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Integrative Physiology of the Circadian Clock

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (25 December 2019) | Viewed by 8924

Special Issue Editor

Department of Preclinical Research and Development, BioChron LLC, Worcester, MA 01605, USA
Interests: neurobiology; sleep; circadian rhythms; adult neurogenesis; mathematical modeling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

All the physiological systems have to integrate to provide for the normal functioning of an organism. However, the circadian clock system is a likely champion of integrative physiology. This starts from the molecular level of the clock, forming feedback and feed-forward loops, and is then reflected in the mechanisms synchronizing individual cellular clocks on the local level of tissues and organs. These numerous cellular clocks are then supervised by yet another integrative level of the master clock, assuring an internal synergy of all the physiological systems. Finally, integration into the clock system of the external time cues allows an organism to anticipate and adapt to the periodically changing environment. This issue of IJMS aims to provide a comprehensive view of novel discoveries on the mechanisms of this complex and dynamic process of time keeping, and its role in normal physiology and pathological conditions that are relevant to human health.

Dr. Irina Zhdanova
Guest Editor

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Published Papers (3 papers)

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19 pages, 3679 KiB  
Article
Roles of Direct Photoreception and the Internal Circadian Oscillator in the Regulation of Melatonin Secretion in the Pineal Organ of the Domestic Turkey: A Novel In Vitro Clock and Calendar Model
by Magdalena Prusik and Bogdan Lewczuk
Int. J. Mol. Sci. 2019, 20(16), 4022; https://doi.org/10.3390/ijms20164022 - 17 Aug 2019
Cited by 11 | Viewed by 2554
Abstract
The regulation of melatonin secretion in the avian pineal organ is highly complex and shows prominent interspecies differences. The aim of this study was to determine the roles of direct photoreception and the internal oscillator in the regulation of melatonin secretion in the [...] Read more.
The regulation of melatonin secretion in the avian pineal organ is highly complex and shows prominent interspecies differences. The aim of this study was to determine the roles of direct photoreception and the internal oscillator in the regulation of melatonin secretion in the pineal organ of the domestic turkey. The pineal organs were collected from 12-, 13- and 14-week-old female turkeys reared under a 12 L:12 D cycle with the photophase from 07.00 to 19.00, and were incubated in superfusion culture for 3–6 days. The cultures were subjected to different light conditions including 12 L:12 D cycles with photophases between 07.00 and 19.00, 13.00 and 01.00 or 01.00 and 13.00, a reversed cycle 12 D:12 L, cycles with long (16 L:8 D) and short (8 L:16 D) photophases, and continuous darkness or illumination. The pineal organs were also exposed to light pulses of variable duration during incubation in darkness or to periods of darkness during the photophase. The secretion of melatonin was determined by direct radioimmunoassay. The turkey pineal organs secreted melatonin in a well-entrained diurnal rhythm with a very high amplitude. Direct photoreception as an independently acting mechanism was able to ensure quick and precise adaptation of the melatonin secretion rhythm to changes in light-dark conditions. The pineal organs secreted melatonin in circadian rhythms during incubation in continuous darkness or illumination. The endogenous oscillator of turkey pinealocytes was able to acquire and store information about the light-dark cycle and then to generate the circadian rhythm of melatonin secretion in continuous darkness according to the stored data. The obtained data suggest that the turkey pineal gland is highly autonomous in the generation and regulation of the melatonin secretion rhythm. They also demonstrate that the turkey pineal organ in superfusion culture is a valuable model for chronobiological studies, providing a highly precise clock and calendar. This system has several features which make it an attractive alternative to other avian pineal glands for circadian studies. Full article
(This article belongs to the Special Issue Integrative Physiology of the Circadian Clock)
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17 pages, 2704 KiB  
Article
WC-1 and the Proximal GATA Sequence Mediate a Cis-/Trans-Acting Repressive Regulation of Light-Dependent Gene Transcription in the Dark
by Andrea Brenna and Claudio Talora
Int. J. Mol. Sci. 2019, 20(12), 2854; https://doi.org/10.3390/ijms20122854 - 12 Jun 2019
Cited by 7 | Viewed by 2815
Abstract
Light influences a wide range of physiological processes from prokaryotes to mammals. Neurospora crassa represents an important model system used for studying this signal pathway. At molecular levels, the WHITE COLLAR Complex (WCC), a heterodimer formed by WC-1 (the blue light photo-sensor) and [...] Read more.
Light influences a wide range of physiological processes from prokaryotes to mammals. Neurospora crassa represents an important model system used for studying this signal pathway. At molecular levels, the WHITE COLLAR Complex (WCC), a heterodimer formed by WC-1 (the blue light photo-sensor) and WC-2 (the transcriptional activator), is the critical positive regulator of light-dependent gene expression. GATN (N indicates any other nucleotide) repeats are consensus sequences within the promoters of light-dependent genes recognized by the WCC. The distal GATN is also known as C-box since it is involved in the circadian clock. However, we know very little about the role of the proximal GATN, and the molecular mechanism that controls the transcription of light-induced genes during the dark/light transition it is still unclear. Here we showed a first indication that mutagenesis of the proximal GATA sequence within the target promoter of the albino-3 gene or deletion of the WC-1 zinc finger domain led to a rise in expression of light-dependent genes already in the dark, effectively decoupling light stimuli and transcriptional activation. This is the first observation of cis-/trans-acting repressive machinery, which is not consistent with the light-dependent regulatory mechanism observed in the eukaryotic world so far. Full article
(This article belongs to the Special Issue Integrative Physiology of the Circadian Clock)
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28 pages, 4677 KiB  
Article
Depletion of Gram-Positive Bacteria Impacts Hepatic Biological Functions During the Light Phase
by Hui Yun Penny Oh, Sandrine Ellero-Simatos, Ravikumar Manickam, Nguan Soon Tan, Hervé Guillou and Walter Wahli
Int. J. Mol. Sci. 2019, 20(4), 812; https://doi.org/10.3390/ijms20040812 - 14 Feb 2019
Cited by 9 | Viewed by 3278
Abstract
Living organisms display internal biological rhythms, which are an evolutionarily conserved adaptation to the environment that drives their rhythmic behavioral and physiological activities. The gut microbiota has been proposed, in association with diet, to regulate the intestinal peripheral clock. However, the effect of [...] Read more.
Living organisms display internal biological rhythms, which are an evolutionarily conserved adaptation to the environment that drives their rhythmic behavioral and physiological activities. The gut microbiota has been proposed, in association with diet, to regulate the intestinal peripheral clock. However, the effect of gut dysbiosis on liver remains elusive, despite that germfree mice show alterations in liver metabolic functions and the hepatic daily rhythm. We analyzed whether the disruption of gut microbial populations with various antibiotics would differentially impact liver functions in mice. Our results support the notion of an impact on the hepatic biological rhythm by gram-positive bacteria. In addition, we provide evidence for differential roles of gut microbiota spectra in xenobiotic metabolism that could protect against the harmful pharmacological effects of drugs. Our results underscore a possible link between liver cell proliferation and gram-positive bacteria. Full article
(This article belongs to the Special Issue Integrative Physiology of the Circadian Clock)
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