Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end

Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process

Pattern and Outcome of Chest Injuries at Bugando Medical Centre in Northwestern Tanzania.

Chest injuries constitute a continuing challenge to the trauma or general surgeon practicing in developing countries. This study was conducted to outline the etiological spectrum, injury patterns and short term outcome of these injuries in our setting. This was a prospective study involving chest injury patients admitted to Bugando Medical Centre over a six-month period from November 2009 to April 2010 inclusive. A total of 150 chest injury patients were studied. Males outnumbered females by a ratio of 3.8:1. Their ages ranged from 1 to 80 years (mean = 32.17 years). The majority of patients (72.7%) sustained blunt injuries. Road traffic crush was the most common cause of injuries affecting 50.7% of patients. Chest wall wounds, hemothorax and rib fractures were the most common type of injuries accounting for 30.0%, 21.3% and 20.7% respectively. Associated injuries were noted in 56.0% of patients and head/neck (33.3%) and musculoskeletal regions (26.7%) were commonly affected. The majority of patients (55.3%) were treated successfully with non-operative approach. Underwater seal drainage was performed in 39 patients (19.3%). One patient (0.7%) underwent thoracotomy due to hemopericardium. Thirty nine patients (26.0%) had complications of which wound sepsis (14.7%) and complications of long bone fractures (12.0%) were the most common complications. The mean LOS was 13.17 days and mortality rate was 3.3%. Using multivariate logistic regression analysis, associated injuries, the type of injury, trauma scores (ISS, RTS and PTS) were found to be significant predictors of the LOS (P < 0.001), whereas mortality was significantly associated with pre-morbid illness, associated injuries, trauma scores (ISS, RTS and PTS), the need for ICU admission and the presence of complications (P < 0.001). Chest injuries resulting from RTCs remain a major public health problem in this part of Tanzania. Urgent preventive measures targeting at reducing the occurrence of RTCs is necessary to reduce the incidence of chest injuries in this region

Hospitality employers’ perceptions of technology for sustainable development: The implications for graduate employability

This paper investigates hospitality employers’ perspectives of two key inter-disciplinary subjects, i.e. sustainable development (SD) and information technology in the context of hospitality education, particularly graduate employability. A qualitative approach is deployed at this stage of the research with semi-structured interviews conducted with employers of hospitality graduates that represent diverse stakeholders in the industry. Respondents had varying interpretations of the meaning of sustainable development and the role of technology in their businesses. Sustainability is not currently prioritised as a critical employability skill however employers clearly appreciate the value of sustainability for their business and recognise how technology might support SD. This is the first effort to investigate employers’ perspectives of the interdisciplinary subjects of technology and sustainable development in hospitality management undergraduate education

The 'Parekh Report' - national identities with nations and nationalism

‘Multiculturalists’ often advocate national identities. Yet few study the ways in which ‘multiculturalists’ do so and in this article I will help to fill this gap. I will show that the Commission for Multi-Ethnic Britain’s report reflects a previously unnoticed way of thinking about the nature and worth of national identities that the Commission’s chair, and prominent political theorist, Bhikhu Parekh, had been developing since the 1970s. This way of thinking will be shown to avoid the questionable ways in which conservative and liberal nationalists discuss the nature and worth of national identities while offering an alternative way to do so. I will thus show that a report that was once criticised for the way it discussed national identities reflects how ‘multiculturalists’ think about national identities in a distinct and valuable way that has gone unrecognised

Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration

Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 × 10−11 for rs4733781; P = 1.0 × 10−10 for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosis–infected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB

Strain-dependent host transcriptional responses to toxoplasma infection are largely conserved in mammalian and avian hosts

Toxoplasma gondii has a remarkable ability to infect an enormous variety of mammalian and avian species. Given this, it is surprising that three strains (Types I/II/III) account for the majority of isolates from Europe/North America. The selective pressures that have driven the emergence of these particular strains, however, remain enigmatic. We hypothesized that strain selection might be partially driven by adaptation of strains for mammalian versus avian hosts. To test this, we examine in vitro, strain-dependent host responses in fibroblasts of a representative avian host, the chicken (Gallus gallus). Using gene expression profiling of infected chicken embryonic fibroblasts and pathway analysis to assess host response, we show here that chicken cells respond with distinct transcriptional profiles upon infection with Type II versus III strains that are reminiscent of profiles observed in mammalian cells. To identify the parasite drivers of these differences, chicken fibroblasts were infected with individual F1 progeny of a Type II x III cross and host gene expression was assessed for each by microarray. QTL mapping of transcriptional differences suggested, and deletion strains confirmed, that, as in mammalian cells, the polymorphic rhoptry kinase ROP16 is the major driver of strain-specific responses. We originally hypothesized that comparing avian versus mammalian host response might reveal an inversion in parasite strain-dependent phenotypes; specifically, for polymorphic effectors like ROP16, we hypothesized that the allele with most activity in mammalian cells might be less active in avian cells. Instead, we found that activity of ROP16 alleles appears to be conserved across host species; moreover, additional parasite loci that were previously mapped for strain-specific effects on mammalian response showed similar strain-specific effects in chicken cells. These results indicate that if different hosts select for different parasite genotypes, the selection operates downstream of the signaling occurring during the beginning of the host's immune response. © 2011 Ong et al

Supersymmetric contributions to Bˉs→ϕπ0\bar{B}_s \to \phi \pi^0 and Bˉs→ϕρ0\bar{B}_s \to \phi \rho^0 decays in SCET

We study the decay modes $\bar{B}_s\to \phi \pi^0$ and $\bar{B}_s\to \phi \rho^0$ using Soft Collinear Effective Theory. Within Standard Model and including the error due to the SU(3) breaking effect in the SCET parameters we find that BR $\bar{B}_s\to \phi \pi^0 =7_{-1-2}^{+1+2}\times 10^{-8}$ and BR $\bar{B}_s\to \phi \pi^0=9_{-1-4}^{+1+3}\times 10^{-8}$ corresponding to solution 1 and solution 2 of the SCET parameters respectively.For the decay mode $\bar{B}_s\to \phi \rho^0$, we find that BR $\bar{B}_s\to \phi \rho^0 = 20.2^{+1+9}_{-1-12}\times 10^{-8}$ and BR $\bar{B}_s\to \phi \rho^0 = 34.0^{+1.5 + 15}_{-1.5-22}\times 10^{-8}$ corresponding to solution 1 and solution 2 of the SCET parameters respectively. We extend our study to include supersymmetric models with non-universal A-terms where the dominant contributions arise from diagrams mediated by gluino and chargino exchanges. We show that gluino contributions can not lead to an enhancement of the branching ratios of $\bar{B}_s\to \phi \pi^0$ and $\bar{B}_s\to \phi \rho^0$. In addition, we show that SUSY contributions mediated by chargino exchange can enhance the branching ratio of $\bar{B}_s\to \phi \pi^0$ by about 14% with respect to the SM prediction. For the branching ratio of $\bar{B}_s\to \phi \rho^0$, we find that SUSY contributions can enhance its value by about 1% with respect to the SM prediction.Comment: 25 pages,5 figures, version accepted for publicatio

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

Search for astronomical neutrinos from blazar TXS 0506+056 in super-kamiokande

We report a search for astronomical neutrinos in the energy region from several GeV to TeV in the direction of the blazar TXS 0506+056 using the Super-Kamiokande detector following the detection of a 100 TeV neutrinos from the same location by the IceCube collaboration. Using Super-Kamiokande neutrino data across several data samples observed from 1996 April to 2018 February we have searched for both a total excess above known backgrounds across the entire period as well as localized excesses on smaller timescales in that interval. No significant excess nor significant variation in the observed event rate are found in the blazar direction. Upper limits are placed on the electron- and muon-neutrino fluxes at the 90% confidence level as 6.0 × 10−7 and 4.5 × 10−7–9.3 × 10−10 [erg cm−2 s−1], respectively

A non-tight junction function of claudin-7—Interaction with integrin signaling in suppressing lung cancer cell proliferation and detachment

Background Claudins are a family of tight junction (TJ) membrane proteins involved in a broad spectrum of human diseases including cancer. Claudin-7 is a unique TJ membrane protein in that it has a strong basolateral membrane distribution in epithelial cells and in tissues. Therefore, this study aims to investigate the functional significance of this non-TJ localization of claudin-7 in human lung cancer cells. Methods Claudin-7 expression was suppressed or deleted by lentivirus shRNA or by targeted-gene deletion. Cell cycle analysis and antibody blocking methods were employed to assay cell proliferation and cell attachment, respectively. Electron microscopy and transepthelial electrical resistance measurement were performed to examine the TJ ultrastructure and barrier function. Co-immunolocalization and co-immunoprecipitation was used to study claudin-7 interaction with integrin β1. Tumor growth in vivo were analyzed using athymic nude mice. Results Claudin-7 co-localizes and forms a stable complex with integrin β1. Both suppressing claudin-7 expression by lentivirus shRNA in human lung cancer cells (KD cells) and deletion of claudin-7 in mouse lungs lead to the reduction in integrin β1 and phospho-FAK levels. Suppressing claudin-7 expression increases cell growth and cell cycle progression. More significantly, claudin-7 KD cells have severe defects in cell-matrix interactions and adhere poorly to culture plates with a remarkably reduced integrin β1 expression. When cultured on uncoated glass coverslips, claudin-7 KD cells grow on top of each other and form spheroids while the control cells adhere well and grow as a monolayer. Reintroducing claudin-7 reduces cell proliferation, upregulates integrin β1 expression and increases cell-matrix adhesion. Integrin β1 transfection partially rescues the cell attachment defect. When inoculated into nude mice, claudin-7 KD cells produced significantly larger tumors than control cells. Conclusion In this study, we identified a previously unrecognized function of claudin-7 in regulating cell proliferation and maintaining epithelial cell attachment through engaging integrin β1