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MeSH Review

Biological Clocks

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Disease relevance of Biological Clocks


Psychiatry related information on Biological Clocks


High impact information on Biological Clocks

  • Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis [8].
  • The expression of the Clock gene in zebrafish shows a strong circadian oscillation in many tissues in vivo and in culture, showing that endogenous oscillators exist in peripheral organs [9].
  • The mammalian proteins Cryl and Cry2, which are members of the family of plant blue-light receptors (cryptochromes) and photolyases, have been proposed as candidate light receptors for photoentrainment of the biological clock [10].
  • The mechanism of the 'biological clock' which regulates these variations in level of chick pineal NAT activity is unknown [11].
  • The mCry double-mutant mice retain the ability to have mPer1 and mPer2 expression induced by a brief light stimulus known to phase-shift the biological clock in wild-type animals [12].

Biological context of Biological Clocks


Anatomical context of Biological Clocks


Associations of Biological Clocks with chemical compounds


Gene context of Biological Clocks

  • Here we report that nuclear translocation of mPER1 and mPER2 (1) involves physical interactions with mPER3, (2) is accelerated by serum treatment, and (3) still occurs in mCry1/mCry2 double-deficient cells lacking a functional biological clock [27].
  • N-methyl-D-aspartate receptor subtype 2C is not involved in circadian oscillation or photoic entrainment of the biological clock in mice [28].
  • The present results suggest that NR2A plays a weak role in oscillation or entrainment of the biological clock, and that NR2C does not participate in the functions of circadian oscillation and light entrainment [28].
  • Here we propose that the circadian waves of the APRR1/TOC1 family members are most likely a molecular basis of such a biological clock in higher plants [29].
  • Since it is known that these rats show a light-induced behavioral phase-shift throughout the subjective night with being strongest at subjective dawn, the present results suggest that the transient induction of Per1 in ventrolateral SCN neurons is a critical step in the resetting of the biological clock to environmental light-dark schedule [30].

Analytical, diagnostic and therapeutic context of Biological Clocks

  • Our results suggest that melatonin administration to patients in intensive care units may be indicated as a treatment for sleep induction and resynchronization of the "biologic clock." This treatment may also help in the prevention of the "ICU syndrome" and accelerate the healing process [31].


  1. A sigma factor that modifies the circadian expression of a subset of genes in cyanobacteria. Tsinoremas, N.F., Ishiura, M., Kondo, T., Andersson, C.R., Tanaka, K., Takahashi, H., Johnson, C.H., Golden, S.S. EMBO J. (1996) [Pubmed]
  2. Nucleotide sequence of coliphage HK620 and the evolution of lambdoid phages. Clark, A.J., Inwood, W., Cloutier, T., Dhillon, T.S. J. Mol. Biol. (2001) [Pubmed]
  3. Possible involvement of light regulated gonadotropin-releasing hormone neurons in biological clock for reproduction in the cerebral ganglion of the ascidian, Halocynthia roretzi. Ohkuma, M., Katagiri, Y., Nakagawa, M., Tsuda, M. Neurosci. Lett. (2000) [Pubmed]
  4. Dysregulation of photic induction of Fos-related protein in the biological clock during experimental trypanosomiasis. Peng, Z.C., Kristensson, K., Bentivoglio, M. Neurosci. Lett. (1994) [Pubmed]
  5. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Scheer, F.A., Van Montfrans, G.A., van Someren, E.J., Mairuhu, G., Buijs, R.M. Hypertension (2004) [Pubmed]
  6. The daily rhythm in plasma glucagon concentrations in the rat is modulated by the biological clock and by feeding behavior. Ruiter, M., La Fleur, S.E., van Heijningen, C., van der Vliet, J., Kalsbeek, A., Buijs, R.M. Diabetes (2003) [Pubmed]
  7. Daily rhythm of serum melatonin levels and effect of light exposure in patients with dementia of the Alzheimer's type. Ohashi, Y., Okamoto, N., Uchida, K., Iyo, M., Mori, N., Morita, Y. Biol. Psychiatry (1999) [Pubmed]
  8. Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Horwitz, M., Benson, K.F., Person, R.E., Aprikyan, A.G., Dale, D.C. Nat. Genet. (1999) [Pubmed]
  9. Light acts directly on organs and cells in culture to set the vertebrate circadian clock. Whitmore, D., Foulkes, N.S., Sassone-Corsi, P. Nature (2000) [Pubmed]
  10. Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. 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., Yasui, A. Nature (1999) [Pubmed]
  11. Diurnal cycles in serotonin acetyltransferase activity and cyclic GMP content of cultured chick pineal glands. Wainwright, S.D. Nature (1980) [Pubmed]
  12. Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock. Okamura, H., Miyake, S., Sumi, Y., Yamaguchi, S., Yasui, A., Muijtjens, M., Hoeijmakers, J.H., van der Horst, G.T. Science (1999) [Pubmed]
  13. Decreased vasopressin gene expression in the biological clock of Alzheimer disease patients with and without depression. Liu, R.Y., Zhou, J.N., Hoogendijk, W.J., van Heerikhuize, J., Kamphorst, W., Unmehopa, U.A., Hofman, M.A., Swaab, D.F. J. Neuropathol. Exp. Neurol. (2000) [Pubmed]
  14. Circadian secretion patterns of melatonin after major surgery. Nishimura, S., Fujino, Y., Shimaoka, M., Hagihira, S., Taenaka, N., Yoshiya, I. J. Pineal Res. (1998) [Pubmed]
  15. Modeling the VPAC2-activated cAMP/PKA signaling pathway: from receptor to circadian clock gene induction. Hao, H., Zak, D.E., Sauter, T., Schwaber, J., Ogunnaike, B.A. Biophys. J. (2006) [Pubmed]
  16. Diurnal variation in rat liver thyroid hormone receptor (TR)-alpha messenger ribonucleic acid (mRNA) is dependent on the biological clock in the suprachiasmatic nucleus, whereas diurnal variation of TR beta 1 mRNA is modified by food intake. Zandieh Doulabi, B., Platvoet-Ter Schiphorst, M., Kalsbeek, A., Fliers, E., Bakker, O., Wiersinga, W.M. Endocrinology (2004) [Pubmed]
  17. Vasopressin-deficient suprachiasmatic nucleus grafts re-instate circadian rhythmicity in suprachiasmatic nucleus-lesioned arrhythmic rats. Boer, G.J., van Esseveldt, K.E., van der Geest, B.A., Duindam, H., Rietveld, W.J. Neuroscience (1999) [Pubmed]
  18. Ontogenesis of a biological clock for serotonin:acetyl coenzyme A N-acetyltransferase in pineal gland of rat. Deguchi, T. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  19. A Hes1-based oscillator in cultured cells and its potential implications for the segmentation clock. Dale, J.K., Maroto, M. Bioessays (2003) [Pubmed]
  20. Biochemical basis for the biological clock. Morré, D.J., Chueh, P.J., Pletcher, J., Tang, X., Wu, L.Y., Morré, D.M. Biochemistry (2002) [Pubmed]
  21. Circadian genes in a blind subterranean mammal III: molecular cloning and circadian regulation of cryptochrome genes in the blind subterranean mole rat, Spalax ehrenbergi superspecies. Avivi, A., Oster, H., Joel, A., Beiles, A., Albrecht, U., Nevo, E. J. Biol. Rhythms (2004) [Pubmed]
  22. Putative melatonin receptors in a human biological clock. Reppert, S.M., Weaver, D.R., Rivkees, S.A., Stopa, E.G. Science (1988) [Pubmed]
  23. Resetting the biological clock: mediation of nocturnal circadian shifts by glutamate and NO. Ding, J.M., Chen, D., Weber, E.T., Faiman, L.E., Rea, M.A., Gillette, M.U. Science (1994) [Pubmed]
  24. Is histamine the final neurotransmitter in the entrainment of circadian rhythms in mammals? Jacobs, E.H., Yamatodani, A., Timmerman, H. Trends Pharmacol. Sci. (2000) [Pubmed]
  25. D1-dopamine receptors activate c-fos expression in the fetal suprachiasmatic nuclei. Weaver, D.R., Rivkees, S.A., Reppert, S.M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  26. Diurnal variation of the adenylyl cyclase type 1 in the rat pineal gland. Tzavara, E.T., Pouille, Y., Defer, N., Hanoune, J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  27. Dimerization and nuclear entry of mPER proteins in mammalian cells. Yagita, K., Yamaguchi, S., Tamanini, F., van Der Horst, G.T., Hoeijmakers, J.H., Yasui, A., Loros, J.J., Dunlap, J.C., Okamura, H. Genes Dev. (2000) [Pubmed]
  28. N-methyl-D-aspartate receptor subtype 2C is not involved in circadian oscillation or photoic entrainment of the biological clock in mice. Moriya, T., Takahashi, S., Ikeda, M., Suzuki-Yamashita, K., Asai, M., Kadotani, H., Okamura, H., Yoshioka, T., Shibata, S. J. Neurosci. Res. (2000) [Pubmed]
  29. Circadian waves of expression of the APRR1/TOC1 family of pseudo-response regulators in Arabidopsis thaliana: insight into the plant circadian clock. Matsushika, A., Makino, S., Kojima, M., Mizuno, T. Plant Cell Physiol. (2000) [Pubmed]
  30. Phase-dependent responses of Per1 and Per2 genes to a light-stimulus in the suprachiasmatic nucleus of the rat. Miyake, S., Sumi, Y., Yan, L., Takekida, S., Fukuyama, T., Ishida, Y., Yamaguchi, S., Yagita, K., Okamura, H. Neurosci. Lett. (2000) [Pubmed]
  31. Effect of melatonin on sleep quality of COPD intensive care patients: a pilot study. Shilo, L., Dagan, Y., Smorjik, Y., Weinberg, U., Dolev, S., Komptel, B., Shenkman, L. Chronobiol. Int. (2000) [Pubmed]
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