Ribosomally synthesized and post-translationally modified peptide natural products: Overview and recommendations for a universal nomenclature

Covering: 1988 to 2012 This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed

Helium identification with LHCb

The identification of helium nuclei at LHCb is achieved using a method based on measurements of ionisation losses in the silicon sensors and timing measurements in the Outer Tracker drift tubes. The background from photon conversions is reduced using the RICH detectors and an isolation requirement. The method is developed using pp collision data at √(s) = 13 TeV recorded by the LHCb experiment in the years 2016 to 2018, corresponding to an integrated luminosity of 5.5 fb-1. A total of around 105 helium and antihelium candidates are identified with negligible background contamination. The helium identification efficiency is estimated to be approximately 50% with a corresponding background rejection rate of up to O(10^12). These results demonstrate the feasibility of a rich programme of measurements of QCD and astrophysics interest involving light nuclei

Measurement of forward charged hadron flow harmonics in peripheral PbPb collisions at √sNN = 5.02 TeV with the LHCb detector

Flow harmonic coefficients, v n , which are the key to studying the hydrodynamics of the quark-gluon plasma (QGP) created in heavy-ion collisions, have been measured in various collision systems and kinematic regions and using various particle species. The study of flow harmonics in a wide pseudorapidity range is particularly valuable to understand the temperature dependence of the shear viscosity to entropy density ratio of the QGP. This paper presents the first LHCb results of the second- and the third-order flow harmonic coefficients of charged hadrons as a function of transverse momentum in the forward region, corresponding to pseudorapidities between 2.0 and 4.9, using the data collected from PbPb collisions in 2018 at a center-of-mass energy of 5.02 TeV . The coefficients measured using the two-particle angular correlation analysis method are smaller than the central-pseudorapidity measurements at ALICE and ATLAS from the same collision system but share similar features

Curvature-bias corrections using a pseudomass method

Momentum measurements for very high momentum charged particles, such as muons from electroweak vector boson decays, are particularly susceptible to charge-dependent curvature biases that arise from misalignments of tracking detectors. Low momentum charged particles used in alignment procedures have limited sensitivity to coherent displacements of such detectors, and therefore are unable to fully constrain these misalignments to the precision necessary for studies of electroweak physics. Additional approaches are therefore required to understand and correct for these effects. In this paper the curvature biases present at the LHCb detector are studied using the pseudomass method in proton-proton collision data recorded at centre of mass energy √(s)=13 TeV during 2016, 2017 and 2018. The biases are determined using Z→μ + μ - decays in intervals defined by the data-taking period, magnet polarity and muon direction. Correcting for these biases, which are typically at the 10-4 GeV-1 level, improves the Z→μ + μ - mass resolution by roughly 18% and eliminates several pathological trends in the kinematic-dependence of the mean dimuon invariant mass

Supplementary Material for: Methionine Sulfoxide Reductases Protect against Oxidative Stress in <b><i>Staphylococcus aureus</i></b> Encountering Exogenous Oxidants and Human Neutrophils

To establish infection successfully, <i>Staphylococcus aureus</i> must evade clearance by polymorphonuclear neutrophils (PMN). We studied the expression and regulation of the methionine sulfoxide reductases (Msr) that are involved in the repair of oxidized staphylococcal proteins and investigated their influence on the fate of <i>S. aureus </i>exposed to oxidants or PMN. We evaluated a mutant deficient in <i>msrA1 </i>and <i>msrB </i>for susceptibility to hydrogen peroxide, hypochlorous acid and PMN. The expression of <i>msrA1</i> in wild-type bacteria ingested by human PMN was assessed by real-time PCR. The regulation of <i>msr </i>was studied by screening a library of two-component regulatory system (TCS) mutants for altered <i>msr</i> responses. Relative to the wild-type bacteria, bacteria deficient in Msr were more susceptible to oxidants and PMN. Upregulation of staphylococcal <i>msrA1 </i>occurred within the phagosomes of normal PMN and PMN deficient in NADPH oxidase activity. Furthermore, PMN granule-rich extract stimulated the upregulation of <i>msrA1.</i> Modulation of <i>msrA1</i> within PMN was shown to be partly dependent on the VraSR TCS. Msr contributes to staphylococcal responses to oxidative attack and PMN. Our study highlights a novel interaction between the oxidative protein repair pathway and the VraSR TCS that is involved in cell wall homeostasis

Supplementary Material for: The Role of Innate Immunity in Promoting SaeR/S-Mediated Virulence in Staphylococcus aureus

The ability of <i>Staphylococcus aureus</i> to infect tissues is dependent on precise control of virulence through gene-regulatory systems. While the SaeR/S two-component system has been shown to be a major regulator of <i>S. aureus</i> virulence, the influence of the host environment on SaeR/S-regulated genes (<i>saeR/S </i>targets) remains incompletely defined. Using QuantiGene 2.0 transcriptional assays, we examined expression of genes with the SaeR binding site in USA300 exposed to human and mouse neutrophils and host-derived peptides and during subcutaneous skin infection. We found that only some of the <i>saeR/S </i>targets, as opposed to the entire SaeR/S virulon, were activated within 5 and 10 min of interacting with human neutrophils as well as α-defensin. Furthermore, mouse neutrophils promoted transcription of <i>saeR/S</i> targets despite lacking α-defensin, and the murine skin environment elicited a distinctive expression profile of <i>saeR/S</i> targets. These findings indicate that <i>saeR/S</i>-mediated transcription is unique to and dependent on specific host stimuli. By using isogenic USA300Δ<i>saeR/S</i> and USA300Δ<i>agr</i> knockout strains, we also determined that SaeR/S is the major regulator of virulence factors, while Agr, a quorum-sensing two-component system, has moderate influence on transcription of the <i>saeR/S </i>targets under the tested physiological conditions

Staphylococcus aureus Staphopain A inhibits CXCR2-dependent neutrophil activation and chemotaxis

The CXC chemokine receptor 2 (CXCR2) on neutrophils, which recognizes chemokines produced at the site of infection, plays an important role in antimicrobial host defenses such as neutrophil activation and chemotaxis. Staphylococcus aureus is a successful human pathogen secreting a number of proteolytic enzymes, but their influence on the host immune system is not well understood. Here, we identify the cysteine protease Staphopain A as a chemokine receptor blocker. Neutrophils treated with Staphopain A are unresponsive to activation by all unique CXCR2 chemokines due to cleavage of the N-terminal domain, which can be neutralized by specific protease inhibitors. Moreover, Staphopain A inhibits neutrophil migration towards CXCR2 chemokines. By comparing a methicillin-resistant S. aureus (MRSA) strain with an isogenic Staphopain A mutant, we demonstrate that Staphopain A is the only secreted protease with activity towards CXCR2. Although the inability to cleave murine CXCR2 limits in-vivo studies, our data indicate that Staphopain A is an important immunomodulatory protein that blocks neutrophil recruitment by specific cleavage of the N-terminal domain of human CXCR2