Circadian clocks

Introduction of foreign DNA into cyanobacteria has been demonstrated in laboratory for several strains, and is now a common practice [50]. A few unicellular cyanobacteria are naturally competent for transformation, and can uptake foreign DNA from their environment in the form of plasmid or linear DNA [51]. Among naturally competent strains are the model freshwater cyanobacteria S. elongatus PCC 7942 and Synechocystis PCC 6803, as well as the marine Synechococcus PCC 7002 and the thermophile Jhermosynechococcus elongatus BP-1 [52—56]. 

DNA has allowed the generation of mutants with gene disruption or heterologous gene overexpression when the incoming DNA is incorporated into a neutral site. 

Gene expression in cyanobacteria, whether on a self-replicating plasmid or integrated in the genome, needs to be driven by a specific promoter that can be recognized by the host. Only a limited number of promoters have been evaluated for this purpose in cyanobacteria [50]. Most known promoters are native to the host organism from genes required for photosynthesis and expressed in relatively 

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In all types of mammalian cells, the molecular mechanism underlying circadian clock function is based upon interconnected transcription/translation feedback loops [2] (Fig. 2). Two proteins that function as transcriptional... 

However, despite its enormous importance to human physiology, no pharmacological compounds targeting the components of the circadian clock system have been identified to date. There are, nevertheless, two therapeutic approaches that are currently used for treatment of circadian-related disorders - full-spectrum and bright light therapy and melatonin therapy. Melatonin is a hormone that is produced by the pineal gland in... 

Ko CH, Takahashi JS (2006) Molecular components of the mammalian circadian clock. Hum Mol Genet 15 Spec No 2 R271-R277... 

Antoch M, Kondratov R, Takahashi J (2005) Circadian clock genes as modulators of sensitivity to genotoxic stress. Cell Cycle 4901-907... 

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. 

An alteration in the endogenous circadian clock, most often elicited by a change in the light/dark cycle, for example when travelling between time zones. 

Figure 22.1 Pathways projecting to and from the suprachiasmatic nucleus (SCN). Inputs from photoreceptors in the retina help to reset the circadian clock in response to changes in the light cycle. Other inputs derive from the lateral geniculate complex and the serotonergic, Raphe nuclei and help to reset the SCN in response to non-photic stimuli. Neurons in the SCN project to the hypothalamus, which has a key role in the regulation of the reproductive cycle, mood and the sleep-waking cycle. These neurons also project to the pineal gland which shows rhythmic changes in the rate of synthesis and release of the hormone, melatonin...

Sancar, A., Regulation of the mammalian circadian clock by cryptochrome, J. Biol. Chem., 279, 34079, 2004. 

Partch, C. L. et al., Postranslational regulation of mammalian circadian clock by cryptochrome and proteinphosphatase 5, Proc Aarf Acad. Sci. USA, 103, 10467, 2006. Briggs, W.R., Christie, J.M., and Salomon, M., Phototropins a new family of flavinbinding blue light receptors in plants, Antioxid. Redox Signal, 3, 775, 2001. Briggs,W.R. et al.. The phototropin family of photoreceptors. Plant Cell, 13, 993, 2001. 

The most common CRDs include jet lag, shift-work sleep disruption, delayed sleep-phase disorder, and advanced sleep-phase disorder. Jet lag occurs when a person travels across time zones, and the external environmental time is mismatched with the internal circadian clock. Delayed and advanced sleep-phase disorders occur when bed and wake times are delayed or advanced (by 3 or more hours) compared with socially prescribed bed and wake times. 

Besharse J., Zhunag M., Freeman K., Fogerty J. (2004). Regulation of photoreceptor Perl and Per2 by light, dopamine and a circadian clock. Eur. J. Neurosci. 20, 167-4. 

Ribelayga C., Wang Y., Mangel S. (2004). A circadian clock in the fish retina regulates dopamine release via activation of melatonin receptors. J. Physiol. 554(2),... 

Steenhard B., Besharse J. (2000). Phase shifting the retinal circadian clock xPer2 mRNS induction by light and dopamine. J. Neurosci 20, 8572-7. 

Glass, J. D., Grossman, G. H., Farnbauch L. 8r DiNardo, L. (2003). Midbrain raphe modulation of nonphotic circadian clock resetting and 5-HT release in the mammalian suprachiasmatic nucleus. J. Neurosci. 23, 7451-60. 

Berson, D. M., Dunn, F. A. Takao, M. (2002). Phototransduction by retinal ganglion cells that set the circadian clock. Science 295, 1070-3. 

Hunt, A. E., A1 Ghoul, W. M., Gillette, M. U. Dubocovich, M. L. (2001). Activation of MT2 melatonin receptors in rat suprachiasmatic nucleus phase advances the circadian clock. Am. J. Physiol. Cell. Physiol. 280, 010-18. 

Iuvone, P. M., Tosini, G., Pozdeyev, N. et al. (2005). Circadian clocks, clock networks, arylalkylamine N-acetyltransferase, and melatonin in the retina. Prog. Retin. Eye Res. 24, 433-56. 

A role for the 5-HT7 receptor in the regulation of circadian rhythms has been implicated. As discussed above, 5-HT has been known for some time to induce phase shifts in behavioral circadian rhythms and modulate neuronal activity in the suprachiasmatic nucleus, the likely site of the mammalian circadian clock. The pharmacological characteristics of the effect of 5-HT on circadian rhythms are consistent with 5-HT7 receptor. Moreover, mRNA for the 5-HT7 receptor is found in the suprachiasmatic nucleus. There is also increasing evidence that the 5-HT7 receptor may play a role in psychiatric disorders. The regional distribution of 5-HT7 receptors in brain includes limbic areas and cortex. Atypical antipsychotics, such as clozapine and risperidone, and some antidepressants display high affinity for this receptor. In the periphery, 5-HT7 receptors havebeenshown to mediate relaxation of vascular smooth muscle. 

The most ubiquitous biological rhythms are those that occur with a period close to 24 h in all eukaryotes and in some prokaryotes such as cyanobacteria. These circadian rhythms allow organisms to adapt to the natural periodicity of the terrestrial environment, which is characterized by the alternation of day and night due to rotation of the earth on its axis. Circadian clocks provide cells with an endogenous mechanism, allowing them to anticipate the time of day. 

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... 

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