A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection

There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining and homologous recombination. Here we identify and characterize novel factors involved in choosing between these pathways; in this study we took advantage of the SeeSaw Reporter, in which the repair of double-strand breaks by homology-independent or -dependent mechanisms is distinguished by the accumulation of green or red fluorescence, respectively. Using a genome-wide human esiRNA (endoribonuclease- prepared siRNA) library, we isolate genes that control the recombination/endjoining ratio. Here we report that two distinct sets of genes are involved in the control of the balance between NHEJ and HR: those that are required to facilitate recombination and those that favour NHEJ. This last category includes CCAR2/DBC1, which we show inhibits recombination by limiting the initiation and the extent of DNA end resection, thereby acting as an antagonist of CtIP

Streptomyces aridus sp. nov., isolated from a high altitude Atacama Desert soil and emended description of Streptomyces noboritoensis Isono et al. 1957.

A polyphasic study was undertaken to determine the taxonomic status of a Streptomyces strain which had been isolated from a high altitude Atacama Desert soil and shown to have bioactive properties. The strain, isolate H9(T), was found to have chemotaxonomic, cultural and morphological properties that place it in the genus Streptomyces. 16S rRNA gene sequence analyses showed that the isolate forms a distinct branch at the periphery of a well-delineated subclade in the Streptomyces 16S rRNA gene tree together with the type strains of Streptomyces crystallinus, Streptomyces melanogenes and Streptomyces noboritoensis. Multi-locus sequence analysis (MLSA) based on five house-keeping gene alleles showed that isolate H9(T) is closely related to the latter two type strains and to Streptomyces polyantibioticus NRRL B-24448(T). The isolate was distinguished readily from the type strains of S. melanogenes, S. noboritoensis and S. polyantibioticus using a combination of phenotypic properties. Consequently, the isolate is considered to represent a new species of Streptomyces for which the name Streptomyces aridus sp. nov. is proposed; the type strain is H9(T) (=NCIMB 14965(T)=NRRL B65268(T)). In addition, the MLSA and phenotypic data show that the S. melanogenes and S. noboritoensis type strains belong to a single species, it is proposed that S. melanogenes be recognised as a heterotypic synonym of S. noboritoensis for which an emended description is given. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10482-017-0838-2) contains supplementary material, which is available to authorized users

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

publishersversionPeer reviewe

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI.Peer reviewe

Study of eta-eta ' mixing from measurement of B-(s)(0) -> J/psi eta((')) decay rates

A study of B and Bs meson decays into J/ψ η and J/ψ η′ final states is performed using a data set of proton-proton collisions at centre-of-mass energies of 7 and 8 TeV, collected by the LCHb experiment and corresponding to 3.0 fb−1 of integrated luminosity. The decay B0 → J/ψ η′ is observed for the first time. The following ratios of branching fractions are measured: B(B0→J/ψη′)B(B0s→ J/ψη′)=(2.28±0.65 (stat)±0.10 (syst)±0.13 (fs/fd))×10−2,B(B0→ J/ψη)B(B0s→ J/ψη)=(1.85±0.61 (stat)±0.09 (syst)±0.11 (fs/fd))×10−2, where the third uncertainty is related to the present knowledge of fs/fd, the ratio between the probabilities for a b quark to form a Bs or a B0 meson. The branching fraction ratios are used to determine the parameters of η − η′ meson mixing. In addition, the first evidence for the decay Bs → ψ(2S)η′ is reported, and the relative branching fraction is measured, B(B0s→ ψ(2S)η′)B(B0s→ J/ψη′)=(38.7±9.0 (stat)±1.3 (syst)±0.9(B))×10−2, where the third uncertainty is due to the limited knowledge of the branching fractions of J/ψ and ψ(2S) mesons

Search for the Λb0→Λη′\Lambda^0_b \rightarrow \Lambda \eta^\prime and Λb0→Λη\Lambda^0_b \rightarrow \Lambda \eta decays with the LHCb detector

A search is performed for the as yet unobserved baryonic $\Lambda_b \rightarrow \Lambda \eta^\prime$ and $\Lambda_b \rightarrow \Lambda \eta$ decays with 3$fb^{-1}$ of proton-proton collision data recorded by the LHCb experiment. The $B^0 \rightarrow K_S^0 \eta^\prime$ decay is used as a normalisation channel. No significant signal is observed for the $\Lambda_b \rightarrow \Lambda \eta^\prime$ decay. An upper limit is found on the branching fraction of $\mathcal{B}(\Lambda_b \rightarrow \Lambda \eta^\prime)<3.1\times10^{-6}$} at 90\% confidence level. Evidence is seen for the presence of the $\Lambda_b \rightarrow \Lambda \eta$ decay at the level of $3\sigma$ significance, with a branching fraction $\mathcal{B}(\Lambda_b \rightarrow \Lambda \eta)=(9.3^{+7.3}_{-5.3})\times10^{-6}$}.Comment: 22 pages, 6 figures. v2 is published version (very minor revisions

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI