Impaired muscle growth as a result of IUGR is a major contributor to lifelong reductions in muscle mass (sarcopenia) and metabolic disease risk. We use an ovine model of chronic placental insufficiency which restricts nutrient supply from mother to fetus and results in intrauterine growth restriction. In our model of placental insufficiency and IUGR, fetal hindlimb muscles weigh less than normally-grown control fetuses and have smaller myofiber diameters.
Myoblast replication is reduced in the IUGR fetus despite maintained proliferative capacity in vitro.
Specimen part
View SamplesThe response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate NF-kB family members. We have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways, and triggered activation of a STAT binding activity. Genetic experiments showed that the JAK kinase Hopscotch was involved in the control of the viral load in infected flies, and was required, though not sufficient, for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third evolutionary conserved innate immunity pathway operates in drosophila and counters viral infection.
The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila.
No sample metadata fields
View SamplesThe fruit fly Drosophila melanogaster is a good model to unravel the molecular mechanisms of innate immunity, and has led to some important discoveries on the sensing and signalling of microbial infections. The response of drosophila to virus infections remains poorly characterized, and appears to involve two facets. On one hand RNA interference (RNAi) involves the recognition and processing of dsRNA into small interfering (si) RNAs by the host ribonuclease Dicer-2 (Dcr-2), whereas on the other hand an inducible response controlled by the evolutionarily conserved JAK/STAT pathway contributes to the antiviral host defence. In order to clarify the contribution of the siRNA and JAK/STAT pathways to the control of viral infections, we have compared the resistance of flies wild-type or mutant for Dcr-2 or the JAK kinase Hopscotch (Hop) to infections by seven RNA or DNA viruses belonging to different families. Our results reveal a unique susceptibility of hop mutant flies to infection by DCV and CrPV, two members of the Dicistroviridae family. Genome-wide microarray analysis confirmed that different sets of genes were induced following infection by DCV (GSE2828) or two unrelated RNA viruses, FHV and SINV. Overall, our data reveal that RNAi is an efficient antiviral mechanism, operating against a large range of viruses, including a DNA virus. By contrast, the antiviral contribution of the JAK/STAT pathway appears to be virus-specific.
Broad RNA interference-mediated antiviral immunity and virus-specific inducible responses in Drosophila.
Time
View SamplesBlimp-1 expression in T cells extinguishes the T follicular helper cell fate and drives terminal differentiation, but also limits autoimmunity. Although various factors have been described to control Blimp-1 expression in T cells, little is known about what regulates Blimp-1 expression in Th2 cells and the molecular basis of its actions. Herein, we report that STAT3 unexpectedly played a critical role in regulating Blimp-1 in Th2 cells. Furthermore, we found that the cytokine IL-10 acted directly on Th2 cells and was necessary and sufficient to induce optimal Blimp-1 expression through STAT3. Together, Blimp-1 and STAT3 amplified IL-10 production in Th2 cells, creating a strong autoregulatory loop that enhanced Blimp-1 expression. Increased Blimp-1 in T cells antagonized STAT5-regulated cell cycle and anti-apoptotic genes to limit cell expansion. These data elucidate the signals required for Blimp-1 expression in Th2 cells and reveal an unexpected mechanism of action of IL-10 in T cells, providing insights into the molecular underpinning by which Blimp-1 constrains T cell expansion to limit autoimmunity. Overall design: RNAseq of activated undifferentiated CD4 T cells with or without exogenous expression of Blimp-1.
IL-10 induces a STAT3-dependent autoregulatory loop in T<sub>H</sub>2 cells that promotes Blimp-1 restriction of cell expansion via antagonism of STAT5 target genes.
Specimen part, Subject
View SamplesBackground: Several genetic defects of the nucleotide excision repair (NER) pathway, including deficiency of the Excision Repair Cross-Complementing rodent repair deficiency, complementation group 1 (ERCC1), result in pre-mature aging, impaired growth, microcephaly and delayed development of the cerebellum. Such a phenotype also occurs in ERCC1-knockout mice which survive for up to 4 weeks after birth. Therefore, we analyzed cerebellar and hippocamapal transcriptomes of these animals at 3 weeks of age to identify the candidate mechanisms underlying brain consequences of reduced ERCC1 activity.
Downregulation of cholesterol biosynthesis genes in the forebrain of ERCC1-deficient mice.
No sample metadata fields
View SamplesThe edible mushroom Agaricus blazei Murill has immunomodulating and antiproliferative effects. In a clinical study 33 patients with multiple myeloma were randomized to receive treatment with Agaricus (16 patients) or placebo (17 patients) in addition to chemotherapy.
Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: a randomized, double blinded clinical study.
Specimen part, Treatment, Subject, Time
View SamplesAging is associated with the decline of protein, cell, and organ function. Here, we use an integrated approach to characterize gene expression, bulk translation, and cell biology in the brains and livers of young and old rats. We identify 468 differences in protein abundance between young and old animals. The majority are a consequence of altered translation output, that is, the combined effect of changes in transcript abundance and translation efficiency. In addition, we identify 130 proteins whose overall abundance remains unchanged but whose sub-cellular localization, phosphorylation state, or splice-form varies. While some protein-level differences appear to be a generic property of the rats' chronological age, the majority are specific to one organ. These may be a consequence of the organ's physiology or the chronological age of the cells within the tissue. Taken together, our study provides an initial view of the proteome at the molecular, sub-cellular, and organ level in young and old rats. Overall design: RNA-Seq and ribosome profiling from matched young and old rat liver and brain
Integrated Transcriptome and Proteome Analyses Reveal Organ-Specific Proteome Deterioration in Old Rats.
No sample metadata fields
View SamplesThis work examines sarcoma formation within discrete subsets of KRAS(G12V)-expressing p16p19null myogenic and mesenchymal cells found normally in skeletal muscle. We show that prospectively isolated skeletal muscle precursor cells (SMPs) within the satellite cell pool can serve as cancer cells-of-origin for mouse rhabdomyosarcomas (soft tissue sarcomas with features of myogenic differentiation). Alternatively, non-myogenic progenitors (ScaPCs) induce sarcomas lacking myogenic differentiation markers.
Sarcomas induced in discrete subsets of prospectively isolated skeletal muscle cells.
Specimen part
View SamplesNovel fluorescence-activated cell sorting (FACS) strategies to prospectively purify functionally distinct cell populations from the human myofiber-associated (hMFA) cell compartment, including human Skeletal Muscle Precursor cells (hSMPs):
Isolation of progenitors that exhibit myogenic/osteogenic bipotency in vitro by fluorescence-activated cell sorting from human fetal muscle.
No sample metadata fields
View SamplesWe compared expression of genes in brains of SIRT1 brain-specific knockouts (BSKO) to those of wild-type littermate controls (WT).
SIRT1 activates MAO-A in the brain to mediate anxiety and exploratory drive.
Sex, Age, Specimen part
View Samples