Abstract
Evidence of a functional role for mast cells in the development of type 1 diabetes mellitus in the BioBreeding rat.
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View SamplesThe complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D, HC, and healthy T1D sibling cohorts. In addition, we examined T1D progression by looking at longitudinal samples.
Molecular signatures differentiate immune states in type 1 diabetic families.
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View SamplesA persistent and non-resolving inflammatory response to accumulating A peptide species is a cardinal feature in the development of Alzheimer's disease (AD). In response to accumulating A peptide species, microglia, the innate immune cells of the brain, generate a toxic inflammatory response that accelerates synaptic and neuronal injury. Many pro-inflammatory signaling pathways are linked to progression of neurodegeneration. However, endogenous anti-inflammatory pathways capable of suppressing A-induced inflammation represent a relatively unexplored area.
Suppression of Alzheimer-associated inflammation by microglial prostaglandin-E2 EP4 receptor signaling.
Specimen part
View SamplesTissue-specific comparison of gene expression levels in T65H translocation mice, either with or without uniparental duplications of Chrs 7 & 11. Identification of highly differentially expressed transcripts.
Chromosome-wide identification of novel imprinted genes using microarrays and uniparental disomies.
Specimen part
View SamplesComparison of gene expression levels between MatDp(dist2) and PatDp(dist2) mice (newborn whole head). Identification of highly differentially expressed transcripts.
Transcript- and tissue-specific imprinting of a tumour suppressor gene.
Specimen part
View SamplesConsider the problem of designing a panel of complex biomarkers to predict a patient's health or disease state when one can pair his or her current test sample, called a target sample, with the patient's previously acquired healthy sample, called a reference sample. As contrasted to a population averaged reference, this reference sample is individualized. Automated predictor algorithms that compare and contrast the paired samples to each other could result in a new generation of test panels that compare to a person's healthy reference to enhance predictive accuracy. This study develops such an individualized predictor and illustrates the added value of including the healthy reference for design of predictive gene expression panels. The objective is to predict each subject's state of infection, e.g., neither exposed nor infected, exposed but not infected, pre-acute phase of infection, acute phase of infection, post-acute phase of infection. Using gene microarray data collected in a large-scale serially sampled respiratory virus challenge study, we quantify the diagnostic advantage of pairing a person's baseline reference with his or her target sample.
An individualized predictor of health and disease using paired reference and target samples.
Specimen part, Subject, Time
View SamplesIn an acute skin wound, newly released serum growth factors in the wound bed drive lateral migration of human keratinocytes (HKs) to re-epithelialize the wound. However, profiling the migration signal-specific genes has long been challenged by pleiotropic effects of a given growth factor, including proliferation, migration and factor-specific responses. To overcome these technical problems, we 1) took advantage of a unique response of HKs to transforming growth factor-beta (TGFbeta) to selectively suppress growth signal-responding genes and identify motility-specific genes and 2) employed dual stimulation of HKs with TGFalpha and insulin to identify the common genes and eliminate factor-specific genes. Under these conditions, DNA microarray analyses were utilized to study the profiles of both TGFalpha-regualted and insulin-regulated immediate early (IE, 30 min), early (E, 60 min) and delayed early (DE, 120 min) genes.
Profiling motility signal-specific genes in primary human keratinocytes.
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View SamplesArabidopsis fc2-1 mutants fail to properly de-etiolate after a prolonged period in the dark. Our goal was to monitor whole genome expression during the first 2 hours of de-etiolation to determine the cuase of this growth arrest.
Ubiquitin facilitates a quality-control pathway that removes damaged chloroplasts.
Specimen part
View SamplesMicroarray Analysis of Space-flown Murine Thymus Tissue Reveals Changes in Gene Expression Regulating Stress and Glucocorticoid Receptors. We used microarrays to detail the gene expression of space-flown thymic tissue and identified distinct classes of up-regulated genes during this process. We report here microarray gene expression analysis in young adult C57BL/6NTac mice at 8 weeks of age after exposure to spaceflight aboard the space shuttle (STS-118) for a period of 13 days. Upon conclusion of the mission, thymus lobes were extracted from space flown mice (FLT) as well as age- and sex-matched ground control mice similarly housed in animal enclosure modules (AEM). mRNA was extracted and an automated array analysis for gene expression was performed. Examination of the microarray data revealed 970 individual probes that had a 1.5 fold or greater change. When these data were averaged (n=4), we identified 12 genes that were significantly up- or down-regulated by at least 1.5 fold after spaceflight (p0.05). Together, these data demonstrate that spaceflight induces significant changes in the thymic mRNA expression of genes that regulate stress, glucocorticoid receptor metabolism, and T cell signaling activity. These data explain, in part, the reported systemic compromise of the immune system after exposure to the microgravity of space.
Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors.
Specimen part
View SamplesMesenchymal stromal cells (MSC) are currently being evaluated in numerous preclinical and clinical cell-based therapy studies. Furthermore, there is an increasing interest in exploring alternative uses of these cells in disease modelling, pharmaceutical screening and regenerative medicine by applying reprogramming technologies. However, the limited availability of MSCs from various sources, restricts their use. Term amniotic fluid has been proposed as an alternative source of MSCs. Previously, only low volumes of term fluid and its cellular constituents have been collected, and current knowledge of the MSCs derived from this fluid is limited. In this study, we collected amniotic fluid at term using a novel collection system and evaluated amniotic fluid MSC content and their characteristics, including their feasibility to undergo cellular reprogramming.
Term amniotic fluid: an unexploited reserve of mesenchymal stromal cells for reprogramming and potential cell therapy applications.
Specimen part
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