L’aérobiologie du pollen de bouleau (Betula spp.) : synergie avec les facteurs environnementaux et impacts sur les maladies respiratoires

Paul Comtois, le directeur initial n'est pas membre du jury en raison de maladie (à long terme). Il n'a pas pu être membre du jury et remplacé par François Courchesne.Plusieurs études publiées à travers le monde ont montré une association entre les enjeux de santé liés aux maladies respiratoires, et les facteurs environnementaux suivants : aéroallergènes, pollution et conditions météorologiques. Cependant, beaucoup moins d'attention a été attribuée à l'impact combiné ou la synergie entre ces différentes familles de co-stresseurs. Ainsi, la notion de synergie entre les facteurs environnementaux et le pollen aéroporté représente le fil conducteur sous-jacent à cette thèse. Par ailleurs, des simulations numériques du pollen allergénique aéroporté (Betula spp.) sont nécessaires pour protéger et informer les citoyens des risques à la santé respiratoire mais aussi pour comprendre dans un contexte régional (à l’aide de cartographie), la variabilité spatio-temporelle à la fois des facteurs environnementaux et celle du pollen. Le système de simulation développé dans le cadre de cette thèse permet l'analyse combinée du transport et de la dispersion à moyenne et longue distance (TDMLD) du pollen anémophile et des polluants atmosphériques. Soumis à de multiples stress environnementaux durant son transport dans l’atmosphère, le grain de pollen peut subir une augmentation des fractures de son enveloppe externe (exine) conduisant à une libération de granules intracytoplasmiques ayant des propriétés allergisantes et une modification des allergènes ayant davantage d’impact sur les patients atopiques. Selon les recherches scientifiques, si ces protéines allergéniques présentes dans les grains de pollen sont inhalées, elles entraînent une attaque d’asthme chez des sujets susceptibles. Bien que la thèse discute d’un grand nombre d’aspects reliés à l’aérobiologie, elle ne permet pas encore de modéliser complètement toutes les facettes du problème mais ouvre la porte à plusieurs avenues de recherche multidisciplinaire. Cinq grandes questions de recherche ou défis méthodologiques sont abordées dans cette thèse : 1. Étant donné la rareté ou l’absence de mesures phénologiques, comment construire un module de phénologie qui sert d’intrant à un modèle d’émission pollinique pour le pollen de Betula (Chapitre 3) ? 2. Comment simuler et intégrer les émissions polliniques et reproduire adéquatement la dispersion du pollen aéroporté dans un modèle couplé météorologie/qualité de l’air déjà existant au Canada tenant compte du fait que ce modèle n’est pas conçu au départ pour simuler le pollen aéroporté (Chapitre 4) ? 3. Quelle est l’origine du pollen de Betula affectant la région de Montréal et quelle est la meilleure façon d’établir sa provenance, tenant compte du fait que les méthodes traditionnelles (rétro-trajectoires, méthode inverses, modèles bi-dimensionnels, etc.) présentent des difficultés qui leur sont propres (Chapitre 4) ? 4. Quels sont les liens synergiques entre l’exposition au pollen allergénique, la pollution et les conditions météorologiques et quels impacts se manifestent sur la santé respiratoire des patients atopiques compte tenu de la présence de facteurs de confusion (i.e. météorologiques, géographiques, socio-économiques, etc.) dans l’analyse des données de pollen de Betula en relation avec les maladies respiratoires à Montréal et au Québec (Chapitres 5 et 6) ? 5. Quelle est la variabilité spatio-temporelle des maladies respiratoires au Québec en relation avec les facteurs de l’environnement atmosphérique (Chapitre 6) ?Several studies published around the world have shown an association between health issues related to respiratory diseases and the following environmental factors: aeroallergens, air pollution and weather conditions. However, much less attention has been attributed to the combined impact or synergy between these different families of co-stressors. Thus, the notion of synergy between environmental factors and airborne pollen represents the main motivation underlying this thesis. Furthermore, numerical simulations of one of the most allergenic pollen (Betula spp.) are necessary to protect and inform citizens of the risks to respiratory health, but also to understand in a regional context (using mapping) the spatial variability of both environmental factors and airborne pollen. In this thesis, the developed simulation system allows the combined analysis of medium and long-distance transport and dispersion (TDMLD) of both anemophilic pollen and atmospheric pollutants. Subjected to multiple environmental stresses the pollen grain may undergo an increase in the fractures of its external envelope (exine) which can lead to a release of allergenic intracytoplasmic granules and a modification of the allergens exacerbating impacts on atopic patients. According to several researchers, these allergenic proteins present within pollen grains when inhaled cause attack of asthma in susceptible humans. Although the thesis discusses many aspects related to aerobiology, it does not yet allow to completely model all the facets of the problem. However, it opens the door to several avenues of multidisciplinary research. Five major research questions or methodological challenges are addressed in this thesis : 1. Given the scarcity or absence of phenological observations, how do we construct a phenology module that is suitable as an input to a pollen emission model for Betula pollen simulation (Chapter 3) ? 2. How to simulate and integrate pollen emissions and adequately reproduce airborne pollen dispersion in an existing coupled meteorology / air quality model developed in Canada, recognizing that this model is not originally designed to simulate airborne pollen (Chapter 4) ? 3. What is the origin of the Betula pollen affecting the Montreal area and what is the best way to establish its provenance, considering that traditional methods (back-trajectories, inverse methods, two-dimensional models, etc.) present their own difficulties (Chapter 4) ? 4. What are the synergistic links between exposure to allergenic pollen, pollution and weather conditions and what impacts are apparent on the respiratory health of atopic patients given the presence of confounding factors (i.e. meteorological, geographical, socio-economic, etc.) in the analysis of Betula pollen data in relation to respiratory diseases in Montreal and the province of Quebec (Chapters 5 and 6)? 5. What is the spatio-temporal variability of respiratory diseases in Quebec in relation to factors of the atmospheric environment (Chapter 6)

Influência, sexualidade e representações familiares nas organizações

Este artigo explora a maneira como as representações familiares e a sexualidade constituem o processo de influência das pessoas em linha de comando no interior das organizações. A vivência familiar é o fundamento da psique primária, da psique familiar e da sexualidade dos indivíduos que são constantemente reelaborados e experimentados quotidianamente na dinâmica dos grupos secundários e nas relações interpessoais no contexto das organizações. Em seguida, esse processo é ilustrado pelo estudo de dois casos:(a)os gerentes de um grupo numa instituição bancária no Canadá e (b)os dirigentes e gerentes de uma empresa do ramo de alimentos no Brasil. Este estudo contribui para ume melhor compreensão das representações familiares em contexto organizacional na medida em que,além de serem determinadas pela sexualidade, elas conferem aos dirigentes e gerentes um repertório de significações que é utilizado e reelaborado para legitimar o exercício de sua influência

Active-site mTOR inhibitors augment HSV1-dICP0 infection in cancer cells via dysregulated eIF4E/4E-BP axis

Herpes Simplex Virus 1 (HSV1) is amongst the most clinically advanced oncolytic virus platforms. However, efficient and sustained viral replication within tumours is limiting. Rapamycin can stimulate HSV1 replication in cancer cells, but active-site dual mTORC1 and mTORC2 (mammalian target of rapamycin complex 1 and 2) inhibitors (asTORi) were shown to suppress the virus in normal cells. Surprisingly, using the infected cell protein 0 (ICP0)-deleted HSV1 (HSV1-dICP0), we found that asTORi markedly augment infection in cancer cells and a mouse mammary cancer xenograft. Mechanistically, asTORi repressed mRNA translation in normal cells, resulting in defective antiviral response but also inhibition of HSV1-dICP0 replication. asTORi also reduced antiviral response in cancer cells, however in contrast to normal cells, transformed cells and cells transduced to elevate the expression of eukaryotic initiation factor 4E (eIF4E) or to silence the repressors eIF4E binding proteins (4E-BPs), selectively maintained HSV1-dICP0 protein synthesis during asTORi treatment, ultimately supporting increased viral replication. Our data show that altered eIF4E/4E-BPs expression can act to promote HSV1-dICP0 infection under prolonged mTOR inhibition. Thus, pharmacoviral combination of asTORi and HSV1 can target cancer cells displaying dysregulated eIF4E/4E-BPs axis.</div

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements