Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors

Objectives—To identify SNPs associated with switching from an ACE-inhibitor to an angiotensin receptor blocker (ARB). Methods—Two cohorts of patients starting ACE-inhibitors were identified within the Rotterdam Study in the Netherlands and the GoDARTS study in Scotland. Cases were intolerant subjects who switched from an ACE-inhibitor to an ARB, controls were subjects who used ACE-inhibitors continuously for at least 2 years and did not switch. GWAS using an additive model was run in these sets and results were meta-analysed using GWAMA. Results—972 cases out of 5 161 ACE-inhibitor starters were identified. 8 SNPs within 4 genes reached the GWAS significance level (P<5×10-8) in the meta-analysis (RBFOX3, GABRG2, SH2B1 and MBOAT1). The strongest associated SNP was located in an intron of RBFOX3, which contains a RNA binding protein (rs2061538: MAF=0.16, OR=1.52[95%CI: 1.32-1.76], p=6.2x10-9). Conclusions—These results indicate that genetic variation in abovementioned genes may increase the risk of ACE-inhibitors induced adverse reactions

Increased Risk of Breast Cancer Associated with CC Genotype of Has-miR-146a Rs2910164 Polymorphism in Europeans

Background: Emerging evidence suggests that microRNAs play a critical role in the pathogenesis of breast cancer. Several molecular epidemiological studies were conducted in recent years to evaluate the association between has-miR-146a rs2910164 polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. Methodology/Principal findings: We performed a meta-analysis of 6 case-control studies that included 4238 breast-cancer cases and 4469 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95 % confidence intervals (CIs). Overall, this meta-analysis showed that the rs2910164 polymorphism was not associated with a significantly increased risk of breast cancer in all genetic models (for GC vs GG: OR = 1.00, 95 % CI = 0.9021.09, Pheterpgeneity = 0.364; for CC vs GG: OR=1.16, 95 % CI=0.9821.36, P heterpgeneity =0.757; for GC+CC vs GG: OR=1.02, 95 % CI=0.9321.12, Pheterpgeneity = 0.562; for CC vs GC+GG: OR = 1.10, 95 % CI = 0.9621.26, Pheterpgeneity = 0.441). However, in the stratified analysis by ethnicity, we found the rs2910164 polymorphism was associated with increased breast cancer risk among Europeans in homozygote comparison (CC vs. GG: OR = 1.29, 95%CI = 1.0221.63, Pheterpgeneity = 0.950, P = 0.032) and recessive model (CC vs. GC+GG: OR = 1.31, 95%CI = 1.0521.65, P heterpgeneity = 0.839, P = 0.019). No publication bias was found in the present study

Forest carbon sequestration:the impact of forest management

In this chapter, we describe alternative ways in which forests and forestry can help to mítigate climate change, along with the potential impact of these activities. The three carbon storage compartments should be considered inall impact estimates. Carbon content in living biomass is easily estimated via species-specific equations or by applying factors to oven-dry biomass weights (e.g.,lbañez et al.,2002, Herrero et al.,2011,Castaño and Bravo, 2012).Litter carbon content has been analysed in many studies on primary forest productivity, though information regarding the influence of forest management on litter carbon content is less abundant (Blanco et al., 2006). In the last decade,efforts have been made to assess soil carbon in forests, but studies on the effect of forest management on soils show discrepancies (Lindner and Karjalainen,2007).Hoover (2011), for example,found no difference in forest floor carbon stocks among stands subjected to partial or complete harvest treatments in the United States.Instituto Universitario de Gestión Forestal Sostenibl

Roles of glial cells in synapse development

Brain function relies on communication among neurons via highly specialized contacts, the synapses, and synaptic dysfunction lies at the heart of age-, disease-, and injury-induced defects of the nervous system. For these reasons, the formation—and repair—of synaptic connections is a major focus of neuroscience research. In this review, I summarize recent evidence that synapse development is not a cell-autonomous process and that its distinct phases depend on assistance from the so-called glial cells. The results supporting this view concern synapses in the central nervous system as well as neuromuscular junctions and originate from experimental models ranging from cell cultures to living flies, worms, and mice. Peeking at the future, I will highlight recent technical advances that are likely to revolutionize our views on synapse–glia interactions in the developing, adult and diseased brain

The Mouse Cytomegalovirus Gene m42 Targets Surface Expression of the Protein Tyrosine Phosphatase CD45 in Infected Macrophages

The receptor-like protein tyrosine phosphatase CD45 is expressed on the surface of cells of hematopoietic origin and has a pivotal role for the function of these cells in the immune response. Here we report that following infection of macrophages with mouse cytomegalovirus (MCMV) the cell surface expression of CD45 is drastically diminished. Screening of a set of MCMV deletion mutants allowed us to identify the viral gene m42 of being responsible for CD45 down-modulation. Moreover, expression of m42 independent of viral infection upon retroviral transduction of the RAW264.7 macrophage cell line led to comparable regulation of CD45 expression. In immunocompetent mice infected with an m42 deletion mutant lower viral titers were observed in all tissues examined when compared to wildtype MCMV, indicating an important role of m42 for viral replication in vivo. The m42 gene product was identified as an 18 kDa protein expressed with early kinetics and is predicted to be a tailanchored membrane protein. Tracking of surface-resident CD45 molecules revealed that m42 induces internalization and degradation of CD45. The observation that the amounts of the E3 ubiquitin ligases Itch and Nedd4 were diminished in cells expressing m42 and that disruption of a PY motif in the N-terminal part of m42 resulted in loss of function, suggest that m42 acts as an activator or adaptor for these Nedd4-like ubiquitin ligases, which mark CD45 for lysosomal degradation. In conclusion, the down-modulation of CD45 expression in MCMV-infected myeloid cells represents a novel pathway of virus-host interaction

Predictive Control Using Fuzzy Models

This paper presents an algorithm for predictive control using fuzzy models.This strategy is a Predictive Control Strategy for Nonlinear systems. The algorithm takes advantage of the already well known methods for linear systems (like Generalized Predictive Control). Analysis of the modified algorithm is presented and performance comparisons are shown. The performance comparisons are made using a model of a chemical process (Continuous Stirring Tank Reactor) where noise and uncertainties are included