Lifetimes of excited states in 16C as a benchmark for ab initio developments

Lifetimes of higher-lying states (2+ 2 and 4+ 1 ) in 16C have been measured, employing the Gammasphere and Microball detector arrays, as key observables to test and refine ab initio calculations based on interactions developed within chiral Effective Field Theory. The presented experimental constraints to these lifetimes of τ(2+ 2 ) = [ 244, 446] fs and τ(4+ 1 ) = [1.8, 4] ps, combined with previous results on the lifetime of the 2+ 1 state of 16C, provide a rather complete set of key observables to benchmark the theoretical developments.We present No-Core Shell-Model calculations using state-of-the-art chiral 2- (NN) and 3-nucleon (3N) interactions at next-to-next-to-next-to-leading order for both the NN and the 3N contributions and a generalized natural-orbital basis (instead of the conventional harmonicoscillator single-particle basis) which reproduce, for the first time, the experimental findings remarkably well. The level of agreement of the new calculations as compared to the CD-Bonn meson-exchange NN interaction is notable and presents a critical benchmark for theory

The long-term survival chances of young massive star clusters

We review the long-term survival chances of young massive star clusters (YMCs), hallmarks of intense starburst episodes often associated with violent galaxy interactions. We address the key question as to whether at least some of these YMCs can be considered proto-globular clusters (GCs), in which case these would be expected to evolve into counterparts of the ubiquitous old GCs believed to be among the oldest galactic building blocks. In the absence of significant external perturbations, the key factor determining a cluster's long-term survival chances is the shape of its stellar initial mass function (IMF). It is, however, not straightforward to assess the IMF shape in unresolved extragalactic YMCs. We discuss in detail the promise of using high-resolution spectroscopy to make progress towards this goal, as well as the numerous pitfalls associated with this approach. We also discuss the latest progress in worldwide efforts to better understand the evolution of entire cluster systems, the disruption processes they are affected by, and whether we can use recently gained insights to determine the nature of at least some of the YMCs observed in extragalactic starbursts as proto-GCs. We conclude that there is an increasing body of evidence that GC formation appears to be continuing until today; their long-term evolution crucially depends on their environmental conditions, however.Comment: invited refereed review article; ChJA&A, in press; 33 pages LaTeX (2 postscript figures); requires chjaa.cls style fil

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

Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways

Insomnia is the second most prevalent mental disorder, with no sufficient treatment available. Despite substantial heritability, insight into the associated genes and neurobiological pathways remains limited. Here, we use a large genetic association sample (n = 1,331,010) to detect novel loci and gain insight into the pathways, tissue and cell types involved in insomnia complaints. We identify 202 loci implicating 956 genes through positional, expression quantitative trait loci, and chromatin mapping. The meta-analysis explained 2.6% of the variance. We show gene set enrichments for the axonal part of neurons, cortical and subcortical tissues, and specific cell types, including striatal, hypothalamic, and claustrum neurons. We found considerable genetic correlations with psychiatric traits and sleep duration, and modest correlations with other sleep-related traits. Mendelian randomization identified the causal effects of insomnia on depression, diabetes, and cardiovascular disease, and the protective effects of educational attainment and intracranial volume. Our findings highlight key brain areas and cell types implicated in insomnia, and provide new treatment targets

Fibrocartilage Tissue Engineering: The Role of the Stress Environment on Cell Morphology and Matrix Expression

Although much is known about the effects of uniaxial mechanical loading on fibrocartilage development, the stress fields to which fibrocartilaginous regions are subjected to during development are mutiaxial. That fibrocartilage develops at tendon-to-bone attachments and in compressive regions of tendons is well established. However, the three-dimensional (3D) nature of the stresses needed for the development of fibrocartilage is not known. Here, we developed and applied an in vitro system to determine whether fibrocartilage can develop under a state of periodic hydrostatic tension in which only a single principal component of stress is compressive. This question is vital to efforts to mechanically guide morphogenesis and matrix expression in engineered tissue replacements. Mesenchymal stromal cells in a 3D culture were exposed to compressive and tensile stresses as a result of an external tensile hydrostatic stress field. The stress field was characterized through mechanical modeling. Tensile cyclic stresses promoted spindle-shaped cells, upregulation of scleraxis and type one collagen, and cell alignment with the direction of tension. Cells experiencing a single compressive stress component exhibited rounded cell morphology and random cell orientation. No difference in mRNA expression of the genes Sox9 and aggrecan was observed when comparing tensile and compressive regions unless the medium was supplemented with the chondrogenic factor transforming growth factor beta3. In that case, Sox9 was upregulated under static loading conditions and aggrecan was upregulated under cyclic loading conditions. In conclusion, the fibrous component of fibrocartilage could be generated using only mechanical cues, but generation of the cartilaginous component of fibrocartilage required biologic factors in addition to mechanical cues. These studies support the hypothesis that the 3D stress environment influences cell activity and gene expression in fibrocartilage development

Genome-wide study identifies association between HLA-B∗55:01 and Self-Reported Penicillin Allergy

Hypersensitivity reactions to drugs are often unpredictable and can be life threatening, underscoring a need for understanding their underlying mechanisms and risk factors. The extent to which germline genetic variation influences the risk of commonly reported drug allergies such as penicillin allergy remains largely unknown. We extracted data from the electronic health records of more than 600,000 participants from the UK, Estonian, and Vanderbilt University Medical Center’s BioVU biobanks to study the role of genetic variation in the occurrence of self-reported penicillin hypersensitivity reactions. We used imputed SNP to HLA typing data from these cohorts to further fine map the human leukocyte antigen (HLA) association and replicated our results in 23andMe’s research cohort involving a total of 1.12 million individuals. Genome-wide meta-analysis of penicillin allergy revealed two loci, including one located in the HLA region on chromosome 6. This signal was further fine-mapped to the HLA-B∗55:01 allele (OR 1.41 95% CI 1.33–1.49, p value 2.04 × 10−31) and confirmed by independent replication in 23andMe’s research cohort (OR 1.30 95% CI 1.25–1.34, p value 1.00 × 10−47). The lead SNP was also associated with lower lymphocyte counts and in silico follow-up suggests a potential effect on T-lymphocytes at HLA-B∗55:01. We also observed a significant hit in PTPN22 and the GWAS results correlated with the genetics of rheumatoid arthritis and psoriasis. We present robust evidence for the role of an allele of the major histocompatibility complex (MHC) I gene HLA-B in the occurrence of penicillin allergy

Ovo em pó na alimentação de leitões recém-desmamados Spray-dried egg for wealing pigs

Foram realizados dois experimentos para determinar a composição química, os coeficientes de digestibilidade de nutrientes e os valores de energia e proteína digestíveis do ovo em pó (OP) e avaliar o desempenho e os componentes sangüíneos e plasmáticos de leitões alimentados com dietas contendo OP. No Experimento I, foram utilizados oito leitões em um ensaio de digestibilidade. Os animais foram distribuídos em dois tratamentos e quatro repetições, sendo uma ração referência e uma teste (70% da ração referência + 30% de OP). Utilizou-se a metodologia da coleta parcial de fezes (0,5% de Cr2O3). Os coeficientes de digestibilidade aparente do OP foram de 80,81; 87,14; 82,00 e 70,55%, respectivamente, para a matéria seca, energia bruta, proteína bruta e extrato etéreo. A partir dos coeficientes de digestibilidade determinados e os valores de proteína bruta (56,53%) e energia bruta (5.897 kcal/kg), foram calculados os valores de 43,90% de proteína digestível e 5.140 kcal/kg de energia digestível para o OP. No Experimento II, foram utilizados 90 animais desmamados com 24 dias e 5,6 kg. Os tratamentos consistiram de cinco rações isonutritivas com níveis crescentes (0, 25, 50, 75 e 100%) de substituição protéica do plasma sangüíneo (PS) da dieta pelo OP. O delineamento experimental foi o de blocos casualizados, com nove repetições por tratamento. Não houve diferença entre os tratamentos para as variáveis de desempenho na fase de 1-14 dias pós-desmame. Para a fase de 15-28 dias e para o período total, foi observada redução linear do GDP e CDR, com o aumento do nível de inclusão da proteína do OP. Para as variáveis dos componentes plasmáticos e sangüíneos não foram observadas diferenças significativas entre os tratamentos. Em função dos resultados obtidos, não foi viável a substituição do plasma sangüíneo pelo ovo em pó nas dietas de leitões durante a fase de creche.<br>Two experiments were carried out to determine the chemical composition, nutrients digestibility and digestible energy and protein of spray-dried egg (OP) and to study the performance and plasma and blood components of weanling pigs fed diets containing OP. In the Experiment I, eight pigs were used for digestibility assay. The animals were assigned to two treatments and four replications/treatment. The treatments consisted of a basal diet and test diet (70% of basal diet + 30% of OP). The method was the partial faeces collection (0.5% Cr2O3). The apparent digestibility coefficients of dry matter, gross energy, crude protein and crude fat were, respectively, 80.81, 87.14, 82.00, and 70.55%. From the results of apparent digestibility coeficients and the values of crude protein (56.53%) and gross energy (5,897 kcal/kg), values of 43.90% of digestible protein and 5,140 kcal/kg of digestible energy for OP were calculated. In the Experiment II, ninety pigs were weaned at 24 days of age with 5.6 kg live weight. The treatments consisted of five dietary levels of 0, 25, 50, 75 and 100%, as a replacement of plasma (PS) protein for OP protein. Pigs were alloted to a randomized block design with nine replications per treatment. No treatment effects were observed on performance for 1-14 day post-weaning phase. For the 15-28 d phase and for the total period, linear reductions of GDP and CDR were observed, as the dietary OP levels increased. No treatment effects were observed on plasma and blood components by the inclusion of spray-dried egg. It was not recommended to replace the PS by OP in nursery diets

Author correction: GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia liability

Several occurrences of the word 'schizophrenia' have been re-worded as 'liability to schizophrenia' or 'schizophrenia risk', including in the title, which should have been "GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability", as well as in Supplementary Figures 1-10 and Supplementary Tables 7-10, to more accurately reflect the findings of the work