Vascular smooth muscle cells (VSMC) are important for contraction, blood flow distribution and regulation of blood vessel diameter, but to what extent they contribute to the integrity of blood vessels and blood-brain barrier function is less well understood. In this report, we explored the impact of the progressive loss of VSMC in the Notch3-/- mouse on blood vessel integrity in the central nervous system
Notch3 is necessary for blood vessel integrity in the central nervous system.
Age, Specimen part
View SamplesThe pathogenic mechanisms of common kidney glomerular diseases, including the vast majority of cases of proteinuria, remain unknown.
Glomerular transcriptome changes associated with lipopolysaccharide-induced proteinuria.
No sample metadata fields
View SamplesThe blood-brain barrier (BBB) consists of specific physical barriers, enzymes and transporters, which together maintain the necessary extracellular environment of the central nervous system (CNS). The main physical barrier is found in the CNS endothelial cell, and depends on continuous complexes of tight junctions combined with reduced vesicular transport. Other possible constituents of the BBB include extracellular matrix, astrocytes and pericytes, but the relative contribution of these different components to the BBB remains largely unknown. Here we demonstrate a direct role of pericytes at the BBB in vivo. Using a set of adult viable pericyte-deficient mouse mutants we show that pericyte deficiency increases the permeability of the BBB to water and a range of low-molecular-mass and high-molecular-mass tracers. The increased permeability occurs by endothelial transcytosis, a process that is rapidly arrested by the drug imatinib. Furthermore, we show that pericytes function at the BBB in at least two ways: by regulating BBB-specific gene expression patterns in endothelial cells, and by inducing polarization of astrocyte end-feet surrounding CNS blood vessels. Our results indicate a novel and critical role for pericytes in the integration of endothelial and astrocyte functions at the neurovascular unit, and in the regulation of the BBB.
Pericytes regulate the blood-brain barrier.
Sex, Age, Specimen part
View SamplesBackground: Preterm birth is the leading cause of all infant mortality. In 2004, 12.5% of all births were preterm. In order to understand preterm labor, we must first understand normal labor. Since many of the myometrial changes that occur during pregnancy are similar in mice and humans and mouse gestation is short, we have studied the uterine genes that change in the mouse during pregnancy. Here, we used microarray analysis to identify uterine genes in the gravid mouse that are differentially regulated in the cyclooxygenase-1 knockout mouse model of delayed parturition.
Identification of 9 uterine genes that are regulated during mouse pregnancy and exhibit abnormal levels in the cyclooxygenase-1 knockout mouse.
No sample metadata fields
View SamplesWe have determined the whole genome sequence of an individual at high accuracy and performed an integrated analysis of omics profiles over a 1.5 year period that included healthy and two virally infected states. Omics profiling of transcriptomes, proteomes, cytokines, metabolomes and autoantibodyomes from blood components have revealed extensive, dynamic and broad changes in diverse molecular components and biological pathways that occurred during healthy and disease states. Many changes were associated with allele- and edit-specific expression at the RNA and protein levels, which may contribute to personalized responses. Importantly, genomic information was also used to predict medical risks, including Type II Diabetes (T2D), whose onset was observed during the course of our study using standard clinical tests and molecular profiles, and whose disease progression was monitored and subsequently partially managed. Our study demonstrates that longitudinal personal omics profiling can relate genomic information to global functional omics activity for physiological and medical interpretation of healthy and disease states. Overall design: Examination of blood component in 20 different time points over 1.5 years which includes 2 disease state and 18 healty state Related exome studies at: SRX083314 SRX083313 SRX083312 SRX083311
Personal omics profiling reveals dynamic molecular and medical phenotypes.
Specimen part, Disease, Subject
View SamplesGlucocorticoids (GC) are used as first line therapies for generalized suppression of inflammation (e.g. allergies or autoimmune diseases), but their long-term use is limited by severe side effects. Our previous work has revealed that GC induced a stable anti-inflammatory phenotype in monocytes, the glucocorticoid-stimulated monocytes (GCsM) that we now exploited for targeted GC-mediated therapeutic effects.
Immune suppression via glucocorticoid-stimulated monocytes: a novel mechanism to cope with inflammation.
Specimen part, Treatment
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