Monomeric ephrinB2 binding induces allosteric changes in Nipah virus G that precede its full activation.

Nipah virus is an emergent paramyxovirus that causes deadly encephalitis and respiratory infections in humans. Two glycoproteins coordinate the infection of host cells, an attachment protein (G), which binds to cell surface receptors, and a fusion (F) protein, which carries out the process of virus-cell membrane fusion. The G protein binds to ephrin B2/3 receptors, inducing G conformational changes that trigger F protein refolding. Using an optical approach based on second harmonic generation, we show that monomeric and dimeric receptors activate distinct conformational changes in G. The monomeric receptor-induced changes are not detected by conformation-sensitive monoclonal antibodies or through electron microscopy analysis of G:ephrinB2 complexes. However, hydrogen/deuterium exchange experiments confirm the second harmonic generation observations and reveal allosteric changes in the G receptor binding and F-activating stalk domains, providing insights into the pathway of receptor-activated virus entry.Nipah virus causes encephalitis in humans. Here the authors use a multidisciplinary approach to study the binding of the viral attachment protein G to its host receptor ephrinB2 and show that monomeric and dimeric receptors activate distinct conformational changes in G and discuss implications for receptor-activated virus entry

The Use of Bronchoscopy During the COVID-19 Pandemic: CHEST/AABIP Guideline and Expert Panel Report

BACKGROUND: The coronavirus disease 2019 (COVID-19) has swept the globe and is causing significant morbidity and mortality. Given that the virus is transmitted via droplets, open airway procedures such as bronchoscopy pose a significant risk to health-care workers (HCWs). The goal of this guideline was to examine the current evidence on the role of bronchoscopy during the COVID-19 pandemic and the optimal protection of patients and HCWs. RESEARCH QUESTION: ▪▪▪ STUDY DESIGN AND METHODS: A group of approved panelists developed key clinical questions by using the Population, Intervention, Comparator, and Outcome (PICO) format that addressed specific topics on bronchoscopy related to COVID-19 infection and transmission. MEDLINE (via PubMed) was systematically searched for relevant literature and references were screened for inclusion. Validated evaluation tools were used to assess the quality of studies and to grade the level of evidence to support each recommendation. When evidence did not exist, suggestions were developed based on consensus using the modified Delphi process. RESULTS: The systematic review and critical analysis of the literature based on six PICO questions resulted in six statements: one evidence-based graded recommendation and 5 ungraded consensus-based statements. INTERPRETATION: The evidence on the role of bronchoscopy during the COVID-19 pandemic is sparse. To maximize protection of patients and HCWs, bronchoscopy should be used sparingly in the evaluation and management of patients with suspected or confirmed COVID-19 infections. In an area where community transmission of COVID-19 infection is present, bronchoscopy should be deferred for nonurgent indications, and if necessary to perform, HCWs should wear personal protective equipment while performing the procedure even on asymptomatic patients

Industrial relations in the UK shipping industry since the Second World War

The shipping industry has undergone a period of rapid and fundamental change during the three decades since the end of the Second World War. While these changes have been experienced world-wide and have promoted the implementation of technological advances and the growth of the world fleet, they have occurred during a period which has also witnessed a substantial relative decline in Britain's maritime position. It is the aim of this study to analyse their effect on industrial relations in the U.K. shipping industry

High-Redshift Quasars Found in Sloan Digital Sky Survey Commissioning Data II: The Spring Equatorial Stripe

This is the second paper in a series aimed at finding high-redshift quasars from five-color (u'g'r'i'z') imaging data taken along the Celestial Equator by the Sloan Digital Sky Survey (SDSS) during its commissioning phase. In this paper, we present 22 high-redshift quasars (z>3.6) discovered from ~250 deg^2 of data in the spring Equatorial Stripe, plus photometry for two previously known high-redshift quasars in the same region of sky. Our success rate of identifying high-redshift quasars is 68%. Five of the newly discovered quasars have redshifts higher than 4.6 (z=4.62, 4.69, 4.70, 4.92 and 5.03). All the quasars have i* < 20.2 with absolute magnitude -28.8 < M_B < -26.1 (h=0.5, q_0=0.5). Several of the quasars show unusual emission and absorption features in their spectra, including an object at z=4.62 without detectable emission lines, and a Broad Absorption Line (BAL) quasar at z=4.92.Comment: 28 pages, AJ in press (Jan 2000), final version with minor changes; high resolution finding charts available at http://www.astro.princeton.edu/~fan/paper/qso2.htm

A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes

GC-biased gene conversion (gBGC) is a recombination-associated process that favors the fixation of G/C alleles over A/T alleles. In mammals, gBGC is hypothesized to contribute to variation in GC content, rapidly evolving sequences, and the fixation of deleterious mutations, but its prevalence and general functional consequences remain poorly understood. gBGC is difficult to incorporate into models of molecular evolution and so far has primarily been studied using summary statistics from genomic comparisons. Here, we introduce a new probabilistic model that captures the joint effects of natural selection and gBGC on nucleotide substitution patterns, while allowing for correlations along the genome in these effects. We implemented our model in a computer program, called phastBias, that can accurately detect gBGC tracts about 1 kilobase or longer in simulated sequence alignments. When applied to real primate genome sequences, phastBias predicts gBGC tracts that cover roughly 0.3% of the human and chimpanzee genomes and account for 1.2% of human-chimpanzee nucleotide differences. These tracts fall in clusters, particularly in subtelomeric regions; they are enriched for recombination hotspots and fast-evolving sequences; and they display an ongoing fixation preference for G and C alleles. They are also significantly enriched for disease-associated polymorphisms, suggesting that they contribute to the fixation of deleterious alleles. The gBGC tracts provide a unique window into historical recombination processes along the human and chimpanzee lineages. They supply additional evidence of long-term conservation of megabase-scale recombination rates accompanied by rapid turnover of hotspots. Together, these findings shed new light on the evolutionary, functional, and disease implications of gBGC. The phastBias program and our predicted tracts are freely available. © 2013 Capra et al

Effectiveness of a telehealth physiotherapist-delivered intensive dietary weight loss program combined with exercise in people with knee osteoarthritis and overweight or obesity: study protocol for the POWER randomized controlled trial.

BACKGROUND: Obesity is associated with knee osteoarthritis (OA). Weight loss, alongside exercise, is a recommended treatment for individuals with knee OA and overweight/obesity. However, many patients cannot access weight loss specialists such as dietitians. Innovative care models expanding roles of other clinicians may increase access to weight loss support for people with knee OA. Physiotherapists may be well placed to deliver such support. This two-group parallel, superiority randomized controlled trial aims to compare a physiotherapist-delivered diet and exercise program to an exercise program alone, over 6 months. The primary hypothesis is that the physiotherapist-delivered diet plus exercise program will lead to greater weight loss than the exercise program. METHODS: 88 participants with painful knee OA and body mass index (BMI) > 27 kg/m2 will be recruited from the community. Following baseline assessment, participants will be randomised to either exercise alone or diet plus exercise groups. Participants in the exercise group will have 6 consultations (20-30 min) via videoconference with a physiotherapist over 6 months for a strengthening exercise program, physical activity plan and educational/exercise resources. Participants in the diet plus exercise group will have 6 consultations (50-75 min) via videoconference with a physiotherapist prescribing a ketogenic very low-calorie diet with meal replacements and educational resources to support weight loss and healthy eating, plus the intervention of the exercise only group. Outcomes are measured at baseline and 6 months. The primary outcome is percentage change in body weight measured by a blinded assessor. Secondary outcomes include self-reported knee pain, physical function, global change in knee problems, quality of life, physical activity levels, and internalised weight stigma, as well as BMI, waist circumference, waist-to-hip ratio, physical performance measures and quadriceps strength, measured by a blinded assessor. Additional measures include adherence, adverse events, fidelity and process measures. DISCUSSION: This trial will determine whether a physiotherapist-delivered diet plus exercise program is more effective for weight loss than an exercise only program. Findings will inform the development and implementation of innovative health service models addressing weight management and exercise for patients with knee OA and overweight/obesity. TRIAL REGISTRATION: NIH US National Library of Medicine, Clinicaltrials.gov NCT04733053 (Feb 1 2021)

Symbiotic starburst-black hole AGN -- I. Isothermal hydrodynamics of the mass-loaded ISM

Compelling evidence associates the nuclei of active galaxies and massive starbursts. The symbiosis between a compact nuclear starburst stellar cluster and a massive black hole can self-consistently explain the properties of active nuclei. The young stellar cluster has a profound effect on the most important observable properties of active galaxies through its gravity, and by mass injection through stellar winds, supernovae and stellar collisions. Mass injection generates a nuclear ISM which flows under gravitational and radiative forces until it leaves the nucleus or is accreted onto the black hole or accretion disc. The radiative force exerted by the black hole--accretion disc radiation field is not spherically symmetric. This results in complex flows in which regions of inflow can coexist with high Mach number outflowing winds and hydrodynamic jets. We present two-dimensional hydrodynamic models of such nISM flows, which are highly complex and time variable. Shocked shells, jets and explosive bubbles are produced, with bipolar winds driving out from the nucleus. Our results graphically illustrate why broad emission line studies have consistently failed to identify any simple, global flow geometry. The real structure of the flows is _inevitably_ yet more complex.Comment: 51 pages, 85 postscript figures, Latex, using MNRAS macros, to be published in MNRAS. Postscript will full resolution pictures and mpeg simulations available via http://ast.leeds.ac.uk/~rjrw/agn.htm

Mock juror perceptions of child witnesses on the autism spectrum: the impact of providing diagnostic labels and information about autism

Research suggests that autistic children can provide accurate and forensically useful eyewitness evidence. However, members of a jury also rely on non-verbal behaviours when judging the credibility of a witness, and this could determine the verdict of a case. We presented mock jurors with videos (from an experimental study) of one of two child witnesses on the autism spectrum being interviewed about a mock minor crime. Results demonstrated that providing jurors with generic information about autism and/or informing them of the child’s diagnostic label differentially affected credibility ratings, but not for both children. Implications for how to present information about child witnesses with autism to a jury – highlighting the need for approaches tailored to individual children – are discussed