We have used microseconds of molecular dynamics simulations with explicit solvent to investigate the unfolding process of human lens gamma D-crystallin protein and its isolated domains. A partially unfolded folding intermediate of gamma D-crystallin is detected in simulations with its C-terminal domain (C-td) folded and N-terminal domain (N-td) unstructured,
in excellent agreement with biochemical experiments. Our simulations strongly indicate that the stability and the folding mechanism of the N-td are regulated by the interdomain interactions, consistent with experimental observations. A hydrophobic folding core was identified within the C-td that is comprised of a and b strands from the Greek key motif 4, the one near the domain interface. Detailed analyses reveal a surprising non-native EPZ 6438 surface salt-bridge between Glu135 and Arg142 located at the end of the ab SB202190 molecular weight folded hairpin turn playing a critical role in stabilizing the folding core. On the other hand, an in silico single E135A substitution that disrupts this non-native Glu135-Arg142 salt-bridge causes significant destabilization to the folding core of the isolated C-td, which, in turn, induces unfolding of the N-td interface. These findings indicate
that certain highly conserved charged residues, that is, Glu135 and Arg142, of gamma D-crystallin are crucial for stabilizing its hydrophobic domain interface in native conformation, and disruption of charges on the gamma D-crystallin surface might lead to unfolding and subsequent aggregation.”
“Purpose: We describe current trends in robotic and open radical prostatectomy in the United States after examining case logs for American Board of Urology
certification.
Materials and Methods: American urologists submit case logs for initial board certification and recertification. We analyzed logs from 2004 to 2010 for trends and used logistic regression to assess the I-BET-762 cost impact of urologist age on robotic radical prostatectomy use.
Results: A total of 4,709 urologists submitted case logs for certification between 2004 and 2010. Of these logs 3,374 included 1 or more radical prostatectomy cases. Of the urologists 2,413 (72%) reported performing open radical prostatectomy only while 961 (28%) reported 1 or more robotic radical prostatectomies and 308 (9%) reported robotic radical prostatectomy only. During this 7-year period we observed a large increase in the number of urologists who performed robotic radical prostatectomy and a smaller corresponding decrease in those who performed open radical prostatectomy. Only 8% of patients were treated with robotic radical prostatectomy by urologists who were certified in 2004 while 67% underwent that procedure in 2010.