Deep learning extends de novo protein modelling coverage of genomes using iteratively predicted structural constraints

The inapplicability of amino acid covariation methods to small protein families has limited their use for structural annotation of whole genomes. Recently, deep learning has shown promise in allowing accurate residue-residue contact prediction even for shallow sequence alignments. Here we introduce DMPfold, which uses deep learning to predict inter-atomic distance bounds, the main chain hydrogen bond network, and torsion angles, which it uses to build models in an iterative fashion. DMPfold produces more accurate models than two popular methods for a test set of CASP12 domains, and works just as well for transmembrane proteins. Applied to all Pfam domains without known structures, confident models for 25% of these so-called dark families were produced in under a week on a small 200 core cluster. DMPfold provides models for 16% of human proteome UniProt entries without structures, generates accurate models with fewer than 100 sequences in some cases, and is freely available.Comment: JGG and SMK contributed equally to the wor

Machine learning methods for predicting protein structure from single sequences

Recent breakthroughs in protein structure prediction have increasingly relied on the use of deep neural networks. These recent methods are notable in that they produce 3-D atomic coordinates as a direct output of the networks, a feature which presents many advantages. Although most techniques of this type make use of multiple sequence alignments as their primary input, a new wave of methods have attempted to use just single sequences as the input. We discuss the make-up and operating principles of these models, and highlight new developments in these areas, as well as areas for future development

Reducing patient delay with symptoms of acute coronary syndrome:a research protocol for a systematic review of previous interventions to investigate which behaviour change techniques are associated with effective interventions

Introduction: Delay to presentation with symptoms of acute coronary syndrome (ACS) is common meaning many fail to achieve optimal benefit from treatments. Interventions have had variable success in reducing delay. Evidence suggests inclusion of behaviour change techniques (BCTs) may improve effectiveness of interventions but this has not yet been systematically evaluated. Data from other time-critical conditions may be relevant.Methods and analysis: A systematic review will be undertaken to identify which BCTs are associated with effective interventions to reduce patient delay (or prompt rapid help-seeking) among people with time-critical conditions (eg, chest pain, ACS, lumps, stroke, cancer and meningitis). A systematic search of a wide range of databases (including Cochrane Library, MEDLINE, EMBASE, CINAHL, PsycInfo) and grey literature will be undertaken to identify all relevant intervention studies (randomised controlled trials, controlled clinical trials and cohort studies). Two independent reviewers will screen abstracts to identify relevant studies, apply inclusion criteria to full papers, assess methodological quality and extract data.Primary outcome measure: Change in patient decision time BCTs reported in each of the included studies will be categorised and presented according to the latest reliable taxonomy. Results of included studies will be synthesised, exploring relationships between inclusion of each BCT and effectiveness of the overall intervention. Where possible, means and SDs for differences in delay time will be calculated and combined within meta-analyses to derive a standardised mean difference and 95% CI. Analysis of (1) all time-critical and (2) ACS-only interventions will be undertaken

Using Common Gardens and AFLP Analyses to Identify Metapopulations of Indigenous Plant Materials for Rangeland Revegetation in Western USA

Past mismanagement, overgrazing, invasive weedy species, wildfires, marginal crop production, mineral and energy extraction, recreation and global climate change are challenges currently facing rangelands (Pierson et al. 2011). These disturbances may lead to long-term reductions in biodiversity, altered nutrient and water cycling, diminished forage production for livestock and wildlife, increased wildfire frequency and increased soil erosion and stream sedimentation (Sheley et al. 2008). Rangeland revegetation with desirable plant materials may be required to improve degraded conditions, speed recovery, and prevent further erosion and degradation. There is a critical need for plant materials to restore and revegetate rangeland ecosystems. Legumes indigenous to western North America are of particular interest for revegetation because they provide biologically fixed nitrogen, increase plant production, enhance forage quality and provide food sources for grazing animals and pollinators. Some land managers in the USA are concerned with the genetic identity of populations used for revegetation. To balance concerns of genetic identity, ecological adaptation, and economical seed production, we assessed genetic variation and its phenotypic expression in Astragalus filipes Torr. ex A. Gray (basalt milkvetch), Dalea ornata (Douglas) Eaton & Wright (western prairie clover) and D. searlsiae (A. Gray) Barneby (Searls’ prairie clover) using common-garden and AFLP (amplified fragment length polymorphism) techniques. These data were used to define population structures (genetically differentiated groups) within each species, which served as a basis for commercial release and rangeland revegetation (Johnson et al. 2012)

A review of ventilation opening area terminology

This is the author accepted manuscript. The final version is available from Elsevier via https://doi.org/10.1016/j.enbuild.2016.02.053The design of a natural ventilation strategy requires the establishment of the location and size of a series of purpose provided ventilation openings (PPOs). The success of the design is dependent on knowledge of the aerodynamic performance of the PPOs often described by their geometry (normally an area) and resistance to airflow. The incorrect interpretation of this information can lead inappropriate ventilation strategies and buildings that overheat and have an excessive energy demand. Many definitions of PPO area are used by standards, guidelines, text books, and software tools. Each can be assigned multiple terms and a single term can be assigned to different definitions. There is evidence that this leads to errors in practice. An effective area of a PPO, defined as the product of its discharge coefficient and its free area, is proposed as a standard description because it is unambiguous and its measurement is governed by recognised standards. It is hoped that PPO manufacturers will provide an effective area as standard and that its use will be recognised as best practice. It is intended that these steps will reduce design errors and lead to successful natural ventilation strategies and better building

Methods to improve recruitment to randomised controlled trials : Cochrane systematic review and meta-analysis

Peer reviewedPublisher PD

Educating for Indigenous health equity: An international consensus statement

The determinants of health inequities between Indigenous and non-Indigenous populations include factors amenable to medical education’s influence, for example, the competence of the medical workforce to provide effective and equitable care to Indigenous populations. Medical education institutions have an important role to play in eliminating these inequities. However, there is evidence that medical education is not adequately fulfilling this role, and in fact may be complicit in perpetuating inequities. This article seeks to examine the factors underpinning medical education’s role in Indigenous health inequity, in order to inform interventions to address these factors. The authors developed a consensus statement that synthesizes evidence from research, evaluation, and the collective experience of an international research collaboration including experts in Indigenous medical education. The statement describes foundational processes that limit Indigenous health development in medical education and articulates key principles that can be applied at multiple levels to advance Indigenous health equity. The authors recognize colonization, racism, and privilege as fundamental determinants of Indigenous health that are also deeply embedded in Western medical education. In order to contribute effectively to Indigenous health development, medical education institutions must engage in decolonization processes and address racism and privilege at curricular and institutional levels. Indigenous health curricula must be formalized and comprehensive, and must be consistently reinforced in all educational environments. Institutions’ responsibilities extend to advocacy for health system and broader societal reform to reduce and eliminate health inequities. These activities must be adequately resourced and underpinned by investment in infrastructure and Indigenous leadership

Effect of Behavioral Activation for Women with Postnatal Depression: A Systematic Review and Meta-Analysis.

Evidence shows that behavioral activation (BA), a simple form of psychological therapy, is as effective as the more complex psychological therapy-cognitive behavioral therapy (CBT)-in treating general depression. However, it remains unclear whether BA when compared with treatment-as-usual (TAU) has greater contributions in reducing postnatal depression. This systematic review compared the effect of BA versus TAU in reducing depression symptoms among postnatal women. Five databases (MEDLINE, Embase, Emcare, Cochrane Library, and PsycINFO) were searched. Risk of bias was assessed using the Cochrane Collaboration's 'risk-of-bias 2 tool'. A random-effects meta-analysis was conducted to examine the effect of BA on postnatal depression. Of 2844 initial studies, only two randomized control trials (RCTs) met the inclusion criteria. The overall quality of evidence of these two RCTs was low. When compared to TAU, meta-analysis showed that BA was associated with reduced depression symptoms in postnatal women (standard mean difference -0.56; 95% confidence interval -0.76 to -0.37). This review suggests that BA might be more effective than TAU for alleviating postnatal depression. However, due to concerns about evidence quality, these findings should be interpreted cautiously

Direct activation of NADPH oxidase 2 by 2-deoxyribose-1-phosphate triggers nuclear factor kappa B-dependent angiogenesis.

AbstractAims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells.Results: Live cell imaging, electron paramagnetic resonance, pull-down of dRP-interacting proteins, followed by immunoblotting, gene silencing of different NADPH oxidases (NOXs), and their regulatory cosubunits by small interfering RNA (siRNA) transfection, and experiments with inhibitors of the sugar transporter glucose transporter 1 (GLUT1) were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NOX2 complex, but not NOX4. Increased reactive oxygen species generation in response to NOX2 activity leads to redox-dependent activation of the transcription factor nuclear factor kappa B (NF-κB), which, in turn, induces vascular endothelial growth factor receptor 2 (VEGFR2) upregulation. Using endothelial tube formation assays, gene silencing by siRNA, and antibody-based receptor inhibition, we demonstrate that the activation of NF-κB and VEGFR2 is necessary for the angiogenic responses elicited by dRP. The upregulation of VEGFR2 and NOX2-dependent stimulation of angiogenesis by dRP were confirmed in excisional wound and Matrigel plug vascularization assays in vivo using NOX2−/− mice.Innovation: For the first time, we demonstrate that dRP acts intracellularly and stimulates superoxide anion generation by direct binding and activation of the NOX2 enzymatic complex.Conclusions: This study describes a novel molecular mechanism underlying the proangiogenic activity of dRP, which involves the sequential activation of NOX2 and NF-κB and upregulation of VEGFR2. Antioxid. Redox Signal. 28, 110–130