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.

Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner.

Abstract: The role of transcription factors in regulating the development of midbrain dopaminergic (mDA) neurons is intensively studied owing to the involvement of these neurons in diverse neurological disorders. Here we demonstrate novel roles for the forkhead/winged helix transcription factors Foxa1 and Foxa2 in the specification and differentiation of mDA neurons by analysing the phenotype of Foxa1 and Foxa2 single- and double-mutant mouse embryos. During specification, Foxa1 and Foxa2 regulate the extent of neurogenesis in mDA progenitors by positively regulating Ngn2 (Neurog2) expression. Subsequently, Foxa1 and Foxa2 regulate the expression of Nurr1 (Nr4a2) and engrailed 1 in immature neurons and the expression of aromatic l-amino acid decarboxylase and tyrosine hydroxylase in mature neurons during early and late differentiation of midbrain dopaminergic neurons. Interestingly, genetic evidence indicates that these functions require different gene dosages of Foxa1 and Foxa2. Altogether, our results demonstrate that Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner.

Interventions to promote cycling: systematic review

Abstract: Objectives To determine what interventions are effective in promoting cycling, the size of the effects of interventions, and evidence of any associated benefits on overall physical activity or anthropometric measures. Design Systematic review. Data sources Published and unpublished reports in any language identified by searching 13 electronic databases, websites, reference lists, and existing systematic reviews, and papers identified by experts in the field. Review methods Controlled “before and after” experimental or observational studies of the effect of any type of intervention on cycling behaviour measured at either individual or population level. Results Twenty five studies (of which two were randomised controlled trials) from seven countries were included. Six studies examined interventions aimed specifically at promoting cycling, of which four (an intensive individual intervention in obese women, high quality improvements to a cycle route network, and two multifaceted cycle promotion initiatives at town or city level) were found to be associated with increases in cycling. Those studies that evaluated interventions at population level reported net increases of up to 3.4 percentage points in the population prevalence of cycling or the proportion of trips made by bicycle. Sixteen studies assessing individualised marketing of “environmentally friendly” modes of transport to interested households reported modest but consistent net effects equating to an average of eight additional cycling trips per person per year in the local population. Other interventions that targeted travel behaviour in general were not associated with a clear increase in cycling. Only two studies assessed effects of interventions on physical activity; one reported a positive shift in the population distribution of overall physical activity during the intervention. Conclusions Community-wide promotional activities and improving infrastructure for cycling have the potential to increase cycling by modest amounts, but further controlled evaluative studies incorporating more precise measures are required, particularly in areas without an established cycling culture. Studies of individualised marketing report consistent positive effects of interventions on cycling behaviour, but these findings should be confirmed using more robust study designs. Future research should also examine how best to promote cycling in children and adolescents and through workplaces. Whether interventions to promote cycling result in an increase in overall physical activity or changes in anthropometric measures is unclear.

Myosin VIIa Participates in Opsin Transport through The Photoreceptor Cilium

Abstract: Two types of Usher syndrome, a blindness–deafness disorder, result from mutations in the myosin VIIa gene. As for most other unconventional myosins, little is known about the function or functions of myosin VIIa. Here, we studied the photoreceptor cells of mice with mutant myosin VIIa by electron immunomicroscopy and microscopic autoradiography. We found evidence that myosin VIIa functions in the connecting cilium of each photoreceptor cell and participates in the transport of opsin through this structure. These findings provide the first direct evidence that opsin travels along the connecting cilium en route to the outer segment. They demonstrate that a myosin may function in a cilium and suggest that abnormal opsin transport might contribute to blindness in Usher syndrome.