wKinMut: An integrated tool for the analysis and interpretation of mutations in human protein kinases

BACKGROUND: Protein kinases are involved in relevant physiological functions and a broad number of mutations in this superfamily have been reported in the literature to affect protein function and stability. Unfortunately, the exploration of the consequences on the phenotypes of each individual mutation remains a considerable challenge. RESULTS: The wKinMut web-server offers direct prediction of the potential pathogenicity of the mutations from a number of methods, including our recently developed prediction method based on the combination of information from a range of diverse sources, including physicochemical properties and functional annotations from FireDB and Swissprot and kinase-specific characteristics such as the membership to specific kinase groups, the annotation with disease-associated GO terms or the occurrence of the mutation in PFAM domains, and the relevance of the residues in determining kinase subfamily specificity from S3Det. This predictor yields interesting results that compare favourably with other methods in the field when applied to protein kinases. Together with the predictions, wKinMut offers a number of integrated services for the analysis of mutations. These include: the classification of the kinase, information about associations of the kinase with other proteins extracted from iHop, the mapping of the mutations onto PDB structures, pathogenicity records from a number of databases and the classification of mutations in large-scale cancer studies. Importantly, wKinMut is connected with the SNP2L system that extracts mentions of mutations directly from the literature, and therefore increases the possibilities of finding interesting functional information associated to the studied mutations. CONCLUSIONS: wKinMut facilitates the exploration of the information available about individual mutations by integrating prediction approaches with the automatic extraction of information from the literature (text mining) and several state-of-the-art databases. wKinMut has been used during the last year for the analysis of the consequences of mutations in the context of a number of cancer genome projects, including the recent analysis of Chronic Lymphocytic Leukemia cases and is publicly available at http://wkinmut.bioinfo.cnio.es

The burden of breast, cervical, and colon and rectum cancer in the Balkan countries, 1990–2019 and forecast to 2030.

Background Despite effective prevention and control strategies, in countries of the Balkan region, cancers are the second leading cause of mortality, closely following circulatory system diseases. Objective To describe trends in the burden of breast, cervical, and colon and rectum cancer in the Balkan region and per country between 1990 and 2019, including a forecast to 2030. Methods We described the 2019 Global Burden of Disease (GBD) estimates for breast, cervical, and colon and rectum cancers in eleven Balkan countries over the period 1990–2019, including incidence, years lived with disability (YLD), years of life lost (YLL), and disability-adjusted life years (DALYs) rates per 100,000 population and accompanied 95% uncertainty interval. With the Autoregressive Integrated Moving Average, we forecasted these rates per country up to 2030. Results In the Balkan region, the highest incidence and DALYs rates in the study period were for colon and rectum, and breast cancers. Over the study period, the DALYs rates for breast cancer per 100,000 population were the highest in Serbia (reaching 670.84 in 2019) but the lowest in Albania (reaching 271.24 in 2019). In 2019, the highest incidence of breast cancer (85 /100,000) and highest YLD rate (64 /100,000) were observed in Greece. Romania had the highest incidence rates, YLD rates, DALY rates, and YLL rates of cervical cancer, with respective 20.59%, 23.39% 4.00%, and 3.47% increases for the 1990/2019 period, and the highest forecasted burden for cervical cancer in 2030. The highest incidence rates, YLD rates and DALY rates of colon and rectum cancers were continuously recorded in Croatia (an increase of 130.75%, 48.23%, and 63.28%, respectively), while the highest YLL rates were in Bulgaria (an increase of 63.85%). The YLL rates due to colon and rectum cancers are forecasted to progress by 2030 in all Balkan countries. Conclusion As most of the DALYs burden for breast, cervical, and colon and rectum cancer is due to premature mortality, the numerous country-specific barriers to cancer early detection and quality and care continuum should be a public priority of multi-stakeholder collaboration in the Balkan region

The genome of the emerging barley pathogen Ramularia collo-cygni

Background Ramularia collo-cygni is a newly important, foliar fungal pathogen of barley that causes the disease Ramularia leaf spot. The fungus exhibits a prolonged endophytic growth stage before switching life habit to become an aggressive, necrotrophic pathogen that causes significant losses to green leaf area and hence grain yield and quality. Results The R. collo-cygni genome was sequenced using a combination of Illumina and Roche 454 technologies. The draft assembly of 30.3 Mb contained 11,617 predicted gene models. Our phylogenomic analysis confirmed the classification of this ascomycete fungus within the family Mycosphaerellaceae, order Capnodiales of the class Dothideomycetes. A predicted secretome comprising 1053 proteins included redox-related enzymes and carbohydrate-modifying enzymes and proteases. The relative paucity of plant cell wall degrading enzyme genes may be associated with the stealth pathogenesis characteristic of plant pathogens from the Mycosphaerellaceae. A large number of genes associated with secondary metabolite production, including homologs of toxin biosynthesis genes found in other Dothideomycete plant pathogens, were identified. Conclusions The genome sequence of R. collo-cygni provides a framework for understanding the genetic basis of pathogenesis in this important emerging pathogen. The reduced complement of carbohydrate-degrading enzyme genes is likely to reflect a strategy to avoid detection by host defences during its prolonged asymptomatic growth. Of particular interest will be the analysis of R. collo-cygni gene expression during interactions with the host barley, to understand what triggers this fungus to switch from being a benign endophyte to an aggressive necrotroph

Search for the production of W^{\pm} W^{\pm} W^{\mp} events at \sqrt{s} = 13 TeV

A search for the production of events containing three W bosons predicted by the standard model is reported. The search is based on a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the CMS experiment at the CERN LHC and corresponding to a total integrated luminosity of 35.9 fb^{-1}. The search is performed in final states with three leptons (electrons or muons), or with two same-charge leptons plus two jets. The observed (expected) significance of the signal for W^{\pm} W^{\pm} W^{\mp} production is 0.60 (1.78) standard deviations, and the ratio of the measured signal yield to that expected from the standard model is 0.34_{-0.34}^{+0.62}. Limits are placed on three anomalous quartic gauge couplings and on the production of massive axionlike particles

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

Search for contact interactions and large extra dimensions in the dilepton mass spectra from proton-proton collisions at \sqrt{s} = 13 TeV

A search for nonresonant excesses in the invariant mass spectra of electron and muon pairs is presented. The analysis is based on data from proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the CMS experiment in 2016, corresponding to a total integrated luminosity of 36 fb^{-1}. No significant deviation from the standard model is observed. Limits are set at 95% confidence level on energy scales for two general classes of nonresonant models. For a class of fermion contact interaction models, lower limits ranging from 20 to 32 TeV are set on the characteristic compositeness scale Λ. For the Arkani-Hamed, Dimopoulos, and Dvali model of large extra dimensions, the first results in the dilepton final state at 13 TeV are reported, and values of the ultraviolet cutoff parameter Λ_{T} below 6.9 TeV are excluded. A combination with recent CMS diphoton results improves this exclusion to Λ_{T} below 7.7 TeV, providing the most sensitive limits to date in nonhadronic final states

Measurement of the WZ production cross section in pp collisions at root s=13 Tev

Peer reviewe

Relative Modification of Prompt psi(2S) and J/psi Yields from pp to PbPb Collisions at root(S)(NN)=5.02 TeV

Peer reviewe

Measurement of B_{s}^{0} meson production in pp and PbPb collisions at \sqrt{SNN}

The production cross sections of B_{s}^{0} mesons and charge conjugates are measured in proton-proton (pp) and PbPb collisions via the exclusive decay channel B_{s}^{0}→J/ψϕ→μ^{+}μ^{−}K^{+}K^{−} at a center-of-mass energy of 5.02 TeV per nucleon pair and within the rapidity range |y|<2.4 using the CMS detector at the LHC. The pp measurement is performed as a function of transverse momentum (p_{T}) of the B_{s}^{0} mesons in the range of 7 to 50 GeV/c and is compared to the predictions of perturbative QCD calculations. The B_{s}^{0} production yield in PbPb collisions is measured in two p_{T} intervals, 7 to 15 and 15 to 50 GeV/c, and compared to the yield in pp collisions in the same kinematic region. The nuclear modification factor (R_{AA}) is found to be 1.5±0.6(stat)±0.5(syst) for 7–15 GeV/c, and 0.87±0.30(stat)±0.17(syst) for 15–50 GeV/c, respectively. Within current uncertainties, the B_{s}^{0} results are consistent with models of strangeness enhancement, and suppression by parton energy loss, as observed for the B+ mesons