Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge.

Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).

A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol.

Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ∼25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.

Ocorrência de fungos endofíticos "dark septate" em raízes de Oryza glumaepatula na Amazônia

O objetivo deste trabalho foi avaliar a ocorrência de fungos endofíticos "dark septate" (DSEF) em Oryza glumaepatula, na Amazônia, e sua capacidade de colonização in vitro. Foram coletadas plantas de O. glumaepatula em área de cerrado e de mata em Roraima. As raízes foram tratadas para a observação de hifas melanizadas septadas e de microescleródios. Os fungos foram isolados em meio ágar malte. Os DSEF foram observados em plantas coletadas em ambos os ambientes, com maior colonização nas coletadas da mata. Um isolado foi capaz de colonizar o hospedeiro original e também plantas de Oryza sativa, exibindo as estruturas características de DSEF em plantas de arroz saudáveis.

Dissecting the compression of mortality in Switzerland, 1876-2005

This paper aims to examine changes in common longevity and variability of the adult life span, and attempts to answer whether or not the compression of mortality continues in Switzerland in the years 1876-2005. The results show that the negative relationships between the large increase in the adult modal age at death, observed at least from the 1920s, and the decrease in the standard deviation of the ages at deaths occurring above it, illustrate a significant compression of adult mortality. Typical adult longevity increased by about 10% during the last fifty years in Switzerland, and adult heterogeneity in the age at death decreased in the same proportion. This analysis has not found any evidence suggesting that we are approaching longevity limits in term of modal or even maximum life spans. It ascertains a slowdown in the reduction of adult heterogeneity in longevity, already observed in Japan and other low mortality countries.

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest

Over the past two decades, several fungal outbreaks have occurred, including the high-profile 'Vancouver Island' and 'Pacific Northwest' outbreaks, caused by Cryptococcus gattii, which has affected hundreds of otherwise healthy humans and animals. Over the same time period, C. gattii was the cause of several additional case clusters at localities outside of the tropical and subtropical climate zones where the species normally occurs. In every case, the causative agent belongs to a previously rare genotype of C. gattii called AFLP6/VGII, but the origin of the outbreak clades remains enigmatic. Here we used phylogenetic and recombination analyses, based on AFLP and multiple MLST datasets, and coalescence gene genealogy to demonstrate that these outbreaks have arisen from a highly-recombining C. gattii population in the native rainforest of Northern Brazil. Thus the modern virulent C. gattii AFLP6/VGII outbreak lineages derived from mating events in South America and then dispersed to temperate regions where they cause serious infections in humans and animals.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

Dietas artificiais para a criação de larvas e adultos da mosca-das-frutas sul-americana

O objetivo deste trabalho foi adequar as dietas artificiais para o desenvolvimento dos estágios de larva e adulto da mosca-das-frutas sul-americana (Anastrepha fraterculus). Para o estágio larval, foram testadas as seguintes dietas: D1, original, com 10 g de ágar; D2, modificada, com 3,6 g de ágar; e, D3, modificada, com bagaço seco de cana-de-açúcar. Para os adultos, foram testadas quatro dietas: A, levedura de cerveja + mel (2:1); B, açúcar refinado + extrato de levedura + gérmen de trigo cru (3:1:1); C, extrato de soja + açúcar mascavo + gérmen de trigo cru (3:1:1); e D, levedura seca de cervejaria + mel (2:1). Avaliaram-se os parâmetros biológicos de duração do período ovo-pupa, duração e viabilidade do estágio de pupa, massa média de pupas, razão sexual e duração e viabilidade do período ovo-adulto. O desenvolvimento larval em D1 e D2 foi semelhante e indicou que a criação de larvas pode ser realizada com 1/3 da quantidade de ágar da utilizada em D1. A utilização do bagaço seco de cana-de-açúcar, na dieta artificial, afetou negativamente o desenvolvimento larval. As dietas artificiais com levedura de cerveja + mel e com açúcar refinado + extrato de levedura + gérmen de trigo cru são as mais adequadas para a criação de adultos.

Complete DNA sequence of Kuraishia capsulata illustrates novel genomic features among budding yeasts (Saccharomycotina)

The numerous yeast genome sequences presently available provide a rich source of information for functional as well as evolutionary genomics but unequally cover the large phylogenetic diversity of extant yeasts. We present here the complete sequence of the nuclear genome of the haploid-type strain of Kuraishia capsulata (CBS1993(T)), a nitrate-assimilating Saccharomycetales of uncertain taxonomy, isolated from tunnels of insect larvae underneath coniferous barks and characterized by its copious production of extracellular polysaccharides. The sequence is composed of seven scaffolds, one per chromosome, totaling 11.4 Mb and containing 6,029 protein-coding genes, ~13.5% of which being interrupted by introns. This GC-rich yeast genome (45.7%) appears phylogenetically related with the few other nitrate-assimilating yeasts sequenced so far, Ogataea polymorpha, O. parapolymorpha, and Dekkera bruxellensis, with which it shares a very reduced number of tRNA genes, a novel tRNA sparing strategy, and a common nitrate assimilation cluster, three specific features to this group of yeasts. Centromeres were recognized in GC-poor troughs of each scaffold. The strain bears MAT alpha genes at a single MAT locus and presents a significant degree of conservation with Saccharomyces cerevisiae genes, suggesting that it can perform sexual cycles in nature, although genes involved in meiosis were not all recognized. The complete absence of conservation of synteny between K. capsulata and any other yeast genome described so far, including the three other nitrate-assimilating species, validates the interest of this species for long-range evolutionary genomic studies among Saccharomycotina yeasts.

Premenopausal serum androgens and breast cancer risk: a nested case-control study.

ABSTRACT: INTRODUCTION: Prospective epidemiologic studies have consistently shown that levels of circulating androgens in postmenopausal women are positively associated with breast cancer risk. However, data in premenopausal women are limited. METHODS: A case-control study nested within the New York University Women's Health Study was conducted. A total of 356 cases (276 invasive and 80 in situ) and 683 individually-matched controls were included. Matching variables included age and date, phase, and day of menstrual cycle at blood donation. Testosterone, androstenedione, dehydroandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) were measured using direct immunoassays. Free testosterone was calculated. RESULTS: Premenopausal serum testosterone and free testosterone concentrations were positively associated with breast cancer risk. In models adjusted for known risk factors of breast cancer, the odds ratios for increasing quintiles of testosterone were 1.0 (reference), 1.5 (95% confidence interval (CI), 0.9 to 2.3), 1.2 (95% CI, 0.7 to 1.9), 1.4 (95% CI, 0.9 to 2.3) and 1.8 (95% CI, 1.1 to 2.9; Ptrend = 0.04), and for free testosterone were 1.0 (reference), 1.2 (95% CI, 0.7 to 1.8), 1.5 (95% CI, 0.9 to 2.3), 1.5 (95% CI, 0.9 to 2.3), and 1.8 (95% CI, 1.1 to 2.8, Ptrend = 0.01). A marginally significant positive association was observed with androstenedione (P = 0.07), but no association with DHEAS or SHBG. Results were consistent in analyses stratified by tumor type (invasive, in situ), estrogen receptor status, age at blood donation, and menopausal status at diagnosis. Intra-class correlation coefficients for samples collected from 0.8 to 5.3 years apart (median 2 years) in 138 cases and 268 controls were greater than 0.7 for all biomarkers except for androstenedione (0.57 in controls). CONCLUSIONS: Premenopausal concentrations of testosterone and free testosterone are associated with breast cancer risk. Testosterone and free testosterone measurements are also highly reliable (that is, a single measurement is reflective of a woman's average level over time). Results from other prospective studies are consistent with our results. The impact of including testosterone or free testosterone in breast cancer risk prediction models for women between the ages of 40 and 50 years should be assessed. Improving risk prediction models for this age group could help decision making regarding both screening and chemoprevention of breast cancer.

Evaluation d'un Espace de Prévention dans le cadre du Festival de Jazz de Montreux 2001: la Scène Bleue

L'initiative Scène Bleue (SB) se veut un espace, lieu de rencontre de jeunes adolescents âgés de 10 à 18 ans, dans le cadre de l'édition 2001 du Festival de Jazz de Montreux. Il s'agit de proposer une série d'animations permettant de faire la fête sans consommation de substances (légales et/ou illégales). Ce document fait l'historique du projet et de l'évaluation conduite par l'IUMSP. Cette évaluation comprend trois volets, correspondant à des temps différents : 1. Avant - documenter la perception des objectifs et les attentes des jeunes et des animateurs, avant le démarrage du projet SB. 2. Pendant - analyser la réalisation du projet in situ et recueillir informations et réactions auprès de la clientèle de la SB. 3. Après - examiner l'évolution des perceptions des différents acteurs, après le festival. Les résultats peuvent être résumés comme suit : la SB a rencontré un vif succès. La démonstration a été faite que le public concerné pouvait être attiré par un lieu avec des interdits relatifs à la consommation de substances : ainsi l'objectif de prévention primaire ciblant des jeunes âgés de 13 ans en moyenne a été atteint. Les visiteurs plus âgés, moins impliqués, ont malgré tout pu réaliser que faire la fête sans alcool ni drogues était possible. Le projet peut à l'avenir être consolidé en définissant des objectifs et des stratégies de prévention explicites. La participation des jeunes à cette entreprise collective partagée avec les animateurs et les reponsables peut être sollicitée davantage, notamment pour ce qui est de l'organisation et des choix concrets relatifs aux diverses animations. [Résumé]

Interrelation among Economic Growth, Income Inequality, and Fiscal Performance: Evidence from Anglo-Saxon Countries

The interrelation among economic growth, income inequality, and fiscal performance is very complex. The paper provides the analysis of the interrelations among these variables jointly by the structural VAR methodology, examining also transmission channels among them. This approach allows exploring dynamic interactions among them and feedback effects on each other. The empirical analysis is implemented for the Anglo-Saxon countries, the UK, the USA, and Canada. We find that income inequality has negative effect on economic growth in the case of the UK. The effect is positive in the cases of the USA and Canada. The increase in income inequality worsens fiscal performance for all the countries