Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis

The discovery of novel antigens is an essential requirement in devising new diagnostics or vaccines for use in control programmes against human tuberculosis (TB) and bovine tuberculosis (bTB). Identification of potential epitopes recognised by CD4+ T cells requires prediction of peptide binding to MHC class-II, an obligatory prerequisite for T cell recognition. To comprehensively prioritise potential MHC-II-binding epitopes from Mycobacterium bovis, the agent of bTB and zoonotic TB in humans, we integrated three binding prediction methods with the M. bovisproteome using a subset of human HLA alleles to approximate the binding of epitope-containing peptides to the bovine MHC class II molecule BoLA-DRB3. Two parallel strategies were then applied to filter the resulting set of binders: identification of the top-scoring binders or clusters of binders. Our approach was tested experimentally by assessing the capacity of predicted promiscuous peptides to drive interferon-γ secretion from T cells of M. bovis infected cattle. Thus, 376 20-mer peptides, were synthesised (270 predicted epitopes, 94 random peptides with low predictive scores and 12 positive controls of known epitopes). The results of this validation demonstrated significant enrichment (>24 %) of promiscuously recognised peptides predicted in our selection strategies, compared with randomly selected peptides with low prediction scores. Our strategy offers a general approach to the identification of promiscuous epitopes tailored to target populations where there is limited knowledge of MHC allelic diversity

Physical and technical demands and preparatory strategies in female field collision sports: a scoping review

Women’s participation in field collision sports is growing world- wide. Scoping reviews provide an overview of scientific litera- ture in a developing area to support practitioners, policy, and research priorities. Our aim is to explore published research and synthesise information on the physical and technical de- mands and preparation strategies of female field collision sports. We searched four databases and identified relevant published studies. Data were extracted to form (1) a numerical analysis and (2) thematic summary. Of 2318 records identified, 43 studies met the inclusion criteria. Physical demands were the most highly investigated (n = 24), followed by technical demands (n = 18), tactical considerations (n = 8) and preparatory strategies (n = 1). The key themes embody a holistic model contributing to both performance and injury prevention outcomes in the context of female field collision sports. Find- ings suggest a gender data gap across all themes and a low evidence base to inform those preparing female athletes for match demands. Given the physical and technical differences in match-demands the review findings do not support the generalisation of male-derived training data to female athletes. To support key stakeholders working within female field collision sports there is a need to increase the visibility of female athletes in the literature.<br/

Cardiovascular risk and systemic inflammation in male professional rugby: a cross-sectional study

Objective: To investigate cardiovascular risk factors’ prevalence and association with systemic inflammation in professional male rugby players (RP). Methods: A cross-sectional investigation of 46 professional male RP (26.1±4.1 years) cardiovascular risk factors were compared by position. Inflammatory markers were compared with healthy controls (n=13) and patients with rheumatoid arthritis (RA) (n=10). Results: Twenty-six per cent of RP had no risk factors, 49% had 1–2 cardiovascular risk factors and 25% had 3–4 risk factors. Forwards had greater body fat (p<0.001), visceral fat (p<0.001), glucose (p=0.025), and C reactive protein (CRP) (p=0.023) compared with backs. RP demonstrated more favourable lipid and glucose profiles than reference values for the general population. Most RP (n=28, 61%) had elevated blood pressure (≥140/90 mm Hg). RP had higher vascular adhesion molecule-1 (VCAM-1) (p=0.004) and intracellular adhesion molecule-1 (ICAM-1) (p=0.002) than healthy controls. RP had lower CRP than patients with RA (p=0.009), while one-third (n=15) displayed equivalent ICAM-1 and VCAM-1 levels. Multivariate clustering and principal component analysis biplots revealed higher triglycerides, inflammatory markers, and worse body composition were associated with forwards. Conclusions: Despite athletic status, most of this rugby cohort had at least one cardiovascular risk factor. Concomitantly, these RP demonstrated increased levels of inflammation, with one-third, primarily forwards, displaying equivalent levels to patients with inflammatory disease. Further studies are needed to unravel the prognostic implications of increased inflammation in RP because unchecked, chronic inflammation may lead to increased cardiovascular disease risk

Collaboration between academics and teachers : a complex relationship

Collaboration between academics and teachers has become increasingly prevalent over recent years. Whether its aim is joint research or continuing professional development for teachers, collaboration seems to offer a realistic opportunity for reducing the perceived gap between theory and practice. However, collaboration is not merely academics and teachers working together on a common project. It is complex in nature and involves a range of requirements that must be satisfied in order to maximise the potential of the relationship. In this paper we will theorise on the nature of academics and teachers working together and suggest that a working relationship between academic researchers and teachers can be one of three models: client–supplier, a coercive relationship or a collaborative relationship. We identify and unpack specific factors that underpin collaboration and suggest a number of concrete actions to establish collaboration between academics and teachers. We draw heavily from existing literature and our own reflections on two collaborative projects with which we have recently been involved. We use data from these projects to provide a number of anecdotes from the teachers who participated to support our own reflections. Finally, we suggest that further research should investigate the different ways attempts to collaborate fail, to build a more complete sense of the problems and potential of this special relationship. Keywords: collaboration; continuing professional development; action research; science teacher

Pore directionality and correlation lengths of mesoporous silica channels aligned by physical epitaxy

Herein we report on the alignment of mesoporous silica, a potential host for sub-10 nm nanostructures, by controlling its deposition within patterned substrates. In-depth characterization of the correlation lengths (length of a linear porous channel), defects of the porous network (delamination), and how the silica mesopores register to the micrometer-sized substrate pattern was achieved by means of novel focused ion beam (FIB) sectioning and in situ SEM imaging, which to our knowledge has not previously been reported for such a system. Our findings establish that, under confinement, directed deposition of the sol within channeled substrates, where the cross-sectional aspect ratio of the channels approaches unity, induces alignment of the mesopores along the length of the channels. The pore correlation length was found to extend beyond the micrometer scale, with high pore uniformity from channel to channel observed with infrequent delamination defects. Such information on pore correlation lengths and defect densities is critical for subsequent nanowire growth within the mesoporous channels, contact layout (electrode deposition etc.), and possible device architectures

A robust system for RNA interference in the chicken using a modified microRNA operon

AbstractRNA interference (RNAi) provides an effective method to silence gene expression and investigate gene function. However, RNAi tools for the chicken embryo have largely been adapted from vectors designed for mammalian cells. Here we present plasmid and retroviral RNAi vectors specifically designed for optimal gene silencing in chicken cells. The vectors use a chicken U6 promoter to express RNAs modelled on microRNA30, which are embedded within chicken microRNA operon sequences to ensure optimal Drosha and Dicer processing of transcripts. The chicken U6 promoter works significantly better than promoters of mammalian origin and in combination with a microRNA operon expression cassette (MOEC), achieves up to 90% silencing of target genes. By using a MOEC, we show that it is also possible to simultaneously silence two genes with a single vector. The vectors express either RFP or GFP markers, allowing simple in vivo tracking of vector delivery. Using these plasmids, we demonstrate effective silencing of Pax3, Pax6, Nkx2.1, Nkx2.2, Notch1 and Shh in discrete regions of the chicken embryonic nervous system. The efficiency and ease of use of this RNAi system paves the way for large-scale genetic screens in the chicken embryo

Author Correction: A consensus-based transparency checklist.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Transforming growth factor- directly induces p53-up-regulated modulator of apoptosis (PUMA) during the rapid induction of apoptosis in myc-driven B-cell lymphomas

Background: TGF-β induces apoptosis in Burkitt's lymphoma cells. Results: PUMA is a direct target gene of TGF-β signaling and is required for rapid apoptosis. Conclusion: TGF-β-mediated direct induction of PUMA contributes to apoptosis in human and murine c-Myc-driven lymphomas. Significance: These studies link TGF-β signaling and transcriptional activation of PUMA, two factors with critical roles in regulating B-cell survival

A consensus-based transparency checklist

We present a consensus-based checklist to improve and document the transparency of research reports in social and behavioural research. An accompanying online application allows users to complete the form and generate a report that they can submit with their manuscript or post to a public repository

Regional variability in peatland burning at mid- to high-latitudes during the Holocene

Acknowledgements This work developed from the PAGES (Past Global Changes) C-PEAT (Carbon in Peat on EArth through Time) working group. PAGES has been supported by the US National Science Foundation, Swiss National Science Foundation, Swiss Academy of Sciences and Chinese Academy of Sciences. We acknowledge the following financial support: UK Natural Environment Research Council Training Grants NE/L002574/1 (T.G.S.) and NE/S007458/1 (R.E.F.); Dutch Foundation for the Conservation of Irish Bogs, Quaternary Research Association and Leverhulme Trust RPG-2021-354 (G.T.S); the Academy of Finland (M.V); PAI/SIA 80002 and FONDECYT Iniciación 11220705 - ANID, Chile (C.A.M.); R20F0002 (PATSER) ANID Chile (R.D.M.); Swedish Strategic Research Area (SRA) MERGE (ModElling the Regional and Global Earth system) (M.J.G.); Polish National Science Centre Grant number NCN 2018/29/B/ST10/00120 (K.A.); Russian Science Foundation Grant No. 19-14-00102 (Y.A.M.); University of Latvia Grant No. AAp2016/B041/Zd2016/AZ03 and the Estonian Science Council grant PRG323 (TrackLag) (N.S. and A.M.); U.S. Geological Survey Land Change Science/Climate Research & Development Program (M.J., L.A., and D.W.); German Research Foundation (DFG), grant MA 8083/2-1 (P.M.) and grant BL 563/19-1 (K.H.K.); German Academic Exchange Service (DAAD), grant no. 57044554, Faculty of Geosciences, University of Münster, and Bavarian University Centre for Latin America (BAYLAT) (K.H.K). Records from the Global Charcoal Database supplemented this work and therefore we would like to thank the contributors and managers of this open-source resource. We also thank Annica Greisman, Jennifer Shiller, Fredrik Olsson and Simon van Bellen for contributing charcoal data to our analyses. Any use of trade, firm, or product name is for descriptive purposes only and does not imply endorsement by the U.S. Government.Peer reviewedPostprin