scholarly journals Induction of Internal Circadian Desynchrony by Misaligning Zeitgebers

Author(s):  
Isabel Heyde ◽  
Henrik Oster

Abstract 24-hour rhythms in physiology and behaviour are orchestrated by an endogenous circadian clock system. In mammals, these clocks are hierarchically organized with a master pacemaker residing in the hypothalamic suprachiasmatic nucleus (SCN). External time signal – so-called zeitgebers – align internal with geophysical time. During shift work, zeitgeber input conflicting with internal time induces circadian desynchrony which, in turn, promotes metabolic and psychiatric disorders. However, little is known about how internal desynchrony is expressed at the molecular level under chronodisruptive environmental conditions. We here investigated the effects of zeitgeber misalignment on circadian molecular organisation by combining 28-hour light-dark (LD-28) cycles with either 24-hour (FF-24) or 28-hour feeding-fasting (FF-28) regimes in mice. We found that FF cycles showed strong effects on peripheral clocks, while having little effect on centrally coordinated activity rhythms. Systemic, i.e., across-tissue internal circadian desynchrony was induced within four days in LD-28/FF-24, while phase coherence between tissue clocks was largely maintained under LD-28/FF-28 conditions. In contrast, temporal coordination of clock gene activity across tissues was reduced under LD-28/FF-28 conditions compared to LD-28/FF-24. These results indicate that timed food intake may improve internal synchrony under disruptive zeitgeber conditions but may, at the same time, weaken clock function at the tissue level.

2020 ◽  
Vol 21 (5) ◽  
pp. 1884 ◽  
Author(s):  
Kanami Orihara ◽  
Atsushi Haraguchi ◽  
Shigenobu Shibata

The circadian clock system works not only as a cellular time-keeper but also as a coordinator for almost all physiological functions essential to maintaining human health. Therefore, disruptions or malfunctions of this system can cause many diseases and pre-symptomatic conditions. Indeed, previous studies have indicated that disrupted clock gene expression rhythm is closely related to obesity, and that allergic diseases can be regulated by controlling peripheral clocks in organs and tissues. Moreover, recent studies have found that obesity can lead to immune disorders. Accordingly, in this review, we assess the connection between obesity and allergy from the point of view of the circadian clock system anew and summarize the relationships among the circadian clock system, obesity, and allergy.


2021 ◽  
Vol 6 ◽  
pp. 20-25
Author(s):  
Alexey Bogatyrev

Wind turbines and wind farms can be connected to the major electricity distribution system. This paper presents the research results on synchronization of wind farm power supply into the utility grid depending on parameters of the grid at the moment. Measurement time gets synchronized with the external time signal delivered from a navigating system like GLONASS. This can help eliminate antiphase operation of individual wind turbines. Connection diagrams and the whole methodology presented in this paper aim to make wind farm power supply into the grid more effective and loss-eliminating.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Philipp Schlegel ◽  
Michael J Texada ◽  
Anton Miroschnikow ◽  
Andreas Schoofs ◽  
Sebastian Hückesfeld ◽  
...  

NeuromedinU is a potent regulator of food intake and activity in mammals. In Drosophila, neurons producing the homologous neuropeptide hugin regulate feeding and locomotion in a similar manner. Here, we use EM-based reconstruction to generate the entire connectome of hugin-producing neurons in the Drosophila larval CNS. We demonstrate that hugin neurons use synaptic transmission in addition to peptidergic neuromodulation and identify acetylcholine as a key transmitter. Hugin neuropeptide and acetylcholine are both necessary for the regulatory effect on feeding. We further show that subtypes of hugin neurons connect chemosensory to endocrine system by combinations of synaptic and peptide-receptor connections. Targets include endocrine neurons producing DH44, a CRH-like peptide, and insulin-like peptides. Homologs of these peptides are likewise downstream of neuromedinU, revealing striking parallels in flies and mammals. We propose that hugin neurons are part of an ancient physiological control system that has been conserved at functional and molecular level.


2020 ◽  
Vol 128 (4) ◽  
pp. 847-854 ◽  
Author(s):  
Yoshiaki Tanaka ◽  
Hitomi Ogata ◽  
Momoko Kayaba ◽  
Akira Ando ◽  
Insung Park ◽  
...  

Mammals have circadian clocks, which consist of the central clock in the suprachiasmatic nucleus and the peripheral clocks in the peripheral tissues. The effect of exercise on phase of peripheral clocks have been reported in rodents but not in humans. Continuous sampling is necessary to assess the phase of the circadian rhythm of peripheral clock gene expressions. It has been assumed that the expression of the genes in leukocyte may be “an accessible window to the multiorgan transcriptome.” The present study aimed to examine whether exercise affects the level and phase of clock gene expression in human leukocytes. Eleven young men participated in three trials, in which they performed a single bout of exercise at 60% V̇o2max for 1 h beginning either at 0700 (morning exercise) or 1600 (afternoon exercise) or no exercise (control). Blood samples were collected at 0600, 0900, 1200, 1500, 1800, 2100, and 2300 and at 0600 the next morning, to assess diurnal changes of clock gene expression in leukocytes. Brain and muscle ARNT-like protein 1 ( Bmal1) expression level increased after morning and afternoon exercise, and Cryptochrome 1 ( Cry1) expression level increased after morning exercise. Compared with control trial, acrophase of Bmal1 expression tended to be earlier in morning exercise trial and later in afternoon exercise trial. Acrophase of Cry1 expression was earlier in morning exercise trial but not affected by afternoon exercise. Circadian locomotor output cycles kaput ( Clock), Period 1–3 ( Per1–3), and Cry2 expression levels and those acrophases were not affected by exercise. The present results suggest a potential role of a single bout of exercise to modify peripheral clocks in humans. NEW & NOTEWORTHY The present study showed that a single bout of exercise affected peripheral clock gene expression in human leukocytes and the effect of exercise depended on when it was performed. Brain and muscle ARNT-like protein 1 ( Bmal1) expression was increased after exercises performed in the morning and afternoon. Cryptochrome 1 ( Cry1) expression was also increased after the morning exercise. The effect of exercise on acrophase of Bmal1 depended on the time of the exercise: advanced after morning exercise and delayed after afternoon exercise.


2015 ◽  
Vol 112 (48) ◽  
pp. E6691-E6698 ◽  
Author(s):  
Atish Mukherji ◽  
Ahmad Kobiita ◽  
Manohar Damara ◽  
Nisha Misra ◽  
Hamid Meziane ◽  
...  

The light-entrained master central circadian clock (CC) located in the suprachiasmatic nucleus (SCN) not only controls the diurnal alternance of the active phase (the light period of the human light-dark cycle, but the mouse dark period) and the rest phase (the human dark period, but the mouse light period), but also synchronizes the ubiquitous peripheral CCs (PCCs) with these phases to maintain homeostasis. We recently elucidated in mice the molecular signals through which metabolic alterations induced on an unusual feeding schedule, taking place during the rest phase [i.e., restricted feeding (RF)], creates a 12-h PCC shift. Importantly, a previous study showed that the SCN CC is unaltered during RF, which creates a misalignment between the RF-shifted PCCs and the SCN CC-controlled phases of activity and rest. However, the molecular basis of SCN CC insensitivity to RF and its possible pathological consequences are mostly unknown. Here we deciphered, at the molecular level, how RF creates this misalignment. We demonstrate that the PPARα and glucagon receptors, the two instrumental transducers in the RF-induced shift of PCCs, are not expressed in the SCN, thereby preventing on RF a shift of the master SCN CC and creating the misalignment. Most importantly, this RF-induced misalignment leads to a misexpression (with respect to their normal physiological phase of expression) of numerous CC-controlled homeostatic genes, which in the long term generates in RF mice a number of metabolic pathologies including diabetes, obesity, and metabolic syndrome, which have been reported in humans engaged in shift work schedules.


2016 ◽  
Vol 31 (6) ◽  
pp. 577-587 ◽  
Author(s):  
Isa Kolbe ◽  
Jana Husse ◽  
Gabriela Salinas ◽  
Thomas Lingner ◽  
Mariana Astiz ◽  
...  

The circadian master pacemaker in the suprachiasmatic nucleus (SCN) orchestrates peripheral clocks in various organs and synchronizes them with external time, including those in adipose tissue, which displays circadian oscillations in various metabolic and endocrine outputs. Because our knowledge about the instructive role of the SCN clock on peripheral tissue function is based mainly on SCN lesion studies, we here used an alternative strategy employing the Cre/ loxP system to functionally delete the SCN clock in mice. We performed whole-genome microarray hybridizations of murine epididymal white adipose tissue (eWAT) RNA preparations to characterize the role of the SCN clock in eWAT circadian transcriptome regulation. Most of the rhythmic transcripts in control animals were not rhythmic in SCN mutants, but a significant number of transcripts were rhythmic only in mutant eWAT. Core clock genes were rhythmic in both groups, but as was reported before for other tissues, rhythms were dampened and phase advanced in mutant animals. In SCN-mutant mice, eWAT lost the rhythm of metabolic pathway–related transcripts, while transcripts gaining rhythms in SCN-mutant mice were associated with various immune functions. These data reveal a complex interaction of SCN-derived and local circadian signals in the regulation of adipose transcriptome programs.


2021 ◽  
Author(s):  
Waqas Badar ◽  
Husna Ali ◽  
Olivia N Brooker ◽  
E. Newham ◽  
Tim Snow ◽  
...  

AbstractThe bone-cartilage interface (BCI) and underlying calcified plate is a universal feature in diarthrodial joints. The BCI is an important mechanically-graded interface subjected to shear and compressive strains, and changes at the BCI have been linked to osteoarthritis progression. Here we report the existence of a physiological internal strain gradient (pre-strain) across the BCI at the ultrastructural scale of the extracellular matrix constituents, specifically the collagen fibril. We use X-ray scattering that probes changes in the axial periodicity of fibril-level D-stagger of tropocollagen molecules in the matrix fibrils, as a measure of microscopic pre-strain. We find that mineralized collagen nanofibrils in the calcified BCI are in tension pre-strain relative to the underlying trabecular bone. This behaviour contrasts with the previously accepted notion that fibrillar pre-strain (or D-stagger) in collagenous tissues always reduces with mineralization due to reduced hydration and associated swelling pressure. Within the calcified tissue, a finer-scale gradient in pre-strain over ~50μm is likely linked to the tidemark. The increased fibrillar pre-strain at the BCI is linked to prior research reporting large tissue-level residual strains under compression. The findings may have biomechanical adaptative significance: higher in-built molecular level resilience/damage resistance to physiological compression, and the disruption of the molecular-level pre-strains during remodelling of the BCI may be a potential factor in osteoarthritis-based degeneration.


2010 ◽  
Vol 298 (3) ◽  
pp. R635-R641 ◽  
Author(s):  
Tao Wu ◽  
Yinhua Ni ◽  
Yue Dong ◽  
Jiafeng Xu ◽  
Xiaohong Song ◽  
...  

Although studies involving the circadian response to external time cues indicate that the peripheral clocks are dominated mainly by food cues, whether and how changes in the light and food cues affect the circadian rhythm of the renal clock is still largely unknown. In the present study, we found that the circadian phases of Bmal1, Clock, Cry1, Per1, and Per2 were altered differently by the stimuli of food and light cues in the kidney. After the individual reversal of the light-dark (LD) cycle for 7 days, Per1 displayed a 4-h phase delay, whereas the peak phases of Bmal1, Clock, Cry1 and Per2 almost remained the same as those in the control condition. With regard to the feeding-induced circadian resetting of the renal clock, we found that the resetting processes of clock genes could not be completed within 7 days, suggesting a weak synchronization effect of the food cue on the renal circadian clock. Moreover, the reentrainment of the clock genes was greatly enhanced after the reversal of both the feeding schedule and the LD cycle. Noticeably, the phases of Per1 and Clock were shifted most rapidly by 12 h within 3 days after the simultaneous reversal of the feeding schedule and the LD cycle, whereas their peak phases were only shifted by 4 h and 8 h, respectively, on the 7th day after the individual reversal of the feeding schedule. Thus Per1 and Clock may play important roles in the light-induced resetting of the circadian rhythms in the kidney.


2020 ◽  
Author(s):  
Kai Wang

The mind and consciousness are pretty complex to observe and analyze quantitatively since the complexity of neuron and mystery of consciousness. Recent years, many scientists try to explain our mind from physical viewpoint or elucidate the physics of the mind. In the paper, we reveal a new approach to understand our mind and present a tentative theory to describe how our mind works respect to physics. Two significant concept of time, namely, the internal time of mind and external time of the outside are introduced to measure our mind quantitatively on some degree. The related law of these two types of time is similar to the special relativity proposed by Einstein. Our theory aims to provide a new perspective to understand and know ourselves and lead our life better. At the end of paper, we design an experiment to check the correctness of our results.


2020 ◽  
Author(s):  
Kai Wang

The mind and consciousness are pretty complex to observe and analyze quantitatively since the complexity of neuron and mystery of consciousness. Recent years, many scientists try to explain our mind from physical viewpoint or elucidate the physics of the mind. In the paper, we reveal a new approach to understand our mind and present a tentative theory to describe how our mind works respect to physics. Two significant concept of time, namely, the internal time of mind and external time of the outside are introduced to measure our mind quantitatively on some degree. The related law of these two types of time is similar to the special relativity proposed by Einstein. Our theory aims to provide a new perspective to understand and know ourselves and lead our life better. At the end of paper, we design an experiment to check the correctness of our results.


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