No description available.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Zirkadiane Rhythmen haben sich in allen Lebensbereichen aufgrund täglicher Wechselwirkungen zwischen internen Zeitgebern und Umweltreizen entwickelt. Molekulare Oszillatoren bestehen aus einer Transkriptions-Translations-Rückkopplungsschleife (TTFL), die selbsterregte Rhythmen ermöglicht. Eine verzögerte negative Rückkopplungsschleife ist zentral für dieses genregulatorische Netzwerk. Die Theorie sagt voraus, dass selbsterregte Oszillationen robuste Verzögerungen und Nichtlinearitäten (Ultrasensitivität) erfordern. Wir untersuchen die zirkadianen Rhythmen in dem filamentösen Pilz Neurospora crassa, um die zugrundeliegenden Uhrmechanismen zu studieren. Seine TTFL umfasst den aktivierenden White Collar Complex (WCC) und den hemmenden FFCKomplex, der aus FRQ (Frequency), FRH (FRQ-interacting RNA Helicase) und CK1a (Caseinkinase 1a) besteht. Darüber hinaus gibt es mehrere Phosphorylierungsstellen auf FRQ (~100) und WCC (~ 95). FRQ wird durch CK1a phosphoryliert. Während wir die zeitliche Dynamik dieser Proteine erforschen, untersuchen wir: 1) wie multiple, langsame und zufällige Phosphorylierungen die Verzögerung und Nichtlinearität in der negativen Rückkopplungsschleife bestimmen. 2) wie Grenzzyklus-Oszillationen entstehen und wie molekulare Schalter selbsterregte Rhythmen unterstützen. In der ersten Veröffentlichung simulieren wir FRQ-Multisite-Phosphorylierungen mit Hilfe gewöhnlicher Differentialgleichungen. Das Modell zeigt zeitliche und stationäre Schalter für die freie Kinase und das phosphorylierte Protein. In der zweiten Veröffentlichung haben wir ein mathematisches Modell von 10 Variablen mit 26 Parametern entwickelt. Unser Modell offenbarte einen Wechsel zwischen WC1-induzierter Transkription und FFC-unterstützter Inaktivierung von WC1. Zusammenfassend wurde die Kernuhr von Neurospora untersucht und dabei die Mechanismen, die den molekularen Schaltern zugrunde liegen, aufgedeckt. / Circadian rhythms have evolved across the kingdoms of life due to daily interactions between internal timing and environmental cues. Molecular oscillators consist of a transcription-translation feedback loop (TTFL) allowing self-sustained rhythms. A delayed negative feedback loop is central to this gene regulatory network. Theory predicts that self-sustained oscillations require robust delays and nonlinearities (ultrasensitivity). We study the circadian rhythms in the filamentous fungi Neurospora crassa to investigate the underlying clock mechanisms. Its TTFL includes the activator White Collar Complex (WCC) (heterodimer of WC1 and WC2) and the inhibitory FFC complex, which is made of FRQ (Frequency protein), FRH (Frequency interacting RNA Helicase) and CK1a (Casein kinase 1a). Moreover, there are multiple phosphorylation sites on FRQ (~ 100) and WCC (~ 95). FRQ is phosphorylated by CK1a. While exploring the temporal dynamics of these proteins, we investigate: 1) how multiple, slow and random phosphorylations govern delay and nonlinearity in the negative feedback loop. 2) how limit cycle oscillations arise and how molecular switches support selfsustained rhythms. In the first publication, we simulate FRQ multisite phosphorylations using ordinary differential equations. The model shows temporal and steady state switches for the free kinase and the phosphorylated protein. In the second publication, we developed a mathematical model of 10 variables with 26 parameters consisting of WC1 and FFC elements in nuclear and cytoplasmic compartments. Control and bifurcation analysis showed that the model produces robust oscillations. Our model revealed a switch between WC1-induced transcription and FFC-assisted inactivation of WC1. Using this model, we also studied possible mechanisms of glucose compensation. In summary, the core clock of Neurospora was examined and mechanisms underlying molecular switches were revealed.

Zirkadiane Uhren sind Zell-autonome Oszillatoren. Aus diesem Grund ist deren interzelluläre Kopplung essentiell, um die Synchronität zirkadianer Oszillatornetzwerke zu erhalten und die Störung zirkadianer Gewebsfunktionen zu verhindern. Neuronale Oszillatoren des Nucleus suprachiasmaticus (SCN), der Schrittmacher-Uhr im Zentralnervensystem der Säugetiere, koppeln interzellulär und über den Austausch sekretierter Neurotransmitter. Die Fähigkeit zirkadianen Oszillatoren peripherer Gewebe interzellulär zu koppeln ist hingegen stark umstritten und molekulare Mechanismen sind unbekannt. In dieser Dissertation zeigen wir, dass periphere Oszillatoren in der Tat interzellulär über den Austausch sekretierter Signalmoleküle koppeln und identifizieren TGF-b als peripheren Kopplungsfaktor. Weiterhin zeigen wir, dass TGF-b die cAMP Enhancer-Motiv abhängige, als auch Immediate Early Expression des Uhr-Gens PER2 induziert und folglich die Phasenanpassung molekularer zirkadianer Oszillationen reguliert. Genetische und pharmakologische Störeinflüsse verursachen die Dysregulation des TGF-b Signalweges und begünstigen die Desynchronisierung zellulärer Oszillatoren, welche sich in Amplitudenreduktion und verstärkter Sensitivität gegenüber Zeitgeber-Signalen äußert. Die in dieser Dissertation präsentierten Ergebnisse, legen einen bisher unbekannten molekularen Mechanismus intrazellulärer Kopplung peripherer zirkadianer Oszillatoren dar und eröffnen neue Perspektiven auf die Bedeutung der Synchronität peripher zirkadianer Uhren für rhythmische Organfunktionen und zirkadiane Gesundheit. / Circadian clocks are cell-autonomous oscillators. Intercellular coupling is crucial to prevent desynchronization of oscillator networks and thus, the disruption of circadian tissue functions. While neuronal oscillators within the mammalian central clock, the suprachiasmatic nucleus (SCN), couple intercellularly via the exchange of secreted neurotransmitters, intercellular coupling among peripheral oscillators is highly debated and molecular mechanisms are unknown. Here, we show that peripheral circadian oscillators couple intercellularly via exchange of secreted signaling molecules and identify TGF-ß as peripheral coupling factor. TGF-ß signaling induces the cAMP response element dependent, immediate-early expression of the clock gene PER2, thereby phase-adjusting the molecular circadian oscillator. Genetic or pharmacologic disruption of TGF-ß signaling causes desynchronization of cellular oscillators resulting in amplitude reduction and increased sensitivity towards Zeitgeber cues. Our findings reveal a previously unknown mechanism of peripheral coupling and open new perspectives on the importance of peripheral clock synchrony for rhythmic organ functions and circadian health.

Lynne Michelle Brocco. / Orginally presented as author's thesis (M.S.--Massachusetts Institute of Technology), 1987. / "References": p. 92-94. / Supported by the U.S. Air Force grant AFOSR-86-0164

This research examines the understandings and practices of inclusive minded principals toward facilitating the development of inclusive school environments for intermediate level (Grade 7 and 8) students who are experiencing behavioural problems in their schools. Qualitative interviews with 16 principals across 4 school districts were conducted to explore how these inclusive minded principals conceptualize and understand the needs of this particular group of students, and what they consider to be their roles and responsibilities as principals in meeting these needs. The data suggest that despite the number of barriers that serve to hamper principals’ efforts to develop the ideal inclusive school, there are a great many strategies principals intentionally use to facilitate change toward more inclusive school cultures and pedagogy. These strategies emanate from, and are reflective of, an inclusive philosophy that is common among participants. Principals’ individual philosophies and ideologies serve as a compass in guiding decision-making and actions that affect staff, students, and the wider school community. In an inclusive school, these ideologies are reflective of the principles of inclusion, such as the need to create a culture of care wherein all students feel valued, supported, and experience a sense of belonging and individual self worth. The implications of this research toward improving the schooling experiences of students with behavioural problems as well as other marginalized groups of learners are discussed in the context of the call for a re-culturing of schools toward more inclusive environments.

This research examines the understandings and practices of inclusive minded principals toward facilitating the development of inclusive school environments for intermediate level (Grade 7 and 8) students who are experiencing behavioural problems in their schools. Qualitative interviews with 16 principals across 4 school districts were conducted to explore how these inclusive minded principals conceptualize and understand the needs of this particular group of students, and what they consider to be their roles and responsibilities as principals in meeting these needs. The data suggest that despite the number of barriers that serve to hamper principals’ efforts to develop the ideal inclusive school, there are a great many strategies principals intentionally use to facilitate change toward more inclusive school cultures and pedagogy. These strategies emanate from, and are reflective of, an inclusive philosophy that is common among participants. Principals’ individual philosophies and ideologies serve as a compass in guiding decision-making and actions that affect staff, students, and the wider school community. In an inclusive school, these ideologies are reflective of the principles of inclusion, such as the need to create a culture of care wherein all students feel valued, supported, and experience a sense of belonging and individual self worth. The implications of this research toward improving the schooling experiences of students with behavioural problems as well as other marginalized groups of learners are discussed in the context of the call for a re-culturing of schools toward more inclusive environments.

La littérature de jeunesse, l'un des supports les plus utilisés dans le contexte scolaire, est considérée comme un objet culturel de l'enfant. Cette thèse porte plus précisément sur les albums de jeunesse dont le personnage principal est un enfant noir. Ces livres sont envoyés aux écoles publiques brésiliennes par le ministère de l'Éducation en vue de « l'éducation aux relations ethnico-raciales » prévue dans les politiques scolaires promulguées en 2003 et 2004, rendant obligatoire « l'enseignement de l'histoire et de la culture afro-brésilienne et africaine » dans tous les établissements scolaires, ainsi que « l'inclusion de personnages noirs [...] dans les supports d'enseignement » (Brasil, 2005). Si, depuis les années 1950, de nombreux chercheurs brésiliens en sciences de l'éducation et en sociologie ont étudié la représentation de ces personnages, les différentes thématiques auxquelles ils sont actuellement associés et la manière dont les enseignant-e-s font usage de ces ouvrages en classe n'ont en revanche fait l'objet que de bien peu d'investigations. Nous étudierons donc ici l'image de l'enfant noir à travers l'analyse du contenu textuel et iconographique de 80 albums contemporains, mais aussi les usages que les enseignantes de huit écoles publiques de Salvador de Bahia font de ces ouvrages, par le bais de deux méthodologies complémentaires : des entretiens collectifs et des observations directes dans une classe de CE2. Nous nous appuierons tout particulièrement sur le concept de race qui, d'un côté, se trouve au cœur de ces politiques scolaires, de ces ouvrages et de leurs usages auprès des enfants et, de l'autre, constitue un outil d'analyse permettant de rendre compte des rapports sociaux. Ce sera alors l'occasion de mettre en lumière les enjeux et limites de ces politiques scolaires et des usages de ces livres en tant que supports de nouvelles modalités pédagogiques pour l'apprentissage de ladite diversité ethno-raciale à l'école. / Children's literature, one of the most widely used aids in a school context, is also considered a child's cultural object. This dissertation focuses specifically on children's books in which the main character is a black child. The Brazilian public schools receive this material from the Department of Education in an aim to promote "education in ethnic-racial relationships" which is present in the school policies that were promulgated in 2003 and 2004, and that made mandatory "the teaching of history and of African-Brazilian and African cultures" in every educational institution as well as "the inclusion of black characters [...] in educational aids" (Brazil, 2005). Numerous Brazilian researchers in the fields of education and sociology have, since the 1950's, studied the representation of this character. Nonetheless, the different subjects to which it is today associated, and the way educators make use of these books inside the classroom, remain yet to be researched. We will therefore, study here, the image of the black child through the analysis of textual and iconographic contents of 80 contemporary children's books, but also the usage that educators of eight public schools of Salvador de Bahia make of these books, while using two complementary approaches: collective interviews and direct observation of a CE2 class. We will focus particularly on the concept of race, which on the one hand, is at the heart of these school policies, of these books and of their usage on children. On the other hand, it constitutes a category of analysis, allowing us to report on social relations. Consequently, this will be the opportunity to bring to light the interests and limitations that these school policies and books entail, as a way to support new educational approaches for the learning of the above mentioned ethnic-racial relationships at school. / A literatura infantojuvenil, um dos suportes mais utilizados no contexto escolar, é considerada como um objeto cultural da criança. Esta tese se interessa especificamente sobre os livros ilustrados infantojuvenis cuja personagem principal é uma criança negra. Estes livros são enviados para as escolas públicas brasileiras pelo Ministério da Educação a fim de atender a "Educação das Relações Étnico-Raciais" prevista nas políticas educacionais promulgadas em 2003 e 2004, tornando obrigatório "o ensino da história e da cultura afro-brasileira e africana" em todos os estabelecimentos de ensino, assim como "a inclusão de personagens negros [...] nos materiais de ensino" (BRASIL, 2005). Se, desde 1950 alguns pesquisadores brasileiros em educação e em sociologia estudaram a representação desses personagens, as diferentes temáticas pelas quais eles são atualmente associados e a maneira como os professores-as fazem uso desses livros em sala de aula têm, porém, sido pouco investigada. Estudamos aqui a imagem da criança negra através da análise de conteúdo textual e iconográfica de 80 livros contemporâneos, mas também os usos que os professores de oito escolas públicas de Salvador - Bahia fazem desses livros através de duas metodologias complementares: entrevistas coletivas e observações diretas em uma turma do terceiro ano do ensino fundamental. Nos apoiaremos particularmente no conceito de raça que, de um lado, se encontra no interior dessas políticas educacionais, desses livros e nos seus usos com as crianças, e por outro lado, constitui uma categoria de análise permitindo observar as relações sociais. Esta será uma ocasião para destacar as perspectivas e limites dessas políticas educacionais e os usos desses livros como suportes de novas modalidades pedagógicas para a aprendizagem da dita diversidade étnico-racial na escola. / La literatura infantil, uno de los recursos más utilizados en el contexto escolar, es considerada como un objeto cultural del niño. Esta tesis se enfoca más precisamente en los álbumes infantiles en los que el personaje principal es un niño negro. El Ministerio de Educación envía estos libros a las escuelas públicas brasileñas con el objetivo de promulgar "la educación para las relaciones étnico-raciales" prevista en las políticas escolares promulgadas en los años 2003 y 2004, haciendo obligatoria "la enseñanza de la historia y de la cultura afro-brasileña y africana" en todos los establecimientos escolares, así como "la inclusión de personajes negros [...] en los recursos de enseñanza" (Brasil, 2005). Si bien, desde los años cincuenta, algunos investigadores brasileños en ciencias de la educación y en sociología han estudiado la representación de este personaje, las diferentes temáticas a las que está actualmente ligado y la manera en que los educadores hacen uso de estos libros dentro de la clase han sido poco investigada. Estudiaremos así la imagen del niño negro a través del análisis del contenido textual e iconográfico de 80 álbumes contemporáneos, así como también los usos que los educadores de ocho escuelas públicas de Salvador de Bahía hacen de estos textos, utilizando dos metodologías complementarias: entrevistas colectivas y observaciones directas dentro de una clase de CE2. Nos apoyaremos particularmente en el concepto de raza la cual, por un lado, se encuentra en el núcleo de estas políticas escolares, de estas obras y de su uso con los niños; y, por otro lado, constituye una categoría de análisis, permitiendo informar sobre las relaciones sociales. De este modo, tendremos la oportunidad de poner de relieve los intereses y las limitaciones de estas políticas escolares, así como de los usos de estos libros, como recursos para nuevas modalidades pedagógicas que facilitan el aprendizaje de dicha diversidad étnico-racial en la escuela.