Circadian rhythm 56565 224300776 2008-07-08T06:30:35Z Hordaland 4755260 Removed new text to Talk. A '''circadian rhythm''' is an approximate daily periodicity, a roughly-24-hour cycle in the biochemical, physiological or behavioral processes of living beings, including [[plant]]s, [[animal]]s, [[fungi]] and [[cyanobacteria]]. The term "circadian", coined by [[Franz Halberg]],<ref>http://www.msi.umn.edu/~halberg Halberg Chronobiology Center</ref> comes from the [[Latin]] ''[[circa]]'', "around", and ''diem'' or ''dies'', "day", meaning literally "approximately one day." The formal study of biological temporal rhythms such as daily, [[tide|tidal]], weekly, seasonal, and annual rhythms, is called [[chronobiology]]. Circadian rhythms are [[endogenous]]ly generated, and can be entrained by external cues, called [[Zeitgeber]]s. The primary one is [[daylight]]. These rhythms allow organisms to anticipate and prepare for precise and regular environmental changes. ==History== The first endogenous circadian oscillation was observed in the 1700s by the French scientist [[Jean-Jacques d'Ortous de Mairan]] who noticed that 24-hour patterns in the movement of the leaves of the plant ''[[Mimosa pudica]]'' continued even when the plants were isolated from external stimuli. In 1918 J. S. Szymanski showed that animals are capable of maintaining 24-hour activity patterns in the absence of external cues such as light and changes in temperature.<ref>{{cite journal | last = Danchin | first = Antoine | date = | year = | month = | title = Important dates 1900-1919 | journal = HKU-Pasteur Research Centre | publisher = | location = Paris | url = http://www.pasteur.fr/recherche/unites/REG/causeries/dates_1900.html | accessdate = 2008-01-12 | quote = }}</ref> The earliest known account of a circadian rhythm dates from the fourth century BC, when Androsthenes, in descriptions of the marches of [[Alexander the Great]], described [[diurnal]] leaf movements of the tamarind tree. ==Criteria== Three general criteria of circadian rhythms are necessary to differentiate genuinely endogenous rhythms from coincidental or apparent ones: the rhythms persist in the absence of cues, they can be brought to match the local time, and will do so in a precise manner over a range of temperatures. * The rhythm persists in constant conditions (for example, constant dark) with a period of about 24 hours. The rationale for this criterion is to distinguish circadian rhythms from those "apparent" rhythms which merely are responses to external periodic cues. A rhythm cannot be declared to be endogenous unless it has been tested in conditions without external periodic input. * The rhythm is temperature-compensated, i.e. it maintains the same period over a range of temperatures. The rationale for this criterion is to distinguish circadian rhythms from other biological rhythms arising due to the circular nature of a reaction pathway. At a low enough or high enough temperature, the period of a circular reaction may reach 24 hours, but it will be merely coincidental. * The rhythm can be reset by exposure to an external stimulus. The rationale for this criterion is to distinguish circadian rhythms from other imaginable endogenous 24-hour rhythms that are immune to resetting by external cues and hence do not serve the purpose of estimating the local time. Travel across [[time zone]]s illustrates the necessity of the ability to adjust the biological clock so that it can reflect the local time and anticipate what will happen next. ==Origin== {{Unreferencedsection|date=October 2007}} Photosensitive proteins and circadian rhythms are believed to have originated in the earliest cells, with the purpose of protecting the replicating of DNA from high [[ultraviolet]] radiation during the daytime. As a result, replication was relegated to the dark. The fungus ''[[Neurospora]]'', which exists today, retains this clock-regulated mechanism. Rhythmicity appears to be as important in regulating cyclic biochemical processes within an individual, as in coordinating with the environment. This is suggested by the maintenance (heritability) of circadian rhythms in fruit flies after several hundred generations in constant laboratory conditions (Sheeba et al. 1999), as well as the experimental elimination of behavioral but not physiological circadian rhythms in quail (Guyomarc'h et al. 1998, Zivkovic et al. 1999). The simplest known circadian clock is that of the prokaryotic [[cyanobacteria]]. Recent research has demonstrated that the circadian clock of ''Synechococcus elongatus'' can be reconstituted ''in vitro'' with just the three proteins of their central oscillator. This clock has been shown to sustain a 22-hour rhythm over several days upon the addition of [[Adenosine triphosphate|ATP]]. Previous explanations of the [[prokaryotic]] circadian timekeeper were dependent upon a DNA transcription / translation feedback mechanism. It is an outstanding question whether circadian clocks in eukaryotic organisms require translation/transcription-derived oscillations. For although the circadian systems of eukaryotes and prokaryotes have the same basic architecture: input - central oscillator - output, they do not share any homology. This implies probable independent origins. In 1971, Konopka and Benzer first identified a genetic component of the biological clock using the fruit fly as a model system. Three mutant lines of flies displayed aberrant behavior - one had a shorter period, another had a longer one and the third had none. All three mutations mapped to the same gene, which was named ''[[period (gene)|period]]''.<ref>{{cite book |last= Purves |first= Dale ''et al'' |title= NEUROSCIENCE |origdate= |origyear= 2001 |url= http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=.0-X5CQEZnQIQrizQvUwzgMbTAG |format= e-book |accessdate= 2008-05-30 |edition= second edition |series= |date= |year= |month= |publisher= Sinauer Associates |location= Sunderland, MA, U.S.A. |isbn= 0-87893-742-0 |oclc= |doi= |id= |pages= |chapter= Molecular Mechanisms of Biological Clocks |chapterurl= http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=neurosci.box.1963 |quote= }}</ref> The same gene was identified to be defective in the sleep disorder FASPS (Familial Advanced Sleep Phase Syndrome) in human beings thirty years later - underscoring the conserved nature of the molecular circadian clock through evolution. We now know many more genetic components of the biological clock. Their interactions result in an interlocked feedback loop of gene products resulting in periodic fluctuations that the cells of the body interpret as a specific time of the day. A great deal of research on biological clocks was done in the last half of the 20th century. It is now known that the molecular circadian clock can function within a single cell; i.e., it is cell-autonomous.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/15550250 Circadian gene expression in individual fibroblast...[Cell. 2004&#93; - PubMed Result<!-- Bot generated title -->]</ref> At the same time, different cells may communicate with each other resulting in a synchronized output of electrical signaling. These may interface with endocrine glands of the brain to result in periodic release of hormones. The receptors for these hormones may be located far across the body and synchronize the peripheral clocks of various organs. Thus, the information of the time of the day as relayed by the [[eye]]s travels to the clock in the brain, and, through that, clocks in the rest of the body may be synchronized. This is how the timing of, for example, sleep/wake, body temperature, thirst, and appetite are coordinately controlled by the biological clock. ==Importance in animals== Circadian rhythms are important in determining the [[sleep]]ing and feeding patterns of all animals, including human beings. There are clear patterns of core body temperature, [[brain wave]] activity, [[hormone]] production, cell regeneration and other biological activities linked to this daily cycle. In addition, [[photoperiodism]], the physiological reaction of organisms to the length of day or night, is vital to both plants and animals, and the circadian system plays a role in the measurement and interpretation of daylength. <blockquote>«Timely prediction of seasonal periods of weather conditions, food availability or predator activity is crucial for survival of many species. Although not the only parameter, the changing length of the photoperiod ('daylength') is the most predictive environmental cue for the seasonal timing of physiology and behavior, most notably for timing of migration, hibernation and reproduction.»<ref>{{cite web |url= http://scienceblogs.com/clock/2007/07/clock_tutorial_16_photoperiodi_1.php |title=Clock Tutorial #16: Photoperiodism - Models and Experimental Approaches |accessdate=2007-12-09 |last=Zivkovic |first=Bora "Coturnix" |date=2005-08-13 / July 25, 2007 |work=A Blog Around the Clock |publisher=ScienceBlogs |quote= }}</ref></blockquote> ===Impact of light-dark cycle=== The rhythm is linked to the light-dark cycle. Animals, including humans, kept in total darkness for extended periods eventually function with a [[Free-running sleep|freerunning]] rhythm. Each "day," their sleep cycle is pushed back or forward, depending on whether their endogenous period is shorter or longer than 24 hours. The environmental cues that each day reset the rhythms are called ''[[Zeitgeber]]s'' (from the German, ''Time Givers'').<ref name=health.am>{{cite web | Shneerson JM, Ohayon MM, Carskadon MA | title =Circadian rhythms | publisher=Armenian Medical Network | work = Rapid eye movement (REM) sleep | url=http://www.sleep.health.am/sleep/more/circadian-rhythms/ | year = 2007 | accessdate=2007-09-19}}</ref> It is interesting to note that totally-blind subterranean mammals (e.g., blind mole rat ''Spalax'' sp.) are able to maintain their endogenous clocks in the apparent absence of external stimuli. Freerunning organisms that normally have one consolidated sleep episode will still have it when in an environment shielded from external cues, but the rhythm is, of course, not entrained to the 24-hour light/dark cycle in nature. The sleep/wake rhythm may, in these circumstances, become out of phase with other circadian or [[ultradian]] rhythms such as [[temperature]] and [[digestion]].{{Fact|date=November 2007}} Recent research has influenced the design of [[human spaceflight|spacecraft]] environments, as systems that mimic the light/dark cycle have been found to be highly beneficial to astronauts. ===Arctic animals=== Norwegian researchers at the [[University of Tromsø]] have shown that some Arctic animals ([[ptarmigan]], [[reindeer]]) show circadian rhythms only in the parts of the year that have daily sunrises and sunsets. In one study of reindeer, animals at 70 degrees North showed circadian rhythms in the autumn, winter, and spring, but not in the summer. Reindeer at 78 degrees North showed such rhythms only autumn and spring. The researchers suspect that other Arctic animals as well may not show circadian rhythms in the constant light of summer and the constant dark of winter.<ref>{{cite news |first=Ingrid |last=Spilde |author= |title=Reinsdyr uten døgnrytme |url= http://www.forskning.no/Artikler/2005/desember/1135264557.29 |format= |work= |publisher=forskning.no |date=December 2005 |accessdate=2007-11-24 |language=Language: Norwegian, Bokmål |quote= |archiveurl= |archivedate= }}</ref><ref>{{cite web |url=http://scienceblogs.com/clock/2007/07/circadian_rhythms_or_not_in_ar_1.php |title=Circadian Rhythms, or Not, in Arctic Reindeer |accessdate=2007-11-24 |author= |last=Zivkovic |first=Bora, aka Coturnix, chronobiologist |authorlink= |date= |year= |month= |format= |work=A Blog around the Clock |publisher=ScienceBlogs.com }}</ref> However, another study in northern Alaska found that [[ground squirrel]]s and [[porcupine]]s strictly maintained their circadian rhythms through 82 days and nights of sunshine. The researchers speculate that these two small mammals see that the apparent distance between the sun and the horizon is shortest once a day, and, thus, a sufficient signal to adjust by.<ref>{{cite web |url= http://scienceblogs.com/clock/2007/02/small_arctic_mammals_entrain_t.php |title=Small Arctic Mammals Entrain to Something during the Long Summer Day |accessdate=2007-11-26 |author= Zivkovic, Bora, aka Coturnix, chronobiologist |date= 2007-02-11 |format= |work= A Blog Around the Clock |publisher= ScienceBlogs.com |quote= }}</ref> ==The biological clock== The primary circadian "clock" in [[mammal]]s is located in the [[suprachiasmatic nucleus]] (or nuclei) (SCN), a pair of distinct groups of [[cell (biology)|cell]]s located in the [[hypothalamus]]. Destruction of the SCN results in the complete absence of a regular sleep/wake rhythm. The SCN receives information about illumination through the eyes. The [[retina]] of the eyes contains not only "classical" [[photoreceptor]]s but also photoresponsive retinal [[ganglion cells]]. These cells, which contain a photo pigment called [[melanopsin]], follow a pathway called the [[retinohypothalamic tract]], leading to the SCN. If cells from the SCN are removed and cultured, they maintain their own rhythm in the absence of external cues. It appears that the SCN takes the information on day length from the retina, interprets it, and passes it on to the [[pineal gland]], a tiny structure shaped like a [[pine cone]] and located on the [[epithalamus]]. In response the pineal secretes the hormone [[melatonin]]. Secretion of melatonin peaks at night and ebbs during the day. The circadian rhythms of humans can be entrained to slightly shorter and longer periods than the earth's 24 hours. Researchers at Harvard have recently shown that human subjects can at least be entrained to a 23.5-hour cycle and a 24.65-hour cycle (the latter being the natural solar day-night cycle on the planet [[Mars]]).<ref>{{cite journal | last = Scheer | first = Frank A. J. L. | coauthors = Kenneth P. Wright, Jr., Richard E. Kronauer, Charles A. Czeisler | date = 2007-08-08 | title = Plasticity of the Intrinsic Period of the Human Circadian Timing System | journal = PLoS ONE | volume = 2| issue = | pages = e721| publisher = | location = | url = http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0000721 | accessdate = 2007-12-31 | quote = | doi = 10.1371/journal.pone.0000721 }}</ref> ===Determining the human circadian rhythm=== [[Image:Biological clock human.PNG|thumb|300px|Overview of human circadian biological clock with some physiological parameters.]] The classic phase markers for measuring the timing of a mammal's circadian rhythm are '''melatonin secretion''' by the pineal gland and '''core body temperature'''. For temperature studies, people must remain awake but calm and semi-reclined in near darkness while their rectal temperatures are taken continuously. The average human adult's temperature reaches its minimum at about 05:00 (5 a.m.), about two hours before habitual wake time, though variation is great among normal [[chronotype]]s. Melatonin is absent from the system or undetectably low during daytime. Its onset in dim light, ''dim-light melatonin onset'' (DLMO), at about 21:00 (9 p.m.) can be measured in the blood or the saliva. Both DLMO and the midpoint (in time) of the presence of the hormone in the blood or saliva have been used as circadian markers. However, newer research indicates that the melatonin ''offset'' may be the most reliable marker. Benloucif ''et al'' in Chicago in 2005 found that melatonin phase markers were more stable and more highly correlated with the timing of sleep than the core temperature minimum. They found that both sleep offset and melatonin offset were more strongly correlated with the various phase markers than sleep onset. In addition, the declining phase of the melatonin levels was more reliable and stable than the termination of melatonin synthesis.<ref>{{cite journal | last = Benloucif | first = S. | coauthors = Guico, M.J.; Reid, K.J.; Wolfe, L.F.; L'Hermite-Baleriaux, M.; Zee, P.C. | year = 2005 | title = Stability of melatonin and temperature as circadian phase markers and their relation to sleep times in humans. | journal = J Biol Rhythms | volume = 20 | issue = 2 | pages = pages 178–88 | publisher = Center for Sleep and Circadian Biology, Departments of Neurology, Northwestern University Feinberg School of Medicine | location = Chicago, Illinois, USA | url = http://www.websciences.org/cftemplate/NAPS/archives/indiv.cfm?ID=20045590 | accessdate =2007-12-18 | quote = | doi = 10.1177/0748730404273983 | pmid = 15834114 }}</ref> One method used for measuring melatonin offset is to analyze a sequence of urine samples throughout the morning <!--and day--> for the presence of the melatonin [[metabolite]] 6-sulphatoxymelatonin (aMT6s). Laberge ''et al'' in Quebec in 1997 used this method in a study which confirmed the frequently found delayed circadian phase in healthy adolescents.<ref>{{cite journal | last = Laberge | first = L. | coauthors = Lesperance, P.; Tremblay, R.; Lambert, C.; Montplaisir, J. | year = 1997 | title = Phase delay of 6-sulphatoxymelatonin in normal adolescents | journal = Sleep Research | volume = 26 | pages = p. 727 | publisher = Centre d'etude du Sommeil, Hopital du Sacre-Coeur, Département de Psychologie, Département de Pharmacologie, Departement de Psychiatrie, Université de Montréal | location = Québec, Canada | url = http://www.websciences.org/cftemplate/NAPS/archives/indiv.cfm?ID=19979287 | language = English | accessdate = 2007-12-18 | quote = }}</ref> ===Outside the "master clock"=== More-or-less independent circadian rhythms are found in many organs and cells in the body outside the suprachiasmatic nuclei (SCN), the "master clock." These clocks, called peripheral oscillators, are found in the esophagus, lung, liver, pancreas, spleen, thymus and the skin.<ref>Zanello, S. et al., J. Inv. Dermatol. 2000, Vol. 115, 4 Oct.: Expression of the Circadian Clock Genes clock and period1 in Human Skin </ref> Though oscillators in the skin respond to light, a systemic influence has not been proven so far.<ref>Kawara, S. et al. J. Inv. Derm. 2002, Vol 119, 6 Dec.: Low-dose UVB Rays Alter the mRNA Expression of the Circadian Clock Genes in cultured Human Keratinocytes</ref><ref>Campbell, S. and Murphy, P, Science 1998, Vol 279, 16 Jan.: Extraocular Circadian Phototransduction in Humans </ref> There is some evidence that also the olfactory bulb and prostate may experience oscillations when cultured, suggesting that also these structures may be weak oscillators. Furthermore, [[liver]] cells, for example, appear to respond to feeding rather than to [[light]]. Cells from many parts of the body appear to have freerunning rhythms. ==Light and the biological clock== Light resets the biological clock in accordance with the [[phase response curve]] (PRC). Depending on the timing, light can advance or delay the circadian rhythm. Both the PRC and the required [[illuminance]] vary from species to species; much lower light levels are required to reset the clocks in nocturnal rodents than in humans. In addition to light intensity, wavelength (or color) of light is an important factor in the degree to which the clock is reset. [[Melanopsin]] is most efficiently excited by blue light, 420-440 nm<ref>Newman LA, Walker MT, Brown RL, Cronin TW, Robinson PR: "Melanopsin forms a functional short-wavelength photopigment", ''Biochemistry.'' 2003 Nov 11;42(44):12734-8.</ref> according to some researchers while others have reported 470-485nm. ==== The myth of the 25-hour day ==== Early investigators determined the human circadian period to be 25 hours or more. They went to great lengths to shield subjects from time cues and daylight, but they were not aware of the effects of indoor electric lights. The subjects were allowed to turn on light when they were awake and to turn it off when they wanted to sleep. Electric light in the evening delayed their circadian phase. These results became well known.<ref name=hno /> ==== The human circadian period ==== Modern research under very controlled conditions has shown the human period for adults to be just slightly longer than 24 hours on average. Czeisler ''et al'' at Harvard found the range for normal, healthy adults of all ages to be quite narrow: 24 hours and 11 minutes ± 16 minutes. The "clock" resets itself daily to the 24-hour cycle of the earth's rotation.<ref name=hno>{{cite web | Charles A. Czeisler MD, PhD | title =Human Biological Clock Set Back an Hour | url=http://www.hno.harvard.edu/gazette/1999/07.15/bioclock24.html | year = 1999 | accessdate=2007-09-23}}</ref> ==Human health== There are many health problems associated with a disturbance in the human circadian rhythm, such as [[Seasonal Affective Disorder]] (SAD), [[delayed sleep phase syndrome]] (DSPS) and other [[circadian rhythm disorder]]s.<ref name=brynmawr>{{cite web | Sabah Quraishi | title =Circadian Rhythms and Sleep | publisher=Serendip | work = Circadian Rhythms and Sleep | url=http://serendip.brynmawr.edu/bb/neuro/neuro01/web1/Quirashi.html | year = 2007 | accessdate=2007-09-19}}</ref> Circadian rhythms also play a part in the [[reticular activating system]] which is crucial for maintaining a state of consciousness. ===Disruption=== Disruption to rhythms usually has a negative effect. Many travelers have experienced the condition known as [[jet lag]], with its associated symptoms of [[fatigue (physical)|fatigue]], disorientation and [[insomnia]]. A number of other disorders, for example [[bipolar disorder]] and some [[sleep disorder]]s, are associated with irregular or pathological functioning of circadian rhythms. Recent research suggests that circadian rhythm disturbances found in [[bipolar disorder]] are positively influenced by [[lithium]]'s effect on clock genes.<ref>[http://www.nimh.nih.gov/press/lithiumenzyme.cfm NIMH · Science News from 2006 · Lithium Blocks Enzyme To Help Cells’ Clocks Keep On Tickin’<!-- Bot generated title -->]</ref> Disruption to rhythms in the longer term is believed to have significant adverse health consequences on peripheral organs outside the brain, particularly in the development or exacerbation of cardiovascular disease. Timing of medical treatment in coordination with the body clock may significantly increase efficacy and reduce drug toxicity or adverse reactions. For example, appropriately timed treatment with [[angiotensin converting enzyme inhibitors]] (ACEi) may reduce nocturnal blood pressure and also benefit [[left ventricular]] (reverse) remodeling. [[Shift work]], particularly the night shift, has in December 2007 been listed by the [[World Health Organization]] (WHO) as a "probable cause" of cancer.<ref> [http://www.iarc.fr/ENG/Press_Releases/pr180a.html IARC: Press Release Nr. 180] «Shiftwork that involves circadian disruption is “probably carcinogenic to humans”.»</ref> ==Effects on cocaine sensitization in mice== Circadian rhythms and clock genes expressed in brain regions outside the SCN may significantly influence the effects produced by drugs such as [[cocaine]].<ref>{{cite journal |author=Uz T, Akhisaroglu M, Ahmed R, Manev H |title=The pineal gland is critical for circadian Period1 expression in the striatum and for circadian cocaine sensitization in mice |journal=Neuropsychopharmacology |volume=28 |issue=12 |pages=2117–23 |year=2003 |pmid=12865893 |doi=10.1038/sj.npp.1300254}}</ref><ref>{{cite journal |author=Kurtuncu M, Arslan A, Akhisaroglu M, Manev H, Uz T |title=Involvement of the pineal gland in diurnal cocaine reward in mice |journal=Eur J Pharmacol |volume=489 |issue=3 |pages=203–5 |year=2004 |pmid=15087244 | doi = 10.1016/j.ejphar.2004.03.010 <!--Retrieved from CrossRef by DOI bot-->}}</ref> Moreover, genetic manipulations of clock genes profoundly affect cocaine's actions.<ref>{{cite journal |author=McClung C, Sidiropoulou K, Vitaterna M, Takahashi J, White F, Cooper D, Nestler E |title=Regulation of dopaminergic transmission and cocaine reward by the Clock gene |journal=Proc Natl Acad Sci U S A |volume=102 |issue=26 |pages=9377–81 |year=2005 |pmid=15967985 | doi = }}</ref> ==See also== * [[Actigraphy]] (also known as Actimetry) * [[Advanced sleep phase syndrome]] * [[ARNTL]] * [[ARNTL2]] * [[Chronobiology]] * [[Chronotype]] * [[Circadian rhythm sleep disorders]] * [[Cryptochrome]] * [[CRY1]] and [[CRY2]], the cryptochrome family genes * [[Jet lag]] * [[Light effects on circadian rhythm]] * [[PER1]], [[PER2]], and [[PER3]], the period family genes ==Notes== <!--<nowiki> See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for an explanation of how to generate footnotes using the <ref> and </ref> tags, and the template below. </nowiki>--> {{reflist|2}} ==Further reading== *Aschoff J (ed.) (1965) ''Circadian Clocks''. North Holland Press, Amsterdam *Avivi A, Albrecht U, Oster H, Joel A, Beiles A, Nevo E. 2001. Biological clock in total darkness: the Clock/MOP3 circadian system of the blind subterranean mole rat. ''Proc Natl Acad Sci USA'' 98:13751- 13756. *Avivi A, Oster H, Joel A, Beiles A, Albrecht U, Nevo E. 2002. Circadian genes in a blind subterranean mammal II: conservation and uniqueness of the three ''Period homologs'' in the blind subterranean mole rat, ''Spalax ehrenbergi'' superspecies. ''Proc Natl Acad Sci USA'' 99:11718-11723. *Ditty JL, Williams SB, Golden SS (2003) A cyanobacterial circadian timing mechanism. ''Annu Rev Genet'' 37:513-543 *Dunlap JC, Loros J, DeCoursey PJ (2003) ''Chronobiology: Biological Timekeeping''. Sinauer, Sunderland *Dvornyk V, Vinogradova ON, Nevo E (2003) Origin and evolution of circadian clock genes in prokaryotes. ''Proc Natl Acad Sci USA'' 100:2495-2500 *Koukkari WL, Sothern RB (2006) ''Introducing Biological Rhythms''. Springer, New York *Martino T, Arab S, Straume M, Belsham DD, Tata N, Cai F, Liu P, Trivieri M, Ralph M, Sole MJ. Day/night rhythms in gene expression of the normal murine heart. J Mol Med. 2004 Apr;82(4):256-64. Epub 2004 Feb 24. PMID: 14985853 *Refinetti R (2006) ''Circadian Physiology, 2nd ed''. CRC Press, Boca Raton *Takahashi JS, Zatz M (1982) Regulation of circadian rhythmicity. ''Science'' 217:1104–1111 *Tomita J, Nakajima M, Kondo T, Iwasaki H (2005) No transcription–translation feedback in circadian rhythm of KaiC phosphorylation. ''Science'' 307: 251–254 Moore-Ede, Martin C., Sulszman, Frank M., and Fuller, Charles A. (1982) "The Clocks that Time Us: Physiology of the Circadian Timing System." Harvard University Press, Cambridge, MA. ISBN 0-674-13581-4. ==External links== * [http://www.express.co.uk/posts/view/27268/Can-you-reset-your-body-clock- Can you reset your body clock?] by John Triggs in the Daily Express December 4 2007 * {{dmoz|Health/Conditions_and_Diseases/Sleep_Disorders/Biological_Rhythms}} *[http://www.circadian.org www.circadian.org] *[http://www.hhmi.org/biointeractive/museum/exhibit00/02_1.html Biological Clocks] A description of circadian rhythms in plants by de Mairan, Linnaeus, and Darwin *{{cite web | date= 2006-01-18 | language = English | format = html | publisher = The University of Texas Health Science Center | url = http://www.uthouston.edu/Media/newsreleases/nr2006/metabolic_fuel.html | title = Darkness Unveils Vital Metabolic Fuel Switch Between Sugar and Fat | accessdate =2007-10-17}} *[http://www.nature.com/msb/journal/v1/n1/full/msb4100027.html Circadian clocks go in vitro: purely post-translational oscillators in cyanobacteria] *[http://jbr.sagepub.com Journal of Biological Rhythms] *[http://today.uci.edu/news/release_detail.asp?key=1705 Genetic switch for circadian rhythms discovered], [[University of California, Irvine]], December 12, 2007. *[http://www.nature.com/nature/journal/v450/n7172/full/nature06394.html CLOCK-mediated acetylation of BMAL1 controls circadian function], [[Nature (journal)]], 450, 1086-1090 (13 December 2007). 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