Intermediate Filaments: Vimentin Moves in

AbstractVimentin intermediate filaments move bi-directionally along microtubules in the cell. Recent work has identified the microtubule motor cytoplasmic dynein as the missing inward-directed motor that drives this movement

Analysis of microtubule movement on isolated Xenopus egg cortices provides evidence that the cortical rotation involves dynein as well as Kinesin Related Proteins and is regulated by local microtubule polymerisation

AbstractIn amphibians, the cortical rotation, a translocation of the egg cortex relative to the cytoplasm, specifies the dorsoventral axis. The cortical rotation involves an array of subcortical microtubules whose alignment is mediated by Kinesin–related proteins (KRPs), and stops as M-phase promoting factor (MPF) activation propagates across the egg. To dissect the role of different motor proteins in the cortical rotation and to analyse their regulation, we have developed an open cell assay system involving reactivation of microtubule movement on isolated cortices. Microtubule movements were dependent on ATP and consisted mainly of wriggling and flailing without net displacement, consistent with a tethering of microtubules to the cortex. Reactivated movements were inhibited by anti-KRP and anti-dynein antibodies perfused together but not separately, the KRP antibody alone becoming fixed to the cortex. Neither antibody could inhibit movement in the presence of MPF, indicating that arrest of the cortical rotation is not due to MPF-dependent inhibition of motor molecules. In contrast, D2O treatment of live eggs to protect microtubules from progressive depolymerisation prolonged the cortical rotation. We conclude that the cortical rotation probably involves cytoplasmic dynein as well as cortical KRPs and terminates as a result of local MPF-dependent microtubule depolymerisation

Effects of Wnt3A and mechanical load on cartilage chondrocyte homeostasis

Introduction Articular cartilage functions in withstanding mechanical loads and provides a lubricating surface for frictionless movement of joints. Osteoarthritis, characterised by cartilage degeneration, develops due to the progressive erosion of structural integrity and eventual loss of functional performance. Osteoarthritis is a multi-factorial disorder; two important risk factors are abnormal mechanical load and genetic predisposition. A single nucleotide polymorphism analysis demonstrated an association of hip osteoarthritis with an Arg324Gly substitution mutation in FrzB, a Wnt antagonist. The purpose of this study was two-fold: to assess whether mechanical stimulation modulates β-catenin signalling and catabolic gene expression in articular chondrocytes, and further to investigate whether there is an interplay of mechanical load and Wnt signalling in mediating a catabolic response. Methods Chondrocytes were pre-stimulated with recombinant Wnt3A for 24 hours prior to the application of tensile strain (7.5%, 1 Hz) for 30 minutes. Activation of Wnt signalling, via β-catenin nuclear translocation and downstream effects including the transcriptional activation of c-jun, c-fos and Lef1, markers of chondrocyte phenotype (type II collagen (col2a1), aggrecan (acan), SOX9) and catabolic genes (MMP3, MMP13, ADAMTS-4, ADAMTS-5) were assessed. Results Physiological tensile strain induced col2a1, acan and SOX9 transcription. Load-induced acan and SOX9 expression were repressed in the presence of Wnt3A. Load induced partial β-catenin nuclear translocation; there was an additive effect of load and Wnt3A on β-catenin distribution, with both extensive localisation in the nucleus and cytoplasm. Immediate early response (c-jun) and catabolic genes (MMP3, ADAMTS-4) were up-regulated in Wnt3A stimulated chondrocytes. With load and Wnt3A there was an additive up-regulation of c-fos, MMP3 and ADAMTS-4 transcription, whereas there was a synergistic interplay on c-jun, Lef1 and ADAMTS-5 transcription. Conclusion Our data suggest that load and Wnt, in combination, can repress transcription of chondrocyte matrix genes, whilst enhancing expression of catabolic mediators. Future studies will investigate the respective roles of abnormal loading and genetic predisposition in mediating cartilage degeneration

Importance of fundamental movement skills to predict technical skills in youth grassroots soccer:a machine learning approach

This study determined the contributors to soccer technical skill in grassroots youth soccer players using a machine learning approach. One hundred and sixty two boys aged 7-14 (Mean ± SD = 10.5 ± 2.1) years, who were regularly engaged in grassroots soccer undertook assessments of anthropometry and maturity offset (the time from age at peak height velocity (APHV)), Fundamental Movement skills (FMS), perceived physical competence, and physical fitness and technical soccer skill using the university of Ghent (UGent) dribbling test. Coaches rated player’s overall soccer skill for their age. Statistical analysis was undertaken, using machine learning models to predict technical skill from the other variables. A stepwise recursive feature elimination with a 5-fold cross-validation (RFECV) method was used to eliminate the worst performing features and both L1 and L2 regularisation were evaluated during the process. Five models (linear, ridge, lasso, random forest, boosted trees) were then used in a heuristic approach using a small subset of suitable algorithms to achieve a reasonable level of accuracy within a reasonable time frame) to make predictions and compare them to a test set to understand the predictive capabilities of the models. Results from the machine learning analysis indicated that total FMS score (0-50) was the most important feature in predicting technical soccer skill followed by coach rating of child skill for their age, years playing experience and APHV. Using a random forest, technical skill could be predicted with 99% accuracy in boys who play grassroots soccer, with FMS being the most important contributor

The impact of a school-based gardening intervention on intentions and behaviour related to fruit and vegetable consumption in children

A total of 77 children (34 boys, 43 girls, mean age ± standard deviation = 9 ± 1 years) participated in this study; 46 children (intervention) undertook a 12-week school gardening programme and 31 children acted as controls. Measures of the Theory of Planned Behaviour and fruit and vegetable consumption were taken pre- and post-intervention. Repeated measures analysis of variance and hierarchical regression analysis indicated that the intervention group increased daily consumption of fruits and vegetables and increased intentions, attitudes, norms, and perceived behavioural control related to fruit and vegetable consumption. Attitudes, norms and perceived behavioural control significantly predicted changes in fruit and vegetable consumption

We need to talk about AI: the case for citizens’ think-ins for citizen-researcher dialogue and deliberation

Artificial Intelligence (AI) has become one of the most important and ubiquitous technologies across the world. On a daily basis, we interact with powerful AI-based technologies through our use of mobile phones, voice assistants, and even our cars. Despite the widespread adoption of AI, questions and concerns exist around the ethical use of these technologies and their potential to reconfigure our personal and working lives. The Science Foundation Ireland ADAPT Research Centre has developed the Citizens’ Think-Ins model of citizen-researcher dialogue. ADAPT’s Think-In series to date has focused specifically on AI and the role it increasingly plays in our lives, and its impact on culture and society. This white paper presents an analysis of the various discussions that took place within the Citizens’ Think-Ins series. The discussions are presented with specific reference to citizens and civic society, academia, industry, and policymakers, and provide concrete recommendations to each stakeholder group, to draw parallels between their requirements, and to encourage the periodic use of Citizens’ Think-Ins as part of a larger deliberative and participatory approach comprising all stakeholders

Morality and markets in the NHS

Since its establishment in 1948, the history of the National Health Service (NHS) has been characterized by organisational turbulence and system reform. At the same time, progress in science, medicine and technology throughout the western world have revolutionized the delivery of healthcare. The NHS has become a much loved, if much critiqued, national treasure. It is against this backdrop that the role of this state-funded health service has been brought into moral question. Certainly, the challenges facing healthcare policy-makers are numerous and complex, but in the wake of the Health and Social Care Act (2012), no issue is more divisive than that of market-based reform. Here we explore the turbulent history of the NHS, from its foundation to the birth of the healthcare marketplace. We explore arguments for and against the healthcare market and resolve that, amid an evolving economic and moral framework, the NHS must ensure that its original tenets of equity and autonomy remain at its core. We propose a values-explicit, systems-based approach to renew focus on both the processes and the outcomes of care

Simulation studies for dielectric wakefield programme at CLARA facility

Short, high charge electron bunches can drive high magnitude electric fields in dielectric lined structures. The interaction of the electron bunch with this field has several applications including high gradient dielectric wakefield acceleration (DWA) and passive beam manipulation. The simulations presented provide a prelude to the commencement of an experimental DWA programme at the CLARA accelerator at Daresbury Laboratory. The key goals of this program are: tunable generation of THz radiation, understanding of the impact of transverse wakes, and design of a dechirper for the CLARA FEL. Computations of longitudinal and transverse phase space evolution were made with Impact-T and VSim to support both of these goals.Comment: 10 Pages, 4 Figures, Proceedings of EAAC2017 Conferenc