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Articles 1 - 4 of 4

Full-Text Articles in Molecular Biology

Transient High Glucose Causes Persistent Epigenetic Changes And Altered Gene Expression During Subsequent Normoglycemia, Assam El-Osta, Daniella Brasacchio, Dachun Yao, Alessandro Pocai, Peter L. Jones, Robert G. Roeder, Mark E. Cooper, Michael Brownlee Sep 2008

Transient High Glucose Causes Persistent Epigenetic Changes And Altered Gene Expression During Subsequent Normoglycemia, Assam El-Osta, Daniella Brasacchio, Dachun Yao, Alessandro Pocai, Peter L. Jones, Robert G. Roeder, Mark E. Cooper, Michael Brownlee

Peter Jones Lab Publications

The current goal of diabetes therapy is to reduce time-averaged mean levels of glycemia, measured as HbA1c, to prevent diabetic complications. However, HbA1c only explains <25% of the variation in risk of developing complications. Because HbA1c does not correlate with glycemic variability when adjusted for mean blood glucose, we hypothesized that transient spikes of hyperglycemia may be an HbA1c-independent risk factor for diabetic complications. We show that transient hyperglycemia induces long-lasting activating epigenetic changes in the promoter of the nuclear factor kappaB (NF-kappaB) subunit p65 in aortic endothelial cells both in vitro and in nondiabetic mice, which cause increased p65 gene expression. Both the epigenetic changes and the gene expression changes persist for at least 6 d of subsequent normal glycemia, as do NF-kappaB-induced increases in monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 expression. Hyperglycemia-induced epigenetic changes and increased p65 expression are prevented by reducing mitochondrial superoxide production or superoxide-induced alpha-oxoaldehydes. These results highlight the dramatic and long-lasting effects that short-term hyperglycemic spikes can have on vascular cells and suggest that transient spikes of hyperglycemia may be an HbA1c-independent risk factor for diabetic complications.


Drosophila Let-7 Microrna Is Required For Remodeling Of The Neuromusculature During Metamorphosis, Nicholas S. Sokol, Peizhang Xu, Yuh-Nung Jan, Victor R. Ambros Jun 2008

Drosophila Let-7 Microrna Is Required For Remodeling Of The Neuromusculature During Metamorphosis, Nicholas S. Sokol, Peizhang Xu, Yuh-Nung Jan, Victor R. Ambros

Program in Molecular Medicine Publications and Presentations

The Drosophila let-7-Complex (let-7-C) is a polycistronic locus encoding three ancient microRNAs: let-7, miR-100, and fly lin-4 (miR-125). We find that the let-7-C locus is principally expressed in the pupal and adult neuromusculature. let-7-C knockout flies appear normal externally but display defects in adult behaviors (e.g., flight, motility, and fertility) as well as clear juvenile features in their neuromusculature. We find that the function of let-7-C to ensure the appropriate remodeling of the abdominal neuromusculature during the larval-to-adult transition is carried out predominantly by let-7 alone. This heterochronic role of let-7 is likely just one of the ways in ...


Bmp Signaling Goes Posttranscriptional In A Microrna Sort Of Way, Catherine A. Reinke, Richard W. Carthew Jan 2008

Bmp Signaling Goes Posttranscriptional In A Microrna Sort Of Way, Catherine A. Reinke, Richard W. Carthew

Faculty Publications

Aberrant microRNA (miRNA) expression correlates with human diseases such as cardiac disorders and cancer. Treatment of such disorders using miRNA-targeted therapeutics requires a thorough understanding of miRNA regulation in vivo. A recent paper in Nature by Davis et al. expands our understanding of miRNA biogenesis and maturation, elucidating a mechanism by which extracellular signaling directs cell differentiation via posttranscriptional regulation of miRNA expression.


A Molecular Phylogeny Of The Genus Bonamia Based On Sequence Data Of The Ribosomal Rna (Rrna) Gene Complex, Delonna M. White Jan 2008

A Molecular Phylogeny Of The Genus Bonamia Based On Sequence Data Of The Ribosomal Rna (Rrna) Gene Complex, Delonna M. White

Dissertations, Theses, and Masters Projects

No abstract provided.