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.

Diversity of alpha-fetoprotein gene expression in mice is generated by a combination of separate enhancer elements

Abstract: The 59 flanking region of the mouse alpha-fetoprotein (AFP) gene contains a tissue-specific promoter and three upstream regulatory elements that behave as classical enhancers. At least one of these enhancers is now shown to be required for the tissue-specific expression of the AFP gene when it is introduced into the mouse genome by microinjection of cloned DNA fragments into fertilized eggs. Each enhancer can direct expression in the appropriate tissues, the visceral endoderm of the yolk sac, the fetal liver, and the gastrointestinal tract, but each exerts different influence in these three tissues. These differences may explain the tissue-specific diversity in the levels of expression characteristic of the AFP gene. The postnatal repression of transcription of the AFP gene in both liver and gut, as well as the reinitiation of its transcription during liver regeneration, is mimicked by the introduced gene when it is linked to the enhancer domains together or singly. Thus, the DNA sequence elements responsible for directing the activation of AFP transcription, its repression, and reinduction are contained in a limited segment of DNA within or 59 to the gene (or both) and are operative in the absence of the closely linked albumin gene.

An ACF1-ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin.

Abstract: The mechanism by which the eukaryotic DNA-replication machinery penetrates condensed chromatin structures to replicate the underlying DNA is poorly understood. Here we provide evidence that an ACF1-ISWI chromatin-remodeling complex is required for replication through heterochromatin in mammalian cells. ACF1 (ATP-utilizing chromatin assembly and remodeling factor 1) and an ISWI isoform, SNF2H (sucrose nonfermenting-2 homolog), become specifically enriched in replicating pericentromeric heterochromatin. RNAi-mediated depletion of ACF1 specifically impairs the replication of pericentromeric heterochromatin. Accordingly, depletion of ACF1 causes a delay in cell-cycle progression through the late stages of S phase. In vivo depletion of SNF2H slows the progression of DNA replication throughout S phase, indicating a functional overlap with ACF1. Decondensing the heterochromatin with 5-aza-2-deoxycytidine reverses the effects of ACF1 and SNF2H depletion. Expression of an ACF1 mutant that cannot interact with SNF2H also interferes with replication of condensed chromatin. Our data suggest that an ACF1-SNF2H complex is part of a dedicated mechanism that enables DNA replication through highly condensed regions of chromatin.

Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer--Norfolk prospective study.

Abstract: Background Epidemiologic studies suggest that greater consumption of fruit and vegetables may decrease the risk of diabetes mellitus, but the evidence is limited and inconclusive. Plasma vitamin C level is a good biomarker of fruit and vegetable intake, but, to our knowledge, no prospective studies have examined its association with diabetes risk. This study aims to examine whether fruit and vegetable intake and plasma vitamin C level are associated with the risk of incident type 2 diabetes. Methods We administered a semiquantitative food frequency questionnaire to men and women from a population-based prospective cohort (European Prospective Investigation of Cancer–Norfolk) study who were aged 40 to 75 years at baseline (1993-1997) when plasma vitamin C level was determined and habitual intake of fruit and vegetables was assessed. During 12 years of follow-up between February 1993 and the end of December 2005, 735 clinically incident cases of diabetes were identified among 21 831 healthy individuals. We report the odds ratios of diabetes associated with sex-specific quintiles of fruit and vegetable intake and of plasma vitamin C levels. Results A strong inverse association was found between plasma vitamin C level and diabetes risk. The odds ratio of diabetes in the top quintile of plasma vitamin C was 0.38 (95% confidence interval, 0.28-0.52) in a model adjusted for demographic, lifestyle, and anthropometric variables. In a similarly adjusted model, the odds ratio of diabetes in the top quintile of fruit and vegetable consumption was 0.78 (95% confidence interval, 0.60-1.00). Conclusions Higher plasma vitamin C level and, to a lesser degree, fruit and vegetable intake were associated with a substantially decreased risk of diabetes. Our findings highlight a potentially important public health message on the benefits of a diet rich in fruit and vegetables for the prevention of diabetes.

Association of Weight Gain in Infancy and Early Childhood with Metabolic Risk in Young Adults

Abstract: Context: Early postnatal life has been suggested as an important window during which risks for long-term health may be influenced. Objective: The aim of this study was to examine the independent associations between weight gain during infancy (0–6 months) and early childhood (3–6 yr) with components of the metabolic syndrome in young adults. Design: This was a prospective cohort study (The Stockholm Weight Development Study). Setting: The study was conducted in a general community. Participants: Subjects included 128 (54 males) singletons, followed from birth to 17 yr. Main Outcome Measure: None of these young adults met the full criteria for the metabolic syndrome. We therefore calculated a continuous clustered metabolic risk score by averaging the standardized values of the following components: waist circumference, blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, glucose, and insulin level. Results: Clustered metabolic risk at age 17 yr was predicted by weight gain during in...