This SuperSeries is composed of the SubSeries listed below.
Foxp3-dependent programme of regulatory T-cell differentiation.
Sex
View SamplesThis data set is comprised of all peripheral (pooled lymph nodes and spleen) T cell subsets presented in this manuscript. These include T-N, T-25, T-FN and T-R cells; T-25, T-FN and T-R cells from mice treated with IL-2; and T-R cells transduced with empty, PDE3B-expressing or PDE3B(H801A)-expressing retroviral vectors (after transfer into recipient mice).
Foxp3-dependent programme of regulatory T-cell differentiation.
Sex
View SamplesIt is unknown how soon the diaphragm begins to start the process of atrophy following the start of MV. We hypothesized that genes responsible for maintaining diaphragmatic contractile function, stress response, energy transduction would be altered over the course of a 5 hour cardiothoracic surgery.
Gene expression changes in the human diaphragm after cardiothoracic surgery.
Sex, Age
View SamplesThis data set is comprised of all thymic T cell subsets presented in this manuscript. These include T-N, T-25, T-FN and T-R thymocytes.
Foxp3-dependent programme of regulatory T-cell differentiation.
Sex
View SamplesEpidemiological studies provide strong evidence that consumption of cruciferous vegetables, such as broccoli, can significantly reduce the risk of developing cancers. Sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for these specific chemopreventive properties remain unclear. We utilized RNA sequencing to test the hypothesis that SFN modifies the expression of genes that are critical in prostate cancer progression. Normal prostate epithelial cells, and androgen-dependent and androgen-independent prostate cancer cells were treated with 15 µM SFN and the transcriptome was determined at 6 and 24 hour time points. SFN altered the expression of ~3,000 genes in each cell line and the response was highly dynamic over time. SFN influenced the expression of genes in functional groups and pathways that are critical in cancer including cell cycle, apoptosis and angiogenesis, but the specific effects of SFN differed depending on the state of cancer progression. Network analysis suggested that a transcription factor that is overexpressed in many cancers, Specificity protein 1 (Sp1), is a major mediator of SFN-induced changes in gene expression. Nuclear Sp1 protein was significantly decreased by 24 hour SFN treatment in prostate cancer cells, while a related transcription factor, Sp3 protein was only modestly decreased in androgen-independent prostate cancer cells. Overall, the data show that SFN significantly affects gene expression in normal and cancer cells, with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent. Overall design: Examination of how the transcriptome of normal and prostate cancer cells is altered by treatment with sulforaphane
Transcriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention.
Specimen part, Subject, Time
View SamplesMast cells, activated by antigen via the high affinity receptor for IgE (FcRI), release an array of pro-inflammatory mediators that contribute to allergic disorders such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation and survival, and, under acute conditions, enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal antigen-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcRI-mediated degranulation and cytokine production. The hypo-responsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization, with evidence implicating a down-regulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders.
Stem cell factor programs the mast cell activation phenotype.
Specimen part, Treatment
View SamplesInterleukin-33 (IL-33) is elevated in afflicted tissues of patients with mast cell-dependent chronic allergic diseases. Based on its acute effects on mouse mast cells (MCs), IL-33 is thought to play a role in the pathogenesis of allergic disease through MC activation. However, the manifestations of chronic IL-33 exposure on human MC function, which best reflect the conditions associated with chronic allergic disease, are unknown. We now find that long-term exposure of human and mouse MCs to IL-33 results in a substantial reduction of MC activation in response to antigen. This reduction required >72 h exposure to IL-33 for onset and 1-2 wk for reversion following IL-33 removal. This hypo-responsive phenotype was determined to be a consequence of MyD88-dependent attenuation of signaling processes necessary for MC activation including antigen-mediated calcium mobilization and cytoskeletal reorganization; potentially as a consequence of down-regulation of the expression of PLCg1 and Hck. These findings suggest that IL-33 may play a protective, rather than a causative role in MC activation under chronic conditions and, furthermore, reveal regulated plasticity in the MC activation phenotype. The ability to down-regulate MC activation in this manner may provide alternative approaches for treatment of MC-driven disease.
IL-33 induces a hyporesponsive phenotype in human and mouse mast cells.
Specimen part, Treatment
View SamplesThis study focused on transcription in the medial PFC (mPFC) as a function of age and cognition. Young and aged F344 rats were characterized on tasks, attentional set shift and spatial memory, which depend on the mPFC and hippocampus, respectively. Differences in transcription associated with age and cognitive function were examined using RNA sequencing to construct transcriptomic profiles for the mPFC, white matter, and region CA1 of the hippocampus. The results indicate regional differences in vulnerability to aging associated with increased expression of immune and defense response genes and a decline in synaptic and neural activity genes. Importantly, we provide evidence for region specific transcription related to behavior. In particular, expression of transcriptional regulators and neural activity-related immediate-early genes (IEGs) are increased in the mPFC of aged animals that exhibit delayed set shift behavior; relative to age-matched animals that exhibit set shift behavior similar to younger animals. Overall design: The study contains 11 young and 20 aged rats for the mPFC and CA1 samples, which were used to investigate expression patterns associated with aging and behavior. White matter samples were used to investigate an age-related effect with 8 young and 9 aged rats.
Transcription Profile of Aging and Cognition-Related Genes in the Medial Prefrontal Cortex.
No sample metadata fields
View SamplesStaphylococcus aureus is a major human pathogen and resistant to numerous clinically used antibiotics. The first antibiotic developed for S. aureus infections was the nonribosomal petide secondary metabolite penicillin. We discovered cryptic nonribosomal peptide secondary metabolites, the aureusimines, made by S. aureus itself that are not antibiotics, but function as small molecule regulators of virulence factor expression. Using established rules and codes for nonribosomal peptide assembly we predicted these nonribosomal peptides, and used these predictions to identify them from S. aureus culture broths. Functional studies using global microarray and mouse bacteremia models established that the aureusimines control virulence factor expression and are necessary for productive infections. This is the first report of the aureusimines and has important implications for the treatment of drug resistant S. aureus. Targeting aureusimine synthesis may provide novel anti-infectives.
Staphylococcus aureus nonribosomal peptide secondary metabolites regulate virulence.
No sample metadata fields
View SamplesAn evaluation of biopsies from patients with in-transit extremity melanoma who have been treated with ADH-1 followed by melphalan in the setting of isolated limb infusion
Prospective multicenter phase II trial of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with advanced extremity melanoma.
Disease, Disease stage, Treatment
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