with alcohol consumption. Several genes in this group were involved in toll-like receptor signaling and production of the inflammatory cytokine interferon-gamma. Coordinate expression of these genes is not ascertained from an admixture of CNS cell-types, underscoring the importance of examining isolated cellular populations to reveal systematic gene expression changes arising from mature microglia. We identified a distinctive microglial gene expression signature for neuroimmune responses related to alcohol consumption that provides valuable insight into microglia-specific changes underlying the development of substance abuse, as well as related CNS disorders. Overall design: We examined mRNA from both total homogenate (mixture of all cell types) and microglia from the cortex of control mice and mice that have undergone chronic voluntary ethanol consumption
Microglial-specific transcriptome changes following chronic alcohol consumption.
Specimen part, Cell line, Treatment, Subject
View SamplesGlobal gene expression patterns were determined from microarray results on day 1, 3, 5, 7, 10 and 14 during plantaris muscle hypertrophy induced by synergist ablation in young adult mice (5 months).
Time course of gene expression during mouse skeletal muscle hypertrophy.
Sex, Age, Specimen part, Treatment, Time
View SamplesPathogen-specific polyfunctional T cell responses have been associated with favorable clinical outcomes but it is not known whether polyfunctional T cells are distinct from monofunctional cytokine producing T cells. In this study we compared the transcriptomic profile of P. falciparum reactive polyfunctional and IFNg monofunctional CD4 T cells by microarray analysis and show that polyfunctional CD4 T cells are associated with a unique transcriptomic signature.
Polyfunctional and IFN-<b>γ</b> monofunctional human CD4<sup>+</sup> T cell populations are molecularly distinct.
No sample metadata fields
View SamplesTranscriptome analysis of skeletal muscle during hypertrophic growth in aged mice
Blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis.
Sex, Age, Specimen part, Time
View SamplesThe gastrointestinal tract is a major site of early HIV-1 replication and death of CD4+ T cells. As HIV-1 replicates in the gut, the protective epithelial barrier gets disrupted, leading to the entry of bacteria into the underlying tissue and the bloodstream, leading to inflammation and clinical complications even in HIV-1-infected patients taking antiviral drugs. Counteracting these pathogenic processes may require in-depth understanding of the molecular pathways that HIV-1 and microbes utilize to infect, functionally alter and/or kill CD4+ T cells. However, to date, the nature of the genes altered by relevant HIV-1 strains and bacteria in intestinal CD4+ T cells remains unclear.
The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Time-course analysis of the effect of embedded metal on skeletal muscle gene expression.
Sex, Specimen part, Treatment, Time
View SamplesAs a consequence of military operations, many veterans suffer from penetrating wounds and long-term retention of military grade heavy metal fragments. Fragments vary in size and location, and complete surgical removal may not be feasible or beneficial in all cases. Increasing evidence suggests retention of heavy metal fragments may have serious biological implications, including increased risks for malignant transformation. Previous studies assessed the tumorigenic effects of metal alloys in rats, demonstrating combinations of metals are sufficient to induce tumor formation after prolonged retention in skeletal muscle tissue. In this study, we analyzed transcriptional changes in skeletal muscle tissue in response to eight different military-relevant pure metals over 12 months. We found that most transcriptional changes occur at 1 and 3 months after metal pellets are embedded in skeletal muscle and these effects resolve at 6 and 12 months. We also report significant immunogenic effects of nickel and cobalt and suppressive effects of lead and depleted uranium on gene expression. Overall, skeletal muscle exhibits a remarkable capacity to adapt to and recover from internalized metal fragments; however, the cellular response to chronic exposure may be restricted to the metal-tissue interface. This data suggests that unless affected regions are specifically captured by biopsy, it would be difficult to reliably detect changes in muscle gene expression that would be indicative of long-term adverse health outcomes.
Time-course analysis of the effect of embedded metal on skeletal muscle gene expression.
Sex, Specimen part, Treatment, Time
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