Oscillation circadian clock

Period 1) Clock gene and transcriptional repressor and negative limb (complex with CRY, PER2) of molecular circadian oscillators, essential for circadian clock plasticity and entrainment. 

Further extensions of the model are required to address the dynamical consequences of these additional regulatory loops and of the indirect nature of the negative feedback on gene expression. Such extended models have been proposed for Drosophila [112, 113] and mammals [113]. The model for the circadian clock mechanism in mammals is schematized in Fig. 3C. The presence of additional mRNA and protein species, as well as of multiple complexes formed between the various clock proteins, complicates the model, which is now governed by a system of 16 or 19 kinetic equations. Sustained or damped oscillations can occur in this model for parameter values corresponding to continuous darkness. As observed in the experiments on the mammalian clock. Email mRNA oscillates in opposite phase with respect to Per and Cry mRNAs [97]. The model displays the property of entrainment by the ED cycle... 

Only deterministic models for cellular rhythms have been discussed so far. Do such models remain valid when the numbers of molecules involved are small, as may occur in cellular conditions Barkai and Leibler [127] stressed that in the presence of small amounts of mRNA or protein molecules, the effect of molecular noise on circadian rhythms may become significant and may compromise the emergence of coherent periodic oscillations. The way to assess the influence of molecular noise on circadian rhythms is to resort to stochastic simulations [127-129]. Stochastic simulations of the models schematized in Fig. 3A,B show that the dynamic behavior predicted by the corresponding deterministic equations remains valid as long as the maximum numbers of mRNA and protein molecules involved in the circadian clock mechanism are of the order of a few tens and hundreds, respectively [128]. In the presence of molecular noise, the trajectory in the phase space transforms into a cloud of points surrounding the deterministic limit cycle. 

Controlled chaos may also factor into the generation of rhythmic behavior in living systems. A recently proposed modeL describes the central circadian oscillator as a chaotic attractor. Limit cycle mechanisms have been previously offered to explain circadian clocks and related phenomena, but they are limited to a single stable periodic behavior. In contrast, a chaotic attractor can generate rich dynamic behavior. Attractive features of such a model include versatility of period selection as well as use of control elements of the type already well known for metabolic circuitry. 

Circadian clock-controlled rhythms provide most organisms with an orchestrated temporal programme that allows for appropriate timing of physiology (i.e. blood pressure, hormonal levels) and behaviour (i.e. alertness, sleep-wake cycle). The mammalian central circadian pacemaker resides in the suprachiasmatic nucleus (SCN) of the brain (Weaver 1998). At the molecular level, the core oscillator driving the mammahan clock consists of interconnected autoregulatory... 

Stephan FK 2001 Food entrainable oscillators in mammals. In Turek TJFW, Moore RY (eds) Handbook of behavioral neurobiology 12. Circadian clocks. Kluwer Academic/Plenum Publishers, New York, p 223-241... 

What is special about the testis that requires the absence of the circadian clock so pervasive in other tissues The testis has a number of characteristics, which make it quite different from other tissues. The testis contains spermatogenic cells that perform a constant and complex cell differentiation program where reductive cell divisions occur. It may be that the complex pattern of gene expression engendered by the circadian clock leads to unfavourable interactions with the developmental process of paramount importance to the testis. Alternatively, the normal oscillation of clock gene expression may be distorted by other transcriptional regulators or co-activators which are only present in seminiferous tubules (Sassone-Corsi 2002). 

Dunlap It would be an enormous amount of work to execute a screen for mutants in the FLO. When you think about it, the situation now with respect to the non-circadian rhythms represented by FLO and similar oscillators is very similar to where we all were with circadian clocks in the early 1980s we had some putative mutants that affected clock expression/function but we had no idea whether they were core circadian clock molecules or simply had pleiotropic effects on the expression of the circadian rhythm. We had no selection, only screens. As we all know it was a lot of work to convincingly show that molecules like FRQ and PER were essential for the circadian clock. I m not sure it s worth making the investment in positional cloning of an allele that might not inform you at all of a mechanism for FLO. And even if you did, since the FLO rhythm is not a circadian rhythm, where is this going to be published In our experience, a gene that affects an oscillator like the FLO that is really not circadian and that no one thinks is involved with the circadian mechanism won t interest a student. 

Zylka MJ, Shearman LP, Weaver DR, Reppert SM 1998 Three period homologs in mammals differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain. Neuron 20 1103—1110... 

The top panels in Fig. 10.2 show the oscillations in the fraction of cells in the different cell cycle phases, as a function of time, in the absence of entrainment by the circadian clock. In the case considered, the duration of the cell cycle is 22 h, and the variability V is equal to 0% (Fig. 10.2a) or 15% (Fig. 10.2b). When variability is set to zero, no desynchronization occurs and the oscillations in the successive phases of the cell cycle are manifested as square waves that keep a constant amplitude in a given phase. Conversely, when variability increases up to 15% in the absence of entrainment (Fig. 10.2b), the amplitude of the oscillations decreases, reflecting enhanced desynchronization. 

To some extent the idea of resonance is also present in the case of circadian 5-FU delivery. Indeed, the circadian patterns of 5-FU which peak at 4 a.m. or 4 p.m. correspond to oscillations that are, respectively, in antiphase or in corresponding phase with the circadian variation of the fraction of cells in S phase. This effect can be seen even for cell cycle durations that differ from 24 h, because of the entrainment of the cell cycle by the circadian clock. 

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