Inactivation of polyketide synthase and related genes results in the loss of complex lipids in Mycobacterium tuberculosis H37Rv

Aims: Phthiocerol dimycocerosate (PDIM) waxes and other lipids are necessary for successful Mycobacterium tuberculosis infection, although the exact role of PDIM in host-pathogen interactions remains unclear. In this study, we investigated the contribution of tesA, drrB, pks6 and pks11 genes in complex lipid biosynthesis in M. tuberculosis. Methods and Results: Four mutants were selected from M. tuberculosis H37Rv transposon mutant library. The transposon insertion sites were confirmed to be within the M. tuberculosis open reading frames for tesA (a probable thioesterase), drrB (predicted ABC transporter), pks11 (putative chalcone synthase) and pks6 (polyketide synthase). The first three of these transposon mutants were unable to generate PDIM and the fourth lacked novel polar lipids. Conclusions: Mycobacterium tuberculosis can be cultivated in vitro without the involvement of certain lipid synthesis genes, which may be necessary for in vivo pathogenicity. Significance and Impact of the Study: The use of transposon mutants is a new functional genomic approach for the eventual definition of the mycobacterial ‘lipidome’

Leishmania aethiopica field isolates bearing an endosymbiontic dsRNA virus induce pro-inflammatory cytokine response.

BACKGROUND: Infection with Leishmania parasites causes mainly cutaneous lesions at the site of the sand fly bite. Inflammatory metastatic forms have been reported with Leishmania species such as L. braziliensis, guyanensis and aethiopica. Little is known about the factors underlying such exacerbated clinical presentations. Leishmania RNA virus (LRV) is mainly found within South American Leishmania braziliensis and guyanensis. In a mouse model of L. guyanensis infection, its presence is responsible for an hyper-inflammatory response driven by the recognition of the viral dsRNA genome by the host Toll-like Receptor 3 leading to an exacerbation of the disease. In one instance, LRV was reported outside of South America, namely in the L. major ASKH strain from Turkmenistan, suggesting that LRV appeared before the divergence of Leishmania subgenera. LRV presence inside Leishmania parasites could be one of the factors implicated in disease severity, providing rationale for LRV screening in L. aethiopica. METHODOLOGY/PRINCIPAL FINDINGS: A new LRV member was identified in four L. aethiopica strains (LRV-Lae). Three LRV-Lae genomes were sequenced and compared to L. guyanensis LRV1 and L. major LRV2. LRV-Lae more closely resembled LRV2. Despite their similar genomic organization, a notable difference was observed in the region where the capsid protein and viral polymerase open reading frames overlap, with a unique -1 situation in LRV-Lae. In vitro infection of murine macrophages showed that LRV-Lae induced a TLR3-dependent inflammatory response as previously observed for LRV1. CONCLUSIONS/SIGNIFICANCE: In this study, we report the presence of an immunogenic dsRNA virus in L. aethiopica human isolates. This is the first observation of LRV in Africa, and together with the unique description of LRV2 in Turkmenistan, it confirmed that LRV was present before the divergence of the L. (Leishmania) and (Viannia) subgenera. The potential implication of LRV-Lae on disease severity due to L. aethiopica infections is discussed

Magnetoplasmon excitations in an array of periodically modulated quantum wires

Motivated by the recent experiment of Hochgraefe et al., we have investigated the magnetoplasmon excitations in a periodic array of quantum wires with a periodic modulation along the wire direction. The equilibrium and dynamic properties of the system are treated self-consistently within the Thomas-Fermi-Dirac-von Weizsaecker approximation. A calculation of the dynamical response of the system to a far-infrared radiation field reveals a resonant anticrossing between the Kohn mode and a finite-wavevector longitudinal excitation which is induced by the density modulation along the wires. Our theoretical calculations are found to be in excellent agreement with experiment.Comment: 9 pages, 8 figure

Viral discovery and diversity in trypanosomatid protozoa with a focus on relatives of the human parasite <i>Leishmania</i>.

Knowledge of viral diversity is expanding greatly, but many lineages remain underexplored. We surveyed RNA viruses in 52 cultured monoxenous relatives of the human parasite &lt;i&gt;Leishmania&lt;/i&gt; ( &lt;i&gt;Crithidia&lt;/i&gt; and &lt;i&gt;Leptomonas&lt;/i&gt; ), as well as plant-infecting &lt;i&gt;Phytomonas&lt;/i&gt; &lt;i&gt;Leptomonas pyrrhocoris&lt;/i&gt; was a hotbed for viral discovery, carrying a virus (Leptomonas pyrrhocoris ostravirus 1) with a highly divergent RNA-dependent RNA polymerase missed by conventional BLAST searches, an emergent clade of tombus-like viruses, and an example of viral endogenization. A deep-branching clade of trypanosomatid narnaviruses was found, notable as &lt;i&gt;Leptomonas seymouri&lt;/i&gt; bearing Narna-like virus 1 (LepseyNLV1) have been reported in cultures recovered from patients with visceral leishmaniasis. A deep-branching trypanosomatid viral lineage showing strong affinities to bunyaviruses was termed " &lt;i&gt;Leishbunyavirus&lt;/i&gt; " (LBV) and judged sufficiently distinct to warrant assignment within a proposed family termed " &lt;i&gt;Leishbunyaviridae&lt;/i&gt; " Numerous relatives of trypanosomatid viruses were found in insect metatranscriptomic surveys, which likely arise from trypanosomatid microbiota. Despite extensive sampling we found no relatives of the totivirus &lt;i&gt;Leishmaniavirus&lt;/i&gt; (LRV1/2), implying that it was acquired at about the same time the &lt;i&gt;Leishmania&lt;/i&gt; became able to parasitize vertebrates. As viruses were found in over a quarter of isolates tested, many more are likely to be found in the &gt;600 unsurveyed trypanosomatid species. Viral loss was occasionally observed in culture, providing potentially isogenic virus-free lines enabling studies probing the biological role of trypanosomatid viruses. These data shed important insights on the emergence of viruses within an important trypanosomatid clade relevant to human disease

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Search for invisible decays of the Higgs boson produced in association with a hadronically decaying vector boson in pp collisions at √s=8 TeV with the ATLAS detector

A search for Higgs boson decays to invisible particles is performed using 20.3 fb −1 of pp collision data at a centre-of-mass energy of 8 TeV recorded by the ATLAS detector at the Large Hadron Collider. The process considered is Higgs boson production in association with a vector boson (V=W or Z) that decays hadronically, resulting in events with two or more jets and large missing transverse momentum. No excess of candidates is observed in the data over the background expectation. The results are used to constrain VH production followed by H decaying to invisible particles for the Higgs boson mass range 115<mH<300 GeV. The 95 % confidence-level observed upper limit on σVH×BR(H→inv.) varies from 1.6 pb at 115 GeV to 0.13 pb at 300 GeV. Assuming Standard Model production and including the gg→H contribution as signal, the results also lead to an observed upper limit of 78 % at 95 % confidence level on the branching ratio of Higgs bosons decays to invisible particles at a mass of 125 GeV

Search for metastable heavy charged particles with large ionisation energy loss in pp collisions at √s = 8 TeV using the ATLAS experiment

Many extensions of the Standard Model predict the existence of charged heavy long-lived particles, such as R-hadrons or charginos. These particles, if produced at the Large Hadron Collider, should be moving non-relativistically and are therefore identifiable through the measurement of an anomalously large specific energy loss in the ATLAS pixel detector. Measuring heavy long-lived particles through their track parameters in the vicinity of the interaction vertex provides sensitivity to metastable particles with lifetimes from 0.6 ns to 30 ns. A search for such particles with the ATLAS detector at the Large Hadron Collider is presented, based on a data sample corresponding to an integrated luminosity of 18.4 8.4 fb −1 −1 of pp collisions at s √ =8 s=8 TeV. No significant deviation from the Standard Model background expectation is observed, and lifetime-dependent upper limits on R-hadrons and chargino production are set. Gluino R-hadrons with 10 ns lifetime and masses up to 1185 GeV are excluded at 95 % % confidence level, and so are charginos with 15 ns lifetime and masses up to 482 GeV

Search for the associated production of the Higgs boson with a top quark pair in multilepton final states with the ATLAS detector

A search for the associated production of the Higgs boson with a top quark pair is performed in multilepton final states using 20.3 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s=8 TeV at the Large Hadron Collider. Five final states, targeting the decays H→WW⁎H→WW⁎, ττ, and ZZ⁎, are examined for the presence of the Standard Model (SM) Higgs boson: two same-charge light leptons (e or μ) without a hadronically decaying τ lepton; three light leptons; two same-charge light leptons with a hadronically decaying τ lepton; four light leptons; and one light lepton and two hadronically decaying τ leptons. No significant excess of events is observed above the background expectation. The best fit for the tt¯H production cross section, assuming a Higgs boson mass of 125 GeV, is 2.1 −1.2+1.4 times the SM expectation, and the observed (expected) upper limit at the 95% confidence level is 4.7 (2.4) times the SM rate. The p-value for compatibility with the background-only hypothesis is 1.8σ; the expectation in the presence of a Standard Model signal is 0.9σ

Measurement of charged-particle spectra in Pb plus Pb collisions at root s(NN)=2.76 TeV with the ATLAS detector at the LHC

We thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWFW and FWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; EPLANET, ERC and NSRF, European Union; IN2P3-CNRS, CEA-DSM/IRFU, France; GNSF, Georgia; BMBF, DFG, HGF, MPG and AvH Foundation, Germany; GSRT and NSRF, Greece; RGC, Hong Kong SAR, China; ISF, MINERVA, GIF, I-CORE and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; BRF and RCN, Norway; MNiSW and NCN, Poland; GRICES and FCT, Portugal; MNE/IFA, Romania; MES of Russia and NRC KI, Russian Federation; JINR; MSTD, Serbia; MSSR, Slovakia; ARRS and MIZS, Slovenia; DST/NRF, South Africa; MINECO, ˇ Spain; SRC and Wallenberg Foundation, Sweden; SER, SNSF and Cantons of Bern and Geneva, Switzerland; NSC, Taiwan; TAEK, Turkey; STFC, the Royal Society and Leverhulme Trust, United Kingdom; DOE and NSF, United States of America. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN and the ATLAS Tier-1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NL-T1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (U.K.) and BNL (U.S.A.) and in the Tier-2 facilities worldwide