The role of melanin pathways in extremotolerance and virulence of <em>Fonsecaea</em> revealed by <em>de novo</em> assembly transcriptomics using illumina paired-end sequencing

AbstractMelanisation has been considered to be an important virulence factor of Fonsecaea monophora. However, the biosynthetic mechanisms of melanisation remain unknown. We therefore used next generation sequencing technology to investigate the transcriptome and digital gene expression data, which are valuable resources to better understand the molecular and biological mechanisms regulating melanisation in F. monophora. We performed de novo transcriptome assembly and digital gene expression (DGE) profiling analyses of parent (CBS 122845) and albino (CBS 125194) strains using the Illumina RNA-seq system. A total of 17 352 annotated unigenes were found by BLAST search of NR, Swiss-Prot, Gene Ontology, Clusters of Orthologous Groups and Kyoto Encyclopedia of Genes and Genomes (KEGG) (E-value <1e‒5). A total of 2 283 unigenes were judged to be the differentially expressed between the two genotypes. We identified most of the genes coding for key enzymes involved in melanin biosynthesis pathways, including polyketide synthase (pks), multicopper oxidase (mco), laccase, tyrosinase and homogentisate 1,2-dioxygenase (hmgA). DEG analysis showed extensive down-regulation of key genes in the DHN pathway, while up-regulation was noted in the DOPA pathway of the albino mutant. The transcript levels of partial genes were confirmed by real time RT-PCR, while the crucial role of key enzymes was confirmed by either inhibitor or substrate tests in vitro. Meanwhile, numbers of genes involved in light sensing, cell wall synthesis, morphology and environmental stress were identified in the transcriptome of F. monophora. In addition, 3 353 SSRs (Simple Sequence Repeats) markers were identified from 21 600 consensus sequences. Blocking of the DNH pathway is the most likely reason of melanin deficiency in the albino strain, while the production of pheomelanin and pyomelanin were probably regulated by unknown transcription factors on upstream of both pathways. Most of genes involved in environmental tolerance to oxidants, irradiation and extreme temperatures were also assembled and annotated in transcriptomes of F. monophora. In addition, thousands of identified cSSR (combined SSR) markers will favour further genetic linkage studies. In conclusion, these data will contribute to understanding the regulation of melanin biosynthesis and help to improve the studies of pathogenicity of F. monophora

Renal replacement therapy in Europe : A summary of the 2013 ERA-EDTA Registry Annual Report with a focus on diabetes mellitus

Publisher Copyright: © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.Background: This article provides a summary of the 2013 European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report (available at http://www.era-edta-reg.org), with a focus on patients with diabetes mellitus (DM) as the cause of end-stage renal disease (ESRD). Methods: In 2015, the ERA-EDTA Registry received data on renal replacement therapy (RRT) for ESRD from 49 national or regional renal registries in 34 countries in Europe and bordering the Mediterranean Sea. Individual patient datawere provided by 31 registries, while 18 registries provided aggregated data. The total population covered by the participating registries comprised 650 million people. Results: In total, 72 933 patients started RRT for ESRD within the countries and regions reporting to the ERA-EDTA Registry, resulting in an overall incidence of 112 per million population (pmp). The overall prevalence on 31 December 2013was 738 pmp (n = 478 990). Patients with DM as the cause of ESRD comprised 24% of the incident RRT patients (26 pmp) and 17% of the prevalent RRT patients (122 pmp).Whencompared with the USA, the incidence of patients starting RRTpmpsecondary toDMin Europe was five times lower and the incidence of RRT due to other causes of ESRD was two times lower. Overall, 19 426 kidney transplants were performed (30 pmp). The 5-year adjusted survival for all RRT patients was 60.9% [95% confidence interval (CI) 60.5-61.3] and 50.6% (95% CI 49.9-51.2) for patients with DM as the cause of ESRD.publishersversionPeer reviewe

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

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Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

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Search for heavy resonances decaying into a vector boson and a Higgs boson in final states with charged leptons, neutrinos, and b quarks

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Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

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Search for heavy resonances decaying to a top quark and a bottom quark in the lepton+jets final state in proton–proton collisions at 13 TeV

A search is presented for narrow heavy resonances decaying to a top quark and a bottom quark using data collected by the CMS experiment at √s = 13TeV in 2016. The data set analyzed corresponds to an integrated luminosity of 35.9 fb−1. Final states that include a single lepton (e, μ), multiple jets, and missing transverse momentum are analyzed. No evidence is found for the production of a W′ boson, and the production of right-handed W′ bosons is excluded at 95% confidence level for masses up to 3.6 TeV depending on the scenario considered. Exclusion limits for W′ bosons are also presented as a function of their coupling strength to left- and right-handed fermions. These limits on a W′ boson decaying via a top and a bottom quark are the most stringent published to date

Search for single production of a heavy vector-like T quark decaying to a Higgs boson and a top quark with a lepton and jets in the final state

A search for single production of vector-like top quark partners (T) decaying into a Higgs boson and a top quark is performed using data from pp collisions at a centre-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC, corresponding to an integrated luminosity of 2.3 fb−1. The top quark decay includes an electron or a muon while the Higgs boson decays into a pair of b quarks. No significant excess over standard model backgrounds is observed. Exclusion limits on the product of the production cross section and the branching fraction are derived in the T quark mass range 700 to 1800 GeV. For a mass of 1000 GeV, values of the product of the production cross section and the branching fraction greater than 0.8 and 0.7 pb are excluded at 95% confidence level, assuming left- and right-handed coupling of the T quark to standard model particles, respectively. This is the first analysis setting exclusion limits on the cross section of singly produced vector-like T quarks at a centre-of-mass energy of 13 TeV