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.

cAMP-dependent signaling as a core component of the mammalian circadian pacemaker.

Abstract: The mammalian circadian clockwork is modeled as transcriptional and posttranslational feedback loops, whereby circadian genes are periodically suppressed by their protein products. We show that adenosine 3',5'-monophosphate (cAMP) signaling constitutes an additional, bona fide component of the oscillatory network. cAMP signaling is rhythmic and sustains the transcriptional loop of the suprachiasmatic nucleus, determining canonical pacemaker properties of amplitude, phase, and period. This role is general and is evident in peripheral mammalian tissues and cell lines, which reveals an unanticipated point of circadian regulation in mammals qualitatively different from the existing transcriptional feedback model. We propose that daily activation of cAMP signaling, driven by the transcriptional oscillator, in turn sustains progression of transcriptional rhythms. In this way, clock output constitutes an input to subsequent cycles.

Detecting epistasis in human complex traits

Abstract: Genome-wide association studies (GWASs) have become the focus of the statistical analysis of complex traits in humans, successfully shedding light on several aspects of genetic architecture and biological aetiology. Single-nucleotide polymorphisms (SNPs) are usually modelled as having additive, cumulative and independent effects on the phenotype. Although evidently a useful approach, it is often argued that this is not a realistic biological model and that epistasis (that is, the statistical interaction between SNPs) should be included. The purpose of this Review is to summarize recent directions in methodology for detecting epistasis and to discuss evidence of the role of epistasis in human complex trait variation. We also discuss the relevance of epistasis in the context of GWASs and potential hazards in the interpretation of statistical interaction terms.

Face mask use and control of respiratory virus transmission in households.

Abstract: Many countries are stockpiling face masks for use as a nonpharmaceutical intervention to control virus transmission during an influenza pandemic. We conducted a prospective cluster-randomized trial comparing surgical masks, non–fit-tested P2 masks, and no masks in prevention of influenza-like illness (ILI) in households. Mask use adherence was self-reported. During the 2006 and 2007 winter seasons, 286 exposed adults from 143 households who had been exposed to a child with clinical respiratory illness were recruited. We found that adherence to mask use significantly reduced the risk for ILI-associated infection, but <50% of participants wore masks most of the time. We concluded that household use of face masks is associated with low adherence and is ineffective for controlling seasonal respiratory disease. However, during a severe pandemic when use of face masks might be greater, pandemic transmission in households could be reduced. Many countries are stockpiling face masks for use as nonpharmaceutical interventions to reduce viral transmission during an influenza pandemic. We conducted a prospective cluster-randomized trial comparing surgical masks, non–fit-tested P2 masks, and no masks in prevention of influenza-like illness (ILI) in households. During the 2006 and 2007 winter seasons, 286 exposed adults from 143 households who had been exposed to a child with clinical respiratory illness were recruited. Intent-to-treat analysis showed no significant difference in the relative risk of ILI in the mask use groups compared with the control group; however, <50% of those in the mask use groups reported wearing masks most of the time. Adherence to mask use was associated with a significantly reduced risk of ILI-associated infection. We concluded that household use of masks is associated with low adherence and is ineffective in controlling seasonal ILI. If adherence were greater, mask use might reduce transmission during a severe influenza pandemic.