Spreading of perturbations in myosin group kinetics along actin filaments

Global changes in the state of spatially distributed systems can often be traced back to perturbations that arise locally. Whether such local perturbations grow into global changes depends on the system geometry and the spatial spreading of these perturbations. Here, we investigate how different spreading behaviors of local perturbations determine their global impact in 1-dimensional systems of different size. Specifically, we assessed sliding arrest events in in vitro motility assays where myosins propel actin, and simulated the underlying mechanochemistry of myosins that bind along the actin filament. We observed spontaneous sliding arrest events that occurred more frequently for shorter actin filaments. This observation could be explained by spontaneous local arrest of myosin kinetics that stabilizes once it spreads throughout an entire actin filament. When we introduced intermediate concentrations of the actin cross-linker filamin, longer actin was arrested more frequently. This observation was reproduced by simulations where filamin binding induces persistent local arrest of myosin kinetics, which subsequently spreads throughout the actin filament. A spin chain model with nearest-neighbor coupling reproduced key features of our experiments and simulations, thus extending to other linear systems with nearest-neighbor coupling the following conclusions: 1) perturbations that are persistent only once they spread throughout the system are more effective in smaller systems, and 2) perturbations that are persistent upon their establishment are more effective in larger systems. Beyond these general conclusions, our work also provides a theoretical model of collective myosin kinetics with a finite range of mechanical coupling along the actin filament

Le rôle de la logique formelle dans le raisonnement judiciaire

Au cours des années 1990, en Ontario, au moins quatorze individus furent accusés et déclarés responsables de la mort d’un enfant qui, au moment du décès, était seul en compagnie de l’inculpé. Plusieurs de ces condamnés furent acquittés à la suite de la découverte d’erreurs commises par le pathologiste médicolégal, tant durant l’autopsie qu’au cours de ses témoignages. Pourtant, il n’était pas le seul à en porter la responsabilité. Les erreurs judiciaires survenues lors de ces procès auraient-elles pu être atténuées par l’application de logique formelle au raisonnement judiciaire ? L’analyse qui suit comprend l’élucidation des erreurs, l’étude de théories de logique et du raisonnement, ainsi qu’un survol de la logique symbolique. L’aide-mémoire ainsi conçu représente un recours possible dans le but de rehausser le raisonnement judiciaire. La symbiose entre la logique et le raisonnement judiciaire s’avère possible, malgré l’écart entre les domaines de la science et du droit

Les facteurs qui influencent l'utilisation de Twitter dans un contexte politique.

De plus en plus, des gens utilisent les sites de réseaux sociaux pour partager du contenu politique ou émettre leurs opinions à ce sujet principalement lors des campagnes électorales. L’objectif principal du mémoire est d’identifier les facteurs qui ont influencé les individus à émettre des commentaires politiques ou à partager du contenu politique par l’intermédiaire du réseau social Twitter lors de la campagne de 2012 au Québec

Birth Weight, Body Silhouette Over the Life Course, and Incident Diabetes in 91,453 Middle-Aged Women From the French Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) Cohort

International audienceOBJECTIVE: Obesity and increases in body weight in adults are considered to be among the most important risk factors for type 2 diabetes. Low birth weight is also associated with a higher diabetes incidence. We aimed to examine to what extent the evolution of body shape, from childhood to adulthood, is related to incident diabetes in late adulthood. RESEARCH DESIGN AND METHODS: Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) is a cohort study of French women born in 1925-1950 and followed by questionnaire every 2 years. At baseline, in 1990, women were asked to report their current weight, height, and body silhouette at various ages. Birth weight was recorded in 2002. Cases of diabetes were self-reported or obtained by drug reimbursement record linkage and further validated. RESULTS: Of the 91,453 women who were nondiabetic at baseline, 2,534 developed diabetes over the 15 years of follow-up. Birth weight and body silhouette at 8 years, at menarche, and in young adulthood (20-25 years) were inversely associated with the risk of diabetes, independently of adult BMI during follow-up (all P(trend) < 0.001). In mid-adulthood (35-40 years), the association was reversed, with an increase in risk related to a larger body silhouette. An increase in body silhouette from childhood to mid-adulthood amplified the risk of diabetes. CONCLUSIONS: Low birth weight and thinness until young adulthood may increase the risk of diabetes, independently of adult BMI during follow-up. Young women who were lean children should be especially warned against weight gain

Intérêt de la clientèle d’un programme de méthadone quant aux services offerts par un groupe de pairs aidants

L’étude porte sur l’intérêt de la clientèle d’un programme de méthadone à exigences peu élevées pour des activités de soutien offertes par des pairs aidants (PA). Des entrevues semi-dirigées ont été menées auprès de 25 clients de Relais-Méthadone à l’admission et après trois mois afin de connaître leur intérêt à participer à des activités organisées par des PA de Méta d’Âme, un groupe d’entraide du centre-sud de Montréal. En dépit du fait que les services paraissaient pertinents pour cette clientèle marginalisée, un intérêt modéré a été manifesté pour les services de PA, alors que peu de clients ont participé à l’activité d’initiation qui leur était proposée. Après trois mois, seulement six des 25 clients invités à participer aux activités y avaient pris part. Le principal intérêt exprimé chez les clients réside dans la possibilité de recevoir de l’aide et du soutien de la part des PA, bien que certains craignent l’influence négative de PA qui n’auraient pas complètement cessé leur consommation. Ces résultats démontrent l’importance d’étudier les préférences des personnes en traitement à la méthadone en ce qui a trait aux modalités de traitement, et plus particulièrement pour ce qui est de l’implication de PA dans les services qu’elles reçoivent.This study investigates the interest shown by clients of a low-threshold methadone program in activities organized by a peer help group in the South-centre region of Montreal. Semi-structured interviews were conducted with 25 new clients in a methadone program, at the admission, and three months later, in order to identify the elements which favor or hinder attendance of peer-helper resources. Although peer-helpers’ support services and activities appear to be suitable for this clientele, the results revealed that clients express only moderate interest in the resource. For example, after three months, only six of 25 study participants were attending peer help group activities. Despite the fact that some participants expressed an interest in receiving help and support from peers, others feared being influenced by those who were still consuming. These results demonstrate the importance of conducting research on the preferences of methadone treatment clientele, to determine the grounds under which they would want peer helpers involved in their treatment, and to determine the most appropriate way to deliver these services.El estudio se refiere al interés de la clientela de un programa de metadona de baja exigencia por las actividades de sostén ofrecidas por un grupo de compañeros de apoyo. Se realizaron entrevistas semi dirigidas con 25 clientes de Relais-Méthadone, en el momento de la admisión y luego de tres meses de tratamiento, con el fin de conocer su interés por la participación en actividades organizadas por los compañeros de apoyo de Méta d’Âme, un grupo de asistencia mutua del sur de Montreal. A pesar del hecho de que los servicios parecían pertinentes para esta clientela marginalizada, la misma manifestó un interés moderado por los servicios de los compañeros de apoyo, ya que pocos clientes participaron en la actividad de iniciación que se les propuso. Luego de tres meses, solamente seis de los 25 clientes invitados a participar lo habían hecho. El interés principal que expresaron fue la posibilidad de recibir ayuda y sostén por parte de los compañeros de apoyo, aunque hay quienes temen la influencia negativa de los compañeros que no han cesado completamente el consumo de drogas. Estos resultados demuestran la importancia de estudiar las preferencias de las personas bajo tratamiento con metadona en lo que respecta a las modalidades de tratamiento y, en particular, a la implicación de los compañeros de apoyo en los servicios que dichas personas reciben

Associations between Children's Genetic Susceptibility to Obesity, Infant's Appetite and Parental Feeding Practices in Toddlerhood.

Previous findings suggest that parental feeding practices may adapt to children's eating behavior and sex, but few studies assessed these associations in toddlerhood. We aimed to study the associations between infant's appetite or children's genetic susceptibility to obesity and parental feeding practices. We assessed infant's appetite (three-category indicator: low, normal or high appetite, labelled 4-to-24-month appetite) and calculated a combined obesity risk-allele score (genetic risk score of body mass index (BMI-GRS)) in a longitudinal study of respectively 1358 and 932 children from the EDEN cohort. Parental feeding practices were assessed at 2-year-follow-up by the CFPQ. Three of the five tested scores were used as continuous variables; others were considered as binary variables, according to the median. Associations between infant's appetite or child's BMI-GRS and parental feeding practices were assessed by linear and logistic regression models, stratified on child's sex if interactions were significant. 4-to-24-month appetite was positively associated with restrictive feeding practices among boys and girls. Among boys, high compared to normal 4-to-24-month appetite was associated with higher use of food to regulate child's emotions (OR [95% CI] = 2.24 [1.36; 3.68]). Child's BMI-GRS was not related to parental feeding practices. Parental feeding practices may adapt to parental perception of infant's appetite and child's sex

A Multi-Scale Approach to Airway Hyperresponsiveness: From Molecule to Organ

Airway hyperresponsiveness (AHR), a characteristic of asthma that involves an excessive reduction in airway caliber, is a complex mechanism reflecting multiple processes that manifest over a large range of length and time scales. At one extreme, molecular interactions determine the force generated by airway smooth muscle (ASM). At the other, the spatially distributed constriction of the branching airways leads to breathing difficulties. Similarly, asthma therapies act at the molecular scale while clinical outcomes are determined by lung function. These extremes are linked by events operating over intermediate scales of length and time. Thus, AHR is an emergent phenomenon that limits our understanding of asthma and confounds the interpretation of studies that address physiological mechanisms over a limited range of scales. A solution is a modular computational model that integrates experimental and mathematical data from multiple scales. This includes, at the molecular scale, kinetics, and force production of actin-myosin contractile proteins during cross-bridge and latch-state cycling; at the cellular scale, Ca2+ signaling mechanisms that regulate ASM force production; at the tissue scale, forces acting between contracting ASM and opposing viscoelastic tissue that determine airway narrowing; at the organ scale, the topographic distribution of ASM contraction dynamics that determine mechanical impedance of the lung. At each scale, models are constructed with iterations between theory and experimentation to identify the parameters that link adjacent scales. This modular model establishes algorithms for modeling over a wide range of scales and provides a framework for the inclusion of other responses such as inflammation or therapeutic regimes. The goal is to develop this lung model so that it can make predictions about bronchoconstriction and identify the pathophysiologic mechanisms having the greatest impact on AHR and its therapy