Background and Aims: Recent identification of intracellular DNA sensing pathways and involvement in numerous diverse disease processes including viral pathogenesis and autoimmunity suggests a role for these processes in liver pathology. The presence of these pathways in the liver and their role in HBV infection is unknown. Methods: In order to characterize the role of DNA sensing pathways in the liver, we utilized in vitro models. Microarray was performed on DNA treated and HBV infected hepatoma primary human hepatocytes. Results: Here we show that HBV infection and foreign DNA results in a significant innate immune response characterized by the production of inflammatory chemokines.
Hepatitis B Virus and DNA Stimulation Trigger a Rapid Innate Immune Response through NF-κB.
Specimen part, Treatment
View SamplesBACKGROUND: Patients with HIV that are coinfected with HCV are at increased risk for rapidly progressive liver disease and subsequently the development of Hepatocellular Carcinoma (HCC). Specifically, HCC develops earlier in coinfected patients and these patients are more symptomatic than those with only HCV infection at diagnosis suggesting that both viruses increase the propensity for malignant transformation. Consequently, HCV coinfection and the associated liver disease is a major health burden for HIV infected persons in the U.S. However, the genetic and cellular based mechanisms underpinning how HCV initiates and subsequently induces liver pathology and why coinfection with HIV results in significantly worse hepatic disease remains to be clarified. In addition, the specific cell types that contribute to these clinical outcomes are unknown. METHODS: The goal of this project is focused on understanding the molecular mechanisms underlying the hepatic sequela in coinfected patients specifically focusing on the innate inflammatory responses activated by HIV in liver cells. To this end, we have developed novel in-vitro models that utilize HIV stimulated primary kupffer cells (PKCs). RESULTS: HIV stimulation of primary kupffer cells resulted in rapid and robust upregulation of an inflammatory gene signature.
No associated publication
Specimen part, Treatment
View SamplesThe rates of obesity and sedentary lifestyle are on a dramatic incline, with associated detrimental health effects among women in particular. Although exercise prescriptions are useful for overcoming these problems, success can be hampered by differential responsiveness among individuals in cardiovascular fitness indices (i.e., improvements in strength, lipids, VO2max). Genetic factors appear to play an important role in determining this inter-individual variation in responsiveness. We performed microarray analyses on mRNA in whole blood from 60 sedentary women from a multi-ethnic cohort who underwent 12 weeks of exercise, to identify gene subsets that were differentially expressed between individuals who experienced the greatest and least improvements in fitness based upon a composite fitness score index. We identified 43 transcripts in 39 unique genes (FDR<10%; FC>1.5) whose expression increased the most in high versus low premenopausal female responders. Several (TIGD7, UQCRH, PSMA6, WDR12, TFB2M, USP15) have reported associations with fitness-related phenotypes. Bioinformatic analysis of the 39 genes identified 4 miRNAs whose expression has been linked to cardiovascular diseases (ANKRD22: miR-637, LRRFIP1: miR-132, PRKAR2B: miR-92a, RSAD2:miR-192). These 39 genes were enriched in 6 biological pathways, including the oxidative phosphorylation pathway (p=8.08 x 10-3). Two genes, LRRFIP1 and SNORD30, were also identified with lower expression in high responding postmenopausal women. In summary, we identified gene signatures based on mRNA analysis that define responsiveness to exercise in a largely minority-based female cohort. Importantly, this study validates several genes/pathways previously associated with exercise responsiveness and extends these findings with additional novel genes.
Genomic signatures of a global fitness index in a multi-ethnic cohort of women.
Sex, Race, Time
View SamplesFive Cardiac Progenitor Clones Isolated were from the left ventricle of mouse heart. The 5 cardiac progenitor clones differ in morphology and vasculogenic potential. Total RNA was isolated and hybridized on mouse Affymetrix MOE_430_2 arrays to compare basal gene expression levels and correlate the gene expression with fuctional studies.
No associated publication
Specimen part
View SamplesAlthough evidence has shown that very small electric currents produce a beneficial therapeutic result for wounds, non-invasive EMF therapy has consisted mostly of anecdotal clinical reports with very few well controlled laboratory mechanistic studies. In this study, we evaluated the effects and potential mechanisms of a non-invasive EMF device on skin wound repair. In vitro analyses with human skin keratinocyte cultures demonstrated that the non-invasive EMF has a very strong effect on accelerating keratinocyte migration and a relatively weaker effect on promoting keratinocyte proliferation. The positive effects of the non-invasive EMF on cell migration and proliferation seem keratinocyte specific without such effects seen on dermal fibroblasts. cDNA microarray and RT-PCR performed revealed increased expression of CRK7 and HOXC8 genes in treated keratinocytes. This study suggests that a non-invasive electric magnetic field accelerates wound reepithelialization through a mechanism of promoting keratinocyte migration and proliferation, possibly due to upregulation of CRK7 and HOXC8 genes.
No associated publication
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrator regulates transcriptional initiation and pause release following activation.
Disease, Cell line, Treatment
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Genome-wide analysis reveals a role for BRCA1 and PALB2 in transcriptional co-activation.
Specimen part, Disease, Cell line
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No associated publication
Cell line
View SamplesParental flies (y1v1;P{TRiP.JF01138}attP2 and y1w*;P{Act5C-GAL4}25FO1/CyO,y+) were mated and 4-7 day old flies were used for all subsequent experiments. dSTING RNAi flies expressed the dsRNA hairpin targeting dSTING and had straight wings, while sibling flies not expressing dSTING dsRNA had curly wings.
No associated publication
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
No sample metadata fields
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