The last two decades have significantly advanced our understanding of the organization of the circadian system at all levels of regulation-molecular, cellular, tissue, and systemic. It has been recognized that the circadian system represents a complex temporal regulatory network, which plays an important role in synchronizing various biological processes within an organism and coordinating them with the environment. It is believed that deregulation of this synchronization may result in the development of various pathologies. However, recent studies using various circadian mutant mouse models have demonstrated that at least some of the components of the molecular oscillator are actively involved in physiological processes not directly related to their role in the circadian clock. The growing amount of evidence suggests that, in addition to their circadian function, circadian proteins are important in maintaining tissue homeostasis under normal and stress conditions. In this chapter, we will summarize recent data about the regulation of the mammalian molecular circadian oscillator and will focus on a new role of the circadian system and individual circadian proteins in the organism's physiology and response to genotoxic stress in connection with diseases treatment and prevention.
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http://dx.doi.org/10.1016/S0070-2153(06)78005-X | DOI Listing |
Int J Biol Macromol
January 2025
Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China; Shandong Energy Institute, Qingdao 266101, China; Qingdao New Energy Shandong Laboratory, Qingdao 266101, China. Electronic address:
Metamorphic proteins switch reversibly between distinctly different folds often with different functions under physiological conditions. Here, the kinetics and thermodynamics of the fold-switching at different temperatures in a metamorphic protein, KaiB, involved in cyanobacterial circadian clock, reveal that enthalpy-driven the fold-switching to form fold-switched KaiB (fsKaiB) and the fsKaiB and ground-state KaiB (gsKaiB) are more dominantly at lower and higher temperatures, respectively. Thermodynamic analysis indicates that conformational and solvent entropy have opposing effects on KaiB's fold-switching.
View Article and Find Full Text PDFPLoS One
January 2025
Center for Computation and Integrative Biology, Rutgers, The State of New Jersey, Camden, NJ, United States of America.
Melatonin, a molecule with diverse biological functions, is ubiquitously present in living organisms. There is significant interest in understanding melatonin signal transduction pathways in humans, particularly due to its critical role in regulating the sleep-wake cycle. However, a knowledge gap remains in fully elucidating the mechanisms by which melatonin influences circadian regulation.
View Article and Find Full Text PDFNPJ Biol Timing Sleep
January 2025
Section of Chronobiology, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH UK.
Time-of-day variation in the molecular profile of biofluids and tissues is a well-described phenomenon, but-especially for proteomics-is rarely considered in terms of the challenges this presents to reproducible biomarker identification. We provide a case study analysis of human circadian and ultradian rhythmicity in proteins, including in the complement and coagulation cascades and apolipoproteins, with PLG, CFAH, ZA2G and ITIH2 demonstrated as rhythmic for the first time. We also show that rhythmicity increases the risk of Type II errors due to the reduction in statistical power from increased variance, and that controlling for rhythmic time-of-day variation improves statistical power and reduces the chances of Type II errors.
View Article and Find Full Text PDFBone Res
January 2025
Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Circadian rhythm is ubiquitous in nature. Circadian clock genes such as Bmal1 and Clock form a multi-level transcription-translation feedback network, and regulate a variety of physiological and pathological processes, including bone and cartilage metabolism. Deletion of the core clock gene Bmal1 leads to pathological bone alterations, while the phenotypes are not consistent.
View Article and Find Full Text PDFNeuroscience
January 2025
Laboratory of Epileptogenesis, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur St, 02-093 Warsaw, Poland. Electronic address:
Our previous in silico data indicated an overrepresentation of the ZF5 motif in the promoters of genes in which circadian oscillations are altered in the ventral hippocampus in the pilocarpine model of temporal lobe epilepsy in mice. In this study, we test the hypothesis that the Zbtb14 protein oscillates in the hippocampus in a diurnal manner and that this oscillation is disrupted by epilepsy. We found that Zbtb14 immunostaining is present in the cytoplasm and cell nuclei.
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