Intestinal helminth co-infection is an unrecognised risk factor for increased pneumococcal carriage density and invasive disease.

Infection with Streptococcus pneumoniae is the leading cause of death in children and burden of disease is greatest where helminth infections are also common. We investigated the impact of intestinal helminth co-infection on pneumococcal carriage; a risk factor for invasive disease. We used a mouse co-infection model and clinical data to assess the impact of co-infection on carriage density. Co-infection in mice was associated with increased pneumococcal carriage density and dissemination into lungs. Helminth-infected children also exhibited increased carriage density as compared to uninfected children. Anthelmintic treatment may be a cost-effective method of reducing pneumococcal disease burden in lower-income countries

Exposure to diesel exhaust particles increases susceptibility to invasive pneumococcal disease.

BACKGROUND: The World Health Organization estimates that air pollution is responsible for 7 million deaths per annum, with 7% of these attributable to pneumonia. Many of these fatalities have been linked to exposure to high levels of airborne particulates, such as diesel exhaust particles (DEPs). OBJECTIVES: We sought to determine whether exposure to DEPs could promote the progression of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae to invasive pneumococcal disease. METHODS: We used mouse models and in vitro assays to provide a mechanistic understanding of the link between DEP exposure and pneumococcal disease risk, and we confirmed our findings by using induced sputum macrophages isolated from healthy human volunteers. RESULTS: We demonstrate that inhaled exposure to DEPs disrupts asymptomatic nasopharyngeal carriage of S pneumoniae in mice, leading to dissemination to lungs and blood. Pneumococci are transported from the nasopharynx to the lungs following exposure to DEPs, leading to increased proinflammatory cytokine production, reduced phagocytic function of alveolar macrophages, and consequently, increased pneumococcal loads within the lungs and translocation into blood. These findings were confirmed by using DEP-exposed induced sputum macrophages isolated from healthy volunteers, demonstrating that impaired innate immune mechanisms following DEP exposure are also at play in humans. CONCLUSION: Lung inhaled DEPs increase susceptibility to pneumococcal disease by leading to loss of immunological control of pneumococcal colonisation, increased inflammation, tissue damage, and systemic bacterial dissemination

Analysis of inositol phosphate metabolism by capillary electrophoresis electrospray ionization mass spectrometry

The analysis of myo-inositol phosphates (InsPs) and myo-inositol pyrophosphates (PP-InsPs) is a daunting challenge due to the large number of possible isomers, the absence of a chromophore, the high charge density, the low abundance, and the instability of the esters and anhydrides. Given their importance in biology, an analytical approach to follow and understand this complex signaling hub is desirable. Here, capillary electrophoresis (CE) coupled to electrospray ionization mass spectrometry (ESI-MS) is implemented to analyze complex mixtures of InsPs and PP-InsPs with high sensitivity. Stable isotope labeled (SIL) internal standards allow for matrix-independent quantitative assignment. The method is validated in wild-type and knockout mammalian cell lines and in model organisms. SIL-CE-ESI-MS enables the accurate monitoring of InsPs and PP-InsPs arising from compartmentalized cellular synthesis pathways, by feeding cells with either [13C6]-myo-inositol or [13C6]-D-glucose. In doing so, we provide evidence for the existence of unknown inositol synthesis pathways in mammals, highlighting the potential of this method to dissect inositol phosphate metabolism and signalling

Impaired alanine transport or exposure to d-cycloserine increases the susceptibility of MRSA to β-lactam antibiotics

Prolonging the clinical effectiveness of β-lactams, which remain first-line antibiotics for many infections, is an important part of efforts to address antimicrobial resistance. We report here that inactivation of the predicted d-cycloserine (DCS) transporter gene cycA re-sensitized MRSA to β-lactam antibiotics. The cycA mutation also resulted in hyper-susceptibility to DCS, an alanine analogue antibiotic that inhibits alanine racemase and d-alanine ligase required for d-alanine incorporation into cell wall peptidoglycan (PG). Alanine transport was impaired in the cycA mutant and this correlated with increased susceptibility to oxacillin and DCS. The cycA mutation or exposure to DCS were both associated with the accumulation of muropeptides with tripeptide stems lacking the terminal d-ala-d-ala and reduced PG crosslinking, prompting us to investigate synergism between β-lactams and DCS. DCS re-sensitised MRSA to β-lactams in vitro and significantly enhanced MRSA eradication by oxacillin in a mouse bacteraemia model. These findings reveal alanine transport as a new therapeutic target to enhance the susceptibility of MRSA to β-lactam antibiotics.</jats:p

Measurement of the running of the QED coupling in small-angle Bhabha scattering at LEP

Using the OPAL detector at LEP, the running of the effective QED coupling alpha(t) is measured for space-like momentum transfer from the angular distribution of small-angle Bhabha scattering. In an almost ideal QED framework, with very favourable experimental conditions, we obtain: Delta alpha(-6.07GeV^2) - Delta alpha(-1.81GeV^2) = (440 pm 58 pm 43 pm 30) X 10^-5, where the first error is statistical, the second is the experimental systematic and the third is the theoretical uncertainty. This agrees with current evaluations of alpha(t).The null hypothesis that alpha remains constant within the above interval of -t is excluded with a significance above 5sigma. Similarly, our results are inconsistent at the level of 3sigma with the hypothesis that only leptonic loops contribute to the running. This is currently the most significant direct measurment where the running alpha(t) is probed differentially within the measured t range.Comment: 43 pages, 12 figures, Submitted to Euro. Phys. J.

A Measurement of Rb using a Double Tagging Method

The fraction of Z to bbbar events in hadronic Z decays has been measured by the OPAL experiment using the data collected at LEP between 1992 and 1995. The Z to bbbar decays were tagged using displaced secondary vertices, and high momentum electrons and muons. Systematic uncertainties were reduced by measuring the b-tagging efficiency using a double tagging technique. Efficiency correlations between opposite hemispheres of an event are small, and are well understood through comparisons between real and simulated data samples. A value of Rb = 0.2178 +- 0.0011 +- 0.0013 was obtained, where the first error is statistical and the second systematic. The uncertainty on Rc, the fraction of Z to ccbar events in hadronic Z decays, is not included in the errors. The dependence on Rc is Delta(Rb)/Rb = -0.056*Delta(Rc)/Rc where Delta(Rc) is the deviation of Rc from the value 0.172 predicted by the Standard Model. The result for Rb agrees with the value of 0.2155 +- 0.0003 predicted by the Standard Model.Comment: 42 pages, LaTeX, 14 eps figures included, submitted to European Physical Journal

Measurement of the B+ and B-0 lifetimes and search for CP(T) violation using reconstructed secondary vertices

The lifetimes of the B+ and B-0 mesons, and their ratio, have been measured in the OPAL experiment using 2.4 million hadronic Z(0) decays recorded at LEP. Z(0) --> b (b) over bar decays were tagged using displaced secondary vertices and high momentum electrons and muons. The lifetimes were then measured using well-reconstructed charged and neutral secondary vertices selected in this tagged data sample. The results aretau(B+) = 1.643 +/- 0.037 +/- 0.025 pstau(Bo) = 1.523 +/- 0.057 +/- 0.053 pstau(B+)/tau(Bo) = 1.079 +/- 0.064 +/- 0.041,where in each case the first error is statistical and the second systematic.A larger data sample of 3.1 million hadronic Z(o) decays has been used to search for CP and CPT violating effects by comparison of inclusive b and (b) over bar hadron decays, No evidence fur such effects is seen. The CP violation parameter Re(epsilon(B)) is measured to be Re(epsilon(B)) = 0.001 +/- 0.014 +/- 0.003and the fractional difference between b and (b) over bar hadron lifetimes is measured to(Delta tau/tau)(b) = tau(b hadron) - tau((b) over bar hadron)/tau(average) = -0.001 +/- 0.012 +/- 0.008

Connectivity within and among a Network of Temperate Marine Reserves

Networks of marine reserves are increasingly being promoted as a means of conserving marine biodiversity. One consideration in designing systems of marine reserves is the maintenance of connectivity to ensure the long-term persistence and resilience of populations. Knowledge of connectivity, however, is frequently lacking during marine reserve design and establishment. We characterise patterns of genetic connectivity of 3 key species of habitat-forming macroalgae across an established network of temperate marine reserves on the east coast of Australia and the implications for adaptive management and marine reserve design. Connectivity varied greatly among species. Connectivity was high for the subtidal macroalgae Ecklonia radiata and Phyllospora comosa and neither species showed any clear patterns of genetic structuring with geographic distance within or among marine parks. In contrast, connectivity was low for the intertidal, Hormosira banksii, and there was a strong pattern of isolation by distance. Coastal topography and latitude influenced small scale patterns of genetic structure. These results suggest that some species are well served by the current system of marine reserves in place along this temperate coast but it may be warranted to revisit protection of intertidal habitats to ensure the long-term persistence of important habitat-forming macroalgae. Adaptively managing marine reserve design to maintain connectivity may ensure the long-term persistence and resilience of marine habitats and the biodiversity they support

Measurement of the W+W−γW^{+}W^{-} \gamma Cross-section and First direct Limits on Anomalous Electroweak Quartic Gauge Couplings

A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W + W − events accompanied by hard photon radiation produced in e + e − collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183 pb −1 of data recorded at s =189 GeV. From these data, 17 W + W − γ candidates are selected with photon energy greater than 10 GeV, consistent with the Standard Model expectation. These events are used to measure the e + e − →W + W − γ cross-section within a set of geometric and kinematic cuts, σ ̂ WW γ =136±37±8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the W + W − γγ and W + W − γ Z 0 vertices: −0.070 GeV −