A specific N-terminal extension of the 8 kDa domain is required for DNA end-bridging by human Polµ and Polλ

Human DNA polymerases mu (Polµ) and lambda (Polλ) are X family members involved in the repair of double-strand breaks in DNA during non-homologous end joining. Crucial abilities of these enzymes include bridging of the two 3′ single-stranded overhangs and trans-polymerization using one 3′ end as primer and the other as template, to minimize sequence loss. In this context, we have studied the importance of a previously uncharacterised sequence (‘brooch’), located at the N-terminal boundary of the Polß-like polymerase core, and formed by Tyr141, Ala142, Cys143, Gln144 and Arg145 in Polµ, and by Trp239, Val240, Cys241, Ala242 and Gln243 in Polλ. The brooch is potentially implicated in the maintenance of a closed conformation throughout the catalytic cycle, and our studies indicate that it could be a target of Cdk phosphorylation in Polµ. The brooch is irrelevant for 1 nt gap filling, but of specific importance during end joining: single mutations in the conserved residues reduced the formation of two ended synapses and strongly diminished the ability of Polµ and polymerase lambda to perform non-homologous end joining reactions in vitro

Lumbalgia mecánica crónica en pacientes con vértebra limbus anterior

La vértebra limbus es un hallazgo radiológico de prevalencia desconocida y significado incierto. Se trata de un defecto óseo que afecta al margen de los cuerpos vertebrales, con un fragmento desprendido de morfología triangular y bordes escleróticos. Se produce como consecuencia de una herniación intraósea del núcleo pulposo a través del anillo apofisario vertebral, antes de la fusión completa del cuerpo vertebral. En este artículo se describen tres casos clínicos de pacientes jóvenes (de 19, 20 y 22 años), reclusos en el Centro Penitenciario de Jóvenes (Barcelona, España), diagnosticados de lumbalgia mecánica crónica, y portadores de vértebra limbus lumbar. Nuestros hallazgos, y la revisión sistemática de la escasa literatura disponible, ponen en duda algunas convicciones actuales sobre la vértebra limbus

A Methodological Approach for Implementing an Integrated Multimorbidity Care Model: Results from the Pre-Implementation Stage of Joint Action CHRODIS-PLUS

Patients with multimorbidity (defined as the co-occurrence of multiple chronic diseases) frequently experience fragmented care, which increases the risk of negative outcomes. A recently proposed Integrated Multimorbidity Care Model aims to overcome many issues related to fragmented care. In the context of Joint Action CHRODIS-PLUS, an implementation methodology was developed for the care model, which is being piloted in five sites. We aim to (1) explain the methodology used to implement the care model and (2) describe how the pilot sites have adapted and applied the proposed methodology. The model is being implemented in Spain (Andalusia and Aragon), Lithuania (Vilnius and Kaunas), and Italy (Rome). Local implementation working groups at each site adapted the model to local needs, goals, and resources using the same methodological steps: (1) Scope analysis; (2) situation analysis-"strengths, weaknesses, opportunities, threats" (SWOT) analysis; (3) development and improvement of implementation methodology; and (4) final development of an action plan. This common implementation strategy shows how care models can be adapted according to local and regional specificities. Analysis of the common key outcome indicators at the post-implementation phase will help to demonstrate the clinical effectiveness, as well as highlight any difficulties in adapting a common Integrated Multimorbidity Care Model in different countries and clinical settings

Ground/space, passive/active remote sensing observations coupled with particle dispersion modelling to understand the inter-continental transport of wildfire smoke plumes

During the 2017 record-breaking burning season in Canada/United States, intense wild fires raged during the first week of September in the Pacific northwestern region (British Columbia, Alberta, Washington, Oregon, Idaho, Montana and northern California) burning mostly temperate coniferous forests. The heavy loads of smoke particles emitted in the atmosphere reached the Iberian Peninsula (IP) a few days later on 7 and 8 September. Satellite imagery allows to identify two main smoke clouds emitted during two different periods that were injected and transported in the atmosphere at several altitude levels. Columnar properties on 7 and 8 September at two Aerosol Robotic Network (AERONET) mid-altitude, background sites in northern and southern Spain are: aerosol optical depth (AOD) at 440 nm up to 0.62, Ångström exponent of 1.6–1.7, large dominance of small particles (fine mode fraction >0.88), low absorption AOD at 440 nm (0.98). Profiles from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) show the presence of smoke particles in the stratosphere during the transport, whereas the smoke is only observed in the troposphere at its arrival over the IP. Portuguese and Spanish ground lidar stations from the European Aerosol Research Lidar Network/Aerosols, Clouds, and Trace gases Research InfraStructure Network (EARLINET/ACTRIS) and the Micro-Pulse Lidar NETwork (MPLNET) reveal smoke plumes with different properties: particle depolarization ratio and color ratio, respectively, of 0.05 and 2.5 in the mid troposphere (5–9 km) and of 0.10 and 3.0 in the upper troposphere (10–13 km). In the mid troposphere the particle depolarization ratio does not seem time-dependent during the transport whereas the color ratio seems to increase (larger particles sediment first). To analyze the horizontal and vertical transport of the smoke from its origin to the IP, particle dispersion modelling is performed with the Hybrid Single Particle Lagrangian Integrated Trajectory Model (HYSPLIT) parameterized with satellite-derived biomass burning emission estimates from the Global Fire Assimilation System (GFAS) of the Copernicus Atmosphere Monitoring Service (CAMS). Three compounds are simulated: carbon monoxide, black carbon and organic carbon. The results show that the first smoke plume which travels slowly reaches rapidly (~1 day) the upper troposphere and lower stratosphere (UTLS) but also shows evidence of large scale horizontal dispersion, while the second plume, entrained by strong subtropical jets, reaches the upper troposphere much slower (~2.5 days). Observations and dispersion modelling all together suggest that particle depolarization properties are enhanced during their vertical transport from the mid to the upper troposphere.Spanish groups acknowledge the Spanish Ministry of Economy and Competitivity (MINECO) (ref. CGL2013-45410-R, CGL2014-52877-R, CGL2014-55230-R, TEC2015-63832-P, CGL2015-73250-JIN, CGL2016-81092-R and CGL2017-85344-R)European Union through H2020 programme ACTRIS-2, grant 654109European Union through H2020 programme EUNADICS-AV, grant 723986European Union through H2020 programme GRASP-ACE, grant 77834

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 inverse femtobarns. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO

Measurement of isolated photon production in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV

Isolated photon production is measured in proton-proton and lead-lead collisions at nucleon-nucleon centre-of-mass energies of 2.76 TeV in the pseudorapidity range |eta|<1.44 and transverse energies ET between 20 and 80 GeV with the CMS detector at the LHC. The measured ET spectra are found to be in good agreement with next-to-leading-order perturbative QCD predictions. The ratio of PbPb to pp isolated photon ET-differential yields, scaled by the number of incoherent nucleon-nucleon collisions, is consistent with unity for all PbPb reaction centralities.Comment: Submitted to Physics Letters

Modifiable risk factors associated with prediabetes in men and women: A cross-sectional analysis of the cohort study in primary health care on the evolution of patients with prediabetes

Background: Prediabetes is a high-risk state for diabetes development, but little is known about the factors associated with this state. The aim of the study was to identify modifiable risk factors associated with the presence of prediabetes in men and women. Methods: Cohort Study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS-Study) is a prospective study on a cohort of 1184 subjects with prediabetes and another cohort of 838 subjects without glucose metabolism disorders. It is being conducted by 125 general practitioners in Spain. Data for this analysis were collected during the baseline stage in 2012. The modifiable risk factors included were: smoking habit, alcohol consumption, low physical activity, inadequate diet, hypertension, dyslipidemia, and obesity. To assess independent association between each factor and prediabetes, odds ratios (ORs) were estimated using logistic regression models. Results: Abdominal obesity, low plasma levels of high-density lipoprotein cholesterol (HDL-cholesterol), and hypertension were independently associated with the presence of prediabetes in both men and women. After adjusting for all factors, the respective ORs (95% Confidence Intervals) were 1.98 (1.41-2.79), 1.88 (1.23-2.88) and 1.86 (1.39-2.51) for men, and 1.89 (1.36-2.62), 1.58 (1.12-2.23) and 1.44 (1.07-1.92) for women. Also, general obesity was a risk factor in both sexes but did not reach statistical significance among men, after adjusting for all factors. Risky alcohol consumption was a risk factor for prediabetes in men, OR 1.49 (1.00-2.24). Conclusions: Obesity, low HDL-cholesterol levels, and hypertension were modifiable risk factors independently related to the presence of prediabetes in both sexes. The magnitudes of the associations were stronger for men than women. Abdominal obesity in both men and women displayed the strongest association with prediabetes. The findings suggest that there are some differences between men and women, which should be taken into account when implementing specific recommendations to prevent or delay the onset of diabetes in adult population