We sought to ascertain the time-course of transcriptional events that occur in human skeletal muscle at the outset of resistance exercise (RE) training in RE nave individuals, and determine if the magnitude of any response was associated with exercise induced muscle damage. Sixteen RE nave males were recruited, 8 underwent 2 sessions of 5x30 maximum, isokinetic knee extensions (180.s-1) separated by 48 hrs. Muscle biopsies of the vastus lateralis were taken at baseline and 24 hrs after each exercise bout. Eight individuals acted as non-exercise controls with biopsies obtained at the same time intervals. Transcriptional changes were assessed by microarray, and binding of HSP27 and B-crystallin to insoluble proteins by immunohistochemistry as a measure of muscle damage. In control subjects, no probesets were significantly altered (FDR<0.05) and HSP27 and B-crystallin binding remained unchanged throughout the study. In exercised subjects, significant inter-subject variability following the initial bout of RE was observed in the muscle transcriptome, with greatest changes occurring when HSP27 and B-crystallin binding was elevated. Following the second bout of RE, the transcriptome response was more consistent among subjects revealing a cohort of probesets associated with immune activation, the suppression of oxidative metabolism and protein ubiquitination as differentially regulated. The results reveal that the initial transcriptional response to RE is highly variable in RE nave volunteers, is associated with muscle damage, and unlikely to reflect longer-term adaptations to RE training. These results highlight the importance of considering multiple time-points when determining the transcriptional response to RE and associated physiological adaptation.
Transient transcriptional events in human skeletal muscle at the outset of concentric resistance exercise training.
Sex, Specimen part, Subject, Time
View SamplesPeripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMfs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMfs to populate the niche and that the presence of beMfs does not alter behavior. Furthermore, beMfs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMfs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMfs may be possible with irradiation-free conditioning regimens. Overall design: Microglia were isolated from the brains of adult male c57BL/6 mice given bone marrow tranplants (BMT) with or without head shield. All mice received PLX5622 for 2 weeks, then placed and normal chow to recoever. Some mice were then challenged with LPS. Cells were isolated by MACS using CD11b magnetic beads.
Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.
Age, Specimen part, Cell line, Treatment, Subject
View SamplesThis dataset describe the transcriptomic profiling of cecum, stomach and ileum from wild type, cdx2 conditional knock out and cdx2 ; apc deficient mice, by mRNA-seq. Each condition was analyzed in triplicated experiment to analyze the role of cdx2 in colorectal cancer susceptibilities Overall design: Biological samples from dissected tissue were tested by RNASeq in triplicates resulting into a total of 24 samples.
The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non-cell-autonomous mechanisms.
Specimen part, Treatment, Subject
View SamplesPeripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMfs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMfs to populate the niche and that the presence of beMfs does not alter behavior. Furthermore, beMfs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMfs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMfs may be possible with irradiation-free conditioning regimens. Overall design: Mice were given 1000rad whole body irradiation, followed by bone marrow transplant with UBC-GFP bone marrow at 8 weeks of age. Engraftment was allowed to occur for 8 months, then engrafting macrophages and microglia were isolated from whole brains for RNA-Seq.
Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.
Age, Specimen part, Cell line, Subject
View SamplesThe aim of this experiment was to investigate differential gene expression in splenocytes stimulated with BCG from nave and BCG vaccinated mice. The differences between nave and BCG vaccinated mice might indicate the mechanisms by which BCG vaccination confers an enhanced ability of splenocytes from BCG vaccinated mice to inhibit growth of BCG in splenocyte cultures as compared with splenocytes from naive animals.
Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb).
Sex, Age, Specimen part
View SamplesRaw expression values (CHP data) for transcriptional profiling of the response of Saccharomyces cerevisiae to challenges with lactic acid at pH 3 and pH 5.
Physiological and transcriptional responses to high concentrations of lactic acid in anaerobic chemostat cultures of Saccharomyces cerevisiae.
No sample metadata fields
View SamplesSelective RAF inhibitors including vemurafenib (PLX4032) have demonstrated clinical efficacy in mutant BRAF driven metastatic melanoma. The clinical effectiveness of RAF inhibitors depends on near complete abolition of the MAPK pathway output in tumors harboring BRAF mutations. However these compounds paradoxically activate the MAPK pathway in cells bearing oncogenic RAS or elevated upstream receptor signaling. This paradox can promote cellular proliferation and can manifest clinically with progression of secondary malignancies such as cutaneous squamous cell carcinomas (cuSCC). We have identified next generation RAF inhibitors (paradox breakers, e.g. PLX7904) that inhibit mutant BRAF cells without activating the MAPK pathway in cells bearing upstream activation.
RAF inhibitors that evade paradoxical MAPK pathway activation.
Specimen part, Treatment
View SamplesTransient expression of two factors, or from Oct4 alone, resulted in efficient generation of human iPSCs. The reprogramming strategy described revealed a potential transcriptional signature for human iPSCs yet retaining the gene expression of donor cells in human reprogrammed cells free of viral and transgene interference.
Transcriptional signature and memory retention of human-induced pluripotent stem cells.
Sex, Specimen part
View SamplesThe irreversible decarboxylation step, which commits 2-oxo acids to the Ehrlich pathway, was initially attributed to pyruvate decarboxylase. However, the yeast genome was shown to harbour no fewer than 5 genes that show sequence similarity with thiamine-diphosphate dependent decarboxylase genes. Three of these (PDC1, PDC5 and PDC6) encode pyruvate decarboxylases { while ARO10 and THI3 represent alternative candidates for Ehrlich-pathway decarboxylases.
The Ehrlich pathway for fusel alcohol production: a century of research on Saccharomyces cerevisiae metabolism.
No sample metadata fields
View SamplesHuman medulloblastoma (MB) can be segregated into four major categories based on gene expression patterns: Hedgehog (HH) subtype, Wnt subtype, Group 3, and Group 4. However, they all exhibit strikingly different gene expression profiles from Atypical Teratoid/Rhabdoid Tumor (AT/RT). We re-analyzed published gene expression microarray dataset of pediatric brain tumors to identify a gene expression profile that clearly distinguished human AT/RT from human MB. We used this profile, choosing only genes that have clear murine orthologs, to compare tumors from Snf5F/Fp53L/LGFAP-Cre mice (in C57Bl/6 strain background) with MB from Ptc1+/- mice (in mixed C57Bl/6 and 129Sv strain background). Snf5F/Fp53L/LGFAP-Cre tumors are clearly very different from mouse MB and the markers that distinguish human AT/RT from human MB also distinguish the mouse tumors.
Generation of a mouse model of atypical teratoid/rhabdoid tumor of the central nervous system through combined deletion of Snf5 and p53.
No sample metadata fields
View Samples