This SuperSeries is composed of the SubSeries listed below.
Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes.
Sex, Specimen part
View SamplesWe examined molecular responses using transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) iron (56Fe) particles 1, 3, 7, 14 and 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the radiation (IR) response, and time after exposure with 56Fe-IR showing the greatest level of gene modulation. 1H-IR exposures showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Individual transcription factors were inferred to be active at 1, 3, 7, 14 and 28 days after exposure. Validation of the signal transduction network by protein analysis showed that particle IR clearly regulates a long lived signaling mechanism for p38 MAPK signaling and NFATc4 activation. Electrophoresis mobility shift assays supported the role of additional key transcription factors GATA-4, STAT-3 and NF-B as regulators of the response at specific time points. These data suggest that the molecular response to 56Fe-IR is unique and shows long-lasting gene expression in cardiomyocytes, up to 28 days after exposure. Additionally, proteins involved in signal transduction and transcriptional activation via DNA binding play a role in the response to high charge (Z) and energy (E) particles (HZE). Our study may have implications for NASAs efforts to develop heart disease risk estimates for astronauts safety via identification of specific HZE-IR molecular markers and for patients receiving conventional and particle radiotherapy.
Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes.
Sex, Specimen part
View SamplesA congenic mouse line was constructed by introgressing a C3H chromosome 9 region harboring Ath29 into the C57BL/6 apoE-deficient background. RNA was extracted from aorta using a QIAGEN kit . Total RNA was pooled in an equal amount from 3 mice for each group. Standard Affymetrix procedures were performed using 8ug of total RNA.
Characterization of Ath29, a major mouse atherosclerosis susceptibility locus, and identification of Rcn2 as a novel regulator of cytokine expression.
Disease, Disease stage
View SamplesRobust type I interferon (IFN-alpha/beta) production in plasmacytoid dendritic cells (pDCs) is critical for anti-viral immunity. Here we demonstrated a role for the mammalian target of rapamycin (mTOR) pathway in regulating interferon production by pDCs. Inhibition of mTOR or the downstream mediators of mTOR p70S6K1,2 kinases during pDC activation via Toll-like receptor 9 (TLR9) blocked the interaction of TLR9 with the adaptor MyD88 and the subsequent activation of interferon response factor 7 (IRF7), resulting in impaired IFN-alpha production. Microarray analysis confirmed that inhibition of mTOR by the immunosuppressive drug rapamycin suppressed anti-viral and anti-inflammatory gene expression. Consistent with this, targeting rapamycin-encapsulated microparticles to antigen-presenting cells in vivo resulted in a diminution of IFN-alpha production in response to CpG DNA or the yellow fever vaccine virus strain 17D. Thus, mTOR signaling plays a critical role in TLR-mediated IFN-alpha responses by pDCs.
Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway.
Sex, Specimen part
View SamplesDendritic cells play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens, food antigens and intestinal commensals. However, the intracellular signaling networks that program DCs to become tolerogenic are largely unknown. To address this, we analyzed gene expression profiles using microarray analysis of purified intestinal lamina propria DCs (CD11c+ CD11b+ DCs and CD11c+ CD11b- DCs) and compared it to splenic DCs (CD11c+ DC), from mice.
Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine.
Specimen part
View SamplesDendritic cells play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens, food antigens and intestinal commensals. However, the intracellular signaling networks that program DCs to become tolerogenic are largely unknown. To address this, we analyzed gene expression profiles using microarray analysis of purified intestinal lamina propria DCs (CD11c+ CD11b+ DCs and CD11c+ CD11b- DCs) from mice.
Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine.
Specimen part
View SamplesDendritic cells (DCs) play a vital role in innate immunity. Transcriptome of DCs isolated from mouse spleen was obtained and deposited here.
Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine.
Specimen part
View Samplesp63 mutations have been associated with several human hereditary disorders characterized by ectodermal dysplasia such as EEC syndrome, ADULT syndrome and AEC syndrome . The location and functional effects of the mutations that underlie these syndromes reveal a striking genotype-phenotype correlation. Unlike EEC and ADULT that result from missense mutations in the DNA-binding domain of p63, AEC is solely caused by missense mutations in the SAM domain of p63. We report a study on the TAp63a isoform, the first to be expressed during development of the embryonic epithelia, and on its naturally occurring Q540L mutant derived from an AEC patient. To assess the effects of the Q540L mutation, we generated stable cell lines expressing TAp63a wt, DeltaNp63 alpha or the TAp63 alpha-Q540L mutant protein and used them to systematically compare the cell growth regulatory activity of the mutant and wt p63 proteins and to generate, by microarray analysis, a comprehensive profile of differential gene expression. We found that the Q540L substitution impairs the transcriptional activity of TAp63a and causes misregulation of genes involved in the control of cell growth and epidermal differentiation.
The Hay Wells syndrome-derived TAp63alphaQ540L mutant has impaired transcriptional and cell growth regulatory activity.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Positional identification of variants of Adamts16 linked to inherited hypertension.
No sample metadata fields
View SamplesWe used Affymetrix GeneChips to expression profile rat kidney NRK-52E cells treated with control scrambled siRNA or siRNA specifically targeting Adamts16. The goal of this project was to identify the downstream genes regulated by Adamts16 (the function of Adamts16 has yet to be fully delineated). Gene expression differences resulting from these siRNA-mediated gene knockdown experiments will be compared to the gene expression profiling experiments comparing kidneys from Dahl salt-senstive hypertensive inbred strain versus less hypertensive S.LEW(D1MCO4x1x3Bx1) congenic strain. The S.LEW(D1MCO4x1x3Bx1) congenic animal is an S rat containing the LEWIS allele for Adamts16 instead of the S allele. Gene expression differences in the kidneys of S.LEW(D1MCO4x1x3Bx1) versus S are hypothesized to result from sequence differences between the S and LEWIS alleles for Adamts16. It is further hypothesized that allelic differences in Adamts16 in inbred rats is responsible for blood pressure variance. The downstream genes regulated by Adamts16 may provide insight pertaining to the mechanism of blood pressure differences.
Positional identification of variants of Adamts16 linked to inherited hypertension.
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