Vimentin downregulation is an inherent feature of murine erythropoiesis and occurs independently of lineage

In mammalian erythropoiesis, the mature cells of the primitive lineage remain nucleated while those of the definitive lineage are anuclear. One of the molecular and structural changes that precedes enucleation in cells of the definitive lineage is the cessation in the expression of the gene for the intermediate filament (IF) protein vimentin and the removal of all vimentin filaments from the cytoplasm. We show here that in immature primitive cells vimentin is synthesized and forms a cytoplasmic network of IFs. As differentiation proceeds in vivo, vimentin gene expression is downregulated in these cells; this is accompanied by the loss of vimentin filaments from the cytoplasm. This loss temporally coincides with the nucleus becoming freely mobile within the cytoplasm, suggesting that, while IF removal is not directly linked to the physical process of enucleation, it may be a prerequisite for the initiation of nuclear mobility in both lineages. These changes are also observed in early primitive cells cultured in vitro, suggesting that they constitute an intrinsic part of the murine erythroid differentiation program independent of lineage and hematopoietic microenvironment

Control of erythroid differentiation: asynchronous expression of the anion transporter and the peripheral components of the membrane skeleton in AEV- and S13-transformed cells

Chicken erythroblasts transformed with avian erythroblastosis virus or S13 virus provide suitable model systems with which to analyze the maturation of immature erythroblasts into erythrocytes. The transformed cells are blocked in differentiation at around the colony-forming unit- erythroid stage of development but can be induced to differentiate in vitro. Analysis of the expression and assembly of components of the membrane skeleton indicates that these cells simultaneously synthesize alpha-spectrin, beta-spectrin, ankyrin, and protein 4.1 at levels that are comparable to those of mature erythroblasts. However, they do not express any detectable amounts of anion transporter. The peripheral membrane skeleton components assemble transiently and are subsequently rapidly catabolized, resulting in 20-40-fold lower steady-state levels than are found in maturing erythrocytes. Upon spontaneous or chemically induced terminal differentiation of these cells expression of the anion transporter is initiated with a concommitant increase in the steady- state levels of the peripheral membrane-skeletal components. These results suggest that during erythropoiesis, expression of the peripheral components of the membrane skeleton is initiated earlier than that of the anion transporter. Furthermore, they point a key role for the anion transporter in conferring long-term stability to the assembled erythroid membrane skeleton during terminal differentiation

Identifying High and Low Walkable Neighbourhoods Using Multi-disciplinary Walkability Criteria

Neighbourhood features contributing to the walkability (pedestrian friendliness) of a neighbourhood are diverse and depend on both its physical and social attributes. Earlier work in the Cleaner, Greener, Leaner (CGL) Study identified differences in opinion between professional stakeholder groups (planners, designers, engineers, public representatives, and public health and advocacy professionals) on what constitutes a walkable environment [1]. This diversity has implications for neighbourhood design and planning policy. The findings of a multi-disciplinary focus group study were used to generate a list of walkability criteria to select areas for a population study. In this study twenty areas were shortlisted and grouped under four categories: high walkable deprived, high walkable not deprived, low walkable deprived and low walkable not deprived. This paper presents the process undertaken to identify the study sites. International walkability research has favoured macro-scale objective geographic information systems (GIS) information to identify study areas [2]. While these macro scale attributes are important for walkability, alone they were considered insufficient for site selection by the CGL team as street characteristics were not considered and the attributes had a bias towards transportation walking. Also, indications from the focus group participants were that walkability is perceptual and therefore some resulting criteria were subjective, for example ‘a pleasant atmosphere contextual to area characteristics’ and therefore difficult to measure objectively. The CGL site selection process presented a number of challenges including limitations with available GIS information, unrepresentative neighbourhood boundaries on GIS datasets, and only one deprived neighbourhood identified as high walkable by the focus group participants. An investigation of the role of high and low walkable environments on resident’s behaviours and health can be used to inform future planning, transport, public health and neighbourhood design policies

Active commuting to school: How far is too far?

Walking and cycling to school provide a convenient opportunity to incorporate physical activity into an adolescent's daily routine. School proximity to residential homes has been identified as an important determinant of active commuting among children. The purpose of this study is to identify if distance is a barrier to active commuting among adolescents, and if there is a criterion distance above which adolescents choose not to walk or cycle. Data was collected in 2003-05 from a cross-sectional cohort of 15-17 yr old adolescents in 61 post primary schools in Ireland. Participants self-reported distance, mode of transport to school and barriers to active commuting. Trained researchers took physical measurements of height and weight. The relation between mode of transport, gender and population density was examined. Distance was entered into a bivariate logistic regression model to predict mode choice, controlling for gender, population density socio-economic status and school clusters. Of the 4013 adolescents who participated (48.1% female, mean age 16.02 ± 0.661), one third walked or cycled to school. A higher proportion of males than females commuted actively (41.0 vs. 33.8%, χ2 (1) = 22.21, p < 0.001, r = -0.074). Adolescents living in more densely populated areas had greater odds of active commuting than those in the most sparsely populated areas (χ2 (df = 3) = 839.64, p < 0.001). In each density category, active commuters travelled shorter distances to school. After controlling for gender and population density, a 1-mile increase in distance decreased the odds of active commuting by 71% (χ2 (df = 1) = 2591.86, p < 0.001). The majority of walkers lived within 1.5 miles and cyclists within 2.5 miles. Over 90% of adolescents who perceived distance as a barrier to active commuting lived further than 2.5 miles from school. Distance is an important perceived barrier to active commuting and a predictor of mode choice among adolescents. Distances within 2.5 miles are achievable for adolescent walkers and cyclists. Alternative strategies for increasing physical activity are required for individuals living outside of this criterion

Intraretinal pigmented cells in retinal degenerative disease

PURPOSE: Invasion of pigmented cells into the retina occurs in retinal degenerative diseases, such as macular telangiectasia type 2 (MacTel) and retinitis pigmentosa (RP). These intraretinal pigmented cells may be derived from the retinal pigment epithelium (RPE), but differences and similarities between intraretinal pigmented cells and RPE have so far not been well characterised.Clinicopathologic case report. METHOD: Here, we compared intraretinal pigment cells with RPE cells by immunohistochemistry. Immunohistological stains for classic RPE markers (RPE65, CRALBP and KRT18) and blood vessel markers (lectin and collagen 4) were done on sections from postmortem eye tissue from two MacTel donors, an RP donor and a control donor. MAIN OUTCOME MEASURES: Presence of specific immunohistochemistry markers on intraretinal pigmented and RPE cells. RESULTS: We found that intraretinal pigmented cells did not express RPE65 and CRALBP, with a small subset expressing them weakly. However, they all expressed KRT18, which was also present in normal RPE cells. Interestingly, we also found clusters of KRT18-positive cells in the retina that were not pigmented. CONCLUSIONS: Our findings suggest that RPE cells invading the retina dedifferentiate (losing classic RPE markers) and can be pigmented or unpigmented. Therefore, the number of RPE cells invading the retina in retinal degenerative disease may be underappreciated by funduscopy

Preuve de la validité du score de la qualité de l’évaluation pour l’apprentissage : une mesure de qualité pour les commentaires des superviseurs dans la formation médicale fondée sur les compétences

Background: Competency based medical education (CBME) relies on supervisor narrative comments contained within entrustable professional activities (EPA) for programmatic assessment, but the quality of these supervisor comments is unassessed. There is validity evidence supporting the QuAL (Quality of Assessment for Learning) score for rating the usefulness of short narrative comments in direct observation. Objective: We sought to establish validity evidence for the QuAL score to rate the quality of supervisor narrative comments contained within an EPA by surveying the key end-users of EPA narrative comments: residents, academic advisors, and competence committee members. Methods: In 2020, the authors randomly selected 52 de-identified narrative comments from two emergency medicine EPA databases using purposeful sampling. Six collaborators (two residents, two academic advisors, and two competence committee members) were recruited from each of four EM Residency Programs (Saskatchewan, McMaster, Ottawa, and Calgary) to rate these comments with a utility score and the QuAL score.  Correlation between utility and QuAL score were calculated using Pearson’s correlation coefficient. Sources of variance and reliability were calculated using a generalizability study. Results: All collaborators (n = 24) completed the full study.  The QuAL score had a high positive correlation with the utility score amongst the residents (r = 0.80) and academic advisors (r = 0.75) and a moderately high correlation amongst competence committee members (r = 0.68).  The generalizability study found that the major source of variance was the comment indicating the tool performs well across raters. Conclusion: The QuAL score may serve as an outcome measure for program evaluation of supervisors, and as a resource for faculty development.Contexte : Dans la formation médicale fondée sur les compétences (FMFC), l’évaluation programmatique s’appuie sur les commentaires narratifs des superviseurs en lien avec les activités professionnelles confiables (EPA). En revanche, la qualité de ces commentaires n’est pas évaluée. Il existe des preuves de la validité du score QuAL (qualité de l’évaluation pour l’apprentissage, Quality of Assessment for Learning en anglais) pour l’évaluation de l’utilité des commentaires de rétroaction courts lors de la supervision par observation directe. Objectif : Nous avons tenté de démontrer la validité du score QuAL aux fins de l’évaluation de la qualité des commentaires narratifs des superviseurs pour une APC en interrogeant les principaux utilisateurs finaux des rétroactions : les résidents, les conseillers pédagogiques et les membres du comité de compétence. Méthodes : En 2020, les auteurs ont sélectionné au hasard 52 commentaires narratifs anonymisés dans deux bases de données d’APC en médecine d’urgence au moyen d’un échantillonnage intentionnel. Six collaborateurs (deux résidents, deux conseillers pédagogiques et deux membres de comités de compétence) ont été recrutés dans chacun des quatre programmes de résidence en médecine d’urgence (Saskatchewan, McMaster, Ottawa et Calgary) pour évaluer ces commentaires à l’aide d’un score d’utilité et du score QuAL.  La corrélation entre l’utilité et le score QuAL a été calculée à l’aide du coefficient de corrélation de Pearson. Les sources de variance et la fiabilité ont été calculées à l’aide d’une étude de généralisabilité. Résultats : Tous les collaborateurs (n=24) ont réalisé l’étude complète.  Le score QuAL présentait une corrélation positive élevée avec le score d’utilité parmi les résidents (r=0,80) et les conseillers pédagogiques (r=0,75) et une corrélation modérément élevée parmi les membres du comité de compétence (r=0,68).  L’étude de généralisation a révélé que la principale source de variance était le commentaire, ce qui indique que l’outil a fonctionné avec une efficacité égale pour tous les évaluateurs. Conclusion : Le score QuAL peut servir de mesure des résultats pour l’évaluation des superviseurs par les programmes, et de ressource pour le perfectionnement du corps professoral

Hydrogen evolution from water using heteroatom substituted fluorene conjugated co-polymers

The photocatalytic performance of fluorene-type polymer photocatalysts for hydrogen production from water in the presence of a sacrificial hole scavenger is significantly improved by the incorporation of heteroatoms into the...</p

Genome sequence alterations detected upon passage of Burkholderia mallei ATCC 23344 in culture and in mammalian hosts

BACKGROUND: More than 12,000 simple sequence repeats (SSRs) have been identified in the genome of Burkholderia mallei ATCC 23344. As a demonstrated mechanism of phase variation in other pathogenic bacteria, these may function as mutable loci leading to altered protein expression or structure variation. To determine if such alterations are occurring in vivo, the genomes of various single-colony passaged B. mallei ATCC 23344 isolates, one from each source, were sequenced from culture, a mouse, a horse, and two isolates from a single human patient, and the sequence compared to the published B. mallei ATCC 23344 genome sequence. RESULTS: Forty-nine insertions and deletions (indels) were detected at SSRs in the five passaged strains, a majority of which (67.3%) were located within noncoding areas, suggesting that such regions are more tolerant of sequence alterations. Expression profiling of the two human passaged isolates compared to the strain before passage revealed alterations in the mRNA levels of multiple genes when grown in culture. CONCLUSION: These data support the notion that genome variability upon passage is a feature of B. mallei ATCC23344, and that within a host B. mallei generates a diverse population of clones that accumulate genome sequence variation at SSR and other loci

Early parenting and children\u27s relational and physical aggression in the preschool and home contexts

This study investigated early parent- child relationships and how children\u27s use of relational and physical aggression varies with aspects of those relationships during the preschool years. Specifically, parenting styles, parents\u27 use of psychological control, and parents\u27 report of their children\u27s reunion behaviors were assessed. Analyses revealed significant associations between children\u27s use of both relational and physical aggression and parents\u27 reports of their own and their partner\u27s parenting style, psychological control behaviors, and indicators of the attachment relationship. The results highlight the importance of investigating both mothers\u27 and fathers\u27 parenting and the sex of the child in studies of potential links between parenting behaviors and young children’s relational and physical aggression. Findings were considered in the context of each perspective and suggestions for future research and implications for intervention and prevention are discussed

What is the 'problem' that outreach work seeks to address and how might it be tackled? Seeking theory in a primary health prevention programme

&lt;b&gt;Background&lt;/b&gt; Preventive approaches to health are disproportionately accessed by the more affluent and recent health improvement policy advocates the use of targeted preventive primary care to reduce risk factors in poorer individuals and communities. Outreach has become part of the health service response. Outreach has a long history of engaging those who do not otherwise access services. It has, however, been described as eclectic in its purpose, clientele and mode of practice; its effectiveness is unproven. Using a primary prevention programme in the UK as a case, this paper addresses two research questions: what are the perceived problems of non-engagement that outreach aims to address; and, what specific mechanisms of outreach are hypothesised to tackle these.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Drawing on a wider programme evaluation, the study undertook qualitative interviews with strategically selected health-care professionals. The analysis was thematically guided by the concept of 'candidacy' which theorises the dynamic process through which services and individuals negotiate appropriate service use.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; The study identified seven types of engagement 'problem' and corresponding solutions. These 'problems' lie on a continuum of complexity in terms of the challenges they present to primary care. Reasons for non-engagement are congruent with the concept of 'candidacy' but point to ways in which it can be expanded.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; The paper draws conclusions about the role of outreach in contributing to the implementation of inequalities focused primary prevention and identifies further research needed in the theoretical development of both outreach as an approach and candidacy as a conceptual framework