msbB deletion confers acute sensitivity to CO2 in Salmonella enterica serovar Typhimurium that can be suppressed by a loss-of-function mutation in zwf

<p>Abstract</p> <p>Background</p> <p>Pathogens tolerate stress conditions that include low pH, oxidative stress, high salt and high temperature in order to survive inside and outside their hosts. Lipopolysaccharide (LPS), which forms the outer-leaflet of the outer membrane in Gram-negative bacteria, acts as a permeability barrier. The lipid A moiety of LPS anchors it to the outer membrane bilayer. The MsbB enzyme myristoylates the lipid A precursor and loss of this enzyme, in <it>Salmonella</it>, is correlated with reduced virulence and severe growth defects that can both be compensated with extragenic suppressor mutations.</p> <p>Results</p> <p>We report here that <it>msbB </it>(or <it>msbB somA</it>) <it>Salmonella </it>are highly sensitive to physiological CO₂(5%), resulting in a 3-log reduction in plating efficiency. Under these conditions, <it>msbB Salmonella </it>form long filaments, bulge and lyse. These bacteria are also sensitive to acidic pH and high osmolarity. Although CO₂acidifies LB broth media, buffering LB to pH 7.5 did not restore growth of <it>msbB </it>mutants in CO₂, indicating that the CO₂-induced growth defects are not due to the effect of CO₂on the pH of the media. A transposon insertion in the glucose metabolism gene <it>zwf </it>compensates for the CO₂sensitivity of <it>msbB Salmonella</it>. The <it>msbB zwf </it>mutants grow on agar, or in broth, in the presence of 5% CO₂. In addition, <it>msbB zwf </it>strains show improved growth in low pH or high osmolarity media compared to the single <it>msbB </it>mutant.</p> <p>Conclusion</p> <p>These results demonstrate that <it>msbB </it>confers acute sensitivity to CO₂, acidic pH, and high osmolarity. Disruption of <it>zwf </it>in <it>msbB </it>mutants restores growth in 5% CO₂and results in improved growth in acidic media or in media with high osmolarity. These results add to a growing list of phenotypes caused by <it>msbB </it>and mutations that suppress specific growth defects.</p

Mechanical thrombectomy in acute basilar artery stroke: a systematic review and Meta-analysis of randomized controlled trials

Background: The evidence for mechanical thrombectomy in acute basilar artery occlusion has until now remained inconclusive with basilar artery strokes associated with high rates of death and disability. This systematic review and meta-analysis will summarize the available evidence for the effectiveness of mechanical thrombectomy in acute basilar artery occlusion compared to best medical therapy. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials using Embase, Medline and the Cochrane Central Register of Controlled Trials (CENTRAL). We calculated risk ratios (RRs) and 95% confidence intervals (CIs) to summarize the effect estimates for each outcome. Results: We performed a random effects (Mantel-Haenszel) meta-analysis of the four included randomized controlled trials comprising a total of 988 participants. We found a statistically significant improvement in the rates of those with a good functional outcome (mRS 0–3, RR 1.54, 1.16–2.06, p = 0.003) and functional independence (mRS 0–2, RR 1.69, 1.05–2.71, p = 0.03) in those who were treated with thrombectomy when compared to best medical therapy alone. Thrombectomy was associated with a higher level of sICH (RR 7.12, 2.16–23.54, p = 0.001) but this was not reflected in a higher mortality rate, conversely the mortality rate was significantly lower in the intervention group (RR 0.76, 0.65–0.89, p = 0.0004). Conclusions: Our meta-analysis of the recently presented randomized controlled studies is the first to confirm the disability and mortality benefit of mechanical thrombectomy in basilar artery stroke

QSO Absorption Systems Detected in Ne VIII: High-Metallicity Clouds with a Large Effective Cross Section

Using high resolution, high signal-to-noise ultraviolet spectra of the z = 0.9754 quasar PG1148+549 obtained with the Cosmic Origins Spectrograph (COS) on the Hubble Space Telescope, we study the physical conditions and abundances of NeVIII+OVI absorption line systems at z(abs) =0.68381, 0.70152, 0.72478. In addition to NeVIII and OVI, absorption lines from multiple ionization stages of oxygen (OII, OIII, OIV) are detected and are well-aligned with the more highly ionized species. We show that these absorbers are multiphase systems including hot gas (T ~ 10^{5.7} K) that produces NeVIII and OVI, and the gas metallicity of the cool phase ranges from Z = 0.3 Z_{solar} to supersolar. The cool (~10^{4} K) phases have densities n_{H} ~ 10^{-4} cm^{-3} and small sizes (< 4kpc); these cool clouds are likely to expand and dissipate, and the NeVIII may be within a transition layer between the cool gas and a surrounding, much hotter medium. The NeVIII redshift density, dN/dz = 7^{+7}_{-3}, requires a large number of these clouds for every L > 0.1L* galaxy and a large effective absorption cross section (>~ 100 kpc), and indeed, we find a star forming ~L* galaxy at the redshift of the z(abs)=0.72478 system, at an impact parameter of 217 kpc. Multiphase absorbers like these NeVIII systems are likely to be an important reservoir of baryons and metals in the circumgalactic media of galaxies.Comment: Final published version (Astrophysical Journal

Muon to electron conversion in the Littlest Higgs model with T-parity

Little Higgs models provide a natural explanation of the little hierarchy between the electroweak scale and a few TeV scale, where new physics is expected. Under the same inspiring naturalness arguments, this work completes a previous study on lepton flavor-changing processes in the Littlest Higgs model with T-parity exploring the channel that will eventually turn out to be the most sensitive, \mu-e conversion in nuclei. All one-loop contributions are carefully taken into account, results for the most relevant nuclei are provided and a discussion of the influence of the quark mixing is included. The results for the Ti nucleus are in good agreement with earlier work by Blanke et al., where a degenerate mirror quark sector was assumed. The conclusion is that, although this particular model reduces the tension with electroweak precision tests, if the restrictions on the parameter space derived from lepton flavor violation are taken seriously, the degree of fine tuning necessary to meet these constraints also disfavors this model.Comment: 26 pages, 7 figures, 4 tables; discussion improved, results unchanged, one reference added, version to appear in JHE

Lepton flavor violation decays τ−→μ−P1P2\tau^-\to \mu^- P_1 P_2 in the topcolor-assisted technicolor model and the littlest Higgs model with TT parity

The new particles predicted by the topcolor-assisted technicolor ($TC2$) model and the littlest Higgs model with T-parity (called $LHT$ model) can induce the lepton flavor violation ($LFV$) couplings at tree level or one loop level, which might generate large contributions to some $LFV$ processes. Taking into account the constraints of the experimental data on the relevant free parameters, we calculate the branching ratios of the $LFV$ decay processes $\tau^-\to\mu^- P_1 P_2$ with $P_1 P_2$ = $\pi^+\pi^-$, $K^+K^-$ and $K^0\bar{K^0}$ in the context of these two kinds of new physics models. We find that the $TC2$ model and the $LHT$ model can indeed produce significant contributions to some of these $LFV$ decay processes.Comment: 24 pages, 7 figure

Bulge growth through disk instabilities in high-redshift galaxies

The role of disk instabilities, such as bars and spiral arms, and the associated resonances, in growing bulges in the inner regions of disk galaxies have long been studied in the low-redshift nearby Universe. There it has long been probed observationally, in particular through peanut-shaped bulges. This secular growth of bulges in modern disk galaxies is driven by weak, non-axisymmetric instabilities: it mostly produces pseudo-bulges at slow rates and with long star-formation timescales. Disk instabilities at high redshift (z>1) in moderate-mass to massive galaxies (10^10 to a few 10^11 Msun of stars) are very different from those found in modern spiral galaxies. High-redshift disks are globally unstable and fragment into giant clumps containing 10^8-10^9 Msun of gas and stars each, which results in highly irregular galaxy morphologies. The clumps and other features associated to the violent instability drive disk evolution and bulge growth through various mechanisms, on short timescales. The giant clumps can migrate inward and coalesce into the bulge in a few 10^8 yr. The instability in the very turbulent media drives intense gas inflows toward the bulge and nuclear region. Thick disks and supermassive black holes can grow concurrently as a result of the violent instability. This chapter reviews the properties of high-redshift disk instabilities, the evolution of giant clumps and other features associated to the instability, and the resulting growth of bulges and associated sub-galactic components.Comment: 37 pages, 9 figures. Invited refereed review to appear in "Galactic Bulges", E. Laurikainen, D. Gadotti, R. Peletier (eds.), Springe

Measurement of the diffractive structure function in deep inelastic scattering at HERA

This paper presents an analysis of the inclusive properties of diffractive deep inelastic scattering events produced in $ep$ interactions at HERA. The events are characterised by a rapidity gap between the outgoing proton system and the remaining hadronic system. Inclusive distributions are presented and compared with Monte Carlo models for diffractive processes. The data are consistent with models where the pomeron structure function has a hard and a soft contribution. The diffractive structure function is measured as a function of \xpom, the momentum fraction lost by the proton, of $\beta$, the momentum fraction of the struck quark with respect to \xpom, and of $Q^2$. The \xpom dependence is consistent with the form \xpoma where $a~=~1.30~\pm~0.08~(stat)~^{+~0.08}_{-~0.14}~(sys)$ in all bins of $\beta$ and $Q^2$. In the measured $Q^2$ range, the diffractive structure function approximately scales with $Q^2$ at fixed $\beta$. In an Ingelman-Schlein type model, where commonly used pomeron flux factor normalisations are assumed, it is found that the quarks within the pomeron do not saturate the momentum sum rule.Comment: 36 pages, latex, 11 figures appended as uuencoded fil

Development of Social Variation in Reproductive Schedules: A Study from an English Urban Area

Background: There is striking social variation in the timing of the onset of childbearing in contemporary England, with the mean age at first motherhood about 8 years earlier in the most deprived compared to the least deprived neighbourhoods. However, relatively little is known about how these social differences in reproductive schedule develop in childhood. Methodology/Principal Findings: We studied the development of differences in reproductive schedules, using a crosssectional survey over 1000 school students aged 9–15 in the metropolitan borough of North Tyneside. Students from more deprived neighbourhoods had earlier ideal ages for parenthood than those from more affluent ones, and these differences were fully apparent by age 11. We found evidence consistent with three mechanisms playing a role in maintaining the socioeconomic gradient. These were: vertical intergenerational transmission (students whose own parents were younger at their birth wanted children younger); oblique intergenerational transmission (students in neighbourhoods where parents were younger in general wanted children earlier); and low parental investment (students who did not feel emotionally supported by their own parents wanted children at a younger age). Conclusions/Significance: Our results shed some light on the proximate factors which may be involved in maintaining early childbearing in disadvantaged communities. They help understand why educational initiatives aimed at adolescents tend to have no effect, whereas improving the well-being of poor families with young children may do so. Our results also sugges