Alginate overproduction by P. aeruginosa, also known as mucoidy is associated with chronic endobronchial infections in cystic fibrosis (CF). Alginate biosynthesis in this bacterium is initiated by the extracytoplasmic function sigma factor (22, AlgU/T). In the wild type (wt) nonmucoid strains, such as PAO1, AlgU is sequestered by the anti-sigma factor MucA that inhibits alginate production. However, the degradation of MucA by activated intramembrane proteases AlgW and/or MucP can lead to the conversion from nonmucoid strains to mucoid. Previously we reported that the absence of the sensor kinase KinB in PAO1 causes the initiation of AlgW-dependent proteolysis of MucA resulting in alginate overproduction. In the kinB mutant this activation requires alternate sigma factor RpoN (54). To determine the RpoN-dependent KinB regulon, microarray and proteomic analyses were performed on a mucoid kinB mutant and an isogenic nonmucoid kinB rpoN double mutant. In the kinB mutant, RpoN controlled the expression of approximately 20% of the genome. Besides alginate biosynthesis and regulator genes such as AlgW, KinB, in concert with RpoN, also control a large number of genes including: those involved in carbohydrate metabolism, quorum sensing, iron regulation, rhamnolipid production, and motility. In an acute pneumonia murine infection model, mice exhibited better survival when challenged with the kinB mutant than wt PAO1. Together, these data strongly suggest that KinB controls virulence factors important for acute pneumonia and conversion to mucoidy.
Analysis of the Pseudomonas aeruginosa regulon controlled by the sensor kinase KinB and sigma factor RpoN.
Treatment
View SamplesThis experiment tests the hypothesis that interleukin-1 promotes SMC phenotypic modulation to a distinct inflammatory state relative to the growth factor PDGF-DD.
Interleukin-1β modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-κB-dependent mechanisms.
No sample metadata fields
View SamplesGiven the heterogeneity of disease evident from study of the presentation, histomorphology, disease course, and molecular lesions of bladder cancer, a cohort of 8 non-muscle invasive and 11 muscle invasive bladder cancers were profiled for gene expression using the Affymetrix HG-U133A platform.
Transcriptional signatures of Ral GTPase are associated with aggressive clinicopathologic characteristics in human cancer.
No sample metadata fields
View SamplesThe global prevalence of obesity is increasing across age and gender. The rising burden of obesity in young people contributes to the early emergence of type 2 diabetes. Having one parent obese is an independent risk factor for childhood obesity. While the detrimental impact of diet-induced maternal obesity on offspring is well established, the extent of the contribution of obese fathers is unclear, as is the role of non-genetic factors in the casual pathway. Here we show that paternal high fat diet exposure programmed -cell dysfunction in their F1 female offspring. Chronic high fat diet consumption in Sprague Dawley fathers led to increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had lower body weight at day-1, increased pubertal growth rate, impaired insulin secretion and glucose tolerance, in the absence of obesity or increased adiposity. Paternal high fat diet altered the expression of 211 pancreatic islet genes in adult female offspring (P < 0.001); genes belonged to 8 functional clusters, including calcium ion binding, primary metabolic processes and ATP binding, and organ/system development. Broader KEGG pathway analysis of 2014 genes differentially expressed at the P < 0.01 level further demonstrated involvement of insulin and calcium signaling, and MAPK pathways. This is the first reported study in mammals describing non-genetic, intergenerational transmission of metabolic sequelae of high fat diet from father to offspring. These findings support a role of fathers in metabolic programming of offspring and form a framework for further studies.
Paternal high-fat diet consumption induces common changes in the transcriptomes of retroperitoneal adipose and pancreatic islet tissues in female rat offspring.
Sex, Specimen part, Treatment
View SamplesThe global prevalence of obesity is increasing across age and gender. The rising burden of obesity in young people contributes to the early emergence of type 2 diabetes. Having one parent obese is an independent risk factor for childhood obesity. While the detrimental impact of diet-induced maternal obesity on offspring is well established, the extent of the contribution of obese fathers is unclear, as is the role of non-genetic factors in the casual pathway. Here we show that paternal high fat diet exposure programmed -cell dysfunction in their F1 female offspring. Chronic high fat diet consumption in Sprague Dawley fathers led to increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had lower body weight at day-1, increased pubertal growth rate, impaired insulin secretion and glucose tolerance, in the absence of obesity or increased adiposity. Paternal high fat diet was observed to alter gene expression of pancreatic islet genes in adult female offspring (P < 0.001); affected functional clusters includes calcium ion binding, insulin, apoptosis, Wnt and cell cycle organ/system development. This is the first reported study in mammals describing non-genetic, intergenerational transmission of metabolic sequelae of high fat diet from father to offspring. These findings support a role of fathers in metabolic programming of offspring and form a framework for further studies.
Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Paternal high-fat diet consumption induces common changes in the transcriptomes of retroperitoneal adipose and pancreatic islet tissues in female rat offspring.
Sex, Specimen part, Treatment
View SamplesLoss of Amylo-alpha-1-6-glucosidase-4-alpha-glucanotransferase (AGL) drives bladder cancer growth. Low AGL expression predicts poor patient outcome. Currently no specific therapeutically tractable targets/pathways exist that could be used to treat patients with low AGL expressing bladder tumors.
Loss of Glycogen Debranching Enzyme AGL Drives Bladder Tumor Growth via Induction of Hyaluronic Acid Synthesis.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma.
No sample metadata fields
View SamplesA673 Ewing's sarcoma cells, with inducible EWS/FLI cDNA, harboring the EF-2-RNAi retrovirus, induced (or uninduced) for the indicated time period.
Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma.
No sample metadata fields
View SamplesA673 Ewing's sarcoma cells containing either control RNAi retroviral constructs (luc-RNAi), or RNAi retroviral constructs targeting the endogenous EWS/FLI fusion transcript (either EF-2-RNAi or EF-4-RNAi).
Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma.
No sample metadata fields
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