Medical Research Council

About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.

Alleviating Neuropathic Pain Hypersensitivity by Inhibiting PKMζ in the Anterior Cingulate Cortex

Abstract: Synaptic plasticity is a key mechanism for chronic pain It occurs at different levels of the central nervous system, including spinal cord and cortex Studies have mainly focused on signaling proteins that trigger these plastic changes, whereas few have addressed the maintenance of plastic changes related to chronic pain We found that protein kinase M zeta (PKMζ) maintains pain-induced persistent changes in the mouse anterior cingulate cortex (ACC) Peripheral nerve injury caused activation of PKMζ in the ACC, and inhibiting PKMζ by a selective inhibitor, ζ-pseudosubstrate inhibitory peptide (ZIP), erased synaptic potentiation Microinjection of ZIP into the ACC blocked behavioral sensitization These results suggest that PKMζ in the ACC acts to maintain neuropathic pain PKMζ could thus be a new therapeutic target for treating chronic pain

Body mass index, waist circumference, and waist-hip ratio: which is the better discriminator of cardiovascular disease mortality risk? Evidence from an individual-participant meta-analysis of 82,864 participants from nine cohort studies

Abstract: Few studies have examined both the relative magnitude of association and the discriminative capability of multiple indicators of obesity with cardiovascular disease (CVD) mortality risk. We conducted an individual-participant meta-analysis of nine cohort studies of men and women drawn from the British general population resulting in sample of 82 864 individuals. Body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were measured directly. There were 6641 deaths (1998 CVD) during a mean of 8.1 years of follow-up. After adjustment, a one SD higher in WHR and WC was related to a higher risk of CVD mortality (hazard ratio [95% CI]): 1.15 (1.05-1.25) and 1.15 (1.04-1.27), respectively. The risk of CVD mortality also increased linearly across quintiles of both these abdominal obesity markers with a 66% increased risk in the highest quintile of WHR. In age- and sex-adjusted models only, BMI was related to CVD mortality but not in any other analyses. No major differences were revealed in the discrimination capabilities of models with BMI, WC or WHR for cardiovascular or total mortality outcomes. In conclusion, measures of abdominal adiposity, but not BMI, were related to an increased risk of CVD mortality. No difference was observed in discrimination capacities between adiposity markers.

Structure of the rotor of the V-Type Na^+-ATPase from Enterococcus hirae

Abstract: The membrane rotor ring from the vacuolar-type (V-type) sodium ion-pumping adenosine triphosphatase (Na+-ATPase) from Enterococcus hirae consists of 10 NtpK subunits, which are homologs of the 16-kilodalton and 8-kilodalton proteolipids found in other V-ATPases and in F1Fo- or F-ATPases, respectively. Each NtpK subunit has four transmembrane alpha helices, with a sodium ion bound between helices 2 and 4 at a site buried deeply in the membrane that includes the essential residue glutamate-139. This site is probably connected to the membrane surface by two half-channels in subunit NtpI, against which the ring rotates. Symmetry mismatch between the rotor and catalytic domains appears to be an intrinsic feature of both V- and F-ATPases.