Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis

National Institutes of Health grants GM-38765 and P50-DE016191 (C.N.S.), Welcome Trust Programme grant 086867/Z/08/Z (R.J.F. and M.P.) and Project grant 085903/Z/08 (R.J.F.) and Arthritis Research Campaign UK fellowships 18445 and 18103 (to L.V.N. and D.C., respectively). M.S. received a National Research Service Award from the NHLBI (HL087526)

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

VASP: A Volumetric Analysis of Surface Properties Yields Insights into Protein-Ligand Binding Specificity

Many algorithms that compare protein structures can reveal similarities that suggest related biological functions, even at great evolutionary distances. Proteins with related function often exhibit differences in binding specificity, but few algorithms identify structural variations that effect specificity. To address this problem, we describe the Volumetric Analysis of Surface Properties (VASP), a novel volumetric analysis tool for the comparison of binding sites in aligned protein structures. VASP uses solid volumes to represent protein shape and the shape of surface cavities, clefts and tunnels that are defined with other methods. Our approach, inspired by techniques from constructive solid geometry, enables the isolation of volumetrically conserved and variable regions within three dimensionally superposed volumes. We applied VASP to compute a comparative volumetric analysis of the ligand binding sites formed by members of the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains and the serine proteases. Within both families, VASP isolated individual amino acids that create structural differences between ligand binding cavities that are known to influence differences in binding specificity. Also, VASP isolated cavity subregions that differ between ligand binding cavities which are essential for differences in binding specificity. As such, VASP should prove a valuable tool in the study of protein-ligand binding specificity

Interdisciplinary and transdisciplinary research: Finding the common ground of multi-faceted concepts

Inter- and transdisciplinarity are increasingly relevant concepts and practices within academia. While various definitions exist, a clear distinction between inter- and transdisciplinarity remains difficult. Although there is a wide consensus about the need to define and apply these approaches, there is no agreement over definitions. Building on data collected during the first year of the COST Action TD1408 “Interdisciplinarity in research programming and funding cycles” (INTREPID), this paper describes both tensions and common ground about the characteristics and building blocks of interand trans-disciplinarity. Drawing on empirical data from participatory workshops involving INTREPID network members coming from 27 different countries, the paper shows that diverse definitions of inter and trans-disciplinarity coexist within scientific literature and in the mind of researchers and practitioners. The understanding about the involvement of actors outside of academia also differs widely across scientific communities irrespective of disciplinary training or the research subjects. The focus should be on the knowledge that is required to deal with a specific problem, rather than discussing “if” and “how” to integrate actors outside the academia, and collaboration should start with joint problem framing. This diversity is, however, not an absolute obstacle to practice, since the latter is made possible through building blocks such as knowledge domains, problem- and solution- oriented approaches, common goals, as well as target knowledge. In order to move towards more effective inter- and transdisciplinary research, we identify the need for trained interdisciplinarity facilitators and ‘accompanying research’ (derived from the Danish term ‘følgeforskning’). These two roles can be essential to inter- and transdisciplinarity practices including the promotion of reflexivity

Antibacterial and antioxidant effects of five spice and herb extracts as natural preservatives of raw pork

BACKGROUND: The aim of this study was to find natural spice and herb extracts with antibacterial and antioxidant capacities that could be potentially used as natural preservatives in raw pork. RESULTS: The inhibitory effects of cinnamon stick, oregano, clove, pomegranate peel and grape seed extracts on Listeria monocytogenes, Staphylococcus aureus and Salmonella enterica were evaluated in raw pork at room temperature (~20°C). The influences of these extracts on lipid oxidation in the meat were also investigated. The pH, colour parameters and TBARS (thiobarbituric acid-reactive substances) values were tested periodically. The results showed that all five natural extracts, especially clove, were effective against the bacteria. During storage the colour parameters of the extract-treated pork samples changed slightly, in comparison with significant changes in the control. Treatments with these extracts increased the stability of raw pork against lipid oxidation. Clove was the most effective for retarding lipid oxidation and presented the highest antioxidant activity in raw pork. CONCLUSION: This study suggests that the tested extracts, especially clove, have potential as natural preservatives to reduce numbers of pathogenic bacteria, colour degradation and lipid oxidation in raw pork. © 2009 Society of Chemical Industry.link_to_subscribed_fulltex

Experimental heart failure modelled by the cardiomyocyte-specific loss of an epigenome modifier, DNMT3B

Differential DNA methylation exists in the epigenome of end-stage failing human hearts but whether it contributes to disease progression is presently unknown. Here, we report that cardiac specific deletion of Dnmt3b, the predominant DNA methyltransferase in adult mouse hearts, leads to an accelerated progression to severe systolic insufficiency and myocardial thinning without a preceding hypertrophic response. This was accompanied by widespread myocardial interstitial fibrosis and myo-sarcomeric disarray. By targeted candidate gene quantitative RT-PCR, we discovered an over-activity of cryptic splice sites in the sarcomeric gene Myh7, resulting in a transcript with 8 exons missing. Moreover, a region of differential methylation overlies the splice site locus in the hearts of the cardiac-specific conditional knockout (CKO) mice. Although abundant and complex forms of alternative splice variants have been reported in diseased hearts and the contribution of each remains to be understood in further detail, our results demonstrate for the first time that a link may exist between alternative splicing and the cardiac epigenome. In particular, this gives the novel evidence whereby the loss of an epigenome modifier promotes the development and progression of heart disease.status: publishe