Nitric Oxide Antagonizes the Acid Tolerance Response that Protects Salmonella against Innate Gastric Defenses

Reactive nitrogen species (RNS) derived from dietary and salivary inorganic nitrogen oxides foment innate host defenses associated with the acidity of the stomach. The mechanisms by which these reactive species exert antimicrobial activity in the gastric lumen are, however, poorly understood.The genetically tractable acid tolerance response (ATR) that enables enteropathogens to survive harsh acidity was screened for signaling pathways responsive to RNS. The nitric oxide (NO) donor spermine NONOate derepressed the Fur regulon that controls secondary lines of resistance against organic acids. Despite inducing a Fur-mediated adaptive response, acidified RNS largely repressed oral virulence as demonstrated by the fact that Salmonella bacteria exposed to NO donors during mildly acidic conditions were shed in low amounts in feces and exhibited ameliorated oral virulence. NO prevented Salmonella from mounting a de novo ATR, but was unable to suppress an already functional protective response, suggesting that RNS target regulatory cascades but not their effectors. Transcriptional and translational analyses revealed that the PhoPQ signaling cascade is a critical ATR target of NO in rapidly growing Salmonella. Inhibition of PhoPQ signaling appears to contribute to most of the NO-mediated abrogation of the ATR in log phase bacteria, because the augmented acid sensitivity of phoQ-deficient Salmonella was not further enhanced after RNS treatment.Since PhoPQ-regulated acid resistance is widespread in enteric pathogens, the RNS-mediated inhibition of the Salmonella ATR described herein may represent a common component of innate host defenses

Evidence for collectivity in pp collisions at the LHC

Measurements of two- and multi-particle angular correlations in pp collisions at s=5,7, and 13TeV are presented as a function of charged-particle multiplicity. The data, corresponding to integrated luminosities of 1.0pb−1 (5 TeV), 6.2pb−1 (7 TeV), and 0.7pb−1 (13 TeV), were collected using the CMS detector at the LHC. The second-order (v2) and third-order (v3) azimuthal anisotropy harmonics of unidentified charged particles, as well as v2 of KS0 and Λ/Λ‾ particles, are extracted from long-range two-particle correlations as functions of particle multiplicity and transverse momentum. For high-multiplicity pp events, a mass ordering is observed for the v2 values of charged hadrons (mostly pions), KS0, and Λ/Λ‾, with lighter particle species exhibiting a stronger azimuthal anisotropy signal below pT≈2GeV/c. For 13 TeV data, the v2 signals are also extracted from four- and six-particle correlations for the first time in pp collisions, with comparable magnitude to those from two-particle correlations. These observations are similar to those seen in pPb and PbPb collisions, and support the interpretation of a collective origin for the observed long-range correlations in high-multiplicity pp collisions.BMWFW and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MOST, and NSFC (China); COLCIEN-CIAS (Colombia); MSES and CSF (Croatia); RPF (Cyprus); SENESCYT (Ecuador); MoER, ERC IUT and ERDF (Estonia); Academy of Fin-land, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NIH (Hun-gary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); MSIP and NRF (Republic of Korea); LAS (Lithuania); MOE and UM (Malaysia); BUAP, CINVESTAV, CONACYT, LNS, SEP, and UASLP-FAI (Mexico); MBIE (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Dubna); MON, RosAtom, RAS and RFBR (Russia); MESTD (Serbia); SEIDI and CPAN (Spain); Swiss Funding Agencies (Switzerland); MST (Taipei); ThEPCenter, IPST, STAR and NSTDA (Thailand); TUBITAK and TAEK (Turkey); NASU and SFFR (Ukraine); STFC (United Kingdom); DOE and NSF (USA)

Measurement of the mass of the top quark in decays with a J/ψ meson in pp collisions at 8 TeV

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