Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway

Dysfunction or death of pancreatic β cells underlies both types of diabetes. This functional decline begins with β cell stress and de-differentiation. Current drugs for type 2 diabetes (T2D) lower blood glucose levels but they do not directly alleviate β cell stress nor prevent, let alone reverse, β cell de-differentiation. We show here that Urocortin 3 (Ucn3), a marker for mature β cells, is down-regulated in the early stages of T2D in mice and when β cells are stressed in vitro. Using an insulin expression-coupled lineage tracer, with Ucn3 as a reporter for the mature β cell state, we screen for factors that reverse β cell de-differentiation. We find that a small molecule inhibitor of TGFβ receptor I (Alk5) protects cells from the loss of key β cell transcription factors and restores a mature β cell identity even after exposure to prolonged and severe diabetes. DOI: http://dx.doi.org/10.7554/eLife.02809.00

More than rugby: A scoping review of coaches in rugby

Introduction It is well-recognised that fulfilling the role of a coach is multi-faceted. In rugby, some of these coaching facets have been studied, however the research has not been reviewed. Reviewing the literature on rugby coaches will inform and guide policies, coach education, research and practice. Therefore, the purpose of this study is to provide a scoping review of the current coach focused literature on rugby union, rugby league and rugby sevens. Methods A scoping review was conducted on five electronic databases (EBSCOhost, PubMed, Scopus, SPORTDiscus, Web of Science) until January 2022 using the PRISMA-ScR guidelines. Participants had to be coaches within rugby union, sevens and league to be included. Data were extracted and analyzed to form a numerical and thematic summary. Results 105 articles were included. 76% of the studies were on rugby union, 14% on league, 1% on sevens and the remainder focused on a combination of rugby cohorts or did not specify. Three themes were identified via a thematic analysis based on the content of the articles, these were coach knowledge (68%), coach pedagogies (29%), and coach development (4%). Conclusion The main finding in this review is that research on rugby coaches understood the risk, prevention, and management of injuries. Educational resources should include all aspects of rugby play or training injuries. The importance of the athlete-coach relationship and coach reflective practices was another significant finding. Coaches are encouraged to have a broad understanding of various aspects related to the player's welfare, which can be developed using formal and/or nonformal learning

Quantifying Collision Frequency and Intensity in Rugby Union and Rugby Sevens: A Systematic Review

BACKGROUND: Collisions in rugby union and sevens have a high injury incidence and burden, and are also associated with player and team performance. Understanding the frequency and intensity of these collisions is therefore important for coaches and practitioners to adequately prepare players for competition. The aim of this review is to synthesise the current literature to provide a summary of the collision frequencies and intensities for rugby union and rugby sevens based on video-based analysis and microtechnology. METHODS: A systematic search using key words was done on four different databases from 1 January 1990 to 1 September 2021 (PubMed, Scopus, SPORTDiscus and Web of Science). RESULTS: Seventy-three studies were included in the final review, with fifty-eight studies focusing on rugby union, while fifteen studies explored rugby sevens. Of the included studies, four focused on training-three in rugby union and one in sevens, two focused on both training and match-play in rugby union and one in rugby sevens, while the remaining sixty-six studies explored collisions from match-play. The studies included, provincial, national, international, professional, experienced, novice and collegiate players. Most of the studies used video-based analysis (n = 37) to quantify collisions. In rugby union, on average a total of 22.0 (19.0-25.0) scrums, 116.2 (62.7-169.7) rucks, and 156.1 (121.2-191.0) tackles occur per match. In sevens, on average 1.8 (1.7-2.0) scrums, 4.8 (0-11.8) rucks and 14.1 (0-32.8) tackles occur per match. CONCLUSIONS: This review showed more studies quantified collisions in matches compared to training. To ensure athletes are adequately prepared for match collision loads, training should be prescribed to meet the match demands. Per minute, rugby sevens players perform more tackles and ball carries into contact than rugby union players and forwards experienced more impacts and tackles than backs. Forwards also perform more very heavy impacts and severe impacts than backs in rugby union. To improve the relationship between matches and training, integrating both video-based analysis and microtechnology is recommended. The frequency and intensity of collisions in training and matches may lead to adaptations for a "collision-fit" player and lend itself to general training principles such as periodisation for optimum collision adaptation. Trial Registration PROSPERO registration number: CRD42020191112

Affinity enrichment of extracellular vesicles from plasma reveals mRNA changes associated with acute ischemic stroke

Currently there is no in vitro diagnostic test for acute ischemic stroke (AIS), yet rapid diagnosis is crucial for effective thrombolytic treatment. We previously demonstrated the utility of CD8(+) T-cells’ mRNA expression for AIS detection; however extracellular vesicles (EVs) were not evaluated as a source of mRNA for AIS testing. We now report a microfluidic device for the rapid and efficient affinity-enrichment of CD8(+) EVs and subsequent EV’s mRNA analysis using droplet digital PCR (ddPCR). The microfluidic device contains a dense array of micropillars modified with anti-CD8α monoclonal antibodies that enriched 158 ± 10 nm sized EVs at 4.3 ± 2.1 × 109 particles/100 µL of plasma. Analysis of mRNA from CD8(+) EVs and their parental T-cells revealed correlation in the expression for AIS-specific genes in both cell lines and healthy donors. In a blinded study, 80% test positivity for AIS patients and controls was revealed with a total analysis time of 3.7 h

Tackle Technique and Changes in Playerload™ During a Simulated Tackle: An Exploratory Study.

In collision sports, the tackle has the highest injury incidence, and is key to a successful performance. Although the contact load of players has been measured using microtechnology, this has not been related to tackle technique. The aim of this study was to explore how PlayerLoad™ changes between different levels of tackling technique during a simulated tackle. Nineteen rugby union players performed twelve tackles on a tackle contact simulator (n = 228 tackles). Each tackle was recorded with a video-camera and each player wore a Catapult OptimEyeS5. Tackles were analysed using tackler proficiency criteria and split into three categories: Low scoring(≤5 Arbitrary units (AU), medium scoring(6 and 7AU) and high scoring tackles(≥8AU). High scoring tackles recorded a higher PlayerLoad™ at tackle completion. The PlayerLoad™ trace was also less variable in the high scoring tackles. The variability in the PlayerLoad™ trace may be a consequence of players not shortening their steps before contact. This reduced their ability to control their movement during the contact and post-contact phase of the tackle and increased the variability. Using the PlayerLoad™ trace in conjunction with subjective technique assessments offers coaches and practitioners insight into the physical-technical relationship of each tackle to optimise tackle skill training and match preparation

Genetic Circuitry of Survival Motor Neuron, the Gene Underlying Spinal Muscular Atrophy

The clinical severity of the neurodegenerative disorder spinal muscular atrophy (SMA) is dependent on the levels of functional Survival Motor Neuron (SMN) protein. Consequently, current strategies for developing treatments for SMA generally focus on augmenting SMN levels. To identify additional potential therapeutic avenues and achieve a greater understanding of SMN, we applied in vivo, in vitro, and in silico approaches to identify genetic and biochemical interactors of the Drosophila SMN homolog. We identified more than 300 candidate genes that alter an Smn-dependent phenotype in vivo. Integrating the results from our genetic screens, large-scale protein interaction studies, and bioinformatic analysis, we define a unique interactome for SMN that provides a knowledge base for a better understanding of SMA.Stem Cell and Regenerative Biolog

Airborne Infection with Bacillus anthracis—from Mills to Mail

The lack of identified exposures in 2 of the 11 cases of bioterrorism-related inhalation anthrax in 2001 raised uncertainty about the infectious dose and transmission of Bacillus anthracis. We used the Wells-Riley mathematical model of airborne infection to estimate 1) the exposure concentrations in postal facilities where cases of inhalation anthrax occurred and 2) the risk for infection in various hypothetical scenarios of exposure to B. anthracis aerosolized from contaminated mail in residential settings. These models suggest that a small number of cases of inhalation anthrax can be expected when large numbers of persons are exposed to low concentrations of B. anthracis. The risk for inhalation anthrax is determined not only by bacillary virulence factors but also by infectious aerosol production and removal rates and by host factors

The Internet as a Small Business E-Commerce Ecosystem.

The purpose of this chapter is to analyse how the ecosystem concept can be applied to small businesses and how the Internet and e-commerce can help SMEs harness the required resources to enhance their competitive performance in the marketplace. The chapter will investigate the wide variety of e-commerce applications that are available to small businesses to help address the issue of limited resources. It will provide an ecosystem map illustrating how each functional area of a small business can utilise Internet e-commerce applications to enhance their resource base. The chapter also explores the opportunities and threats that the e-commerce ecosystem model poses for small, medium-sized enterprises (SMEs). This is based upon empirical research consisting of three focus group interviews undertaken with small and medium-sized retail service firms located in the Herefordshire and Worcestershire regions of the United Kingdom in January–February 2014