Analyse des interactions entre lymphocytes T CD8 et neurones au moyen du modèle de neuroinflammation induite par le Bornavirus

Les lymphocytes T CD8 cytotoxiques (CTL) sont aujourd'hui considérés comme des acteurs clés dans diverses pathologies neuroinflammatoires ou neurodégénératives, telles que la sclérose en plaques, l'encéphalite de Rasmussen ou la maladie d'Alzheimer. On présume qu'ils participent aux lésions neuronales observées dans ces pathologies bien que leur contribution précise reste à déterminer. En effet, la possibilité que les neurones puissent représenter une cible pour les CTL reste controversée, notamment parce que les neurones expriment peu de molécules du complexe majeur d'histocompatibilité de classe I (CMH-I) en conditions physiologiques. Dans ce contexte, l'objectif général de ma thèse était donc d'analyser les interactions entre CTL et neurones, ainsi que leurs conséquences, au moyen d'un modèle original de neuroinflammation. Pour cela, j'ai utilisé le modèle de neuroinflammation induite par l'infection avec le virus de Borna (BDV). L'infection intracérébrale du rat Lewis avec ce virus neurotrope, absolument non cytolytique aussi bien in vivo qu'in vitro, est connue pour induire une inflammation médiée par les CTL. Les CTL purifiés à partir du cerveau de rats infectés sont incubés ex vivo avec des cultures primaires de neurones corticaux de rats Lewis, préalablement infectées par le BDV. Ainsi, j'ai pu analyser la dynamique et les conséquences de l'interaction entre CTL et neurones, en utilisant notamment des techniques d'imagerie en temps réel. D'une part, j'ai pu observer que l'infection par le BDV induit l'expression de CMH-I à la surface des neurones, les rendant potentiellement susceptibles à l'attaque par les CTL. D'autre part, les CTL sont préférentiellement recrutés dans le cerveau des rats infectés et surexpriment fortement des effecteurs cytolytiques en terme d'ARNm. De plus, suite à l'incubation avec des neurones infectés, les CTL purifiés à partir du cerveau peuvent sécréter de l'IFN-gamma, alors que ce n'est pas le cas suite à une stimulation avec des neurones non infectés ou lorsque les CTL sont purifiés à partir de la périphérie. Par la suite, l'enregistrement en temps réel des interactions CTL-neurones a révélé que la mobilité des CTL est sévèrement réduite, et ce de façon dépendante de l'interaction avec le complexe CMH-I/antigène viral, suggérant une interaction spécifique avec les neurones. En outre, l'observation de neurones marqués à la calcéine a permit de montrer des changements rapides de la morphologie neuronale, dépendant encore une fois du CMH-I. Afin d'étudier les propriétés électrophysiologiques des neurones pendant cette attaque par les CTL, nous avons enregistré l'activité électrique de réseaux de neurones corticaux mis en culture sur des supports à électrodes multiples en collaboration avec le Pr. Le Masson (Inserm U862). De façon surprenante, l'analyse fonctionnelle des neurones montre que le réseau neuronal reste électriquement actif durant cette période. De plus, les neurones semblent assez résistant à l'attaque par les CTL puisque l'activation des caspases 3 et 7, indiquant l'induction de l'apoptose, n'est détectée qu'au bout de 4 heures de co-incubation. Dans leur ensemble, ces données suggèrent que la dynamique de l'attaque neuronale par les CTL semble être différente de celle d'une cible conventionnelle.Cytotoxic CD8 T cells (CTLs) are increasingly recognized as key players in various inflammatory and degenerative central nervous system (CNS) disorders, such as multiple sclerosis, Rasmussen's encephalitis or Alzheimer's disease. CTLs are believed to actively contribute to neuronal damage in these CNS conditions although their relative contribution remains elusive. Indeed, the possibility that neurons could represent a target for CTLs is still controversial, in part due to the paucity of Major Histocompatibility Complex (MHC) class I expression by neurons. Given this context, the general aim of my thesis was to analyze the dynamics of interaction between CTLs and neurons and bring new information about the mechanisms of neuronal injury caused by CTLs. To address this question, I used the model of neuroinflammation induced by neurotropic Borna Disease Virus (BDV). Intracerebral infection of adult Lewis rat with BDV, a non-cytolytic virus, is known to induce a CD8 T cell-mediated inflammation. CTLs ex vivo purified from brains of BDV-infected animals were co-incubated with primary cultures of cortical neurons infected by BDV. I could then assess the dynamics and consequences of CTL interaction with neurons, using live-cell imaging and time-lapse microscopy techniques. On one hand, I observed that BDV infection induces MHC class I expression on neurons, rendering them susceptible to CTL attack. On another hand, CTLs are preferentially recruited in the CNS of infected rats, expressing high amounts of cytolytic effector mRNA. Moreover, upon incubation with infected neurons, ex vivo brain-purified CTL produce IFN-gamma, which is not the case when incubated with non-infected neurons or for peripheral CTLs. Thereafter, live-cell imaging of CTL-neuron interaction revealed that CTL mobility was dramatically reduced in an MHC class I-dependent manner, suggesting specific interaction with neurons. Analysis using calcein staining showed changes in neuronal morphology, once again dependent on MHC class I expression. In order to investigate the effect of CTL attack on neuronal electrical properties, we recorded electrical activity of neuronal networks seeded on MicroElectrode Array (MEA), in collaboration with Pr. Le Masson (Inserm U862). Surprisingly, this analysis revealed that the neuronal network remains functionally active during this period. Moreover, neurons appeared to resist quite well to this initial CTL contact, since caspase-3 and -7 activation, indicating apoptosis induction, was detected only 4 hours after co-incubation. Taken together, these data suggest that the dynamics of CTL-neuron interaction may be quite different to that of a classical CTL target. Taken together, these data suggest that the dynamics of CTL-neuron interaction may be quite different to that of a classical CTL target

Sistematización del proceso participativo para la creación de la política de innovación en la UNED

Las universidades, como organizaciones sociales requieren transitar en un proceso de transformación que les permita repensar su quehacer y, alcanzar una mayor cercanía a las comunidades educativas, por medio del trabajo en sus áreas sustantivas. La innovación, se constituye en este contexto, en un acicate para la educación superior; que invoca cambio y transformación profunda en lo que hace y en las formas, procesos y herramientas que emplea para lograrlo. Esta concepción de innovación va más allá de lo que se considera en estos días y en diferentes contextos, reducida al uso intensivo de las tecnologías de la información y comunicación. La necesidad de sistematizar y generar conocimiento que permitiera comprender y fortalecer las capacidades innovadoras en la UNED, propició que un grupo interdisciplinario, conformado por decisión abierta e individual de sus integrantes y, con representación de las distintas Vicerrectorías de la universidad, se organizara y conformara el Nodo de Innovación. Este grupo asumió la tarea de investigar el quehacer innovador de la institución y el estudio de distintos marcos de referencia teórico-conceptuales sobre la innovación y la organización para ofrecer a las autoridades universitarias y la comunidad educativa en general, un diseño de sistema de innovación particular orientado a la UNED; sustentado en la aprobación de una política institucional y su respectivo plan de implementación. Esta ponencia explica la sistematización diseñada especialmente por el Nodo de Innovación, en la definición de esa propuesta de la política de innovación como sistema y que desde el mes de julio del 2017, se encuentra en discusión dentro de dos comisiones del Consejo Universitario, con la intención de ser llevada y aprobada al seno del plenario de ese órgano político colegiado

Teaching of English in French-Canada

Thesis (Ed.M.)--Boston University, 1935. This item was digitized by the Internet Archive

Outcomes reported in randomised trials of surgical prehabilitation: a scoping review

BACKGROUND: Heterogeneity of reported outcomes can impact the certainty of evidence for prehabilitation. The objective of this scoping review was to systematically map outcomes and assessment tools used in trials of surgical prehabilitation. METHODS: MEDLINE, EMBASE, PsychInfo, Web of Science, CINAHL, and Cochrane were searched in February 2023. Randomised controlled trials of unimodal or multimodal prehabilitation interventions (nutrition, exercise, psychological support) lasting at least 7 days in adults undergoing elective surgery were included. Reported outcomes were classified according to the International Society for Pharmacoeconomics and Outcomes Research framework. RESULTS: We included 76 trials, mostly focused on abdominal or orthopaedic surgeries. A total of 50 different outcomes were identified, measured using 184 outcome assessment tools. Observer-reported outcomes were collected in 86% of trials (n=65), with hospital length of stay being most common. Performance outcomes were reported in 80% of trials (n=61), most commonly as exercise capacity assessed by cardiopulmonary exercise testing. Clinician-reported outcomes were included in 78% (n=59) of trials and most frequently included postoperative complications with Clavien-Dindo classification. Patient-reported outcomes were reported in 76% (n=58) of trials, with health-related quality of life using the 36- or 12-Item Short Form Survey being most prevalent. Biomarker outcomes were reported in 16% of trials (n=12) most commonly using inflammatory markers assessed with C-reactive protein. CONCLUSIONS: There is substantial heterogeneity in the reporting of outcomes and assessment tools across surgical prehabilitation trials. Identification of meaningful outcomes, and agreement on appropriate assessment tools, could inform the development of a prehabilitation core outcomes set to harmonise outcome reporting and facilitate meta-analyses

Neurons are MHC Class I-Dependent Targets for CD8 T Cells upon Neurotropic Viral Infection

Following infection of the central nervous system (CNS), the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL) because they do not express major histocompatibility class I (MHC I) molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV), in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and uncover the unusual modalities of CTL-induced neuronal damage

La communication (un outil indispensable à la relation praticien-patient en odontologie)

NANCY1-SCD Pharmacie-Odontologie (543952101) / SudocPARIS-BIUM (751062103) / SudocNANCY1-Bib. numérique (543959902) / SudocSudocFranceF

Floristic surveys for monitoring plant biodiversity in forest ecosystems - Material for reflection to make the right choices

Confronted with the various threats facing forest ecosystems (climate change, eutrophication, increased wood removals) managers of natural spaces feel a need to monitor biodiversity. The aim of this article is to provide guidance for survey planners to assist them in choosing the practical methods for conducting floristic recordings in a forest environment. It begins with a general description of the method (representativeness, exhaustivity, reproductibility, feasibility) and goes on to discuss various implementation options such as the overall surface area of the plots surveyed, the latters’ shape, factoring in the operator effect, seasonality, the relevance of considering the abundance and stratification of the species, with a view to fulfilling the monitoring objectives. The article does not propose a standard protocol and instead reports hands-on feedback from some ten or so years of studies of methodologies for floristic inventories steered by Cemagref at Nogent-sur-Vernisson (Loiret).Face aux multiples menaces qui planent sur les écosystèmes forestiers (changement climatique, eutrophisation, augmentation des prélèvements de bois), les gestionnaires d’espaces naturels ressentent le besoin d’y réaliser des suivis de biodiversité. Dans ce contexte, le présent article a pour objectif de guider les chargés d’études dans le choix des modalités de réalisation du relevé floristique en forêt. Après en avoir présenté les qualités génériques (représentativité, exhaustivité, reproductibilité, faisabilité), les options de réalisation telles que la surface du relevé, la forme de la placette, la maîtrise de l’effet opérateur, la prise en compte de la saisonnalité, l’intérêt de prendre en compte l’abondance et la stratification des espèces sont discutés au regard des objectifs du suivi. L’article ne propose pas un protocole standard mais rend compte du retour d’expérience, utile au praticien, d’une dizaine d’années d’études méthodologiques sur les inventaires floristiques, pilotées par le Cemagref de Nogent-sur-Vernisson (Loiret)

Analyse des interactions entre lymphocytes T CD8 et neurones au moyen du modèle de neuroinflammation induite par le Bornavirus

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Inventaire des applications pédagogiques de l'ordinateur dans les collèges du Québec, 1973-1974 /

Bibliogr.: p. 150-15

Does perceived cohesion mediate the student personality–engagement relationship in the university setting?

International audienceStudent engagement has been established as a robust predictor of several positive outcomes related to academic development and success. Increasing our knowledge on what variables affect engagement can assist lecturers and other educational agents in maximizing student engagement within the university setting. The purpose of this study was to investigate the relationship between personality and student engagement via the mediational role of perceived cohesion in the university classroom. The model was tested using multilevel structural equation modelling and cross-sectional data from 1500 students (72% female) belonging to 72 different university classrooms. The mediation model linking the personality dimensions with engagement via perceived cohesion, including task and social orientations, was partially supported by the data. Task cohesion mediated the positive relationship between three personality dimensions (i.e., agreeableness, extraversion, and emotional stability) and student engagement. No significant results were found with social cohesion as a mediator of the personality-engagement relationship. These findings suggest that building and developing a cohesive environment in the university setting, especially with regards to task cohesion, may be an effective strategy to promote student engagement. However, the specific characteristics of the university environment should be also considered (e.g., academic major or time spent in small work groups vs time spent in large ‘traditional’ lecture theatres). Recommendations for future research are discussed