Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10 ? ? ). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

Longer-term assessment of trastuzumab-related cardiac adverse events in the Herceptin Adjuvant (HERA) trial

We investigated the incidence of cardiac adverse events in patients with early breast cancer in the Herceptin Adjuvant (HERA) trial who were treated with 1 year of trastuzumab after completion of (neo)adjuvant chemotherapy.

Evidence for selection on coloration in a Panamanian poison frog: a coalescent-based approach

Aim The strawberry poison frog, Oophaga pumilio, has undergone a remarkable radiation of colour morphs in the Bocas del Toro archipelago in Panama. This species shows extreme variation in colour and pattern between populations that have been geographically isolated for < 10,000 years. While previous research has suggested the involvement of divergent selection, to date no quantitative test has examined this hypothesis. Location Bocas del Toro archipelago, Panama. Methods We use a combination of population genetics, phylogeography and phenotypic analyses to test for divergent selection in coloration in O. pumilio. Tissue samples of 88 individuals from 15 distinct populations were collected. Using these data, we developed a gene tree using the mitochondrial DNA (mtDNA) d-loop region. Using parameters derived from our mtDNA phylogeny, we predicted the coalescence of a hypothetical nuclear gene underlying coloration. We collected spectral reflectance and body size measurements on 94 individuals from four of the populations and performed a quantitative analysis of phenotypic divergence. Results The mtDNA d-loop tree revealed considerable polyphyly across populations. Coalescent reconstructions of gene trees within population trees revealed incomplete genotypic sorting among populations. The quantitative analysis of phenotypic divergence revealed complete lineage sorting by colour, but not by body size: populations showed non-overlapping variation in spectral reflectance measures of body coloration, while variation in body size did not separate populations. Simulations of the coalescent using parameter values derived from our empirical analyses demonstrated that the level of sorting among populations seen in colour cannot reasonably be attributed to drift. Main conclusions These results imply that divergence in colour, but not body size, is occurring at a faster rate than expected under neutral processes. Our study provides the first quantitative support for the claim that strong diversifying selection underlies colour variation in the strawberry poison frog.

Mechanisms of species divergence through visual adaptation and sexual selection: Perspectives from a cichlid model system

The theory of ecological speciation suggests that assortative mating evolves most easily when mating preferences are;directly linked to ecological traits that are subject to divergent selection. Sensory adaptation can play a major role in this process,;because selective mating is often mediated by sexual signals: bright colours, complex song, pheromone blends and so on. When;divergent sensory adaptation affects the perception of such signals, mating patterns may change as an immediate consequence.;Alternatively, mating preferences can diverge as a result of indirect effects: assortative mating may be promoted by selection;against intermediate phenotypes that are maladapted to their (sensory) environment. For Lake Victoria cichlids, the visual environment;constitutes an important selective force that is heterogeneous across geographical and water depth gradients. We investigate;the direct and indirect effects of this heterogeneity on the evolution of female preferences for alternative male nuptial colours;(red and blue) in the genus Pundamilia. Here, we review the current evidence for divergent sensory drive in this system, extract;general principles, and discuss future perspectives

Female mating preferences and male coloration covary with water transparency in a Lake Victoria cichlid fish

Rapid speciation in Lake Victoria cichlid fish of the genus Pundamilia may be facilitated by sexual selection: female mate choice exerts sexual selection on male nuptial coloration within species and maintains reproductive isolation between species. However, declining water transparency coincides with increasingly dull coloration and increasing hybridization. In the present study, we investigated the mechanism underlying this pattern in Pundamilia nyererei, a species that interbreeds with a sister species in turbid but not in clear water. We compared measures of intraspecific sexual selection between two populations from locations that differ in water transparency. First, in laboratory mate-choice experiments, conducted in clear water and under broad-spectrum illumination, we found that females originating from turbid water have significantly weaker preferences for male coloration than females originating from clear water. Second, both the hue and body coverage of male coloration differ between populations, which is consistent with adaptation to different photic habitats. These findings suggest that the observed relationship between male coloration and water transparency is not mediated by environmental variation alone. Rather, female mating preferences are indicated to have changed in response to this variation, constituting the first evidence for intraspecific preference-trait co-evolution in cichlid fish. (C) 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 99, 398-406.

Monitoring and Assessment of Desertification and Land Degradation: Knowledge Management, Institutions and Economics: White Paper of the DSD Working Group 3

The White Paper is a review of leading scientific knowledge on the role of knowledge management, institutions and economics in monitoring and assessment of land degradation and desertification. It provides key recommendations for more effective policies and actions for combating desertification both withn the UNCCD and beyond. This White Paper is the result of an international collaboration and consultation led jointly by the Association of DesertNet International and the United Nations University - Institute for Water, Environment and Health (UNU-INWEH), of the Dryland Science for Development Consortium (DSD). The findings were presented at the First UNCCD Scientific Conference held during the COP-9 in Buenos Aires, 2009.

Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV

The prognostic relevance of additional cytogenetic findings at diagnosis of chronic myeloid leukemia (CML) is unclear. The impact of additional cytogenetic findings at diagnosis on time to complete cytogenetic (CCR) and major molecular remission (MMR) and progression-free (PFS) and overall survival (OS) was analyzed using data from 1151 Philadelphia chromosome-positive (Ph(+)) CML patients randomized to the German CML Study IV. At diagnosis, 1003 of 1151 patients (87%) had standard t(9;22)(q34;q11) only, 69 patients (6.0%) had variant t(v;22), and 79 (6.9%) additional cytogenetic aberrations (ACAs). Of these, 38 patients (3.3%) lacked the Y chromosome (-Y) and 41 patients (3.6%) had ACAs except -Y; 16 of these (1.4%) were major route (second Philadelphia [Ph] chromosome, trisomy 8, isochromosome 17q, or trisomy 19) and 25 minor route (all other) ACAs. After a median observation time of 5.3 years for patients with t(9;22), t(v;22), -Y, minor- and major-route ACAs, the 5-year PFS was 90%, 81%, 88%, 96%, and 50%, and the 5-year OS was 92%, 87%, 91%, 96%, and 53%, respectively. In patients with major-route ACAs, the times to CCR and MMR were longer and PFS and OS were shorter (P < .001) than in patients with standard t(9;22). We conclude that major-route ACAs at diagnosis are associated with a negative impact on survival and signify progression to the accelerated phase and blast crisis.

Long-term impact of treated congenital toxoplasmosis on quality of life and visual performance

Background: Long-term evolution of congenital toxoplasmosis is not documented. We assessed the outcome of treated congenital toxoplasmosis in a cohort of adult individuals who had undergone ante- and postnatal treatment to provide information for pediatricians and parents on the evolution of the disease. Methods: We conducted a questionnaire study on 126 adults with congenital toxoplasmosis (mean age: 22.2 years; age range: 18–31 years) monitored regularly until the time of inclusion. The main outcome measures were quality of life (Psychological General Well-Being Index) and visual function (VF14 questionnaire), and the outcomes were correlated with disease-specific factors. Results: Of the 102 patients (80.9%) who were finally included in the study, 12 (11.8%) presented neurologic effects and 60 (58.8%) manifested ocular lesions; in the latter category, 13 individuals (12.7%) had reduced visual function. The overall global quality-of-life score (74.7 ± 14.2) was close to the expected normal range for the general population (73.7 ± 15.3). Overall, visual function was only slightly impaired (M = 97.3; 95% confidence interval, 95.8–98.8). Although disease-independent critical life circumstances were associated with a reduced Psychological General Well-Being Index, this index was not influenced by any of the clinical characteristics of congenital toxoplasmosis. Neurologic pathologies, reduced visual acuity, foveal location of the retinal lesion, and squinting contributed to decreased visual function at follow-up. Conclusions: Our data reveal that treated congenital toxoplasmosis has little effect on the quality of life and visual function of the affected individuals. These encouraging findings may help to alleviate the anxiety of affected individuals and their parents.

European birth cohorts for environmental health research

Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning.

Estimation of physiologic ability and surgical stress score does not predict immediate outcome after pancreatic surgery

The Estimation of Physiologic Ability and Surgical Stress score was designed to predict postoperative morbidity and mortality in general surgery. Our study aims to evaluate its use and accuracy in estimating postoperative outcome after elective pancreatic surgery.

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.