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A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e.,
endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...
) and responds to the environment ( entrained by the environment). These 24-hour rhythms are driven by a
circadian clock A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase (waves), phase and is synchronized with solar time. Such a clock's ''in vivo'' period is necessarily almost exactly 24 hours (the earth's curre ...
, and they have been widely observed in animals, plants, fungi and
cyanobacteria Cyanobacteria (), also known as Cyanophyta, are a phylum of gram-negative bacteria that obtain energy via photosynthesis. The name ''cyanobacteria'' refers to their color (), which similarly forms the basis of cyanobacteria's common name, blu ...
. The term ''circadian'' comes from the Latin ''
circa Circa is a word of Latin origin meaning 'approximately'. Circa or CIRCA may also refer to: * CIRCA (art platform), art platform based in London * Circa (band), a progressive rock supergroup * Circa (company), an American skateboard footwear com ...
'', meaning "approximately", and ''dies'', meaning "day". Processes with 24-hour cycles are more generally called diurnal rhythms; diurnal rhythms should not be called circadian rhythms unless they can be confirmed as endogenous, and not environmental. Although circadian rhythms are endogenous, they are adjusted to the local environment by external cues called zeitgebers (German for "time givers"), which include light, temperature and redox cycles. In clinical settings, an abnormal circadian rhythm in humans is known as a
circadian rhythm sleep disorder Circadian rhythm sleep disorders (CRSD), also known as circadian rhythm sleep-wake disorders (CRSWD), are a family of sleep disorders which affect the timing of sleep. CRSDs arise from a persistent pattern of sleep/wake disturbances that can be ...
.


History

While there are multiple mentions of "natural body cycle" in Eastern and Native American cultures, the earliest recorded Western account of a circadian process is credited to Theophrastus, dating from the 4th century BC, probably provided to him by report of Androsthenes, a
ship's captain A sea captain, ship's captain, captain, master, or shipmaster, is a high-grade licensed mariner who holds ultimate command and responsibility of a merchant vessel.Aragon and Messner, 2001, p.3. The captain is responsible for the safe and efficie ...
serving under Alexander the Great. In his book, 'Περὶ φυτῶν ἱστορία', or 'Enquiry into plants', Theophrastus describes a "tree with many leaves like the rose, and that this closes at night, but opens at sunrise, and by noon is completely unfolded; and at evening again it closes by degrees and remains shut at night, and the natives say that it goes to sleep." The tree mentioned by him was much later identified as the tamarind tree by the botanist, H Bretzl, in his book on the botanical findings of the Alexandrian campaigns. The observation of a circadian or diurnal process in humans is mentioned in Chinese medical texts dated to around the 13th century, including the ''Noon and Midnight Manual'' and the ''Mnemonic Rhyme to Aid in the Selection of Acu-points According to the Diurnal Cycle, the Day of the Month and the Season of the Year''. In 1729, French scientist
Jean-Jacques d'Ortous de Mairan Jean-Jacques d'Ortous de Mairan (26 November 1678 – 20 February 1771) was a French geophysicist, astronomer and most notably, chronobiologist, was born in the town of Béziers on 26 November 1678. De Mairan lost his father, François d'Ortou ...
conducted the first experiment designed to distinguish an endogenous clock from responses to daily stimuli. He noted that 24-hour patterns in the movement of the leaves of the plant '' Mimosa pudica'' persisted, even when the plants were kept in constant darkness. In 1896, Patrick and Gilbert observed that during a prolonged period of
sleep deprivation Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either chronic or acute and may vary ...
, sleepiness increases and decreases with a period of approximately 24 hours. In 1918,
J.S. Szymanski JS or js may refer to: Computing * JavaScript, a high-level, just-in-time compiled, object-oriented programming language * JScript, Microsoft's dialect of the ECMAScript standard used in Internet Explorer Businesses and organizations * Jonge Soc ...
showed that animals are capable of maintaining 24-hour activity patterns in the absence of external cues such as light and changes in temperature. In the early 20th century, circadian rhythms were noticed in the rhythmic feeding times of bees. Auguste Forel,
Ingeborg Beling Ingeborg Beling (1904-1988) was a German Ethology, ethologist from the early 20th century who worked in the field of chronobiology. She studied at the University of Munich under the direction of Karl Von Frisch and is known for her research on the ...
, and Oskar Wahl conducted numerous experiments to determine whether this rhythm was attributable to an endogenous clock. The existence of circadian rhythm was independently discovered in fruit flies in 1935 by two German zoologists,
Hans Kalmus Hans may refer to: __NOTOC__ People * Hans (name), a masculine given name * Hans Raj Hans, Indian singer and politician ** Navraj Hans, Indian singer, actor, entrepreneur, cricket player and performer, son of Hans Raj Hans ** Yuvraj Hans, Punjabi a ...
and
Erwin Bünning Erwin Bünning (23 January 1906 – 4 October 1990) was a German biologist. His most famous contributions were to the field of chronobiology, where he proposed a model for the endogenous circadian rhythms governing plant photoperiodism. From ...
. In 1954, an important experiment reported by
Colin Pittendrigh Colin Stephenson Pittendrigh (October 13, 1918 – March 19, 1996)
"Colin Pittendrigh, 'Father of biological clock,' ...
demonstrated that eclosion (the process of pupa turning into adult) in ''
Drosophila pseudoobscura ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
'' was a circadian behaviour. He demonstrated that while temperature played a vital role in eclosion rhythm, the period of eclosion was delayed but not stopped when temperature was decreased. The term ''circadian'' was coined by
Franz Halberg Franz Halberg (July 5, 1919 – June 9, 2013 ) was a scientist and one of the founders of modern chronobiology. He first began his experiments in the 1940s and later founded the Chronobiology Laboratories at the University of Minnesota. Halberg p ...
in 1959. According to Halberg's original definition: In 1977, the International Committee on Nomenclature of the
International Society for Chronobiology International is an adjective (also used as a noun) meaning "between nations". International may also refer to: Music Albums * International (Kevin Michael album), ''International'' (Kevin Michael album), 2011 * International (New Order album), ' ...
formally adopted the definition:
Ron Konopka Ronald J. Konopka (1947-2015) was an American geneticist who studied chronobiology. He made his most notable contribution to the field while working with ''Drosophila'' in the lab of Seymour Benzer at the California Institute of Technology. Durin ...
and
Seymour Benzer Seymour Benzer (October 15, 1921 – November 30, 2007) was an American physicist, molecular biologist and behavioral geneticist. His career began during the molecular biology revolution of the 1950s, and he eventually rose to prominence in the ...
identified the first clock mutation in ''Drosophila'' in 1971, naming the gene " period" (''per'') gene, the first discovered genetic determinant of behavioral rhythmicity. ''per'' gene was isolated in 1984 by two teams of researchers. Konopka, Jeffrey Hall, Michael Roshbash and their team showed that ''per'' locus is the centre of the circadian rhythm, and that loss of ''per'' stops circadian activity. At the same time, Michael W. Young's team reported similar effects of ''per'', and that the gene covers 7.1-kilobase (kb) interval on the X chromosome and encodes a 4.5-kb poly(A)+ RNA. They went on to discover the key genes and neurones in ''Drosophila'' circadian system, for which Hall, Rosbash and Young received the Nobel Prize in Physiology or Medicine 2017. Joseph Takahashi discovered the first mammalian circadian clock mutation (''clockΔ19'') using mice in 1994. However, recent studies show that deletion of ''clock'' does not lead to a behavioral phenotype (the animals still have normal circadian rhythms), which questions its importance in rhythm generation. The first human clock mutation was identified in an extended Utah family by Chris Jones, and genetically characterized by Ying-Hui Fu and Louis Ptacek. Affected individuals are extreme ' morning larks' with 4-hour advanced sleep and other rhythms. This form of familial advanced sleep phase syndrome is caused by a single amino acid change, S662➔G, in the human PER2 protein.


Criteria

To be called circadian, a biological rhythm must meet these three general criteria: # The rhythm has an endogenous free-running period that lasts approximately 24 hours. The rhythm persists in constant conditions, i.e. constant darkness, with a period of about 24 hours. The period of the rhythm in constant conditions is called the free-running period and is denoted by the Greek letter τ (tau). The rationale for this criterion is to distinguish circadian rhythms from simple responses to daily external cues. A rhythm cannot be said to be
endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...
unless it has been tested and persists in conditions without external periodic input. In diurnal animals (active during daylight hours), in general τ is slightly greater than 24 hours, whereas, in nocturnal animals (active at night), in general τ is shorter than 24 hours. # The rhythms are entrainable. The rhythm can be reset by exposure to external stimuli (such as light and heat), a process called
entrainment Entrainment may refer to: * Air entrainment, the intentional creation of tiny air bubbles in concrete * Brainwave entrainment, the practice of entraining one's brainwaves to a desired frequency * Entrainment (biomusicology), the synchronization o ...
. The external stimulus used to entrain a rhythm is called the Zeitgeber, or "time giver". Travel across time zones illustrates the ability of the human biological clock to adjust to the local time; a person will usually experience jet lag before entrainment of their circadian clock has brought it into sync with local time. # The rhythms exhibit temperature compensation. In other words, they maintain circadian periodicity over a range of physiological temperatures. Many organisms live at a broad range of temperatures, and differences in thermal energy will affect the
kinetics Kinetics ( grc, κίνησις, , kinesis, ''movement'' or ''to move'') may refer to: Science and medicine * Kinetics (physics), the study of motion and its causes ** Rigid body kinetics, the study of the motion of rigid bodies * Chemical ki ...
of all molecular processes in their . In order to keep track of time, the organism's circadian clock must maintain roughly a 24-hour periodicity despite the changing kinetics, a property known as temperature compensation. The Q10 temperature coefficient is a measure of this compensating effect. If the Q10 coefficient remains approximately 1 as temperature increases, the rhythm is considered to be temperature-compensated.


Origin

Circadian rhythms allow organisms to anticipate and prepare for precise and regular environmental changes. They thus enable organisms to make better use of environmental resources (e.g. light and food) compared to those that cannot predict such availability. It has therefore been suggested that circadian rhythms put organisms at a selective advantage in evolutionary terms. However, rhythmicity appears to be as important in regulating and coordinating ''internal'' metabolic processes, 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, as well as in creatures in constant darkness in the wild, and by the experimental elimination of behavioral—but not physiological—circadian rhythms in quail. What drove circadian rhythms to evolve has been an enigmatic question. Previous hypotheses emphasized that photosensitive proteins and circadian rhythms may have originated together in the earliest cells, with the purpose of protecting replicating DNA from high levels of damaging ultraviolet radiation during the daytime. As a result, replication was relegated to the dark. However, evidence for this is lacking: in fact the simplest organisms with a circadian rhythm, the cyanobacteria, do the opposite of this: they divide more in the daytime. Recent studies instead highlight the importance of co-evolution of redox proteins with circadian oscillators in all three domains of life following the Great Oxidation Event approximately 2.3 billion years ago. The current view is that circadian changes in environmental oxygen levels and the production of reactive oxygen species (ROS) in the presence of daylight are likely to have driven a need to evolve circadian rhythms to preempt, and therefore counteract, damaging redox reactions on a daily basis. The simplest known
circadian clock A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase (waves), phase and is synchronized with solar time. Such a clock's ''in vivo'' period is necessarily almost exactly 24 hours (the earth's curre ...
s are bacterial circadian rhythms, exemplified by the prokaryote
cyanobacteria Cyanobacteria (), also known as Cyanophyta, are a phylum of gram-negative bacteria that obtain energy via photosynthesis. The name ''cyanobacteria'' refers to their color (), which similarly forms the basis of cyanobacteria's common name, blu ...
. Recent research has demonstrated that the circadian clock of ''
Synechococcus elongatus ''Synechococcus elongatus'' is a unicellular cyanobacterium that has a rapid autotrophic growth comparable to yeast. Its ability to grow rapidly using sunlight has implications for biotechnological applications, especially when incorporating gene ...
'' can be reconstituted ''in vitro'' with just the three proteins ( KaiA, KaiB,
KaiC KaiC is a gene belonging to the KaiABC gene cluster (with KaiA, and KaiB) that, together, regulate bacterial circadian rhythms, specifically in cyanobacteria. KaiC encodes for the KaiC protein, which interacts with the KaiA and KaiB proteins in ...
) of their central oscillator. This clock has been shown to sustain a 22-hour rhythm over several days upon the addition of
ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals, men's professional tennis governing body * American Technical Publishers, employee-owned publishing company * ', a Danish pension * Armenia Tree Project, non ...
. Previous explanations of the prokaryotic circadian timekeeper were dependent upon a DNA transcription/translation feedback mechanism. A defect in the human homologue of the '' Drosophila'' " period" gene was identified as a cause of the sleep disorder FASPS ( Familial advanced sleep phase syndrome), underscoring the conserved nature of the molecular circadian clock through evolution. Many more genetic components of the biological clock are now known. 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. It is now known that the molecular circadian clock can function within a single cell. That is, it is cell-autonomous. This was shown by
Gene Block Gene David Block (born August 17, 1948) is an American biologist who has served as the current and 6th chancellor of the University of California, Los Angeles since August 2007. Block has served as provost and professor of biology at the Univer ...
in isolated mollusk basal retinal neurons (BRNs). At the same time, different cells may communicate with each other resulting in a synchronised 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 synchronise the peripheral clocks of various organs. Thus, the information of the time of the day as relayed by the
eye Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...
s travels to the clock in the brain, and, through that, clocks in the rest of the body may be synchronised. 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 rhythmicity is present in the sleeping and feeding patterns of animals, including human beings. There are also clear patterns of core body temperature,
brain wave ''Brain Wave'' is a science fiction novel by American writer Poul Anderson, first published in serial form in ''Space Science Fiction'' in 1953, and then as a novel in 1954. Anderson had said that he could consider it one of his top five books. Th ...
activity, hormone production, cell regeneration, and other biological activities. 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 day length. 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 (day length) is the most predictive environmental cue for the seasonal timing of physiology and behavior, most notably for timing of migration, hibernation, and reproduction.


Effect of circadian disruption

Mutations or deletions of clock genes in mice have demonstrated the importance of body clocks to ensure the proper timing of cellular/metabolic events; clock-mutant mice are
hyperphagic Polyphagia or hyperphagia is an abnormally strong, incessant sensation of hunger or desire to eat often leading to overeating. In contrast to an increase in appetite following exercise, polyphagia does not subside after eating and often leads to ...
and obese, and have altered glucose metabolism. In mice, deletion of the Rev-ErbA alpha clock gene can result in diet-induced obesity and changes the balance between glucose and lipid utilization, predisposing to diabetes. However, it is not clear whether there is a strong association between clock gene polymorphisms in humans and the susceptibility to develop the metabolic syndrome.


Effect 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 rhythm. Their sleep cycle is pushed back or forward each "day", depending on whether their "day", their
endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...
period, is shorter or longer than 24 hours. The environmental cues that reset the rhythms each day are called zeitgebers (from the German, "time-givers"). Totally blind subterranean mammals (e.g.,
blind mole rat The blind mole-rats, also known as the fossorial or subterranean mole rats, are a subfamily (Spalacinae) of rodents in the family Spalacidae, found in eastern Europe and western & central Asia. The hystricognath mole-rats of the family Bathyergi ...
''Spalax'' sp.) are able to maintain their endogenous clocks in the apparent absence of external stimuli. Although they lack image-forming eyes, their photoreceptors (which detect light) are still functional; they do surface periodically as well. Free-running organisms that normally have one or two consolidated sleep episodes will still have them when in an environment shielded from external cues, but the rhythm is 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 In chronobiology, an ultradian rhythm is a recurrent period or cycle repeated throughout a 24-hour day. In contrast, circadian rhythms complete one cycle daily, while infradian rhythms such as the human menstrual cycle have periods longer than a ...
rhythms such as metabolic, hormonal, CNS electrical, or neurotransmitter rhythms. Recent research has influenced the design of spacecraft environments, as systems that mimic the light–dark cycle have been found to be highly beneficial to astronauts. Light therapy has been trialed as a treatment for sleep disorders.


Arctic animals

Norwegian researchers at the University of Tromsø have shown that some Arctic animals (e.g., 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 on
Svalbard Svalbard ( , ), also known as Spitsbergen, or Spitzbergen, is a Norwegian archipelago in the Arctic Ocean. North of mainland Europe, it is about midway between the northern coast of Norway and the North Pole. The islands of the group range ...
at 78 degrees North showed such rhythms only in 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. A 2006 study in northern Alaska found that day-living ground squirrels and nocturnal
porcupine Porcupines are large rodents with coats of sharp spines, or quills, that protect them against predation. The term covers two families of animals: the Old World porcupines of family Hystricidae, and the New World porcupines of family, Erethizont ...
s strictly maintain their circadian rhythms through 82 days and nights of sunshine. The researchers speculate that these two rodents notice that the apparent distance between the sun and the horizon is shortest once a day, and thus have a sufficient signal to entrain (adjust) by.


Butterfly and moth

The navigation of the fall migration of the Eastern North American monarch butterfly (''Danaus plexippus'') to their overwintering grounds in central Mexico uses a time-compensated sun compass that depends upon a circadian clock in their antennae. Circadian rhythm is also known to control mating behavior in certain moth species such as '' Spodoptera littoralis'', where females produce specific pheromone that attracts and resets the male circadian rhythm to induce mating at night.


In plants

Plant circadian rhythms tell the plant what season it is and when to flower for the best chance of attracting pollinators. Behaviors showing rhythms include leaf movement, growth, germination, stomatal/gas exchange, enzyme activity, photosynthetic activity, and fragrance emission, among others. Circadian rhythms occur as a plant entrains to synchronize with the light cycle of its surrounding environment. These rhythms are endogenously generated, self-sustaining and are relatively constant over a range of ambient temperatures. Important features include two interacting transcription-translation feedback loops: proteins containing PAS domains, which facilitate protein-protein interactions; and several photoreceptors that fine-tune the clock to different light conditions. Anticipation of changes in the environment allows appropriate changes in a plant's physiological state, conferring an adaptive advantage. A better understanding of plant circadian rhythms has applications in agriculture, such as helping farmers stagger crop harvests to extend crop availability and securing against massive losses due to weather. Light is the signal by which plants synchronize their internal clocks to their environment and is sensed by a wide variety of photoreceptors. Red and blue light are absorbed through several phytochromes and cryptochromes. One phytochrome, phyA, is the main phytochrome in seedlings grown in the dark but rapidly degrades in light to produce Cry1. Phytochromes B–E are more stable with , the main phytochrome in seedlings grown in the light. The cryptochrome (cry) gene is also a light-sensitive component of the circadian clock and is thought to be involved both as a photoreceptor and as part of the clock's endogenous pacemaker mechanism. Cryptochromes 1–2 (involved in blue–UVA) help to maintain the period length in the clock through a whole range of light conditions. The central oscillator generates a self-sustaining rhythm and is driven by two interacting feedback loops that are active at different times of day. The morning loop consists of CCA1 (Circadian and Clock-Associated 1) and LHY (Late Elongated Hypocotyl), which encode closely related MYB transcription factors that regulate circadian rhythms in ''Arabidopsis'', as well as PRR 7 and 9 (Pseudo-Response Regulators.) The evening loop consists of GI (Gigantea) and ELF4, both involved in regulation of flowering time genes. When CCA1 and LHY are overexpressed (under constant light or dark conditions), plants become arrhythmic, and mRNA signals reduce, contributing to a negative feedback loop. Gene expression of CCA1 and LHY oscillates and peaks in the early morning, whereas TOC1 gene expression oscillates and peaks in the early evening. While it was previously hypothesised that these three genes model a negative feedback loop in which over-expressed CCA1 and LHY repress TOC1 and over-expressed TOC1 is a positive regulator of CCA1 and LHY, it was shown in 2012 by Andrew Millar and others that TOC1, in fact, serves as a repressor not only of CCA1, LHY, and PRR7 and 9 in the morning loop but also of GI and ELF4 in the evening loop. This finding and further computational modeling of TOC1 gene functions and interactions suggest a reframing of the plant circadian clock as a triple negative-component
repressilator The repressilator is a genetic regulatory network consisting of at least one feedback loop with at least three genes, each expressing a protein that represses the next gene in the loop. In biological research, repressilators have been used to build ...
model rather than the positive/negative-element feedback loop characterizing the clock in mammals. In 2018, researchers found that the expression of PRR5 and TOC1 hnRNA nascent transcripts follows the same oscillatory pattern as processed mRNA transcripts rhythmically in A.thaliana.LNKs binds to the 5'region of PRR5 and TOC1 and interacts with RNAP II and other transcription factors. Moreover, RVE8-LNKs interaction enables a permissive histone-methylation pattern (H3K4me3) to be modified and the histone-modification itself parallels the oscillation of clock gene expression. It has previously been found that matching a plant's circadian rhythm to its external environment's light and dark cycles has the potential to positively affect the plant. Researchers came to this conclusion by performing experiments on three different varieties of ''
Arabidopsis thaliana ''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant native to Eurasia and Africa. ''A. thaliana'' is considered a weed; it is found along the shoulders of roads and in disturbed land. A winter a ...
''. One of these varieties had a normal 24-hour circadian cycle. The other two varieties were mutated, one to have a circadian cycle of more than 27 hours, and one to have a shorter than normal circadian cycle of 20 hours. The ''Arabidopsis'' with the 24-hour circadian cycle was grown in three different environments. One of these environments had a 20-hour light and dark cycle (10 hours of light and 10 hours of dark), the other had a 24-hour light and dark cycle (12 hours of light and 12 hours of dark),and the final environment had a 28-hour light and dark cycle (14 hours of light and 14 hours of dark). The two mutated plants were grown in both an environment that had a 20-hour light and dark cycle and in an environment that had a 28-hour light and dark cycle. It was found that the variety of ''Arabidopsis'' with a 24-hour circadian rhythm cycle grew best in an environment that also had a 24-hour light and dark cycle. Overall, it was found that all the varieties of ''Arabidopsis thaliana'' had greater levels of
chlorophyll Chlorophyll (also chlorophyl) is any of several related green pigments found in cyanobacteria and in the chloroplasts of algae and plants. Its name is derived from the Greek words , ("pale green") and , ("leaf"). Chlorophyll allow plants to a ...
and increased growth in environments whose light and dark cycles matched their circadian rhythm. Researchers suggested that a reason for this could be that matching an ''Arabidopsis'' circadian rhythm to its environment could allow the plant to be better prepared for dawn and dusk, and thus be able to better synchronize its processes. In this study, it was also found that the genes that help to control chlorophyll peaked a few hours after dawn. This appears to be consistent with the proposed phenomenon known as metabolic dawn. According to the metabolic dawn hypothesis, sugars produced by photosynthesis have potential to help regulate the circadian rhythm and certain photosynthetic and metabolic pathways. As the sun rises, more light becomes available, which normally allows more photosynthesis to occur. The sugars produced by photosynthesis repress PRR7. This repression of PRR7 then leads to the increased expression of CCA1. On the other hand, decreased photosynthetic sugar levels increase PRR7 expression and decrease CCA1 expression. This feedback loop between CCA1 and PRR7 is what is proposed to cause metabolic dawn.


In ''Drosophila''

The molecular mechanism of circadian rhythm and light perception are best understood in ''Drosophila''. Clock genes are discovered from ''Drosophila'', and they act together with the clock neurones. There are two unique rhythms, one during the process of hatching (called eclosion) from the pupa, and the other during mating. The clock neurones are located in distinct clusters in the central brain. The best-understood clock neurones are the large and small lateral ventral neurons (l-LNvs and s-LNvs) of the optic lobe. These neurones produce pigment dispersing factor (PDF), a neuropeptide that acts as a circadian neuromodulator between different clock neurones. ''Drosophila'' circadian rhythm is through a transcription-translation feedback loop. The core clock mechanism consists of two interdependent feedback loops, namely the PER/TIM loop and the CLK/CYC loop. The CLK/CYC loop occurs during the day and initiates the transcription of the ''per'' and ''tim'' genes. But their proteins levels remain low until dusk, because during daylight also activates the ''doubletime'' (''dbt'') gene. DBT protein causes phosphorylation and turnover of monomeric PER proteins. TIM is also phosphorylated by shaggy until sunset. After sunset, DBT disappears, so that PER molecules stably bind to TIM. PER/TIM dimer enters the nucleus several at night, and binds to CLK/CYC dimers. Bound PER completely stops the transcriptional activity of CLK and CYC. In the early morning, light activates the ''cry'' gene and its protein CRY causes the breakdown of TIM. Thus PER/TIM dimer dissociates, and the unbound PER becomes unstable. PER undergoes progressive phosphorylation and ultimately degradation. Absence of PER and TIM allows activation of ''clk'' and ''cyc'' genes. Thus, the clock is reset to start the next circadian cycle.


PER-TIM model

This protein model was developed based on the oscillations of the PER and TIM proteins in the ''Drosophila''. It is based on its predecessor, the PER model where it was explained how the PER gene and its protein influence the biological clock. The model includes the formation of a nuclear PER-TIM complex which influences the transcription of the PER and the TIM genes (by providing negative feedback) and the multiple phosphorylation of these two proteins. The circadian oscillations of these two proteins seem to synchronise with the light-dark cycle even if they are not necessarily dependent on it. Both PER and TIM proteins are phosphorylated and after they form the PER-TIM nuclear complex they return inside the nucleus to stop the expression of the PER and TIM mRNA. This inhibition lasts as long as the protein, or the mRNA is not degraded. When this happens, the complex releases the inhibition. Here can also be mentioned that the degradation of the TIM protein is sped up by light.


In mammals

The primary
circadian clock A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase (waves), phase and is synchronized with solar time. Such a clock's ''in vivo'' period is necessarily almost exactly 24 hours (the earth's curre ...
in
mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
s is located in the
suprachiasmatic nucleus The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regula ...
(or nuclei) (SCN), a pair of distinct groups of
cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
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 eye contains "classical" photoreceptors (" rods" and " cones"), which are used for conventional vision. But the retina also contains specialized ganglion cells that are directly photosensitive, and project directly to the SCN, where they help in the entrainment (synchronization) of this master circadian clock. The proteins involved in the SCN clock are homologous to those found in the fruit fly. These cells contain the photopigment
melanopsin Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene ''Opn4''. In the mammalian retina, there are two additional categories of opsins, both involved in the for ...
and their signals 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. The SCN takes the information on the lengths of the day and night from the retina, interprets it, and passes it on to the
pineal gland The pineal gland, conarium, or epiphysis cerebri, is a small endocrine gland in the brain of most vertebrates. The pineal gland produces melatonin, a serotonin-derived hormone which modulates sleep, sleep patterns in both circadian rhythm, circ ...
, a tiny structure shaped like a pine cone and located on the epithalamus. In response, the pineal secretes the hormone
melatonin Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle. In vertebrates ...
. Secretion of melatonin peaks at night and ebbs during the day and its presence provides information about night-length. Several studies have indicated that pineal melatonin feeds back on SCN rhythmicity to modulate circadian patterns of activity and other processes. However, the nature and system-level significance of this feedback are unknown. The circadian rhythms of humans can be entrained to slightly shorter and longer periods than the Earth's 24 hours. Researchers at Harvard have shown that human subjects can at least be entrained to a 23.5-hour cycle and a 24.65-hour cycle.


Humans

Early research into circadian rhythms suggested that most people preferred a day closer to 25 hours when isolated from external stimuli like daylight and timekeeping. However, this research was faulty because it failed to shield the participants from artificial light. Although subjects were shielded from time cues (like clocks) and daylight, the researchers were not aware of the phase-delaying 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. A more stringent study conducted in 1999 by Harvard University estimated the natural human rhythm to be closer to 24 hours and 11 minutes: much closer to the solar day. Consistent with this research was a more recent study from 2010, which also identified sex differences, with the circadian period for women being slightly shorter (24.09 hours) than for men (24.19 hours). In this study, women tended to wake up earlier than men and exhibit a greater preference for morning activities than men, although the underlying biological mechanisms for these differences are unknown.


Biological markers and effects

The classic phase markers for measuring the timing of a mammal's circadian rhythm are: *
melatonin Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle. In vertebrates ...
secretion by the
pineal gland The pineal gland, conarium, or epiphysis cerebri, is a small endocrine gland in the brain of most vertebrates. The pineal gland produces melatonin, a serotonin-derived hormone which modulates sleep, sleep patterns in both circadian rhythm, circ ...
, *
core body temperature Normal human body-temperature (normothermia, euthermia) is the typical temperature range found in humans. The normal human body temperature range is typically stated as . Human body temperature varies. It depends on sex, age, time of day, exert ...
minimum, and * plasma level of
cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
. For temperature studies, subjects must remain awake but calm and semi-reclined in near darkness while their rectal temperatures are taken continuously. Though variation is great among normal chronotypes, the average human adult's temperature reaches its minimum at about 5:00 a.m., about two hours before habitual wake time. Baehr et al. found that, in young adults, the daily body temperature minimum occurred at about 04:00 (4 a.m.) for morning types, but at about 06:00 (6 a.m.) for evening types. This minimum occurred at approximately the middle of the eight-hour sleep period for morning types, but closer to waking in evening types. Melatonin is absent from the system or undetectably low during daytime. Its onset in dim light, ''dim-light melatonin onset'' (DLMO), at roughly 21:00 (9 p.m.) can be measured in the blood or the saliva. Its major
metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
can also be measured in morning urine. 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 more reliable marker. Benloucif et al. 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 are more strongly correlated with phase markers than the onset of sleep. In addition, the declining phase of the melatonin levels is more reliable and stable than the termination of melatonin synthesis. Other physiological changes that occur according to a circadian rhythm include heart rate and many cellular processes "including oxidative stress,
cell metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
, immune and inflammatory responses,
epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
modification,
hypoxia Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the tis ...
/ hyperoxia response pathways, endoplasmic reticular stress,
autophagy Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
, and regulation of the
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
environment." In a study of young men, it was found that the heart rate reaches its lowest average rate during sleep, and its highest average rate shortly after waking. In contradiction to previous studies, it has been found that there is no effect of body temperature on performance on psychological tests. This is likely due to evolutionary pressures for higher cognitive function compared to the other areas of function examined in previous studies.


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". Indeed, neuroscientist Joseph Takahashi and colleagues stated in a 2013 article that "almost every cell in the body contains a circadian clock." For example, these clocks, called peripheral oscillators, have been found in the adrenal gland, oesophagus, lungs, liver, pancreas, spleen, thymus, and skin. There is also some evidence that the olfactory bulb and prostate may experience oscillations, at least when cultured. Though oscillators in the skin respond to light, a systemic influence has not been proven. In addition, many oscillators, such as liver cells, for example, have been shown to respond to inputs other than light, such as feeding.


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, and lower light levels are required to reset the clocks in
nocturnal Nocturnality is an animal behavior characterized by being active during the night and sleeping during the day. The common adjective is "nocturnal", versus diurnal meaning the opposite. Nocturnal creatures generally have highly developed sens ...
rodents than in humans.


Enforced longer or shorter cycles

Various studies on humans have made use of enforced sleep/wake cycles strongly different from 24 hours, such as those conducted by
Nathaniel Kleitman Nathaniel Kleitman (April 26, 1895 – August 13, 1999) was an American physiologist and sleep researcher who served as Professor Emeritus in Physiology at the University of Chicago. He is recognized as the father of modern sleep research, an ...
in 1938 (28 hours) and
Derk-Jan Dijk Derk-Jan Dijk (born 1958 in Zwollerkerspel, Netherlands) is a researcher of sleep and circadian rhythms. As of 2005 he is a Distinguished Professor at the University of Surrey and the director of its Sleep Research Centre. Education and early ...
and Charles Czeisler in the 1990s (20 hours). Because people with a normal (typical)
circadian clock A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase (waves), phase and is synchronized with solar time. Such a clock's ''in vivo'' period is necessarily almost exactly 24 hours (the earth's curre ...
cannot entrain to such abnormal day/night rhythms, this is referred to as a forced desynchrony protocol. Under such a protocol, sleep and wake episodes are uncoupled from the body's endogenous circadian period, which allows researchers to assess the effects of circadian phase (i.e., the relative timing of the circadian cycle) on aspects of sleep and wakefulness including sleep latency and other functions - both physiological, behavioral, and cognitive. Studies also show that '' Cyclosa turbinata'' is unique in that its locomotor and web-building activity cause it to have an exceptionally short-period circadian clock, about 19 hours. When ''C. turbinata'' spiders are placed into chambers with periods of 19, 24, or 29 hours of evenly split light and dark, none of the spiders exhibited decreased longevity in their own circadian clock. These findings suggest that ''C. turbinata'' do not have the same costs of extreme desynchronization as do other species of animals.


Human health


Foundation of circadian medicine

The leading edge of circadian biology research is translation of basic body clock mechanisms into clinical tools, and this is especially relevant to the treatment of cardiovascular disease. This is leading to the development of an entirely new field of medicine, termed Circadian Medicine. Pioneering research reveals that Circadian Medicine can lead to longer and healthier lives. For example: 1) "Circadian Lighting" or reducing adverse light at night in hospitals may improve patient outcomes post-myocardial infarction (heart attack). 2) "Circadian Chronotherapy" or timing of medications can reduce adverse cardiac remodeling in patients with heart disease. Timing of medical treatment in coordination with the body clock, chronotherapeutics, may also benefit patients with hypertension (high blood pressure) by significantly increasing efficacy and reduce drug toxicity or adverse reactions. 3) "Circadian Pharmacology" or drugs targeting the circadian clock mechanism have been shown experimentally in rodent models to significantly reduce the damage due to heart attacks and prevent heart failure. Importantly, for rational translation of the most promising Circadian Medicine therapies to clinical practice, it is imperative that we understand how it helps treats disease in both biological sexes.


Relationship with cardiovascular disease

One of the first studies to determine how disruption of circadian rhythms causes cardiovascular disease was performed in the Tau hamsters, which have a genetic defect in their circadian clock mechanism. When maintained in a 24-hour light-dark cycle that was "out of sync" with their normal 22 circadian mechanism they developed profound cardiovascular and renal disease; however, when the Tau animals were raised for their entire lifespan on a 22-hour daily light-dark cycle they had a healthy cardiovascular system. The adverse effects of circadian misalignment on human physiology has been studied in the laboratory using a misalignment protocol, and by studying shift workers.


Circadian desynchrony

Subsequent studies have shown that maintaining normal sleep and circadian rhythms is important for many aspects of brain and health. A number of studies have also indicated that a
power-nap A power nap or cat nap is a short sleep that terminates before deep sleep (slow-wave sleep; SWS). A power nap is intended to quickly revitalize the sleeper. Cornell University social psychologist James Maas coined the term. A power nap combine ...
, a short period of sleep during the day, can reduce stress and may improve productivity without any measurable effect on normal circadian rhythms. Circadian rhythms also play a part in the
reticular activating system The reticular formation is a set of interconnected nuclei that are located throughout the brainstem. It is not anatomically well defined, because it includes neurons located in different parts of the brain. The neurons of the reticular formatio ...
, which is crucial for maintaining a state of consciousness. A reversal in the sleep–wake cycle may be a sign or complication of uremia, azotemia or acute kidney injury. Studies have also helped elucidate how light has a direct effect on human health through its influence on the circadian biology.


Indoor lighting

Lighting requirements for circadian regulation are not simply the same as those for vision; planning of indoor lighting in offices and institutions is beginning to take this into account. Animal studies on the effects of light in laboratory conditions have until recently considered light intensity (
irradiance In radiometry, irradiance is the radiant flux ''received'' by a ''surface'' per unit area. The SI unit of irradiance is the watt per square metre (W⋅m−2). The CGS unit erg per square centimetre per second (erg⋅cm−2⋅s−1) is often used ...
) but not color, which can be shown to "act as an essential regulator of biological timing in more natural settings".


Obesity and diabetes

Obesity and diabetes are associated with lifestyle and genetic factors. Among those factors, disruption of the circadian clockwork and/or misalignment of the circadian timing system with the external environment (e.g., light–dark cycle) might play a role in the development of metabolic disorders. Shift work or chronic jet lag have profound consequences for circadian and metabolic events in the body. Animals that are forced to eat during their resting period show increased body mass and altered expression of clock and metabolic genes. In humans, shift work that favors irregular eating times is associated with altered insulin sensitivity and higher body mass. Shift work also leads to increased metabolic risks for cardio-metabolic syndrome,
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, and inflammation.


Airline pilots and cabin crew

Due to the work nature of airline pilots, who often cross several time zones and regions of sunlight and darkness in one day, and spend many hours awake both day and night, they are often unable to maintain sleep patterns that correspond to the natural human circadian rhythm; this situation can easily lead to
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
. The NTSB cites this as contributing to many accidents, and has conducted several research studies in order to find methods of combating fatigue in pilots.


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 Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
,
disorientation Orientation is a function of the mind involving awareness of three dimensions: time, Location (geography), place and person. Problems with orientation lead to ''dis''orientation, and can be due to various conditions, from delirium to Substance int ...
and insomnia. A number of other disorders, such as bipolar disorder and some sleep disorders such as delayed sleep phase disorder (DSPD), are associated with irregular or pathological functioning of circadian rhythms. Disruption to rhythms in the longer term is believed to have significant adverse health consequences for peripheral organs outside the brain, in particular in the development or exacerbation of cardiovascular disease. Blue LED lighting suppresses melatonin production five times more than the orange-yellow high-pressure sodium (HPS) light; a metal halide lamp, which is white light, suppresses melatonin at a rate more than three times greater than HPS. Depression symptoms from long term nighttime light exposure can be undone by returning to a normal cycle.


Effect of drugs

Studies conducted on both animals and humans show major bidirectional relationships between the circadian system and abusive drugs. It is indicated that these abusive drugs affect the central circadian pacemaker. Individuals with substance use disorder display disrupted rhythms. These disrupted rhythms can increase the risk for substance abuse and relapse. It is possible that genetic and/or environmental disturbances to the normal sleep and wake cycle can increase the susceptibility to addiction. It is difficult to determine if a disturbance in the circadian rhythm is at fault for an increase in prevalence for substance abuse—or if other environmental factors such as stress are to blame. Changes to the circadian rhythm and sleep occur once an individual begins abusing drugs and alcohol. Once an individual chooses to stop using drugs and alcohol, the circadian rhythm continues to be disrupted. The stabilization of sleep and the circadian rhythm might possibly help to reduce the vulnerability to addiction and reduce the chances of relapse. Circadian rhythms and clock genes expressed in brain regions outside the
suprachiasmatic nucleus The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regula ...
may significantly influence the effects produced by drugs such as cocaine. Moreover, genetic manipulations of clock genes profoundly affect cocaine's actions.


Society and culture

In 2017,
Jeffrey C. Hall Jeffrey Connor Hall (born May 3, 1945) is an American geneticist and Chronobiology, chronobiologist. Hall is Professor Emeritus of Biology at Brandeis University and currently resides in Cambridge, Maine. Hall spent his career examining the neu ...
,
Michael W. Young Michael Warren Young (born March 28, 1949) is an American biologist and geneticist. He has dedicated over three decades to research studying genetically controlled patterns of sleep and wakefulness within ''Drosophila melanogaster''. At Rock ...
, and Michael Rosbash were awarded Nobel Prize in Physiology or Medicine "for their discoveries of molecular mechanisms controlling the circadian rhythm". Circadian rhythms was taken as an example of scientific knowledge being transferred into the public sphere.


See also

*
Actigraphy Actigraphy is a non-invasive method of monitoring human rest/activity cycles. A small actigraph unit, also called an actimetry sensor, is worn for a week or more to measure gross motor activity. The unit is usually in a wristwatch-like package wo ...
(also known as actimetry) * ARNTL * ARNTL2 * Bacterial circadian rhythms *
Circadian rhythm sleep disorders Circadian rhythm sleep disorders (CRSD), also known as circadian rhythm sleep-wake disorders (CRSWD), are a family of sleep disorders which affect the timing of sleep. CRSDs arise from a persistent pattern of sleep/wake disturbances that can be ...
, such as ** Advanced sleep phase disorder ** Delayed sleep phase disorder ** Non-24-hour sleep–wake disorder * Chronobiology * CLOCK * Circasemidian rhythm * Circaseptan, 7-day biological cycle * Cryptochrome *
CRY1 Cryptochromes (from the Greek κρυπτός χρώμα, "hidden colour") are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields i ...
and CRY2: the cryptochrome family genes *
Diurnal cycle A diurnal cycle (or diel cycle) is any pattern that recurs every 24 hours as a result of one full rotation of the planet Earth around its axis. Earth's rotation causes surface temperature fluctuations throughout the day and night, as well as w ...
*
Light effects on circadian rhythm Light effects on circadian rhythm are the effects that light has on circadian rhythm. Most animals and other organisms have "built-in clocks" in their brains that regulate the timing of biological processes and daily behavior. These "clocks" are ...
*
Light in school buildings Light in school buildings traditionally is from a combination of daylight and electric light to illuminate learning spaces (e.g. classrooms, labs, studios, etc.), hallways, cafeterias, offices and other interior areas. Light fixtures currently in us ...
* PER1, PER2, and PER3: the period family genes * Photosensitive ganglion cell: part of the eye which is involved in regulating circadian rhythm. *
Polyphasic sleep Biphasic sleep (or ''diphasic'', ''bifurcated'', or bimodal sleep) is the practice of sleeping during two periods over the course of 24 hours, while polyphasic sleep refers to sleeping multiple times—usually more than two. Each of these is in ...
* Rev-ErbA alpha *
Segmented sleep Biphasic sleep (or ''diphasic'', ''bifurcated'', or bimodal sleep) is the practice of sleeping during two periods over the course of 24 hours, while polyphasic sleep refers to sleeping multiple times—usually more than two. Each of these is in ...
*
Sleep architecture Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefulness by a d ...
(sleep in humans) *
Sleep in non-human animals Sleep in animals refers to a behavioral and physiological state characterized by altered consciousness, reduced responsiveness to external stimuli, and homeostatic regulation observed in various animals. Sleep has been observed in mammals, birds, ...
*
Stefania Follini Stefania Follini (born 16 August 1961) is an Italian interior designer. She is known for being involved in a 1989 experiment on circadian rhythms, in which she voluntarily isolated herself for four months in an underground room thirty feet down a ...
*
Ultradian rhythm In chronobiology, an ultradian rhythm is a recurrent period or cycle repeated throughout a 24-hour day. In contrast, circadian rhythms complete one cycle daily, while infradian rhythms such as the human menstrual cycle have periods longer than a ...


References


Further reading

* * * * * * * * * * * * *


External links

* {{DEFAULTSORT:Circadian Rhythm Sleep Biology of bipolar disorder Plant cognition