Matrix metalloproteinase 2 overexpression and prognosis in colorectal cancer: a meta-analysis

Many studies investigated the relationship between matrix metalloproteinase 2 (MMP-2) overexpression and survival in patients with colorectal cancer (CRC), but yielded inconsistent results. To derive a more precise estimate of the prognostic significance of MMP-2 overexpression, we reviewed published studies and carried out a meta-analysis. Eligible articles were identified for the period up to March 2012 in electronic databases. To evaluate the correlation between MMP-2 overexpression and the prognosis in CRC, pooled hazard ratio (HR) and its 95?% confidence interval (95?% CI) for poorer overall and progression-free survival were appropriately derived from fixed-effects or random-effects models using standard meta-analysis techniques. Thirteen studies with a total of 1,919 CRC patients stratifying overall survival (OS) and/or progression-free survival in CRC patients by MMP-2 expression status were eligible for analysis. Ten studies investigated the OS in a total of 1,612 cases with CRC, and five studies investigated the progression-free survival in a total of 508 patients CRC. The combined HR estimate for OS and progression-free survival was 1.74 (95?% CI, 1.34?C2.26) and 1.35 (95?% CI, 1.07?C1.80), respectively. Both subgroup analyses and sensitivity analysis further identified the prognostic role of MMP-2 overexpression in patients with CRC. There was no evidence for publication bias. In conclusion, MMP-2 overexpression is associated with poorer overall and progression-free survival in patients with CRC.     

An estimation of Canadian population exposure to cosmic rays from air travel

Based on air travel statistics in 1984, it was estimated that less than 4 % of the population dose from cosmic ray exposure would result from air travel. In the present study, cosmic ray doses were calculated for more than 3,000 flights departing from more than 200 Canadian airports using actual flight profiles. Based on currently available air travel statistics, the annual per capita effective dose from air transportation is estimated to be 32 μSv for Canadians, about 10 % of the average cosmic ray dose received at ground level (310 μSv per year).     

Association study between of Tie2/Angiopoietin-2 and VEGF/KDR pathway gene polymorphisms and vascular malformations

Vascular malformations (VMs) are common congenital and neonatal dysmorphogenesis. VMs mostly occur sporadically with a few exceptions of inheritability. Tie2/angiopoietins-2 (Ang-2) and VEGF/KDR pathways are known to be involved in normal and pathogenic angiogenesis. Our study was aimed to test the contribution of these pathway gene variants to VMs. A total of 8 variants were found among 103 VM patients and 142 healthy controls. These variants comprised rs638203, rs639225, rs80338908 and rs80338909 in Tie2 gene, rs1870377 and rs2305949 in KDR gene, rs79337921 and rs34590960 in ANTXR1 gene. Our results indicated that rs638203 (p = 0.029) and rs639225 (p = 0.018) in Tie2 gene were associated with VM. A further bioinformatics analysis suggested the rs638203-G and rs639225-G might cause an abnormal splicing of Tie2 gene into to a defective protein. Our results identified two novel Tie2 gene polymorphisms with genetic susceptibility to VMs, although future functional validation of the two polymorphisms is warranted in the future.     

水稻Rop基因OsRac5表达特性

Rop在植物生长、发育、免疫及环境信号应答等多种生物学过程中具有重要作用。已有研究显示水稻Rop基因OsRac5可能与育性控制有关,但是该基因的表达特性,以及非生物胁迫和植物生长物质对其表达的影响尚不清楚。本文采用qRT-PCR技术检测了OsRac5在水稻生长发育过程中、非生物胁迫以及植物生长物质处理条件下的表达特性,结果显示OsRac5在水稻生长发育过程中在多种组织广泛表达,尤其在根和雌雄蕊形成期的幼穗中高表达;干旱、高盐和低温等非生物胁迫均能诱导OsRac5表达;ABA、GAs、6-BA等植物生长物质能上调OsRac5基因表达,提示该基因与水稻幼穗发育、抗逆性及细胞生长等过程相关。     

π–π Stacking mediated drug–drug interactions in human CYP2E1

Because of having many low molecular mass substrates, CYP2E1 is of particular interests to the pharmaceutical industry. Many evidences showed that this enzyme can adopt multiple substrates to significantly reduce the oxidation rate of the substrates. The detailed mechanism for this observation is still unclear. In the current study, we employed GPU‐accelerated molecular dynamics simulations to study the multiple‐binding mode of human CYP2E1, with an aim of offering a mechanistic explanation for the unexplained multiple‐substrate binding. Our results showed that Thr303 and Phe478 were key factors for the substrate recognition and multiple‐substrate binding. The former can form a significant hydrogen bond to recognize and position the substrate in the productive binding orientation in the active site. The latter acted as a mediator for the substrate communications via π–π stacking interactions. In the multiple‐binding mode, the aforementioned π–π stacking interactions formed by the aromatic rings of both substrates and Phe478 drove the first substrate far away from the catalytic center, orienting in an additional binding position and going against the substrate metabolism. All these findings could give atomic insights into the detailed mechanism for the multiple‐substrate binding in human CYP2E1, providing useful information for the drug metabolism mechanism and personalized use of clinical drugs. Proteins 2013; © 2012 Wiley Periodicals, Inc.     

Amyloid aggregation of lysozyme: The synergy study of red wine polyphenols

The amyloidoses are diseases associated with nonnative folding of proteins and characterized by the presence of protein amyloid aggregates. The ability of quercetin, resveratrol, caffeic acid, and their equimolar mixtures to affect amyloid aggregation of hen egg white lysozyme in vitro was detected by Thioflavin T fluorescence assay. The anti‐amyloid activities of tested polyphenols were evaluated by the median depolymerization concentrations DC₅₀ and median inhibition concentrations IC₅₀. Single substances are more efficient (by at least one order) in the depolymerization of amyloid aggregates assay than in the inhibition of the amyloid formation with IC₅₀ in 10^?4 to 10^?5M range. Analyzed mixture samples showed synergic or antagonistic effects in both assays. DC₅₀ values ranged from 10^?5 to 10^?8M and IC₅₀ from 10^?5 to 10^?9M, respectively. We observed that certain mixtures of studied polyphenols can synergistically inhibit production of amyloids aggregates and are also effective in depolymerization of the aggregates. Synergic or antagonistic effects of studied mixtures were correlated with protein–small ligand docking studies and AFM results. Differences in these activities could be explained by binding of each polyphenol to a different amino acid sequence within the protein. Our results indicate that synergic/antagonistic anti‐amyloid effects of studied mixtures depend on the selective binding of polyphenols to the known amyloidogenic sequences in the lysozyme chain. Our findings of the effective reduction of amyloid aggregation of lysozyme by polyphenol mixtures in vitro are of the utter physiological relevance considering the bioavailability and low toxicity of tested phenols. Proteins 2013; © 2012 Wiley Periodicals, Inc.     

Isolation and metagenomic characterization of bacteria associated with calcium carbonate and struvite precipitation in a pure moving bed biofilm reactor-membrane bioreactor

A bench-scale pure moving bed bioreactor-membrane bioreactor (MBBR-MBR) used for the treatment of urban wastewater was analyzed for the identification of bacterial strains with the potential capacity for calcium carbonate and struvite biomineral formation. Isolation of mineral-forming strains on calcium carbonate and struvite media revealed six major colonies with a carbonate or struvite precipitation capacity in the biofouling on the membrane surface and showed that heterotrophic bacteria with the ability to precipitate calcium carbonate and struvite constituted ~7.5% of the total platable bacteria. These belonged to the genera Lysinibacillus, Trichococcus, Comamomas and Bacillus. Pyrosequencing analysis of the microbial communities in the suspended cells and membrane biofouling showed a high degree of similarity in all the samples collected with respect to bacterial assemblage. The study of operational taxonomic units (OTUs) identified through pyrosequencing suggested that ~21% of the total bacterial community identified in the biofouling could potentially form calcium carbonate or struvite crystals in the pure MBBR-MBR system used for the treatment of urban wastewater.     

Molecular Dynamics Study on Protein and it's Water Structure at High Pressure

Abstract

We have performed NPT molecular dynamics simulations (Langevin Piston Method) on two types of solvated proteins-‘denaturation-unfavorable’ protein (insulin) and ‘denaturation-favorable protein’ (ribonuclease A) at high pressure (from 1 bar up to 20 kbar). The method is based on the extended system formalism introduced by Andersen, where the deterministic equations of motion for the piston degree of freedom are replaced by Langevin equation. We report the structural changes of proteins (ribonuclease A and insulin) and water molecules through radius of gyration, solvent accessible surface area, hydrogen bond pattern, and the topology of water clusters connected by the hydrogen bonded circular network. The solvent accessibility of ribonuclease A is mainly decreased by hydrophilic residues rather than hydrophobic residues under high pressure. From the results of hydrogen bond analysis, we have found that α-helix is more stable than β-sheet under high pressure. In addition, from the analysis of the water cluster, we have observed that for ribonuclease A, 5-membered ring structure is more favorable than 6-membered ring at higher pressure. However, for insulin, the ratio of 5 to 6-ring is constant over the pressure ranges for which we have performed MD simulation. This indicates that the water structure around insulin does not change under high pressure.