Glatiramer Acetate (GA) has provided safe and effective treatment for multiple sclerosis (MS) patients for two decades. It acts as an antigen, yet the precise mechanism of action remains to be fully elucidated, and no validated pharmacokinetic or pharmacodynamic biomarkers exist. In order to better characterize GAs biological impact, genome-wide expression studies were conducted with a human monocyte (THP-1) cell line. Consistent with previous literature, branded GA upregulated antiinflammatory markers (e.g. IL10), and modulated multiple immune-related pathways. Despite some similarities, significant differences were observed between expression profiles induced by branded GA and Probioglat, a differently-manufactured glatiramoid purported to be a generic GA.
Gene expression studies of a human monocyte cell line identify dissimilarities between differently manufactured glatiramoids.
Cell line, Treatment, Time
View SamplesVitamin A (VA) restriction for beef cattle improves meat marbling. However, its molecular mechanisms are not completely elucidated.
Microarray analysis of Longissimus thoracis muscle gene expressions in vitamin A-restricted Japanese Black steers in middle fattening stage.
Sex, Age, Specimen part
View SamplesBackground
Expression quantitative trait loci mapping identifies new genetic models of glutathione S-transferase variation.
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View SamplesMicroarray analysis of isolated lymphatic endothelial cells from cervical lymph nodes (CLNs) of ischemic mice showed the activation of transmembrane tyrosine kinase pathways.
Brain-to-cervical lymph node signaling after stroke.
Treatment
View SamplesXBP1 is a transcription factor that is induced by unconventional splicing associated with endoplasmic reticulum stress and plays a role in development of liver and plasma cells. We previously reported that brain derived neurotrophic factor (BDNF) leads to splicing of XBP1 mRNA in neurites, and that XBP1 is required for BDNF-induced neurite extension and branching. To search for the molecular mechanisms of how XBP1 plays a role in neural development, comprehensive gene expression analysis was performed in primary telencephalic neurons obtained from Xbp1 knockout mice at embryonic day 12.5. By searching for the genes induced by BDNF in wild type neurons but this induction was reduced in Xbp1 knockout mice, we found that upregulation of three GABAergic markers, somatostatin (Sst), neuropeptide Y (Npy), and calbindin (Calb1), were compromised in Xbp1 knockout neurons. Attenuated induction of Npy and Calb1 was confirmed by quantitative RT-PCR. In neurons lacking in Xbp1, upregulation of GABAergic markers was attenuated. Impaired BDNF-induced neurite extension in Xbp1 knockout neurons might be mediated by disturbed BDNF-induced differentiation of GABAergic interneurons.
Attenuated BDNF-induced upregulation of GABAergic markers in neurons lacking Xbp1.
Specimen part
View SamplesRationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses.
A pathway-based analysis on the effects of obstructive sleep apnea in modulating visceral fat transcriptome.
Subject
View SamplesAeromonas caviae has been associated with human gastrointestinal disease. Strains of this species typically lack virulence factors (VFs) such as enterotoxins and hemolysins that are produced by other human pathogens of the Aeromonas genus. Microarray profiling of murine small intestinal extracts, 24 hours after oral infection with an A. caviae strain, provides evidence of a Th1 type immune response. A large number of gamma-interferon (-IFN) induced genes are up-regulated as well as several tumor necrosis factor-alpha (TNF-) transcripts. A. caviae has always been considered an opportunistic pathogen because it lacks obvious virulence factors. This current effort suggests A. caviae colonizes murine intestinal tract and causes what has been described by others as a dysregulatory cytokine response leading to an irritable bowel-like syndrome. This response would explain why a number of diarrheal waterborne outbreaks have been attributed to A. caviae even though it lacks obvious enteropathogenic properties.
Aeromonas caviae strain induces Th1 cytokine response in mouse intestinal tract.
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View SamplesHyperthermia (HT) treatments in combination with either chemotherapy, radiotherapy or both are used for patients with cancer in various organs. However, the acquisition of thermotolerance in cancer cells due to the increase in cytoprotective proteins attenuates the therapeutic effects of HT. BAG3 (BCL2-associated athanogene 3) is a cytoprotective protein that acts against various stresses including heat stress. Recently, we demonstrated that the inhibition of BAG3 improves cell death sensitivity to HT in cancer cells. However, a detailed molecular mechanism involved in the enhancement of HT sensitivity by BAG3-knockdown (KD) in cancer cells is unclear.
Network analysis of genes involved in the enhancement of hyperthermia sensitivity by the knockdown of BAG3 in human oral squamous cell carcinoma cells.
Sex, Age, Specimen part, Cell line
View SamplesRationale: Obstructive sleep apnea (OSA) has been associated with a number of chronic disorders that may improve with effective therapy. However, the molecular pathways affected by continuous positive airway pressure (CPAP) treatment are largely unknown. We sought to assess the system-wide consequences of CPAP therapy by transcriptionally profiling peripheral blood leukocytes (PBLs). Methods: Subjects diagnosed with severe OSA were treated with CPAP, and whole-genome expression measurement of PBLs was performed at baseline and following therapy. We used Gene Set Enrichment Analysis (GSEA) to identify gene sets that were differentially enriched. Network analysis was then applied to identify key drivers of pathways influenced by CPAP. Results: 18 subjects with severe OSA (apnea hypopnea index 30 events/hour) underwent CPAP therapy and microarray analysis of their PBLs. Treatment with CPAP improved AHI, daytime sleepiness and blood pressure but did not affect anthropometric measures. GSEA revealed a number of enriched gene sets, many of which were involved in neoplastic processes and displayed down-regulated expression patterns in response to CPAP. Network analysis identified several densely connected genes that are important modulators of cancer and tumor growth. Conclusions: Effective therapy of OSA with CPAP is associated with alterations in circulating leukocyte gene expression. Functional enrichment and network analyses highlighted transcriptional suppression in cancer-related pathways suggesting potentially novel mechanisms linking OSA with neoplastic signatures.
Treatment of obstructive sleep apnea alters cancer-associated transcriptional signatures in circulating leukocytes.
Treatment, Subject
View SamplesThe generation of properly functioning gametes in vitro, a key goal in developmental/reproductive biology, requires multi-step reconstitutions of complex germ cell development. Based on the logic of primordial germ cell (PGC)-specification, we demonstrate here the generation of PGC-like cells (PGCLCs) in mice with robust capacity for spermatogenesis from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) through epiblast-like cells (EpiLCs), a cellular state highly similar to pre-gastrulating epiblasts, but distinct from epiblast stem cells (EpiSCs). The global transcription profiles, epigenetic reprogramming, and cellular dynamics during PGCLC induction from EpiLCs are a meticulous capture of those associated with PGC specification from the epiblasts. Furthermore, we identify Integrin-beta 3 and SSEA1 as markers that purify PGCLCs with spermatogenic capacity free from tumorigenic undifferentiated cells. With the reconstitution of PGC specification pathway from the naive inner cell mass state, our study defines a paradigm for the essential step of in vitro gametogenesis.
Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells.
Specimen part
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