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Biological Clocks
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Biological Clocks

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (31 August 2018) | Viewed by 107549

Special Issue Editor

Prof. Dr. Russell Foster

E-Mail Website
Guest Editor
Sleep & Circadian Neuroscience Institute (SCNi), Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, OMPI, Sir William Dunn School of Pathology University of Oxford, Oxford, UK
Interests: circadian rhythms; sleep; photoreceptor biology; circadian entrainment; sleep disruption; neuroscience

Special Issue Information

Dear Colleagues,

There have been over a trillion dawns and dusks since life began some 3.8 billion years ago. During that time the earth’s daily rotation has slowed to a shade less than 24 hours. This predictable daily solar cycle results in regular and profound changes in environmental light, temperature and food availability. Almost all life on earth, including humans, employs an internal biological timer to anticipate these daily changes. The possession of some form of clock permits organisms to optimise physiology and behaviour in advance of the varied demands of the day/night cycle. Organisms effectively ‘know’ the time of day. Such internally generated daily rhythms are called “circadian rhythms” from the Latin circa (about) and dies (day). Despite the diversity of life on our planet there are many similarities in the way in which circadian rhythms are generated and synchronised to the solar cycle. There is a molecular feedback loop – the transcription-translation feedback loop (TTFL) – that underpins all these processes, and our understanding of this molecular clockwork provides the best example to date of how genes and their protein products interact to generate complex behaviour. The TTFL is invariably set or “entrained” to the solar day by specialized photoreceptors that detect the changes in environmental light. This special issue will explain how circadian rhythms are generated and regulated across the diversity of life on earth, why these rhythms are important in regulating physiology and behavior and what happens when these rhythms break-down in humans under conditions of disease and/or imposed environmental disruption such as shift-work and 24/7 life-styles.

Prof. Dr. Russell Foster
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Circadian
  • Biological Clocks
  • Clock Genes
  • Photoreceptors
  • Entrainment
  • Life on Earth
  • Evolution
  • Human Health
  • Shift-Work
  • 24/7 Life Styles

Published Papers (11 papers)

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Research

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17 pages, 4366 KiB  
Article
Norpa Signalling and the Seasonal Circadian Locomotor Phenotype in Drosophila
by Carlo Breda, Ezio Rosato and Charalambos P. Kyriacou
Biology 2020, 9(6), 130; https://doi.org/10.3390/biology9060130 - 16 Jun 2020
Cited by 3 | Viewed by 3758
Abstract
In this paper, we review the role of the norpA-encoded phospholipase C in light and thermal entrainment of the circadian clock in Drosophila melanogaster. We extend our discussion to the role of norpA in the thermo-sensitive splicing of the per 3′ UTR [...] Read more.
In this paper, we review the role of the norpA-encoded phospholipase C in light and thermal entrainment of the circadian clock in Drosophila melanogaster. We extend our discussion to the role of norpA in the thermo-sensitive splicing of the per 3′ UTR, which has significant implications for seasonal adaptations of circadian behaviour. We use the norpA mutant-generated enhancement of per splicing and the corresponding advance that it produces in the morning (M) and evening (E) locomotor component to dissect out the neurons that are contributing to this norpA phenotype using GAL4/UAS. We initially confirmed, by immunocytochemistry and in situ hybridisation in adult brains, that norpA expression is mostly concentrated in the eyes, but we were unable to unequivocally reveal norpA expression in the canonical clock cells using these methods. In larval brains, we did see some evidence for co-expression of NORPA with PDF in clock neurons. Nevertheless, downregulation of norpA in clock neurons did generate behavioural advances in adults, with the eyes playing a significant role in the norpA seasonal phenotype at high temperatures, whereas the more dorsally located CRYPTOCHROME-positive clock neurons are the likely candidates for generating the norpA behavioural effects in the cold. We further show that knockdown of the related plc21C encoded phospholipase in clock neurons does not alter per splicing nor generate any of the behavioural advances seen with norpA. Our results with downregulating norpA and plc21C implicate the rhodopsins Rh2/Rh3/Rh4 in the eyes as mediating per 3′ UTR splicing at higher temperatures and indicate that the CRY-positive LNds, also known as ‘evening’ cells are likely mediating the low-temperature seasonal effects on behaviour via altering per 3′UTR splicing. Full article
(This article belongs to the Special Issue Biological Clocks)
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Review

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45 pages, 3962 KiB  
Review
Circadian Photoentrainment in Mice and Humans
by Russell G. Foster, Steven Hughes and Stuart N. Peirson
Biology 2020, 9(7), 180; https://doi.org/10.3390/biology9070180 - 21 Jul 2020
Cited by 77 | Viewed by 7818
Abstract
Light around twilight provides the primary entrainment signal for circadian rhythms. Here we review the mechanisms and responses of the mouse and human circadian systems to light. Both utilize a network of photosensitive retinal ganglion cells (pRGCs) expressing the photopigment melanopsin (OPN4). In [...] Read more.
Light around twilight provides the primary entrainment signal for circadian rhythms. Here we review the mechanisms and responses of the mouse and human circadian systems to light. Both utilize a network of photosensitive retinal ganglion cells (pRGCs) expressing the photopigment melanopsin (OPN4). In both species action spectra and functional expression of OPN4 in vitro show that melanopsin has a λmax close to 480 nm. Anatomical findings demonstrate that there are multiple pRGC sub-types, with some evidence in mice, but little in humans, regarding their roles in regulating physiology and behavior. Studies in mice, non-human primates and humans, show that rods and cones project to and can modulate the light responses of pRGCs. Such an integration of signals enables the rods to detect dim light, the cones to detect higher light intensities and the integration of intermittent light exposure, whilst melanopsin measures bright light over extended periods of time. Although photoreceptor mechanisms are similar, sensitivity thresholds differ markedly between mice and humans. Mice can entrain to light at approximately 1 lux for a few minutes, whilst humans require light at high irradiance (>100’s lux) and of a long duration (>30 min). The basis for this difference remains unclear. As our retinal light exposure is highly dynamic, and because photoreceptor interactions are complex and difficult to model, attempts to develop evidence-based lighting to enhance human circadian entrainment are very challenging. A way forward will be to define human circadian responses to artificial and natural light in the “real world” where light intensity, duration, spectral quality, time of day, light history and age can each be assessed. Full article
(This article belongs to the Special Issue Biological Clocks)
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14 pages, 1357 KiB  
Review
Circadian Clock Regulation of Hepatic Energy Metabolism Regulatory Circuits
by Ann Louise Hunter and David W. Ray
Biology 2019, 8(4), 79; https://doi.org/10.3390/biology8040079 - 19 Oct 2019
Cited by 3 | Viewed by 4954
Abstract
The liver is a critical organ of energy metabolism. At least 10% of the liver transcriptome demonstrates rhythmic expression, implying that the circadian clock regulates large programmes of hepatic genes. Here, we review the mechanisms by which this rhythmic regulation is conferred, with [...] Read more.
The liver is a critical organ of energy metabolism. At least 10% of the liver transcriptome demonstrates rhythmic expression, implying that the circadian clock regulates large programmes of hepatic genes. Here, we review the mechanisms by which this rhythmic regulation is conferred, with a particular focus on the transcription factors whose actions combine to impart liver- and time-specificity to metabolic gene expression. Full article
(This article belongs to the Special Issue Biological Clocks)
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19 pages, 1041 KiB  
Review
Chronotype and Social Jetlag: A (Self-) Critical Review
by Till Roenneberg, Luísa K. Pilz, Giulia Zerbini and Eva C. Winnebeck
Biology 2019, 8(3), 54; https://doi.org/10.3390/biology8030054 - 12 Jul 2019
Cited by 340 | Viewed by 26165
Abstract
The Munich ChronoType Questionnaire (MCTQ) has now been available for more than 15 years and its original publication has been cited 1240 times (Google Scholar, May 2019). Additionally, its online version, which was available until July 2017, produced almost 300,000 entries from all [...] Read more.
The Munich ChronoType Questionnaire (MCTQ) has now been available for more than 15 years and its original publication has been cited 1240 times (Google Scholar, May 2019). Additionally, its online version, which was available until July 2017, produced almost 300,000 entries from all over the world (MCTQ database). The MCTQ has gone through several versions, has been translated into 13 languages, and has been validated against other more objective measures of daily timing in several independent studies. Besides being used as a method to correlate circadian features of human biology with other factors—ranging from health issues to geographical factors—the MCTQ gave rise to the quantification of old wisdoms, like “teenagers are late”, and has produced new concepts, like social jetlag. Some like the MCTQ’s simplicity and some view it critically. Therefore, it is time to present a self-critical view on the MCTQ, to address some misunderstandings, and give some definitions of the MCTQ-derived chronotype and the concept of social jetlag. Full article
(This article belongs to the Special Issue Biological Clocks)
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19 pages, 2431 KiB  
Review
Are There Circadian Clocks in Non-Photosynthetic Bacteria?
by Francesca Sartor, Zheng Eelderink-Chen, Ben Aronson, Jasper Bosman, Lauren E. Hibbert, Antony N. Dodd, Ákos T. Kovács and Martha Merrow
Biology 2019, 8(2), 41; https://doi.org/10.3390/biology8020041 - 22 May 2019
Cited by 30 | Viewed by 8811
Abstract
Circadian clocks in plants, animals, fungi, and in photosynthetic bacteria have been well-described. Observations of circadian rhythms in non-photosynthetic Eubacteria have been sporadic, and the molecular basis for these potential rhythms remains unclear. Here, we present the published experimental and bioinformatical evidence for [...] Read more.
Circadian clocks in plants, animals, fungi, and in photosynthetic bacteria have been well-described. Observations of circadian rhythms in non-photosynthetic Eubacteria have been sporadic, and the molecular basis for these potential rhythms remains unclear. Here, we present the published experimental and bioinformatical evidence for circadian rhythms in these non-photosynthetic Eubacteria. From this, we suggest that the timekeeping functions of these organisms will be best observed and studied in their appropriate complex environments. Given the rich temporal changes that exist in these environments, it is proposed that microorganisms both adapt to and contribute to these daily dynamics through the process of temporal mutualism. Understanding the timekeeping and temporal interactions within these systems will enable a deeper understanding of circadian clocks and temporal programs and provide valuable insights for medicine and agriculture. Full article
(This article belongs to the Special Issue Biological Clocks)
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15 pages, 1048 KiB  
Review
Telling the Time with a Broken Clock: Quantifying Circadian Disruption in Animal Models
by Laurence A. Brown, Angus S. Fisk, Carina A. Pothecary and Stuart N. Peirson
Biology 2019, 8(1), 18; https://doi.org/10.3390/biology8010018 - 21 Mar 2019
Cited by 21 | Viewed by 7535
Abstract
Circadian rhythms are approximately 24 h cycles in physiology and behaviour that enable organisms to anticipate predictable rhythmic changes in their environment. These rhythms are a hallmark of normal healthy physiology, and disruption of circadian rhythms has implications for cognitive, metabolic, cardiovascular and [...] Read more.
Circadian rhythms are approximately 24 h cycles in physiology and behaviour that enable organisms to anticipate predictable rhythmic changes in their environment. These rhythms are a hallmark of normal healthy physiology, and disruption of circadian rhythms has implications for cognitive, metabolic, cardiovascular and immune function. Circadian disruption is of increasing concern, and may occur as a result of the pressures of our modern 24/7 society—including artificial light exposure, shift-work and jet-lag. In addition, circadian disruption is a common comorbidity in many different conditions, ranging from aging to neurological disorders. A key feature of circadian disruption is the breakdown of robust, reproducible rhythms with increasing fragmentation between activity and rest. Circadian researchers have developed a range of methods for estimating the period of time series, typically based upon periodogram analysis. However, the methods used to quantify circadian disruption across the literature are not consistent. Here we describe a range of different measures that have been used to measure circadian disruption, with a particular focus on laboratory rodent data. These methods include periodogram power, variability in activity onset, light phase activity, activity bouts, interdaily stability, intradaily variability and relative amplitude. The strengths and limitations of these methods are described, as well as their normal ranges and interrelationships. Whilst there is an increasing appreciation of circadian disruption as both a risk to health and a potential therapeutic target, greater consistency in the quantification of disrupted rhythms is needed. Full article
(This article belongs to the Special Issue Biological Clocks)
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16 pages, 2466 KiB  
Review
Circadian Clocks in Fish—What Have We Learned so far?
by Inga A. Frøland Steindal and David Whitmore
Biology 2019, 8(1), 17; https://doi.org/10.3390/biology8010017 - 19 Mar 2019
Cited by 70 | Viewed by 7875
Abstract
Zebrafish represent the one alternative vertebrate, genetic model system to mice that can be easily manipulated in a laboratory setting. With the teleost Medaka (Oryzias latipes), which now has a significant following, and over 30,000 other fish species worldwide, there is [...] Read more.
Zebrafish represent the one alternative vertebrate, genetic model system to mice that can be easily manipulated in a laboratory setting. With the teleost Medaka (Oryzias latipes), which now has a significant following, and over 30,000 other fish species worldwide, there is great potential to study the biology of environmental adaptation using teleosts. Zebrafish are primarily used for research on developmental biology, for obvious reasons. However, fish in general have also contributed to our understanding of circadian clock biology in the broadest sense. In this review, we will discuss selected areas where this contribution seems most unique. This will include a discussion of the issue of central versus peripheral clocks, in which zebrafish played an early role; the global nature of light sensitivity; and the critical role played by light in regulating cell biology. In addition, we also discuss the importance of the clock in controlling the timing of fundamental aspects of cell biology, such as the temporal control of the cell cycle. Many of these findings are applicable to the majority of vertebrate species. However, some reflect the unique manner in which “fish” can solve biological problems, in an evolutionary context. Genome duplication events simply mean that many fish species have more gene copies to “throw at a problem”, and evolution seems to have taken advantage of this “gene abundance”. How this relates to their poor cousins, the mammals, remains to be seen. Full article
(This article belongs to the Special Issue Biological Clocks)
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20 pages, 3326 KiB  
Review
Episodic Ultradian Events—Ultradian Rhythms
by Grace H. Goh, Shane K. Maloney, Peter J. Mark and Dominique Blache
Biology 2019, 8(1), 15; https://doi.org/10.3390/biology8010015 - 14 Mar 2019
Cited by 47 | Viewed by 8033
Abstract
In the fast lane of chronobiology, ultradian events are short-term rhythms that have been observed since the beginning of modern biology and were quantified about a century ago. They are ubiquitous in all biological systems and found in all organisms, from unicellular organisms [...] Read more.
In the fast lane of chronobiology, ultradian events are short-term rhythms that have been observed since the beginning of modern biology and were quantified about a century ago. They are ubiquitous in all biological systems and found in all organisms, from unicellular organisms to mammals, and from single cells to complex biological functions in multicellular animals. Since these events are aperiodic and last for a few minutes to a few hours, they are better classified as episodic ultradian events (EUEs). Their origin is unclear. However, they could have a molecular basis and could be controlled by hormonal inputs—in vertebrates, they originate from the activity of the central nervous system. EUEs are receiving increasing attention but their aperiodic nature requires specific sampling and analytic tools. While longer scale rhythms are adaptations to predictable changes in the environment, in theory, EUEs could contribute to adaptation by preparing organisms and biological functions for unpredictability. Full article
(This article belongs to the Special Issue Biological Clocks)
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17 pages, 1411 KiB  
Review
The Plant Circadian Oscillator
by C. Robertson McClung
Biology 2019, 8(1), 14; https://doi.org/10.3390/biology8010014 - 12 Mar 2019
Cited by 95 | Viewed by 10624
Abstract
It has been nearly 300 years since the first scientific demonstration of a self-sustaining circadian clock in plants. It has become clear that plants are richly rhythmic, and many aspects of plant biology, including photosynthetic light harvesting and carbon assimilation, resistance to abiotic [...] Read more.
It has been nearly 300 years since the first scientific demonstration of a self-sustaining circadian clock in plants. It has become clear that plants are richly rhythmic, and many aspects of plant biology, including photosynthetic light harvesting and carbon assimilation, resistance to abiotic stresses, pathogens, and pests, photoperiodic flower induction, petal movement, and floral fragrance emission, exhibit circadian rhythmicity in one or more plant species. Much experimental effort, primarily, but not exclusively in Arabidopsis thaliana, has been expended to characterize and understand the plant circadian oscillator, which has been revealed to be a highly complex network of interlocked transcriptional feedback loops. In addition, the plant circadian oscillator has employed a panoply of post-transcriptional regulatory mechanisms, including alternative splicing, adjustable rates of translation, and regulated protein activity and stability. This review focuses on our present understanding of the regulatory network that comprises the plant circadian oscillator. The complexity of this oscillatory network facilitates the maintenance of robust rhythmicity in response to environmental extremes and permits nuanced control of multiple clock outputs. Consistent with this view, the clock is emerging as a target of domestication and presents multiple targets for targeted breeding to improve crop performance. Full article
(This article belongs to the Special Issue Biological Clocks)
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22 pages, 1875 KiB  
Review
The Mammalian Circadian Timing System and the Suprachiasmatic Nucleus as Its Pacemaker
by Michael H. Hastings, Elizabeth S. Maywood and Marco Brancaccio
Biology 2019, 8(1), 13; https://doi.org/10.3390/biology8010013 - 11 Mar 2019
Cited by 98 | Viewed by 12114
Abstract
The past twenty years have witnessed the most remarkable breakthroughs in our understanding of the molecular and cellular mechanisms that underpin circadian (approximately one day) time-keeping. Across model organisms in diverse taxa: cyanobacteria (Synechococcus), fungi (Neurospora), higher plants ( [...] Read more.
The past twenty years have witnessed the most remarkable breakthroughs in our understanding of the molecular and cellular mechanisms that underpin circadian (approximately one day) time-keeping. Across model organisms in diverse taxa: cyanobacteria (Synechococcus), fungi (Neurospora), higher plants (Arabidopsis), insects (Drosophila) and mammals (mouse and humans), a common mechanistic motif of delayed negative feedback has emerged as the Deus ex machina for the cellular definition of ca. 24 h cycles. This review will consider, briefly, comparative circadian clock biology and will then focus on the mammalian circadian system, considering its molecular genetic basis, the properties of the suprachiasmatic nucleus (SCN) as the principal circadian clock in mammals and its role in synchronising a distributed peripheral circadian clock network. Finally, it will consider new directions in analysing the cell-autonomous and circuit-level SCN clockwork and will highlight the surprising discovery of a central role for SCN astrocytes as well as SCN neurons in controlling circadian behaviour. Full article
(This article belongs to the Special Issue Biological Clocks)
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19 pages, 3555 KiB  
Review
Role of Rhodopsins as Circadian Photoreceptors in the Drosophila melanogaster
by Pingkalai R. Senthilan, Rudi Grebler, Nils Reinhard, Dirk Rieger and Charlotte Helfrich-Förster
Biology 2019, 8(1), 6; https://doi.org/10.3390/biology8010006 - 10 Jan 2019
Cited by 28 | Viewed by 8249
Abstract
Light profoundly affects the circadian clock and the activity levels of animals. Along with the systematic changes in intensity and spectral composition, over the 24-h day, light shows considerable irregular fluctuations (noise). Using light as the Zeitgeber for the circadian clock is, therefore, [...] Read more.
Light profoundly affects the circadian clock and the activity levels of animals. Along with the systematic changes in intensity and spectral composition, over the 24-h day, light shows considerable irregular fluctuations (noise). Using light as the Zeitgeber for the circadian clock is, therefore, a complex task and this might explain why animals utilize multiple photoreceptors to entrain their circadian clock. The fruit fly Drosophila melanogaster possesses light-sensitive Cryptochrome and seven Rhodopsins that all contribute to light detection. We review the role of Rhodopsins in circadian entrainment, and of direct light-effects on the activity, with a special emphasis on the newly discovered Rhodopsin 7 (Rh7). We present evidence that Rhodopsin 6 in receptor cells 8 of the compound eyes, as well as in the extra retinal Hofbauer-Buchner eyelets, plays a major role in entraining the fly’s circadian clock with an appropriate phase-to-light–dark cycles. We discuss recent contradictory findings regarding Rhodopsin 7 and report original data that support its role in the compound eyes and in the brain. While Rhodopsin 7 in the brain appears to have a minor role in entrainment, in the compound eyes it seems crucial for fine-tuning light sensitivity to prevent overshooting responses to bright light. Full article
(This article belongs to the Special Issue Biological Clocks)
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