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A search for narrow resonances decaying to bottom quark-antiquark pairs is presented, using a data sample of proton-proton collisions at root s = 8 TeV corresponding to an integrated luminosity of 19.7 fb(-1). The search is extended to masses lower than those reached in typical searches for resonances decaying into jet pairs at the LHC, by taking advantage of triggers that identify jets originating from bottom quarks. No significant excess of events is observed above the background predictions. Limits are set on the product of cross section and branching fraction to bottom quarks for spin 0, 1, and 2 resonances in the mass range of 325-1200 GeV. These results improve on the limits for resonances decaying into jet pairs in the 325-500 GeV mass range.

The abundance of available static protein structural data makes the more effective analysis and interpretation of this data a valuable tool to supplement the experimental study of protein mechanics. Structural displacements can be difficult to analyze and interpret. Previously, we showed that strains provide a more natural and interpretable representation of protein deformations, revealing mechanical coupling between spatially distinct sites of allosteric proteins. Here, we demonstrate that other transformations of displacements yield additional insights. We calculate the divergence and curl of deformations of the transmembrane channel KcsA. Additionally, we introduce quantities analogous to bend, splay, and twist deformation energies of nematic liquid crystals. These transformations enable the decomposition of displacements into different modes of deformation, helping to characterize the type of deformation a protein undergoes. We apply these calculations to study the filter and gating regions of KcsA. We observe a continuous path of rotational deformations physically coupling these two regions, and, we propose, underlying the allosteric interaction between these regions. Bend, splay, and twist distinguish KcsA gate opening, filter opening, and filter-gate coupling, respectively. In general, physically meaningful representations of deformations (like strain, curl, bend, splay, and twist) can make testable predictions and yield insights into protein mechanics, augmenting experimental methods and more fully exploiting available structural data.

Purpose: Previous studies have revealed multiple common variants associated with known risk factors for cardiovascular disease (CVD). Ischemic stroke (IS) and CVD share several risk factors with each having substantial heritability. We aimed to generate a multi-locus genetic risk score (GRS) for IS based on CVD related SNPs to evaluate their combined effects on IS. Methods: A total of 851 patients and 977 controls were selected from Beijing, Tianjin, Shandong, Shanxi, Shaanxi and Heilongjiang communities. The candidate genes were genotyped by PCR-hybridization. Information about demographic factors, history of disease (such as hypertension), and lifestyle was obtained using structured questionnaires. A GRS model weighted by the absolute value of regression coefficient 13 was established to comprehensively assess the association between candidate SNPs and IS. Using the area under the receiver operating characteristic curve (AUC) to evaluate the value of GRS on predicting IS. Results: The GRS of cases was 2.87 +/- 0.28, which was significantly higher than controls' GRS (2.78 0.30) (P < 0.000). With the increase of the GRS, the risk of IS became higher (P-trend < 0.000). Subjects in the top quartile of the GRS had about 1.9-fold increased risk of IS compared with subjects in the lowest quartile (OR (adjusted) = 1.880, 95%CI = 1.442-2.452, P < 0.000). The AUC = 0.580, P < 0.000. Conclusion: 13 CVD related SNPs had combined effects on IS. The GRS of cases was significantly higher than controls' GRS. As the GRS increased, the risk of IS increased. The GRS model has some value for the prediction of IS.

A search for supersymmetry (SUSY) is performed in final states comprising one or more jets and missing transverse momentum using data from proton-proton collisions at a centre-of-mass energy of 13 TeV. The data were recorded with the CMS detector at the CERN LHC in 2016 and correspond to an integrated luminosity of 35.9 fb(-1). The number of signal events is found to agree with the expected background yields from standard model processes. The results are interpreted in the context of simplified models of SUSY that assume the production of gluino or squark pairs and their prompt decay to quarks and the lightest neutralino. The masses of bottom, top, and mass-degenerate light-flavour squarks are probed up to 1050, 1000, and 1325 GeV, respectively. The gluino mass is probed up to 1900, 1650, and 1650 GeV when the gluino decays via virtual states of the aforementioned squarks. The strongest mass bounds on the neutralinos from gluino and squark decays are 1150 and 575 GeV, respectively. The search also provides sensitivity to simplified models inspired by split SUSY that involve the production and decay of long-lived gluinos. Values of the proper decay length CT0 from 10(-3) to 10(5) mm are considered, as well as a metastable gluino scenario. Gluino masses up to 1750 and 900 GeV are probed for CT0 = 1mm and for the metastable state, respectively. The sensitivity is moderately dependent on model assumptions for CT0 greater than or similar to 1 m. The search provides coverage of the CT0 parameter space for models involving long-lived gluinos that is complementary to existing techniques at the LHC.

Results are presented from a search for supersymmetry in events with a single electron or muon and hadronic jets. The data correspond to a sample of proton-proton collisions at root s = 13 TeV with an integrated luminosity of 35.9 fb(-1), recorded in 2016 by the CMS experiment. A number of exclusive search regions are defined according to the number of jets, the number of b-tagged jets, the scalar sum of the transverse momenta of the jets, and the scalar sum of the missing transverse momentum and the transverse momentum of the lepton. Standard model background events are reduced significantly by requiring a large azimuthal angle between the direction of the lepton and of the reconstructed W boson, computed under the hypothesis that all of the missing transverse momentum in the event arises from a neutrino produced in the leptonic decay of the W boson. The numbers of observed events are consistent with the expectations from standard model processes, and the results are used to set lower limits on supersymmetric particle masses in the context of two simplified models of gluino pair production. In the first model, where each gluino decays to a top quark-antiquark pair and a neutralino, gluino masses up to 1.8 TeV are excluded at the 95% CL. The second model considers a three-body decay to a light quark-antiquark pair and a chargino, which subsequently decays to a W boson and a neutralino. In this model, gluinos are excluded up to 1.9 TeV. (C) 2018 The Author. Published by Elsevier B.V.

Testosterone (T) can act directly through neural androgen receptors (AR) to facilitate male sexual behavior; however, T's metabolites also can play complicated and interesting roles in the control of mating. One metabolite, dihydrotestosterone (DHT) binds to AR with significantly greater affinity than that of T. Is that important behaviorally? Another metabolite, estradiol (E), offers a potential alternative route of facilitating male mating behavior by acting through estradiol receptors (ER). In this review we explore the roles and relative importance of T as well as E and DHT at various levels of the neuroaxis for the activation of male sex behavior in common laboratory animals and, when relevant research findings are available, in man. (C) 2017 Elsevier B.V. All rights reserved.

A robust network of transcription factors and an open chromatin landscape are hallmarks of the naive pluripotent state. Recently, the acetyllysine reader Brd4 has been implicated in stem cell maintenance, but the relative contribution of Brd4 to pluripotency remains unclear. Here, we show that Brd4 is dispensable for self-renewal and pluripotency of embryonic stem cells (ESCs). When maintained in their ground state, ESCs retain transcription factor binding and chromatin accessibility independent of Brd4 function or expression. In metastable ESCs, Brd4 independence can be achieved by increased expression of pluripotency transcription factors, including STAT3, Nanog or Klf4, so long as the DNA methylcytosine oxidases Tet1 and Tet2 are present. These data reveal that Brd4 is not essential for ESC self-renewal. Rather, the levels of pluripotency transcription factor abundance and Tet1/2 function determine the extent to which bromodomain recognition of protein acetylation contributes to the maintenance of gene expression and cell identity.

Transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable cation channel required for immune cell activation, insulin secretion, and body heat control. TRPM2 is activated by cytosolic Ca2+, phosphatidyl-inositol-4,5-bisphosphate and ADP ribose. Here, we present the 3 A resolution electron cryo-microscopic structure of TRPM2 from Nematostella vectensis, 63% similar in sequence to human TRPM2, in the Ca2+-bound closed state. Compared to other TRPM channels, TRPM2 exhibits unique structural features that correlate with its function. The pore is larger and more negatively charged, consistent with its high Ca2+ selectivity and larger conductance. The intracellular Ca2+ binding sites are connected to the pore and cytosol, explaining the unusual dependence of TRPM2 activity on intra- and extracellular Ca2+. In addition, the absence of a post filter motif is likely the cause of the rapid inactivation of human TRPM2. Together, our cryo-EM and electrophysiology studies provide a molecular understanding of the unique gating mechanism of TRPM2.