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Master's Dissertation
DOI
https://doi.org/10.11606/D.47.2004.tde-30102006-185144
Document
Author
Full name
José Ricardo Lopes
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2004
Supervisor
Committee
Barreto, Luiz Silveira Menna (President)
Oda, Gisele Akemi
Sameshima, Koichi
Title in Portuguese
Modelo matemático do sistema de temporização biológica circadiana
Keywords in Portuguese
cronobiologia
feedback
modelo matemático
ritmos biológicos
Abstract in Portuguese
Tanto as evidências experimentais que demonstraram a geração endógena de ritmos com períodos circadianos, quanto as investigações sobre os diferentes mecanismos de sincronização dos ritmos circadianos aos marcadores temporais externos de períodos fixos de 24h forneceram material para a elaboração de proposições importantes sobre as características do sistema de temporização biológica circadiana. Dentro desse cenário, foi de muita ajuda a aplicação da modelagem matemática. O desenvolvimento desses modelos permitiu a investigação de conjecturas que tentam explicar as características subjacentes aos mecanismos que coordenam esse sistema. Nosso objetivo, neste trabalho, foi de explorar a hipótese de que o mecanismo de controle da ritmicidade circadiana é exercido pela ação de laços de retroalimentação negativa acionados após tempos de retardo característicos do sistema. Para alcançarmos esse objetivo, elaboramos um modelo no qual o controle e a manutenção da expressão rítmica circadiana fossem conseqüentes da ação de dois laços de retroalimentação negativa com tempos de retardo distintos. Adicionalmente, avaliamos a resposta do modelo à ação de oscilações externas. Por meio da dinâmica não-linear resultante do modelo, nós observamos sugestiva similaridade entre as respostas obtidas nas simulações e as descrições experimentais da expressão do sistema de temporização circadiana citadas na literatura. Esses resultados deram suporte a hipótese inicial como explicação do funcionamento do sistema.
Title in English
Mathematical model of the circadian timing system
Keywords in English
biological rhythms
chronobiology
feedback
mathematical modeling
Abstract in English
Both the experimental evidences of generation of biological circadian rhythms and the results of investigation about the mechanisms of synchronization between the circadian rhythms with the external cycles of 24-hour period provided material for the development of important assumptions about the characteristics of the circadian timing system. Inside this scenery, it was helpful the application of mathematical models. The development of these models permited the inquiry of some hypotheses which try to explain the underlying characteristics of this system. Our aim, in this work, was to investigate the hypothesis that explain the controlling mechanism of the circadian system as a result of the action of negative feedback loops triggered after charateristic time delays. For reaching this goal, our porpouse was to build a mathematical model which simulated circadian rhythmic expressions controlled by two feedback loops with different time delays. Additionaly, we also simulated the response of the model under external oscillations. Through the non-linear dynamic resulting from the model we observed suggestive similarity between the simulations and the experimental descriptions of the circadian system expressions present in many works. These results gave support to the validation of the initial hypothesis.
 
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JoseRicardoLopes.pdf (1.11 Mbytes)
Publishing Date
2007-01-08
 
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