Academic literature on the topic 'Circadian'
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Journal articles on the topic "Circadian"
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Pereira, Danyella Silva, Sergio Tufik, and Mario Pedrazzoli. "Moléculas que marcam o tempo: implicações para os fenótipos circadianos." Revista Brasileira de Psiquiatria 31, no. 1 (March 2009): 63–71. http://dx.doi.org/10.1590/s1516-44462009000100015.
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OBJETIVO: Revisar resumidamente a literatura dos últimos 36 anos de pesquisa em cronobiologia molecular a fim de informar aos profissionais de saúde os avanços obtidos nesta área e os potenciais para aplicação na clínica médica. MÉTODO: Buscas na literatura foram realizadas utilizando as bases de dados PubMed e Scopus usando como palavras-chave "clock genes, circadian rhythms, diurnal preference, delayed sleep phase syndrome, advanced sleep phase syndrome, photoperiod and mood disorder". DISCUSSÃO: Atualmente, o mecanismo molecular da regulação da ritmicidade circadiana é compreendido em grande detalhe. Muitos estudos publicados mostram associações de polimorfismos nos genes relógio com transtornos do ritmo circadiano e com transtornos do humor. CONCLUSÕES: De maneira geral, o progresso obtido na área de cronobiologia molecular traz um melhor entendimento da regulação do sistema de temporização biológico. O desenvolvimento de estudos nesta área tem o potencial de ser aplicável ao tratamento dos transtornos dos ritmos circadianos e certos transtornos do humor, além de prevenir riscos à saúde causados por viagens intercontinentais (Jet Lag) e por trabalhos noturnos e por turnos.
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Zepeda Ríos, Paola Alexandra, and María Olga Quintana Zavala. "Disincronía circadiana y su efecto sobre parámetros de síndrome metabólico en trabajadores: revisión integradora de la literatura." Enfermería Global 20, no. 2 (April 1, 2021): 592–613. http://dx.doi.org/10.6018/eglobal.426881.
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Introducción: La pérdida del ritmo circadiano causado por desórdenes del sueño es considerada un factor de riesgo importante para desarrollar enfermedades metabólicas como hiperglicemia y resistencia a la insulina. Objetivo: Analizar la literatura existente referente a estudios sobre disincronía circadiana en trabajadores y su influencia sobre parámetros antropométricos de síndrome metabólico de los mismos.Método: Se realizó una búsqueda en las bases de datos electrónicas EBSCO, Thompson Reuters, PubMed y Scopus, los términos de búsqueda seleccionados fueron: trabajo por turnos, melatonina, cortisol, síndrome metabólico, trabajo nocturno y ritmo circadiano, en los idiomas español e inglés, publicados de enero del 2015 a diciembre de 2018. La extracción se llevó a cabo utilizando un formulario prediseñado. Resultados: La búsqueda en las bases de datos arrojó 5,953 artículos, posterior a la indagación y depuración de los mismos aplicando los criterios de elegibilidad, se obtuvieron 13 artículos los cuales se organizaron en dos dimensiones para su análisis, estas se denominaron a) trabajo en turnos y factores de riesgo metabólico y b) trabajo en turnos y ciclo circadiano. Conclusiones: Es consistente la relación entre el trabajo nocturno o rotatorio, con diversas alteraciones metabólicas. Introduction: the loss of the circadian rhythm caused by sleep disorders is considered an important risk factor for developing metabolic diseases such as hyperglycemia and insulin resistance.Aim: to analyze the existing information regarding studies on circadian dyssynchrony in workers and its influence on anthropometric parameters of their metabolic syndrome.Method: The literature review was carried out by searching the EBSCO, Thompson Reuters, PubMed and Scopus electronic databases, the selected search terms were: shift work, melatonin, cortisol, metabolic syndrome, night work and circadian rhythm in the Spanish and English languages published from January 2015 to December 2018. The extraction was carried out using a predesigned form. Results: The search in the databases yielded 5,953 articles, after the investigation and purification of the same ones applying the eligibility criteria, 13 articles were obtained which were organized in two dimensions for their analysis, these were called a) work in shifts and metabolic risk factors and b) shift work and the circadian cycle.Conclusions: The relationship between night or rotating work with various metabolic disorders is consistent.
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Bernardi, Fabiana, Ana Beatriz Cauduro Harb, Rosa Maria Levandovski, and Maria Paz Loayza Hidalgo. "Transtornos alimentares e padrão circadiano alimentar: uma revisão." Revista de Psiquiatria do Rio Grande do Sul 31, no. 3 (December 2009): 170–76. http://dx.doi.org/10.1590/s0101-81082009000300006.
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Este artigo tem como objetivo revisar aspectos relacionados a transtornos alimentares e suas relações com as alterações no ritmo circadiano. Realizou-se uma busca sistematizada das informações nas bases de dados PubMed usando os seguintes descritores: eating disorders, circadian rhythm, night eating syndrome, binge eating disorder e sleep patterns. Os transtornos alimentares, como a síndrome do comer noturno e o transtorno da compulsão alimentar periódica, têm sido considerados e relacionados a um atraso no ritmo circadiano da ingestão alimentar e saciedade prejudicada. Os ritmos circadianos são aqueles que apresentam um período de 24 h, como, por exemplo, o ciclo sono-vigília, temperatura corporal, atividade e comportamento alimentar. Distúrbios provocados pelas alterações nos horários de sono/vigília influenciam o apetite, a saciedade e, consequentemente, a ingestão alimentar, o que parece favorecer o aumento desses transtornos. Percebe-se que o comportamento alimentar pode ser influenciado por ritmos circadianos. Porém, mais estudos e o maior conhecimento sobre a ritmicidade alimentar podem contribuir com o melhor entendimento do comportamento alimentar atual, atuando na prevenção e/ou tratamento de transtornos alimentares.
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Mishra, Shital Kumar, Zhaomin Zhong, and Han Wang. "Hundreds of LncRNAs Display Circadian Rhythmicity in Zebrafish Larvae." Cells 10, no. 11 (November 15, 2021): 3173. http://dx.doi.org/10.3390/cells10113173.
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Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in various life processes, including circadian rhythms. Although next generation sequencing technologies have facilitated faster profiling of lncRNAs, the resulting datasets require sophisticated computational analyses. In particular, the regulatory roles of lncRNAs in circadian clocks are far from being completely understood. In this study, we conducted RNA-seq-based transcriptome analysis of zebrafish larvae under both constant darkness (DD) and constant light (LL) conditions in a circadian manner, employing state-of-the-art computational approaches to identify approximately 3220 lncRNAs from zebrafish larvae, and then uncovered 269 and 309 lncRNAs displaying circadian rhythmicity under DD and LL conditions, respectively, with 30 of them are coexpressed under both DD and LL conditions. Subsequently, GO, COG, and KEGG pathway enrichment analyses of all these circadianly expressed lncRNAs suggested their potential involvement in numerous biological processes. Comparison of these circadianly expressed zebrafish larval lncRNAs, with rhythmically expressed lncRNAs in the zebrafish pineal gland and zebrafish testis, revealed that nine (DD) and twelve (LL) larval lncRNAs are coexpressed in the zebrafish pineal gland and testis, respectively. Intriguingly, among peptides encoded by these coexpressing circadianly expressed lncRNAs, three peptides (DD) and one peptide (LL) were found to have the known domains from the Protein Data Bank. Further, the conservation analysis of these circadianly expressed zebrafish larval lncRNAs with human and mouse genomes uncovered one lncRNA and four lncRNAs shared by all three species under DD and LL conditions, respectively. We also investigated the conserved lncRNA-encoded peptides and found one peptide under DD condition conserved in these three species and computationally predicted its 3D structure and functions. Our study reveals that hundreds of lncRNAs from zebrafish larvae exhibit circadian rhythmicity and should help set the stage for their further functional studies.
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Clark, Gretchen T., Yanlei Yu, Cooper A. Urban, Guo Fu, Chunyu Wang, Fuming Zhang, Robert J. Linhardt, and Jennifer M. Hurley. "Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates." PLOS Genetics 18, no. 2 (February 10, 2022): e1009994. http://dx.doi.org/10.1371/journal.pgen.1009994.
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Alzheimer’s Disease (AD) is a neuroinflammatory disease characterized partly by the inability to clear, and subsequent build-up, of amyloid-beta (Aβ). AD has a bi-directional relationship with circadian disruption (CD) with sleep disturbances starting years before disease onset. However, the molecular mechanism underlying the relationship of CD and AD has not been elucidated. Myeloid-based phagocytosis, a key component in the metabolism of Aβ, is circadianly-regulated, presenting a potential link between CD and AD. In this work, we revealed that the phagocytosis of Aβ42 undergoes a daily circadian oscillation. We found the circadian timing of global heparan sulfate proteoglycan (HSPG) biosynthesis was the molecular timer for the clock-controlled phagocytosis of Aβ and that both HSPG binding and aggregation may play a role in this oscillation. These data highlight that circadian regulation in immune cells may play a role in the intricate relationship between the circadian clock and AD.
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Powell, Weston, Lindsay Clark, Maria White, Lucille Rich, Camille Gates, Elizabeth Vanderwall, and Jason Debley. "0006 Circadian Cyclic Gene Expression in Human Airway Epithelial Cells in Asthma and Viral Infections." SLEEP 47, Supplement_1 (April 20, 2024): A3. http://dx.doi.org/10.1093/sleep/zsae067.0006.
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Abstract Introduction Cellular circadian rhythms regulate gene expression and innate immune pathways related to airway diseases in animal models of disease. However, circadian regulation of gene expression remains uninvestigated in human airway epithelial cells. Primary human airway epithelial cells can be grown at an air-liquid interface as an ex vivo organotypic model to characterize molecular circadian rhythms in the human airway. Using cells from healthy and donors with disease, we hypothesized that circadian cyclic gene expression would be altered in asthma and would display altered viral responses. Methods Cells were synchronized with temperature cycled incubators and RNA isolated every 4 hours over a 48 hour period for RNA-sequencing from primary human airway epithelial cells from healthy and asthmatic children. CompareRhythms in R was used to identify differential rhythmicity using the cosinor method. EnrichR pathway analysis for Reactome, Panther, GO molecular functions, and GO biological processes was used to identify relevant biological pathways with altered circadian rhythmic expression. Human rhinovirus 16 was applied to the apical surface at a multiplicity of infection of 0.5 and RNA isolated 96 hours later for genome copy number assessment with PCR. Results Circadain clock genes were rhythmic in airway epithelial cells from health and donors with asthma with preserved phase relationships indicating an intact core circadian clock. Analysis of circadian cyclic gene expression identified 4% of genes with circadian cyclic gene expression following temperature synchronization. Approximately 100 genes demonstrated altered circadian rhythmicity in airway epithelial cells from donors with asthma. Circadian rhythm and nuclear receptors had common rhythmicity in healthy and asthma. IL-17 signalling, cytokine receptor, and neutrophil chemotaxis pathways had altered circadian rhythmicity in asthma. Infection at time zero (end of temperature cycling) was associated with a two-fold lower viral replication than infection 12 hours later in healthy airway epithelial cells. Conclusion The core circadian clock genes maintain rhythmicity in healthy and asthma airway epithelia. Circadian regulation in immune and cytokine signaling pathways is altered in asthma. Support (if any) Sleep Research Society Foundation Career Development Award (WTP), ATS ASPIRE (WTP), Parker B Francis Fellowship (WTP), NIH R01AI163160 (JSD); NIH K24AI150991 (JSD)
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Menaker, M. "CIRCADIAN RHYTHMS: Circadian Photoreception." Science 299, no. 5604 (January 10, 2003): 213–14. http://dx.doi.org/10.1126/science.1081112.
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Harb, Ana Beatriz Cauduro, Wolnei Caumo, Priscila Raupp, and Maria Paz Loayza Hidalgo. "Síndrome do comer noturno: aspectos conceituais, epidemiológicos, diagnósticos e terapêuticos." Revista de Nutrição 23, no. 1 (February 2010): 127–36. http://dx.doi.org/10.1590/s1415-52732010000100014.
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O comportamento e o padrão alimentar são complexos, envolvendo aspectos metabólicos, fisiológicos e ambientais, e apresentando ritmicidade circadiana, herdada e espécie específica, sendo a humana essencialmente diurna. Este estudo tem como objetivo descrever a Síndrome do Comer Noturno, caracterizada por um atraso circadiano do padrão alimentar, mediado por alterações neuroendócrinas ao estresse. Procedeu-se à revisão da bibliografia existente, a partir do exame de artigos publicados pela literatura internacional nas bases de dados dos sites Pubmed, Lilacs, Sirus, referentes ao período de 1955 até as últimas publicações em 2007. Realizou-se um levantamento bibliográfico usando os seguintes descritores: night eating syndrome, sleep, circadian rhythm, appetite, nocturnal eating. Foram localizados 74 artigos e destes foram selecionados 26, cujo tema central era a Síndrome do Comer Noturno. Apesar dos estudos realizados, ainda existe longo percurso a ser percorrido para compreender a gênese da Síndrome do Comer Noturno e as relações intrínsecas desta com outros processos fisiopatogênicos. Tendo em conta que esta síndrome está vinculada ao controle da fome e da saciedade e à dessincronização entre o ritmo alimentar e o ritmo sono/vigília, a compreensão do seu processo gênico poderá demonstrar o impacto da dessincronização dos ritmos circadianos da alimentação no processo saúde-doença, e auxiliar a compreensão de fatores implicados no índice crescente de obesidade da sociedade moderna.
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Cenek, Lisa, Liubou Klindziuk, Cindy Lopez, Eleanor McCartney, Blanca Martin Burgos, Selma Tir, Mary E. Harrington, and Tanya L. Leise. "CIRCADA: Shiny Apps for Exploration of Experimental and Synthetic Circadian Time Series with an Educational Emphasis." Journal of Biological Rhythms 35, no. 2 (January 28, 2020): 214–22. http://dx.doi.org/10.1177/0748730419900866.
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Circadian rhythms are daily oscillations in physiology and behavior that can be assessed by recording body temperature, locomotor activity, or bioluminescent reporters, among other measures. These different types of data can vary greatly in waveform, noise characteristics, typical sampling rate, and length of recording. We developed 2 Shiny apps for exploration of these data, enabling visualization and analysis of circadian parameters such as period and phase. Methods include the discrete wavelet transform, sine fitting, the Lomb-Scargle periodogram, autocorrelation, and maximum entropy spectral analysis, giving a sense of how well each method works on each type of data. The apps also provide educational overviews and guidance for these methods, supporting the training of those new to this type of analysis. CIRCADA-E (Circadian App for Data Analysis–Experimental Time Series) allows users to explore a large curated experimental data set with mouse body temperature, locomotor activity, and PER2::LUC rhythms recorded from multiple tissues. CIRCADA-S (Circadian App for Data Analysis–Synthetic Time Series) generates and analyzes time series with user-specified parameters, thereby demonstrating how the accuracy of period and phase estimation depends on the type and level of noise, sampling rate, length of recording, and method. We demonstrate the potential uses of the apps through 2 in silico case studies.
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Bertolucci, Cristiano, Nicola Cavallari, Ilaria Colognesi, Jacopo Aguzzi, Zheng Chen, Pierpaolo Caruso, Augusto Foá, Gianluca Tosini, Francesco Bernardi, and Mirko Pinotti. "Evidence for an Overlapping Role of CLOCK and NPAS2 Transcription Factors in Liver Circadian Oscillators." Molecular and Cellular Biology 28, no. 9 (March 3, 2008): 3070–75. http://dx.doi.org/10.1128/mcb.01931-07.
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ABSTRACT The mechanisms underlying the circadian control of gene expression in peripheral tissues and influencing many biological pathways are poorly defined. Factor VII (FVII), the protease triggering blood coagulation, represents a valuable model to address this issue in liver since its plasma levels oscillate in a circadian manner and its promoter contains E-boxes, which are putative DNA-binding sites for CLOCK-BMAL1 and NPAS2-BMAL1 heterodimers and hallmarks of circadian regulation. The peaks of FVII mRNA levels in livers of wild-type mice preceded those in plasma, indicating a transcriptional regulation, and were abolished in Clock −/−; Npas2 −/− mice, thus demonstrating a role for CLOCK and NPAS2 circadian transcription factors. The investigation of Npas2 −/− and Clock Δ19/Δ19 mice, which express functionally defective heterodimers, revealed robust rhythms of FVII expression in both animal models, suggesting a redundant role for NPAS2 and CLOCK. The molecular bases of these observations were established through reporter gene assays. FVII transactivation activities of the NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers were (i) comparable (a fourfold increase), (ii) dampened by the negative circadian regulators PER2 and CRY1, and (iii) abolished upon E-box mutagenesis. Our data provide the first evidence in peripheral oscillators for an overlapping role of CLOCK and NPAS2 in the regulation of circadianly controlled genes.
Dissertations / Theses on the topic "Circadian"
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Zhang, Yuan. "Circadian clocks and cancer : The implication of BMAL1 (brain and muscle Arnt-like protein-1) in colorectal and breast carcinoma development and treatment." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS422.
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BMAL1, une protéine centrale de l'horloge circadienne.L’inactivation de BMAL1 (BMAL1-KO) entraîne une perte complète de la rythmicité dans les horloges central et périphérique. Le travail de ma thèse se concentre sur le rôle du gène BMAL1 dans la développement et le traitement des cancers du sein et du côlon.1. Pharmacodynamique in vitro de l’Everolimus en fonction du temps d’administration malgré une horloge circadienne défectueuse ((Zhang et al., 2018) (Zhang, Levi and Chang, 2018)L’everolimus (EV) est un inhibiteur de la mTOR chez les mammifères et il est utilisé pour traiter le cancer du sein positif aux oestrogènes (ER+). Nous avons focalisé nos recherches sur la chronopharmacologie de l’Everolimus administré sur des cellules MCF-7 (ER+). Les MCF-7 présentent une oscillation circadienne de l’activité de mTOR sans mise en évidence d’une oscillation des gènes d’horloge. L’oscillation d’activité de mTOR induirait une oscillation de synthèse et/ou de phosphorylation de protéines importantes dans la progression de la phase G1, notamment la Cycline D1 et RB phosphorylée. Ces variations rythmiques des MCF-7 synchronisées expliquent la chrono-efficacité de l’Everolimus selon des temps différents d’administration.Ce travail a révélé que même dans un système de cellules cancéreuses dont l’horloge était perturbée, l'intégration d'autres rythmes cellulaires dans la chronothérapie pouvait augmenter l'efficacité du médicament. Ce principe peut être appliqué à des traitements du cancer pour optimiser la chronothérapie du cancer.2. Le Knockdown BMAL1 a déclenché différents destins de cellules du carcinome du côlon (CRC) en modifiant l'équilibre délicat entre les voies AKT / mTOR et P21 / P53 (Article soumis)Premièrement, nos résultats ont révélé que le knockdown BMAL1 par le shRNA (BMAL1-KD) avait déclenché une activation plus évidente de l’AKT / mTOR dans deux lignées cellulaires primaires (HCT116 et SW480) que une lignée métastatique de CRC, SW620. De plus, bien que les deux lignées cellulaires primaires de CRC aient présenté une augmentation significative de l'activité de l'AKT/mTOR, elles avaient des statuts différents de P53 (WT ou mutant). Dans ce contexte, les cellules SW480 BMAL1-KD avec P53 mutant présentaient une sénescence accrue, mais les cellules HCT116 BMAL1-KD avec P53 WT présentaient d’abord une apoptose transitoire, puis un taux de prolifération plus élevé.Ainsi, nos travaux ont révélé le rôle crucial de BMAL1 pour équilibrer un régulateur central du métabolisme AKT / mTOR et une voie de réponse au stress P53 / P21 dans des lignées cellulaires de CRC, ce qui met en évidence l’importance de BMAL1 dans le développement de CRC et la progression du vieillissement.3. BMAL1 renforce les propriétés épithéliales et diminue la chimiorésistance des cellules du CRC (article en préparation)La transition épithélo-mésenchymateuse (EMT) est un événement critique dans l'invasion et la métastase des carcinomes, y compris le CRC.Dans ce travail, nous avons étudié comment BMAL1 knockdown (Bmal1-KD) altère l’équilibre délicat entre les propriétés épithéliales et mésenchymateuse de trois lignées cellulaires de CRC (HCT116, SW480 et SW620).Après BMAL1-KD, la diminution de l’expression Twist, un facteur de transcription favorisé l’EMT et des marqueurs mésenchymateux (N-Cadhérine, Vimentine) étaient associées à une expression accrue des marqueurs épithéliaux (E-cadhérine, CK20 et EpCAM). De manière constante, l'augmentation de l'expression de l’E-cadhérine après BMAL1-KD était accompagnée d'une co-localisation membranaire accrue de la β-caténine avec l'E-cadhérine, ainsi que d'une diminution de la localisation nucléaire de la β-caténine, suggérant une diminution de l'activation de la voie Wnt. De plus, les cellules BMAL1-KD ont montré une diminution des capacités de migration et de la résistance aux médicaments.Au total, ces données soulignent l’importance de BMAL1 dans l’EMT des cellules de CRCBMAL1 is a core circadian clock protein, forming a heterodimer with CLOCK to initiate the transcription of circadian and output genes. Among canonical clock genes, only BMAL1 knockout results in complete loss of rhythmicity in both the SCN and peripheral tissues. My thesis work focuses on exploring the important role of BMAL1 in human breast and colon cancer progression and treatment. My work is divided into three main parts:1. Dosing time dependent in vitro pharmacodynamics of Everolimus despite a defective circadian clock (Zhang et al., 2018)(Zhang, Levi and Chang, 2018) Everolimus (EV) is an inhibitor of mammalian target of Rapamycin (mTOR) and is used to treat estrogen positive (ER+) breast cancer. Here, we investigated whether EV efficacy varied according to administration timing by using the ER+ breast cancer cell line MCF-7 as a model system. Serum shock synchronization induced a circadian oscillation in mTOR activity in MCF-7 cells, which rhythmically regulated the synthesis or phosphorylation of key G1 progression proteins, such as Cyclin D1 and phosphorylated RB, ultimately resulting in different G0/G1 blockage efficiency according to different EV administration timing. Thus, the different delivery schedule of EV presented different efficacy in G0/G1 phase blockage in serum shocked MCF-7 cells.This investigation revealed that, even in a breast cancer cell system with disrupted circadian organization, modulating drug administration according to other protein rhythms could still increase drug efficacy. This principle may be applied to many other cancer systems and treatment types to optimize cancer chronotherapy.2. Knockdown BMAL1 triggered different colon carcinoma cells fates by altering the delicate equilibrium between AKT/mTOR and P21/P53 pathways (Article in preparation)We tried to evaluate in vitro how knockdown BMAL1 (BMAL1-KD) by shRNA influences human colorectal cancer cell (CRC) behavior.The results revealed that BMAL1-KD triggered different CRC cell fates based on distinct p53 status in different cell lines. First, after BMAL1 knockdown, two primary CRC cell lines (HCT116 and SW480) presented a more evident AKT/mTOR activation than the metastatic colon carcinoma cell line, SW620. Furthermore, although both primary CRC cell lines presented a significant increase of AKT/mTOR activity, they had different P53 status (WT or mutant) and activation pattern. Under these context, SW480 BMAL1-KD cells exhibited increased senescence but HCT116 BMAL1-KD cells showed firstly a transient apoptosis and then higher proliferation rate.Thus, our work uncovered the crucial role of BMAL1 to balance a central metabolism regulator AKT/mTOR and a stress response pathway P53/P21 in CRC cell lines, which highlighted the importance of BMAL1 in CRC development and aging progression.3. BMAL1 knockdown leans epithelial–mesenchymal balance toward epithelial properties and decreased the chemoresistance of colon carcinoma cell (Article in preparation)Epithelial-mesenchymal transition (EMT) is a critical early event in the invasion and metastasis of carcinoma, including colorectal cancer (CRC). In this work, we studied how BMAL1-KD alters the delicate equilibrium between epithelial and mesenchymal properties of three colon carcinoma cell lines (HCT116, SW480 and SW620).The results showed the molecular alterations after BMAL1-KD promote mesenchymal-to-epithelial transition-like changes mostly appeared in two primary CRC cell lines (HCT116 and SW480) compared to the metastatic cell line SW620. Subsequently, BMAL1-KD HCT116 and SW480 cells harbored a decreased migration, invasiveness and drug resistance capacities relative to their scramble counterpart cells. All these data suggested the importance of BMAL1 on EMT inducing in colon carcinoma cells
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Cervela, Cardona Luis Manuel. "Functional studies on the circadian regulation of mitochondrial activity in Arabidopsis thaliana." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/669786.
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El reloj circadiano es un mecanismo celular endógeno capaz de medir el paso del tiempo y traducir
las señales medioambientales, principalmente luz y temperatura, en respuestas temporales que
resultan en ritmos metabólicos y fisiológicos de aproximadamente 24 horas. Esta coordinación
temporal les permite a los seres vivos predecir y anticipar cambios periódicos en el medioambiente.
A pesar de su importancia para la adaptación y supervivencia de las plantas, la posible función
regulatoria del reloj circadiano sobre la actividad y homeostasis mitocondrial ha sido difícil de
elucidar. En esta Tesis Doctoral, hemos seguido un enfoque integral para demostrar el mecanismo
molecular mediante el cual uno de los componentes clave del reloj circadiano, TOC1 (TIMING OF
CAB EXPRESSION 1), controla la actividad mitocondrial. Con este fin, hemos estudiado la
fluctuación in vivo de los niveles del ATP citosólico mediante la utilización de un biosensor de ATP
basado en la tecnología FRET. También hemos realizado análisis transcriptómicos
correlacionándolos con datos de los cambios en la acumulación de metabolitos observados en
plantas sobre-expresantes y mutantes de TOC1. Hemos identificado el mecanismo molecular por
el cual TOC1 regula la actividad mitocondrial a través de la unión directa al promotor del gen
relacionado con el ciclo del ácido tricarboxílico, FUMARASE 2. Nuestros estudios de interacción
genética también han validado este mecanismo. Las plantas que sobre-expresan TOC1 acumulan
menos biomasa y tienden a presentar un fenotipo similar al de plantas sometidas a inanición. La
sobre-expresión del gen FUMARASE 2 en estas plantas ayuda a la recuperación de la biomasa y
alivia el fenotipo de inanición. En general, con este estudio se ha demostrado el papel que ejerce el
reloj circadiano en la regulación de la demanda energética celular en sincronización con el
medioambiente.Circadian clocks are molecular timekeeping mechanisms that translate environmental cues, mostly light and temperature, into temporal information to generate ~24h rhythms in metabolism and physiology. The temporal coordination by the clock enables organisms to predict and anticipate periodic changes in the environment. Despite its importance for plant fitness and survival, the possible role of the circadian clock directly regulating plant mitochondrial activity and energy homeostasis has remained elusive. In this Doctoral Thesis, we have followed a comprehensive approach to demonstrate the molecular mechanism by which the key clock component TOC1 (TIMING OF CAB EXPRESSION 1) sets the time of mitochondrial activity. To that end, we have followed the in vivo dynamics of cytosolic ATP production using a FRET-based ATP biosensor. We have also performed transcriptomic analyses and examined their correlation with actual changes in metabolite content using plants miss-expressing TOC1. We have identified the molecular mechanism by which TOC1 regulates the mitochondrial activity through direct binding to the promoter of the tricarboxylic acid cycle related gene FUMARASE 2. Our genetic interaction studies have validated this mechanism, as over-expression of FUMARASE 2 in TOC1 over-expressing plants alleviates the reduced biomass and the starvation-like phenotypes observed in TOC1 overexpressing plants. Overall, ours studies uncover the role of the circadian clock controlling the cell energetic demands in synchronization with the environment.
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Chen, Weiwei. "Characterization of the movement of a circadian protein in the temperature-dependent root synchronization of Arabidopsis thaliana." Doctoral thesis, Universitat Autònoma de Barcelona, 2020. http://hdl.handle.net/10803/670449.
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El rellotge circadià està sincronitzat per senyals mediambientals externes, principalment la llum i la temperatura. Entendre com respon el rellotge circadià de la planta a les oscil·lacions de temperatura és crucial per comprendre la capacitat de resposta de la planta a l'entorn. En aquesta tesi doctoral, trobem una funció prevalent depenent de la temperatura de l'component de el rellotge d'Arabidopsis EARLY Flowering 4 (ELF4) en el rellotge circadià de l'arrel. En plantes en les quals l'àpex aeri s'ha eliminat, el rellotge pot funcionar en les arrels, tot i que exhibeix un període més curt i una fase avançada en comparació amb les arrels de plantes completes. Els assajos de microempelt mostren que ELF4 es mou des de l'àpex aeri per regular els ritmes en les arrels. El moviment de la proteïna ELF4 no transmet informació fotoperiòdica, sinó que és essencial per controlar el període de el rellotge circadià en l'arrel d'una manera depenent de la temperatura. Les baixes temperatures afavoreixen la mobilitat de ELF4, el que resulta en un rellotge de de ritme lent, mentre que les altes temperatures disminueixen el moviment, el que porta a un rellotge més ràpid. Per tant, el moviment de la proteïna ELF4 mòbil proporciona informació sobre la temperatura i ajuda a establir un diàleg entre l'àpex aeri i l'arrel de la planta per controlar el ritme circadià en l'arrel.El reloj circadiano está sincronizado por señales medioambientales externas, principalmente la luz y la temperatura. Entender cómo responde el reloj circadiano de la planta a las oscilaciones de temperatura es crucial para comprender la capacidad de respuesta de la planta al medio ambiente. En esta Tesis Doctoral, encontramos una función prevalente dependiente de la temperatura del componente del reloj de Arabidopsis EARLY FLOWERING 4 (ELF4) en el reloj circadiano de la raíz. En plantas en las que el ápice aéreo se ha eliminado, el reloj puede funcionar correctamente en las raíces, aunque exhibe un período más corto y una fase avanzada en comparación con las raíces de plantas completas. Los ensayos de microinjerto muestran que ELF4 se mueve desde el ápice aéreo para regular los ritmos en las raíces. El movimiento de la proteína ELF4 no transmite información fotoperiódica, sino que es esencial para controlar el período del reloj circadiano en la raíz de una manera dependiente de la temperatura. Las bajas temperaturas favorecen la movilidad de ELF4, lo que resulta en un reloj de de ritmo lento, mientras que las altas temperaturas disminuyen el movimiento, lo que lleva a un reloj más rápido. Por lo tanto, el movimiento de la proteína ELF4 móvil proporciona información sobre la temperatura y ayuda a establecer un diálogo entre el ápice aéreo y la raíz de la planta para controlar el ritmo circadiano en la raíz.
The circadian clock is synchronized by external environment cues, mostly through light and temperature. Explaining how the plant circadian clock responds to temperature oscillations is crucial to understanding plant responsiveness to the environment. In this thesis, we found a prevalent temperature-dependent function of the Arabidopsis clock component EARLY FLOWERING 4 (ELF4) in the root clock. The clocks in roots are able to run properly in the absence of shoots although shoot excision leads to a shorter period and advanced phase in excised roots compared to entire roots. Micrografting assays show that ELF4 moves from shoots to regulate rhythms in roots. ELF4 movement does not convey photoperiodic information, but trafficking is essential for controlling the period of the root clock in a temperature-dependent manner. Low temperatures favour ELF4 mobility, resulting in a slow paced root clock, whereas high temperatures decrease movement, leading to a faster clock. Hence, the mobile ELF4 delivers temperature information and establishes a shoot-to-root dialogue that sets the pace of the clock in roots.
Universitat Autònoma de Barcelona. Programa de Doctorat en Biologia i Biotecnologia Vegetal
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Murphy, Barbara Anne. "INVESTIGATIONS OF CIRCADIAN REGULATION AND IMMUNE-CIRCADIAN INTERACTION IN THE HORSE." UKnowledge, 2007. http://uknowledge.uky.edu/gradschool_diss/546.
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The circadian system provides animals with a means to adapt internal physiology to the constantly changing environmental stimuli that exists on a rotating planet. Light information is translated into molecular timing mechanisms within individual pacemaker cells of the mammalian hypothalamic suprachiasmatic nucleus (SCN) via transcriptionaltranslational feedback loops. Humoral and neural outputs from this master clock result in circadian rhythms of physiology and behavior. The hierarchy of the circadian system involves SCN synchronization of cellular clocks within peripheral tissues so that differential transcriptional profiles in individual organs reflect their specific function. The first step to investigating equine circadian regulation was to identify and isolate the core components of the molecular clock in the horse. Successful isolation and sequencing of equine Bmal1, Per2, Cry1 and Clock cDNAs revealed high sequence homology with their human counterparts. Real Time RT-PCR assays were subsequently designed to quantitatively assess clock gene expression in equine peripheral tissues. Synchronization of equine fibroblasts revealed temporal profiles of clock gene expression identical to those of the SCN and peripheral tissues of other species. However, while clock gene expression varies over time in equine adipose tissue, there was no observable oscillation of clock gene transcripts in equine blood. Spurred by recent reports of immune-circadian interactions, this novel finding prompted an investigation of clock gene expression in equine blood during a systemic inflammatory response. The results demonstrated that acute inflammation upregulates Per2 and Bmal1 in equine blood. Subsequent experiments identified neutrophils as the source of this upregulation and highlighted exciting new immunecircadian interplay during an innate immune response. Finally, the effect of a 6-h phase advance of the light/dark cycle, mimicking an easterly transmeridian journey, on circadian melatonin and core body temperature rhythms was investigated. In contrast to the gradual adaptation observed in other species, these markers of equine circadian phase adapt immediately to a time zone transition. Combined, the results of these experiments highlight important interspecies differences in circadian regulation with practical implications regarding the potential impact of jet lag on equine athletes. Furthermore, the results underline the relevance of chronobiological investigation in a large mammalian species such as the horse.
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Jaeger, Cassie Danielle. "Chronic Circadian Misalignment Disrupts the Circadian Clock and Promotes Metabolic Syndrome." OpenSIUC, 2015. https://opensiuc.lib.siu.edu/dissertations/1081.
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Obesity, metabolic syndrome, and diabetes represent a major source of morbidity and mortality in the United States and worldwide. Chronic misalignment of an organism’s internal circadian clock with diurnal, cyclic changes in the external environment, prevalent in professions that require shift work, contributes significantly to Type 2 Diabetes development. Experimentally, only short-term models of circadian disruption have been explored. Therefore, the goal of this study was to establish an animal model of chronic circadian disruption, which would more closely mimic the harmful misalignment associated with metabolic syndrome in clinical studies. Moreover, since high fat diet consumption alters circadian behavior and rhythmic gene expression, contributing to the diet-induced phenotype, I hypothesized that chronic circadian disruption interacts with a high fat diet to worsen metabolic syndrome. To investigate circadian misalignment and diet-induced metabolic syndrome, I examined the contribution of the Aryl Hydrocarbon Receptor (AhR). AhR has similar PAS domain containing motifs as circadian clock proteins allowing for protein/protein interactions and crosstalk between AhR signaling and circadian rhythms. Furthermore, AhR activation is implicated in Type 2 Diabetes risk. To examine chronic circadian disruption, male wild-type (WT; C57Bl/6J) and AhR +/- mice were entrained to 12/12-hour light/dark cycles where lights were on from 10pm-10am and off from 10am-10pm. Misalignment was initiated by delaying the time of lights on by 8 hours on Monday. Mice were exposed to the misalignment schedule Monday-Friday then returned to the entrainment schedule Saturday and Sunday to mimic readjustment to society during the weekend. Circadian misaligned mice were exposed to the altered light schedule for 15 weeks and control animals remained on the12/12-hour light/dark cycle. Mice were fed a normal chow diet (10% fat) or a high fat diet (60% fat). Animals were sacrificed and samples were collected at 4-hour intervals on day 2 of the weekend. Exposure to chronic circadian misalignment by light disruption or high fat diet altered circadian rhythms of behavior, metabolic outputs, and expression of circadian clock, clock-controlled nuclear receptor, and lipid metabolism genes. A combination of light misalignment and high fat diet exacerbated the effects of either treatment alone further disrupting behavior, enhancing % body fat and fasting glucose, and dampening circadian clock gene expression. AhR +/- mice also were protected from the metabolic consequences of chronic misalignment and a high fat diet by resistance to altered behavioral and molecular circadian rhythms and disruption of metabolic outputs. With metabolic syndrome and Type 2 Diabetes occurrence on the rise, it is important to understand all contributing factors, including circadian disruption. Differences between chronic circadian misalignment and high fat diet-induced obesity in WT and AhR +/- mice furthers our understanding of the complex mechanisms that underlie Type 2 Diabetes development and advocates the discovery of potential therapeutic targets for the development of novel treatment options.
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Gegnaw, Shumet T. "The connection between circadian clock impairment and retinal disease." Electronic Thesis or Diss., Strasbourg, 2023. http://www.theses.fr/2023STRAJ120.
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Cette thèse a étudié comment une dérégulation de l'horloge circadienne, qui n'avait pas été clairement associée à une maladie rétinienne jusqu'à présent, pourrait contribuer à la dégénérescence et influencer le développement et la fonction de la rétine. L'inactivation spécifique du gène horloge Bmal1 (rod-Bmal1KO) dans la lignée de souris portant la mutation P23H de la rhodopsine aggrave les symptômes de dégénérescence rétinienne, tels que la réduction de la réponse ERG et la perte de bâtonnets, induits par la seule mutation P23H. Ces observations ont été corroborées par l'analyse RNA-Seq qui a révélé des changements majeurs dans l'expression des gènes, liés à la phototransduction et aux processus métaboliques, entre le double mutant (rod-Bmal1KO/P23H) et les rétines P23H. Nous avons montré qu'au cours du développement, l’invalidation des gènes horloge Per1 et Per2 chez la souris affecte de manière significative l'expression des gènes de la phototransduction et du cycle cellulaire. Nous avons observé que les souris adultes déficientes en Per1 et Per2 ne modulent pas quotidiennement leur sensibilité à la lumière, dans des conditions scotopiques et mésopiques. Nous avons également constaté une altération de la régulation journalière de la sensibilité à la lumière chez les souris déficientes en gène d'horloge Bmal1 dans les bâtonnets. De plus, nous avons investigué comment la dégénérescence des bâtonnets pourrait influencer la capacité rythmique globale de la rétine en mesurant les rythmes de bioluminescence PER2::LUC chez des souris P23H. Nos résultats montrent que l'horloge rétinienne chez les souris hétérozygotes P23H/+ présente des rythmes circadiens avec une robustesse et une amplitude significativement accrues. Ces effets impliquent probablement l’activation des cellules glialesThis thesis investigated how circadian clock misregulation, which has not been clearly associated with retinal genetic disease so far, could contribute to degeneration and influence development and function in the retina. The rod-specific knockout of Bmal1 clock gene (rod-Bmal1KO) from the mouse line carrying the P23H mutation of rhodopsin exacerbated the retinal degeneration phenotypes, such as reduction in ERG response and rods loss, induced by the P23H mutation alone. These observations were corroborated by RNA-Seq analysis, where we found major changes in expression of genes related to phototransduction and metabolic processes, between the (rod-Bmal1KO/P23H) double mutant and P23H retinas. We showed that during development, Per1 and Per2 clock genes deficiency in mice significantly affects gene expression of phototransduction and cell cycle components. We found that adult mice deficient for Per1 and Per2 genes lack a daily modulation of light sensitivity, under scotopic and mesopic conditions. We also found an impaired daily modulation of light sensitivity in mice deficient for Bmal1 clock gene in rods. Additionally, we investigated how rod degeneration could impact on the global rhythmic capacity of the retina by measuring PER2::LUC bioluminescence rhythms in P23H mice. We showed that the retinal clock in P23H/+ heterozygous mice displays circadian rhythms with significantly increased robustness and amplitude. These effects likely involve activation of glial cells
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Cretenet, Gaspard. "Coordination par l'horloge circadienne de l'activation rythmique du stress du RE et de la traduction dans le foie de souris." Thesis, Montpellier 2, 2010. http://www.theses.fr/2010MON20115/document.
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En premier lieu, l'horloge circadienne des mammifères joue un rôle fondamental dans le foie en régulant le métabolisme des acides gras, du glucose et des xénobiotiques. L'altération de ce rythme a été montrée comme menant à diverses pathologies incluant le syndrome métabolique. Il est supposé que l'horloge circadienne régule principalement le métabolisme en régulant l'expression des enzymes hépatiques au niveau transcriptionnel. Nous montrons que l'horloge circadienne contrôle au ssi le métabolisme hépatique en synchronisant un rythme secondaire d'une période de 12 heures caractérisé par l'activation rythmique de la voie IRE1a dans le RE. L'absence d'horloge circadienne perturbe cette horloge secondaire et provoque une dérégulation des enzymes localisées dans le RE. Cela mène à une altération du métabolisme lipidique, résultant en une activation aberrante du facteur de transcription SREBP. Cette altération dans le métabolisme lipidique circadien chez les souris sans horloge pourrait être impliquée dans l'apparition du syndrome métabolique. D'autre part, la croissance cellulaire animale est principalement régulée par la détection des nutriments et est principalement médiée par la voie TOR. Chez la souris, un gène est identifié pour la kinase TOR et son association en complexe avec d'autres protéines permet de discriminer TORC1 et TORC2. TORC1 est la forme majeure sensible à la rapamycine et est le premier médiateur de la détection d'énergie et d'acides aminés pour le contrôle de la croissance. Ce contrôle consiste en la régulation de la traduction par la phosphorylation de S6 Kinase et 4E-BP et le contrôle de la biogenèse des ribosomes. Nous sommes intéressés de montrer si l'horloge circadienne régule la traduction régulée par TOR dans le foie de sourisIn one hand, The mammalian circadian clock plays a fundamental role in the liver by regulating fatty acid, glucose, and xenobiotic metabolism. Impairment of this rhythm has been shown to lead to diverse pathologies, including metabolic syndrome. Currently, it is supposed that the circadian clock regulates metabolism mostly by regulating expression of liver enzymes at the transcriptional level. We show that the circadian clock also controls hepatic metabolism by synchronizing a secondary 12 hr period rhythm characterized by rhythmic activation of the IRE1a pathway in the endoplasmic reticulum. The absence of circadian clock perturbs this secondary clock and provokes deregulation of endoplasmic reticulum localized enzymes. This leads to impaired lipid metabolism, resulting in aberrant activation of the sterol-regulated SREBP transcription factors. The resulting aberrant circadian lipid metabolism in mice devoid of the circadian clock could be inv olved in the appearance of the associated metabolic syndrome.In a second hand, the tissue growth in animals is principally regulated by nutrient sensing and principally by the protein kinase TOR. In mice one gene is identified as TOR kinase and the association of Tor protein associated with 2 different complex of protein (TORC1 and TORC2). TORC1 is the major rapamycin sensitive form and is the primary mediator of energy and amino acid sensing for growth control. This control consists in the regulation of translation through the phosphorylation of S6 Kinase (ribosomal S6 kinase) and 4E-BP (Eif4E binding protein) and the control of ribosome biogenesis. We are interested to show if the circadian clock regulate TOR translation regulation in mice liver
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Gon?alves, Bruno da Silva Brand?o. "Estudo da organiza??o funcional do sistema circadiano por meio de ferramentas computacionais e matem?ticas." Universidade Federal do Rio Grande do Norte, 2013. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17232.
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Previous issue date: 2013-04-03Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Circadian rhythms are variations in physiological processes that help living beings to adapt to environmental cycles. These rhythms are generated and are synchronized to the dark light cycle through the suprachiasmatic nucleus. The integrity of circadian rhythmicity has great implication on human health. Currently it is known that disturbances in circadian rhythms are related to some problems of today such as obesity, propensity for certain types of cancer and mental disorders for example. The circadian rhythmicity can be studied through experiments with animal models and in humans directly. In this work we use computational models to gather experimental results from the literature and explain the results of our laboratory. Another focus of this study was to analyze data rhythms of activity and rest obtained experimentally. Here we made a review on the use of variables used to analyze these data and finally propose an update on how to calculate these variables. Our models were able to reproduce the main experimental results in the literature and provided explanations for the results of experiments performed in our laboratory. The new variables used to analyze the rhythm of activity and rest in humans were more efficient to describe the fragmentation and synchronization of this rhythm. Therefore, the work contributed improving existing tools for the study of circadian rhythms in mammals
Os ritmos circadianos s?o varia??es em processos fisiol?gicos que auxiliam os seres vivos na adapta??o aos ciclos ambientais. Esses ritmos s?o gerados e se sincronizam ao ciclo claro escuro por meio do n?cleo supraquiasm?tico. A integridade da ritmicidade circadiana tem grande implica??o na sa?de dos seres humanos. Atualmente sabe-se que dist?rbios nos ritmos circadianos est?o relacionados com alguns problemas da atualidade como a obesidade, propens?o a determinados tipos de c?ncer e transtornos mentais por exemplo. A ritmicidade circadiana pode ser estudada por meio de experimentos com modelos animais e diretamente nos seres humanos. Nesse trabalho utilizamos modelos computacionais para reunir resultados experimentais da literatura e explicar resultados de nosso laborat?rio. Outro foco desse trabalho foi na an?lise de dados de ritmos de atividade e repouso obtidos experimentalmente. Aqui fizemos uma revis?o sobre o uso de vari?veis utilizadas para analisar esses dados e por ?ltimo propomos uma atualiza??o na forma de calcular essas vari?veis. Os nossos modelos foram capazes de reproduzir os principais resultados experimentais da literatura e nos forneceram explica??es para resultados de experimentos realizados em nosso laborat?rio. As novas vari?veis utilizadas para analisar o ritmo de atividade e repouso em humanos se mostraram mais eficiente para descrever a fragmenta??o e sincroniza??o desse ritmo. Assim esse trabalho contribuiu aperfei?oando as ferramentas existentes para o estudo da ritmicidade circadiana nos mam?feros
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Reilly, Thomas P. "Circadian rhythms and exercise." Thesis, Liverpool John Moores University, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297911.
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Brettschneider, Christian. "The cyanobacterial circadian clock." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2011. http://dx.doi.org/10.18452/16385.
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Cyanobakterien zŠhlen zu den Šltesten Lebewesen auf der Erde. Diese Bakterien, auch Blaualgen genannt, trugen wesentlich zur Sauerstoffanreicherung der Erde bei, da sie eine ausgeprŠgte FŠhigkeit zur Photosynthese besitzen. Der produzerte Sauerstoff der Photosynthese hemmt jedoch eine weitere AktivitŠt von Cyanobakterien, die Stickstofffixierung. Um die Hemmung zu vermeiden, werden diese AktivitŠten zeitlich getrennt und optimal dem tŠglichen Hell-Dunkel-Rhythmus angepasst. Ein evolutionŠrer Vorteil wird erzielt, wenn der Organismus diesen Rhythmus antizipiert und sich darauf vorbereitet. Aus diesem Grund haben Cyanobakterien eine innere Uhr entwickelt, deren Rhythmus zirkadian ist, ãzirka diemÒ bedeutet ãungefŠhr ein TagÒ. Cyanobakterien der Spezies Synechococcus elongatus PCC 7942 haben sich als Modellorganismus etabliert, weil in ihnen die ersten bakteriellen zirkadianen Oszillationen auf molekularer Ebene entdeckt worden sind. Ihre zirkadiane Uhr entspringt dreier, auf der DNS beieinanderliegenden, Gene (kaiA, kaiB, kaiC) und ihrer dazugehšrigen Proteine. Phosphorylierte KaiC-Proteine Ÿben eine RŸckkopplung auf die Transkription von kaiB und kaiC aus, wodurch die AktivitŠt des kaiBC-Promotors zirkadian oszilliert. Eines der wichtigsten Experimente der letzten Jahre hat gezeigt, dass dieser Transkriptions-Translations-Oszillator mit einem weiteren Oszillator gekoppelt ist, der nicht von Transkription und Translation abhŠngt. Das Experiment des Kondo Labors rekonstruiert zirkadiane Oszillationen mit nur drei Proteinen KaiA, KaiB, KaiC und ATP. Die Proteine bilden Komplexe verschiedener Stoichiometrie, die durchschnittliche Phosphorylierung des Proteins KaiC zeigt stabile Oszillationen mit einer zirkadianen Periode. Da ein Entfernen von einem der Proteine zum Verlust der Oszillationen fŸhrt, wird dieser Post-Translations-Oszillator auch als Kernoszillator bezeichnet. Der Phosphorylierungszyklus von KaiC wird bestimmt durch fortlaufende Phosphorylierung und Dephosphorylierung an zwei Positionen des Proteins, den AminosŠuren Serin 431 und Threonin 432. Die Phase des Kernoszillators kann an der Verteilung der vier PhosphorylierungszustŠnde (nicht-, serin-, threonin- und doppeltphosphoryliert) abgelesen werden. KaiC wechselwirkt mit KaiA und KaiB, damit verschieden phosphorylierte KaiC synchronisieren und die Uhr Ÿber mehrere Tage konstante Oszillationen zeigt. Die Details dieser Wechselwirkung sind jedoch unbekannt. In dieser Dissertation erstelle ich ein mathematisches Modell des Kernoszillators und simuliere die vorliegenden Experimente des O''Shea Labors. Die Simulation reproduziert den KaiC Phosphorylierungszyklus der Uhr quantitativ. Um die wichtigsten experimentellen Nebenbedingungen zu erfŸllen, muss das theoretische Modell zwei molekulare Eigenschaften von KaiC berŸcksichtigen, wodurch ich wichtige Vorhersagen treffe. Die erste Nebenbedingung ist durch die Robustheit des Systems gegeben. Die KaiC-Phosphorylierung Šndert sich nicht, wenn die Gesamtkonzentrationen der drei Proteine in gleicher Weise variiert werden. Um diese Bedingung zu erfŸllen, muss das Modell zwei verschiedenartige Komplexe von KaiA und KaiC berŸcksichtigen. ZusŠtzlich zu einem KaiAC Komplex, der die Autophosphorylierung von KaiC unterstŸtzt, muss KaiC den grš§ten Teil von KaiA unabhŠngig vom Phosphorylierungszustand sequestrieren. Diese zweite Bindestelle ist meine erste theoretische Vorhersage. Die zweite Nebenbedingung ist durch das Ÿbergangsverhalten nach Hinzugabe von KaiB gegeben. KaiB induziert eine Dephosphorylierung von KaiC, die abhŠngig vom Phosphorylierungsniveau ist. Ein Umschalten zwischen phosphoylierendem und dephosphorylierendem KaiC ist deshalb nur in bestimmten Zeitfenstern mšglich. Um die gemessenen Zeitfenster in der Simulation zu reproduzieren, postuliere ich im Modell, dass sechsfach Serin phosphorylierte KaiBC Komplexe KaiA inaktivieren. Diese hochgradig nichtlineare RŸckkopplung ist meine zweite theoretische Vorhersage. Die beiden Vorhersagen werden anschlie§end experimentell ŸberprŸft. HierfŸr werden aufgereinigte Kai-Proteine mit ATP gemischt. Proben an ausgewŠhlten Zeitpunkten werden mit der nativen Massenspektrometrie untersucht. Diese ist eine neuartige Methode, die es erlaubt, intakte Proteinkomplexe zu untersuchen. Die Spektren bestŠtigen sowohl die zweite KaiAC-Bindestelle als auch die nichtlineare RŸckkopplung. Das mathematische Modell erlaubt es au§erdem, die drei definierenden Prinzipien von zirkadianen Uhren fŸr den Kernoszillator zu erklŠren. Erstens sichern konstante Phosphorylierungs- und Dephosphorylierungsraten von KaiC und ein pŸnktliches Umschalten zwischen beiden Phasen den Freilauf des Oszillators. Dieser Freilauf bewirkt, dass die zirkadiane Uhr auch unter konstanten Bedingungen, vor allem gleichbleibenden LichtverhŠltnissen, weiterlaufen kann. Zweitens muss die Periodendauer des Oszillators zu unterschiedlichen Šu§eren Bedingungen erhalten bleiben (Temperaturkompensation). Diese Bedingung wird realisiert, indem temperaturabhŠngige Dissoziationskonstanten von KaiAC und KaiBC Komplexen Phasenverschiebungen erzeugen, die sich gegenseitig kompensieren. Drittens muss die Phase des Oszillators sich dem Tagesrhythmus anpassen kšnnen. Diese Anpassung folgt aus einem Šu§eren Warm-Kalt-Rhythmus, der die drei temperaturabhŠngigen Phasenverschiebungen nur zum Teil einschaltet und damit die Kompensation verhindert. Eine in silico Evolutionsanalyse zeigt, dass eine zweite phosphorylierbare AminosŠure einen evolutionŠren Vorteil bringt und die Verteilung der PhosphorylierungszustŠnde optimiert ist, um eindeutig die Zeit zu bestimmen. Das Ergebnis weist darauf hin, dass diese Verteilung die physiologisch wichtige Ausgangsgrš§e der Uhr ist und die vier PhosphroylierungszustŠnde die Funktionen der zirkadianen Uhr von Cyanobakterien sichern.Biological activities in cyanobacteria are coordinated by an internal clock. The rhythm of the cyanobacterium Synechococcus elongatus PCC 7942 originates from the kai gene cluster and its corresponding proteins. In a test tube, the proteins KaiA, KaiB and KaiC form complexes of various stoichiometry and the average phosphorylation level of KaiC exhibits robust circadian oscillations in the presence of ATP. The characteristic cycle of individual KaiC proteins is determined by phosphorylation of serine 431 and threonine 432. Differently phosphorylated KaiC synchronize due to an interaction with KaiA and KaiB. However, the details of this interaction are unknown. Here, I quantitatively investigate the experimentally observed characteristic phosphorylation cycle of the KaiABC clockwork using mathematical modeling. I thereby predict the binding properties of KaiA to both KaiC and KaiBC complexes by analyzing the two most important experimental constraints for the model. In order to reproduce the KaiB-induced dephosphorylation of KaiC a highly non-linear feedback loop has been identified. This feedback originates from KaiBC complexes, which are exclusively phosphorylated at the serine residue. The observed robustness of the KaiC phosphorylation level to concerted changes of the total protein concentrations demands an inclusion of two KaiC binding sites to KaiA in the mathematical model. Besides the formation of KaiAC complexes enhancing the autophosphorylation activity of KaiC, the model accounts for a KaiC binding site, which constantly sequestrates a large fraction of free KaiA. These theoretical predictions have been confirmed by the novel method of native mass spectrometry, which was applied in collaboration with the Heck laboratory. The mathematical model elucidates the mechanism by which the circadian clock satisfies three defining principles. First, the highly non-linear feedback loop assures a rapid and punctual switch to dephosphorylation which is essential for a precise period of approximately 24 h (free-running rhythm). Second, the dissociation of the protein complexes increases with increasing temperatures. These perturbations induce opposing phase shifts, which exactly compensate during one period (temperature compensation). Third, a shifted external rhythm of low and high temperature affects only a part of the three compensating phase perturbations, which leads to phase shifts (phase entrainment). An in silico evolution analysis shows that the existing second phosphorylatable residue of KaiC is not necessary for the existence of sustained oscillations but provides an evolutionary benefit. The analysis demonstrates that the distribution of four phosphorylated states of KaiC is optimized in order for the organism to uniquely distinguish between dusk and dawn. Consequently, this thesis emphasizes the importance of the four phosphorylated states of KaiC, which assure the outstanding performance of the core oscillator.
Books on the topic "Circadian"
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1949-, Young Michael W., ed. Circadian rhythms. San Diego: Elsevier Academic Press, 2005.
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Circadian. New York: Penguin Books, 2007.
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Klink, Joanna. Circadian. New York: Penguin Group (USA), Inc., 2008.
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Derek, Chadwick, Ackrill Kate, and Symposium on Circadian Clocks and Their Adjustment (1993 : Ciba Foundation), eds. Circadian clocks and their adjustment. Chichester: Wiley, 1995.
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Ezio, Rosato. Circadian Rhythms. New Jersey: Humana Press, 2007. http://dx.doi.org/10.1385/1597452572.
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Solanas, Guiomar, and Patrick Simon Welz, eds. Circadian Regulation. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2249-0.
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Hirota, Tsuyoshi, Megumi Hatori, and Satchidananda Panda, eds. Circadian Clocks. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2577-4.
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Brown, Steven A., ed. Circadian Clocks. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-0381-9.
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Colwell, Christopher S., ed. Circadian Medicine. Hoboken, NJ: John Wiley & Sons, Inc, 2015. http://dx.doi.org/10.1002/9781118467831.
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Wu, Baojian, Danyi Lu, and Dong Dong, eds. Circadian Pharmacokinetics. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8807-5.
Full textBook chapters on the topic "Circadian"
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Lack, Leon C. "Circadian rhythms: Circadian rhythm disorders." In Encyclopedia of psychology, Vol. 2., 85–87. Washington: American Psychological Association, 2000. http://dx.doi.org/10.1037/10517-036.
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Zhao, Mengjing, Danyi Lu, Min Chen, and Baojian Wu. "Introduction to Mammalian Circadian Clock System." In Circadian Pharmacokinetics, 1–21. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8807-5_1.
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Wang, Shuai, Yanke Lin, Lu Gao, Zemin Yang, and Dong Dong. "Role of Non-Pharmacokinetic Factors in Chronoefficacy." In Circadian Pharmacokinetics, 239–53. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8807-5_10.
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Zhao, Mengjing, Yi Wang, Min Chen, and Baojian Wu. "Introduction to Pharmacokinetics." In Circadian Pharmacokinetics, 23–40. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8807-5_2.
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Wang, Shuai, Feng Li, Ziyue Zhou, Zemin Yang, Jingpan Lin, and Dong Dong. "Circadian Clock and Metabolic Diseases." In Circadian Pharmacokinetics, 41–63. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8807-5_3.
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Zhang, Tianpeng, Fangjun Yu, Lianxia Guo, and Dong Dong. "Circadian Clock and CYP Metabolism." In Circadian Pharmacokinetics, 65–87. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8807-5_4.
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Chen, Min, Tianpeng Zhang, Danyi Lu, and Baojian Wu. "Circadian Clock and Non-CYP Phase I Metabolism." In Circadian Pharmacokinetics, 89–111. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8807-5_5.
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Guo, Lianxia, Dong Dong, Tianpeng Zhang, and Baojian Wu. "Circadian Clock and Phase II Metabolism." In Circadian Pharmacokinetics, 113–29. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8807-5_6.
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Lu, Danyi, Menglin Chen, Yi Wang, Min Chen, and Baojian Wu. "Circadian Clock and Uptake Transporters." In Circadian Pharmacokinetics, 131–58. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8807-5_7.
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Lu, Danyi, Huan Zhao, and Baojian Wu. "Circadian Clock and Efflux Transporters." In Circadian Pharmacokinetics, 159–86. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8807-5_8.
Full textConference papers on the topic "Circadian"
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Yin, Jiawei, Agung Julius, and John T. Wen. "Rapid Circadian Entrainment in Models of Circadian Genes Regulation." In 2019 IEEE 58th Conference on Decision and Control (CDC). IEEE, 2019. http://dx.doi.org/10.1109/cdc40024.2019.9029374.
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Abdullah, Saeed, Mark Matthews, Elizabeth L. Murnane, Geri Gay, and Tanzeem Choudhury. "Towards circadian computing." In UbiComp '14: The 2014 ACM Conference on Ubiquitous Computing. New York, NY, USA: ACM, 2014. http://dx.doi.org/10.1145/2632048.2632100.
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Abdullah, Saeed. "Towards circadian computing." In the 2015 ACM International Joint Conference. New York, New York, USA: ACM Press, 2015. http://dx.doi.org/10.1145/2800835.2801657.
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Figueiredo, Erika Ciconelli de, and Maria Augusta Justi Pisani. "Office building typologies and circadian potential." In XVII ENCONTRO NACIONAL DE CONFORTO NO AMBIENTE CONSTRUÍDO. ANTAC, 2023. http://dx.doi.org/10.46421/encac.v17i1.3878.
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Circadian rhythms are internal manifestations of the solar day that allow adaptations to environmental-temporal changes. Mood disorders are often associated with disrupted circadian clock-controlled responses, whereas circadian rhythm disruption is correlated to jet lag, night-shift work, or to exposure to artificial light at night. Modern lifestyle patterns lead to circadian rhythm disruption, and it results in several diseases. Circadian rhythm disruption is one of the factors most often investigated, besides smoking, diet, fatigue and quality sleep, increased body mass index and obesity. Lack of enough daylight at daytime and the exposure to electric light at nighttime can disconnect people from the natural environment and lead to psychological issues. The aims of the current research are to analyze the circadian potential of three building models based on WELL Certification, to compare their performance, and to draw design guidelines about circadian rhythm and users’ well-being to be applied to office buildings in São Paulo City, São Paulo State, Brazil. Adaptive Lighting for Alertness (ALFA tool) was used to calculate the Equivalent Melanopic Lux for WELL Certification criteria in the investigated scenarios. Results have indicated that shallow office plans can benefit users by providing them with regular circadian rhythm o help improving their sleep quality, reducing their stress and preventing severe diseases.
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Jiaxiang Zhang, John T. Wen, and Agung Julius. "Adaptive circadian argument estimator and its application to circadian argument control." In 2013 American Control Conference (ACC). IEEE, 2013. http://dx.doi.org/10.1109/acc.2013.6580176.
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Pigeon, E., J. B. Fabin, M. Pouliquen, B. Mauvieux, O. Gehan, T. Menard, A. Goudjil, and S. Moussay. "Identification of circadian rhythm." In 2016 24th Mediterranean Conference on Control and Automation (MED). IEEE, 2016. http://dx.doi.org/10.1109/med.2016.7535961.
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Matheson, Tom. "Circadian biology ofSchistocerca gregariaForskål." In 2016 International Congress of Entomology. Entomological Society of America, 2016. http://dx.doi.org/10.1603/ice.2016.95194.
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Cerny, M., and M. Penhaker. "The circadian cycle monitoring." In 2008 5th International Summer School and Symposium on Medical Devices and Biosensors. IEEE, 2008. http://dx.doi.org/10.1109/issmdbs.2008.4575021.
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Castaneda, R. "Circadian Rhythm Light Watch." In 2019 IEEE International Symposium on Measurement and Control in Robotics (ISMCR). IEEE, 2019. http://dx.doi.org/10.1109/ismcr47492.2019.8955710.
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Dos Santos, Angélica T., Catia M. S. Machado, and Diana F. Adamatti. "Circadian rhythm and pain: a modeling using multiagent systems." In XV Encontro Nacional de Inteligência Artificial e Computacional. Sociedade Brasileira de Computação - SBC, 2018. http://dx.doi.org/10.5753/eniac.2018.4450.
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The circadian rhythm is responsible for the daily routines without metabolism and its disorders have great repercussion, such as obesity and mental disorders. This study is, the work approach has metate the study of synchronization and synchronization cycle circadian and influenced the variable of the, in the perspective of an integrated system with an computational system and computational. Results show the circadian rhythm periodicity is modified by the pain variable.
Reports on the topic "Circadian"
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Johnson, Carl H. Cell-permeable Circadian Clock Proteins. Fort Belvoir, VA: Defense Technical Information Center, June 2002. http://dx.doi.org/10.21236/ada405529.
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Kelly, Tamsin L., Deborah Smith, and Paul Naitoh. Melatonin, Light and Circadian Cycles. Fort Belvoir, VA: Defense Technical Information Center, December 1989. http://dx.doi.org/10.21236/ada223196.
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Heller, H. C., and Mark Smith. Short-Wavelength Countermeasures for Circadian Desynchrony. Fort Belvoir, VA: Defense Technical Information Center, June 2008. http://dx.doi.org/10.21236/ada487453.
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Moore, Robert Y. Organization of the Human Circadian System. Fort Belvoir, VA: Defense Technical Information Center, May 1994. http://dx.doi.org/10.21236/ada288223.
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Moore, Robert Y. Organization of the Human Circadian System. Fort Belvoir, VA: Defense Technical Information Center, May 1994. http://dx.doi.org/10.21236/ada288468.
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Moore, Robert Y. Organization of the Human Circadian System. Fort Belvoir, VA: Defense Technical Information Center, May 1996. http://dx.doi.org/10.21236/ada311778.
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Forger, Daniel. Modeling the Physiology of Circadian Timekeeping. Fort Belvoir, VA: Defense Technical Information Center, August 2011. http://dx.doi.org/10.21236/ada564079.
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Cahill, Gregory M. Genetic Analysis of Vertbrate Circadian Rhythmicity. Fort Belvoir, VA: Defense Technical Information Center, May 1998. http://dx.doi.org/10.21236/ada349604.
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Moore, Robert Y. Organization of the Human Circadian System. Fort Belvoir, VA: Defense Technical Information Center, January 2001. http://dx.doi.org/10.21236/ada387044.
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Rajaratnam, Shanthakumar. Video: The power of circadian rhythms. Edited by Michael Joiner. Monash University, February 2024. http://dx.doi.org/10.54377/5cc4-ba46.
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