Wolfram Syndrome protein, Miner1, regulates sulphydryl redox status, the unfolded protein response, and Ca2+ homeostasis.

Miner1 is a redox-active 2Fe2S cluster protein. Mutations in Miner1 result in Wolfram Syndrome, a metabolic disease associated with diabetes, blindness, deafness, and a shortened lifespan. Embryonic fibroblasts from Miner1(-/-) mice displayed ER stress and showed hallmarks of the unfolded protein response. In addition, loss of Miner1 caused a depletion of ER Ca(2+) stores, a dramatic increase in mitochondrial Ca(2+) load, increased reactive oxygen and nitrogen species, an increase in the GSSG/GSH and NAD(+)/NADH ratios, and an increase in the ADP/ATP ratio consistent with enhanced ATP utilization. Furthermore, mitochondria in fibroblasts lacking Miner1 displayed ultrastructural alterations, such as increased cristae density and punctate morphology, and an increase in O2 consumption. Treatment with the sulphydryl anti-oxidant N-acetylcysteine reversed the abnormalities in the Miner1 deficient cells, suggesting that sulphydryl reducing agents should be explored as a treatment for this rare genetic disease

tiotropium reduces airflow obstruction in asthma patients independent of body mass index

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Inside Hollins (1954)

https://digitalcommons.hollins.edu/insideh/1007/thumbnail.jp

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Symposium on Obesity and Asthma-November 2006

L’asthme et l’obésité sont fréquemment associés et l’obésité est considérée comme un facteur impliqué tant dans l’augmentation de la sévérité que dans le développement de l’asthme. Ce document est un compte-rendu des présentations effectuées dans le cadre d’un symposium du Réseau en santé respiratoire du Fonds de la recherche en santé du Québec qui a eu lieu à Montréal le 2 novembre 2006, en collaboration avec le McGill University – Strauss Severe Asthma Program, l’Université Laval (Québec) et l’Université de Montréal. Au cours de cette rencontre, divers aspects de la relation entre obésité et asthme ont été abordés, en regard des modèles animaux, des influences génétiques, hormonales et physiologiques, de l’influence des comorbidités (ex : syndrome d’apnée du sommeil), de l’épidémiologie, des aspects cliniques et psychologiques et, enfin, du traitement de l’asthme chez la personne obèse.Asthma and obesity are frequently associated, and obesity has been considered a factor contributing to both an increase in severity of asthma and to its development. The present document summarizes the proceedings of a symposium held in Montreal, Quebec, on November 2, 2006, under the auspices of the Réseau en santé respiratoire du Fonds de la recherche en santé du Québec in collaboration with the McGill University - Strauss Severe Asthma Program, Université Laval (Quebec City) and Université de Montréal. It includes an overview of the various aspects of the relationships between asthma and obesity with regard to animal models; genetic, hormonal and physiological determinants; influence of comorbidities (eg, sleep apnea syndrome); epidemiology; clinical and psychological features; and management of asthma in the obese population