The purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1a treatment (Rebif, 22 g or 44 g three times a week) in patients with relapsing-remitting form of multiple sclerosis (MS). By using Affymetrix DNA microarrays, we obtained genome-wide expression profiles of peripheral blood mononuclear cells from 12 MS patients within the first two years of IFN-beta administration.
Elevated type I interferon-like activity in a subset of multiple sclerosis patients: molecular basis and clinical relevance.
Sex
View SamplesReduced eukaryotic Initiation Factor 2 (eIF2)a phosphorylation (p-eIF2a) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2a has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2a in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2a in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ?FosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2a and the gateway drug properties of psychoactive cannabinoids. Overall design: RNAseq from PC12 cell line with a 6 hour DMSO or WIN treatment.
Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats.
No sample metadata fields
View SamplesThe aim of the dataset was to study on a genome-wide level the effect of GTPase of the human immune associated protein 4 (GIMAP4) knockdown on the gene expression of resting T cells and immediately after T cell activation and Th1(Act+IL12) polarizing conditions of human cord blood-derived CD4+ T cells.
Tubulin- and actin-associating GIMAP4 is required for IFN-γ secretion during Th cell differentiation.
Specimen part, Treatment
View SamplesWe deep sequenced chromatin-associated RNAs (CARs) from human fibroblast (HF) cells. This resulted in the identification of 141 intronic regions and 74 intergenic regions harbouring CARS. Overall design: We purified CARs from normal HFs by isolating soluble chromatin after MNase treatment, followed by separation of chromatin fragments of different lengths on a sucrose gradient. CARs were converted into double-stranded cDNAs and sequenced using the Illumina Genome Analyzer I.
Characterization of the RNA content of chromatin.
No sample metadata fields
View SamplesWe asked whether combining Notch and VEGF blockade would enhance suppression of tumor angiogenesis and growth, using the NGP neuroblastoma model. NGP tumors were engineered to express a Notch1 decoy construct (N1D), which restricts Notch signaling, and then treated with either the anti-VEGF antibody bevacizumab or vehicle. Combining Notch and VEGF blockade led to blood vessel regression, increasing endothelial cell apoptosis and disrupting pericyte coverage of endothelial cells. Combined Notch and VEGF blockade did not affect tumor weight, but did additively reduce tumor viability. Our results indicate that Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis, and show that concurrent blockade disrupts primary tumor vasculature and viability further than inhibition of either pathway alone.
Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis.
Specimen part
View SamplesWe carried out a global survey of age-related changes in mRNA levels in the C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged mice displayed a mild but specific deficit in spatial memory in the Morris water maze.
Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice.
Sex, Age, Specimen part
View SamplesThe aim of the dataset was to study the effect of music exposure on human blood transcriptome.
The effect of listening to music on human transcriptome.
Specimen part, Treatment, Race
View SamplesBackground: The biological mechanisms underlying cancer cell motility and invasiveness remain unclear, although it has been hypothesized that they involve some type of epithelial-mesenchymal transition (EMT).
Human cancer cells express Slug-based epithelial-mesenchymal transition gene expression signature obtained in vivo.
Specimen part
View SamplesMice overexpressing galectin-8 (gal-8 Tg), a secreted mammalian lectin, exhibit enhanced bone turnover and reduced bone mass, similar to cases of post-menopausal osteoporosis. Gal-8 knockout (KO) mice have increased bone mass accrual at young age, but exhibit accelerated bone loss during adulthood. These phenotypes can be attributed to gal-8-mediated increase in RANKL expression that promotes osteoclastogenesis, combined with direct inhibition of osteoblasts differentiation, evident by reduced BMP signaling, SMAD phosphorylation, and reduced expression of osteoblasts differentiation markers OSX, OCN, RUNX2, DMP-1 and ALP. Gal-8 mRNA positively correlates with the mRNA levels of osteoclastogenic markers RANKL, TRAP and CTSK in human femurs. Collectively, these findings identify gal-8 as a new physiological player in the regulation of bone mass.
Ablation of the mammalian lectin galectin-8 induces bone defects in mice.
Specimen part, Cell line, Treatment
View SamplesTo identify the CAR-, PXR- and PPAR-specific genome-wide expression changes, hepatocyte cultures from six individual donors were treated with the prototypical ligands for
Genomewide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR and PPARα in primary human hepatocytes.
Sex, Age
View Samples