Infection with Nippostrongylus brasiliensis results in persistent changes to the lung environment. Cytokine profiling reveals a sustained increase in both Th1 and Th2 transcripts. Cellular populations of macrophages display an alternative phenotype, with upregulation of YM1, Arg1, Mrc1 as well as Class II MHC. These alternatively activated alveolar macrophages (AAAMs) also increase drastically in number. Subsequent challenge with house dust mite (HDM) Dermatophagoides pteronyssinus shows a reduced allergic phenotype, with decreased fold changes in effector cell cytokines of both the Th1 and Th2 variety indicative of the new regulatory environment established in the lung by helminth infection. Histological examination of the lung environment reveals a significant decrease in eosinophila and reduced mucous production by bronchial epithelial cells.
Hookworm-induced persistent changes to the immunological environment of the lung.
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View SamplesWe use RNA-sequencing to generate gene expression profiles of fetal mammary cells that have been induced to overexpress Sox10. These data highlight multiple important molecular mechanisms that are altered in response to this perturbation, and offer a resource to probe the basis of the stem/progenitor and EMT-like functions that are mediated by Sox10 in mammary cells. Overall design: Expression profiling of fetal mammary cells that express ectopic levels of Sox10
Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells.
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View SamplesWe use RNA-sequencing to generate gene expression profiles of fetal mammary cells with unique sorting strategies. These analyses reveal that sorting fetal mammary cells with Sox10 and EpCAM sorting markers provides a stroma-free fMaSC-enriched cell population. The gene expression profiling of these cells offers a resources to probe the molecular mechanisms that specify this unique cell state. Overall design: Examination of 2 different sorting strategies for fetal mammary cells
Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells.
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View SamplesThe circadian clock generates biological rhythms with a period of approximately 24 hours. Using microarray experiments, we have previously shown that approximately 16% of the Arabidopsis genome is regulated in a circadian manner (Edwards et al., 2006). Previous work from our lab in modelling the molecular oscillator of Arabidopsis introduced a hypothetical component Y into an evening loop of the clock gene network (Locke et al., 2005). GIGANTEA (GI) was suggested as a strong candidate for Y based on genetic evidence and its close matching of the expression profile predicted by the mathematical modelling. Recent experimental evidence suggests that GI may only partially account for the function of Y. Thus, we are undertaking a genomics approach to identify other candidate genes that match the predicted expression profile of Y. Samples were taken from wild type and lhy cca1 double mutant seedlings from 4 timepoints around the night to day transition (-15mins, +15mins, +30mins and +60mins) after 9 days of growth in 18:6 light dark cycles. We aim to identify genes showing the light induction response predicted for Y around dawn.
The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops.
Specimen part, Time
View SamplesThe overall aim of this experiment was to identify specific genes and molecular pathways regulated by ML290, a small molecule agonist of the relaxin receptor, RXFP1, in the context of liver fibrosis. Overall design: Whole transcriptome mRNA sequencing of transformed LX-2 cells using HiSeq platforms with paired-end 150 bp (PE 150) sequencing strategy, with four biological replicates in each treatment group.
Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis.
Specimen part, Cell line, Subject
View SamplesA number of macrophage and macrophage-like cells are responsible for immune response to challenges. Despite their shared role, these immune cells differ in the inflammatory response and impact on physiology and behavior. The purpose of this study was to profile mRNA levels (transcriptome) to better understand differences between immune cells under homeostasis using two mouse strains. Overall design: total RNA samples were obtained from 12 mice per strain and immune cell type and were subjected to paired-end RNA sequencing
Microglia Transcriptome Changes in a Model of Depressive Behavior after Immune Challenge.
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View SamplesSystemic vaccination with the attenuated virus SIVmac239-Nef provides sterilizing or partial protection to rhesus monkeys challenged with WT SIV strains, providing important opportunities to study key immunological components of a protective host response. Here we show that intravenous vaccination with SIVmac239-Nef provides two potentially crucial immunological barriers localized at mucosal surfaces that correlate with the vaccines protective effects against WT SIVmac251 vaginal challenge: 1) a conditioned and coordinated response from the mucosal epithelium that blunts the early inflammatory and chemotactic signalling cascade that aids virus propagation and expansion; 2) early on-site generation/diversification of SIV-specific Abs from ectopic germinal center-like lymphoid aggregates. This unique host response to WT SIVmac251 in the female reproductive tract of SIVmac239-Nef-vaccinated animals points to a multi-layered strategy for a protective host response during immunodeficiency virus exposurerapid induction of humroal immunity at mucosal surfaces without the deleterious inflammatory side effects tied to innate recognition of virus. This vaccine-induced host response highlights potential key protective mechanisms needed for an effective HIV vaccine
Live simian immunodeficiency virus vaccine correlate of protection: immune complex-inhibitory Fc receptor interactions that reduce target cell availability.
Sex, Specimen part
View SamplesDupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of the extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD.
Genome-wide analysis using exon arrays demonstrates an important role for expression of extra-cellular matrix, fibrotic control and tissue remodelling genes in Dupuytren's disease.
Specimen part, Disease, Disease stage
View SamplesAnthrax lethal toxin directly targets human peripheral monocytes and causes multiple aberrant gene responses that would be expected to result in defects in human monocytes normal signaling transduction pathways and nction. This study provides further insights into the mechanisms associated with the host immune system collapse during an anthrax infection, and suggests that anthrax LT may have additional targets outside the well-known MAPK pathway.
Bacillus anthracis' lethal toxin induces broad transcriptional responses in human peripheral monocytes.
Sex, Age, Specimen part
View SamplesThe peroxisome proliferator-activated receptor-coactivator-11 (PGC-11) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-11 activation has been suggested to be beneficial for systemic metabolism. Pharmacological PGC-11 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-11 is a transcriptional coactivator with no known ligand-binding activities. Importantly, PGC-11 activation is regulated by several mechanisms but protein stabilization is a limiting step as the protein has a short half-life under unstimulated conditions.
Small molecule PGC-1α1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration.
Specimen part
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