Identification of Epstein-Barr virus replication proteins in Burkitt’s lymphoma cells

The working model to describe the mechanisms used to replicate the cancer-associated virus Epstein-Barr virus (EBV) is partly derived from comparisons with other members of the Herpes virus family. Many genes within the EBV genome are homologous across the herpes virus family. Published transcriptome data for the EBV genome during its lytic replication cycle show extensive transcription, but the identification of the proteins is limited. We have taken a global proteomics approach to identify viral proteins that are expressed during the EBV lytic replication cycle. We combined an enrichment method to isolate cells undergoing EBV lytic replication with SILAC-labeling coupled to mass-spectrometry and identified viral and host proteins expressed during the OPEN ACCESS Pathogens 2015, 4 740 EBV lytic replication cycle. Amongst the most frequently identified viral proteins are two components of the DNA replication machinery, the single strand DNA binding protein BALF2, DNA polymerase accessory protein BMRF1 and both subunits of the viral ribonucleoside-diphosphate reductase enzyme (BORF2 and BaRF1). An additional 42 EBV lytic cycle proteins were also detected. This provides proteomic identification for many EBV lytic replication cycle proteins and also identifies post-translational modifications

The Mini-Addenbrooke's Cognitive Examination: a new assessment tool for dementia.

BACKGROUND/AIMS: We developed and validated the Mini-Addenbrooke's Cognitive Examination (M-ACE) in dementia patients. Comparisons were also made with the Mini Mental State Examination (MMSE). METHOD: The M-ACE was developed using Mokken scaling analysis in 117 dementia patients [behavioural variant frontotemporal dementia (bvFTD), n = 25; primary progressive aphasia (PPA), n = 49; Alzheimer's disease (AD), n = 34; corticobasal syndrome (CBS), n = 9] and validated in an independent sample of 164 dementia patients (bvFTD, n = 23; PPA, n = 82; AD, n = 38; CBS, n = 21) and 78 controls, who also completed the MMSE. RESULTS: The M-ACE consists of 5 items with a maximum score of 30. Two cut-offs were identified: (1) ≤25/30 has both high sensitivity and specificity, and (2) ≤21/30 is almost certainly a score to have come from a dementia patient regardless of the clinical setting. The M-ACE is more sensitive than the MMSE and is less likely to have ceiling effects. CONCLUSION: The M-ACE is a brief and sensitive cognitive screening tool for dementia. Two cut-offs (25 or 21) are recommended.This work was supported by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neurone disease, by the National Health and Medical Research council (NHMRC) of Australia program grant (1037746) and the Australian Research Council (ARC) Centre of Excellence in Cognition and Its Disorders Memory Node (CE110001021). S.H. is supported by the Graham Linford Fellowship from the Motor Neurone Disease Research Institute of Australia. S.M. is supported by Alzheimer Scotland (PhD Studentship). F.L. is supported by an Australian Postgraduate Award (PhD Scholarship). K.D. is supported by NIHR Cambridge Biomedical Research Centre. S.A. is supported by the NIHR Biomedical Research Centre, Oxford. C.R.B. is supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/K010395/1). J.B.R. is supported by the Wellcome Trust (088324), Medical Research Council, McDonnell Foundation and the NIHR (Cambridge Biomedical Research Centre and Biomedical Research Unit in Dementia). E.M. is supported by the NHMRC Early Career Fellowship (1016399) and Alzheimer Association USA. J.R.H. is supported by an ARC Federation Fellowship (FF0776229).This is the final version of the article. It first appeared from Karger via http://dx.doi.org/10.1159/00036604

Search Engine for Antimicrobial Resistance: A Cloud Compatible Pipeline and Web Interface for Rapidly Detecting Antimicrobial Resistance Genes Directly from Sequence Data.

BACKGROUND: Antimicrobial resistance remains a growing and significant concern in human and veterinary medicine. Current laboratory methods for the detection and surveillance of antimicrobial resistant bacteria are limited in their effectiveness and scope. With the rapidly developing field of whole genome sequencing beginning to be utilised in clinical practice, the ability to interrogate sequencing data quickly and easily for the presence of antimicrobial resistance genes will become increasingly important and useful for informing clinical decisions. Additionally, use of such tools will provide insight into the dynamics of antimicrobial resistance genes in metagenomic samples such as those used in environmental monitoring. RESULTS: Here we present the Search Engine for Antimicrobial Resistance (SEAR), a pipeline and web interface for detection of horizontally acquired antimicrobial resistance genes in raw sequencing data. The pipeline provides gene information, abundance estimation and the reconstructed sequence of antimicrobial resistance genes; it also provides web links to additional information on each gene. The pipeline utilises clustering and read mapping to annotate full-length genes relative to a user-defined database. It also uses local alignment of annotated genes to a range of online databases to provide additional information. We demonstrate SEAR's application in the detection and abundance estimation of antimicrobial resistance genes in two novel environmental metagenomes, 32 human faecal microbiome datasets and 126 clinical isolates of Shigella sonnei. CONCLUSIONS: We have developed a pipeline that contributes to the improved capacity for antimicrobial resistance detection afforded by next generation sequencing technologies, allowing for rapid detection of antimicrobial resistance genes directly from sequencing data. SEAR uses raw sequencing data via an intuitive interface so can be run rapidly without requiring advanced bioinformatic skills or resources. Finally, we show that SEAR is effective in detecting antimicrobial resistance genes in metagenomic and isolate sequencing data from both environmental metagenomes and sequencing data from clinical isolates.This research was funded by GlaxoSmithKline, the Centre for Environment, Fisheries and Aquaculture Science and the Biotechnology and Biological Sciences Research Council under an industrial CASE studentship. The funder Centre for Environment, Fisheries and Aquaculture Science provided support in the form of salaries, research materials and facilities for authors DVJ and CBA, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder GlaxoSmithKline provided support in the form of salaries for author JR, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version. It was first published by PLOS at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133492

Hypothalamic volume loss is associated with reduced melatonin output in Parkinson's disease.

BACKGROUND: Recent studies have suggested that melatonin-a hormone produced by the pineal gland under circadian control-contributes to PD-related sleep dysfunction. We hypothesized that degenerative changes to the neural structures controlling pineal function (especially the suprachiasmatic nuclei of the anterior hypothalamus) may be responsible for reduced melatonin output in these patients. We compared hypothalamic volumes in PD patients with matched controls and determined whether volume loss correlated with reduced melatonin output in the PD group. METHODS: A total of 12 PD patients and 12 matched controls underwent magnetic resonance imaging to determine hypothalamic volume. In addition, PD patients underwent 24-hour blood sampling in a controlled environment to determine serum melatonin concentrations using enzyme-linked immunosorbent assays. RESULTS: PD patients had significantly reduced hypothalamic gray matter volume when compared with matched controls. Melatonin levels were significantly associated with hypothalamic gray matter volume and disease severity in PD patients. CONCLUSION: Melatonin levels are associated with hypothalamic gray matter volume loss and disease severity in PD patients. This provides anatomical and physiological support for an intrinsic sleep and circadian phenotype in PD. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.The authors would like to acknowledge the study funders: the Big Lottery Fund (C498A738) and Parkinson’s UK (J-0802). The research was supported by a National Institute of Health Research Biomedical Research Award (to Addenbrooke’s Hospital/University of Cambridge), the Wellcome Trust (103838, 100333/Z/12/Z) and a Raymond and Beverly Sackler Studentship (to DPB). We would like to thank staff at the Wellcome Trust Clinical Research Facility in Addenbrooke’s Hospital, Cambridge for performing the melatonin blood sampling.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/mds.2659

Computer coding and choreography: Contrasting experiences of learning about collaboration in engineering and creative arts

This article argues that how collaboration is taught can have a significant impact on the ways in which collaboration is experienced, understood and valued. In doing so, the study draws attention to performing arts studio-pedagogies, and their potential relevance to enhancing creativity within science, technology, engineering, and mathematics (STEM) education. Through a mixed-methods study of teachers’ and students’ experiences of group work, this article compares two disciplines that maintain distinct discourses on teaching collaboration: Software design and choreography. The quantitative data reveals that despite significant demographic differences, students from the two disciplines maintain a common enthusiasm for group learning. There are significant distinctions however, on student perceptions of the teaching and learning of collaboration, their learning achievements about group work, and the relevance of group work in their discipline. Qualitative commentaries from students and teachers extend the arguments across both the distinctions and the similarities, emphasizing the impact of particular teaching practices and establishing standpoints for further research into the pedagogy of collaboration in higher education.publishedVersio

The diversity, evolution and ecology of Salmonella in venomous snakes

BACKGROUND: Reptile-associated Salmonella bacteria are a major, but often neglected cause of both gastrointestinal and bloodstream infection in humans globally. The diversity of Salmonella enterica has not yet been determined in venomous snakes, however other ectothermic animals have been reported to carry a broad range of Salmonella bacteria. We investigated the prevalence and diversity of Salmonella in a collection of venomous snakes and non-venomous reptiles. METHODOLOGY/PRINCIPLE FINDINGS: We used a combination of selective enrichment techniques to establish a unique dataset of reptilian isolates to study Salmonella enterica species-level evolution and ecology and used whole-genome sequencing to investigate the relatedness of phylogenetic groups. We observed that 91% of venomous snakes carried Salmonella, and found that a diverse range of serovars (n = 58) were carried by reptiles. The Salmonella serovars belonged to four of the six Salmonella enterica subspecies: diarizonae, enterica, houtanae and salamae. Subspecies enterica isolates were distributed among two distinct phylogenetic clusters, previously described as clade A (52%) and clade B (48%). We identified metabolic differences between S. diarizonae, S. enterica clade A and clade B involving growth on lactose, tartaric acid, dulcitol, myo-inositol and allantoin. SIGNIFICANCE: We present the first whole genome-based comparative study of the Salmonella bacteria that colonise venomous and non-venomous reptiles and shed new light on Salmonella evolution. Venomous snakes examined in this study carried a broad range of Salmonella, including serovars which have been associated with disease in humans such as S. Enteritidis. The findings raise the possibility that venomous snakes could be a reservoir for Salmonella serovars associated with human salmonellosis

Teaching collaborative dexterity in higher education: Threshold concepts for educators

This article draws on a multi-phase study of collaboration in tertiary education programmes. This commenced with a survey of 111 students in Engineering and Creative Arts, contrasting their experiences of the teaching of collaboration in different faculties. This led to an iterative action research cycle, in which the conceptual boundaries that surrounded teachers’ approaches to teaching collaboration were explored through qualitative interviews with teachers and observations of teaching practices. Within this article we discuss five specific threshold concepts that subsequently informed the design of the SALAM professional development programme for tertiary educators: enhancing explicit metacognition, scaffolding socialization, animating symmetry, animating pluralism, and embedding values. By bringing greater clarity to the graduate attribute of ‘collaborative dexterity’, we argue how these five threshold concepts present pedagogic responsibilities to teachers in Higher Education who are seeking to constructively align the teaching of collaborative dexterity with assessment procedures, teaching activities and course content.acceptedVersionLocked until 22.10.2021 due to copyright restrictions. This is an [Accepted Manuscript] of an article published by Taylor & Franci

Remote medico-legal assessment by telephone during COVID-19: Monitoring safety and quality when documenting evidence of torture for UK asylum applicants

Due to the Covid-19 pandemic, we developed remote assessment to provide interim medicolegal reports, ensuring people could obtain medical evidence to support their asylum claim. The Freedom from Torture research ethics committee approved the project. To audit this new way of working we collected feedback from the doctors, interpreters, individuals being assessed, and senior medical and legal staff who reviewed the reports. This paper presents findings from the first 20 assessments. Individuals reported that the doctors developed good rapport, but in 35% of assessments reported that there were some experiences they felt unable to disclose. In 70% of assessments, doctors felt that rapport was not as good as when face-to-face. In a majority of assessments the doctor was unable to gain a full account of the torture or its impact. Doctors reported feeling cautious about pressing for more information on the telephone, mindful of individuals’ vulnerability and the difficulty of providing support remotely. Nevertheless, in 85% of assessments doctors felt able to assess the consistency of the account of torture that was given with the psychological findings, in accordance with the Istanbul Protocol. The surveys indicated factors that hindered the assessment: inability to observe body language, the person’s ill health, and confidentiality concerns.  The limitations of these assessments underline the need for a follow-up face-to-face assessment to expand the psychological assessment and undertake a physical assessment. This research indicates that psychological medico-legal reports can safely be produced by telephone assessment, but are more likely to be incomplete in terms of both full disclosure of torture experiences and psychological assessment

Track 1.b Introduction: Re-Designing Health: Transforming Systems, Practices and Care

The Re-Designing Health: Transforming Systems, Practices and Care track explores the increasing role and possibility for a wide range of design practices and methods to contribute to health care products, provision, and systems. There is growing recognition of the increasing complexity faced by healthcare systems; critical issues and challenges include ageing populations, chronic diseases, growing drug ineffectiveness, and lack of access to comprehensive services (to name only a few examples). Concurrently design thinking, methods and practices are increasingly recognized as means of addressing complex, multi-levelled and systemic problems. The track session brought together design academics, researchers and practitioners that are working in—and across—areas of design, medicine and health. Employing design methods, practices, and thinking to address a range of healthcare challenges—from individual product to large-scale policy. This track provided a forum for researchers, practitioners, students, and designers to provide evidence for these relationships, document challenges and successes and to provide theoretical and practical models for healthcare and design to work collaboratively to address complex healthcare problems