Mutational analysis of Sse1 (Hsp110) suggests an integral role for this chaperone in yeast prion propagation in vivo.

The yeast Hsp110 chaperone Sse1 is a conserved protein that is a noncanonical member of the Hsp70 protein superfamily. Sse1 influences the cellular response to heat stress and has also been implicated in playing a role in the propagation of prions in yeast. Sse1 can seemingly exert its effects in vivo through direct or indirect actions by influencing the nucleotide exchange activity of canonical cytosolic Hsp70s. Using a genetic screen based on the inability to propagate the yeast [PSI(+)] prion, we have identified 13 new Sse1 mutants that are predicted to alter chaperone function through a variety of different mechanisms. Not only are these new Sse1 mutants altered in the ability to propagate and cure yeast prions but also to varying degrees in the ability to grow at elevated temperatures. The expression levels of chaperone proteins known to influence yeast prion propagation are unaltered in the Sse1 mutants, suggesting that the observed phenotypic effects are caused by direct functional alterations in these mutants. Mapping the location of the mutants onto the Sse1 crystal structure suggests that more than one functional alteration in Sse1 may result in changes in prion propagation and ability to function at elevated temperatures. All Sse1 mutants isolated provide essential functions in the cell under normal growth conditions, further demonstrating that essential chaperone functions in vivo can to some degree at least be detached from those related to propagation of prions. Our results suggest that Sse1 can influence prion propagation through a variety of different mechanisms

Social training reconfigures prediction errors to shape Self-Other boundaries

Selectively attributing beliefs to specific agents is core to reasoning about other people and imagining oneself in different states. Evidence suggests humans might achieve this by simulating each other’s computations in agent-specific neural circuits, but it is not known how circuits become agent-specific. Here we investigate whether agent-specificity adapts to social context. We train subjects on social learning tasks, manipulating the frequency with which self and other see the same information. Training alters the agent-specificity of prediction error (PE) circuits for at least 24 h, modulating the extent to which another agent’s PE is experienced as one’s own and influencing perspective-taking in an independent task. Ventromedial prefrontal myelin density, indexed by magnetisation transfer, correlates with the strength of this adaptation. We describe a frontotemporal learning network, which exploits relationships between different agents’ computations. Our findings suggest that Self-Other boundaries are learnable variables, shaped by the statistical structure of social experience

Prospects for policy advances in science and technology in the Gulf Arab States: the role of international partnerships

Science, technology, engineering and mathematics (STEM) policies in the Gulf Arab States are as diverse as the individual economies and political processes that characterize its member states. During the past decade, a number of expert review groups have argued that science and technology policy needs to be reformed and revitalized in the Gulf Arab States. Several reports and studies have identified the need to develop and adopt more rigorous plans to raise the level of research and development (R&D) in the region. In several of the Gulf Arab States, policy makers have sought to address this issue through establishment of new “Education Cities” wherein university campuses have been co-located with industrial parks in order to build regional knowledge economies. Many of these initiatives have attracted foreign talent and global R&D firms. Our research aims to understand the etiology of the under-performance of the R & D efforts in the region. In this paper, we report on results obtained from in-person interviews with the Ministers of Education and other educators in the Gulf Arab States. We interviewed experts in the field of science and technology policy in the Gulf region to address the following major questions: 1) how can science (e.g. biomedical, agriculture, engineering) be strengthened in the Gulf Arab States; 2) how effective are the science policies enacted by regional governments in the Gulf, and how can these policies be enhanced; 3) what role do regional or international collaborations play in a research and training network system, and how can these regional partnerships be bolstered; and, 4) how can the international community assist to accelerate progress and reduce the science knowledge gap. Our results show that the under-performance of the Gulf region in science and technology appears to be due to a: 1) lack of early exposure of young adults to science, 2) low perception of the societal value of science, 3) lack of institutional (e.g. university) resources, 4) too few scientists who make science their long-term careers, 5) lack of an integrated, international research network of collaboration, and 6) lack of motivation among students. We also report on our findings regarding the state-of-the-art of the research enterprise, and the strengths and weaknesses of the research and training environment as perceived by educators/administrators in the region

Multiperspectival designs and processes in interpretative phenomenological analysis research

Researchers using interpretative phenomenological analysis (IPA) within applied research typically use homogenous samples exploring shared perspectives on a single phenomenon of interest. This article explores the challenges and opportunities involved with developing rigorous and epistemologically coherent research designs for capturing more complex and systemic experiential phenomena, through the use of multiple perspectives to explore the same phenomenon. We outline a series of multiple perspective designs and analytic procedures that can be adapted and used across many diverse settings and populations. Whilst building upon existing approaches within qualitative methods and IPA, these designs and procedures are intended to scaffold clear routes to practical application, psychological intervention, the design of behaviour change interventions, and other recommendations for policy and practice. We discuss a variety of conceptual antecedents which situate these designs within phenomenology, pluralistic idiography, qualitative psychology, and wider debates within psychology and other social and behavioural sciences

Forty years studying British politics : the decline of Anglo-America

The still present belief some 40 years ago that British politics was both exceptional and superior has been replaced by more theoretically sophisticated analyses based on a wider and more rigorously deployed range of research techniques, although historical analysis appropriately remains important. The American influence on the study of British politics has declined, but the European Union dimension has not been fully integrated. The study of interest groups has been in some respects a fading paradigm, but important questions related to democratic health have still to be addressed. Public administration has been supplanted by public policy, but economic policy remains under-studied. A key challenge for the future is the study of the management of expectations

Propagation of an Earth-directed coronal mass ejection in three dimensions

Solar coronal mass ejections (CMEs) are the most significant drivers of adverse space weather at Earth, but the physics governing their propagation through the heliosphere is not well understood. While stereoscopic imaging of CMEs with the Solar Terrestrial Relations Observatory (STEREO) has provided some insight into their three-dimensional (3D) propagation, the mechanisms governing their evolution remain unclear due to difficulties in reconstructing their true 3D structure. Here we use a new elliptical tie-pointing technique to reconstruct a full CME front in 3D, enabling us to quantify its deflected trajectory from high latitudes along the ecliptic, and measure its increasing angular width and propagation from 2-46 solar radii (approximately 0.2 AU). Beyond 7 solar radii, we show that its motion is determined by an aerodynamic drag in the solar wind and, using our reconstruction as input for a 3D magnetohydrodynamic simulation, we determine an accurate arrival time at the Lagrangian L1 point near Earth.Comment: 5 figures, 2 supplementary movie

Patients’ Preference and Experiences of Forced Medication and Seclusion

This study examined patients’ preferences for coercive methods and the extent to which patients’ choices were determined by previous experience, demographic, clinical and intervention-setting variables. Before discharge from closed psychiatric units, 161 adult patients completed a questionnaire. The association between patients’ preferences and the underlying variables was analyzed using logistic regression. We found that patients’ preferences were mainly defined by earlier experiences: patients without coercive experiences or who had had experienced seclusion and forced medication, favoured forced medication. Those who had been secluded preferred seclusion in future emergencies, but only if they approved its duration. This suggests that seclusion, if it does not last too long, does not have to be abandoned from psychiatric practices. In an emergency, however, most patients prefer to be medicated. Our findings show that patients’ preferences cannot guide the establishment of international uniform methods for managing violent behaviour. Therefore patients’ individual choices should be considered

MetaMine – A tool to detect and analyse gene patterns in their environmental context

Background Modern sequencing technologies allow rapid sequencing and bioinformatic analysis of genomes and metagenomes. With every new sequencing project a vast number of new proteins become available with many genes remaining functionally unclassified based on evidences from sequence similarities alone. Extending similarity searches with gene pattern approaches, defined as genes sharing a distinct genomic neighbourhood, have shown to significantly improve the number of functional assignments. Further functional evidences can be gained by correlating these gene patterns with prevailing environmental parameters. MetaMine was developed to approach the large pool of unclassified proteins by searching for recurrent gene patterns across habitats based on key genes. Results MetaMine is an interactive data mining tool which enables the detection of gene patterns in an environmental context. The gene pattern search starts with a user defined environmentally interesting key gene. With this gene a BLAST search is carried out against the Microbial Ecological Genomics DataBase (MEGDB) containing marine genomic and metagenomic sequences. This is followed by the determination of all neighbouring genes within a given distance and a search for functionally equivalent genes. In the final step a set of common genes present in a defined number of distinct genomes is determined. The gene patterns found are associated with their individual pattern instances describing gene order and directions. They are presented together with information about the sample and the habitat. MetaMine is implemented in Java and provided as a client/server application with a user-friendly graphical user interface. The system was evaluated with environmentally relevant genes related to the methane-cycle and carbon monoxide oxidation. Conclusion MetaMine offers a targeted, semi-automatic search for gene patterns based on expert input. The graphical user interface of MetaMine provides a user-friendly overview of the computed gene patterns for further inspection in an ecological context. Prevailing biological processes associated with a key gene can be used to infer new annotations and shape hypotheses to guide further analyses. The use-cases demonstrate that meaningful gene patterns can be quickly detected using MetaMine

Implementation of the 2017 Berlin Concussion in Sport Group Consensus Statement in contact and collision sports: a joint position statement from 11 national and international sports organisations.

The 2017 Berlin Concussion in Sport Group Consensus Statement provides a global summary of best practice in concussion prevention, diagnosis and management, underpinned by systematic reviews and expert consensus. Due to their different settings and rules, individual sports need to adapt concussion guidelines according to their specific regulatory environment. At the same time, consistent application of the Berlin Consensus Statement's themes across sporting codes is likely to facilitate superior and uniform diagnosis and management, improve concussion education and highlight collaborative research opportunities. This document summarises the approaches discussed by medical representatives from the governing bodies of 10 different contact and collision sports in Dublin, Ireland in July 2017. Those sports are: American football, Australian football, basketball, cricket, equestrian sports, football/soccer, ice hockey, rugby league, rugby union and skiing. This document had been endorsed by 11 sport governing bodies/national federations at the time of being published

Membranes by the Numbers

Many of the most important processes in cells take place on and across membranes. With the rise of an impressive array of powerful quantitative methods for characterizing these membranes, it is an opportune time to reflect on the structure and function of membranes from the point of view of biological numeracy. To that end, in this article, I review the quantitative parameters that characterize the mechanical, electrical and transport properties of membranes and carry out a number of corresponding order of magnitude estimates that help us understand the values of those parameters.Comment: 27 pages, 12 figure