Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Shells and humans: molluscs and other coastal resources from the earliest human occupations at the Mesolithic shell midden of El Mazo (Asturias, Northern Spain)

Human populations exploited coastal areas with intensity during the Mesolithic in Atlantic Europe, resulting in the accumulation of large shell middens. Northern Spain is one of the most prolific regions, and especially the so-called Asturian area. Large accumulations of shellfish led some scholars to propose the existence of intensification in the exploitation of coastal resources in the region during the Mesolithic. In this paper, shell remains (molluscs, crustaceans and echinoderms) from stratigraphic units 114 and 115 (dated to the early Mesolithic c. 9 kys cal BP) at El Mazo cave (Asturias, northern Spain) were studied in order to establish resource exploitation patterns and environmental conditions. Species representation showed that limpets, top shells and sea urchins were preferentially exploited. One-millimetre mesh screens were crucial in establishing an accurate minimum number of individuals for sea urchins and to determine their importance in exploitation patterns. Environmental conditions deduced from shell assemblages indicated that temperate conditions prevailed at the time of the occupation and the morphology of the coastline was similar to today (rocky exposed shores). Information recovered relating to species representation, collection areas and shell biometry reflected some evidence of intensification (reduced shell size, collection in lower areas of exposed shores, no size selection in some units and species) in the exploitation of coastal resources through time. However, the results suggested the existence of changes in collection strategies and resource management, and periods of intense shell collection may have alternated with times of shell stock recovery throughout the Mesolithic.This research was performed as part of the project “The human response to the global climatic change in a littoral zone: the case of the transition to the Holocene in the Cantabrian coast (10,000–5000 cal BC) (HAR2010-22115-C02-01)” funded by the Spanish Ministry of Economy and Competitiveness. AGE was funded by the University of Cantabria through a predoctoral grant and IGZ was funded by the Spanish Ministry of Economy and Competitiveness through a Juan de la Cierva grant. We also would like to thank the University of Cantabria and the IIIPC for providing support, David Cuenca-Solana, Alejandro García Moreno and Lucia Agudo Pérez for their help. We also thank Jennifer Jones for correcting the English. Comments from two anonymous reviewers helped to improve the paper

We're in this Together: Sensation of the Host Cell Environment by Endosymbiotic Bacteria

Bacteria inhabit diverse environments, including the inside of eukaryotic cells. While a bacterial invader may initially act as a parasite or pathogen, a subsequent mutualistic relationship can emerge in which the endosymbiotic bacteria and their host share metabolites. While the environment of the host cell provides improved stability when compared to an extracellular environment, the endosymbiont population must still cope with changing conditions, including variable nutrient concentrations, the host cell cycle, host developmental programs, and host genetic variation. Furthermore, the eukaryotic host can deploy mechanisms actively preventing a bacterial return to a pathogenic state. Many endosymbionts are likely to use two-component systems (TCSs) to sense their surroundings, and expanded genomic studies of endosymbionts should reveal how TCSs may promote bacterial integration with a host cell. We suggest that studying TCS maintenance or loss may be informative about the evolutionary pathway taken toward endosymbiosis, or even toward endosymbiont-to-organelle conversion.Peer reviewe

Brazilian Abstracts Presented at the American Urological Association Annual Meetings: Contribution, Publication Rates, and Comparison with Oncology Abstracts

Purpose Scientific research originating from Brazil appears to be rising in several medical fields. Research results are often presented at scientific meetings before publication in peer-reviewed journals. We investigated the publication rate of Brazilian studies presented in American Urological Association (AUA) meetings and compared with the rate of publication of Brazilian oncological studies presented at the American Society of Clinical Oncology (ASCO) meetings. Materials and Methods a hand search of 12,454 abstracts presented at aua meetings 2001-2007 was conducted. abstracts for which at least two-thirds of institutions were from brazil were considered as brazilian. final publication was searched in pubmed and lilacs databases. oncological abstracts were also hand searched in the asco meetings proceedings in the same years. Results There was no significant temporal trend in the proportion of AUA studies originating from Brazil along those 7 years. A total of 195 abstracts (1.57%) were from Brazil. One hundred (51.3%) abstracts were published in full, and the estimated 5-year publication rate was 48.2%. There was a progressive increase in publication rates for studies categorized as video, poster, and podium presentations. Considering abstracts presented in years 2001-2005, urologic publication rate was significantly higher than for abstracts presented at the ASCO meeting. Conclusions Our results suggest that the Brazilian contribution to AUA meetings is at a plateau and that the Brazilian literature contribution is greater in urology than in oncology. Efforts must be invested towards raising this plateau and understanding qualitative aspects of the urology scientific output from Brazil

Cluster multi-spacecraft observations of electron and ion holes in the Auroral Acceleration Region

International audienceIn spring 2013, the Cluster spacecraft visited the Auroral Acceleration Region (AAR) for the second and final time. The spacecraft constellation was arranged to produce very small separation magnetic field aligned conjunctions (~10s km) between C3 and C4, with C1 relatively nearby. The goal was to allow study of electron and ion holes, including their propagation between C3 and C4, and their roles in generating waves that may be observed locally and also at C1. Detailed planning work has tried to maximize the opportunities to use the Cluster payload effectively during these conjunctions, but the presence of auroral activity during the relatively few AAR passes could be guaranteed in advance. The dataset may also be valuable for other aspects of auroral science, as data is collected throughout the AAR crossings, not only at the conjunctions. We intend to present first results from this campaign