New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Student Perceptions of a High-Quality Undergraduate Experience: Implications for Teaching and Learning in Natural Resources

Richard Light (2001) recently published what many consider to be one of the most insightful treatments of what students think constitutes a high-quality undergraduate experience and what can be done by the academy to create an environment that fosters this experience. It is based on a decade of research involving interviews with more than 1,600 undergraduates (mostly seniors), with questions designed by more than 60 faculty members from more than 20 colleges and universities, and results shared more widely with more than 90 colleges and universities (suggesting broad applicability). We highlighted Light\u27s ten major findings for the participants (largely faculty) in our facilitated discussion session. Then, using breakout groups, we asked them to reflect on their own experiences relative to these major findings and indicate positive and/or negative aspects of each for undergraduate education in natural resources. Below we state each finding and summarize participant responses

IgG subclass profile of serum antibodies to Leishmania chagasi in naturally infected and vaccinated dogs

Leishmaniosis is a zoonotic disease that is caused by Leishmania chagasi and transmitted by sandflies. In Brazil, canine visceral leishmaniosis (CVL) is an emerging disease in urban areas and dogs are the main reservoir host. The aim of the present study was to analyze IgG seroconversion of dogs to L. chagasi and to determine whether there was dominance of any particular IgG subclasses in this immune response. Antibody detection was performed by ELISA with 120 sera from confirmed seropositive dogs (obtained from epidemiological surveys), 24 samples from naturally infected dogs with clinical signs of the disease, and 40 sera from animals immunized with a commercially available vaccine. Ninety percent of seropositive survey population samples had detectable levels of anti-Leishmania total IgG by ELISA, compared with 70% of samples from symptomatic animals and only 13% of samples from the immunized dogs. The serological response in each group displayed a distinct bias in IgG subclass usage as detected by application of a panel of monoclonal antibodies specific for canine IgG1-IgG4. The survey population, which comprised predominantly asymptomatic dogs, had a dominant IgG1 response, while symptomatic dogs had a mixed pattern of IgG subclass usage. In contrast, sera from vaccinated animals had high titres of IgG2 Leishmania antibody. These distinctive IgG subclass profiles may be related to the infection status of the dogs. Moreover, detection of antigen-specific IgG subclasses may provide a valuable diagnostic tool for predicting the clinical outcome of visceral leishmaniasis, as well as differentiating infected dogs from vaccinated animals. (C) 2009 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

International Study of Health Care Organization and Financing of renal services in England and Wales

Renal replacement therapy, Health expenditures, Financing, organized, Health services, needs and demand, Kidney failure, chronic, United Kingdom, H51, I10, I11, I18,

Genetic insights into biological mechanisms governing human ovarian ageing.

Reproductive longevity is essential for fertility and influences healthy ageing in women &lt;sup&gt;1,2&lt;/sup&gt; , but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations &lt;sup&gt;3&lt;/sup&gt; . The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease