Phosphorylation of survivin at threonine 34 inhibits its mitotic function and enhances its cytoprotective activity

Survivin is an essential chromosomal passenger protein required for mitotic progression. It is also an inhibitor of apoptosis and can prevent caspase-mediated cell death. In addition, survivin levels are elevated in cancer cells where its presence correlates with increased resistance to chemo- and radio-therapy, which makes it an attractive target for novel anti-cancer strategies. Interestingly, survivin is phosphorylated by the mitotic kinase, cdk1, and a non-phosphorylatable form, survivin(T34A), cannot inhibit apoptosis. Here we rigorously test the ability of survivin(T34A) and its corresponding phosphomimetic, survivin(T34E), to promote cell viability through survivin's dual roles. The effects of these mutations are diametrically opposed: survivin(T34A) accelerates cell proliferation and promotes apoptosis, whereas survivin(T34E) retards growth and promotes survival. Thus the phosphorylation status of survivin at T34 is pivotal to a cell's decision to live or die

Evidence that heat acclimation training may alter sleep and incidental activity

This randomized cross-over study tested the hypothesis that heat acclimation training would detrimentally affect sleep variables and alter incidental physical activity compared to a thermoneutral training control condition. Eight recreationally trained males (V̇ O2peak 49±4.9 mL. kg-1.min-1) completed two separate interventions separated by at least 31 days: 5 consecutive day training blocks of moderate-intensity cycling (60 min·day-1 at 50% peak power output) in a hot (34.9±0.7 °C and 53±4 % relative humidity) and a temperate (22.2±2.6 °C; 65±8 % relative humidity) environment. Wrist-mounted accelerometers were worn continuously for the length of the training blocks and recorded physical activity, sleep quality and quantity. Data were analysed in a Bayesian framework, with the results presented as the posterior probability that a coefficient was greater or less than zero. Compared to the temperate training environment, heat acclimation impaired sleep efficiency (Pr β0 = .917). Daily sedentary time was, on average, 35 min longer (Pr β>0 = .973) and light physical activity time 18 min shorter (Pr β>0 = .960) during the heat acclimation period. No differences were observed between conditions in sleep duration, subjective sleep quality, or moderate or vigorous physical activity. These findings may suggest that athletes and coaches need to be cognisant that heat acclimation training may alter sleep quality and increase sedentary behaviour

Who funded the research behind the Oxford-AstraZeneca COVID-19 vaccine?

Objectives The Oxford-AstraZeneca COVID-19 vaccine (ChAdOx1 nCoV-19, Vaxzevira or Covishield) builds on two decades of research and development (R&D) into chimpanzee adenovirus-vectored vaccine (ChAdOx) technology at the University of Oxford. This study aimed to approximate the funding for the R&D of ChAdOx and the Oxford-AstraZeneca vaccine and to assess the transparency of funding reporting mechanisms. Methods We conducted a scoping review and publication history analysis of the principal investigators to reconstruct R&D funding the ChAdOx technology. We matched award numbers with publicly accessible grant databases. We filed freedom of information (FOI) requests to the University of Oxford for the disclosure of all grants for ChAdOx R&D. Results We identified 100 peer-reviewed articles relevant to ChAdOx technology published between January 2002 and October 2020, extracting 577 mentions of funding bodies from acknowledgements. Government funders from overseas (including the European Union) were mentioned 158 times (27.4%), the UK government 147 (25.5%) and charitable funders 138 (23.9%). Grant award numbers were identified for 215 (37.3%) mentions; amounts were publicly available for 121 (21.0%). Based on the FOIs, until December 2019, the biggest funders of ChAdOx R&D were the European Commission (34.0%), Wellcome Trust (20.4%) and Coalition for Epidemic Preparedness Innovations (17.5%). Since January 2020, the UK government contributed 95.5% of funding identified. The total identified R&D funding was £104 226 076 reported in the FOIs and £228 466 771 reconstructed from the literature search. Conclusion Our study approximates that public and charitable financing accounted for 97%-99% of identifiable funding for the ChAdOx vaccine technology research at the University of Oxford underlying the Oxford-AstraZeneca vaccine until autumn 2020. We encountered a lack of transparency in research funding reporting

Mass-flowering crops have a greater impact than semi-natural habitat on crop pollinators and pollen deposition

Context: Maximising insect pollination of mass-flowering crops is a widely-discussed approach to sustainable agriculture. Management actions can target landscape-scale semi-natural habitat, cropping patterns or field-scale features, but little is known about their relative effectiveness. Objective: To test how landscape composition (area of mass-flowering crops and semi-natural habitat) and field-scale habitat (margins and hedges) affect pollinator species richness, abundance, and pollen deposition within crop fields. Methods: We surveyed all flower visitors (Diptera, Coleoptera and Hymenoptera) in oilseed rape fields and related them to landscape composition and field features. Flower visitors were classified as bees, non-bee pollinators and brassica specialists. Total pollen deposition by individual taxa was estimated using single visit pollen deposition on stigmas combined with insect abundance. Results: The area of mass-flowering crop had a negative effect on the species richness and abundance of bees in fields, but not other flower visitors. The area of semi-natural habitat in the surrounding landscape had a positive effect on bees, but was not as important as the area of mass-flowering crop. Taxonomic richness and abundance varied significantly between years for non-bee pollinators. Greater cover of mass-flowering crops surrounding fields had a negative effect on pollen deposition, but only when non-bee pollinator numbers were reduced. Conclusions: Management choices that result in landscape homogenisation, such as large areas of mass-flowering crops, may reduce pollination services by reducing the numbers of bees visiting fields. Non-bee insect pollinators may buffer these landscape effects on pollen deposition, and management to support their populations should be considered

Comment on "The extent of forest in dryland biomes"

Bastin et al (Reports, 12 May 2017, p. 635) infer forest as more globally extensive than previously estimated using tree cover data. However, their forest definition does not reflect ecosystem function or biotic composition. These structural and climatic definitions inflate forest estimates across the tropics and undermine conservation goals, leading to inappropriate management policies and practices in tropical grassy ecosystems

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Ibrutinib for mantle cell lymphoma at first relapse: a United Kingdom real-world analysis of outcomes in 211 patients.

Funder: Janssen Pharmaceuticals; Id: http://dx.doi.org/10.13039/100008897Ibrutinib is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL) and clinical trial data supports use at second line compared to later relapse. We aimed to investigate outcomes and tolerability for ibrutinib when given second line in a real-world setting. Our multicentre retrospective analysis included 211 R/R MCL patients, median age 73 years, receiving ibrutinib second-line within the United Kingdom's National Health Service. Overall response to ibrutinib was 69% (complete response 27%). The median progression-free survival (PFS) was 17·8 months (95% CI 13·1-22·2) and median overall survival (OS) 23·9 months (95% CI 15·0-32·8). Drug-related adverse event led to dose reduction in 10% of patients and discontinuation in 5%. In patients with progressive disease, accounting for 100 of 152 patients stopping ibrutinib, 43% received further systemic therapy. Post-ibrutinib rituximab, bendamustine and cytarabine (R-BAC) showed a trend toward improved survival compared to alternative systemic treatments (post-ibrutinib median OS 14·0 months, 95% CI 8·1-19·8, vs. 3·6 months, 95% CI 2·6-4·5, P = 0·06). Our study confirms the clinical benefit and good tolerability of ibrutinib at first relapse in a real-world population. Patients progressing on ibrutinib had limited survival but outcomes with R-BAC in select patients were promising