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.

Dynein mutations impair autophagic clearance of aggregate-prone proteins.

Abstract: Mutations that affect the dynein motor machinery are sufficient to cause motor neuron disease. It is not known why there are aggregates or inclusions in affected tissues in mice with such mutations and in most forms of human motor neuron disease. Here we identify a new mechanism of inclusion formation by showing that decreased dynein function impairs autophagic clearance of aggregate-prone proteins. We show that mutations of the dynein machinery enhanced the toxicity of the mutation that causes Huntington disease in fly and mouse models. Furthermore, loss of dynein function resulted in premature aggregate formation by mutant huntingtin and increased levels of the autophagosome marker LC3-II in both cell culture and mouse models, compatible with impaired autophagosome-lysosome fusion.

Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment.

Abstract: Gene expression during development and differentiation is regulated in a cell- and stage-specific manner by complex networks of intergenic and intragenic cis-regulatory elements whose numbers and representation in the genome far exceed those of structural genes. Using chromosome conformation capture, it is now possible to analyze in detail the interaction between enhancers, silencers, boundary elements and promoters at individual loci, but these techniques are not readily scalable. Here we present a high-throughput approach (Capture-C) to analyze cis interactions, interrogating hundreds of specific interactions at high resolution in a single experiment. We show how this approach will facilitate detailed, genome-wide analysis to elucidate the general principles by which cis-acting sequences control gene expression. In addition, we show how Capture-C will expedite identification of the target genes and functional effects of SNPs that are associated with complex diseases, which most frequently lie in intergenic cis-acting regulatory elements.

Lay health workers in primary and community health care.

Abstract: BACKGROUND: Lay health workers (LHWs) are widely used to provide care for a broad range of health issues However, little is known about the effectiveness of LHW interventions OBJECTIVES: To assess the effects of LHW interventions in primary and community health care on health care behaviours, patients' health and wellbeing, and patients' satisfaction with care SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care and Consumers and Communication specialised registers (to August 2001); the Cochrane Central Register of Controlled Trials (to August 2001); MEDLINE (1966- August 2001); EMBASE (1966-August 2001); Science Citations (to August 2001); CINAHL (1966-June 2001); Healthstar (1975-2000); AMED (1966-August 2001); the Leeds Health Education Effectiveness Database and the reference lists of articles SELECTION CRITERIA: Randomised controlled trials of any intervention delivered by LHWs (paid or voluntary) in primary or community health care and intended to promote health, manage illness or provide support to patients A 'lay health worker' was defined as any health worker carrying out functions related to health care delivery; trained in some way in the context of the intervention; and having no formal professional or paraprofessional certificated or degreed tertiary education There were no restrictions on the types of consumers DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data onto a standard form and assessed study quality Studies that compared broadly similar types of interventions were grouped together Where feasible, the results of included studies were combined and an estimate of effect obtained MAIN RESULTS: Forty three studies met the inclusion criteria, involving more than 210,110 consumers These showed considerable diversity in the targeted health issue and the aims, content and outcomes of interventions Most were conducted in high income countries (n=35), but nearly half of these focused on low income and minority populations (n=15) Study diversity limited meta-analysis to outcomes for five subgroups (n=15 studies) (LHW interventions to promote the uptake of breast cancer screening, immunisation and breastfeeding promotion [before two weeks and between two weeks and six months post partum] and to improve diagnosis and treatment for selected infectious diseases) Promising benefits in comparison with usual care were shown for LHW interventions to promote immunisation uptake in children and adults (RR=130 [95% CI 114, 148] p=00001) and LHW interventions to improve outcomes for selected infectious diseases (RR=074 [95% CI 058, 093) p=001) LHWs also appear promising for breastfeeding promotion They appear to have a small effect in promoting breast cancer screening uptake when compared with usual care For the remaining subgroups (n=29 studies), the outcomes were too diverse to allow statistical pooling We can therefore draw no general conclusions on the effectiveness of these subgroups of interventions AUTHORS' CONCLUSIONS: LHWs show promising benefits in promoting immunisation uptake and improving outcomes for acute respiratory infections and malaria, when compared to usual care For other health issues, evidence is insufficient to justify recommendations for policy and practice There is also insufficient evidence to assess which LHW training or intervention strategies are likely to be most effective Further research is needed in these areas