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Clark, Amelia M., and Brian J. Altman. "Circadian control of macrophages in the tumor microenvironment." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 165.06. http://dx.doi.org/10.4049/jimmunol.208.supp.165.06.
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Abstract Introduction All leukocytes tested to date have functional circadian clocks, and nearly every arm of the immune response is subject to circadian regulation. Circadian clocks instruct the time-of-day-dependent, rhythmic expression of genes in a tissue- and cell-specific manner. In macrophages (mΦs), the circadian clock regulates several factors that are critical to executing effective immune responses. Tumor-associated mΦs are major contributors to immune suppression in the tumor microenvironment (TME). Evidence suggests that metabolically stressful factors in the TME such as acidic pH and nutrient limitation promote mΦ-mediated immune suppression, and recent data point to dysregulation of the circadian clock downstream of metabolic stress. Methods We study the effect of TME-associated metabolic stress on the circadian clock of mΦs in vitro by culturing bone marrow-derived mΦs in conditions mimicking acidic pH and nutrient limitations that have been observed in the TME. To study the impact of mΦ-intrinsic circadian rhythms on tumorigenesis in vivo, we use mice genetically engineered to have a myeloid cell-specific disruption of the circadian clock via deletion of the key clock protein BMAL1. Results Oscillation of core clock proteins is altered in mΦs subjected to TME-associated metabolic stress. Additionally, we observe increased tumor growth in mice co-injected with mΦs whose circadian clocks were disrupted compared to mice co-injected with mΦs whose circadian clocks were functional. Conclusion Our data suggests that stressful conditions associated with the TME can alter the mΦ circadian clock, and that a functional circadian clock in mΦs can suppress tumor growth in a syngeneic murine tumor model of pancreatic cancer. This research has been supported by the following fellowships and grants: 2021-Current: Wilmot Predoctoral Cancer Research Fellowship, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 2020-2021: NIH T32 Training Grant in Cellular, Biochemical & Molecular Sciences, University of Rochester Medical Center, Rochester, NY
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Xiao, Yangbo, Ye Yuan, Mariana Jimenez, Neeraj Soni, and Swathi Yadlapalli. "Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms." Proceedings of the National Academy of Sciences 118, no. 28 (July 7, 2021): e2019756118. http://dx.doi.org/10.1073/pnas.2019756118.
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Circadian clocks regulate ∼24-h oscillations in gene expression, behavior, and physiology. While the genetic and molecular mechanisms of circadian rhythms are well characterized, what remains poorly understood are the intracellular dynamics of circadian clock components and how they affect circadian rhythms. Here, we elucidate how spatiotemporal organization and dynamics of core clock proteins and genes affect circadian rhythms in Drosophila clock neurons. Using high-resolution imaging and DNA-fluorescence in situ hybridization techniques, we demonstrate that Drosophila clock proteins (PERIOD and CLOCK) are organized into a few discrete foci at the nuclear envelope during the circadian repression phase and play an important role in the subnuclear localization of core clock genes to control circadian rhythms. Specifically, we show that core clock genes, period and timeless, are positioned close to the nuclear periphery by the PERIOD protein specifically during the repression phase, suggesting that subnuclear localization of core clock genes might play a key role in their rhythmic gene expression. Finally, we show that loss of Lamin B receptor, a nuclear envelope protein, leads to disruption of PER foci and per gene peripheral localization and results in circadian rhythm defects. These results demonstrate that clock proteins play a hitherto unexpected role in the subnuclear reorganization of core clock genes to control circadian rhythms, revealing how clocks function at the subcellular level. Our results further suggest that clock protein foci might regulate dynamic clustering and spatial reorganization of clock-regulated genes over the repression phase to control circadian rhythms in behavior and physiology.
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Weitzman, Jonathan B. "Clock control." Genome Biology 3 (2002): spotlight—20021115–01. http://dx.doi.org/10.1186/gb-spotlight-20021115-01.
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Alvarez, J. D., and Amita Sehgal. "Finer clock control." Nature 419, no. 6909 (October 2002): 798–99. http://dx.doi.org/10.1038/419798a.
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Reed, Ruth. "Body clock control." New Scientist 191, no. 2570 (September 2006): 20. http://dx.doi.org/10.1016/s0262-4079(06)60541-1.
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Guan, Dongyin, Ying Xiong, Trang Minh Trinh, Yang Xiao, Wenxiang Hu, Chunjie Jiang, Pieterjan Dierickx, Cholsoon Jang, Joshua D. Rabinowitz, and Mitchell A. Lazar. "The hepatocyte clock and feeding control chronophysiology of multiple liver cell types." Science 369, no. 6509 (July 30, 2020): 1388–94. http://dx.doi.org/10.1126/science.aba8984.
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Most cells of the body contain molecular clocks, but the requirement of peripheral clocks for rhythmicity and their effects on physiology are not well understood. We show that deletion of core clock components REV-ERBα and REV-ERBβ in adult mouse hepatocytes disrupts diurnal rhythms of a subset of liver genes and alters the diurnal rhythm of de novo lipogenesis. Liver function is also influenced by nonhepatocytic cells, and the loss of hepatocyte REV-ERBs remodels the rhythmic transcriptomes and metabolomes of multiple cell types within the liver. Finally, alteration of food availability demonstrates the hierarchy of the cell-intrinsic hepatocyte clock mechanism and the feeding environment. Together, these studies reveal previously unsuspected roles of the hepatocyte clock in the physiological coordination of nutritional signals and cell-cell communication controlling rhythmic metabolism.
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Shakhmantsir, Iryna, and Amita Sehgal. "Splicing the Clock to Maintain and Entrain Circadian Rhythms." Journal of Biological Rhythms 34, no. 6 (August 7, 2019): 584–95. http://dx.doi.org/10.1177/0748730419868136.
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Circadian clocks drive daily rhythms of physiology and behavior in multiple organisms and synchronize these rhythms to environmental cycles of light and temperature. The basic mechanism of the clock consists of a transcription-translation feedback loop, in which key clock proteins negatively regulate their own transcription. Although much of the focus with respect to clock mechanisms has been on the regulation of transcription and on the stability and activity of clock proteins, it is clear that other regulatory processes also have to be involved to explain aspects of clock function. Here, we review the role of alternative splicing in circadian clocks. Starting with a discussion of the Drosophila clock and then extending to other major circadian model systems, we describe how the control of alternative splicing enables organisms to maintain their circadian clocks as well as to respond to environmental inputs, in particular to temperature changes.
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Costello, Hannah M., and Michelle L. Gumz. "Circadian Rhythm, Clock Genes, and Hypertension: Recent Advances in Hypertension." Hypertension 78, no. 5 (November 2021): 1185–96. http://dx.doi.org/10.1161/hypertensionaha.121.14519.
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Accumulating evidence suggests that the molecular circadian clock is crucial in blood pressure (BP) control. Circadian rhythms are controlled by the central clock, which resides in the suprachiasmatic nucleus of the hypothalamus and peripheral clocks throughout the body. Both light and food cues entrain these clocks but whether these cues are important for the circadian rhythm of BP is a growing area of interest. The peripheral clocks in the smooth muscle, perivascular adipose tissue, liver, adrenal gland, and kidney have been recently implicated in the regulation of BP rhythm. Dysregulation of the circadian rhythm of BP is associated with adverse cardiorenal outcomes and increased risk of cardiovascular mortality. In this review, we summarize the most recent advances in peripheral clocks as BP regulators, highlight the adverse outcomes of disrupted circadian BP rhythm in hypertension, and provide insight into potential future work in areas exploring the circadian clock in BP control and chronotherapy. A better understanding of peripheral clock function in regulating the circadian rhythm of BP will help pave the way for targeted therapeutics in the treatment of circadian BP dysregulation and hypertension.
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Yang, Guang You, Zhi Jian Ye, Shuang Qing Zhang, and Wan Xu. "Research and Implementations of the IEEE 1588 Precision Time Protocol Based on ARM-Linux." Advanced Materials Research 156-157 (October 2010): 1492–96. http://dx.doi.org/10.4028/www.scientific.net/amr.156-157.1492.
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The clock synchronization is the key technology in distributed control system. This paper investigates the method to adjust computer clock frequency and time in embedded control system based on Ethernet. This paper also analyses the basic working principle of the IEEE 1588 Precision Time Protocol. In particular, it outlines the working principle of the free PTPd that is the software only implementations of the IEEE 1588 Precision Time Protocol. In the ARM-Linux environment, it presents a clock synchronization method to achieve high precise clock synchronization in distributed control system using PTPd. The results indicate that it is able to synchronize distributed clocks with the accuracy less than 500 microseconds using PTPd without the support of specialized hardware.
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Li, Shujing, and Luoying Zhang. "Circadian Control of Global Transcription." BioMed Research International 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/187809.
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Circadian rhythms exist in most if not all organisms on the Earth and manifest in various aspects of physiology and behavior. These rhythmic processes are believed to be driven by endogenous molecular clocks that regulate rhythmic expression of clock-controlled genes (CCGs). CCGs consist of a significant portion of the genome and are involved in diverse biological pathways. The transcription of CCGs is tuned by rhythmic actions of transcription factors and circadian alterations in chromatin. Here, we review the circadian control of CCG transcription in five model organisms that are widely used, including cyanobacterium, fungus, plant, fruit fly, and mouse. Comparing the similarity and differences in the five organisms could help us better understand the function of the circadian clock, as well as its output mechanisms adapted to meet the demands of diverse environmental conditions.
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Qiao, Shi Quan, Xiu Qing Zhang, Meng Yang, and Shu Wang Chen. "Design of Digital Clock Based on SCM." Applied Mechanics and Materials 668-669 (October 2014): 822–25. http://dx.doi.org/10.4028/www.scientific.net/amm.668-669.822.
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The digital clock is the timing device by using of the digital circuit to implement the digital display for hours, minutes and seconds. Due to the development of the digital integrated circuit and the wide application of the quartz crystal oscillator, the accuracy of the digital clock is far more than the old clocks’. The control part of the design is SCM AT89C51, and the compiler environment is Keil. The software is developed with C language, and the simulation debugging is used Proteus. The digital clock is convenient to people’s production and life, and it expands the original time function of the clocks greatly. Development trend of electronic instrumentation, and has broad market prospects. The clock can be used in many fields, such as the timing automatic alarm, the automatic schedule bell, the time program automatic control, the regular radio, the automatic lights close, the oven timer switch, etc.
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Okamoto-Uchida, Yoshimi, Akari Nishimura, Junko Izawa, Atsuhiko Hattori, Nobuo Suzuki, and Jun Hirayama. "The Use of Chemical Compounds to Identify the Regulatory Mechanisms of Vertebrate Circadian Clocks." Current Drug Targets 21, no. 5 (April 20, 2020): 425–32. http://dx.doi.org/10.2174/1389450120666190926143120.
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Circadian clocks are intrinsic, time-tracking processes that confer a survival advantage on an organism. Under natural conditions, they follow approximately a 24-h day, modulated by environmental time cues, such as light, to maximize an organism’s physiological efficiency. The exact timing of this rhythm is established by cell-autonomous oscillators called cellular clocks, which are controlled by transcription–translation negative feedback loops. Studies of cell-based systems and wholeanimal models have utilized a pharmacological approach in which chemical compounds are used to identify molecular mechanisms capable of establishing and maintaining cellular clocks, such as posttranslational modifications of cellular clock regulators, chromatin remodeling of cellular clock target genes’ promoters, and stability control of cellular clock components. In addition, studies with chemical compounds have contributed to the characterization of light-signaling pathways and their impact on the cellular clock. Here, the use of chemical compounds to study the molecular, cellular, and behavioral aspects of the vertebrate circadian clock system is described.
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Masri, Selma. "Sirtuin-dependent clock control." Current Opinion in Clinical Nutrition and Metabolic Care 18, no. 6 (November 2015): 521–27. http://dx.doi.org/10.1097/mco.0000000000000219.
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Farina, Marcello, Sergio Bittanti, Patrizia Tavella, and Lorenzo Galleani. "Control of clock signals." Journal of the Franklin Institute 346, no. 5 (June 2009): 449–69. http://dx.doi.org/10.1016/j.jfranklin.2009.01.005.
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Jovanovic, Goran, and Mile Stojcev. "Pulse width control loop as a duty cycle corrector." Serbian Journal of Electrical Engineering 1, no. 2 (2004): 215–26. http://dx.doi.org/10.2298/sjee0402215j.
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The clock distribution and generation circuitry forms a critical component of current synchronous digital systems. A digital system?s clocks must have not only low jitter, low skew, but also well-controlled duty cycle in order to facilitate versatile clocking techniques. In high-speed CMOS clock buffer design, the duty cycle of a clock is liable to be changed when the clock passes through a multistage buffer because the circuit is not pure digital [8]. In this paper, we propose a pulse width control loop referred as MPWCL (modified pulse width control loop) that adopts the same architecture as the conventional PWCL, but with a new pulse generator and new charge pump circuit as a constituent of the duty cycle detector. Thanks to using new building blocks the proposed pulse width control loop can control the duty cycle in a wide range, and what is more important it becomes operative in saturation region too, what provides conditional for fast locking time. For 1.2 ?m double-metal double-poly CMOS process with Vdd = 5 V and operating frequency of 133 MHz, results of SPICE simulation show that the duty cycle can be well controlled in the range from 20 % up to 80 % if the loop parameters are properly chosen.
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Crespo, María, Magdalena Leiva, and Guadalupe Sabio. "Circadian Clock and Liver Cancer." Cancers 13, no. 14 (July 20, 2021): 3631. http://dx.doi.org/10.3390/cancers13143631.
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Circadian clocks control several homeostatic processes in mammals through internal molecular mechanisms. Chronic perturbation of circadian rhythms is associated with metabolic diseases and increased cancer risk, including liver cancer. The hepatic physiology follows a daily rhythm, driven by clock genes that control the expression of several proteins involved in distinct metabolic pathways. Alteration of the liver clock results in metabolic disorders, such as non-alcoholic fatty liver diseases (NAFLD) and impaired glucose metabolism, that can trigger the activation of oncogenic pathways, inducing spontaneous hepatocarcinoma (HCC). In this review, we provide an overview of the role of the liver clock in the metabolic and oncogenic changes that lead to HCC and discuss new potentially useful targets for prevention and management of HCC.
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Helfrich-Förster, C. "Organization of endogenous clocks in insects." Biochemical Society Transactions 33, no. 5 (October 26, 2005): 957–61. http://dx.doi.org/10.1042/bst0330957.
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Insect and mammalian circadian clocks show striking similarities. They utilize homologous clock genes, generating self-sustained circadian oscillations in distinct master clocks of the brain, which then control rhythmic behaviour. The molecular mechanisms of rhythm generation were first uncovered in the fruit fly Drosophila melanogaster, whereas cockroaches were among the first animals where the brain master clock was localized. Despite many similarities, there exist obvious differences in the organization and functioning of insect master clocks. These similarities and differences are reviewed on a molecular and anatomical level.
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Amaral, Ian P. G., and Ian A. Johnston. "Circadian expression of clock and putative clock-controlled genes in skeletal muscle of the zebrafish." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 302, no. 1 (January 2012): R193—R206. http://dx.doi.org/10.1152/ajpregu.00367.2011.
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To identify circadian patterns of gene expression in skeletal muscle, adult male zebrafish were acclimated for 2 wk to a 12:12-h light-dark photoperiod and then exposed to continuous darkness for 86 h with ad libitum feeding. The increase in gut food content associated with the subjective light period was much diminished by the third cycle, enabling feeding and circadian rhythms to be distinguished. Expression of zebrafish paralogs of mammalian transcriptional activators of the circadian mechanism ( bmal1, clock1, and rora) followed a rhythmic pattern with a ∼24-h periodicity. Peak expression of rora paralogs occurred at the beginning of the subjective light period [Zeitgeber time (ZT)07 and ZT02 for roraa and rorab], whereas the highest expression of bmal1 and clock paralogs occurred 12 h later (ZT13–15 and ZT16 for bmal and clock paralogs). Expression of the transcriptional repressors cry1a, per1a/1b, per2, per3, nr1d2a/2b, and nr1d1 also followed a circadian pattern with peak expression at ZT0–02. Expression of the two paralogs of cry2 occurred in phase with clock1a/1b. Duplicated genes had a high correlation of expression except for paralogs of clock1, nr1d2, and per1, with cry1b showing no circadian pattern. The highest expression difference was 9.2-fold for the activator bmal1b and 51.7-fold for the repressor per1a. Out of 32 candidate clock-controlled genes, only myf6, igfbp3, igfbp5b, and hsf2 showed circadian expression patterns. Igfbp3, igfbp5b, and myf6 were expressed in phase with clock1a/1b and had an average of twofold change in expression from peak to trough, whereas hsf2 transcripts were expressed in phase with cry1a and had a 7.2-fold-change in expression. The changes in expression of clock and clock-controlled genes observed during continuous darkness were also observed at similar ZTs in fish exposed to a normal photoperiod in a separate control experiment. The role of circadian clocks in regulating muscle maintenance and growth are discussed.
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Dickmeis, Thomas. "Glucocorticoids and the circadian clock." Journal of Endocrinology 200, no. 1 (October 29, 2008): 3–22. http://dx.doi.org/10.1677/joe-08-0415.
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Glucocorticoids, hormones produced by the adrenal gland cortex, perform numerous functions in body homeostasis and the response of the organism to external stressors. One striking feature of their regulation is a diurnal release pattern, with peak levels linked to the start of the activity phase. This release is under control of the circadian clock, an endogenous biological timekeeper that acts to prepare the organism for daily changes in its environment. Circadian control of glucocorticoid production and secretion involves a central pacemaker in the hypothalamus, the suprachiasmatic nucleus, as well as a circadian clock in the adrenal gland itself. Central circadian regulation is mediated via the hypothalamic–pituitary–adrenal axis and the autonomic nervous system, while the adrenal gland clock appears to control sensitivity of the gland to the adrenocorticopic hormone (ACTH). The rhythmically released glucocorticoids in turn might contribute to synchronisation of the cell-autonomous clocks in the body and interact with them to time physiological dynamics in their target tissues around the day.
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Hadden, Hélène, Steven J. Soldin, and Donald Massaro. "Circadian disruption alters mouse lung clock gene expression and lung mechanics." Journal of Applied Physiology 113, no. 3 (August 1, 2012): 385–92. http://dx.doi.org/10.1152/japplphysiol.00244.2012.
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Most aspects of human physiology and behavior exhibit 24-h rhythms driven by a master circadian clock in the brain, which synchronizes peripheral clocks. Lung function and ventilation are subject to circadian regulation and exhibit circadian oscillations. Sleep disruption, which causes circadian disruption, is common in those with chronic lung disease, and in the general population; however, little is known about the effect on the lung of circadian disruption. We tested the hypothesis circadian disruption alters expression of clock genes in the lung and that this is associated with altered lung mechanics. Female and male mice were maintained on a 12:12-h light/dark cycle (control) or exposed for 4 wk to a shifting light regimen mimicking chronic jet lag (CJL). Airway resistance (Rn), tissue damping (G), and tissue elastance (H) did not differ between control and CJL females. Rn at positive end-expiratory pressure (PEEP) of 2 and 3 cmH2O was lower in CJL males compared with controls. G, H, and G/H did not differ between CJL and control males. Among CJL females, expression of clock genes, Bmal1 and Rev-erb alpha, was decreased; expression of their repressors, Per2 and Cry 2, was increased. Among CJL males, expression of Clock was decreased; Per 2 and Rev-erb alpha expression was increased. We conclude circadian disruption alters lung mechanics and clock gene expression and does so in a sexually dimorphic manner.
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Razzoli, Maria, Carley Karsten, J. Marina Yoder, Alessandro Bartolomucci, and William C. Engeland. "Chronic subordination stress phase advances adrenal and anterior pituitary clock gene rhythms." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 307, no. 2 (July 15, 2014): R198—R205. http://dx.doi.org/10.1152/ajpregu.00101.2014.
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Circadian rhythms in glucocorticoids are the product of interactions between the hypothalamic-pituitary-adrenal (HPA) axis and the mammalian clock gene system. The adrenal clock can generate the glucocorticoid rhythm that in turn synchronizes other peripheral clocks to maintain homeostasis. Stress acutely activates and chronically upregulates the HPA axis, suggesting that the adrenal clock could be modulated by stress. However, there is no direct evidence that stress affects the adrenal clock rhythm. We tested the hypothesis that a model of chronic subordination stress (CSS) that has a major impact on HPA axis regulation, metabolism, and emotional behavior alters adrenal and pituitary clock gene rhythms. Clock gene rhythms were assessed using mPER2::Luciferase (PER2Luc) knockin mice in which in vitro bioluminescence rhythms reflect the Per2 clock gene expression. PER2Luc mice that experienced CSS for 2 wk showed positive energy balance reflected by increased body weight and food intake. Additionally, CSS phase advanced the adrenal (∼2 h) and the pituitary (∼1 h) PER2Luc rhythm compared with control mice. The activity rhythm was not affected. The adrenal clock phase shift was associated with increased feed conversion efficiency, suggesting that the metabolic phenotype in CSS mice may be related to altered adrenal clock rhythmicity. Interestingly, a single subordination experience followed by 8 h sensory housing also phase advanced the adrenal, but not the pituitary, PER2Luc rhythm. Overall, these data demonstrate a stress-induced phase shift in a peripheral clock gene rhythm and differential stress sensitivity of two peripheral clocks within the HPA axis, suggesting a link between clock desynchrony and individual vulnerability to stress.
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Ma, Qianwen, Genlin Mo, and Yong Tan. "Micro RNAs and the biological clock: a target for diseases associated with a loss of circadian regulation." African Health Sciences 20, no. 4 (December 16, 2020): 1887–94. http://dx.doi.org/10.4314/ahs.v20i4.46.
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Background: Circadian clocks are self-sustaining oscillators that coordinate behavior and physiology over a 24 hour peri- od, achieving time-dependent homeostasis with the external environment. The molecular clocks driving circadian rhythmic changes are based on intertwined transcriptional/translational feedback loops that combine with a range of environmental and metabolic stimuli to generate daily internal programing. Understanding how biological rhythms are generated through- out the body and the reasons for their dysregulation can provide avenues for temporally directed therapeutics. Summary: In recent years, microRNAs have been shown to play important roles in the regulation of the circadian clock, particularly in Drosophila, but also in some small animal and human studies. This review will summarize our current un- derstanding of the role of miRNAs during clock regulation, with a particular focus on the control of clock regulated gene expression.
Keywords: MicroRNAs; biological clock; circadian rhythm.
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Castillo, Kathrina D., Emily D. Chapa, and Deborah Bell-Pedersen. "Circadian clock control of tRNA synthetases in Neurospora crassa." F1000Research 11 (December 22, 2022): 1556. http://dx.doi.org/10.12688/f1000research.125351.1.
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Background: In Neurospora crassa, the circadian clock controls rhythmic mRNA translation initiation through regulation of the eIF2α kinase CPC-3 (the homolog of yeast and mammalian GCN2). Active CPC-3 phosphorylates and inactivates eIF2α, leading to higher phosphorylated eIF2α (P-eIF2α) levels and reduced translation initiation during the subjective day. This daytime activation of CPC-3 is driven by its binding to uncharged tRNA, and uncharged tRNA levels peak during the day under control of the circadian clock. The daily rhythm in uncharged tRNA levels could arise from rhythmic amino acid levels or aminoacyl-tRNA synthetase (aaRSs) levels. Methods: To determine if and how the clock potentially controls rhythms in aspartyl-tRNA synthetase (AspRS) and glutaminyl-tRNA synthetase (GlnRS), both observed to be rhythmic in circadian genomic datasets, transcriptional and translational fusions to luciferase were generated. These luciferase reporter fusions were examined in wild type (WT), clock mutant Δfrq, and clock-controlled transcription factor deletion strains. Results: Translational and transcriptional fusions of AspRS and GlnRS to luciferase confirmed that their protein levels are clock-controlled with peak levels at night. Moreover, clock-controlled transcription factors NCU00275 and ADV-1 drive robust rhythmic protein expression of AspRS and GlnRS, respectively. Conclusions: These data support a model whereby coordinate clock control of select aaRSs drives rhythms in uncharged tRNAs, leading to rhythmic CPC-3 activation, and rhythms in translation of specific mRNAs.
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Lu, Renbin, Yufan Dong, and Jia-Da Li. "Necdin regulates BMAL1 stability and circadian clock through SGT1-HSP90 chaperone machinery." Nucleic Acids Research 48, no. 14 (July 15, 2020): 7944–57. http://dx.doi.org/10.1093/nar/gkaa601.
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Abstract Circadian clocks are endogenous oscillators that control ∼24-hour physiology and behaviors in virtually all organisms. The circadian oscillator comprises interconnected transcriptional and translational feedback loops, but also requires finely coordinated protein homeostasis including protein degradation and maturation. However, the mechanisms underlying the mammalian clock protein maturation is largely unknown. In this study, we demonstrate that necdin, one of the Prader-Willi syndrome (PWS)-causative genes, is highly expressed in the suprachiasmatic nuclei (SCN), the pacemaker of circadian clocks in mammals. Mice deficient in necdin show abnormal behaviors during an 8-hour advance jet-lag paradigm and disrupted clock gene expression in the liver. By using yeast two hybrid screening, we identified BMAL1, the core component of the circadian clock, and co-chaperone SGT1 as two necdin-interactive proteins. BMAL1 and SGT1 associated with the N-terminal and C-terminal fragments of necdin, respectively. Mechanistically, necdin enables SGT1-HSP90 chaperone machinery to stabilize BMAL1. Depletion of necdin or SGT1/HSP90 leads to degradation of BMAL1 through the ubiquitin–proteasome system, resulting in alterations in both clock gene expression and circadian rhythms. Taken together, our data identify the PWS-associated protein necdin as a novel regulator of the circadian clock, and further emphasize the critical roles of chaperone machinery in circadian clock regulation.
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Almeida, S., M. Chaves, and F. Delaunay. "Cell cycle period control through modulation of clock inputs." Journal of Bioinformatics and Computational Biology 18, no. 03 (June 2020): 2040006. http://dx.doi.org/10.1142/s0219720020400065.
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In this work, we study period control of the mammalian cell cycle via coupling with the cellular clock. For this, we make use of the oscillators’ synchronization dynamics and investigate methods of slowing down the cell cycle with the use of clock inputs. Clock control of the cell cycle is well established via identified molecular mechanisms, such as the CLOCK:BMAL1-mediated induction of the wee1 gene, resulting in the WEE1 kinase that represses the active form of mitosis promoting factor (MPF), the essential cell cycle component. To investigate the coupling dynamics of these systems, we use previously developed models of the clock and cell cycle oscillators and center our studies on unidirectional clock [Formula: see text] cell cycle coupling. Moreover, we propose an hypothesis of a Growth Factor (GF)-responsive clock, involving a pathway of the non-essential cell cycle complex cyclin D/CDK4. We observe a variety of rational ratios of clock to cell cycle period, such as: 1:1, 3:2, 4:3, and 5:4. Finally, our protocols of period control are successful in effectively slowing down the cell cycle by the use of clock modulating inputs, some of which correspond to existing drugs.
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Ciuffoletti, Augusto. "Power-Aware Synchronization of a Software Defined Clock." Journal of Sensor and Actuator Networks 8, no. 1 (January 18, 2019): 11. http://dx.doi.org/10.3390/jsan8010011.
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In a distributed system, a common time reference allows each component to associate the same timestamp to events that occur simultaneously. It is a design option with benefits and drawbacks since it simplifies and makes more efficient a number of functions, but requires additional resources and control to keep component clocks synchronized. In this paper, we quantify how much power is spent to implement such a function, which helps to solve the dilemma in a system of low-power sensors. To find widely applicable results, the formal model used in our investigation is agnostic of the communication pattern that components use to synchronize their clocks, and focuses on the scheduling of clock synchronization operations needed to correct clock drift. This model helps us to discover that the dynamic calibration of clock drift significantly reduces power consumption. We derive an optimal algorithm to keep a software defined clock (SDCk) synchronized with the reference, and we find that its effectiveness is strongly influenced by hardware clock quality. To demonstrate the soundness of formal statements, we introduce a proof of concept. For its implementation, we privilege low-cost components and standard protocols, and we use it to find that the power needed to keep a clock within 200 ms from UTC (Universal Time Coordinate) as on the order of 10−5 W . The prototype is fully documented and reproducible.
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Moon, Francis C., and Preston D. Stiefel. "Coexisting chaotic and periodic dynamics in clock escapements." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 364, no. 1846 (July 28, 2006): 2539–64. http://dx.doi.org/10.1098/rsta.2006.1839.
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This paper addresses the nature of noise in machines. As a concrete example, we examine the dynamics of clock escapements from experimental, historical and analytical points of view. Experiments on two escapement mechanisms from the Reuleaux kinematic collection at Cornell University are used to illustrate chaotic-like noise in clocks. These vibrations coexist with the periodic dynamics of the balance wheel or pendulum. A mathematical model is presented that shows how self-generated chaos in clocks can break the dry friction in the gear train. This model is shown to exhibit a strange attractor in the structural vibration of the clock. The internal feedback between the oscillator and the escapement structure is similar to anti-control of chaos models.
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Tanaka, Yoshiaki, Hitomi Ogata, Momoko Kayaba, Akira Ando, Insung Park, Katsuhiko Yajima, Akihiro Araki, et al. "Effect of a single bout of exercise on clock gene expression in human leukocyte." Journal of Applied Physiology 128, no. 4 (April 1, 2020): 847–54. http://dx.doi.org/10.1152/japplphysiol.00891.2019.
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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.
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Wei, Hong, Guo Ping Zhou, and Jian Wen Ding. "Design of Control System of GPS-Based Tower Clock." Key Engineering Materials 568 (July 2013): 157–61. http://dx.doi.org/10.4028/www.scientific.net/kem.568.157.
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The design consists of STC89C51 MCU, the GPS15-XL receivers, LED display, servo motors, voice timekeeping and other components .And it is the GPS control system for tower clock, with timekeeping, display, automatic error correction functions. The design captures accurate time information from satellites by GPS15XL-W receiver chip, and collects and deals with time information received from SCM. And then it adjusts the clock. The SCM system consists master clock, and drives the secondary clock through giving out pulse to a servo motor. The system can also achieve the automatic error correction after power on, to change inconvenience of the traditional correction, reduce the mechanical errors. And the tower clock accurate up to ±1µs. There is no cumulative error.
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Ando, Hitoshi, Masafumi Kumazaki, Yuya Motosugi, Kentarou Ushijima, Tomohiro Maekawa, Eiko Ishikawa, and Akio Fujimura. "Impairment of Peripheral Circadian Clocks Precedes Metabolic Abnormalities in ob/ob Mice." Endocrinology 152, no. 4 (February 1, 2011): 1347–54. http://dx.doi.org/10.1210/en.2010-1068.
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Abstract Recent studies have demonstrated relationships between the dysfunction of circadian clocks and the development of metabolic abnormalities, but the chicken-and-egg question remains unresolved. To address this issue, we investigated the cause-effect relationship in obese, diabetic ob/ob mice. Compared with control C57BL/6J mice, the daily mRNA expression profiles of the clock and clock-controlled genes Clock, Bmal1, Cry1, Per1, Per2, and Dbp were substantially dampened in the liver and adipose tissue, but not the hypothalamic suprachiasmatic nucleus, of 10-wk-old ob/ob mice. Four-week feeding of a low-calorie diet and administration of leptin over a 7-d period attenuated, to a significant and comparable extent, the observed metabolic abnormalities (obesity, hyperglycemia, hyperinsulinemia, and hypercholesterolemia) in the ob/ob mice. However, only leptin treatment improved the impaired peripheral clocks. In addition, clock function, assessed by measuring levels of Per1, Per2, and Dbp mRNA at around peak times, was also reduced in the peripheral tissues of 3-wk-old ob/ob mice without any overt metabolic abnormalities. Collectively these results indicate that the impairment of peripheral clocks in ob/ob mice does not result from metabolic abnormalities but may instead be at least partially caused by leptin deficiency itself. Further studies are needed to clarify how leptin deficiency affects peripheral clocks.
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Li, Chengwei, Changxia Gong, Shuang Yu, Jianguo Wu, and Xiaodong Li. "Epigenetic Control of Circadian Clock Operation during Development." Genetics Research International 2012 (March 18, 2012): 1–8. http://dx.doi.org/10.1155/2012/845429.
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The molecular players of circadian clock oscillation have been identified and extensively characterized. The epigenetic mechanisms behind the circadian gene expression control has also been recently studied, although there are still details to be illucidated. In this review, we briefly summarize the current understanding of the mammalian clock. We also provide evidence for the lack of circadian oscillation in particular cell types. As the circadian clock has intimate interaction with the various cellular functions in different type of cells, it must have plasticity and specicity in its operation within different epigenetic environments. The lack of circadian oscillation in certain cells provide an unique opportunity to study the required epigenetic environment in the cell that permit circadian oscillation and to idenfify key influencing factors for proper clock function. How epigenetic mechansims, including DNA methylaiton and chromatin modifications, participate in control of clock oscillation still awaits future studies at the genomic scale.
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Kalsbeek, Andries, Chun-Xia Yi, Cathy Cailotto, Susanne E. la Fleur, Eric Fliers, and Ruud M. Buijs. "Mammalian clock output mechanisms." Essays in Biochemistry 49 (June 30, 2011): 137–51. http://dx.doi.org/10.1042/bse0490137.
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In mammals many behaviours (e.g. sleep–wake, feeding) as well as physiological (e.g. body temperature, blood pressure) and endocrine (e.g. plasma corticosterone concentration) events display a 24 h rhythmicity. These 24 h rhythms are induced by a timing system that is composed of central and peripheral clocks. The highly co-ordinated output of the hypothalamic biological clock not only controls the daily rhythm in sleep–wake (or feeding–fasting) behaviour, but also exerts a direct control over many aspects of hormone release and energy metabolism. First, we present the anatomical connections used by the mammalian biological clock to enforce its endogenous rhythmicity on the rest of the body, especially the neuro-endocrine and energy homoeostatic systems. Subsequently, we review a number of physiological experiments investigating the functional significance of this neuro-anatomical substrate. Together, this overview of experimental data reveals a highly specialized organization of connections between the hypothalamic pacemaker and neuro-endocrine system as well as the pre-sympathetic and pre-parasympathetic branches of the autonomic nervous system.
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Miranda, Jonatan, María P. Portillo, Juan Antonio Madrid, Noemí Arias, M. Terasa Macarulla, and Marta Garaulet. "Effects of resveratrol on changes induced by high-fat feeding on clock genes in rats." British Journal of Nutrition 110, no. 8 (March 28, 2013): 1421–28. http://dx.doi.org/10.1017/s0007114513000755.
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In mammals, the main component of the circadian system is the suprachiasmatic nucleus in the hypothalamus. However, circadian clocks are also present in most peripheral tissues, such as adipose tissue. The aim of the present study was to analyse the potential effects of resveratrol on changes induced by high-fat feeding in the expression of clock genes and clock-controlled genes in the white adipose tissue from rats. For this purpose, rats were divided into three groups: a control group, fed a standard diet, and two other groups, either fed a high-fat diet supplemented with resveratrol (RSV) or no resveratrol (HF). The expression of clock genes and clock-controlled genes was analysed by RT-PCR. Protein expression and fatty acid synthase (FAS) activity were also analysed. When comparing the controls, the RSV group showed similar patterns of response to the HF group, except for reverse erythroblastosis virus α (Rev-Erbα), which was down-regulated. The expression of this gene reached the same levels as in control rats. The response pattern of protein expression forRev-Erbαwas similar to that found for gene expression. High-fat feeding up-regulated all adipogenic genes and resveratrol did not modify them. In the HF group, the activity of FAS tended to increase, while resveratrol decreased. In conclusion, resveratrol reverses the change induced by high-fat feeding in the expression ofRev-Erbαin adipose tissue, which means that clock machinery is a target for this polyphenol. This change seems to be related to reduced lipogenesis, which might be involved in the body fat-lowering effect of this molecule.
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Fahrenkrug, J., B. Georg, J. Hannibal, and H. L. Jørgensen. "Hypophysectomy abolishes rhythms in rat thyroid hormones but not in the thyroid clock." Journal of Endocrinology 233, no. 3 (June 2017): 209–16. http://dx.doi.org/10.1530/joe-17-0111.
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The endocrine body rhythms including the hypothalamic–pituitary–thyroid axis seem to be regulated by the circadian timing system, and daily rhythmicity of circulating thyroid-stimulating hormone (TSH) is well established. The circadian rhythms are generated by endogenous clocks in the central brain oscillator located in the hypothalamic suprachiasmatic nucleus (SCN) as well as multiple peripheral clocks, but information on the existence and function of a thyroid clock is limited. The molecular machinery in all clock cells is composed of a number of clock genes and their gene products are connected by autoregulatory feedback loops. Here, we provide evidence for a thyroid clock in the rat by demonstrating 24-h antiphase oscillations for the mRNA of the canonical clock genes Per1 and Bmal1, which was unaffected by hypophysectomy. By immunostaining, we supported the existence of a core oscillator in the individual thyroid cells by demonstrating a daily cytoplasmatic–nuclear shuttling of PER1 protein. In normal rats, we found a significant daily rhythmicity in the circulating thyroid hormones preceded by a peak in TSH. In hypophysectomised rats, although the thyroid clock was not affected, the oscillations in circulating thyroid hormones were abolished and the levels were markedly lowered. No daily oscillations in the expression of TSH receptor mRNA were observed in neither control rats nor hypophysectomised rats. Our findings indicate that the daily rhythm of thyroid hormone secretion is governed by SCN signalling via the rhythmic TSH secretion rather than by the local thyroid clock, which was still ticking after hypophysectomy.
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Baek, Mokryun, Stela Virgilio, Teresa M. Lamb, Oneida Ibarra, Juvana Moreira Andrade, Rodrigo Duarte Gonçalves, Andrey Dovzhenok, et al. "Circadian clock regulation of the glycogen synthase (gsn) gene by WCC is critical for rhythmic glycogen metabolism inNeurospora crassa." Proceedings of the National Academy of Sciences 116, no. 21 (May 2, 2019): 10435–40. http://dx.doi.org/10.1073/pnas.1815360116.
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Circadian clocks generate rhythms in cellular functions, including metabolism, to align biological processes with the 24-hour environment. Disruption of this alignment by shift work alters glucose homeostasis. Glucose homeostasis depends on signaling and allosteric control; however, the molecular mechanisms linking the clock to glucose homeostasis remain largely unknown. We investigated the molecular links between the clock and glycogen metabolism, a conserved glucose homeostatic process, inNeurospora crassa. We find that glycogen synthase (gsn) mRNA, glycogen phosphorylase (gpn) mRNA, and glycogen levels, accumulate with a daily rhythm controlled by the circadian clock. Because the synthase and phosphorylase are critical to homeostasis, their roles in generating glycogen rhythms were investigated. We demonstrate that whilegsnwas necessary for glycogen production, constitutivegsnexpression resulted in high and arrhythmic glycogen levels, and deletion ofgpnabolishedgsnmRNA rhythms and rhythmic glycogen accumulation. Furthermore, we show thatgsnpromoter activity is rhythmic and is directly controlled by core clock component white collar complex (WCC). We also discovered that WCC-regulated transcription factors, VOS-1 and CSP-1, modulate the phase and amplitude of rhythmicgsnmRNA, and these changes are similarly reflected in glycogen oscillations. Together, these data indicate the importance of clock-regulatedgsntranscription over signaling or allosteric control of glycogen rhythms, a mechanism that is potentially conserved in mammals and critical to metabolic homeostasis.
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Burger, David W. "Intermittent Mist Control via Solar Cells." HortTechnology 4, no. 3 (July 1994): 273–74. http://dx.doi.org/10.21273/horttech.4.3.273.
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Comparisons were made between a commercially available, solar-activated mist control device (Weather Watcher®) and time clocks to determine their relative effectiveness, usefulness, and water-use characteristics on a greenhouse mist propagation bench. Coleus cuttings produced more roots per cutting and had greater average root lengths under Weather Watcher-controlled mist than those cuttings on a mist bench controlled by time. Paulownia cuttings produced the same number of roots under solar- or time-activated mist; however, the average root length was greater under Weather Watcher control. Mist benches controlled by the Weather Watcher used only one-third the water used by benches controlled by a time clock.
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Chambers, W. G., and J. Dj Golić. "Fast reconstruction of clock-control sequence." Electronics Letters 38, no. 20 (2002): 1174. http://dx.doi.org/10.1049/el:20020799.
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Kåhrström, Christina Tobin. "Bacteria seize control of the clock." Nature Reviews Microbiology 11, no. 6 (April 22, 2013): 362–63. http://dx.doi.org/10.1038/nrmicro3027.
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Gamble, Karen L., Ryan Berry, Stuart J. Frank, and Martin E. Young. "Circadian clock control of endocrine factors." Nature Reviews Endocrinology 10, no. 8 (May 27, 2014): 466–75. http://dx.doi.org/10.1038/nrendo.2014.78.
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Harrington, Monica. "Shedding light on circadian clock control." Lab Animal 44, no. 7 (June 19, 2015): 247. http://dx.doi.org/10.1038/laban.808.
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Honma, Aya, Yoshiko Yamada, Yuji Nakamaru, Satoshi Fukuda, Ken-ichi Honma, and Sato Honma. "Glucocorticoids Reset the Nasal Circadian Clock in Mice." Endocrinology 156, no. 11 (September 10, 2015): 4302–11. http://dx.doi.org/10.1210/en.2015-1490.
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The symptoms of allergic rhinitis show marked day-night changes that are likely to be under the control of the circadian clock, but the mechanism of this control is poorly understood. Because most peripheral tissues have endogenous circadian clocks, we examined the circadian rhythm of the clock gene product PERIOD2 (PER2) in the nasal mucosa of male mice using a luciferase reporter and demonstrated for the first time the phase-dependent effects of dexamethasone (DEX) on nasal PER2 rhythm in vivo and ex vivo. The phase shifts in PER2 rhythm caused by DEX were observed around the peak phase of serum glucocorticoids, suggesting that the circadian rhythm of endogenous glucocorticoids regulates the peripheral clock of the mouse nasal mucosa. From the viewpoint of circadian physiology, the best time to administer intranasal steroid treatment for allergic rhinitis would be when no phase shift is caused by DEX: in the early evening in diurnal humans.
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Wu, Tao, Fen ZhuGe, Lu Sun, Yinhua Ni, Ou Fu, Guangang Gao, Junjie Chen, Hisanori Kato, and Zhengwei Fu. "Enhanced effect of daytime restricted feeding on the circadian rhythm of streptozotocin-induced type 2 diabetic rats." American Journal of Physiology-Endocrinology and Metabolism 302, no. 9 (May 1, 2012): E1027—E1035. http://dx.doi.org/10.1152/ajpendo.00651.2011.
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There is increasing awareness of the link between impaired circadian clocks and multiple metabolic diseases. However, the impairment of the circadian clock by type 2 diabetes has not been fully elucidated. To understand whether and how the function of circadian clock is impaired under the diabetic condition, we examined not only the expression of circadian genes in the heart and pineal gland but also the behavioral rhythm of type 2 diabetic and control rats in both the nighttime restricted feeding (NRF) and daytime restricted feeding (DRF) conditions. In the NRF condition, the circadian expression of clock genes in the heart and pineal gland was conserved in the diabetic rats, being similar to that in the control rats. DRF shifted the circadian phases of peripheral clock genes more efficiently in the diabetic rats than those in the control rats. Moreover, the activity rhythm of rats in the diabetic group was completely shifted from the dark phase to the light phase after 5 days of DRF treatment, whereas the activity rhythm of rats in the control group was still under the control of the suprachiasmatic nucleus (SCN) after the same DRF treatment. Furthermore, the serum glucose rhythm of type 2 diabetic rats was also shifted and controlled by the external feeding schedule, ignoring the SCN rhythm. Therefore, DRF shows stronger effect on the reentrainment of circadian rhythm in the type 2 diabetic rats, suggesting that the circadian system in diabetes is unstable and more easily shifted by feeding stimuli.
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Yang, Chuan Shun, and Xiang Ying Kong. "Application of Precision Time Protocol on Networked Control Systems." Applied Mechanics and Materials 203 (October 2012): 192–97. http://dx.doi.org/10.4028/www.scientific.net/amm.203.192.
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In order to overcome the problem of the clock synchronization accuracy between scattered nodes was not high on traditional networked control systems, proposed a new method of using the IEEE 1588 standard for precision time protocol. First studied the principle and algorithm of precision time protocol, the best master clock algorithm and timestamp detection methods. Then presented the timestamp detection method with the use of software and hardware on networked control systems to improve clock synchronization accuracy, and analyzed the feasibility of the method in theory. Finally, tested accuracy of the clock synchronization, and the test results showed that synchronization accuracy can reach nanosecond, can meet the application requirements of the networked control systems.
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Kim, Hyunmin, Hyo Jung Kim, Quy Thi Vu, Sukjoon Jung, C. Robertson McClung, Sunghyun Hong, and Hong Gil Nam. "Circadian control of ORE1 by PRR9 positively regulates leaf senescence in Arabidopsis." Proceedings of the National Academy of Sciences 115, no. 33 (July 31, 2018): 8448–53. http://dx.doi.org/10.1073/pnas.1722407115.
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The circadian clock coordinates the daily cyclic rhythm of numerous biological processes by regulating a large portion of the transcriptome. In animals, the circadian clock is involved in aging and senescence, and circadian disruption by mutations in clock genes frequently accelerates aging. Conversely, aging alters circadian rhythmicity, which causes age-associated physiological alterations. However, interactions between the circadian clock and aging have been rarely studied in plants. Here, we investigated potential roles for the circadian clock in the regulation of leaf senescence in plants. Members of the evening complex in Arabidopsis circadian clock, EARLY FLOWERING 3 (ELF3), EARLY FLOWERING 4 (ELF4), and LUX ARRHYTHMO (LUX), as well as the morning component PSEUDO-RESPONSE REGULATOR 9 (PRR9), affect both age-dependent and dark-induced leaf senescence. The circadian clock regulates the expression of several senescence-related transcription factors. In particular, PRR9 binds directly to the promoter of the positive aging regulator ORESARA1 (ORE1) gene to promote its expression. PRR9 also represses miR164, a posttranscriptional repressor of ORE1. Consistently, genetic analysis revealed that delayed leaf senescence of a prr9 mutant was rescued by ORE1 overexpression. Thus, PRR9, a core circadian component, is a key regulator of leaf senescence via positive regulation of ORE1 through a feed-forward pathway involving posttranscriptional regulation by miR164 and direct transcriptional regulation. Our results indicate that, in plants, the circadian clock and leaf senescence are intimately interwoven as are the clock and aging in animals.
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Yari Kamrani, Yousef, Aida Shomali, Sasan Aliniaeifard, Oksana Lastochkina, Moein Moosavi-Nezhad, Nima Hajinajaf, and Urszula Talar. "Regulatory Role of Circadian Clocks on ABA Production and Signaling, Stomatal Responses, and Water-Use Efficiency under Water-Deficit Conditions." Cells 11, no. 7 (March 29, 2022): 1154. http://dx.doi.org/10.3390/cells11071154.
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Plants deploy molecular, physiological, and anatomical adaptations to cope with long-term water-deficit exposure, and some of these processes are controlled by circadian clocks. Circadian clocks are endogenous timekeepers that autonomously modulate biological systems over the course of the day–night cycle. Plants’ responses to water deficiency vary with the time of the day. Opening and closing of stomata, which control water loss from plants, have diurnal responses based on the humidity level in the rhizosphere and the air surrounding the leaves. Abscisic acid (ABA), the main phytohormone modulating the stomatal response to water availability, is regulated by circadian clocks. The molecular mechanism of the plant’s circadian clock for regulating stress responses is composed not only of transcriptional but also posttranscriptional regulatory networks. Despite the importance of regulatory impact of circadian clock systems on ABA production and signaling, which is reflected in stomatal responses and as a consequence influences the drought tolerance response of the plants, the interrelationship between circadian clock, ABA homeostasis, and signaling and water-deficit responses has to date not been clearly described. In this review, we hypothesized that the circadian clock through ABA directs plants to modulate their responses and feedback mechanisms to ensure survival and to enhance their fitness under drought conditions. Different regulatory pathways and challenges in circadian-based rhythms and the possible adaptive advantage through them are also discussed.
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Ben-Moshe, Zohar, Nicholas S. Foulkes, and Yoav Gothilf. "Functional Development of the Circadian Clock in the Zebrafish Pineal Gland." BioMed Research International 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/235781.
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The zebrafish constitutes a powerful model organism with unique advantages for investigating the vertebrate circadian timing system and its regulation by light. In particular, the remarkably early and rapid development of the zebrafish circadian system has facilitated exploring the factors that control the onset of circadian clock function during embryogenesis. Here, we review our understanding of the molecular basis underlying functional development of the central clock in the zebrafish pineal gland. Furthermore, we examine how the directly light-entrainable clocks in zebrafish cell lines have facilitated unravelling the general mechanisms underlying light-induced clock gene expression. Finally, we summarize how analysis of the light-induced transcriptome and miRNome of the zebrafish pineal gland has provided insight into the regulation of the circadian system by light, including the involvement of microRNAs in shaping the kinetics of light- and clock-regulated mRNA expression. The relative contributions of the pineal gland central clock and the distributed peripheral oscillators to the synchronization of circadian rhythms at the whole animal level are a crucial question that still remains to be elucidated in the zebrafish model.
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Zhang, Ya Bin, Chuan Feng Wei, Xing Qian Li, and Xiao Lin Shi. "Research on Spacecraft Attitude Control Simulation Technology Based on Multidisciplinary Integration." Applied Mechanics and Materials 596 (July 2014): 572–75. http://dx.doi.org/10.4028/www.scientific.net/amm.596.572.
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The design of spacecraft attitude control is important during the manufacture of spacecraft, and it is need to be validated adequately. To get the digital simulation validation of attitude control system, this paper discussed the spacecraft attitude control simulation system based on STK, Matlab and ADAMS. Based on the simulation frame, the paper analyzed the simulation model inter-clock. and realized the simulation system clock synchronization mechanism and algorithm. Based on the method of clock synchronization, the clock synchronization and logic correctness of message among multi-disciplinary simulation models could be ensured.
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Jin, Junting, Yuhua Jin, and Yebing Gan. "A 500 kHz to 150 MHz Multi-Output Clock Generator Using Analog PLL and Open-Loop Fractional Divider with 0.13 μm CMOS." Electronics 11, no. 15 (July 27, 2022): 2347. http://dx.doi.org/10.3390/electronics11152347.
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Clocks are widely used in multimedia and electronic devices, and they usually have different frequency demands. This paper presents the design of a multi-output clock generator using an analog integer-N phase-locked loop (PLL) and open-loop fractional dividers. The PLL based on a three-stage ring voltage-controlled oscillator (VCO) is used to transform the lower frequency reference into a high-frequency intermediate clock (600 MHz–900 MHz). Then, relying on the open-loop fractional divider, a wide frequency range of 500 kHz to 150 MHz can be generated. Due to the open-loop control characteristic, the clock generator has instantaneous frequency switching capability. In addition, phase-adjusting circuits added to the divider greatly improved the jitter performance of the output clock; its RMS jitter is 5.2 ps. This work was conducted with 0.13 μm CMOS technology. The open-loop divider occupies an area of 0.032 mm2 and consumes 7.7 mW from a 1.2 V supply.
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Liu, Xiaorong, and Carla B. Green. "Circadian Regulation of nocturnin Transcription by Phosphorylated CREB in Xenopus Retinal Photoreceptor Cells." Molecular and Cellular Biology 22, no. 21 (November 1, 2002): 7501–11. http://dx.doi.org/10.1128/mcb.22.21.7501-7511.2002.
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ABSTRACT Although CLOCK/BMAL1 heterodimers have been implicated in transcriptional regulation of several rhythmic genes in vitro through E-box sequence elements, little is known about how the circadian clock regulates rhythmic genes with diverse phases in vivo. The gene nocturnin is rhythmically transcribed in Xenopus retinal photoreceptor cells, which contain endogenous circadian clocks. Transcription of nocturnin peaks in these cells in the middle of the night, while CLOCK/BMAL1 activity peaks during the early morning. We have identified a novel protein-binding motif within the nocturnin promoter, which we designated the nocturnin element (NE). Although the NE sequence closely resembles an E-box, our data show that it functions as a cyclic AMP response element (CRE) by binding CREB. Furthermore, phosphorylated CREB (P-CREB) levels are rhythmic in Xenopus photoreceptors, with a phase similar to that of nocturnin transcription. Our results suggest that P-CREB controls the rhythmic regulation of nocturnin transcription and perhaps that of other night phase genes. The NE may be an evolutionary intermediate between the E-box and CRE sequences, both of which seem to be involved in the circadian control of transcription, but have evolved to drive transcription with different phases in these clock-containing cells.
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Vandenberghe, Alan, Marc Lefranc, and Alessandro Furlan. "An Overview of the Circadian Clock in the Frame of Chronotherapy: From Bench to Bedside." Pharmaceutics 14, no. 7 (July 6, 2022): 1424. http://dx.doi.org/10.3390/pharmaceutics14071424.
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Most living organisms in both the plant and animal kingdoms have evolved processes to stay in tune with the alternation of day and night, and to optimize their physiology as a function of light supply. In mammals, a circadian clock relying on feedback loops between key transcription factors will thus control the temporally regulated pattern of expression of most genes. Modern ways of life have highly altered the synchronization of human activities with their circadian clocks. This review discusses the links between an altered circadian clock and the rise of pathologies. We then sum up the proofs of concept advocating for the integration of circadian clock considerations in chronotherapy for health care, medicine, and pharmacotherapy. Finally, we discuss the current challenges that circadian biology must face and the tools to address them.