Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

Peer reviewe

MicroRNA Related Polymorphisms and Breast Cancer Risk

Peer reviewe

DBEM Crack Growth Simulation for a Riveted Aeronautic Reinforcement under Non-linear Contact Conditions

A special specimen was created cutting a rectangular notched area from the surrounding of the upper left corner of a wide body aircraft door. Then a fatigue traction load was applied in order to induce an MSD crack initiation and propagation. An innovative DBEM (Dual Boundary Element Method) modelling approach was devised, capable of explicitly modelling the different test article layers with their rivet connections even in a 2d approach. The rivets that are close to the propagating crack are coupled with the corresponding holes by non linear contact conditions, and the accuracy improvements are assessed in comparison with a previous linear analysis, in which traction and displacements continuity conditions on the hole-rivet interface had been imposed. The importance of such influence on the simulation precision need to be assessed due to the strong impact that a non linear analysis produces on computational times. For such a complex problem (three different panels, made of different materials, each one with a variable thickness and connected by numerous rivets), experimental crack propagation data were available for the numerical-experimental comparison. With such non linear approach, a significant improvement on the growth rate correlation is obtained, that justify the increased computational effort

Esterase D is essential for protection of neisseria gonorrhoeae against nitrosative stress and for bacterial growth during interaction with cervical epithelial cells

estD encodes a carboxylic ester hydrolase and is part of the NmlR regulon in Neisseria gonorrhoeae. An estD mutant was found to be susceptible to nitrite and to S-nitrosoglutathione. This mutant was also unable to infect and survive within human cervical epithelial cells, and it showed reduced ability to form a biofilm on these cells. We conclude that esterase D is an integral part of the nitrosative stress defense system of N. gonorrhoeae and that it has potential importance in pathogenesis.Adam J. Potter, Stephen P. Kidd, Jennifer L. Edwards, Megan L. Falsetta, Michael A. Apicella, Michael P. Jennings, and Alastair G. McEwa

Phenotypic Characterization of a copA Mutant of Neisseria gonorrhoeae Identifies a Link between Copper and Nitrosative Stress

NGO0579 is annotated copA in the Neisseria gonorrhoeae chromosome, suggesting that it encodes a cation-transporting ATPase specific for copper ions. Compared to wild-type cells, a copA mutant was more sensitive to killing by copper ions but not to other transition metals. The mutant also accumulated a greater amount of copper, consistent with the predicted role of CopA as a copper efflux pump. The copA mutant showed a reduced ability to invade and survive within human cervical epithelial cells, although its ability to form a biofilm on the surface of these cells was not significantly different from that of the wild type. In the presence of copper, the copA mutant exhibited increased sensitivity to killing by nitrite or nitric oxide. Therefore, we concluded that copper ion efflux catalyzed by CopA is linked to the nitrosative stress defense system of Neisseria gonorrhoeae. These observations suggest that copper may exert its effects as an antibacterial agent in the innate immune system via an interaction with reactive nitrogen species