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The Mammalian Circadian Timekeeping System

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Book cover Ultradian Rhythms from Molecules to Mind

Abstract

In most mammalian species, physiological processes undergo daily oscillations that are controlled by the circadian timekeeping system. This system consists of a master pacemaker located in brain’s suprachiasmatic nucleus (SCN) and peripheral slave oscillators in virtually all body cells. The SCN, whose phase is entrained by daily light-dark cycles, imposes overt rhythms in behaviour and physiology by a variety of neuronal, humoral, and physical outputs. While some of these SCN outputs have direct consequences for circadian behaviour, others serve as inputs to synchronize the countless circadian oscillators in peripheral cell types. Daily feeding-fasting cycles are the major Zeitgebers (timing cues) for the synchronization of oscillators in many peripheral organs. Circadian gene expression and physiology have been particularly well studied in the liver. In this organ, local circadian clocks play an important role in the coordination of food processing and xenobiotic detoxification. Although all investigated mammals contain a lightentrainable master clock in the SCN, some species display ultradian locomotor and feeding rhythm. For example, the common vole Microtus arvalis forages in bouts of 150min throughout the day. In this ultradian rodent circadian clock and clock-controlled genes are expressed rhythmically in the SCN, but at constant intermediate levels in peripheral tissues.

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References

  • Akhtar, R.A., Reddy, A.B., Maywood, E.S., Clayton, J.D., King, V.M., Smith, A.G., Gant, T.W., Hastings, M.H., and Kyriacou, C.P. 2002. Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus. Curr Biol 12(7): 540–550.

    PubMed  CAS  Google Scholar 

  • Albrecht, U., Zheng, B., Larkin, D., Sun, Z.S., and Lee, C.C. 2001. MPer1 and mper2 are essential for normal resetting of the circadian clock. J Biol Rhythms 16(2): 100–104.

    PubMed  CAS  Google Scholar 

  • Bae, K., Jin, X., Maywood, E.S., Hastings, M.H., Reppert, S.M., and Weaver, D.R. 2001. Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock. Neuron 30(2): 525–536.

    PubMed  CAS  Google Scholar 

  • Balabaud, C., Noel, M., Beraud, C., and Dangoumau, J. 1975. Circadian rhythm of bile secretion in the rat. Experientia 31(11): 1299–1301.

    PubMed  CAS  Google Scholar 

  • Balsalobre, A., Damiola, F., and Schibler, U. 1998. A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell 93(6): 929–937.

    PubMed  CAS  Google Scholar 

  • Berman-Frank, I., Lundgren, P., Chen, Y.B., Kupper, H., Kolber, Z., Bergman, B., and Falkowski, P. 2001. Segregation of nitrogen fixation and oxygenic photosynthesis in the marine cyanobacterium Trichodesmium. Science (New York, NY) 294(5546): 1534–1537.

    CAS  Google Scholar 

  • Brown, M.S. and Goldstein, J.L. 1999. A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc Natl Acad Sci USA 96(20): 11041–11048.

    PubMed  CAS  Google Scholar 

  • Brown, S.A., Zumbrunn, G., Fleury-Olela, F., Preitner, N., and Schibler, U. 2002. Rhythms of mammalian body temperature can sustain peripheral circadian clocks. Curr Biol 12(18): 1574–1583.

    PubMed  CAS  Google Scholar 

  • Brown, S.A., Ripperger, J., Kadener, S., Fleury-Olela, F., Vilbois, F., Rosbash, M., and Schibler, U. 2005. PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator. Science 308(5722): 693–696.

    PubMed  CAS  Google Scholar 

  • Bumm, R., Blum, A.L., Bauerfeind, P., and Emde, C. 1987. Lessons from prolonged gastric pH monitoring. Aliment Pharmacol Ther 1(Suppl 1): 518S–526S.

    PubMed  Google Scholar 

  • Bunger, M.K., Wilsbacher, L.D., Moran, S.M., Clendenin, C., Radcliffe, L.A., Hogenesch, J.B., Simon, M.C., Takahashi, J.S., and Bradfield, C.A. 2000. Mop3 Is an Essential Component of the Master Circadian Pacemaker in Mammals. Cell 103(7): 1009–1017.

    PubMed  CAS  Google Scholar 

  • Busino, L., Bassermann, F., Maiolica, A., Lee, C., Nolan, P.M., Godinho, S.I., Draetta, G.F., and Pagano, M. 2007. SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins. Science (New York, NY) 316(5826): 900–904.

    CAS  Google Scholar 

  • Cheng, M.Y., Bullock, C.M., Li, C., Lee, A.G., Bermak, J.C., Belluzzi, J., Weaver, D.R., Leslie, F.M., and Zhou, Q.Y. 2002. Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature 417(6887): 405–410.

    PubMed  CAS  Google Scholar 

  • Comas, M., Beersma, D.G., Spoelstra, K., and Daan, S. 2006. Phase and period responses of the circadian system of mice (Mus musculus) to light stimuli of different duration. J Biol Rhythms 21(5): 362–372.

    PubMed  CAS  Google Scholar 

  • Damiola, F., Le Minh, N., Preitner, N., Kornmann, B., Fleury-Olela, F., and Schibler, U. 2000. Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev 14(23): 2950–2961.

    PubMed  CAS  Google Scholar 

  • Dandona, P., Aljada, A., Chaudhuri, A., Mohanty, P., and Garg, R. 2005. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 111(11): 1448–1454.

    PubMed  Google Scholar 

  • De Mairan, J. 1729. Observation botanique. Histoire de l’Academie Royale des Sciences: 35–36.

    Google Scholar 

  • Dequeant, M.L., Glynn, E., Gaudenz, K., Wahl, M., Chen, J., Mushegian, A., and Pourquie, O. 2006. A complex oscillating network of signaling genes underlies the mouse segmentation clock. Science (New York, NY) 314(5805): 1595–1598.

    CAS  Google Scholar 

  • Dodd, A.N., Salathia, N., Hall, A., Kevei, E., Toth, R., Nagy, F., Hibberd, J.M., Millar, A.J., and Webb, A.A. 2005. Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage. Science (New York, NY) 309(5734): 630–633.

    CAS  Google Scholar 

  • Edmunds, L.N. Jr. and Laval-Martin, D.L. 1984. Cell division cycles and circadian oscillators in Euglena. Chronobiol Int 1(1): 1–9.

    PubMed  Google Scholar 

  • Etchegaray, J.P., Yang, X., DeBruyne, J.P., Peters, A.H., Weaver, D.R., Jenuwein, T., and Reppert, S.M. 2006. The polycomb group protein EZH2 is required for mammalian circadian clock function. J Biol Chem 281(30): 21209–21215.

    PubMed  CAS  Google Scholar 

  • Forger, D.B. and Peskin, C.S. 2005. Stochastic simulation of the mammalian circadian clock. Proc Natl Acad Sci USA 102(2): 321–324.

    PubMed  CAS  Google Scholar 

  • Gachon, F., Nagoshi, E., Brown, S.A., Ripperger, J., and Schibler, U. 2004. The mammalian circadian timing system: from gene expression to physiology. Chromosoma 113(3): 103–112.

    PubMed  Google Scholar 

  • Gachon, F., Fleury Olela, F., Schaad, O., Descombes, P., and Schibler, U. 2006. The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification. Cell Metab 4(1):25–36.

    PubMed  CAS  Google Scholar 

  • Gallego, M. and Virshup, D.M. 2007. Post-translational modifications regulate the ticking of the circadian clock. Nat Rev 8(2): 139–148.

    CAS  Google Scholar 

  • Gerkema, M.P. and van der Leest, F. 1991. Ongoing ultradian activity rhythms in the common vole, Microtus arvalis, during deprivations of food, water and rest. J Comp Physiol 168(5): 591–597.

    CAS  Google Scholar 

  • Gerkema, M.P., Groos, G.A., and Daan, S. 1990. Differential elimination of circadian and ultradian rhythmicity by hypothalamic lesions in the common vole, Microtus arvalis. J Biol Rhythms 5(2): 81–95.

    PubMed  CAS  Google Scholar 

  • Gerkema, M.P., Daan, S., Wilbrink, M., Hop, M.W., and van der Leest, F. 1993. Phase control of ultradian feeding rhythms in the common vole (Microtus arvalis): the roles of light and the circadian system. J Biol Rhythms 8(2): 151–171.

    PubMed  CAS  Google Scholar 

  • Gerkema, M.P., Van der Zee, E.A., and Feitsma, L.E. 1994. Expression of circadian rhythmicity correlates with the number of arginine-vasopressin-immunoreactive cells in the suprachiasmatic nucleus of common voles, Microtus arvalis. Brain Res 639(1): 93–101.

    PubMed  CAS  Google Scholar 

  • Gillette, M.U. and Mitchell, J.W. 2002. Signaling in the suprachiasmatic nucleus: selectively responsive and integrative. Cell Tissue Res 309(1): 99–107.

    PubMed  CAS  Google Scholar 

  • Glass, L. and Winfree, A.T. 1984. Discontinuities in phase-resetting experiments. Am J Physiol 246(2 Pt 2): R251–258.

    PubMed  CAS  Google Scholar 

  • Godinho, S.I., Maywood, E.S., Shaw, L., Tucci, V., Barnard, A.R., Busino, L., Pagano, M., Kendall, R., Quwailid, M.M., Romero, M.R., O’Neill, J., Chesham, J.E., Brooker, D., Lalanne, Z., Hastings, M.H., and Nolan, P.M. 2007. The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period. Science (New York, NY) 316(5826): 897–900.

    CAS  Google Scholar 

  • Guo, H., Brewer, J.M., Lehman, M.N., and Bittman, E.L. 2006. Suprachiasmatic regulation of circadian rhythms of gene expression in hamster peripheral organs: effects of transplanting the pacemaker. J Neurosci 26(24): 6406–6412.

    PubMed  CAS  Google Scholar 

  • Handschin, C. and Meyer, U.A. 2003. Induction of drug metabolism: the role of nuclear receptors. Pharmacol Rev 55(4): 649–673.

    PubMed  CAS  Google Scholar 

  • Hirata, H., Yoshiura, S., Ohtsuka, T., Bessho, Y., Harada, T., Yoshikawa, K., and Kageyama, R. 2002. Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop. Science (New York, NY) 298(5594): 840–843.

    CAS  Google Scholar 

  • Honma, S., Kawamoto, T., Takagi, Y., Fujimoto, K., Sato, F., Noshiro, M., Kato, Y., and Honma, K. 2002. Dec1 and Dec2 are regulators of the mammalian molecular clock. Nature 419(6909): 841–844.

    PubMed  CAS  Google Scholar 

  • Houten, S.M., Watanabe, M., and Auwerx, J. 2006. Endocrine functions of bile acids. The EMBO J 25(7): 1419–1425.

    CAS  Google Scholar 

  • Ishikawa, K. and Shimazu, T. 1976. Daily rhythms of glycogen synthetase and phosphorylase activities in rat liver: influence of food and light. Life Sci 19(12): 1873–1878.

    PubMed  CAS  Google Scholar 

  • Jakubcakova, V., Oster, H., Tamanini, F., Cadenas, C., Leitges, M., van der Horst, G.T., and Eichele, G. 2007. Light entrainment of the mammalian circadian clock by a PRKCA-dependent posttranslational mechanism. Neuron 54(5): 831–843.

    PubMed  CAS  Google Scholar 

  • Jin, X., Shearman, L.P., Weaver, D.R., Zylka, M.J., de Vries, G.J., and Reppert, S.M. 1999. A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. Cell 96(1): 57–68.

    PubMed  CAS  Google Scholar 

  • Kageyama, H., Nishiwaki, T., Nakajima, M., Iwasaki, H., Oyama, T., and Kondo, T. 2006. Cyanobacterial circadian pacemaker: Kai protein complex dynamics in the KaiC phosphorylation cycle in vitro. Mol Cell 23(2): 161–171.

    PubMed  CAS  Google Scholar 

  • Kageyama, R., Masamizu, Y., and Niwa, Y. 2007a. Oscillator mechanism of Notch pathway in the segmentation clock. Dev Dyn 236(6): 1403–1409.

    PubMed  CAS  Google Scholar 

  • Kageyama, R., Ohtsuka, T., and Kobayashi, T. 2007b. The Hes gene family: repressors and oscillators that orchestrate embryogenesis. Development (Cambridge, England) 134(7): 1243–1251.

    CAS  Google Scholar 

  • Kalaany, N.Y. and Mangelsdorf, D.J. 2006. LXRS and FXR: the yin and yang of cholesterol and fat metabolism. Annu Rev Physiol 68: 159–191.

    PubMed  CAS  Google Scholar 

  • Kalsbeek, A., van Heerikhuize, J.J., Wortel, J., and Buijs, R.M. 1996. A diurnal rhythm of stimulatory input to the hypothalamo-pituitary-adrenal system as revealed by timed intrahypothalamic administration of the vasopressin V1 antagonist. J Neurosci 16(17): 5555–5565.

    PubMed  CAS  Google Scholar 

  • Keller, J. and Layer, P. 2002. Circadian pancreatic enzyme pattern and relationship between secretory and motor activity in fasting humans. J Appl Physiol 93(2): 592–600.

    PubMed  CAS  Google Scholar 

  • Khalsa, S.B., Jewett, M.E., Cajochen, C., and Czeisler, C.A. 2003. A phase response curve to single bright light pulses in human subjects. J Physiol 549(Pt 3): 945–952.

    PubMed  CAS  Google Scholar 

  • King, D.P., Zhao, Y., Sangoram, A.M., Wilsbacher, L.D., Tanaka, M., Antoch, M.P., Steeves, T.D., Vitaterna, M.H., Kornhauser, J.M., Lowrey, P.L., Turek, F.W., and Takahashi, J.S. 1997. Positional cloning of the mouse circadian clock gene. Cell 89(4): 641–653.

    PubMed  CAS  Google Scholar 

  • Kornmann, B., Preitner, N., Rifat, D., Fleury-Olela, F., and Schibler, U. 2001. Analysis of circadian liver gene expression by ADDER, a highly sensitive method for the display of differentially expressed mRNAs. Nucleic Acids Res 29(11): E51–51.

    PubMed  CAS  Google Scholar 

  • Kornmann, B., Schaad, O., Bujard, H., Takahashi, J.S., and Schibler, U. 2007. System-driven and oscillator-dependent circadian transcription in mice with a conditionally active liver clock. PLoS Biol 5(2): e34.

    PubMed  Google Scholar 

  • Kornmann, B., Schaad, O., Reinke, H., Saini, C., and Schibler, U. 2007. Regulation of circadian gene expression in liver by systemic signals and hepatocyte oscillators. Cold Spring Harb Symp Quant Biol. 7: 319–330.

    Google Scholar 

  • Kramer, A., Yang, F.C., Snodgrass, P., Li, X., Scammell, T.E., Davis, F.C., and Weitz, C.J. 2001. Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling. Science (New York, NY) 294(5551): 2511–2515.

    CAS  Google Scholar 

  • Kraves, S. and Weitz, C.J. 2006. A role for cardiotrophin-like cytokine in the circadian control of mammalian locomotor activity. Nat Neurosci 9(2): 212–219.

    PubMed  CAS  Google Scholar 

  • Kriegsfeld, L.J. and Silver, R. 2006. The regulation of neuroendocrine function: timing is everything. Horm Behav 49(5): 557–574.

    PubMed  CAS  Google Scholar 

  • Lakin-Thomas, P.L. 2006. Transcriptional feedback oscillators: maybe, maybe not. J Biol Rhythms 21(2): 83–92.

    PubMed  CAS  Google Scholar 

  • Leloup, J.C. and Goldbeter, A. 2003. Toward a detailed computational model for the mammalian circadian clock. Proc Natl Acad Sci USA 100(12): 7051–7056.

    PubMed  CAS  Google Scholar 

  • Leloup, J.C. and Goldbeter, A. 2004. Modeling the mammalian circadian clock: sensitivity analysis and multiplicity of oscillatory mechanisms. J Theor Biol 230(4): 541–562.

    PubMed  Google Scholar 

  • Le Minh, N., Damiola, F., Tronche, F., Schutz, G., and Schibler, U. 2001. Glucocorticoid hormones inhibit food-induced phase-shifting of peripheral circadian oscillators. EMBO J 20(24): 7128–7136.

    PubMed  CAS  Google Scholar 

  • Liu, A.C., Welsh, D.K., Ko, C.H., Tran, H.G., Zhang, E.E., Priest, A.A., Buhr, E.D., Singer, O., Meeker, K., Verma, I.M., Doyle, F.J., 3rd, Takahashi, J.S., and Kay, S.A. 2007. Intercellular coupling confers robustness against mutations in the SCN circadian clock network. Cell 129(3): 605–616.

    PubMed  CAS  Google Scholar 

  • Lloyd, D. and Murray, D.B. 2007. Redox rhythmicity: clocks at the core of temporal coherence. Bioessays 29(5): 465–473.

    PubMed  CAS  Google Scholar 

  • Lowrey, P.L., Shimomura, K., Antoch, M.P., Yamazaki, S., Zemenides, P.D., Ralph, M.R., Menaker, M., and Takahashi, J.S. 2000. Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau. Science (New York, NY) 288(5465): 483–492.

    CAS  Google Scholar 

  • Lundasen, T., Galman, C., Angelin, B., and Rudling, M. 2006. Circulating intestinal fibroblast growth factor 19 has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man. J Intern Med 260(6): 530–536.

    PubMed  CAS  Google Scholar 

  • McPherson, R. and Gauthier, A. 2004. Molecular regulation of SREBP function: the Insig-SCAP connection and isoform-specific modulation of lipid synthesis. Biochem Cell Biol 82(1): 201–211.

    PubMed  CAS  Google Scholar 

  • Minors, D.S., Waterhouse, J.M., and Wirz-Justice, A. 1991. A human phase-response curve to light. Neurosci Lett 133(1): 36–40.

    PubMed  CAS  Google Scholar 

  • Miyoshi, F., Nakayama, Y., Kaizu, K., Iwasaki, H., and Tomita, M. 2007. A mathematical model for the Kai-protein-based chemical oscillator and clock gene expression rhythms in cyanobacteria. J Biol Rhythms 22(1): 69–80.

    PubMed  CAS  Google Scholar 

  • Nagoshi, E., Saini, C., Bauer, C., Laroche, T., Naef, F., and Schibler, U. 2004. Circadian gene expression in individual fibroblasts: cell-autonomous and self-sustained oscillators pass time to daughter cells. Cell 119(5): 693–705.

    PubMed  CAS  Google Scholar 

  • Nakajima, M., Imai, K., Ito, H., Nishiwaki, T., Murayama, Y., Iwasaki, H., Oyama, T., and Kondo, T. 2005. Reconstitution of circadian oscillation of cyanobacterial KaiC phosphorylation in vitro. Science (New York, NY) 308(5720): 414–415.

    CAS  Google Scholar 

  • Noshiro, M., Usui, E., Kawamoto, T., Kubo, H., Fujimoto, K., Furukawa, M., Honma, S., Makishima, M., Honma, K., and Kato, Y. 2007. Multiple mechanisms regulate circadian expression of the gene for cholesterol 7alpha-hydroxylase (Cyp7a), a key enzyme in hepatic bile acid biosynthesis. J Biol Rhythms 22(4): 299–311.

    PubMed  CAS  Google Scholar 

  • Ouyang, Y., Andersson, C.R., Kondo, T., Golden, S.S., and Johnson, C.H. 1998. Resonating circadian clocks enhance fitness in cyanobacteria. Proc Natl Acad Sci USA 95(15): 8660–8664.

    PubMed  CAS  Google Scholar 

  • Panda, S., Antoch, M.P., Miller, B.H., Su, A.I., Schook, A.B., Straume, M., Schultz, P.G., Kay, S.A., Takahashi, J.S., and Hogenesch, J.B. 2002. Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109(3): 307–320.

    PubMed  CAS  Google Scholar 

  • Preitner, N., Damiola, F., Luis Lopez, M., Zakany, J., Duboule, D., Albrecht, U., and Schibler, U. 2002. The Orphan Nuclear Receptor REV-ERBalpha Controls Circadian Transcription within the Positive Limb of the Mammalian Circadian Oscillator. Cell 110(2): 251–260.

    PubMed  CAS  Google Scholar 

  • Ralph, M.R., Foster, R.G., Davis, F.C., and Menaker, M. 1990. Transplanted suprachiasmatic nucleus determines circadian period. Science (New York, NY) 247(4945): 975–978.

    CAS  Google Scholar 

  • Redlin, U. and Mrosovsky, N. 1999. Masking by light in hamsters with SCN lesions. J Comp Physiol 184(4): 439–448.

    CAS  Google Scholar 

  • Reinke, H., Saini., C., Fleury-Olela, F., Dibner, C., Benjamin I.J., and Schibler, U. 2008. Differential Display of DNA-Binding Proteins Reveals Heat Shock Factor 1 as a Circadian Transcription Factor. Genes Dev 22(3): 331–345.

    PubMed  CAS  Google Scholar 

  • Reppert, S.M. and Weaver, D.R. 2001. Molecular analysis of mammalian circadian rhythms. Ann Rev Physiol 63: 647–676.

    CAS  Google Scholar 

  • Roenneberg, T. and Taylor, W. 1994. Light-induced phase responses in Gonyaulax are drastically altered by creatine. J Biol Rhythms 9(1): 1–12.

    PubMed  CAS  Google Scholar 

  • Rust, M.J., Markson, J.S., Lane, W.S., Fisher, D.S., and O’Shea, E.K. 2007. Ordered phosphorylation governs oscillation of a three-protein circadian clock. Science (New York, NY) 318(5851): 809–812.

    CAS  Google Scholar 

  • Sato, T.K., Panda, S., Miraglia, L.J., Reyes, T.M., Rudic, R.D., McNamara, P., Naik, K.A., FitzGerald, G.A., Kay, S.A., and Hogenesch, J.B. 2004. A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron 43(4): 527–537.

    PubMed  CAS  Google Scholar 

  • Schafmeier, T., Kaldi, K., Diernfellner, A., Mohr, C., and Brunner, M. 2006. Phosphorylation-dependent maturation of Neurospora circadian clock protein from a nuclear repressor toward a cytoplasmic activator. Genes Dev 20(3): 297–306.

    PubMed  CAS  Google Scholar 

  • Schibler, U. 2007. The daily timing of gene expression and physiology in mammals. Dialogues Clin Neurosci 9(3): 257–272.

    PubMed  Google Scholar 

  • Scott, E.M., Carter, A.M., and Grant, P.J. 2008. Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man. Int J Obes (Lond) 32(4): 658–662. Epub 2007 Dec 11.

    CAS  Google Scholar 

  • Siepka, S.M., Yoo, S.H., Park, J., Song, W., Kumar, V., Hu, Y., Lee, C., and Takahashi, J.S. 2007. Circadian mutant Overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression. Cell 129(5): 1011–1023.

    PubMed  CAS  Google Scholar 

  • Silver, R., LeSauter, J., Tresco, P.A., and Lehman, M.N. 1996. A diffusible coupling signal from the transplanted suprachiasmatic nucleus controlling circadian locomotor rhythms. Nature 382(6594): 810–813.

    PubMed  CAS  Google Scholar 

  • Smolen, P., Baxter, D.A., and Byrne, J.H. 2001. Modeling circadian oscillations with interlocking positive and negative feedback loops. J Neurosci 21(17): 6644–6656.

    PubMed  CAS  Google Scholar 

  • Stokkan, K.A., Yamazaki, S., Tei, H., Sakaki, Y., and Menaker, M. 2001. Entrainment of the Circadian Clock in the Liver by Feeding. Science (New York, NY) 291(5503): 490–493.

    CAS  Google Scholar 

  • Storch, K.F., Lipan, O., Leykin, I., Viswanathan, N., Davis, F.C., Wong, W.H., and Weitz, C.J. 2002. Extensive and divergent circadian gene expression in liver and heart. Nature 417(6884): 78–83.

    PubMed  CAS  Google Scholar 

  • Toh, K.L., Jones, C.R., He, Y., Eide, E.J., Hinz, W.A., Virshup, D.M., Ptacek, L.J., and Fu, Y.H. 2001. An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science (New York, NY) 291(5506): 1040–1043.

    CAS  Google Scholar 

  • Tomita, J., Nakajima, M., Kondo, T., and Iwasaki, H. 2005. No transcription-translation feedback in circadian rhythm of KaiC phosphorylation. Science (New York, NY) 307(5707): 251–254.

    CAS  Google Scholar 

  • Tu, B.P. and McKnight, S.L. 2006. Metabolic cycles as an underlying basis of biological oscillations. Nat Rev 7(9): 696–701.

    CAS  Google Scholar 

  • Turek, F.W., Joshu, C., Kohsaka, A., Lin, E., Ivanova, G., McDearmon, E., Laposky, A., Losee-Olson, S., Easton, A., Jensen, D.R., Eckel, R.H., Takahashi, J.S., and Bass, J. 2005. Obesity and metabolic syndrome in circadian Clock mutant mice. Science (New York, NY) 308(5724): 1043–1045.

    CAS  Google Scholar 

  • Ueda, H.R., Chen, W., Adachi, A., Wakamatsu, H., Hayashi, S., Takasugi, T., Nagano, M., Nakahama, K., Suzuki, Y., Sugano, S., Iino, M., Shigeyoshi, Y., and Hashimoto, S. 2002. A transcription factor response element for gene expression during circadian night. Nature 418(6897): 534–539.

    PubMed  CAS  Google Scholar 

  • van der Horst, G.T., Muijtjens, M., Kobayashi, K., Takano, R., Kanno, S., Takao, M., de Wit, J., Verkerk, A., Eker, A.P., van Leenen, D., Buijs, R., Bootsma, D., Hoeijmakers, J.H., and Yasui, A. 1999. Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature 398(6728): 627–630.

    PubMed  Google Scholar 

  • van der Veen, D.R., Minh, N.L., Gos, P., Arneric, M., Gerkema, M.P., and Schibler, U. 2006. Impact of behavior on central and peripheral circadian clocks in the common vole Microtus arvalis, a mammal with ultradian rhythms. Proc Natl Acad Sci USA 103(9): 3393–3398.

    PubMed  Google Scholar 

  • van Zon, J.S., Lubensky, D.K., Altena, P.R., and ten Wolde, P.R. 2007. An allosteric model of circadian KaiC phosphorylation. Proc Natl Acad Sci USA 104(18): 7420–7425.

    PubMed  Google Scholar 

  • Vrang, N., Larsen, P.J., and Mikkelsen, J.D. 1995. Direct projection from the suprachiasmatic nucleus to hypophysiotrophic corticotropin-releasing factor immunoreactive cells in the paraventricular nucleus of the hypothalamus demonstrated by means of Phaseolus vulgaris-leucoagglutinin tract tracing. Brain Res 684(1): 61–69.

    PubMed  CAS  Google Scholar 

  • Wahl, M.B., Deng, C., Lewandoski, M., and Pourquie, O. 2007. FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis. Development (Cambridge, England) 134(22): 4033–4041.

    CAS  Google Scholar 

  • Walker, J.R. and Hogenesch, J.B. 2005. RNA profiling in circadian biology. Methods Enzymol 393: 366–376.

    PubMed  CAS  Google Scholar 

  • Waterhouse, J., Reilly, T., Atkinson, G., and Edwards, B. 2007. Jet lag: trends and coping strategies. Lancet 369(9567): 1117–1129.

    PubMed  Google Scholar 

  • Welsh, D.K., Logothetis, D.E., Meister, M., and Reppert, S.M. 1995. Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms. Neuron 14(4): 697–706.

    PubMed  CAS  Google Scholar 

  • William, D.A., Saitta, B., Gibson, J.D., Traas, J., Markov, V., Gonzalez, D.M., Sewell, W., Anderson, D.M., Pratt, S.C., Rappaport, E.F., and Kusumi, K. 2007. Identification of oscillatory genes in somitogenesis from functional genomic analysis of a human mesenchymal stem cell model. Dev Biol 305(1): 172–186.

    PubMed  CAS  Google Scholar 

  • Woelfle, M.A., Ouyang, Y., Phanvijhitsiri, K., and Johnson, C.H. 2004. The adaptive value of circadian clocks: an experimental assessment in cyanobacteria. Curr Biol 14(16): 1481–1486.

    PubMed  CAS  Google Scholar 

  • Woods, S.C., Lutz, T.A., Geary, N., and Langhans, W. 2006. Pancreatic signals controlling food intake; insulin, glucagon and amylin. Philos Trans R Soc London 361(1471): 1219–1235.

    CAS  Google Scholar 

  • Xu, C., Li, C.Y., and Kong, A.N. 2005. Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharmacol Res 28(3): 249–268.

    CAS  Google Scholar 

  • Yoo, S.H., Yamazaki, S., Lowrey, P.L., Shimomura, K., Ko, C.H., Buhr, E.D., Siepka, S.M., Hong, H.K., Oh, W.J., Yoo, O.J., Menaker, M., and Takahashi, J.S. 2004. PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. Proc Natl Acad Sci USA 101(15): 5339–5346.

    PubMed  CAS  Google Scholar 

  • Yu, W. and Hardin, P.E. 2006. Circadian oscillators of Drosophila and mammals. J Cell Sci 119(Pt 23): 4793–4795.

    PubMed  CAS  Google Scholar 

  • Zabielski, R. 2004. Reefs in experimental gastroenterology–cyclic activities of the gastrointestinal tract. J Physiol Pharmacol 55(Suppl 2): 19–32.

    PubMed  Google Scholar 

  • Zangar, R.C., Davydov, D.R., and Verma, S. 2004. Mechanisms that regulate production of reactive oxygen species by cytochrome P450. Toxicol Appl Pharmacol 199(3): 316–331.

    PubMed  CAS  Google Scholar 

  • Zheng, B., Albrecht, U., Kaasik, K., Sage, M., Lu, W., Vaishnav, S., Li, Q., Sun, Z.S., Eichele, G., Bradley, A., and Lee, C.C. 2001. Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock. Cell 105(5): 683–694.

    PubMed  CAS  Google Scholar 

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Schibler, U. (2008). The Mammalian Circadian Timekeeping System. In: Lloyd, D., Rossi, E.L. (eds) Ultradian Rhythms from Molecules to Mind. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8352-5_12

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