Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Consistent patterns of common species across tropical tree communities

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees

Identification and characterization of QTL controlling Agrobacterium-mediated transient and stable transformation of Brassica oleracea

A commonly encountered difficulty with the genetic engineering of crop plants is that different varieties of a particular species can show great variability in the efficiency with which they can be transformed. This increases the effort required to introduce transgenes into particular genetic backgrounds. The use of Substitution Lines has allowed the finer mapping of three Quantitative Trait Loci (tf1, tf2 and tf3) that explain 26% of the variation in the efficiency of Agrobacterium-mediated transformation in Brassica oleracea. Use of an ‘orthogonal set’ of genotypes (containing all eight possible combinations of ‘positive’ and ‘negative’ alleles at the three QTL), along with time course studies of transgene expression, has allowed the determination of the stages at which these genes have their effects during transformation. With regard to control of the level of transient transgene expression, tf1 (on LGO1) alone has no detectable effect, whilst tf2 (on LGO3) and tf3 (on LGO7) have highly significant effects (P \u3c 0.001). All three loci have highly significant (P \u3c 0.001) effects on the levels of expression of stably integrated transgene. The use of RFLP markers has shown that tf1 and tf2 are in duplicated regions of the B. oleracea genome and appear to be paralogous in origin. Colinearity of these regions with the A. thaliana genome has been identified. The results allow the selection of progeny Brassica oleracea genotypes that are more efficiently transformed than either parent used in the original cross

Modeling nonresponse in multiwave panel studies using discrete-time Markov models

Abstract. Nonresponse is of major concern to social scientists, due to the possibility of selectiv-ity: not all groups in the population are equally represented in the final sample, when some groups have a larger probability to be in the sample than others. It is dangerous to base conclusions on such biased samples. Therefore, it is of importance to study nonresponse patterns. First it is shown that a decreasing nonresponse for every successive wave indicates that nonre-sponse is selective to a degree. Successively we discuss how Markov models can be used to get some idea of the seriousness of this bias in the sample, by examining how many chains are needed to reproduce the observed pattern of nonresponse acceptably well, and what the probability is that members of these chains will participate in a particular wave of the study. A small application is given, after which the implications of the findings are discussed. 1

Description of mandibular finite helical axis pathways in asymptomatic subjects.

Despite wide use of systems to record jaw motion with six degrees of freedom, most studies have analyzed only the movement of a single mandibular point. The finite helical axis (FHA) is a mathematical model which can be used to describe comprehensively the movements of a rigid body. The aim of this investigation was to describe the FHA of the mandible during habitual jaw movements. Thirty subjects (13 females, 17 males; mean age, 26 years; range, 18 to 34 years) without myoarthropathies of the masticatory system participated in the study. Opening and closing movements, performed at 1-Hz frequency, were recorded with the optoelectronic system Jaws-3D. Three opening and closing movements were recorded from the right side and three from the left side of the jaw. The movement data were low-pass-filtered for noise reduction prior to the computation of the finite helical axis by means of a software program developed in our laboratory. The following parameters were calculated: the rotation of the FHA, its spatial orientation, and the translation along it, as well as its position and distance relative to an intracondylar point. In addition, methodological errors of the model were calculated. During opening and closing, the group mean FHA rotation was 24.3 degrees +/- 4.2 degrees. The group mean of the maximum total translation along the FHA was 0.9 +/- 0.7 mm. The group mean distance between the FHA and the intracondylar point was 48.9 +/- 9.9 mm. The FHA pathways were smooth and varied between individuals. Furthermore, the finite helical axes were never localized within the condyle, and often were located outside of the mandible. The analysis of the FHA pathways yields more information on whole mandibular movements than simply the movements of a single condylar point

Fitotoxicidade de três antibióticos na cultura in vitro de abacateiro Phytotoxicity of three antibiotics to avocado tissue culture

Desenvolveram-se dois experimentos para verificar o efeito do ácido nalidíxico, do cloranfenicol e da estreptomicina sobre a cultura in vitro do abacateiro 'Ouro Verde'. No primeiro, testou-se a influência de diversas concentrações (0, 12,5, 25, 50, 100 e 200 mg/L) desses antibióticos sobre a calogênese de discos foliares e, no segundo, o efeito sobre a brotação de gemas de segmentos nodais. Enquanto a formação de calos foi reduzida à metade com o uso de 50 mg/L de cloranfenicol, sua massa foi drasticamente reduzida já na concentração de 12,5 mg/L. Restringiu-se o comprimento das brotações, adicionando os antibióticos ao meio de cultura, concluindo-se que os três foram tóxicos para o abacateiro, sendo recomendados apenas em casos de extrema necessidade, dependendo da suscetibilidade do microorganismo contaminante e da concentração necessária para seu controle.<br>Two experiments were carried out in order to verify the toxicity of nalidixic acid, chloramphenicol and streptomycin to avocado 'Ouro Verde' in vitro culture. In the first experiment, it was tested the effect of the antibiotics to callus initiation on leave explants, using a concentration range of 0, 12.5, 25, 50, 100 and 200 mg/L. In the second experiment, sprouting from nodal segments were tested. The callus formation was reduced by 50% with 50 mg/L of chloramphenicol and the highest reduction in callus weight was observed with 12.5 mg/L. The length of sprouts was reduced by incorporating antibiotics into plant growth medium. Results showed that the three antibiotics were toxic to avocado, and they must be used only in real necessity cases, depending on the bacterial susceptibility and the adequate concentration to control the contaminants

EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow&apos;s milk, hen&apos;s egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd