Circadian clocks are responsible for scheduling many behavioral and physiological processes to occur at the most appropriate time of day. The resulting daily rhythms also synchronize (entrain) to external environmental cues, known as zeitgebers. This phenomenon of entrainment enables organisms to anticipate daily changes in environmental conditions such as sunrise/sunset, temperature variations, availability of prey, etc. Given the critical nature of entrainment to survival, it is no surprise that the mechanism is conserved across taxa. The misalignment of the intrinsic clock with the external environment results in a plethora of negative consequences, made apparent by studies involving shift work and jet lag. The focus of the present study is to investigate the chronobiology of Larinioides cornutus (Araneidae), a nocturnal orb-weaving spider, with an emphasis on its entrainment to light:dark cycles. Because spiders have received scarce attention with respect to their chronobiology, it is instructive to compare the properties of spider circadian systems with those of the more established circadian model systems, such as Drosophilaand Murines. We found that both lights-off and lights-on are equally influential zeitgeber cues for (determines the phasing of) both activity onset and offset. Locomotor activity typically begins within a half hour after nightfall, continues throughout the night, and ceases just prior to dawn. Phase shifting experiments show that these spiders can re-entrain within 2 days to a light/dark cycle shifted by 6 hours, and within 3 days when shifted by 12 hours. These rates of re-entrainment occur at an extremely accelerated rate compared to mammals, which readjust to a time shift at a rate of around 1 day/ 1 hour of phase shift. In other words, spiders have a minimal jet-lag response. This suggests an increased level of plasticity in the spider circadian clock that has yet to be observed in other organisms. Typical of circadian rhythms in nearly all organisms, activity also persisted (free-runs) under constant conditions. However, in constant darkness (DD), a drastic change in periodicity was revealed in 66% of individuals, from 23.4 to 25.2. This particular phenomenon is rare and likely indicates the possible interaction of multiple oscillators. Further evidence to support this interpretation is the consistent periods of the rhythm displayed before and after the change. In contrast, under constant light (LL) conditions, 65% of spiders were arrhythmic, with 4 individuals ceasing activity completely. Significant periods detected in LL were normally distributed over an unusually broad range, from 16.7 to 34.9 hours, suggesting a high sensitivity to light. Because of the unusual rates of re-entrainment to light/dark cycles, the spontaneous changes in free-running period under DD, and arrhythmicity in LL, we propose that spiders are valuable comparative model organism for elucidating fundamental mechanisms of circadian clocks.

As plântulas de jatobá apresentam grandes quantidades de reserva de carbono, na forma de polissacarídeos constituintes de parede, presentes em seus cotilédones. Estas reservas são inicialmente utilizadas para expansão dos eófilos. Após esta fase, as plântulas passam a dispor de duas fontes de carbono, sendo elas, as reservas (que ainda não se esgotaram totalmente) e a autotrófica (compreendida pela fotossíntese) (Santos e Buckeridge, 2004). O acompanhamento em condições constantes de diversas variáveis nos permitiu concluir que a maioria dos parâmetros envolvidos com a fotossíntese são controlados circadianamente. Este controle apresenta, ao menos, dois sistemas oscilatórios independentes, que atuam, quando sob um ciclo ambiental, em conjunto. O controle da degradação das reservas é mais incerto, apesar de apresentarmos fortes evidências que apontam para a existência de um controle temporal endógeno. Conseguimos identificar, em alguns casos, uma influência forte do ambiente agindo diretamente sobra a expressão de algumas variáveis, como a concentração de clorofila. Por fim, desenhamos um quadro geral do controle temporal envolvido na questão fonte dreno (durante a fase de estabelecimento desta espécie), no qual, pudemos integrar os dados de todas as variáveis aferidas, definindo os principais mecanismos de controle envolvidos / Jatobá seedlings have large amounts of carbon reserves in the form of wall constituent polysaccharides, present in their cotyledons. These reserves are initially used in the expansion of the eophylls. After this stage, the seedlings have two sources of carbon, the reserves (which are not fully degraded yet) and autotrophic (understood as photosynthesis) (Santos and Buckeridge, 2004). The constant conditions allowed us to conclude that most of the parameters involved in the photosynthesis process are circadian controlled. This control mechanism has at least two independent oscillatory systems, which are coupled when under the influence of an environmental cycle. The nature of the temporal control of the reserves degradation is yet unclear. Although, evidences are that it\'s being controlled by an endogenous component. We were able to identify, in some cases, a strong influence of the environment, acting directly on the expression of some variables (such as chlorophyll concentration). Finally, we draw a general picture of the temporal control mechanism involved in the source-sink balance (during the establishment phase of this species), in which we were able to integrate all our data and therefore, identify some important control mechanisms involved

O câncer de mama é o tipo de câncer que mais acomete as mulheres e a principal causa de morte na faixa entre 40 e 55 anos. Apesar de apresentar variação internacional, suas taxas seguem aumentando mundialmente, sendo até cinco vezes mais frequente em países desenvolvidos. A industrialização gera aumento da exposição à luz durante a noite, o que causa supressão de melatonina. A melatonina é o principal hormônio secretado pela glândula pineal e possui atividade oncostática e antioxidante, interfere no controle do ciclo celular, função imunológica e nos hormônios esteróides. O objetivo desta dissertação e apresentar o racional e o desenvolvimento do estudo cujo objetivo foi avaliar o efeito da terapia com melatonina sobre o desenvolvimento de tumores mamários em ratas expostas ou não a dessincronização circadiana. A indução da carcinogênese mamária foi através de administração intragástrica de DMBA em 39 ratas Sprague-dawley entre 41 e 46 dias. Os animais foram randomizados em 04 grupos, Sincronizados sem tratamento, Dessincronizados sem tratamento, Sincronizados com melatonina e Dessincronizados com melatonina. Os grupos Sincronizados foram mantidos em ciclo claro/escuro de 12/12 horas e os dessincronizados a ciclo claro/escuro de 11/11 horas, durante 8 semanas. O desenvolvimento tumoral ocorreu em 32 animais (82,05%), totalizando 73 tumores. A melatonina apresentou efeitos benéficos quanto a multiplicidade tumoral, grau histológico, tamanho dos tumores e peso dos animais, enquanto que a dessincronização não interferiu de forma significativa na carcinogênese mamária. / Breast cancer is the type of cancer that most affects women and the leading cause of death in the age between 40 and 55 years. Despite presenting international variation, their rates continue to increase worldwide, with up to five times more common in developed countries. The industrialization generates increased exposure to light at night, which causes suppression of melatonin. Melatonin is the main hormone secreted by the pineal gland and has oncostatic and antioxidant activity, interferes with cell cycle control, immune function and steroid hormones. The aim of this dissertation and present the rationale and development of the study whose objective was to evaluate the effect of melatonin therapy on the development of mammary tumors in rats exposed or not the circadian desynchronization. Induction of mammary carcinogenesis was via intragastric administration of DMBA in 39 Sprague- Dawley rats between 41 and 46 days. The animals were randomized into 04 groups, Synchronized and untreated, desynchronized and untreated, synchronized and with melatonin, desynchronized and with melatonin. Synchronized Groups were kept in a light / dark cycle of 12/12 hours and the desynchronized in a light / dark cycle of 11/11 hours for 8 weeks. The tumor development occurred in 32 animals (82.05%), totaling 73 tumors. Melatonin showed beneficial effects on tumor multiplicity, histological grade, tumor size and weight of the animals, while desynchronization did not interfere significantly in breast carcinogenesis.

As plântulas de jatobá apresentam grandes quantidades de reserva de carbono, na forma de polissacarídeos constituintes de parede, presentes em seus cotilédones. Estas reservas são inicialmente utilizadas para expansão dos eófilos. Após esta fase, as plântulas passam a dispor de duas fontes de carbono, sendo elas, as reservas (que ainda não se esgotaram totalmente) e a autotrófica (compreendida pela fotossíntese) (Santos e Buckeridge, 2004). O acompanhamento em condições constantes de diversas variáveis nos permitiu concluir que a maioria dos parâmetros envolvidos com a fotossíntese são controlados circadianamente. Este controle apresenta, ao menos, dois sistemas oscilatórios independentes, que atuam, quando sob um ciclo ambiental, em conjunto. O controle da degradação das reservas é mais incerto, apesar de apresentarmos fortes evidências que apontam para a existência de um controle temporal endógeno. Conseguimos identificar, em alguns casos, uma influência forte do ambiente agindo diretamente sobra a expressão de algumas variáveis, como a concentração de clorofila. Por fim, desenhamos um quadro geral do controle temporal envolvido na questão fonte dreno (durante a fase de estabelecimento desta espécie), no qual, pudemos integrar os dados de todas as variáveis aferidas, definindo os principais mecanismos de controle envolvidos / Jatobá seedlings have large amounts of carbon reserves in the form of wall constituent polysaccharides, present in their cotyledons. These reserves are initially used in the expansion of the eophylls. After this stage, the seedlings have two sources of carbon, the reserves (which are not fully degraded yet) and autotrophic (understood as photosynthesis) (Santos and Buckeridge, 2004). The constant conditions allowed us to conclude that most of the parameters involved in the photosynthesis process are circadian controlled. This control mechanism has at least two independent oscillatory systems, which are coupled when under the influence of an environmental cycle. The nature of the temporal control of the reserves degradation is yet unclear. Although, evidences are that it\'s being controlled by an endogenous component. We were able to identify, in some cases, a strong influence of the environment, acting directly on the expression of some variables (such as chlorophyll concentration). Finally, we draw a general picture of the temporal control mechanism involved in the source-sink balance (during the establishment phase of this species), in which we were able to integrate all our data and therefore, identify some important control mechanisms involved

O câncer de mama é o tipo de câncer que mais acomete as mulheres e a principal causa de morte na faixa entre 40 e 55 anos. Apesar de apresentar variação internacional, suas taxas seguem aumentando mundialmente, sendo até cinco vezes mais frequente em países desenvolvidos. A industrialização gera aumento da exposição à luz durante a noite, o que causa supressão de melatonina. A melatonina é o principal hormônio secretado pela glândula pineal e possui atividade oncostática e antioxidante, interfere no controle do ciclo celular, função imunológica e nos hormônios esteróides. O objetivo desta dissertação e apresentar o racional e o desenvolvimento do estudo cujo objetivo foi avaliar o efeito da terapia com melatonina sobre o desenvolvimento de tumores mamários em ratas expostas ou não a dessincronização circadiana. A indução da carcinogênese mamária foi através de administração intragástrica de DMBA em 39 ratas Sprague-dawley entre 41 e 46 dias. Os animais foram randomizados em 04 grupos, Sincronizados sem tratamento, Dessincronizados sem tratamento, Sincronizados com melatonina e Dessincronizados com melatonina. Os grupos Sincronizados foram mantidos em ciclo claro/escuro de 12/12 horas e os dessincronizados a ciclo claro/escuro de 11/11 horas, durante 8 semanas. O desenvolvimento tumoral ocorreu em 32 animais (82,05%), totalizando 73 tumores. A melatonina apresentou efeitos benéficos quanto a multiplicidade tumoral, grau histológico, tamanho dos tumores e peso dos animais, enquanto que a dessincronização não interferiu de forma significativa na carcinogênese mamária. / Breast cancer is the type of cancer that most affects women and the leading cause of death in the age between 40 and 55 years. Despite presenting international variation, their rates continue to increase worldwide, with up to five times more common in developed countries. The industrialization generates increased exposure to light at night, which causes suppression of melatonin. Melatonin is the main hormone secreted by the pineal gland and has oncostatic and antioxidant activity, interferes with cell cycle control, immune function and steroid hormones. The aim of this dissertation and present the rationale and development of the study whose objective was to evaluate the effect of melatonin therapy on the development of mammary tumors in rats exposed or not the circadian desynchronization. Induction of mammary carcinogenesis was via intragastric administration of DMBA in 39 Sprague- Dawley rats between 41 and 46 days. The animals were randomized into 04 groups, Synchronized and untreated, desynchronized and untreated, synchronized and with melatonin, desynchronized and with melatonin. Synchronized Groups were kept in a light / dark cycle of 12/12 hours and the desynchronized in a light / dark cycle of 11/11 hours for 8 weeks. The tumor development occurred in 32 animals (82.05%), totaling 73 tumors. Melatonin showed beneficial effects on tumor multiplicity, histological grade, tumor size and weight of the animals, while desynchronization did not interfere significantly in breast carcinogenesis.

Introdução: O horário de realização de atividades, nos seres humanos, pode influenciar fatores fisiológicos, comportamentais e sociais. Podendo interferir, então, em questões relacionadas à atividade física e consumo alimentar. Objetivos: Identificar características acerca da atividade física e alimentação em esportistas que treinavam pela manhã e à noite. Métodos: Foi realizado através da aplicação de questionários (cronotipo, atividade física habitual e recordatório alimentar de vinte e quatro horas) e aferição de medidas antropométricas (peso e altura). Resultados: Foram encontradas correlações positivas entre a matutinidade e a prevalência de indivíduos treinando pela manhã, maior escore total de atividade física, e maior consumo de quilocalorias e proteínas pela manhã. Conclusão: Os achados sugerem que a tipologia circadiana está envolvida com a preferência pela prática de exercícios em determinados turnos, e tendências no consumo energético e proteico, além do nível de atividade física. Mas ainda são necessárias mais pesquisas na crescente área da cronobiologia associada à nutrição e exercícios. / Background: The time of conducting activities, in humans, may influence physiological, behavioral and social factors. And may interfere, then, on physical activity and food intake issues. Objective: Identify characteristics about physical activity and feeding in sportspeople who trained in the morning and the evening. Methods: Was conducted through the use of questionnaires (chronotype, habitual physical activity and twenty-four hours food recall) and anthropometric measurements (height and weight). Results: Positive correlations were found between morningness and morning training, higher total score of physical activity, and higher intake of kilocalories and protein in the morning. Conclusion: The findings suggests that the circadian typology is involved with preference for exercises practicing in certain shifts, and trends in energy and protein intake, beyond the physical activity level. But still more research is needed in the growing area of chronobiology associated with nutrition and exercise.

O câncer de mama é o tipo de câncer que mais acomete as mulheres e a principal causa de morte na faixa entre 40 e 55 anos. Apesar de apresentar variação internacional, suas taxas seguem aumentando mundialmente, sendo até cinco vezes mais frequente em países desenvolvidos. A industrialização gera aumento da exposição à luz durante a noite, o que causa supressão de melatonina. A melatonina é o principal hormônio secretado pela glândula pineal e possui atividade oncostática e antioxidante, interfere no controle do ciclo celular, função imunológica e nos hormônios esteróides. O objetivo desta dissertação e apresentar o racional e o desenvolvimento do estudo cujo objetivo foi avaliar o efeito da terapia com melatonina sobre o desenvolvimento de tumores mamários em ratas expostas ou não a dessincronização circadiana. A indução da carcinogênese mamária foi através de administração intragástrica de DMBA em 39 ratas Sprague-dawley entre 41 e 46 dias. Os animais foram randomizados em 04 grupos, Sincronizados sem tratamento, Dessincronizados sem tratamento, Sincronizados com melatonina e Dessincronizados com melatonina. Os grupos Sincronizados foram mantidos em ciclo claro/escuro de 12/12 horas e os dessincronizados a ciclo claro/escuro de 11/11 horas, durante 8 semanas. O desenvolvimento tumoral ocorreu em 32 animais (82,05%), totalizando 73 tumores. A melatonina apresentou efeitos benéficos quanto a multiplicidade tumoral, grau histológico, tamanho dos tumores e peso dos animais, enquanto que a dessincronização não interferiu de forma significativa na carcinogênese mamária. / Breast cancer is the type of cancer that most affects women and the leading cause of death in the age between 40 and 55 years. Despite presenting international variation, their rates continue to increase worldwide, with up to five times more common in developed countries. The industrialization generates increased exposure to light at night, which causes suppression of melatonin. Melatonin is the main hormone secreted by the pineal gland and has oncostatic and antioxidant activity, interferes with cell cycle control, immune function and steroid hormones. The aim of this dissertation and present the rationale and development of the study whose objective was to evaluate the effect of melatonin therapy on the development of mammary tumors in rats exposed or not the circadian desynchronization. Induction of mammary carcinogenesis was via intragastric administration of DMBA in 39 Sprague- Dawley rats between 41 and 46 days. The animals were randomized into 04 groups, Synchronized and untreated, desynchronized and untreated, synchronized and with melatonin, desynchronized and with melatonin. Synchronized Groups were kept in a light / dark cycle of 12/12 hours and the desynchronized in a light / dark cycle of 11/11 hours for 8 weeks. The tumor development occurred in 32 animals (82.05%), totaling 73 tumors. Melatonin showed beneficial effects on tumor multiplicity, histological grade, tumor size and weight of the animals, while desynchronization did not interfere significantly in breast carcinogenesis.

Introdução: O horário de realização de atividades, nos seres humanos, pode influenciar fatores fisiológicos, comportamentais e sociais. Podendo interferir, então, em questões relacionadas à atividade física e consumo alimentar. Objetivos: Identificar características acerca da atividade física e alimentação em esportistas que treinavam pela manhã e à noite. Métodos: Foi realizado através da aplicação de questionários (cronotipo, atividade física habitual e recordatório alimentar de vinte e quatro horas) e aferição de medidas antropométricas (peso e altura). Resultados: Foram encontradas correlações positivas entre a matutinidade e a prevalência de indivíduos treinando pela manhã, maior escore total de atividade física, e maior consumo de quilocalorias e proteínas pela manhã. Conclusão: Os achados sugerem que a tipologia circadiana está envolvida com a preferência pela prática de exercícios em determinados turnos, e tendências no consumo energético e proteico, além do nível de atividade física. Mas ainda são necessárias mais pesquisas na crescente área da cronobiologia associada à nutrição e exercícios. / Background: The time of conducting activities, in humans, may influence physiological, behavioral and social factors. And may interfere, then, on physical activity and food intake issues. Objective: Identify characteristics about physical activity and feeding in sportspeople who trained in the morning and the evening. Methods: Was conducted through the use of questionnaires (chronotype, habitual physical activity and twenty-four hours food recall) and anthropometric measurements (height and weight). Results: Positive correlations were found between morningness and morning training, higher total score of physical activity, and higher intake of kilocalories and protein in the morning. Conclusion: The findings suggests that the circadian typology is involved with preference for exercises practicing in certain shifts, and trends in energy and protein intake, beyond the physical activity level. But still more research is needed in the growing area of chronobiology associated with nutrition and exercise.

Introdução: O horário de realização de atividades, nos seres humanos, pode influenciar fatores fisiológicos, comportamentais e sociais. Podendo interferir, então, em questões relacionadas à atividade física e consumo alimentar. Objetivos: Identificar características acerca da atividade física e alimentação em esportistas que treinavam pela manhã e à noite. Métodos: Foi realizado através da aplicação de questionários (cronotipo, atividade física habitual e recordatório alimentar de vinte e quatro horas) e aferição de medidas antropométricas (peso e altura). Resultados: Foram encontradas correlações positivas entre a matutinidade e a prevalência de indivíduos treinando pela manhã, maior escore total de atividade física, e maior consumo de quilocalorias e proteínas pela manhã. Conclusão: Os achados sugerem que a tipologia circadiana está envolvida com a preferência pela prática de exercícios em determinados turnos, e tendências no consumo energético e proteico, além do nível de atividade física. Mas ainda são necessárias mais pesquisas na crescente área da cronobiologia associada à nutrição e exercícios. / Background: The time of conducting activities, in humans, may influence physiological, behavioral and social factors. And may interfere, then, on physical activity and food intake issues. Objective: Identify characteristics about physical activity and feeding in sportspeople who trained in the morning and the evening. Methods: Was conducted through the use of questionnaires (chronotype, habitual physical activity and twenty-four hours food recall) and anthropometric measurements (height and weight). Results: Positive correlations were found between morningness and morning training, higher total score of physical activity, and higher intake of kilocalories and protein in the morning. Conclusion: The findings suggests that the circadian typology is involved with preference for exercises practicing in certain shifts, and trends in energy and protein intake, beyond the physical activity level. But still more research is needed in the growing area of chronobiology associated with nutrition and exercise.

The hair follicle (HF) is a human mini-organ that autonomously cycles between phases of growth (anagen), regression (catagen) and relative quiescence (telogen). Whilst many molecular controls are now appreciated to influence hair cycle, what ultimately choreographs the switch between each cycle stage is yet to be elucidated. With the increasing link between molecular clock activities in controlling local tissue physiology, we began by studying the hypothesis that the human HF has a functional molecular clock. Utilising human HF organ culture, qRT-PCR and immunofluorescence we found that the HF does indeed have oscillating clock gene expression over 24 and 48 hours in situ, separate from the suprachiasmatic-nucleus. Moreover, core clock proteins BMAL1 and PER1 are expressed in the human HF with PER1 increasing as HFs enter catagen. Next utilising siRNA mediated gene knock-down of either BMAL1 or PER1 in situ, we were able to show that silencing either clock gene leads to anagen prolongation in cultured HFs, demonstrating that the molecular clock modulates the human hair cycle, namely the anagen-catagen switch in situ. As human pigmentation is tightly coupled to the hair cycle and both human HFs and epidermal melanocytes express clock genes/proteins, this led us to investigate the hypothesis that the molecular clock modulates human pigmentation. By silencing BMAL1 or PER1 in HFs an increase in melanin content (Masson-Fontana) was observed in a hair-cycle independent manner. Furthermore, tyrosinase expression/activity as well as TYRP1 and 2 expression, gp100 protein expression, melanocyte dendricity and the number of HF melanocytes were all significantly increased in BMAL1 and/or PER1-silenced HFs. Mechanistically, BMAL1 knockdown reduced PER1 transcription, and PER1 silencing was found to induce phosphorylation of the master regulator of melanogenesis, MITF, thus stimulating human melanogenesis and melanocyte activity. This provides the first evidence that the peripheral molecular clock influences human pigmentation. Finally, the thyroid hormone (T4) has strong links with peripheral clock activity and has been shown to prolong anagen and increase human HF pigmentation. Moreover, T4 is a commonly prescribed treatment for thyroid disorder. As such, we investigated the hypothesis that T4 influences HF clock gene activity. It was observed that transient T4 treatment reduces the amplitude of clock gene oscillations whilst circadian rhythmicity is maintained. Conversely with longer term treatment clock gene activity was significantly increased compared to a scrambled oligo-control. Here we have demonstrated that the human HF has peripheral molecular clock activity which influences the human hair cycle and pigmentation. Finally we were able to uncover a potential novel target, T4, whose pulsatile administration may potentially be used to treat not only hair growth and pigmentation disorders but may be able to modulate circadian activity in peripheral tissues and treat clock-related disease.