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.

The structure of collagen.

Abstract: During the 1950s Crick made crucial contributions not only to the study of DNA and the genetic code, but to X-ray structure analysis of important biological molecules. He was instrumental in extending helical diffraction theory to construct three-dimensional maps of protein molecules from X-ray data. In particular, he calculated the complicated X-ray diffraction pattern produced by a helix that was itself wound around a second axis into a larger super helix, or coiled coil. In this paper, Crick and Alexander Rich, a visiting physical chemist in the Cavendish laboratory who had studied the structure of RNA with James Watson at the California Institute of Technology, applied helical diffraction theory to deduce the three-chain, coiled coil structure of collagen, a family of extracellular proteins that are a major component of connective tissue and make up one-third of all proteins in the human body. The discovery of the three-dimensional structure of a protein was an important event in molecular biology during the 1950s.

Intracortical inhibition and facilitation in different representations of the human motor cortex.

Abstract: Chen, Robert, Alda Tam, Cathrin Butefisch, Brian Corwell, Ulf Ziemann, John C. Rothwell, and Leonardo G. Cohen. Intracortical inhibition and facilitation in different representations of the human m...

Two classes of cortical gaba neurons defined by differential calcium binding protein immunoreactivities

Abstract: Calcium ions play a key role in many aspects of neuronal behavior and certain calcium binding proteins that may influence this behavior are differentially distributed in the central nervous system. In this study it is shown that immunoreactivity for calbindin-28 and for parvalbumin is localized in separate populations of inhibitory GABA interneurons in all areas of the neocortex of Old World monkeys. Virtually all GABA neurosn show immunoreactivity for one or other calcium binding protein but, except for a few cells in layer IV, GABA cells do not show immunoreactivity for both proteins. Among the two cell populations, parvalbumin immunoreactivity characterizes basket neurons while calbindin immunoreactivity characterizes double bouquet neurons. These findings suggest that the two GABA cell types differ in their regulation of calcium homeostasis and may yield clues to their different roles in intracortical circuitry.

Humanization of a mouse monoclonal antibody by CDR-grafting: the importance of framework residues on loop conformation.

Abstract: A mouse monoclonal antibody (mAb 425) with therapeutic potential was 'humanized' in two ways. Firstly the mouse variable regions from mAb 425 were spliced onto human constant regions to create a chimeric 425 antibody. Secondly, the mouse complementarity-determining regions (CDRs) from mAb 425 were grafted into human variable regions, which were then joined to human constant regions, to create a reshaped human 425 antibody. Using a molecular model of the mouse mAb 425 variable regions, framework residues (FRs) that might be critical for antigen-binding were identified. To test the importance of these residues, nine versions of the reshaped human 425 heavy chain variable (VH) regions and two versions of the reshaped human 425 light chain variable (VL) regions were designed and constructed. The recombinant DNAs coding for the chimeric and reshaped human light and heavy chains were co-expressed transiently in COS cells. In antigen-binding assays and competition-binding assays, the reshaped human antibodies were compared with mouse 425 antibody and to chimeric 425 antibody. The different versions of 425-reshaped human antibody showed a wide range of avidities for antigen, indicating that substitutions at certain positions in the human FRs significantly influenced binding to antigen. Why certain individual FR residues influence antigen-binding is discussed. One version of reshaped human 425 antibody bound to antigen with an avidity approaching that of the mouse 425 antibody.