Higher dimensional operators and LHC Higgs data : the role of modified kinematics

The inclusion of higher-dimensional gauge invariant operators induces new Lorentz structures in Higgs couplings with electroweak gauge boson pairs. This in principle affects the kinematics of Higgs production and decay, thereby modifying the efficiencies of the experimental cuts compared to what simulations based on the standard model interactions yield. Taking some sample cases, we perform a rigorous analysis of how the efficiencies differ for various strengths of the additional operator vis-a-vis the standard model interactions, scanning over the values of both of them. While the response to cuts can be markedly different in some regions, we find that the sensitivity to new operator structures is relatively limited, so long as we remain confined to the 2-sigma regions around the best fit signal strengths measured at the Large Hadron Collider. We also show modifications to certain kinematical distributions including the new operators in the diphoton final state.Comment: 26 pages, 9 figures; v2: Some numerical factors corrected, conclusions unchanged. Comments and references added. Version to be published in Phys.Rev.

Dilepton and Four-Lepton Signals at the LHC in the Littlest Higgs Model with T-parity Violation

In the presence of the T-parity violating Wess-Zumino-Witten (WZW) anomaly term, the otherwise stable heavy photon A_H in the Littlest Higgs model with T-parity (LHT) decays to either Standard Model (SM) gauge boson pairs, or to SM fermions via loop diagrams. We make a detailed study of the collider signatures where the A_H can be reconstructed from invariant mass peaks in the opposite sign same flavor dilepton or the four-lepton channels. This enables us to obtain information about the fundamental symmetry breaking scale f in the LHT and thereby the low-lying mass spectrum of the theory. In addition, indication of the presence of the WZW term gives us hints of the possible UV completion of the LHT via strong dynamics. The crucial observation is that the sum of all production processes of heavy T-odd quark pairs has a sizeable cross-section at the LHC and these T-odd particles eventually all cascade decay down to the heavy photon A_H. We show that for certain regions of the parameter space with either a small f of around 500 GeV or relatively light T-odd quarks with a mass of around 400 GeV, one can reconstruct the A_H even at the early LHC run with \sqrt{s}=10 TeV and a modest integrated luminosity of 200 pb^{-1}. At \sqrt{s} = 14 TeV and with an integrated luminosity of 30 fb^{-1}, it is possible to cover a large part of the typical parameter space of the LHT, with the scale f up to 1.5 TeV and with T-odd quark masses almost up to 1 TeV. In this region of the parameter space, the mass of the reconstructed A_H ranges from 66 GeV to 230 GeV.Comment: 35 pages, 4 figures; v2: additional multiple hard jets included in background simulation using ALPGEN, main conclusions unchanged, references added, version as published in JHEP

Same-sign trileptons and four-leptons as signatures of new physics at the Large Hadron Collider

We point out that same-sign multilepton events, not given due attention yet for new physics search, can be extremely useful at the Large Hadron Collider. After showing the easy reducibility of the standard model backgrounds, we demonstrate the viability of same-sign trilepton signals for R-parity breaking supersymmetry, at both 7 and 14 TeV. We find that same-sign four-leptons, too, can have appreciable rates. Same-sign trileptons are also expected, for example, in Little Higgs theories with T-parity broken by anomaly terms.Comment: 5 pages, 1 figure; v2: minor additions to text, references added, version to appear in Physical Review D (Rapid Communications

F420H2 Is Required for Phthiocerol Dimycocerosate Synthesis in Mycobacteria

Phthiocerol dimycocerosates (PDIM) are a group of cell surface-associated apolar lipids of Mycobacterium tuberculosis and closely related mycobacteria, such as Mycobacterium bovis and Mycobacterium leprae. A characteristic methoxy group of these lipids is generated from the methylation of a hydroxyl group of the direct precursors, the phthiotriols. The precursors arise from the reduction of phthiodiolones, the keto intermediates, by a ketoreductase. The putative phthiodiolone ketoreductase (PKR) is encoded by Rv2951c in M. tuberculosis and BCG_2972c in M. bovis BCG, and these open reading frames (ORFs) encode identical amino acid sequences. We investigated the cofactor requirement of the BCG_2972c protein. A comparative analysis based on the crystallographic structures of similar enzymes identified structural elements for binding of coenzyme F(420) and hydrophobic phthiodiolones in PKR. Coenzyme F(420) is a deazaflavin coenzyme that serves several key functions in pathogenic and nonpathogenic mycobacteria. We found that an M. bovis BCG mutant lacking F(420)-dependent glucose-6-phosphate dehydrogenase (Fgd), which generates F(420)H(2) (glucose-6-phosphate + F(420) → 6-phosphogluconate + F(420)H(2)), was devoid of phthiocerols and accumulated phthiodiolones. When the mutant was provided with F(420)H(2), a broken-cell slurry of the mutant converted accumulated phthiodiolones to phthiocerols; F(420)H(2) was generated in situ from F(420) and glucose-6-phosphate by the action of Fgd. Thus, the reaction mixture was competent in reducing phthiodiolones to phthiotriols (phthiodiolones + F(420)H(2) → phthiotriols + F(420)), which were then methylated to phthiocerols. These results established the mycobacterial phthiodiolone ketoreductase as an F(420)H(2)-dependent enzyme (fPKR). A phylogenetic analysis of close homologs of fPKR revealed potential F(420)-dependent lipid-modifying enzymes in a broad range of mycobacteria. IMPORTANCE Mycobacterium tuberculosis is the causative agent of tuberculosis, and phthiocerol dimycocerosates (PDIM) protect this pathogen from the early innate immune response of an infected host. Thus, the PDIM synthesis system is a potential target for the development of effective treatments for tuberculosis. The current study shows that a PDIM synthesis enzyme is dependent on the coenzyme F(420). F(420) is universally present in mycobacteria and absent in humans. This finding expands the number of experimentally validated F(420)-dependent enzymes in M. tuberculosis to six, each of which helps the pathogen to evade killing by the host immune system, and one of which activates an antituberculosis drug, PA-824. This work also has relevance to leprosy, since similar waxy lipids are found in Mycobacterium leprae

Whole genome sequence analysis reveals the broad distribution of the RtxA type 1 secretion system and four novel putative type 1 secretion systems throughout the Legionella genus.

Type 1 secretion systems (T1SSs) are broadly distributed among bacteria and translocate effectors with diverse function across the bacterial cell membrane. Legionella pneumophila, the species most commonly associated with Legionellosis, encodes a T1SS at the lssXYZABD locus which is responsible for the secretion of the virulence factor RtxA. Many investigations have failed to detect lssD, the gene encoding the membrane fusion protein of the RtxA T1SS, in non-pneumophila Legionella, which has led to the assumption that this system is a virulence factor exclusively possessed by L. pneumophila. Here we discovered RtxA and its associated T1SS in a novel Legionella taurinensis strain, leading us to question whether this system may be more widespread than previously thought. Through a bioinformatic analysis of publicly available data, we classified and determined the distribution of four T1SSs including the RtxA T1SS and four novel T1SSs among diverse Legionella spp. The ABC transporter of the novel Legionella T1SS Legionella repeat protein secretion system shares structural similarity to those of diverse T1SS families, including the alkaline protease T1SS in Pseudomonas aeruginosa. The Legionella bacteriocin (1-3) secretion systems T1SSs are novel putative bacteriocin transporting T1SSs as their ABC transporters include C-39 peptidase domains in their N-terminal regions, with LB2SS and LB3SS likely constituting a nitrile hydratase leader peptide transport T1SSs. The LB1SS is more closely related to the colicin V T1SS in Escherichia coli. Of 45 Legionella spp. whole genomes examined, 19 (42%) were determined to possess lssB and lssD homologs. Of these 19, only 7 (37%) are known pathogens. There was no difference in the proportions of disease associated and non-disease associated species that possessed the RtxA T1SS (p = 0.4), contrary to the current consensus regarding the RtxA T1SS. These results draw into question the nature of RtxA and its T1SS as a singular virulence factor. Future studies should investigate mechanistic explanations for the association of RtxA with virulence

Comparative Genomics and Proteomic Analysis of Assimilatory Sulfate Reduction Pathways in Anaerobic Methanotrophic Archaea

Sulfate is the predominant electron acceptor for anaerobic oxidation of methane (AOM) in marine sediments. This process is carried out by a syntrophic consortium of anaerobic methanotrophic archaea (ANME) and sulfate reducing bacteria (SRB) through an energy conservation mechanism that is still poorly understood. It was previously hypothesized that ANME alone could couple methane oxidation to dissimilatory sulfate reduction, but a genetic and biochemical basis for this proposal has not been identified. Using comparative genomic and phylogenetic analyses, we found the genetic capacity in ANME and related methanogenic archaea for sulfate reduction, including sulfate adenylyltransferase, APS kinase, APS/PAPS reductase and two different sulfite reductases. Based on characterized homologs and the lack of associated energy conserving complexes, the sulfate reduction pathways in ANME are likely used for assimilation but not dissimilation of sulfate. Environmental metaproteomic analysis confirmed the expression of 6 proteins in the sulfate assimilation pathway of ANME. The highest expressed proteins related to sulfate assimilation were two sulfite reductases, namely assimilatory-type low-molecular-weight sulfite reductase (alSir) and a divergent group of coenzyme F420-dependent sulfite reductase (Group II Fsr). In methane seep sediment microcosm experiments, however, sulfite and zero-valent sulfur amendments were inhibitory to ANME-2a/2c while growth in their syntrophic SRB partner was not observed. Combined with our genomic and metaproteomic results, the passage of sulfur species by ANME as metabolic intermediates for their SRB partners is unlikely. Instead, our findings point to a possible niche for ANME to assimilate inorganic sulfur compounds more oxidized than sulfide in anoxic marine environments

TmpL, a Transmembrane Protein Required for Intracellular Redox Homeostasis and Virulence in a Plant and an Animal Fungal Pathogen

The regulation of intracellular levels of reactive oxygen species (ROS) is critical for developmental differentiation and virulence of many pathogenic fungi. In this report we demonstrate that a novel transmembrane protein, TmpL, is necessary for regulation of intracellular ROS levels and tolerance to external ROS, and is required for infection of plants by the necrotroph Alternaria brassicicola and for infection of mammals by the human pathogen Aspergillus fumigatus. In both fungi, tmpL encodes a predicted hybrid membrane protein containing an AMP-binding domain, six putative transmembrane domains, and an experimentally-validated FAD/NAD(P)-binding domain. Localization and gene expression analyses in A. brassicicola indicated that TmpL is associated with the Woronin body, a specialized peroxisome, and strongly expressed during conidiation and initial invasive growth in planta. A. brassicicola and A. fumigatus ΔtmpL strains exhibited abnormal conidiogenesis, accelerated aging, enhanced oxidative burst during conidiation, and hypersensitivity to oxidative stress when compared to wild-type or reconstituted strains. Moreover, A. brassicicola ΔtmpL strains, although capable of initial penetration, exhibited dramatically reduced invasive growth on Brassicas and Arabidopsis. Similarly, an A. fumigatus ΔtmpL mutant was dramatically less virulent than the wild-type and reconstituted strains in a murine model of invasive aspergillosis. Constitutive expression of the A. brassicicola yap1 ortholog in an A. brassicicola ΔtmpL strain resulted in high expression levels of genes associated with oxidative stress tolerance. Overexpression of yap1 in the ΔtmpL background complemented the majority of observed developmental phenotypic changes and partially restored virulence on plants. Yap1-GFP fusion strains utilizing the native yap1 promoter exhibited constitutive nuclear localization in the A. brassicicola ΔtmpL background. Collectively, we have discovered a novel protein involved in the virulence of both plant and animal fungal pathogens. Our results strongly suggest that dysregulation of oxidative stress homeostasis in the absence of TmpL is the underpinning cause of the developmental and virulence defects observed in these studies