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Träfflista för sökning "WFRF:(Bader Joel S.) "

Sökning: WFRF:(Bader Joel S.)

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  • van Setten, Jessica, et al. (författare)
  • PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
  • 2018
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
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  • Rivera, Corban G., et al. (författare)
  • Analysis of VEGF-A Regulated Gene Expression in Endothelial Cells to Identify Genes Linked to Angiogenesis
  • 2011
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:9, s. e24887-
  • Tidskriftsartikel (refereegranskat)abstract
    • Angiogenesis is important for many physiological processes, diseases, and also regenerative medicine. Therapies that inhibit the vascular endothelial growth factor (VEGF) pathway have been used in the clinic for cancer and macular degeneration. In cancer applications, these treatments suffer from a "tumor escape phenomenon'' where alternative pathways are upregulated and angiogenesis continues. The redundancy of angiogenesis regulation indicates the need for additional studies and new drug targets. We aimed to (i) identify novel and missing angiogenesis annotations and (ii) verify their significance to angiogenesis. To achieve these goals, we integrated the human interactome with known angiogenesis-annotated proteins to identify a set of 202 angiogenesis-associated proteins. Across endothelial cell lines, we found that a significant fraction of these proteins had highly perturbed gene expression during angiogenesis. After treatment with VEGF-A, we found increasing expression of HIF-1 alpha, APP, HIV-1 tat interactive protein 2, and MEF2C, while endoglin, liprin beta 1 and HIF-2 alpha had decreasing expression across three endothelial cell lines. The analysis showed differential regulation of HIF-1 alpha and HIF-2 alpha. The data also provided additional evidence for the role of endothelial cells in Alzheimer's disease.
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