Based on genetic and biochemical advances on the molecular mechanism of circadian rhythms, a computational model for the mammalian circadian clock is used to examine the dynamical bases of circadian‐clock‐related physiological disorders in humans. Entrainment by the light–dark cycle with a phase advance or a phase delay is associated with the Familial advanced sleep phase syndrome (FASPS) or the Delayed sleep phase syndrome (DSPS), respectively. Lack of entrainment corresponding to the occurrence of quasiperiodic oscillations with or without phase jump can (...) be associated with the non‐24 h sleep–wake syndrome. In the close vicinity of the entrainment domain, the model uncovers the possibility of infradian oscillations of very long period. Perturbation in the form of chronic jet lag, as used in mice, prevents entrainment of the circadian clock and results in chaotic or quasiperiodic oscillations. It is important to clarify the conditions for entrainment and for its failure because dysfunctions of the circadian clock may lead to physiological disorders, which pertain not only to the sleep–wake cycle but also to mood and cancer. BioEssays 30:590–600, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Thanks to genetic and biochemical advances on the molecular mechanism of circadian rhythms in Drosophila, theoretical models closely related to experimental observations can be considered for the regulatory mechanism of the circadian clock in this organism. Modeling is based on the autoregulatory negative feedback exerted by a complex between PER and TIM proteins on the expression of per and tim genes. The model predicts the occurrence of sustained circadian oscillations in continuous darkness. When incorporating light‐induced TIM degradation, the model accounts (...) for damping of oscillations in constant light, entrainment of the rhythm by light‐dark cycles of varying period or photoperiod, and phase shifting by light pulses. The model further provides a molecular dynamical explanation for the permanent or transient suppression of circadian rhythmicity triggered in a variety of organisms by a critical pulse of light. Finally, the model shows that to produce a robust rhythm the various clock genes must be expressed at the appropriate levels since sustained oscillations only occur in a precise range of parameter values. BioEssays 22:84–93, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

Oscillations in cytosolic Ca2+ occur in a wide variety of cells, either spontaneously or as a result of external stimulation. This process is often accompanied by intracellular Ca2+ waves. A number of theoretical models have been proposed to account for the periodic generation and spatial propagation of Ca2+ signals. These models are reviewed and their predictions compared with experimental observations. Models for Ca2+ oscillations can be distinguished according to whether or not they rely on the concomitant, periodic variation in inositol (...) 1,4,5‐trisphosphate. Such a variation, however, is not required in models based on Ca2+‐induced Ca2+ release. When Ca2+diffusion is incorporated into these models, propagating waves of cytosolic Ca2+ arise, with profiles and rates comparable to those seen in the experiments. (shrink)