AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

Study of the rare B-s(0) and B-0 decays into the pi(+) pi(-) mu(+) mu(-) final state

A search for the rare decays B-s(0) -> pi(+) pi-mu(+) mu-and B-0 -> pi(+) pi-mu(+) mu-is performed in a data set corresponding to an integrated luminosity of 3.0 fb(-1) collected by the LHCb detector in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. Decay candidates with pion pairs that have invariant mass in the range 0.5-1.3GeV/c(2) and with muon pairs that do not originate from a resonance are considered. The first observation of the decay B-s(0) -> pi(+) pi-mu(+) mu- and the first evidence of the decay B-0 -> pi(+) pi-mu(+) mu-are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be B(B-s(0) -> pi(+) pi-mu(+) mu(-)) =(8.6 +/- 1.5(stat) +/- 0.7(syst) +/- 0.7 (norm)) x 10(-8) and B(B-0 -> pi(+) pi-mu(+) mu(-)) =(2.11 +/- 0.51(stat) +/- 0.15(syst) +/- 0.16(norm)) x10(-8), where the third uncertainty is due to the branching fraction of the decay B-0. -> J/Psi(mu(+) mu(-)) K*(892)(0)(-> K+ pi(-)), used as a normalisation. (C) 2015 The Authors. Published by Elsevier B.V

Measurement of CP violation and constraints on the CKM angle gamma in B-+/- -> DK +/- with D -> K-s(0)pi(+)pi(-) decays

A model-dependent amplitude analysis of B-+/- -> DK +/- with D -> K-s(0)pi(+)pi(-) decays is performed using proton proton collision data, corresponding to an integrated luminosity of 1 fb(-1), recorded by LHCb at a centre-of-mass energy of 7 TeV in 2011. Values of the CP violation observables x +/- and y +/-, which are sensitive to the CKM angle gamma, are measured to be x- = +0.027 +/- 0.0441(-0.008)(+0.010) +/- 0.001, y- = +0.013 +/- 0.0481(-0.007)(+0.009) +/- 0.003, x+ = -0.084 +/- 0.045 +/- 0.009 +/- 0.005, y+ = -0.032 +/- 0.048(-0.009)(+0.010) +/- 0.008, where the first uncertainty is statistical, the second systematic and the third arises from the uncertainty of the D -> K-S(0)pi(+)pi(-) amplitude model. The value of gamma is determined to be (84(-42)(+49))degrees including all sources of uncertainty. Neutral D meson mixing is found to have negligible effect. (C) 2014 The Authors. Published by Elsevier B.V

Evidence for the decay X(3872) -> psi(2S)gamma

Evidence for the decay mode X(3872) -> psi(2S)gamma in B+ -> X(3872)K+ decays is found with a significance of 4.4 standard deviations. The analysis is based on a data sample of proton proton collisions, corresponding to an integrated luminosity of 3 fb(-1), collected with the LHCb detector, at centre-of-mass energies of 7 and 8 TeV. The ratio of the branching fraction of the X(3872) -> psi(2S)gamma decay to that of the X(3872) -> J/psi gamma decay is measured to be B(X(3872) -> psi(2S)gamma)/B(X(3872) -> J/psi gamma) = 2.46 +/- 0.64 +/- 0.29, where the first uncertainty is statistical and the second is systematic. The measured value does not support a pure D (D) over bar* molecular interpretation of the X(3872) state. (C) 2014 CERN for the benefit of the LHCb Collaboration. Published by Elsevier B.V

A study of CP violation in B-+/- -> DK +/- and B-+/- -> D pi(+/-) decays with D -> (KSK +/-)-K-0 pi(-/+) final states

A first study of CP violation in the decay modes B-+/- -> [(KSK +/-)-K-0 pi(-/+)](D)h(+/-) and B-+/- -> [(KSK +/-)-K-0 pi(-/+)](D)h(+/-), where h labels a K or pi meson and D labels a D-0 or (D) over bar (0) meson, is performed. The analysis uses the LHCb data set collected in pp collisions, corresponding to an integrated luminosity of 3 fb(-1). The analysis is sensitive to the CP-violating CKM phase gamma through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of gamma using other decay modes. (C) 2014 The Authors. Published by Elsevier B.V