We have begun to approach gd T cells more as prospective innate cells than as conventional T cells. Recent results indicated that purified gd T cells are primed directly in response to pathogen associated molecular patterns (PAMPs) to better respond to secondary signals and increase expression of chemokine and activation-related genes. In microarray and real time PCR analyses of RNA derived from bovine and human gd T cells, transcripts encoding Nod2 were repeatedly amplified. Nod2 is the intracellular receptor for muramyl dipeptide (MDP), a subunit of PGN, functions in regulating innate activities, and was thought to be expressed primarily in APCs. Given our repeated detection of Nod2 transcripts in gd T cells, the specific direct response of gd T cells to MDP was analyzed by microarray, real time PCR, proteome array and in a functional priming assay. The results indicate a subtle activation in response to MDP akin to priming, and suggest a unique mechanism for differential gene expression.
The distinct response of gammadelta T cells to the Nod2 agonist muramyl dipeptide.
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View SamplesRNA sequencing (RNA-Seq) was performed on rumen papillae from 16 steers with variation in gain and feed intake. Overall design: Sixteen rumen papillae samples were sequenced by Cofactor Genomics (St.Louis, MO).
Transcriptome differences in the rumen of beef steers with variation in feed intake and gain.
Specimen part, Subject
View SamplesSpecific pathogen free wild-type C57Bl/6 male mice fed ketogenic diet (Bio-Serv AIN-76-A) for 4 weeks
Adaptation of myocardial substrate metabolism to a ketogenic nutrient environment.
Sex, Specimen part
View SamplesWith this study we wanted to evaluate the impact of murine norovirus infection of germfree mice and to compare it to germfree mice which have received fecal transplants of conventional mice. Overall design: whole small intestinal tissue analysis of 3 germfree, 3 germfree mice infected with murine norovirus and 3 conventionalized germfree mice
An enteric virus can replace the beneficial function of commensal bacteria.
No sample metadata fields
View SamplesWe used microarray analysis to identify differences in gene expression levels in heart following an 18h (overnight) fast in WT control and KLF15-null mice
Kruppel-like factor 15 is a critical regulator of cardiac lipid metabolism.
Sex, Specimen part
View SamplesSteer spleen transcriptome
Profile of the Spleen Transcriptome in Beef Steers with Variation in Gain and Feed Intake.
Specimen part
View SamplesThe antioxidant response element (ARE) is a cis-acting regulatory enhancer element found in the 5 flanking region of many phase II detoxification enzymes. Upregulation of ARE-dependent target genes is known to have neuroprotective effects; yet, the mechanism of activation is largely unknown. By screening an arrayed collection of approximately 15,000 full-length expression cDNAs in the human neuroblastoma cell line IMR-32 with an ARE-luciferase reporter, we have identified several cDNAs not previously associated with ARE activation. A subset of cDNAs, including sequestosome 1 (SQSTM1) and dipeptidylpeptidase III (DPP3), activated the ARE in primary mouse-derived cortical neurons. Overexpression of SQSTM1 and DPP3 in IMR-32 cells stimulated NRF2 nuclear translocation and led to increased levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), a protein which is transcriptionally regulated by the ARE. When transfected into IMR-32 neuroblastoma cells that were depleted of transcription factor NRF2 by RNA interference, SQSTM1 and DPP3 were unable to activate the ARE or induce NQO1 expression, indicating that the ARE activation upon ectopic expression of these cDNAs is mediated by NRF2. Studies with pharmacological inhibitors indicated that 1-phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) signaling are also essential for activity. Lastly, overexpression of these cDNAs conferred partial resistance to hydrogen peroxide induced toxicity, consistent with the induction of antioxidant and phase II detoxification enzymes which can protect from oxidative stress. This work and other such studies may provide mechanisms for activating the ARE in the absence of general oxidative stress, and a novel therapeutic approach to degenerative diseases and aging.
A genomic screen for activators of the antioxidant response element.
No sample metadata fields
View SamplesCarbon monoxide (CO) is an endogenous messenger that suppresses inflammation, modulates apoptosis and promotes vascular remodeling. Here, microarrays were employed to globally characterize the CO (250 ppm) suppression of early (1 h) LPS-induced inflammation in human monocytic THP-1 cells. CO suppressed 79 of 101 immediate-early genes induced by LPS; 19% (15/79) were transcription factors and most others were cytokines, chemokines and immune response genes. The prototypic effects of CO on transcription and protein production occurred early but decreased rapidly. CO activated p38 MAPK, ERK1/2 and Akt and caused an early and transitory delay in LPS-induced JNK activation. However, selective inhibitors of these kinases failed to block CO suppression of LPS-induced IL-1beta, an inflammation marker. Of CO-suppressed genes, 81% (64/79) were found to have promoters with putative NF-kappaB binding sites. CO was subsequently shown to block LPS-induced phosphorylation and degradation of IkappaBalpha in human monocytes, thereby inhibiting NF-kappaB signal transduction. CO broadly suppresses the initial inflammatory response of human monocytes to LPS by reshaping proximal events in TLR4 signal transduction such as stress kinase responses and early NF-kappaB activation. These rapid, but transient effects of CO may have therapeutic applications in acute pulmonary and vascular injury.
Carbon monoxide blocks lipopolysaccharide-induced gene expression by interfering with proximal TLR4 to NF-kappaB signal transduction in human monocytes.
Specimen part, Treatment
View SamplesTranscriptional profile of monocytes in the colon in response to C. rodentium infection Overall design: Eight samples have been analyzed. All are from Cd11b+Ly6C+ inflammatory monocytes sorted from colonic tissue 9 days after C. rodentium infection from Atg16L1HM(4) and WT(4) mice.
Autophagy proteins suppress protective type I interferon signalling in response to the murine gut microbiota.
Age, Specimen part, Subject
View SamplesEarly epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies. The patients with MDS, chronic myelomonocytic leukemia (CMMoL), and high risk AML were treated with sequential administration of methylation inhibitor drugs (5AC and entinostat). To study gene expresion regulation in treated patients, microarray analysis was done on RNA samples extracted from CD34+ cells from 18 patients before and 15 days after treatment using Affymetrix U133Plus2.0.
Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies.
Specimen part, Disease
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