Relationship between protein O -linked glycosylation and insulin-stimulated glucose transport in rat skeletal muscle following calorie restriction or exposure to O -(2-acetamido-2-deoxy-d-glucopyranosylidene)amino- N -phenylcarbamate

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65566/1/j.1365-201X.2004.01403.x.pd

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Coastal climate is associated with elevated solar irradiance and higher 25(OH)D level

This is the author’s version of a work that was accepted for publication in Environment International. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Environment International, and can be accessed via the DOI in this record.INTRODUCTION: There is evidence that populations living close to the coast have improved health and wellbeing. Coastal environments are linked to promotion of physical activity through provision of safe, opportune, aesthetic and accessible spaces for recreation. Exposure to coastal environments may also reduce stress and induce positive mood. We hypothesised that coastal climate may influence the vitamin D status of residents and thus partly explain benefits to health. MATERIALS AND METHODS: Ecological and cross-sectional analyses were designed to elucidate the connection between coastal residence and vitamin D status. We divided residential data, from developed land use areas and the Lower Super Output Areas or Data Zones (Scotland) of the 1958 Birth Cohort participants, into the following coastal bands: 50km. This relationship was modified by latitude with settlements at a lower latitude exhibiting a greater effect. Individuals living closer to the coast in England had higher vitamin D levels than those inland, particularly in autumn. CONCLUSION: Geographic location may influence biochemistry and health outcomes due to environmental factors. This can provide benefits in terms of vitamin D status but may also pose a risk due to higher skin cancer risk. We provide further evidence in support of the claim that coastal environments can provide opportunities for health and wellbeing.European Social Fund Convergence Programme for Cornwall and the Isles of Scilly.European Regional Development Fund Programme 2007 to 201