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.

New susceptibility locus for coronary artery disease on chromosome 3q22.3

Abstract: We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in similar to 25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 x 10(-13); OR = 1.15, 95% CI = 1.11-1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 x 10(-7); OR = 1.08, 95% CI = 1.05-1.11).

Separate neural subsystems within `Wernicke's area'

Abstract: Over time, both the functional and anatomical boundaries of 'Wernicke's area' have become so broad as to be meaningless. We have re-analysed four functional neuroimaging (PET) studies, three previously published and one unpublished, to identify anatomically separable, functional subsystems in the left superior temporal cortex posterior to primary auditory cortex. From the results we identified a posterior stream of auditory processing. One part, directed along the supratemporal cortical plane, responded to both non-speech and speech sounds, including the sound of the speaker's own voice. Activity in its most posterior and medial part, at the junction with the inferior parietal lobe, was linked to speech production rather than perception. The second, more lateral and ventral part lay in the posterior left superior temporal sulcus, a region that responded to an external source of speech. In addition, this region was activated by the recall of lists of words during verbal fluency tasks. The results are compatible with an hypothesis that the posterior superior temporal cortex is specialized for processes involved in the mimicry of sounds, including repetition, the specific role of the posterior left superior temporal sulcus being to transiently represent phonetic sequences, whether heard or internally generated and rehearsed. These processes are central to the acquisition of long- term lexical memories of novel words.

Validation of a Three-Stage Compound Continuous Culture System for Investigating the Effect of Retention Time on the Ecology and Metabolism of Bacteria in the Human Colon

Abstract: A three-stage compound continuous culture system was used to study the effect of retention time (27.1 and 66.7 h) on the catabolism of organic carbon and nitrogen sources in mixed populations of human colonic bacteria. The fermentation system was designed to reproduce spatial, temporal, nutritional, and physicochemical characteristics of the microbiota in the proximal (vessel 1) and distal (vessels 2 and 3) colons, and was validated on the basis of chemical and microbiological measurements on intestinal contents obtained from human sudden death victims. Results showed that the majority of carbohydrate breakdown and short-chain fatty acid production occurred in V1. Conversely, dissimilatory amino acid metabolism, as evidenced by formation of branched-chain fatty acids and phenolic compounds, occurred primarily in V2 and V3. Fermentation of aromatic amino acids was strongly affected by system retention time (R), with concentrations of phenolic metabolites being three times higher in V3, at 66.7 h, compared to 27.1 h. Bacteriological measurements of intestinal contents, in which nine groups of marker organisms were studied, showed that, with the exception of bifidobacteria, no major differences in relative bacterial cell numbers were evident in the proximal and distal colons. These organisms were also studied in the continuous culture system, where marked reductions in Escherichia coli were observed in V2 and V3, especially at R= 27.1 h. Increasing R to 66.7 h reduced numbers of Clostridium perfringens, anaerobic Gram-positive cocci, and total anaerobe counts. Correlations between in vivo chemical and bacteriological measurements and data obtained in vitro demonstrate that the three-stage fermentation system provided a useful model for studying the physiology and ecology of large intestinal microorganisms under different nutritional and environmental conditions.

Infectious HIV-1 assembles in late endosomes in primary macrophages.

Abstract: Although human immunodeficiency virus type 1 (HIV-1) is generally thought to assemble at the plasma membrane of infected cells, virions have been observed in intracellular compartments in macrophages Here, we investigated virus assembly in HIV-1–infected primary human monocyte-derived macrophages (MDM) Electron microscopy of cryosections showed virus particles, identified by their morphology and positive labeling with antibodies to the viral p17, p24, and envelope proteins, in intracellular vacuoles Immunolabeling demonstrated that these compartments contained the late endosomal marker CD63, which was enriched on vesicles within these structures and incorporated into the envelope of budding virions The virus-containing vacuoles were also labeled with antibodies against LAMP-1, CD81, and CD82, which were also incorporated into the viral envelope To assess the cellular source of infectious viruses derived from MDM, virus-containing media from infected cells were precipitated with specific antibodies Only antibodies against antigens found in late endosomes precipitated infectious virus, whereas antibodies against proteins located primarily on the cell surface did not Our data indicate that most of the infectious HIV produced by primary macrophages is assembled on late endocytic membranes and acquires antigens characteristic of this compartment This notion has significant implications for understanding the biology of HIV and its cell–cell transmission

Early development of adiposity and insulin resistance after catch-up weight gain in small-for-gestational-age children.

Abstract: Context and Objective: Low birth weight followed by rapid postnatal weight gain is associated with long-term risks for central obesity and insulin resistance. However, the timing of these changes is unclear. Setting, Design, and Patients: This was a longitudinal cohort study in low birth weight (SGA; birth weight < −2 sd; n = 29) and normal birth weight (AGA; n = 22) children from Barcelona. Main Outcome Measures: Body composition, by dual-energy x-ray absorptiometry scan, and insulin sensitivity, assessed longitudinally at ages 2, 3, and 4 yr, were measured. Results: Mean height, weight, and body mass index at ages 2, 3, and 4 yr were not different between SGA and AGA children. At age 2 yr, SGA children had similar body composition but were more insulin sensitive than AGA children and had lower serum IGF-I levels and lower neutrophil counts. Between ages 2 and 4 yr, despite similar gains in weight and body mass index, SGA children gained more abdominal fat and body adiposity and less lean mass than AGA c...