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.

Philip Cowen papers undated, 1873-1935

Contains primarily correspondence and published material in English, German and Russian relating to anti-Semitism in Russia and Roumania, the Russian passport question, loans from Jewish bankers to the Russian government and immigration from Eastern Europe, especially Russia, to the United States. Includes also correspondence concerning Jewish welfare institutions and agricultural colonies in the United States and the National Farm School in Doylestown, Pa. Also contains correspondence relating to and drafts of articles for the American Hebrew, particularly the Emma Lazarus memorial number, and correspondence relating to the publication of the Jewish encyclopedia and to survey on anti-Semitism conducted in 1890, as well as information on the Jews in China and material relating to Count Arthur Cherep-Spiridovich.

Averting biodiversity collapse in tropical forest protected areas

The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon(1-3). With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses(4-9). As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world's major tropical regions. Our analysis reveals great variation in reserve `health': about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.

Chemical Exposures of Women Workers in the Plastics Industry with Particular Reference to Breast Cancer and Reproductive Hazards.

Despite concern about the harmful effects of substances contained in various
plastic consumer products, little attention has focused on the more heavily
exposed women working in the plastics industry. Through a review of the
toxicology, industrial hygiene, and epidemiology literatures in conjunction
with qualitative research, this article explores occupational exposures in producing
plastics and health risks to workers, particularly women, who make up
a large part of the workforce. The review demonstrates that workers are
exposed to chemicals that have been identified as mammary carcinogens and
endocrine disrupting chemicals, and that the work environment is heavily
contaminated with dust and fumes. Consequently, plastics workers have a
body burden that far exceeds that found in the general public.

Structural-Functional Studies of Burkholderia cenocepacia D-Glycero-beta-D-manno-heptose 7-Phosphate Kinase (HldA) and Characterization of Inhibitors with Antibiotic Adjuvant and Antivirulence Properties

As an essential constituent of the outer membrane of Gram-negative bacteria, lipopolysaccharide contributes significantly to virulence and antibiotic resistance. The lipopolysaccharide biosynthetic pathway therefore serves as a promising therapeutic target for antivirulence drugs and antibiotic adjuvants. Here we report the structural-functional studies of D-glycero-beta-D-manno-heptose 7-phosphate kinase (HldA), an absolutely conserved enzyme in this pathway, from Burkholderia cenocepacia. HldA is structurally similar to members of the PfkB carbohydrate kinase family and appears to catalyze heptose phosphorylation via an in-line mechanism mediated mainly by a conserved aspartate, Asp270. Moreover, we report the structures of HldA in complex with two potent inhibitors in which both inhibitors adopt a folded conformation and occupy the nucleotide-binding sites. Together, these results provide important insight into the mechanism of HldA-catalyzed heptose phosphorylation and necessary information for further development of HldA inhibitors.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

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.

Contribution d'experts, à l'aide de l'Internet, au développement des compétences discursives d'élèves de 6e année

Ce projet de recherche de type quasi-expérimental visait à favoriser le développement de compétences discursives chez des élèves de 6e année par l'application d'une démarche d'écriture associée à l'échange entre pairs et avec des experts. Les éléments discursifs d'un texte font référence à la capacité de juger la qualité d'un texte à partir de critères de cohérence, de structure et d'organisation des idées ainsi qu'à partir de composantes liées au respect du lecteur et de l'intention d'écriture. Trente-neuf élèves provenant d'un milieu socio-économique moyen ont participé à l'expérimentation alors que quarante-trois élèves composaient le groupe témoin. Tous les groupes d'élèves présentaient un niveau académique faible à moyen en français écrit. Dans le cadre de cette expérimentation, trois situations d'écriture ont été réalisées au cours d'une même année scolaire. Pour chacune de ces situations d'écriture, les élèves du groupe expérimental devaient écrire un texte et utiliser les questions-guides de la démarche proposée pour diriger leur attention sur les aspects discursifs du texte. Au cours de la démarche, les élèves participaient à des échanges de commentaires avec leurs pairs quant à la qualité de leur texte. Douze experts provenant des domaines du journalisme, de l'enseignement et de la littérature fournissaient des rétroactions aux élèves quant à la qualité de leur texte sur le plan discursif.

Revue critique d'histoire et de littérature / publiée sous la direction de MM. P. Meyer, Ch. Morel, G. Paris, H. Zotenberg

1873/01 (A7)-1873/06.

Revue critique d'histoire et de littérature / publiée sous la direction de MM. P. Meyer, Ch. Morel, G. Paris, H. Zotenberg

1873/07 (A7)-1873/12.

Revue d'anthropologie / publiée sous la dir. du Dr. Paul Broca

1873 (T2).

Revue française d'histoire d'outre-mer / Société française d'histoire d'outre-mer

1926/04 (A14)-1926/06.

Revue française d'histoire d'outre-mer / Société française d'histoire d'outre-mer

1917 (A5).