Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disease, characterized by ataxia, intellectual disability, epilepsy and premature death. In the majority of cases, PMD is caused by duplication of PLP1 that is expressed in myelinating oligodendrocytes. Despite detailed knowledge of PLP1, there is presently no curative therapy for PMD. We used a Plp1 transgenic PMD mouse model to test the therapeutic effect of Lonaprisan, an antagonist of the nuclear progesterone receptor, in lowering Plp1 mRNA overexpression. We applied placebo-controlled Lonaprisan therapy to PMD mice for 10 weeks and performed the grid slip analysis to assess the clinical phenotype. Additionally, mRNA expression and protein accumulation as well as histological analysis of the central nervous system were performed. While Plp1 mRNA levels are increased about 1.8-fold in PMD mice compared to wildtype controls, daily Lonaprisan treatment reduced overexpression at the RNA level up to 1.5-fold, which was sufficient to significantly improve a poor motor phenotype. Electron microscopy confirmed a 25% increase in the number of myelinated axons in the corticospinal tract when compared to untreated PMD mice. Microarray analysis revealed the upregulation of pro-apoptotic genes in PMD mice that could be partially rescued by Lonaprisan treatment, which also reduced microgliosis, astrogliosis, and lymphocyte infiltration.
Progesterone antagonist therapy in a Pelizaeus-Merzbacher mouse model.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
Specimen part, Cell line
View SamplesAffymetrix exon arrays to identify genes that were differentially expressed after c-Jun inhibition in LPS cell line with and with no Jun amplification.
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
Specimen part, Cell line
View SamplesWe assayed the effect of c-Jun overexpression on gene expression in the three DDLPS cell lines using RNA-Seq (Illumina). Overall design: 141, LPS12 and 510 has been overexpressed with c-Jun or control c-DNA and results were analyzed in high-througput sequencing metadata.
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
No sample metadata fields
View SamplesULT1 and CLF function antagonistically as epigenetic regulators of gene expression in Arabidopsis. We sought to identity their global downstream target genes at two stages of plant development and determine their common targets.
The Trithorax Group Factor ULTRAPETALA1 Regulates Developmental as Well as Biotic and Abiotic Stress Response Genes in Arabidopsis.
No sample metadata fields
View SamplesInadequate protein intake initiates an accommodative response with adverse changes in skeletal muscle function and structure. mRNA level changes due to short-term inadequate dietary protein might be an early indicator of accommodation. The aims of this study were to assess the effects of dietary protein and the diet-by-age interaction on the skeletal muscle transcript profile. Self-organizing maps were used to determine expression patterns across protein trials.
The skeletal muscle transcript profile reflects accommodative responses to inadequate protein intake in younger and older males.
Sex
View SamplesOocyte maturation is accompanied by a transition from mRNA stability to instability. We investigated the role of DCP1A and DCP2, proteins responsible for mRNA decapping, in mRNA destabilization during mouse oocyte maturation.
Maternally recruited DCP1A and DCP2 contribute to messenger RNA degradation during oocyte maturation and genome activation in mouse.
No sample metadata fields
View SamplesIL-10 is an anti-inflammatory cytokine that has been shown to be produced by antigen-specific CD8 T cells at the peak of viral encephalitis. We found that IL-10+CD8 T cells are more activated and cytolytic than IL-10-CD8 T cells.
Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis.
Specimen part
View SamplesBackground: Prostate cancer is the second leading cause of cancer mortality among US men. Epidemiological evidence suggests that high vitamin D status protects men from prostate cancer and the active form of vitamin D, 1,25 dihydroxyvitamin D3 (1,25(OH)2D) has anti-cancer effects in cultured prostate cells. Still, the molecular mechanisms and the gene targets for vitamin D-mediated prostate cancer prevention are unknown.
1,25 dihydroxyvitamin D-mediated orchestration of anticancer, transcript-level effects in the immortalized, non-transformed prostate epithelial cell line, RWPE1.
Specimen part, Cell line, Treatment, Time
View SamplesInadequate dietary protein intake causes adverse changes in the morphology and function of skeletal muscle. These changes may be reflected in early alterations in muscle mRNA levels.
Inadequate protein intake affects skeletal muscle transcript profiles in older humans.
Sex
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