Phase Variation in HMW1A Controls a Phenotypic Switch in Haemophilus influenzae Associated with Pathoadaptation during Persistent Infection

Genetic variants arising from within-patient evolution shed light on bacterial adaptation during chronic infection. Contingency loci generate high levels of genetic variation in bacterial genomes, enabling adaptation to the stringent selective pressures exerted by the host. A significant gap in our understanding of phase-variable contingency loci is the extent of their contribution to natural infections. The human-adapted pathogen nontypeable Haemophilus influenzae (NTHi) causes persistent infections, which contribute to underlying disease progression. The phase-variable high-molecular-weight (HMW) adhesins located on the NTHi surface mediate adherence to respiratory epithelial cells and, depending on the allelic variant, can also confer high epithelial invasiveness or hyperinvasion. In this study, we characterize the dynamics of HMW-mediated hyperinvasion in living cells and identify a specific HMW binding domain shared by hyperinvasive NTHi isolates of distinct pathological origins. Moreover, we observed that HMW expression decreased over time by using a longitudinal set of persistent NTHi strains collected from chronic obstructive pulmonary disease (COPD) patients, resulting from increased numbers of simple-sequence repeats (SSRs) downstream of the functional P2hmw1A promoter, which is the one primarily driving HMW expression. Notably, the increased SSR numbers at the hmw1 promoter region also control a phenotypic switch toward lower bacterial intracellular invasion and higher biofilm formation, likely conferring adaptive advantages during chronic airway infection by NTHi. Overall, we reveal novel molecular mechanisms of NTHi pathoadaptation based on within-patient lifestyle switching controlled by phase variation. IMPORTANCE Human-adapted bacterial pathogens have evolved specific mechanisms to colonize their host niche. Phase variation is a contingency strategy to allow adaptation to changing conditions, as phase-variable bacterial loci rapidly and reversibly switch their expression. Several NTHi adhesins are phase variable. These adhesins are required for colonization but also immunogenic, in such a way that bacteria with lower adhesin levels are better equipped to survive an immune response, making their contribution to natural infections unclear. We show here that the major NTHi adhesin HMW1A displays allelic variation, which can drive a phase-variable epithelial hyperinvasion phenotype. Over time, hmw1A phase variation lowers adhesin expression, which controls an NTHi lifestyle switch from high epithelial invasiveness to lower invasion and higher biofilm formation. This reversible loss of function aligns with the previously stated notion that epithelial infection is essential for NTHi infection establishment, but once established, persistence favors gene inactivation, in this case facilitating biofilm growth

COMPARACIÓN DE LAS PRINCIPALES MOSCAS NECRÓFAGAS ATRAÍDAS POR HÍGADOS HUMANOS EN ESTADO DE DESCOMPOSICIÓN, EXPUESTOS A DIFERENTES INTERVALOS DE TIEMPO, EN UN ÁREA URBANA DE LA PROVINCIA DE PANAMÁ.

Four samples of human´s livers of approximately 150 – 200 g. were obtained from the Judicial Mortuary of Panama. The livers were used at different interval from 12, 24, 48, 72 and 96 hours of decomposition. The flies were captured during 3 hours with intervals of 10, 15 and 20 min, until the 3 hours sampling was completed. A total amount of 1 003 flies were captured, distributed in 3 families: Calliphoridae, Sarcophagide y Muscidae. To capture 11 species, the more abundant species corresponded to Chrysomya megacephala, with 464 specimens, Lucila cuprina, with 117 specimens, Lucilia sericata, with 55 specimens and Lucilia eximia, with 47 specimens. The purpose of this research was knew the colonization of human liver, exposed at different time intervals in an urban area of the province of Panama.Se obtuvieron cuatro muestras de hígados humanos, de aproximadamente de 150 a 200 g. de la Morgue Judicial de Panamá. Los tejidos se expusieron a intervalos de tiempo que iban desde las primeras 12 horas, incluyendo las 24, 48, 72 y hasta 96 horas de descomposición. Las capturas de las moscas se realizaron durante tres horas continuas. En total se capturaron 1003 ejemplares, distribuidos en tres familias y 11 especies: Calliphoridae, Sarcophagidae y Muscida. La familia que mayormente atrapada en los tejidos fue la Calliphoridae seguida de la Sarcophagidae. Las especies más abundantes en el área correspondió a Chrysomya megacephala, con 464 ejemplares y Lucilia cuprina con 117 ejemplares, seguido de Lucilia sericata con 55 ejemplares y Lucilia eximia con 47 ejemplares. El objetivo de esta investigación fue conocer las principales especies de moscas necrófagas que arriban a los hígados humanos, expuestos a diferentes intervalos, en un área urbana de la provincia de Panamá

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Measurement of inclusive jet and dijet cross-sections in proton-proton collisions at s √ =13 TeV with the ATLAS detector

Inclusive jet and dijet cross-sections are measured in proton-proton collisions at a centre-of-mass energy of 13 TeV. The measurement uses a dataset with an integrated luminosity of 3.2 fb−1 recorded in 2015 with the ATLAS detector at the Large Hadron Collider. Jets are identified using the anti-kt algorithm with a radius parameter value of R = 0.4. The inclusive jet cross-sections are measured double-differentially as a function of the jet transverse momentum, covering the range from 100 GeV to 3.5 TeV, and the absolute jet rapidity up to |y| = 3. The double-differential dijet production cross-sections are presented as a function of the dijet mass, covering the range from 300 GeV to 9 TeV, and the half absolute rapidity separation between the two leading jets within |y| < 3, y∗, up to y∗ = 3. Next-to-leading-order, and next-to-next-to-leading-order for the inclusive jet measurement, perturbative QCD calculations corrected for non-perturbative and electroweak effects are compared to the measured cross-sections

Search for additional heavy neutral Higgs and gauge bosons in the ditau final state produced in 36 fb−1 of pp collisions at √s=13 TeV with the ATLAS detector

A search for heavy neutral Higgs bosons and Z′ bosons is performed using a data sample corresponding to an integrated luminosity of 36.1 fb−1 from proton-proton collisions at √s=13 TeV recorded by the ATLAS detector at the LHC during 2015 and 2016. The heavy resonance is assumed to decay to τ+τ− with at least one tau lepton decaying to final states with hadrons and a neutrino. The search is performed in the mass range of 0.2-2.25 TeV for Higgs bosons and 0.2-4.0 TeV for Z′ bosons. The data are in good agreement with the background predicted by the Standard Model. The results are interpreted in benchmark scenarios. In the context of the hMSSM scenario, the data exclude tan β > 1.0 for mA= 0.25 TeV and tan β > 42 for mA=1.5 TeV at the 95% confidence level. For the Sequential Standard Model, ZSSM′ with mZ′< 2.42 TeV is excluded at 95% confidence level, while Z NU′ with mZ ′ < 2.25 TeV is excluded for the non-universal G(221) model that exhibits enhanced couplings to third-generation fermions

Search for doubly charged Higgs boson production in multi-lepton final states with the ATLAS detector using proton-proton collisions at √s = 13TeV

A search for doubly charged Higgs bosons with pairs of prompt, isolated, highly energetic leptons with the same electric charge is presented. The search uses a proton–proton collision data sample at a centre-of-mass energy of 13 TeV corresponding to 36.1 fb −1 of integrated luminosity recorded in 2015 and 2016 by the ATLAS detector at the LHC. This analysis focuses on the decays H±±→e±e±, H±±→e±μ± and H±±→μ±μ±, fitting the dilepton mass spectra in several exclusive signal regions. No significant evidence of a signal is observed and corresponding limits on the production cross-section and consequently a lower limit on m(H±±) are derived at 95% confidence level. With ℓ±ℓ±=e±e±/μ±μ±/e±μ±, the observed lower limit on the mass of a doubly charged Higgs boson only coupling to left-handed leptons varies from 770 to 870 GeV (850 GeV expected) for B(H±±→ℓ±ℓ±)=100% and both the expected and observed mass limits are above 450 GeV for B(H±±→ℓ±ℓ±)=10% and any combination of partial branching ratios

Search for B −L R-parity-violating top squarks in √s=13 TeV pp collisions with the ATLAS experiment

A search is presented for the direct pair production of the stop, the supersymmetric partner of the top quark, that decays through an R-parity-violating coupling to a final state with two leptons and two jets, at least one of which is identified as a b-jet. The data set corresponds to an integrated luminosity of 36.1 fb−1 of proton-proton collisions at a center-of-mass energy of √s=13 TeV, collected in 2015 and 2016 by the ATLAS detector at the LHC. No significant excess is observed over the Standard Model background, and exclusion limits are set on stop pair production at a 95% confidence level. Lower limits on the stop mass are set between 600 GeV and 1.5 TeV for branching ratios above 10% for decays to an electron or muon and a b-quark

Search for supersymmetry in events with b-tagged jets and missing transverse momentum in pp collisions at √s = 13 TeV with the ATLAS detector

A search for the supersymmetric partners of the Standard Model bottom and top quarks is presented. The search uses 36.1 fb−1 of pp collision data at √s = 13 TeV collected by the ATLAS experiment at the Large Hadron Collider. Direct production of pairs of bottom and top squarks (b˜1 and t˜1) is searched for in final states with b-tagged jets and missing transverse momentum. Distinctive selections are defined with either no charged leptons (electrons or muons) in the final state, or one charged lepton. The zero-lepton selection targets models in which the b˜1 is the lightest squark and decays via b˜1 → bχ˜01 , where ˜χ01 is the lightest neutralino. The one-lepton final state targets models where bottom or top squarks are produced and can decay into multiple channels, b˜1 → bχ˜01 and b˜1 → tχ˜±1, or t˜1 → tχ˜01 and t˜1→ bχ˜±1, where ˜χ±1 is the lightest chargino and the mass difference mχ˜±1 − mχ˜01 is set to 1 GeV. No excess above the expected Standard Model background is observed. Exclusion limits at 95% confidence level on the mass of third-generation squarks are derived in various supersymmetry-inspired simplified models

Search for diboson resonances with boson-tagged jets in pp collisions at √s=13 TeV with the ATLAS detector

Narrow resonances decaying into WW, WZ or ZZ boson pairs are searched for in 36.7 fb−1 of proton–proton collision data at a centre-of-mass energy of √s=13 TeV recorded with the ATLAS detector at the Large Hadron Collider in 2015 and 2016. The diboson system is reconstructed using pairs of large-radius jets with high transverse momentum and tagged as compatible with the hadronic decay of high-momentum W or Z bosons, using jet mass and substructure properties. The search is sensitive to diboson resonances with masses in the range 1.2–5.0 TeV. No significant excess is observed in any signal region. Exclusion limits are set at the 95% confidence level on the production cross section times branching ratio to dibosons for a range of theories beyond the Standard Model. Model-dependent lower limits on the mass of new gauge bosons are set, with the highest limit set at 3.5 TeV in the context of mass-degenerate resonances that couple predominantly to bosons