Influence of ARHGEF3 and RHOA Knockdown on ACTA2 and Other Genes in Osteoblasts and Osteoclasts

Osteoporosis is a common bone disease that has a strong genetic component. Genome-wide linkage studies have identified the chromosomal region 3p14-p22 as a quantitative trait locus for bone mineral density (BMD). We have previously identified associations between variation in two related genes located in 3p14-p22, ARHGEF3 and RHOA, and BMD in women. In this study we performed knockdown of these genes using small interfering RNA (siRNA) in human osteoblast-like and osteoclast-like cells in culture, with subsequent microarray analysis to identify genes differentially regulated from a list of 264 candidate genes. Validation of selected findings was then carried out in additional human cell lines/cultures using quantitative real-time PCR (qRT-PCR). The qRT-PCR results showed significant down-regulation of the ACTA2 gene, encoding the cytoskeletal protein alpha 2 actin, in response to RHOA knockdown in both osteoblast-like (P<0.001) and osteoclast-like cells (P = 0.002). RHOA knockdown also caused up-regulation of the PTH1R gene, encoding the parathyroid hormone 1 receptor, in Saos-2 osteoblast-like cells (P<0.001). Other findings included down-regulation of the TNFRSF11B gene, encoding osteoprotegerin, in response to ARHGEF3 knockdown in the Saos-2 and hFOB 1.19 osteoblast-like cells (P = 0.003– 0.02), and down-regulation of ARHGDIA, encoding the Rho GDP dissociation inhibitor alpha, in response to RHOA knockdown in osteoclast-like cells (P<0.001). These studies identify ARHGEF3 and RHOA as potential regulators of a number of genes in bone cells, including TNFRSF11B, ARHGDIA, PTH1R and ACTA2, with influences on the latter evident in both osteoblast-like and osteoclast-like cells. This adds further evidence to previous studies suggesting a role for the ARHGEF3 and RHOA genes in bone metabolism

Search for the decay modes D^0 → e^+e^-, D^0 → μ^+μ^-, and D^0 → e^±μ∓

We present searches for the rare decay modes D^0→e^+e^-, D^0→μ^+μ^-, and D^0→e^±μ^∓ in continuum e^+e^-→cc events recorded by the BABAR detector in a data sample that corresponds to an integrated luminosity of 468  fb^(-1). These decays are highly Glashow–Iliopoulos–Maiani suppressed but may be enhanced in several extensions of the standard model. Our observed event yields are consistent with the expected backgrounds. An excess is seen in the D^0→μ^+μ^- channel, although the observed yield is consistent with an upward background fluctuation at the 5% level. Using the Feldman–Cousins method, we set the following 90% confidence level intervals on the branching fractions: B(D^0→e^+e^-)<1.7×10^(-7), B(D^0→μ^+μ^-) within [0.6,8.1]×10^(-7), and B(D^0→e^±μ^∓)<3.3×10^(-7)

Ancient goat genomes reveal mosaic domestication in the Fertile Crescent

Current genetic data are equivocal as to whether goat domestication occurred multiple times or was a singular process. We generated genomic data from 83 ancient goats (51 with genome-wide coverage) from Paleolithic to Medieval contexts throughout the Near East. Our findings demonstrate that multiple divergent ancient wild goat sources were domesticated in a dispersed process that resulted in genetically and geographically distinct Neolithic goat populations, echoing contemporaneous human divergence across the region. These early goat populations contributed differently to modern goats in Asia, Africa, and Europe. We also detect early selection for pigmentation, stature, reproduction, milking, and response to dietary change, providing 8000-year-old evidence for human agency in molding genome variation within a partner species

Search for the decay modes D0 -> e+e-, D0 -> mu+mu-, and D0 -> e mu

We present searches for the rare decay modes D0 to e+e-, D0 to mu+mu- and D0 to e mu in continuum e+e- to cbar c events recorded by the BABAR detector in a data sample that corresponds to an integrated luminosity of 468 f^-1. These decays are highly GIM suppressed but may be enhanced in several extensions of the Standard Model. Our observed event yields are consistent with the expected backgrounds. An excess is seen in the D0 to mu+mu- channel, although the observed yield is consistent with an upward background fluctuation at the 5% level. Using the Feldman-Cousins method, we set the following 90% confidence level intervals on the branching fractions: B(D0 to e+e-)<1.7 x 10^-7, B(D0 to mu+mu-) within [0.6, 8.1] x 10^-7, and B(D0 to e mu)<3.3 x 10^-7.Comment: 12 pages, 4 figures, submitted to PR

Precise determination of the mass of the Higgs boson and tests of compatibility of its couplings with the standard model predictions using proton collisions at 7 and 8 TeV

Peer reviewe

Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

Peer reviewe

Measurement of the rapidity and transverse momentum distributions of Z bosons in pp collisions at √(s)=7 TeV

Measurements of the normalized rapidity (y) and transverse-momentum (qT) distributions of Drell–Yan muon and electron pairs in the Z-boson mass region (60<Mℓℓ<120  GeV) are reported. The results are obtained using a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, collected by the CMS experiment at the Large Hadron Collider (LHC), corresponding to an integrated luminosity of 36  pb-1. The distributions are measured over the ranges |y|<3.5 and qT<600  GeV and compared with quantum chromodynamics (QCD) calculations using recent parton distribution functions to model the momenta of the quarks and gluons in the protons. Overall agreement is observed between the models and data for the rapidity distribution, while no single model describes the Z transverse-momentum distribution over the full range

Measurement of the differential cross section for isolated prompt photon production in pp collisions at 7 TeV

A measurement of the differential cross section for the inclusive production of isolated prompt photons in proton-proton collisions at a center-of-mass energy of 7 TeV is presented. The data sample corresponds to an integrated luminosity of 36 pb(-1) recorded by the CMS detector at the LHC. The measurement covers the pseudorapidity range vertical bar eta vertical bar < 2.5 and the transverse energy range 25 < E-T < 400 GeV, corresponding to the kinematic region 0.007 < x(T) < 0.114. Photon candidates are identified with two complementary methods, one based on photon conversions in the silicon tracker and the other on isolated energy deposits in the electromagnetic calorimeter. The measured cross section is presented as a function of E-T in four pseudorapidity regions. The next-to-leading-order perturbative QCD calculations are consistent with the measured cross section

Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at s = 13 TeV with the ATLAS detector

This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations

Measurement of the weak mixing angle with the Drell-Yan process in proton-proton collisions at the LHC

This is the Pre-Print version of the Article - Copyright @ 2011 APSA multivariate likelihood method to measure electroweak couplings with the Drell-Yan process at the LHC is presented. The process is described by the dilepton rapidity, invariant mass, and decay angle distributions. The decay angle ambiguity due to the unknown assignment of the scattered constituent quark and antiquark to the two protons in a collision is resolved statistically using correlations between the observables. The method is applied to a sample of dimuon events from proton-proton collisions at sqrt(s) = 7 TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 1.1 inverse femtobarns. From the dominant u-ubar, d-dbar to gamma*/Z to opposite sign dimuons process, the effective weak mixing angle parameter is measured to be sin^2(theta[eff]) = 0.2287 +/- 0.0020 (stat.) +/- 0.0025 (syst.). This result is consistent with measurements from other processes, as expected within the standard model