Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 121-147).

Thesis (Ph. D.)--University of Missouri--Columbia, 2004. / "December 2004" Typescript. Vita. Includes bibliographical references (l. 180-210). Also issued on the Internet.

In spite of its post mitotic nature, skeletal muscle maintains remarkable plasticity. Muscle fibres (myofibres) are capable of large alterations in their size as well as an enormous ability to regenerate following injury – thanks to a potent population of resident stem cells (satellite cells). Deciphering the molecular signalling networks responsible for skeletal muscle growth and regeneration is of key scientific interest – not least because of the therapeutic potential these pathways may hold for the treatment of diseases such as muscular dystrophy. In this thesis, the transcriptional co-factor Yes-Associated protein (Yap), the downstream effector of the Hippo Pathway, was investigated in skeletal muscle. Using gain and loss of function approaches within in vitro, ex vivo and in vivo models, the contribution of Yap in regulating both satellite cell behaviour and myofibre growth was investigated. Yap expression and activity are dynamically regulated during satellite cell activation, proliferation and differentiation ex vivo. Overexpression of Yap increased satellite cell proliferation and maintained cells in a ‘naive’, ‘activated’ state by inhibiting myogenic commitment. Knock-down of Yap impaired satellite cell expansion, but did not influence myogenic differentiation. Yap interacts with Tead transcription factors in myoblasts to upregulate genes such as CyclinD1 and Myf5. Forced expression of Yap eventually led to the oncogenic transformation of myoblasts in vitro. Contrary to predictions, constitutive expression of Yap under an inducible muscle-specific promoter in adult mice failed to induce growth and instead led to muscle wasting, atrophy and degeneration – providing evidence against the notion that Yap represents a universal regulator of tissue growth. These data provide the first insight into the function of Yap in skeletal muscle. Results highlight a novel role for Yap in regulating myogenic progression in satellite cells, as well as its propensity to induce oncogenic transformation. The precise function of Yap in adult myofibres remains unclear however, data presented here demonstrates clear cell-type specific roles for Yap compared to observations made in other tissues.

Orientador: Daniela Micheline dos Santos / Coorientadora: Karina Helga Turcio de Carvalho / Coorientador: Marcelo Coelho Goiato / Banca: Aline Satie Takamiya / Banca: Douglas Roberto Monteiro / Resumo: Atualmente a população tem maior acesso a informações sobre como e porque terem um estilo de vida mais saudável e muitos praticam exercícios físicos regularmente, entre eles os treinos hipertróficos. Em vista do grande esforço físico realizado nesta prática, é necessário avaliar possíveis relações entre o treino hipertrófico e a musculatura do aparelho estomatognático. O objetivo deste estudo foi avaliar a influência da atividade física hipertrófica de membros superiores sobre a eficiência mastigatória e a força máxima de mordida e a correlação entre ambas as análises. Foram selecionados 20 indivíduos (10 homens e 10 mulheres) que praticam atividade física hipertrófica regularmente de acordo com os critérios de inclusão e exclusão. A coleta dos dados sociodemográficos e as análises inicias de eficiência mastigatória e força máxima de mordida foram realizadas previamente a um treino (Grupo Controle) de hipertrofia de membros superiores padronizado e pré-determinado por um educador físico. Logo após o treino, as análises foram repetidas (Grupo teste). A análise estatística foi realizada utilizando o programa SPSS 22.0 (Chicago, EUA). Os valores de eficiência mastigatória e de força máxima de mordida foram submetidos ao teste t de Student e sua correlação foi analisada pelo teste de correlação de Pearson, todos com significância de 5%. Houve uma diminuição significativa da eficiência mastigatória após o treino (p<0,01). Não houve diferença estatística na força de mordida entre o... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Currently, the population has greater access to information about how and why to have a healthier lifestyle and many people practice physical exercises regularly, such as hypertrophic trainings. Considering the great physical effort performed in this practice, it is necessary to evaluate the possible relation between the hypertrophic training and the musculature of the stomatognathic system. The aim of this study was to evaluate the influence superior members hypertrophic physical activity on the masticatory efficiency and the maximum bite force and the correlation between both essays. Twenty individuals (10 men and 10 women) who practice hypertrophic physical activity regularly were selected according to the inclusion and exclusion criteria. Sociodemographic data were collected and the measures of masticatory efficiency, maximum bite force were performed before a standardized, and preset by a physical educator, superior members hypertrophic training (Control Group), and soon after the training, the essays were repeated (Test Group). A statistical analysis was performed using the SPSS 22.0 program (Chicago, USA). The masticatory efficiency and maximum bite force data were submitted to Student's test and their correlation was analyzed by Pearson's test, both with 5% significance. Significant decrease of masticatory efficiency was found after the training (p<0,01). There was no statistical difference in bite force between the assessment periods and there was positive correlation between masticatory efficiency and maximum bite force. Thus, the practice of hypertrophic physical activity decreased the masticatory efficiency but did not alter the maximum bite force and both essays presented positive correlation (p= 0,04) (Complete abstract electronic access below) / Mestre

Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / "May 2001." Typescript. Vita. Includes bibliographical references (leaves 141-150). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri--Columbia, 2003. / "May 2003." Typescript. Vita. Includes bibliographical references (leaves 102-113).

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 91-98).

Lic.-avh. (sammanfattning) Stockholm : Karolinska institutet, 2008. / Härtill 3 uppsatser.

Thesis (Ph. D.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains vii, 141 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.