Anti-CASP9 monoclonal antibody

Residue contact map is essential for protein three-dimensional structure determination. But most of the current contact prediction methods based on residue co-evolution suffer from high false-positives as introduced by indirect and transitive contacts (i.e., residues A-B and B-C are in contact, but A-C are not). Built on the work by Feizi et al. (Nat Biotechnol 2013; 31:726-733), which demonstrated a general network model to distinguish direct dependencies by network deconvolution, this study presents a new balanced network deconvolution (BND) algorithm to identify optimized dependency matrix without limit on the eigenvalue range in the applied network systems. The algorithm was used to filter contact predictions of five widely used co-evolution methods. On the test of proteins from three benchmark datasets of the 9th critical assessment of protein structure prediction (CASP9), CASP10, and PSICOV (precise structural contact prediction using sparse inverse covariance estimation) database experiments, the BND can improve the medium- and long-range contact predictions at the L/5 cutoff by 55.59% and 47.68%, respectively, without additional central processing unit cost. The improvement is statistically significant, with a P-value<5.93 x 10(-3) in the Student's t-test. A further comparison with the ab initio structure predictions in CASPs showed that the usefulness of the current co-evolution-based contact prediction to the three-dimensional structure modeling relies on the number of homologous sequences existing in the sequence databases. BND can be used as a general contact refinement method, which is freely available at http://www.csbio.sjtu.edu.cn/bioinf/BND/. Proteins 2015; 83:485-496. (c) 2014 Wiley Periodicals, Inc.

Carbon monoxide (CO) is a vasoactive molecule that is generated by vascular cells as a by-product of heme catabolism and it plays an important physiological role in circulation system. In order to investigate whether exogenous CO can mediate the growth and proliferation of vascular cells, in this study, we used 250 parts per million (ppm) of CO to treat human umbilical artery smooth muscle cell (hUASMC) and human umbilical vein endothelial cell (HuVEC) and further evaluated the growth and apoptosis status of SMC and HuVEC. After SMC and HuVEC were exposed to CO for 7-day, the growth of SMC and HuVEC was significantly inhibited by CO in vitro on day 5 of CO exposure. And CO blocked cell cycle progress of SMC and HuVEC, more SMC and HuVEC stagnated at G0/G1 phase by flow cytometric analysis. Moreover, CO treatment inhibited SMC and HuVEC apoptosis caused by hydrogen peroxide through decreasing caspase 3 and 9 activities. To confirm the molecular mechanism of CO effect on SMC and HuVEC growth, we compared the gene expression profile in SMC and CO-treated SMC, HuVEC and CO-treated HuVEC. By microarray analysis, we found the expression level of some genes which are related to cell cycle regulation, cell growth and proliferation, and apoptosis were changed during CO exposure. We further identified that the down-regulated CDK2 contributed to arresting cell growth and the down-regulated Caspase 3 (CASP3) and Caspase 9 (CASP9) were associated with the inhibition of cell apoptosis. Therefore, CO exerts a certain growth arrest on SMC and HuVEC by inhibiting cell cycle transition from G0/G1 phase to S phase and has regulatory effect on cell apoptosis by regulating the expression of apoptosis-associated genes.