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Full-Text Articles in Medicine and Health Sciences

Beta3 Integrin Haplotype Influences Gene Regulation And Plasma Von Willebrand Factor Activity, Katie E. Payne, Paul F. Bray, Peter J. Grant, Angela M. Carter Jun 2008

Beta3 Integrin Haplotype Influences Gene Regulation And Plasma Von Willebrand Factor Activity, Katie E. Payne, Paul F. Bray, Peter J. Grant, Angela M. Carter

Department of Medicine Faculty Papers

The Leu33Pro polymorphism of the gene encoding beta(3) integrin (ITGB3) is associated with acute coronary syndromes and influences platelet aggregation. Three common promoter polymorphisms have also been identified. The aims of this study were to (1) investigate the influence of the ITGB3 -400C/A, -425A/C and -468G/A promoter polymorphisms on reporter gene expression and nuclear protein binding and (2) determine genotype and haplotype associations with platelet alpha(IIb)beta(3) receptor density. Promoter haplotypes were introduced into an ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear proteins was assessed by electrophoretic …


Cif Is Negatively Regulated By The Tetr Family Repressor Cifr, Daniel P. Maceachran, Bruce A. Stanton, George A. O'Toole May 2008

Cif Is Negatively Regulated By The Tetr Family Repressor Cifr, Daniel P. Maceachran, Bruce A. Stanton, George A. O'Toole

Dartmouth Scholarship

We previously reported that the novel Pseudomonas aeruginosa toxin Cif is capable of decreasing apical membrane expression of the cystic fibrosis transmembrane conductance regulator (CFTR). We further demonstrated that Cif is capable of degrading the synthetic epoxide hydrolase (EH) substrate S-NEPC [(2S,3S)-trans-3-phenyl-2-oxiranylmethyl 4-nitrophenol carbonate], suggesting that Cif may be reducing apical membrane expression of CFTR via its EH activity. Here we report that Cif is capable of degrading the xenobiotic epoxide epibromohydrin (EBH) to its vicinal diol 3-bromo-1,2-propanediol. We also demonstrate that this epoxide is a potent inducer of cif gene expression. We show that the predicted TetR family transcriptional …


Structural Basis Of Bilayer Deformation By Membrane-Associated Scaffolds, Adam Frost May 2008

Structural Basis Of Bilayer Deformation By Membrane-Associated Scaffolds, Adam Frost

Yale Medicine Thesis Digital Library

The assembly of amphipathic lipids into fluid bilayers that are impermeable to macromolecules is fundamental to the existence of viruses, organelles, and cells. Conversely, membrane compartmentalization poses problems, since essential processes like cell division, cell migration, endo-, exo-, and transcytosis all require cells to remodel and even break their membranes without opening lethal leaks. Evolutionary forces have consequently generated proteins that can reversibly mold membranes into planes, spheres, cylinders, and saddle-shaped surfaces. Principally, the BAR (Bin, Amphiphysin, RVS) domain superfamily of proteins are recruited from the cytoplasm to induce or stabilize states of high membrane curvature, while the Dynamin superfamily …


Celecoxib Concentration Predicts Decrease In Prostaglandin E2 Concentrations In Nipple Aspirate Fluid From High Risk Women, Edward R. Sauter, Wenyi Qin, John E. Hewett, Rachel L. Ruhlen, John T. Flynn, George Rottinghaus, Yin-Chieh Chen Feb 2008

Celecoxib Concentration Predicts Decrease In Prostaglandin E2 Concentrations In Nipple Aspirate Fluid From High Risk Women, Edward R. Sauter, Wenyi Qin, John E. Hewett, Rachel L. Ruhlen, John T. Flynn, George Rottinghaus, Yin-Chieh Chen

Department of Molecular Physiology and Biophysics Faculty Papers

BACKGROUND: Epidemiologic studies suggest that long term low dose celecoxib use significantly lowers breast cancer risk. We previously demonstrated that 400 mg celecoxib taken twice daily for 2 weeks lowered circulating plasma and breast nipple aspirate fluid (NAF) prostaglandin (PG)E2 concentrations in post- but not premenopausal high risk women. We hypothesized that circulating concentrations of celecoxib influenced PGE2 response, and that plasma levels of the drug are influenced by menopausal status. To address these hypotheses, the aims of the study were to determine: 1) if circulating plasma concentrations of celecoxib correlated with the change in plasma or NAF PGE2 concentrations …


Fibulin-2 Is Dispensable For Mouse Development And Elastic Fiber Formation, Francois-Xavier Sicot, Takeshi Tsuda, Dessislava Markova, John Klement, Machiko Arita, Rui-Zhu Zhang, Te-Cheng Pan, Robert P. Mecham, David E. Birk, Mon-Li Chu Feb 2008

Fibulin-2 Is Dispensable For Mouse Development And Elastic Fiber Formation, Francois-Xavier Sicot, Takeshi Tsuda, Dessislava Markova, John Klement, Machiko Arita, Rui-Zhu Zhang, Te-Cheng Pan, Robert P. Mecham, David E. Birk, Mon-Li Chu

Department of Dermatology and Cutaneous Biology Faculty Papers

Fibulin-2 is an extracellular matrix protein belonging to the five-member fibulin family, of which two members have been shown to play essential roles in elastic fiber formation during development. Fibulin-2 interacts with two major constituents of elastic fibers, tropoelastin and fibrillin-1, in vitro and localizes to elastic fibers in many tissues in vivo. The protein is prominently expressed during morphogenesis of the heart and aortic arch vessels and at early stages of cartilage development. To examine its role in vivo, we generated mice that do not express the fibulin-2 gene (Fbln2) through homologous recombination of embryonic stem cells. Unexpectedly, the …


Repression Of Hla By Rot Is Dependent On Sae In Staphylococcus Aureus, Dongmei Li, Ambrose Cheung Jan 2008

Repression Of Hla By Rot Is Dependent On Sae In Staphylococcus Aureus, Dongmei Li, Ambrose Cheung

Dartmouth Scholarship

The regulatory locus sae is a two-component system in Staphylococcus aureus that regulates many important virulence factors, including alpha-toxin (encoded by hla) at the transcriptional level. The SarA homologs Rot and SarT were previously shown to be repressors of hla in selected S. aureus backgrounds. To delineate the interaction of rot and sae and the contribution of sarT to hla expression, an assortment of rot and sae isogenic single mutants, a rot sae double mutant, and a rot sae sarT markerless triple mutant were constructed from wild-type strain COL. Using Northern blot analysis and transcriptional reporter gene green fluorescent protein, …