Abundant variation in microsatellites of the parasitic nematode Trichostrongylus tenuis and linkage to a tandem repeat

An understanding of how genes move between and within populations of parasitic nematodes is important in combating the evolution and spread of anthelmintic resistance. Much has been learned by studying mitochondrial DNA markers, but autosomal markers such as microsatellites have been applied to only a few nematode species, despite their many advantages for studying gene flow in eukaryotes. Here, we describe the isolation of 307 microsatellites from Trichostrongylus tenuis, an intestinal nematode of red grouse. High levels of variation were revealed at sixteen microsatellite loci (including three sex-lined loci) in 111 male T. tenuis nematodes collected from four hosts at a single grouse estate in Scotland (average He = 0.708; mean number of alleles = 12.2). A population genetic analysis detected no deviation from panmixia either between (F(ST) = 0.00) or within hosts (F(IS) = 0.015). We discuss the feasibility of developing microsatellites in parasitic nematodes and the problem of null alleles. We also describe a novel 146-bp repeat element, TteREP1, which is linked to two-thirds of the microsatellites sequenced and is associated with marker development failure. The sequence of TteREP1 is related to the TcREP-class of repeats found in several other trichostrongyloid species including Trichostrongylus colubriformis and Haemonchus contortus

A novel mechanism regulating DNA-damage repair in Mycobacterium tuberculosis.

The intracellular pathogen Mycobacterium tuberculosis (M. tuberculosis) resides in macrophages and is the causative agent of human tuberculosis. Infected macrophages produce reactive oxygen and nitrogen intermediates, known to damage DNA therefore DNA damage repair is thought to be important in survival of M. tuberculosis in the host. The expression of many bacterial DNA repair genes is often regulated by the SOS response, in which RecA is an integral part however, in M. tuberculosis the majority of genes in the DNA-damage regulon are regulated independently of the RecA/LexA system. In this study two potential mechanisms for this alternative mode of gene regulation were investigated. The first hypothesis addressed was that regulation of expression following DNA-damage is controlled by an alternative sigma factor. Sigma factors are protein subunits of RNA polymerase, which confer specificity of binding to particular promoters. The function/expression of alternative sigma factors is usually regulated by various mechanisms. The sigma factor SigG is the most highly induced of all 13 sigma factors of M. tuberculosis in response to DNA-damage in both wild-type and ArecA strains. A knockout of sigG in M. tuberculosis was constructed, and found to be more susceptible to mitomycin C stress than wild-type H37Rv and attenuated in mice. ruvC was shown to possesses 2 transcriptional start sites, and although neither were regulated by SigG, the PI promoter appeared to be dual regulated by LexA and the RecA/LexA independent mechanism. Microarray analysis revealed that SigG was not significantly involved in regulation of the RecA/LexA independent DNA-damage regulon, but that SigG directly or indirectly regulated expression of 127 genes in the absence of DNA-damage. The other possible mode of RecA/LexA independent regulation was via a repressor/activator protein. Gel shifts assays using M. tuberculosis cell free extracts were used to attempt to identify a repressor or activator protein that bound to the operator of the recA PI promoter, known to be induced independently of RecA, but failed to detect specific binding. Published microarray data revealed that Rv2017, a predicted regulatory protein, was upregulated in both wild-type and ArecA strains of M. tuberculosis in response to DNA-damage. Therefore, a gene inactivation knockout of Rv2017 was constructed and analysed in M. tuberculosis. The ARv2017 strain was hyposensitive to mitomycin C stress and preliminary mouse in-vivo infection data suggested that the ARv2017 strain may be hypervirulent. Microarray data revealed that Rv2017 plays a direct/indirect role in regulation of a large regulon, including some genes in the DNA-damage repair regulon

A Measurement of the Cosmic Ray Spectrum and Composition at the Knee

The energy spectrum and primary composition of cosmic rays with energy between $3\times 10^{14}$ and 3\times10^{16}\unit{eV} have been studied using the CASA-BLANCA detector. CASA measured the charged particle distribution of air showers, while BLANCA measured the lateral distribution of Cherenkov light. The data are interpreted using the predictions of the CORSIKA air shower simulation coupled with four different hadronic interaction codes. The differential flux of cosmic rays measured by BLANCA exhibits a knee in the range of 2--3 PeV with a width of approximately 0.5 decades in primary energy. The power law indices of the differential flux below and above the knee are $-2.72\pm0.02$ and $-2.95\pm0.02$. We present our data both as a mean depth of shower maximum and as a mean nuclear mass. A multi-component fit using four elemental species shows the same composition trends given by the mean quantities, and also indicates that QGSJET and VENUS are the preferred hadronic interaction models. We find that an initially mixed composition turns lighter between 1 and 3 PeV, and then becomes heavier with increasing energy above 3 PeV.Comment: 25 pages, 10 figures. Submitted to Astroparticle Physic

Macro and micro diversity of Clostridium difficile isolates from diverse sources and geographical locations.

Clostridium difficile has emerged rapidly as the leading cause of antibiotic-associated diarrheal disease, with the temporal and geographical appearance of dominant PCR ribotypes such as 017, 027 and 078. Despite this continued threat, we have a poor understanding of how or why particular variants emerge and the sources of strains that dominate different human populations. We have undertaken a breadth genotyping study using multilocus sequence typing (MLST) analysis of 385 C. difficile strains from diverse sources by host (human, animal and food), geographical locations (North America, Europe and Australia) and PCR ribotypes. Results identified 18 novel sequence types (STs) and 3 new allele sequences and confirmed the presence of five distinct clonal lineages generally associated with outbreaks of C. difficile infection in humans. Strains of animal and food origin were found of both ST-1 and ST-11 that are frequently associated with human disease. An in depth MLST analysis of the evolutionary distant ST-11/PCR ribotype 078 clonal lineage revealed that ST-11 can be found in alternative but closely related PCR ribotypes and PCR ribotype 078 alleles contain mutations generating novel STs. PCR ribotype 027 and 017 lineages may consist of two divergent subclades. Furthermore evidence of microdiversity was present within the heterogeneous clade 1. This study helps to define the evolutionary origin of dominant C. difficile lineages and demonstrates that C. difficile is continuing to evolve in concert with human activity

Asymptotic properties of Born-improved amplitudes with gauge bosons in the final state

For processes with gauge bosons in the final state we show how to continuously connect with a single Born-improved amplitude the resonant region, where resummation effects are important, with the asymptotic region far away from the resonance, where the amplitude must reduce to its tree-level form. While doing so all known field-theoretical constraints are respected, most notably gauge-invariance, unitarity and the equivalence theorem. The calculations presented are based on the process $f\bar{f}\to ZZ$, mediated by a possibly resonant Higgs boson; this process captures all the essential features, and can serve as a prototype for a variety of similar calculations. By virtue of massive cancellations the resulting closed expressions for the differential and total cross-sections are particularly compact.Comment: 23 pages, Latex, 4 Figures, uses axodra

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