Analysis of occludin trafficking, demonstrating continuous endocytosis, degradation, recycling and biosynthetic secretory trafficking

© 2014 Fletcher et al. Tight junctions (TJs) link adjacent cells and are critical for maintenance of apicalbasolateral polarity in epithelial monolayers. The TJ protein occludin functions in disparate processes, including wound healing and Hepatitis C Virus infection. Little is known about steady-state occludin trafficking into and out of the plasma membrane. Therefore, we determined the mechanisms responsible for occludin turnover in confluent Madin-Darby canine kidney (MDCK) epithelial monolayers. Using various biotin-based trafficking assays we observed continuous and rapid endocytosis of plasma membrane localised occludin (the majority internalised within 30 minutes). By 120 minutes a significant reduction in internalised occludin was observed. Inhibition of lysosomal function attenuated the reduction in occludin signal post-endocytosis and promoted co-localisation with the late endocytic system. Using a similar method we demonstrated that ∼20% of internalised occludin was transported back to the cell surface. Consistent with these findings, significant co-localisation between internalised occludin and recycling endosomal compartments was observed. We then quantified the extent to which occludin synthesis and transport to the plasma membrane contributes to plasma membrane occludin homeostasis, identifying inhibition of protein synthesis led to decreased plasma membrane localised occludin. Significant co-localisation between occludin and the biosynthetic secretory pathway was demonstrated. Thus, under steady-state conditions occludin undergoes turnover via a continuous cycle of endocytosis, recycling and degradation, with degradation compensated for by biosynthetic exocytic trafficking. We developed a mathematical model to describe the endocytosis, recycling and degradation of occludin, utilising experimental data to provide quantitative estimates for the rates of these processes

Trusting homo economicus: a hermeneutical inquiry into the origin, application, and necessity of trust

This hermeneutical inquiry is of trust and it addresses the question, "Can we live a day without trust?" The purpose of this inquiry is to deepen our understanding of the notion of trust by situating it within three historical contexts--modern day, the Middle Ages, and Colonial America. The genesis of trust is known to have begun in the Middle Ages due to sweeping economic changes from feudalism to the rise of capitalism. When European colonists arrived in North America they brought with them their concept of trust. Trust was then introduced to the Native American peoples and was used to define the judico-legal relationship with what became the United States government. Again, trust was used for economic prosperity by creating a "special trust relationship" with the indigenous population so that they would sign over their land rights (Newcomb, 2003). Ultimately, trust was used to further the dream of westward expansion and the eventual industrialization of America. Finally, trust is interpreted in the current modern context where it is ubiquitous and has reached a heightened point of emphasis in the role it is believed to serve in certain social institutions, primarily schools and businesses. Within each historical period, interpretations are offered for how and why the concept of trust was used and often viewed as being essential to the functioning of daily life. By viewing trust situated in the economic, social and political circumstances of each period of time readers will see how trust has become increasingly necessary along with the rise of capitalism. In essence, trust is and was needed in societies whereby individual economic prosperity became the primary focus of daily life. In this same way, trust is currently perceived as necessary in our schools. This concept will be explained as another place where perpetuating the values of capitalism is the primary aim. Finally, I explain how due to the existence of capitalism we cannot live a day without trust; however; our personal relationships should not hinge on the expectations one wants fulfilled through trust but rather an ethic of care

Physical Activity in Individuals with Autism Spectrum Disorders (ASD): A Review

Current recommendations indicate that children and youth ages 5–17 should participate in 60 min and adults in 150 min of moderate-to-vigorous physical activity daily. Research suggests that physical activity levels of individuals with autism spectrum disorder (ASD) are lower than typically developing and developed peers. Despite evidence for PA decreasing negative behaviors and promoting positive behaviors, individuals with ASD may be less motivated and less likely to participate. Individuals with ASD may be more likely to be overweight or obese than their typically developing counterparts as a result of decreased activity levels. Conflicting findings regarding PA levels in individuals with ASD have been reported. Given mixed evidence, further inquiry is warranted. The present chapter provides a review of literature pertaining to PA in individuals with ASD. Four databases were searched. Predetermined search terms and inclusion/exclusion criteria were clearly outlined to identify relevant articles which were then critically appraised. This research provides a greater understanding of the status of PA participation of individuals with ASD

Health improvement and educational attainment in secondary schools: complementary or competing priorities? Exploratory analyses from the School Health Research Network in Wales

Background. Implementing health improvement is often perceived as diverting resource away from schools’ core business, reflecting an assumption of a “zero-sum game” between health and education. There is some evidence that health behaviors may affect young people’s educational outcomes. However, associations between implementation of school health improvement and educational outcomes remains underinvestigated. Methods. The study linked school-level data on free school meal (FSM) entitlement, educational outcomes, and school attendance, obtained from government websites, with data from the School Environment Questionnaire (SEQ) on health improvement activity collected in Wales (2015/2016). Spearman’s rank correlation coefficients and linear regression models tested the extent of association between health improvement activity and attendance and educational outcomes. Results. SEQ data were provided by 100/115 network schools (87%), of whom data on educational performance were obtained from 97. The percentage of pupils entitled to FSM predicted most of the between-school variance in achievement and attendance. Linear regression models demonstrated significant positive associations of all measures of health improvement activity with attainment at Key Stage (KS) 3, apart from mental health education in the curriculum and organizational commitment to health. Student and parent involvement in planning health activities were associated with improved school attendance. There were no significant associations between health improvement and KS4 attainment. Conclusion. Implementing health improvement activity does not have a detrimental effect on schools’ educational performance. There is tentative evidence of the reverse, with better educational outcomes in schools with more extensive health improvement policies and practices. Further research should investigate processes by which this occurs and variations by socioeconomic status

Testing the ‘zero-sum game’ hypothesis: An examination of school health policies and practices and inequalities in educational outcomes

Background There is recognition that health and education are intrinsically linked through, for example, WHO's Health Promoting Schools (HPS) framework. Nevertheless, promoting health via schools is seen by some as a zero-sum game—ie, schools have nothing to gain, and may experience detriments to the core business of academic attainment because of focusing resources on health. Crucially, there is a paucity of evidence around the impacts of health and wellbeing policy and practice on attainment, with recent Cochrane reviews highlighting this gap. This study explored the zero-sum game hypothesis among schools with varying levels of deprivation—ie, the role of health and wellbeing interventions in schools in reducing or widening socioeconomic inequality in educational attainment. Methods Wales-wide, school-level survey data on health policies and practices, reflective of the HPS framework, were captured in 2016 using the School Environment Questionnaire. Questionnaire data were linked with routinely collected data on academic attainment. Primary outcomes included attendance and attainment at Key stages 3 (children aged 12–14 years) and 4 (15–16). Interaction terms were fitted to test whether there was an interaction between free school meals, overall HPS activity, and outcomes. Linear regression models were constructed separately for schools with high uptake of free school meals (>15% of pupils) and low uptake (<15%), adjusting for confounders. Findings The final analyses included 48 schools with low uptake of free school meals and 49 with high uptake. Significant interactions were observed between free school meals and overall HPS activity for Key stage 3 attainment (β=0·28, 95% CI 0·09–0·47) and attendance (0·05, 0·02–0·09), reflecting an association between health improvement activities and education outcomes among high, but not low, free school meal schools. There was no significant interaction for Key stage 4 attainment (0·18, −0·22 to 0·57). Interpretation Our findings did not support the zero-sum game hypothesis; in fact, among more deprived schools, there was a tendency for better attendance and attainment at Key stage 3. Schools must equip students with the skills required for good physical and mental health and wellbeing in addition to academic and cognitive skills. The study included a large, nationally representative sample of secondary schools; however, the cross-sectional nature has implications for causality

International Courts & Judicial Affairs

This chapter reviews some of the most significant developments made by international courts and tribunals in 2020. I. International Court of Justice As of the time of writing (November 2020), this year, the International Court of Justice (Court) has rendered one order on provisional measures, two judgments on appeals from decisions of the International Civil Aviation Organization (ICAO) Council, and two orders relating to expert evidence

The problem with self-management : problematising self-management and power using a Foucauldian lens in the context of stroke care and rehabilitation

Self-management is a concept which is now firmly established in Western healthcare policy and practice. However, the term remains somewhat ambiguous, multi-faceted and contentious. This is evident in stroke care and rehabilitation, in which a self-management approach is increasingly adopted and advocated, yet interpreted in different ways, resulting in contradictions and tensions around control, responsibility, power and discipline. This paper aims to further our understanding of tensions and contradictions in stroke self-management, by critically examining contemporary self-management practices. We use a Foucauldian theoretical lens to explore the various power dynamics in the operationalisation of self-management, in addition to the complexity of the term self-management itself. Conducting a secondary analysis of interview and focus group data from the Self-Management VOICED study, supplemented with analysis of relevant documentary evidence from policy and practice, we describe the multiple aspects of power in operation. These include rhetorical, hierarchical, personal and mutual forms of power, representing interweaving dynamics evident in the data. These aspects of power demonstrate underlying agendas and tacit and explicit understandings of self-management which exist in clinical practice. These aspects of power also give insight into the multiple identities of 'self-management', acting as a simultaneous repressor and liberator, directly in keeping with Foucauldian thinking. The findings are also consistent with Foucault's notions of bodily docility, discussions around governance and biopower, and contemporary discipline. Our analysis positions self-management as a highly nuanced and complex concept, which can fluctuate in its conceptualisation depending on the structures, routines, and the individual. We encourage healthcare professionals, policymakers and commissioners in the field of self-management to reflect on these complexities, to make transparent their assumptions and to explicitly position their own practice accordingly

Buffering against maladaptive perfectionism in bipolar disorder:The role of self-compassion

Background Maladaptive perfectionism is a transdiagnostic risk and maintaining factor for a range of mental health conditions, including bipolar disorder (BD). Self-compassion represents a potential protective factor against maladaptive perfectionism, however no studies to date have examined the relationship of these constructs in BD. The aim of the present study was to examine associations between maladaptive perfectionism, self-compassion and symptoms among individuals with BD. Methods Baseline data were collected from 302 participants with a DSM-IV diagnosis of BD participating in an international randomised controlled trial. Participants completed measures of maladaptive perfectionism, self-compassion, symptom severity and emotion regulation difficulties. Clinician-administered measures of depression and mania severity were additionally collected. Correlation and mediation analyses were conducted. Results Maladaptive perfectionism was positively associated with depression, anxiety and emotion regulation difficulties. Lower levels of self-compassion correlated with greater self-reported depression, anxiety and emotion regulation difficulties. Self-compassion partially mediated relationships between maladaptive perfectionism, depression, anxiety and emotion regulation difficulties. Limitations The cross-sectional design limits conclusions about causal relationships between study variables. Results may not be generalizable to other BD populations. The role of maladaptive perfectionism and self-compassion in elevated mood states of BD remains unclear. Conclusion Self-compassion represents one mechanism through which maladaptive perfectionism influences symptoms of depression, anxiety and emotion regulation difficulties in BD. Self-compassion represents a modifiable treatment target; individuals with BD exhibiting maladaptive perfectionistic tendencies may benefit from interventions fostering self-compassion

Music Therapy for Patients Who Have Undergone Hematopoietic Stem Cell Transplant

Objectives. This study examines the short- and long-term QOL benefits of a music therapy intervention for patients recovering from hematopoietic stem cell transplantation (HSCT). Methods. Ninety allogeneic HSCT patients, after transplant, were randomized to receive ISO-principle (i.e., mood matching) based music therapy (MT; n = 29), unstructured music (UM; n = 30), or usual care (UC; n = 31) for four weeks. The ISO principle posits that patients may shift their mood from one state to another by listening to music that is equal to the individual\u27s initial mood state and subsequently listening to music selections that gradually shift in tempo and mood to match the patient\u27s desired disposition. Participants in MT and UM groups developed two audio CDs to help them feel more relaxed and energized and were instructed to use the CDs to improve their mood as needed. Short-term effects on mood and long-term effects on QOL were examined. Results. MT and UM participants reported improved mood immediately after listening to CDs; the within-group effect was greater for UM participants compared to MT participants. Participant group was not associated with long-term QOL outcomes. Conclusions. Music listening improves mood acutely but was not associated with long-term benefits in this study