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.

Fetal origins of adult disease—the hypothesis revisited

Abstract: The idea that stimuli or insults during critical or sensitive periods in early life can have lifetime consequences is well established in developmental biology and has been termed “programming.”1 The first evidence for programming, obtained over 100 years ago, confirmed the critical period for imprinting in birds.2 Programming stimuli may be generated endogenously (for instance, internal hormonal signals3) or they may be environmental. One important type of environmental programming is that induced by early nutrition. Since McCance's studies in the 1960s on the long term effects of early nutrition in rats,4 numerous animal studies have shown that nutrition in infancy or fetal life can induce lifetime effects on metabolism, growth, and neurodevelopment and on major disease processes such as hypertension, diabetes, atherosclerosis, and obesity.5–8 If these phenomena applied in humans, it would be a matter of major public health and clinical importance. #### Summary points The hypothesis that adult disease has fetal origins is plausible, but much supportive evidence is flawed by incomplete and incorrect statistical interpretation When size in early life is related to later health outcomes only after adjustment for current size, it is probably the change in size between these points (postnatal centile crossing) rather than fetal biology that is implicated Even when birth size is directly related to later outcome, some studies fail to explore whether this is partly or wholly explained by postnatal rather that prenatal factors These considerations are critical to understanding the biology and timing of “programming,” the direction of future research, and future public health interventions The considerable research focused on early programming of adult outcomes in humans has taken two approaches: experimental, using early randomised nutritional interventions with prospective follow up (an approach that we have favoured9), and observational. Inferences from data based on observational approaches …

Single domain ligands, receptors comprising said ligands, methods for their production, and use of said ligands and receptors

Abstract: The present invention relates to single domain ligands derived from molecules in the immunoglobulin (Ig) superfamily, receptors comprising at least one such ligand, methods for cloning, amplifying and expressing DNA sequences encoding such ligands, preferably using the polymerase chain reaction, methods for the use of said DNA sequences in the production of Ig-type molecules and said ligands or receptors, and the use of said ligands or receptors in therapy, diagnosis or catalysis.

Mutational signatures associated with tobacco smoking in human cancer

Abstract: Tobacco smoking increases the risk of at least 17 classes of human cancer. We analyzed somatic mutations and DNA methylation in 5243 cancers of types for which tobacco smoking confers an elevated risk. Smoking is associated with increased mutation burdens of multiple distinct mutational signatures, which contribute to different extents in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens. Others likely reflect indirect activation of DNA editing by APOBEC cytidine deaminases and of an endogenous clocklike mutational process. Smoking is associated with limited differences in methylation. The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence for this mechanism is lacking in some smoking-related cancer types.

Comparative genomics of trypanosomatid parasitic protozoa.

Abstract: A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that-along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions-have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.