Krüppel-like factor 15: Regulator of BCAA metabolism and circadian protein rhythmicity.

Science.gov (United States)

Fan, Liyan; Hsieh, Paishiun N; Sweet, David R; Jain, Mukesh K

2018-04-01

Regulation of nutrient intake, utilization, and storage exhibits a circadian rhythmicity that allows organisms to anticipate and adequately respond to changes in the environment across day/night cycles. The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are important modulators of metabolism and metabolic health - for example, their catabolism yields carbon substrates for gluconeogenesis during periods of fasting. Krüppel-like factor 15 (KLF15) has recently emerged as a critical transcriptional regulator of BCAA metabolism, and the absence of this transcription factor contributes to severe pathologies such as Duchenne muscular dystrophy and heart failure. This review highlights KLF15's role as a central regulator of BCAA metabolism during periods of fasting, throughout day/night cycles, and in experimental models of muscle disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Linking Core Promoter Classes to Circadian Transcription.

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Pål O Westermark

2016-08-01

Full Text Available Circadian rhythms in transcription are generated by rhythmic abundances and DNA binding activities of transcription factors. Propagation of rhythms to transcriptional initiation involves the core promoter, its chromatin state, and the basal transcription machinery. Here, I characterize core promoters and chromatin states of genes transcribed in a circadian manner in mouse liver and in Drosophila. It is shown that the core promoter is a critical determinant of circadian mRNA expression in both species. A distinct core promoter class, strong circadian promoters (SCPs, is identified in mouse liver but not Drosophila. SCPs are defined by specific core promoter features, and are shown to drive circadian transcriptional activities with both high averages and high amplitudes. Data analysis and mathematical modeling further provided evidence for rhythmic regulation of both polymerase II recruitment and pause release at SCPs. The analysis provides a comprehensive and systematic view of core promoters and their link to circadian mRNA expression in mouse and Drosophila, and thus reveals a crucial role for the core promoter in regulated, dynamic transcription.

The cholinergic system, circadian rhythmicity, and time memory

NARCIS (Netherlands)

Hut, R. A.; Van der Zee, E. A.

2011-01-01

This review provides an overview of the interaction between the mammalian cholinergic system and circadian system, and its possible role in time memory. Several studies made clear that circadian (daily) fluctuations in acetylcholine (ACh) release, cholinergic enzyme activity and cholinergic receptor

Daily rhythmicity of body temperature in the dog.

Science.gov (United States)

Refinetti, R; Piccione, G

2003-08-01

Research over the past 50 years has demonstrated the existence of circadian or daily rhythmicity in the body core temperature of a large number of mammalian species. However, previous studies have failed to identify daily rhythmicity of body temperature in dogs. We report here the successful recording of daily rhythms of rectal temperature in female Beagle dogs. The low robustness of the rhythms (41% of maximal robustness) and the small range of excursion (0.5 degrees C) are probably responsible for previous failures in detecting rhythmicity in dogs.

Maternal-fetal communication of circadian phase in a precocious rodent, the spiny mouse

International Nuclear Information System (INIS)

Weaver, D.R.; Reppert, S.M.

1987-01-01

The development of circadian rhythms was examined in a precocious rodent species, the spiny mouse. Spiny mouse pups born and reared in constant darkness expressed robust circadian rhythms in locomotor activity as early as day 5 of live. Free-running activity rhythms of pups born and reared in constant darkness were coordinated with the dam on the day of birth. Postnatal maternal influences on pup rhythmicity are minimal in this species, as pups fostered on the day of birth to dams whose circadian phases were opposite to the pups' original dams were coordinated with their original dams on the day of birth. Studies using 2-deoxy-D-[1- 14 C]-glucose authoradiography showed that there were synchronous (coordinated) rhythms in metabolic activity in the maternal and fetal suprachiasmatic nuclei, directly demonstrating prenatal coordination of maternal and fetal rhythmicity. Maternal-fetal coordination of circadian phase was not the result of direct entrainment of the fetuses to the environmental light-dark cycle. These results demonstrate that there is prenatal communication of circadian phase in this precocious species, without demonstrable postnatal maternal influences on pup circadian rhythmicity. Spiny mice therefore represent an important animal model in which circadian rhythms in the postnatal period can be used to precisely assess prenatal influences on circadian phase

Chronotype-dependent circadian rhythmicity of driving safety.

Science.gov (United States)

Del Rio-Bermudez, Carlos; Diaz-Piedra, Carolina; Catena, Andrés; Buela-Casal, Gualberto; Di Stasi, Leandro Luigi

2014-05-01

Among the factors associated with driving safety, sleep-related variables constitute a leading cause of road accidents. Circadian fluctuations of driver's somnolence has been previously linked to road safety. However, the role of chronotype in this relationship has been poorly investigated. Thus, the aim of the present work was to address whether driving performance is influenced by circadian patterns, in turn modulated by the driver's chronotype and the time of day (i.e. synchrony effect). We assessed 47 healthy young adults with specific chronotypes in several simulated driving sessions, both in the morning and in the evening. We collected driving performance data, along with self-reported levels of activation prior to each driving session and other sleep-related variables. Participants drove less safely when testing times took place outside their optimal time of day, as determined by their chronotype and confirmed by self-reported levels of activation. These differences were more pronounced in the morning, when morning types shown a better driving performance. Our results suggest that chronotype plays an important role as a modulator of the relationship between the time of day and driving safety. Therefore, it is necessary to acknowledge this variable in theoretical models of driving behavior, and for the improvement of occupational accidents prevention programs.

Blood-gene expression reveals reduced circadian rhythmicity in individuals resistant to sleep deprivation.

Science.gov (United States)

Arnardottir, Erna S; Nikonova, Elena V; Shockley, Keith R; Podtelezhnikov, Alexei A; Anafi, Ron C; Tanis, Keith Q; Maislin, Greg; Stone, David J; Renger, John J; Winrow, Christopher J; Pack, Allan I

2014-10-01

To address whether changes in gene expression in blood cells with sleep loss are different in individuals resistant and sensitive to sleep deprivation. Blood draws every 4 h during a 3-day study: 24-h normal baseline, 38 h of continuous wakefulness and subsequent recovery sleep, for a total of 19 time-points per subject, with every 2-h psychomotor vigilance task (PVT) assessment when awake. Sleep laboratory. Fourteen subjects who were previously identified as behaviorally resistant (n = 7) or sensitive (n = 7) to sleep deprivation by PVT. Thirty-eight hours of continuous wakefulness. We found 4,481 unique genes with a significant 24-h diurnal rhythm during a normal sleep-wake cycle in blood (false discovery rate [FDR] sleep. After accounting for circadian effects, two genes (SREBF1 and CPT1A, both involved in lipid metabolism) exhibited small, but significant, linear changes in expression with the duration of sleep deprivation (FDR sleep deprivation was a reduction in the amplitude of the diurnal rhythm of expression of normally cycling probe sets. This reduction was noticeably higher in behaviorally resistant subjects than sensitive subjects, at any given P value. Furthermore, blood cell type enrichment analysis showed that the expression pattern difference between sensitive and resistant subjects is mainly found in cells of myeloid origin, such as monocytes. Individual differences in behavioral effects of sleep deprivation are associated with differences in diurnal amplitude of gene expression for genes that show circadian rhythmicity. © 2014 Associated Professional Sleep Societies, LLC.

Rev-erbα and the circadian transcriptional regulation of metabolism

DEFF Research Database (Denmark)

Gerhart-Hines, Z.; Lazar, M. A.

2015-01-01

The circadian clock orchestrates the coordinated rhythmicity of numerous metabolic pathways to anticipate daily and seasonal changes in energy demand. This vital physiol. function is controlled by a set of individual clock components that are present in each cell of the body, and regulate each ot...... between circadian rhythm and tissue-specific biol. networks and its relevance to organismal physiology.......The circadian clock orchestrates the coordinated rhythmicity of numerous metabolic pathways to anticipate daily and seasonal changes in energy demand. This vital physiol. function is controlled by a set of individual clock components that are present in each cell of the body, and regulate each...

The hormonal Zeitgeber melatonin: Role as a circadian modulator in memory processing

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Oliver eRawashdeh

2012-03-01

Full Text Available The neuroendocrine substance melatonin is a hormone synthesized rhythmically by the pineal gland under the influence of the circadian system and alternating light/dark cycles. Melatonin has been shown to have broad applications, and consequently becoming a molecule of great controversy. Undoubtedly, however, melatonin plays an important role as a time cue for the endogenous circadian system. This review focuses on melatonin as a regulator in the circadian modulation of memory processing. Memory processes (acquisition, consolidation and retrieval are modulated by the circadian system. However, the mechanism by which the biological clock is rhythmically influencing cognitive processes remains unknown. We also discuss, how the circadian system by generating cycling melatonin levels can implant information about daytime into memory processing, depicted as day and nighttime differences in acquisition, memory consolidation and/or retrieval.

The Molecular Circadian Clock and Alcohol-Induced Liver Injury

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Uduak S. Udoh

2015-10-01

Full Text Available Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.

Organization of Circadian Behavior Relies on Glycinergic Transmission.

Science.gov (United States)

Frenkel, Lia; Muraro, Nara I; Beltrán González, Andrea N; Marcora, María S; Bernabó, Guillermo; Hermann-Luibl, Christiane; Romero, Juan I; Helfrich-Förster, Charlotte; Castaño, Eduardo M; Marino-Busjle, Cristina; Calvo, Daniel J; Ceriani, M Fernanda

2017-04-04

The small ventral lateral neurons (sLNvs) constitute a central circadian pacemaker in the Drosophila brain. They organize daily locomotor activity, partly through the release of the neuropeptide pigment-dispersing factor (PDF), coordinating the action of the remaining clusters required for network synchronization. Despite extensive efforts, the basic principles underlying communication among circadian clusters remain obscure. We identified classical neurotransmitters released by sLNvs through disruption of specific transporters. Adult-specific RNAi-mediated downregulation of the glycine transporter or impairment of glycine synthesis in LNv neurons increased period length by nearly an hour without affecting rhythmicity of locomotor activity. Electrophysiological recordings showed that glycine reduces spiking frequency in circadian neurons. Interestingly, downregulation of glycine receptor subunits in specific sLNv targets impaired rhythmicity, revealing involvement of glycine in information processing within the network. These data identify glycinergic inhibition of specific targets as a cue that contributes to the synchronization of the circadian network. Copyright © 2017 Elsevier Inc. All rights reserved.

Circadian Activity Rhythms, Time Urgency, and Achievement Concerns.

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Watts, Barbara L.

Many physiological and psychological processes fluctuate throughout the day in fairly stable, rhythmic patterns. The relationship between individual differences in circadian activity rhythms and a sense of time urgency were explored as well as a number of achievement-related variables. Undergraduates (N=308), whose circadian activity rhythms were…

BK channels regulate spontaneous action potential rhythmicity in the suprachiasmatic nucleus.

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Jack Kent

Full Text Available BACKGROUND: Circadian ( approximately 24 hr rhythms are generated by the central pacemaker localized to the suprachiasmatic nucleus (SCN of the hypothalamus. Although the basis for intrinsic rhythmicity is generally understood to rely on transcription factors encoded by "clock genes", less is known about the daily regulation of SCN neuronal activity patterns that communicate a circadian time signal to downstream behaviors and physiological systems. Action potentials in the SCN are necessary for the circadian timing of behavior, and individual SCN neurons modulate their spontaneous firing rate (SFR over the daily cycle, suggesting that the circadian patterning of neuronal activity is necessary for normal behavioral rhythm expression. The BK K(+ channel plays an important role in suppressing spontaneous firing at night in SCN neurons. Deletion of the Kcnma1 gene, encoding the BK channel, causes degradation of circadian behavioral and physiological rhythms. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that loss of robust behavioral rhythmicity in Kcnma1(-/- mice is due to the disruption of SFR rhythms in the SCN, we used multi-electrode arrays to record extracellular action potentials from acute wild-type (WT and Kcnma1(-/- slices. Patterns of activity in the SCN were tracked simultaneously for up to 3 days, and the phase, period, and synchronization of SFR rhythms were examined. Loss of BK channels increased arrhythmicity but also altered the amplitude and period of rhythmic activity. Unexpectedly, Kcnma1(-/- SCNs showed increased variability in the timing of the daily SFR peak. CONCLUSIONS/SIGNIFICANCE: These results suggest that BK channels regulate multiple aspects of the circadian patterning of neuronal activity in the SCN. In addition, these data illustrate the characteristics of a disrupted SCN rhythm downstream of clock gene-mediated timekeeping and its relationship to behavioral rhythms.

The Circadian Clock Gene BMAL1 Coordinates Intestinal RegenerationSummary

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Kyle Stokes

2017-07-01

Full Text Available Background & Aims: The gastrointestinal syndrome is an illness of the intestine caused by high levels of radiation. It is characterized by extensive loss of epithelial tissue integrity, which initiates a regenerative response by intestinal stem and precursor cells. The intestine has 24-hour rhythms in many physiological functions that are believed to be outputs of the circadian clock: a molecular system that produces 24-hour rhythms in transcription/translation. Certain gastrointestinal illnesses are worsened when the circadian rhythms are disrupted, but the role of the circadian clock in gastrointestinal regeneration has not been studied. Methods: We tested the timing of regeneration in the mouse intestine during the gastrointestinal syndrome. The role of the circadian clock was tested genetically using the BMAL1 loss of function mouse mutant in vivo, and in vitro using intestinal organoid culture. Results: The proliferation of the intestinal epithelium follows a 24-hour rhythm during the gastrointestinal syndrome. The circadian clock runs in the intestinal epithelium during this pathologic state, and the loss of the core clock gene, BMAL1, disrupts both the circadian clock and rhythmic proliferation. Circadian activity in the intestine involves a rhythmic production of inflammatory cytokines and subsequent rhythmic activation of the JNK stress response pathway. Conclusions: Our results show that a circadian rhythm in inflammation and regeneration occurs during the gastrointestinal syndrome. The study and treatment of radiation-induced illnesses, and other gastrointestinal illnesses, should consider 24-hour timing in physiology and pathology. Keywords: Intestine, Circadian Rhythms, Gastrointestinal Syndrome, TNF, Intestinal Stem Cells

Cell-permeable Circadian Clock Proteins

National Research Council Canada - National Science Library

Johnson, Carl

2002-01-01

.... These 'biological clocks' are important to human physiology. For example, psychiatric and medical studies have shown that circadian rhythmicity is involved in some forms of depressive illness, 'jet lag', drug tolerance/efficacy, memory, and insomnia...

Discrepancy between circadian rhythms of inulin and creatinine clearance

NARCIS (Netherlands)

van Acker, B. A.; Koomen, G. C.; Koopman, M. G.; Krediet, R. T.; Arisz, L.

1992-01-01

To elucidate the disparity between circadian rhythmicity of inulin and creatinine clearance, we simultaneously measured inulin and creatinine clearances every 3 hours during 1 day in 14 normal subjects and in 8 patients with nephrotic syndrome. All patients and normal subjects had a circadian rhythm

Meal time shift disturbs circadian rhythmicity along with metabolic and behavioral alterations in mice.

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Ji-Ae Yoon

Full Text Available In modern society, growing numbers of people are engaged in various forms of shift works or trans-meridian travels. Such circadian misalignment is known to disturb endogenous diurnal rhythms, which may lead to harmful physiological consequences including metabolic syndrome, obesity, cancer, cardiovascular disorders, and gastric disorders as well as other physical and mental disorders. However, the precise mechanism(s underlying these changes are yet unclear. The present work, therefore examined the effects of 6 h advance or delay of usual meal time on diurnal rhythmicities in home cage activity (HCA, body temperature (BT, blood metabolic markers, glucose homeostasis, and expression of genes that are involved in cholesterol homeostasis by feeding young adult male mice in a time-restrictive manner. Delay of meal time caused locomotive hyperactivity in a significant portion (42% of subjects, while 6 h advance caused a torpor-like symptom during the late scotophase. Accordingly, daily rhythms of blood glucose and triglyceride were differentially affected by time-restrictive feeding regimen with concurrent metabolic alterations. Along with these physiological changes, time-restrictive feeding also influenced the circadian expression patterns of low density lipoprotein receptor (LDLR as well as most LDLR regulatory factors. Strikingly, chronic advance of meal time induced insulin resistance, while chronic delay significantly elevated blood glucose levels. Taken together, our findings indicate that persistent shifts in usual meal time impact the diurnal rhythms of carbohydrate and lipid metabolisms in addition to HCA and BT, thereby posing critical implications for the health and diseases of shift workers.

The Impact of Sleep and Circadian Disturbance on Hormones and Metabolism

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Tae Won Kim

2015-01-01

Full Text Available The levels of several hormones fluctuate according to the light and dark cycle and are also affected by sleep, feeding, and general behavior. The regulation and metabolism of several hormones are influenced by interactions between the effects of sleep and the intrinsic circadian system; growth hormone, melatonin, cortisol, leptin, and ghrelin levels are highly correlated with sleep and circadian rhythmicity. There are also endogenous circadian mechanisms that serve to regulate glucose metabolism and similar rhythms pertaining to lipid metabolism, regulated through the actions of various clock genes. Sleep disturbance, which negatively impacts hormonal rhythms and metabolism, is also associated with obesity, insulin insensitivity, diabetes, hormonal imbalance, and appetite dysregulation. Circadian disruption, typically induced by shift work, may negatively impact health due to impaired glucose and lipid homeostasis, reversed melatonin and cortisol rhythms, and loss of clock gene rhythmicity.

Paternal irradiation perturbs the expression of circadian genes in offspring

Energy Technology Data Exchange (ETDEWEB)

Gomes, Andre M.G.F.; Barber, Ruth C.; Dubrova, Yuri E., E-mail: yed2@le.ac.uk

2015-05-15

Highlights: • We have analysed gene expression in the offspring of irradiated male mice. • CBA/Ca and BALB/c male mice were used in our study. • The pattern of gene expression was established in four tissues. • Expression of genes in involved in rhythmic process/circadian rhythm is compromised. • Our data may explain the phenomenon of transgenerational genomic instability. - Abstract: The circadian system represents a complex network which influences the timing of many biological processes. Recent studies have established that circadian alterations play an important role in the susceptibility to many human diseases, including cancer. Here we report that paternal irradiation in mice significantly affects the expression of genes involved in rhythmic processes in their first-generation offspring. Using microarrays, the patterns of gene expression were established for brain, kidney, liver and spleen samples from the non-exposed offspring of irradiated CBA/Ca and BALB/c male mice. The most over-represented categories among the genes differentially expressed in the offspring of control and irradiated males were those involved in rhythmic process, circadian rhythm and DNA-dependent regulation of transcription. The results of our study therefore provide a plausible explanation for the transgenerational effects of paternal irradiation, including increased transgenerational carcinogenesis described in other studies.

Paternal irradiation perturbs the expression of circadian genes in offspring

International Nuclear Information System (INIS)

Gomes, Andre M.G.F.; Barber, Ruth C.; Dubrova, Yuri E.

2015-01-01

Highlights: • We have analysed gene expression in the offspring of irradiated male mice. • CBA/Ca and BALB/c male mice were used in our study. • The pattern of gene expression was established in four tissues. • Expression of genes in involved in rhythmic process/circadian rhythm is compromised. • Our data may explain the phenomenon of transgenerational genomic instability. - Abstract: The circadian system represents a complex network which influences the timing of many biological processes. Recent studies have established that circadian alterations play an important role in the susceptibility to many human diseases, including cancer. Here we report that paternal irradiation in mice significantly affects the expression of genes involved in rhythmic processes in their first-generation offspring. Using microarrays, the patterns of gene expression were established for brain, kidney, liver and spleen samples from the non-exposed offspring of irradiated CBA/Ca and BALB/c male mice. The most over-represented categories among the genes differentially expressed in the offspring of control and irradiated males were those involved in rhythmic process, circadian rhythm and DNA-dependent regulation of transcription. The results of our study therefore provide a plausible explanation for the transgenerational effects of paternal irradiation, including increased transgenerational carcinogenesis described in other studies

Physiological effects of light on the human circadian pacemaker

Science.gov (United States)

Shanahan, T. L.; Czeisler, C. A.

2000-01-01

The physiology of the human circadian pacemaker and its influence and on the daily organization of sleep, endocrine and behavioral processes is an emerging interest in science and medicine. Understanding the development, organization and fundamental properties underlying the circadian timing system may provide insight for the application of circadian principles to the practice of clinical medicine, both diagnostically (interpretation of certain clinical tests are dependent on time of day) and therapeutically (certain pharmacological responses vary with the time of day). The light-dark cycle is the most powerful external influence acting upon the human circadian pacemaker. It has been shown that timed exposure to light can both synchronize and reset the phase of the circadian pacemaker in a predictable manner. The emergence of detectable circadian rhythmicity in the neonatal period is under investigation (as described elsewhere in this issue). Therefore, the pattern of light exposure provided in the neonatal intensive care setting has implications. One recent study identified differences in both amount of sleep time and weight gain in infants maintained in a neonatal intensive care environment that controlled the light-dark cycle. Unfortunately, neither circadian phase nor the time of day has been considered in most clinical investigations. Further studies with knowledge of principles characterizing the human circadian timing system, which governs a wide array of physiological processes, are required to integrate these findings with the practice of clinical medicine.

An Approximation to the Temporal Order in Endogenous Circadian Rhythms of Genes Implicated in Human Adipose Tissue Metabolism

Science.gov (United States)

GARAULET, MARTA; ORDOVÁS, JOSÉ M.; GÓMEZ-ABELLÁN, PURIFICACIÓN; MARTÍNEZ, JOSE A.; MADRID, JUAN A.

2015-01-01

Although it is well established that human adipose tissue (AT) shows circadian rhythmicity, published studies have been discussed as if tissues or systems showed only one or few circadian rhythms at a time. To provide an overall view of the internal temporal order of circadian rhythms in human AT including genes implicated in metabolic processes such as energy intake and expenditure, insulin resistance, adipocyte differentiation, dyslipidemia, and body fat distribution. Visceral and subcutaneous abdominal AT biopsies (n = 6) were obtained from morbid obese women (BMI ≥ 40 kg/m2). To investigate rhythmic expression pattern, AT explants were cultured during 24-h and gene expression was analyzed at the following times: 08:00, 14:00, 20:00, 02:00 h using quantitative real-time PCR. Clock genes, glucocorticoid metabolism-related genes, leptin, adiponectin and their receptors were studied. Significant differences were found both in achrophases and relative-amplitude among genes (P 30%). When interpreting the phase map of gene expression in both depots, data indicated that circadian rhythmicity of the genes studied followed a predictable physiological pattern, particularly for subcutaneous AT. Interesting are the relationships between adiponectin, leptin, and glucocorticoid metabolism-related genes circadian profiles. Their metabolic significance is discussed. Visceral AT behaved in a different way than subcutaneous for most of the genes studied. For every gene, protein mRNA levels fluctuated during the day in synchrony with its receptors. We have provided an overall view of the internal temporal order of circadian rhythms in human adipose tissue. PMID:21520059

Dissecting Daily and Circadian Expression Rhythms of Clock-Controlled Genes in Human Blood.

Science.gov (United States)

Lech, Karolina; Ackermann, Katrin; Revell, Victoria L; Lao, Oscar; Skene, Debra J; Kayser, Manfred

2016-02-01

The identification and investigation of novel clock-controlled genes (CCGs) has been conducted thus far mainly in model organisms such as nocturnal rodents, with limited information in humans. Here, we aimed to characterize daily and circadian expression rhythms of CCGs in human peripheral blood during a sleep/sleep deprivation (S/SD) study and a constant routine (CR) study. Blood expression levels of 9 candidate CCGs (SREBF1, TRIB1, USF1, THRA1, SIRT1, STAT3, CAPRIN1, MKNK2, and ROCK2), were measured across 48 h in 12 participants in the S/SD study and across 33 h in 12 participants in the CR study. Statistically significant rhythms in expression were observed for STAT3, SREBF1, TRIB1, and THRA1 in samples from both the S/SD and the CR studies, indicating that their rhythmicity is driven by the endogenous clock. The MKNK2 gene was significantly rhythmic in the S/SD but not the CR study, which implies its exogenously driven rhythmic expression. In addition, we confirmed the circadian expression of PER1, PER3, and REV-ERBα in the CR study samples, while BMAL1 and HSPA1B were not significantly rhythmic in the CR samples; all 5 genes previously showed significant expression in the S/SD study samples. Overall, our results demonstrate that rhythmic expression patterns of clock and selected clock-controlled genes in human blood cells are in part determined by exogenous factors (sleep and fasting state) and in part by the endogenous circadian timing system. Knowledge of the exogenous and endogenous regulation of gene expression rhythms is needed prior to the selection of potential candidate marker genes for future applications in medical and forensic settings. © 2015 The Author(s).

Differential maturation of rhythmic clock gene expression during early development in medaka (Oryzias latipes).

Science.gov (United States)

Cuesta, Ines H; Lahiri, Kajori; Lopez-Olmeda, Jose Fernando; Loosli, Felix; Foulkes, Nicholas S; Vallone, Daniela

2014-05-01

One key challenge for the field of chronobiology is to identify how circadian clock function emerges during early embryonic development. Teleosts such as the zebrafish are ideal models for studying circadian clock ontogeny since the entire process of development occurs ex utero in an optically transparent chorion. Medaka (Oryzias latipes) represents another powerful fish model for exploring early clock function with, like the zebrafish, many tools available for detailed genetic analysis. However, to date there have been no reports documenting circadian clock gene expression during medaka development. Here we have characterized the expression of key clock genes in various developmental stages and in adult tissues of medaka. As previously reported for other fish, light dark cycles are required for the emergence of clock gene expression rhythms in this species. While rhythmic expression of per and cry genes is detected very early during development and seems to be light driven, rhythmic clock and bmal expression appears much later around hatching time. Furthermore, the maturation of clock function seems to correlate with the appearance of rhythmic expression of these positive elements of the clock feedback loop. By accelerating development through elevated temperatures or by artificially removing the chorion, we show an earlier onset of rhythmicity in clock and bmal expression. Thus, differential maturation of key elements of the medaka clock mechanism depends on the developmental stage and the presence of the chorion.

Circadian Enhancers Coordinate Multiple Phases of Rhythmic Gene Transcription In Vivo

Science.gov (United States)

Fang, Bin; Everett, Logan J.; Jager, Jennifer; Briggs, Erika; Armour, Sean M.; Feng, Dan; Roy, Ankur; Gerhart-Hines, Zachary; Sun, Zheng; Lazar, Mitchell A.

2014-01-01

SUMMARY Mammalian transcriptomes display complex circadian rhythms with multiple phases of gene expression that cannot be accounted for by current models of the molecular clock. We have determined the underlying mechanisms by measuring nascent RNA transcription around the clock in mouse liver. Unbiased examination of eRNAs that cluster in specific circadian phases identified functional enhancers driven by distinct transcription factors (TFs). We further identify on a global scale the components of the TF cistromes that function to orchestrate circadian gene expression. Integrated genomic analyses also revealed novel mechanisms by which a single circadian factor controls opposing transcriptional phases. These findings shed new light on the diversity and specificity of TF function in the generation of multiple phases of circadian gene transcription in a mammalian organ. PMID:25416951

SRC-2 is an essential coactivator for orchastrating metabolism and circadian rhythm

Science.gov (United States)

Synchrony of the mammalian circadian clock is achieved by complex transcriptional and translational feedback loops centered on the BMAL1:CLOCK heterodimer. Modulation of circadian feedback loops is essential for maintaining rhythmicity, yet the role of transcriptional coactivators in driving BMAL1:C...

Differentiation of PC12 Cells Results in Enhanced VIP Expression and Prolonged Rhythmic Expression of Clock Genes

DEFF Research Database (Denmark)

Pretzmann, C.P.; Fahrenkrug, J.; Georg, B.

2008-01-01

To examine for circadian rhythmicity, the messenger RNA (mRNA) amount of the clock genes Per1 and Per2 was measured in undifferentiated and nerve-growth-factor-differentiated PC12 cells harvested every fourth hour. Serum shock was needed to induce circadian oscillations, which in undifferentiated...... PC12 cultures lasted only one 24-h period, while in differentiated cultures, the rhythms continued for at least 3 days. Thus, neuronal differentiation provided PC12 cells the ability to maintain rhythmicity for an extended period. Both vasoactive intestinal polypeptide (VIP) and its receptor VPAC(2...

Proteomic identification of rhythmic proteins in rice seedlings.

Science.gov (United States)

Hwang, Heeyoun; Cho, Man-Ho; Hahn, Bum-Soo; Lim, Hyemin; Kwon, Yong-Kook; Hahn, Tae-Ryong; Bhoo, Seong Hee

2011-04-01

Many aspects of plant metabolism that are involved in plant growth and development are influenced by light-regulated diurnal rhythms as well as endogenous clock-regulated circadian rhythms. To identify the rhythmic proteins in rice, periodically grown (12h light/12h dark cycle) seedlings were harvested for three days at six-hour intervals. Continuous dark-adapted plants were also harvested for two days. Among approximately 3000 reproducible protein spots on each gel, proteomic analysis ascertained 354 spots (~12%) as light-regulated rhythmic proteins, in which 53 spots showed prolonged rhythm under continuous dark conditions. Of these 354 ascertained rhythmic protein spots, 74 diurnal spots and 10 prolonged rhythmic spots under continuous dark were identified by MALDI-TOF MS analysis. The rhythmic proteins were functionally classified into photosynthesis, central metabolism, protein synthesis, nitrogen metabolism, stress resistance, signal transduction and unknown. Comparative analysis of our proteomic data with the public microarray database (the Plant DIURNAL Project) and RT-PCR analysis of rhythmic proteins showed differences in rhythmic expression phases between mRNA and protein, suggesting that the clock-regulated proteins in rice are modulated by not only transcriptional but also post-transcriptional, translational, and/or post-translational processes. 2011 Elsevier B.V. All rights reserved.

A circadian gene expression atlas in mammals: implications for biology and medicine.

Science.gov (United States)

Zhang, Ray; Lahens, Nicholas F; Ballance, Heather I; Hughes, Michael E; Hogenesch, John B

2014-11-11

To characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional "rush hours" preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spliceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy.

Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome.

Science.gov (United States)

Kervezee, Laura; Cuesta, Marc; Cermakian, Nicolas; Boivin, Diane B

2018-05-22

Misalignment of the endogenous circadian timing system leads to disruption of physiological rhythms and may contribute to the development of the deleterious health effects associated with night shift work. However, the molecular underpinnings remain to be elucidated. Here, we investigated the effect of a 4-day simulated night shift work protocol on the circadian regulation of the human transcriptome. Repeated blood samples were collected over two 24-hour measurement periods from eight healthy subjects under highly controlled laboratory conditions before and 4 days after a 10-hour delay of their habitual sleep period. RNA was extracted from peripheral blood mononuclear cells to obtain transcriptomic data. Cosinor analysis revealed a marked reduction of significantly rhythmic transcripts in the night shift condition compared with baseline at group and individual levels. Subsequent analysis using a mixed-effects model selection approach indicated that this decrease is mainly due to dampened rhythms rather than to a complete loss of rhythmicity: 73% of transcripts rhythmically expressed at baseline remained rhythmic during the night shift condition with a similar phase relative to habitual bedtimes, but with lower amplitudes. Functional analysis revealed that key biological processes are affected by the night shift protocol, most notably the natural killer cell-mediated immune response and Jun/AP1 and STAT pathways. These results show that 4 days of simulated night shifts leads to a loss in temporal coordination between the human circadian transcriptome and the external environment and impacts biological processes related to the adverse health effects associated to night shift work.

Circadian disc shedding in Xenopus retina in vitro

International Nuclear Information System (INIS)

Flannery, J.G.; Fisher, S.K.

1984-01-01

To further examine the endogenous rhythm of disc shedding and phagocytosis observed in several species, adult Xenopus were entrained to a 12 hr light/12 hr dark cycle and then placed in constant darkness. At various times during a 3-day period of constant darkness, eyes were explanted and placed into culture medium, then processed for light and electron microscopy. A clear rhythmicity of disc shedding was observed, with pronounced peaks at the times light onset occurred in the original entrainment cycle. Modification of the HCO 3 - ion concentration in the medium was found to raise the amplitude of the peak of endogenous disc shedding. Explants maintained in culture medium containing deuterium oxide (a compound known to perturb circadian oscillators) were found to shed with a longer interval between peaks. The addition of the protein synthesis inhibitor, anisomycin, to this preparation suppressed the shedding rhythm. The action of anisomycin was investigated by autoradiographic examination of the pattern of 3 H-leucine uptake and protein synthesis by the explant. The findings suggest the presence of a circadian oscillator for rhythmic disc shedding within the amphibian eye

Circadian rhythms in effects of hypnotics and sleep inducers.

Science.gov (United States)

Reinberg, A

1986-01-01

Chronopharmacology involves the investigation of drug effects as a function of biological time and the investigation of drug effects on rhythm characteristics. Three new concepts must be considered: (a) the chronokinetics of a drug, embracing rhythmic (circadian) changes in drug bioavailability (or pharmacokinetics) and its excretion (urinary among others); (b) the chronaesthesia of a biosystem to a drug, i.e. circadian changes in the susceptibility of any biosystem to a drug (including organ systems, parasites, etc.); skin and bronchial chronaesthesia to various agents have been documented in man; and (c) the chronergy of a drug, taking into consideration its chronokinetics and the chronaesthesia of the involved organismic biosystems. The term chronergy includes rhythmic changes in the overall effects and in the effectiveness of some drugs. Clinical chronopharmacology is useful for solving problems of drug optimization, i.e. enhancing the desired efficiency of a drug and reducing its undesired effects. Circadian rhythms can be demonstrated in various effects of drugs on sleep, anaesthesia and related processes. For example, in the rat the duration of sleep induced by substances such as pentobarbital, hexobarbital, Althesin (alphaxadone and alphadoline in castor oil) is circadian system stage-dependent. Time-dependent changes of liver enzymes (e.g. hexobarbital oxidase) play a role in these circadian rhythms. The clinical chronopharmacokinetics of benzodiazepines have been documented in man. Chronopharmacologic methods can be used to study desired and undesired hypnotic effects of substances. Such is the case of new antihistamines (anti-H1), which do not induce sleepiness, in either acute or chronic administration. Pertinent also is the problem of intolerance to shift-work. Intolerant shift-workers are subject to internal desynchronization between at least two rhythms (e.g. activity-rest cycle and body temperature). Clinically these workers suffer from sleep

Modelling of intercellular synchronization in the Drosophila circadian clock

International Nuclear Information System (INIS)

Jun-Wei, Wang; Ai-Min, Chen; Jia-Jun, Zhang; Zhan-Jiang, Yuan; Tian-Shou, Zhou

2009-01-01

In circadian rhythm generation, intercellular signaling factors are shown to play a crucial role in both sustaining intrinsic cellular rhythmicity and acquiring collective behaviours across a population of circadian neurons. However, the physical mechanism behind their role remains to be fully understood. In this paper, we propose an indirectly coupled multicellular model for the synchronization of Drosophila circadian oscillators combining both intracellular and intercellular dynamics. By simulating different experimental conditions, we find that such an indirect coupling way can synchronize both heterogeneous self-sustained circadian neurons and heterogeneous mutational damped circadian neurons. Moreover, they can also be entrained to ambient light-dark (LD) cycles depending on intercellular signaling. (cross-disciplinary physics and related areas of science and technology)

Meta-analysis of Drosophila circadian microarray studies identifies a novel set of rhythmically expressed genes.

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Kevin P Keegan

2007-11-01

Full Text Available Five independent groups have reported microarray studies that identify dozens of rhythmically expressed genes in the fruit fly Drosophila melanogaster. Limited overlap among the lists of discovered genes makes it difficult to determine which, if any, exhibit truly rhythmic patterns of expression. We reanalyzed data from all five reports and found two sources for the observed discrepancies, the use of different expression pattern detection algorithms and underlying variation among the datasets. To improve upon the methods originally employed, we developed a new analysis that involves compilation of all existing data, application of identical transformation and standardization procedures followed by ANOVA-based statistical prescreening, and three separate classes of post hoc analysis: cross-correlation to various cycling waveforms, autocorrelation, and a previously described fast Fourier transform-based technique. Permutation-based statistical tests were used to derive significance measures for all post hoc tests. We find application of our method, most significantly the ANOVA prescreening procedure, significantly reduces the false discovery rate relative to that observed among the results of the original five reports while maintaining desirable statistical power. We identify a set of 81 cycling transcripts previously found in one or more of the original reports as well as a novel set of 133 transcripts not found in any of the original studies. We introduce a novel analysis method that compensates for variability observed among the original five Drosophila circadian array reports. Based on the statistical fidelity of our meta-analysis results, and the results of our initial validation experiments (quantitative RT-PCR, we predict many of our newly found genes to be bona fide cyclers, and suggest that they may lead to new insights into the pathways through which clock mechanisms regulate behavioral rhythms.

Characterization of circadian behavior in the starlet sea anemone, Nematostella vectensis.

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William D Hendricks

Full Text Available Although much is known about how circadian systems control daily cycles in the physiology and behavior of Drosophila and several vertebrate models, marine invertebrates have often been overlooked in circadian rhythms research. This study focuses on the starlet sea anemone, Nematostella vectensis, a species that has received increasing attention within the scientific community for its potential as a model research organism. The recently sequenced genome of N. vectensis makes it an especially attractive model for exploring the molecular evolution of circadian behavior. Critical behavioral data needed to correlate gene expression patterns to specific behaviors are currently lacking in N. vectensis.To detect the presence of behavioral oscillations in N. vectensis, locomotor activity was evaluated using an automated system in an environmentally controlled chamber. Animals exposed to a 24 hr photoperiod (12 hr light: 12 hr dark exhibited locomotor behavior that was both rhythmic and predominantly nocturnal. The activity peak occurred in the early half of the night with a 2-fold increase in locomotion. Upon transfer to constant lighting conditions (constant light or constant dark, an approximately 24 hr rhythm persisted in most animals, suggesting that the rhythm is controlled by an endogenous circadian mechanism. Fourier analysis revealed the presence of multiple peaks in some animals suggesting additional rhythmic components could be present. In particular, an approximately 12 hr oscillation was often observed. The nocturnal increase in generalized locomotion corresponded to a 24 hr oscillation in animal elongation.These data confirm the presence of a light-entrainable circadian clock in Nematostella vectensis. Additional components observed in some individuals indicate that an endogenous clock of approximately 12 hr frequency may also be present. By describing rhythmic locomotor behavior in N. vectensis, we have made important progress in developing

A Systems-Level Analysis Reveals Circadian Regulation of Splicing in Colorectal Cancer.

Science.gov (United States)

El-Athman, Rukeia; Fuhr, Luise; Relógio, Angela

2018-06-20

Accumulating evidence points to a significant role of the circadian clock in the regulation of splicing in various organisms, including mammals. Both dysregulated circadian rhythms and aberrant pre-mRNA splicing are frequently implicated in human disease, in particular in cancer. To investigate the role of the circadian clock in the regulation of splicing in a cancer progression context at the systems-level, we conducted a genome-wide analysis and compared the rhythmic transcriptional profiles of colon carcinoma cell lines SW480 and SW620, derived from primary and metastatic sites of the same patient, respectively. We identified spliceosome components and splicing factors with cell-specific circadian expression patterns including SRSF1, HNRNPLL, ESRP1, and RBM 8A, as well as altered alternative splicing events and circadian alternative splicing patterns of output genes (e.g., VEGFA, NCAM1, FGFR2, CD44) in our cellular model. Our data reveals a remarkable interplay between the circadian clock and pre-mRNA splicing with putative consequences in tumor progression and metastasis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

An investigation of natural genetic variation in the circadian system of Drosophila melanogaster: rhythm characteristics and methods of quantification.

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Emery, P T; Morgan, E; Birley, A J

1994-04-01

Variation in four characteristics of the circadian locomotor activity rhythm was investigated in 24 true-breeding strains of Drosophila melanogaster with a view to establishing methods of phenotypic measurement sufficiently robust to allow subsequent biometric analysis. Between them, these strains formed a representative sample of the genetic variability of a natural population. Period, phase, definition (the degree to which a rhythmic signal was obscured by noise), and rhythm waveform were all found to vary continuously among the strains, although within each strain the rhythm phenotype was remarkably consistent. Each characteristic was found to be sufficiently robust to permit objective measurement using several different methods of quantification, which were then compared.

Circadian rhythms in handwriting kinematics and legibility

NARCIS (Netherlands)

Jasper, Isabelle; Gordijn, Marijke; Haeussler, Andreas; Hermsdoerfer, Joachim

The aim of the present study was to analyze the circadian rhythmicity in handwriting kinematics and legibility and to compare the performance between Dutch and German writers. Two subject groups underwent a 40 h sleep deprivation protocol under Constant Routine conditions either in Groningen (10

Temporal phasing of locomotor activity, heart rate rhythmicity, and core body temperature is disrupted in VIP receptor 2-deficient mice

DEFF Research Database (Denmark)

Hannibal, Jens; Hsiung, Hansen M; Fahrenkrug, Jan

2011-01-01

Neurons of the brain's biological clock located in the hypothalamic suprachiasmatic nucleus (SCN) generate circadian rhythms of physiology (core body temperature, hormone secretion, locomotor activity, sleep/wake, and heart rate) with distinct temporal phasing when entrained by the light/dark (LD......) cycle. The neuropeptide vasoactive intestinal polypetide (VIP) and its receptor (VPAC2) are highly expressed in the SCN. Recent studies indicate that VIPergic signaling plays an essential role in the maintenance of ongoing circadian rhythmicity by synchronizing SCN cells and by maintaining rhythmicity...... within individual neurons. To further increase the understanding of the role of VPAC2 signaling in circadian regulation, we implanted telemetric devices and simultaneously measured core body temperature, spontaneous activity, and heart rate in a strain of VPAC2-deficient mice and compared...

Light-Dependent Expression of Four Cryptic Archaeal Circadian Gene Homologs

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Michael eManiscalco

2014-03-01

Full Text Available Circadian rhythms are important biological signals that have been found in almost all major groups of life from bacteria to man, yet it remains unclear if any members of the second major prokaryotic domain of life, the Archaea, also possess a biological clock. To investigate this question, we examined the regulation of four cyanobacterial-like circadian gene homologs present in the genome of the haloarchaeon Haloferax volcanii. These genes, designated cirA, cirB, cirC, and cirD, display similarity to the KaiC-family of cyanobacterial clock proteins, which act to regulate rhythmic gene expression and to control the timing of cell division. Quantitative RT-PCR analysis was used to examine the expression of each of the four cir genes in response to 12 h light/12 h dark cycles (LD 12:12 during balanced growth in H. volcanii. Our data reveal that there is an approximately two to sixteen-fold increase in cir gene expression when cells are shifted from light to constant darkness and this pattern of gene expression oscillates with the light conditions in a rhythmic manner. Targeted single- and double-gene knockouts in the H. volcanii cir genes results in disruption of light-dependent, rhythmic gene expression, although it does not lead to any significant effect on growth under these conditions. Restoration of light-dependent, rhythmic gene expression was demonstrated by introducing, in trans, a wild-type copy of individual cir genes into knockout strains. These results are noteworthy as this is the first attempt to characterize the transcriptional expression and regulation of the ubiquitous kaiC homologs found among archaeal genomes.

Rhythmicity and plasticity of digestive physiology in a euryhaline teleost fish, permit (Trachinotus falcatus)

DEFF Research Database (Denmark)

Lazado, Carlo Cabacang; Pedersen, Per Bovbjerg; Nguyen, Huy Quang

2017-01-01

Digestive physiology is considered to be under circadian control, but there is little evidence in teleost fish. The present study explored the rhythmicity and plasticity to feeding schedules of enzymatic digestion in a candidate aquaculture fish, the permit (Trachinotus falcatus). The first...... experiment identified the rhythms of digestive factors throughout the light-dark (LD) cycle. Gastric luminal pH and pepsin activity showed significant daily variation albeit not rhythmic. These dynamic changes were likewise observed in several digestive enzymes, in which the activities of intestinal protease......, chymotrypsin and lipase exhibited significant daily rhythms. In the second experiment, the existence of feed anticipatory activity in the digestive factors was investigated by subjecting the fish to either periodic or random feeding. Anticipatory gastric acidification prior to feeding was identified...

Modeling and analysis of the impacts of jet lag on circadian rhythm and its role in tumor growth

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Azka Hassan

2018-06-01

Full Text Available Circadian rhythms maintain a 24 h oscillation pattern in metabolic, physiological and behavioral processes in all living organisms. Circadian rhythms are organized as biochemical networks located in hypothalamus and peripheral tissues. Rhythmicity in the expression of circadian clock genes plays a vital role in regulating the process of cell division and DNA damage control. The oncogenic protein, MYC and the tumor suppressor, p53 are directly influenced by the circadian clock. Jet lag and altered sleep/wake schedules prominently affect the expression of molecular clock genes. This study is focused on developing a Petri net model to analyze the impacts of long term jet lag on the circadian clock and its probable role in tumor progression. The results depict that jet lag disrupts the normal rhythmic behavior and expression of the circadian clock proteins. This disruption leads to persistent expression of MYC and suppressed expression of p53. Thus, it is inferred that jet lag altered circadian clock negatively affects the expressions of cell cycle regulatory genes and contribute in uncontrolled proliferation of tumor cells.

Sex differences in the circadian regulation of sleep and waking cognition in humans

Science.gov (United States)

Santhi, Nayantara; Lazar, Alpar S.; McCabe, Patrick J.; Lo, June C.; Groeger, John A.; Dijk, Derk-Jan

2016-01-01

The sleep–wake cycle and circadian rhythmicity both contribute to brain function, but whether this contribution differs between men and women and how it varies across cognitive domains and subjective dimensions has not been established. We examined the circadian and sleep–wake-dependent regulation of cognition in 16 men and 18 women in a forced desynchrony protocol and quantified the separate contributions of circadian phase, prior sleep, and elapsed time awake on cognition and sleep. The largest circadian effects were observed for reported sleepiness, mood, and reported effort; the effects on working memory and temporal processing were smaller. Although these effects were seen in both men and women, there were quantitative differences. The amplitude of the circadian modulation was larger in women in 11 of 39 performance measures so that their performance was more impaired in the early morning hours. Principal components analysis of the performance measures yielded three factors, accuracy, effort, and speed, which reflect core performance characteristics in a range of cognitive tasks and therefore are likely to be important for everyday performance. The largest circadian modulation was observed for effort, whereas accuracy exhibited the largest sex difference in circadian modulation. The sex differences in the circadian modulation of cognition could not be explained by sex differences in the circadian amplitude of plasma melatonin and electroencephalographic slow-wave activity. These data establish the impact of circadian rhythmicity and sex on waking cognition and have implications for understanding the regulation of brain function, cognition, and affect in shift-work, jetlag, and aging. PMID:27091961

Sex differences in the circadian regulation of sleep and waking cognition in humans.

Science.gov (United States)

Santhi, Nayantara; Lazar, Alpar S; McCabe, Patrick J; Lo, June C; Groeger, John A; Dijk, Derk-Jan

2016-05-10

The sleep-wake cycle and circadian rhythmicity both contribute to brain function, but whether this contribution differs between men and women and how it varies across cognitive domains and subjective dimensions has not been established. We examined the circadian and sleep-wake-dependent regulation of cognition in 16 men and 18 women in a forced desynchrony protocol and quantified the separate contributions of circadian phase, prior sleep, and elapsed time awake on cognition and sleep. The largest circadian effects were observed for reported sleepiness, mood, and reported effort; the effects on working memory and temporal processing were smaller. Although these effects were seen in both men and women, there were quantitative differences. The amplitude of the circadian modulation was larger in women in 11 of 39 performance measures so that their performance was more impaired in the early morning hours. Principal components analysis of the performance measures yielded three factors, accuracy, effort, and speed, which reflect core performance characteristics in a range of cognitive tasks and therefore are likely to be important for everyday performance. The largest circadian modulation was observed for effort, whereas accuracy exhibited the largest sex difference in circadian modulation. The sex differences in the circadian modulation of cognition could not be explained by sex differences in the circadian amplitude of plasma melatonin and electroencephalographic slow-wave activity. These data establish the impact of circadian rhythmicity and sex on waking cognition and have implications for understanding the regulation of brain function, cognition, and affect in shift-work, jetlag, and aging.

Impaired clock output by altered connectivity in the circadian network.

Science.gov (United States)

Fernández, María de la Paz; Chu, Jessie; Villella, Adriana; Atkinson, Nigel; Kay, Steve A; Ceriani, María Fernanda

2007-03-27

Substantial progress has been made in elucidating the molecular processes that impart a temporal control to physiology and behavior in most eukaryotes. In Drosophila, dorsal and ventral neuronal networks act in concert to convey rhythmicity. Recently, the hierarchical organization among the different circadian clusters has been addressed, but how molecular oscillations translate into rhythmic behavior remains unclear. The small ventral lateral neurons can synchronize certain dorsal oscillators likely through the release of pigment dispersing factor (PDF), a neuropeptide central to the control of rhythmic rest-activity cycles. In the present study, we have taken advantage of flies exhibiting a distinctive arrhythmic phenotype due to mutation of the potassium channel slowpoke (slo) to examine the relevance of specific neuronal populations involved in the circadian control of behavior. We show that altered neuronal function associated with the null mutation specifically impaired PDF accumulation in the dorsal protocerebrum and, in turn, desynchronized molecular oscillations in the dorsal clusters. However, molecular oscillations in the small ventral lateral neurons are properly running in the null mutant, indicating that slo is acting downstream of these core pacemaker cells, most likely in the output pathway. Surprisingly, disrupted PDF signaling by slo dysfunction directly affects the structure of the underlying circuit. Our observations demonstrate that subtle structural changes within the circadian network are responsible for behavioral arrhythmicity.

Post-transcriptional control of the mammalian circadian clock: implications for health and disease.

Science.gov (United States)

Preußner, Marco; Heyd, Florian

2016-06-01

Many aspects of human physiology and behavior display rhythmicity with a period of approximately 24 h. Rhythmic changes are controlled by an endogenous time keeper, the circadian clock, and include sleep-wake cycles, physical and mental performance capability, blood pressure, and body temperature. Consequently, many diseases, such as metabolic, sleep, autoimmune and mental disorders and cancer, are connected to the circadian rhythm. The development of therapies that take circadian biology into account is thus a promising strategy to improve treatments of diverse disorders, ranging from allergic syndromes to cancer. Circadian alteration of body functions and behavior are, at the molecular level, controlled and mediated by widespread changes in gene expression that happen in anticipation of predictably changing requirements during the day. At the core of the molecular clockwork is a well-studied transcription-translation negative feedback loop. However, evidence is emerging that additional post-transcriptional, RNA-based mechanisms are required to maintain proper clock function. Here, we will discuss recent work implicating regulated mRNA stability, translation and alternative splicing in the control of the mammalian circadian clock, and its role in health and disease.

Alteration of circadian rhythm during epileptogenesis: implications for the suprachiasmatic nucleus circuits.

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Xiang, Yan; Li, Zhi-Xiao; Zhang, Ding-Yu; He, Zhi-Gang; Hu, Ji; Xiang, Hong-Bing

2017-01-01

It is important to realize that characterization of the circadian rhythm patterns of seizure occurrence can implicate in diagnosis and treatment of selected types of epilepsy. Evidence suggests a role for the suprachiasmatic nucleus (SCN) circuits in overall circadian rhythm and seizure susceptibility both in animals and humans. Thus, we conclude that SCN circuits may exert modifying effects on circadian rhythmicity and neuronal excitability during epileptogenesis. SCN circuits will be studied in our brain centre and collaborating centres to explore further the interaction between the circadian rhythm and epileptic seizures. More and thorough research is warranted to provide insight into epileptic seizures with circadian disruption comorbidities such as disorders of cardiovascular parameters and core body temperature circadian rhythms.

An approximation to the temporal order in endogenous circadian rhythms of genes implicated in human adipose tissue metabolism

Science.gov (United States)

Although it is well established that human adipose tissue (AT) shows circadian rhythmicity, published studies have been discussed as if tissues or systems showed only one or few circadian rhythms at a time. To provide an overall view of the internal temporal order of circadian rhythms in human AT in...

A survey of genomic studies supports association of circadian clock genes with bipolar disorder spectrum illnesses and lithium response.

Directory of Open Access Journals (Sweden)

Michael J McCarthy

Full Text Available Circadian rhythm abnormalities in bipolar disorder (BD have led to a search for genetic abnormalities in circadian "clock genes" associated with BD. However, no significant clock gene findings have emerged from genome-wide association studies (GWAS. At least three factors could account for this discrepancy: complex traits are polygenic, the organization of the clock is more complex than previously recognized, and/or genetic risk for BD may be shared across multiple illnesses. To investigate these issues, we considered the clock gene network at three levels: essential "core" clock genes, upstream circadian clock modulators, and downstream clock controlled genes. Using relaxed thresholds for GWAS statistical significance, we determined the rates of clock vs. control genetic associations with BD, and four additional illnesses that share clinical features and/or genetic risk with BD (major depression, schizophrenia, attention deficit/hyperactivity. Then we compared the results to a set of lithium-responsive genes. Associations with BD-spectrum illnesses and lithium-responsiveness were both enriched among core clock genes but not among upstream clock modulators. Associations with BD-spectrum illnesses and lithium-responsiveness were also enriched among pervasively rhythmic clock-controlled genes but not among genes that were less pervasively rhythmic or non-rhythmic. Our analysis reveals previously unrecognized associations between clock genes and BD-spectrum illnesses, partly reconciling previously discordant results from past GWAS and candidate gene studies.

Circadian Rhythms in Cyanobacteria

Science.gov (United States)

Golden, Susan S.

2015-01-01

SUMMARY Life on earth is subject to daily and predictable fluctuations in light intensity, temperature, and humidity created by rotation of the earth. Circadian rhythms, generated by a circadian clock, control temporal programs of cellular physiology to facilitate adaptation to daily environmental changes. Circadian rhythms are nearly ubiquitous and are found in both prokaryotic and eukaryotic organisms. Here we introduce the molecular mechanism of the circadian clock in the model cyanobacterium Synechococcus elongatus PCC 7942. We review the current understanding of the cyanobacterial clock, emphasizing recent work that has generated a more comprehensive understanding of how the circadian oscillator becomes synchronized with the external environment and how information from the oscillator is transmitted to generate rhythms of biological activity. These results have changed how we think about the clock, shifting away from a linear model to one in which the clock is viewed as an interactive network of multifunctional components that are integrated into the context of the cell in order to pace and reset the oscillator. We conclude with a discussion of how this basic timekeeping mechanism differs in other cyanobacterial species and how information gleaned from work in cyanobacteria can be translated to understanding rhythmic phenomena in other prokaryotic systems. PMID:26335718

Circadian variation in sports performance.

Science.gov (United States)

Atkinson, G; Reilly, T

1996-04-01

Chronobiology is the science concerned with investigations of time-dependent changes in physiological variables. Circadian rhythms refer to variations that recur every 24 hours. Many physiological circadian rhythms at rest are endogenously controlled, and persist when an individual is isolated from environmental fluctuations. Unlike physiological variables, human performance cannot be monitored continuously in order to describe circadian rhythmicity. Experimental studies of the effect of circadian rhythms on performance need to be carefully designed in order to control for serial fatigue effects and to minimise disturbances in sleep. The detection of rhythmicity in performance variables is also highly influenced by the degree of test-retest repeatability of the measuring equipment. The majority of components of sports performance, e.g. flexibility, muscle strength, short term high power output, vary with time of day in a sinusoidal manner and peak in the early evening close to the daily maximum in body temperature. Psychological tests of short term memory, heart rate-based tests of physical fitness, and prolonged submaximal exercise performance carried out in hot conditions show peak times in the morning. Heart rate-based tests of work capacity appear to peak in the morning because the heart rate responses to exercise are minimal at this time of day. Post-lunch declines are evident with performance variables such as muscle strength, especially if measured frequently enough and sequentially within a 24-hour period to cause fatigue in individuals. More research work is needed to ascertain whether performance in tasks demanding fine motor control varies with time of day. Metabolic and respiratory rhythms are flattened when exercise becomes strenuous whilst the body temperature rhythm persists during maximal exercise. Higher work-rates are selected spontaneously in the early evening. At present, it is not known whether time of day influences the responses of a set

Circadian rhythm asynchrony in man during hypokinesis.

Science.gov (United States)

Winget, C. M.; Vernikos-Danellis, J.; Cronin, S. E.; Leach, C. S.; Rambaut, P. C.; Mack, P. B.

1972-01-01

Posture and exercise were investigated as synchronizers of certain physiologic rhythms in eight healthy male subjects in a defined environment. Four subjects exercised during bed rest. Body temperature (BT), heart rate, plasma thyroid hormone, and plasma steroid data were obtained from the subjects for a 6-day ambulatory equilibration period before bed rest, 56 days of bed rest, and a 10-day recovery period after bed rest. The results indicate that the mechanism regulating the circadian rhythmicity of the cardiovascular system is rigorously controlled and independent of the endocrine system, while the BT rhythm is more closely aligned to the endocrine system.

Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits.

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Erika Navarrete

Full Text Available Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB. We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1, pups were randomly assigned to one of the following conditions: intact pups (INT, intact pups fed by enteral gavage (INT+ENT, sham operated pups (SHAM, pups with unilateral lesions of the olfactory bulb (OBx-UNI, and pups with bilateral lesions of the olfactory bulb (OBx-BI. At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00, and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb.

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

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Wilking, Melissa; Ndiaye, Mary; Mukhtar, Hasan

2013-01-01

Abstract Significance: Oxygen and circadian rhythmicity are essential in a myriad of physiological processes to maintain homeostasis, from blood pressure and sleep/wake cycles, down to cellular signaling pathways that play critical roles in health and disease. If the human body or cells experience significant stress, their ability to regulate internal systems, including redox levels and circadian rhythms, may become impaired. At cellular as well as organismal levels, impairment in redox regulation and circadian rhythms may lead to a number of adverse effects, including the manifestation of a variety of diseases such as heart diseases, neurodegenerative conditions, and cancer. Recent Advances: Researchers have come to an understanding as to the basics of the circadian rhythm mechanism, as well as the importance of the numerous species of oxidative stress components. The effects of oxidative stress and dysregulated circadian rhythms have been a subject of intense investigations since they were first discovered, and recent investigations into the molecular mechanisms linking the two have started to elucidate the bases of their connection. Critical Issues: While much is known about the mechanics and importance of oxidative stress systems and circadian rhythms, the front where they interact has had very little research focused on it. This review discusses the idea that these two systems are together intricately involved in the healthy body, as well as in disease. Future Directions: We believe that for a more efficacious management of diseases that have both circadian rhythm and oxidative stress components in their pathogenesis, targeting both systems in tandem would be far more successful. Antioxid. Redox Signal. 19, 192–208 PMID:23198849

Circadian rhythms and reproduction.

Science.gov (United States)

Boden, Michael J; Kennaway, David J

2006-09-01

There is a growing recognition that the circadian timing system, in particular recently discovered clock genes, plays a major role in a wide range of physiological systems. Microarray studies, for example, have shown that the expression of hundreds of genes changes many fold in the suprachiasmatic nucleus, liver heart and kidney. In this review, we discuss the role of circadian rhythmicity in the control of reproductive function in animals and humans. Circadian rhythms and clock genes appear to be involved in optimal reproductive performance, but there are sufficient redundancies in their function that many of the knockout mice produced do not show overt reproductive failure. Furthermore, important strain differences have emerged from the studies especially between the various Clock (Circadian Locomotor Output Cycle Kaput) mutant strains. Nevertheless, there is emerging evidence that the primary clock genes, Clock and Bmal1 (Brain and Muscle ARNT-like protein 1, also known as Mop3), strongly influence reproductive competency. The extent to which the circadian timing system affects human reproductive performance is not known, in part, because many of the appropriate studies have not been done. With the role of Clock and Bmal1 in fertility becoming clearer, it may be time to pursue the effect of polymorphisms in these genes in relation to the various types of infertility in humans.

Systems Level Regulation of Rhythmic Growth Rate and Biomass Accumulation in Grasses

Energy Technology Data Exchange (ETDEWEB)

Kay, Steve A. [Univ. of Southern California, Los Angeles, CA (United States)

2017-10-20

Objectives: Several breakthroughs have been recently made in our understanding of plant growth and biomass accumulation. It was found that plant growth is rhythmically controlled throughout the day by the circadian clock through a complex interplay of light and phytohormone signaling pathways. While plants such as the C4 energy crop sorghum (Sorghum bicolor (L.) Moench) and possibly the C3 grass Brachypodium distachyon also exhibit daily rhythms in growth rate, the molecular details of its regulation remain to be explored. A better understanding of diurnally regulated growth behavior in grasses may lead to species-specific mechanisms highly relevant to future strategies to optimize energy crop biomass yield. Here we propose to devise a systems approach to identify, in parallel, regulatory hubs associated with rhythmic growth in C3 and C4 plants. We propose to use rhythmicity in daily growth patterns to drive the discovery of regulatory network modules controlling biomass accumulation. Description: The project is divided in three main parts: 1) Performing time-lapse imaging and growth measurement in B. distachyon and S. bicolor to determine growth rate dynamic during the day/night cycle. Identifying growth-associated genes whose expression patterns follow the observed growth dynamics using deep sequencing technology, 2) identifying regulators of these genes by screening for DNA-binding proteins interacting with the growth-associated gene promoters identified in Aim 1. Screens will be performed using a validated yeast-one hybrid strategy paired with a specifically designed B. distachyon and S. bicolor transcription factor libraries (1000 clones each), and 3) Selecting 50 potential growth regulators from the screen for downstream characterization. The selection will be made by using a sytems biology approach by calculating the connectivity between growth rate, rhythmic gene expression profiles and TF expression profile and determine which TF is likely part of a hub

Diel pattern of circadian clock and storage protein gene expression in leaves and during seed filling in cowpea (Vigna unguiculata).

Science.gov (United States)

Weiss, Julia; Terry, Marta I; Martos-Fuentes, Marina; Letourneux, Lisa; Ruiz-Hernández, Victoria; Fernández, Juan A; Egea-Cortines, Marcos

2018-02-14

Cowpea (Vigna unguiculata) is an important source of protein supply for animal and human nutrition. The major storage globulins VICILIN and LEGUMIN (LEG) are synthesized from several genes including LEGA, LEGB, LEGJ and CVC (CONVICILIN). The current hypothesis is that the plant circadian core clock genes are conserved in a wide array of species and that primary metabolism is to a large extent controlled by the plant circadian clock. Our aim was to investigate a possible link between gene expression of storage proteins and the circadian clock. We identified cowpea orthologues of the core clock genes VunLHY, VunTOC1, VunGI and VunELF3, the protein storage genes VunLEG, VunLEGJ, and VunCVC as well as nine candidate reference genes used in RT-PCR. ELONGATION FACTOR 1-A (ELF1A) resulted the most suitable reference gene. The clock genes VunELF3, VunGI, VunTOC1 and VunLHY showed a rhythmic expression profile in leaves with a typical evening/night and morning/midday phased expression. The diel patterns were not completely robust and only VungGI and VungELF3 retained a rhythmic pattern under free running conditions of darkness. Under field conditions, rhythmicity and phasing apparently faded during early pod and seed development and was regained in ripening pods for VunTOC1 and VunLHY. Mature seeds showed a rhythmic expression of VunGI resembling leaf tissue under controlled growth chamber conditions. Comparing time windows during developmental stages we found that VunCVC and VunLEG were significantly down regulated during the night in mature pods as compared to intermediate ripe pods, while changes in seeds were non-significant due to high variance. The rhythmic expression under field conditions was lost under growth chamber conditions. The core clock gene network is conserved in cowpea leaves showing a robust diel expression pattern except VunELF3 under growth chamber conditions. There appears to be a clock transcriptional reprogramming in pods and seeds compared to

A circadian clock in Antarctic krill: an endogenous timing system governs metabolic output rhythms in the euphausid species Euphausia superba.

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Mathias Teschke

Full Text Available Antarctic krill, Euphausia superba, shapes the structure of the Southern Ocean ecosystem. Its central position in the food web, the ongoing environmental changes due to climatic warming, and increasing commercial interest on this species emphasize the urgency of understanding the adaptability of krill to its environment. Krill has evolved rhythmic physiological and behavioral functions which are synchronized with the daily and seasonal cycles of the complex Southern Ocean ecosystem. The mechanisms, however, leading to these rhythms are essentially unknown. Here, we show that krill possesses an endogenous circadian clock that governs metabolic and physiological output rhythms. We found that expression of the canonical clock gene cry2 was highly rhythmic both in a light-dark cycle and in constant darkness. We detected a remarkable short circadian period, which we interpret as a special feature of the krill's circadian clock that helps to entrain the circadian system to the extreme range of photoperiods krill is exposed to throughout the year. Furthermore, we found that important key metabolic enzymes of krill showed bimodal circadian oscillations (∼9-12 h period in transcript abundance and enzymatic activity. Oxygen consumption of krill showed ∼9-12 h oscillations that correlated with the temporal activity profile of key enzymes of aerobic energy metabolism. Our results demonstrate the first report of an endogenous circadian timing system in Antarctic krill and its likely link to metabolic key processes. Krill's circadian clock may not only be critical for synchronization to the solar day but also for the control of seasonal events. This study provides a powerful basis for the investigation into the mechanisms of temporal synchronization in this marine key species and will also lead to the first comprehensive analyses of the circadian clock of a polar marine organism through the entire photoperiodic cycle.

Radioimmunological analysis of circadian rhythms of cortisol and melatonin in saliva

International Nuclear Information System (INIS)

Demel, A.W.

1990-12-01

Since blood cortisol (F) and melatonin (MLT) display a circadian secretion pattern and since the saliva concentration of this hormones is an excellent indicator of its blood levels the measurement of salivary F and MLT may be used for examining circadian rhythmicity. In this study the relationship between salivary F and MLT was explored. For this purpose it was necessary first to establish and validate a radioimmunoassay for F in saliva: salivary F was determined by a direct radioimmunoassay using cortisol-3-(O-carboxymethyl) oximino-(2-( 125 I)iodohistamin) as tracer and cortisol-3-CMO-BSA antiserum. The parallel measurement of F levels in saliva and serum of adults gave an excellent correlation (r=0.87, p 0.00956x ). Serum F was assayed on the Abott TDX-System using a radioimmunofluorescence method. Secondly, using this assay the circadian saliva F pattern was determined as well as the pattern of salivary MLT in 9 young, healthy volunteers. For saliva MLT estimations a previously published method was applied (Schulz et al 1990). Using a computerized program (RHYTHM) written by Eve v. Cauter (1979), the hormone data of each individuum were examined for circadian rhythmicity and its acrophase (time of occurrence of the maximum of a sinusoid fitted to the data). The F acrophase occurred between 7:00 and 12:00 h (mean: 3:33 h, SD: 104.4 min). The easy stress-free non invasive nature of saliva collection makes saliva to one of the most accessible body fluids and of high value in studying the circadian system in healthy humans as well as in infants, children, pregnant women and anaemic patients. Measurements of salivary F and MLT may help to elucidate not only the circadian rhythms of these hormones under normal and pathological conditions but it may also provide insight in physiology and pathology of the circadian system in general. (author)

Circadian clock components in the rat neocortex

DEFF Research Database (Denmark)

Rath, Martin Fredensborg; Rohde, Kristian; Fahrenkrug, Jan

2013-01-01

in the rat neocortex. Among these, Per1, Per2, Per3, Cry1, Bmal1, Nr1d1 and Dbp were found to exhibit daily rhythms. The amplitude of circadian oscillation in neocortical clock gene expression was damped and the peak delayed as compared with the SCN. Lesions of the SCN revealed that rhythmic clock gene...... expression in the neocortex is dependent on the SCN. In situ hybridization and immunohistochemistry showed that products of the canonical clock gene Per2 are located in perikarya throughout all areas of the neocortex. These findings show that local circadian oscillators driven by the SCN reside within...... neurons of the neocortex....

Circadian regulation of hormone signaling and plant physiology.

Science.gov (United States)

Atamian, Hagop S; Harmer, Stacey L

2016-08-01

The survival and reproduction of plants depend on their ability to cope with a wide range of daily and seasonal environmental fluctuations during their life cycle. Phytohormones are plant growth regulators that are involved in almost every aspect of growth and development as well as plant adaptation to myriad abiotic and biotic conditions. The circadian clock, an endogenous and cell-autonomous biological timekeeper that produces rhythmic outputs with close to 24-h rhythms, provides an adaptive advantage by synchronizing plant physiological and metabolic processes to the external environment. The circadian clock regulates phytohormone biosynthesis and signaling pathways to generate daily rhythms in hormone activity that fine-tune a range of plant processes, enhancing adaptation to local conditions. This review explores our current understanding of the interplay between the circadian clock and hormone signaling pathways.

Rhythmic expression of DEC2 protein in vitro and in vivo.

Science.gov (United States)

Sato, Fuyuki; Muragaki, Yasuteru; Kawamoto, Takeshi; Fujimoto, Katsumi; Kato, Yukio; Zhang, Yanping

2016-06-01

Basic helix-loop-helix (bHLH) transcription factor DEC2 (bHLHE41/Sharp1) is one of the clock genes that show a circadian rhythm in various tissues. DEC2 regulates differentiation, sleep length, tumor cell invasion and apoptosis. Although studies have been conducted on the rhythmic expression of DEC2 mRNA in various tissues, the precise molecular mechanism of DEC2 expression is poorly understood. In the present study, we examined whether DEC2 protein had a rhythmic expression. Western blot analysis for DEC2 protein revealed a rhythmic expression in mouse liver, lung and muscle and in MCF-7 and U2OS cells. In addition, AMP-activated protein kinase (AMPK) activity (phosphorylation of AMPK) in mouse embryonic fibroblasts (MEFs) exhibited a rhythmic expression under the condition of medium change or glucose-depleted medium. However, the rhythmic expression of DEC2 in MEF gradually decreased in time under these conditions. The medium change affected the levels of DEC2 protein and phosphorylation of AMPK. In addition, the levels of DEC2 protein showed a rhythmic expression in vivo and in MCF-7 and U2OS cells. The results showed that the phosphorylation of AMPK immunoreactivity was strongly detected in the liver and lung of DEC2 knockout mice compared with that of wild-type mice. These results may provide new insights into rhythmic expression and the regulation between DEC2 protein and AMPK activity.

A Bootstrap Based Measure Robust to the Choice of Normalization Methods for Detecting Rhythmic Features in High Dimensional Data.

Science.gov (United States)

Larriba, Yolanda; Rueda, Cristina; Fernández, Miguel A; Peddada, Shyamal D

2018-01-01

Motivation: Gene-expression data obtained from high throughput technologies are subject to various sources of noise and accordingly the raw data are pre-processed before formally analyzed. Normalization of the data is a key pre-processing step, since it removes systematic variations across arrays. There are numerous normalization methods available in the literature. Based on our experience, in the context of oscillatory systems, such as cell-cycle, circadian clock, etc., the choice of the normalization method may substantially impact the determination of a gene to be rhythmic. Thus rhythmicity of a gene can purely be an artifact of how the data were normalized. Since the determination of rhythmic genes is an important component of modern toxicological and pharmacological studies, it is important to determine truly rhythmic genes that are robust to the choice of a normalization method. Results: In this paper we introduce a rhythmicity measure and a bootstrap methodology to detect rhythmic genes in an oscillatory system. Although the proposed methodology can be used for any high-throughput gene expression data, in this paper we illustrate the proposed methodology using several publicly available circadian clock microarray gene-expression datasets. We demonstrate that the choice of normalization method has very little effect on the proposed methodology. Specifically, for any pair of normalization methods considered in this paper, the resulting values of the rhythmicity measure are highly correlated. Thus it suggests that the proposed measure is robust to the choice of a normalization method. Consequently, the rhythmicity of a gene is potentially not a mere artifact of the normalization method used. Lastly, as demonstrated in the paper, the proposed bootstrap methodology can also be used for simulating data for genes participating in an oscillatory system using a reference dataset. Availability: A user friendly code implemented in R language can be downloaded from http://www.eio.uva.es/~miguel/robustdetectionprocedure.html.

Proteomics and circadian rhythms: It’s all about signaling!

Science.gov (United States)

Mauvoisin, Daniel; Dayon, Loïc; Gachon, Frédéric; Kussmann, Martin

2014-01-01

1. Abstract Proteomic technologies using mass spectrometry (MS) offer new perspectives in circadian biology, in particular the possibility to study posttranslational modifications (PTMs). To date, only very few studies have been carried out to decipher the rhythmicity of protein expression in mammals with large-scale proteomics. Although signaling has been shown to be of high relevance, comprehensive characterization studies of PTMs are even more rare. This review aims at describing the actual landscape of circadian proteomics and the opportunities and challenges appearing on the horizon. Emphasis was given to signaling processes for their role in metabolic heath as regulated by circadian clocks and environmental factors. Those signaling processes are expected to be better and more deeply characterized in the coming years with proteomics. PMID:25103677

Circadian variations of serum thyrotropin, thyroxine, triiodothyronine, reverse triiodothyronine, corticosterone and lipids in starved rats

International Nuclear Information System (INIS)

Zwirska-Korczala, K.; Ostrowska, Z.; Kucharzewski, M.; Marek, B.; Kos-Kudla, B.; Buntner, B.; Swietochowska, E.

1993-01-01

We investigated the circadian variation of serum thyrotropin (TSH), thyroxine (T 4 ), triiodothyronine (T 3 ), reverse triiodothyronine (rT 3 ), corticosterone (B) and lipids in male Wistar rats after one-week starvation. Starvation decreased the TSH level and eliminated its 24-h rhythm. The rhythmicity of oscillations of T 3 and B was maintained. Starvation led to a shift in the acrophase of 24-h T 3 and B oscillation and induced the circadian rhythm of T 4 . The T 3 , T 4 and mesor values were lower, while for rT 3 and B they increased. Lipid concentrations remained unchanged in both experimental and control rats. (author). 27 refs, 3 figs, 2 tabs

Role of type II protein arginine methyltransferase 5 in the regulation of Circadian Per1 gene.

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Jungtae Na

Full Text Available Circadian clocks are the endogenous oscillators that regulate rhythmic physiological and behavioral changes to correspond to daily light-dark cycles. Molecular dissections have revealed that transcriptional feedback loops of the circadian clock genes drive the molecular oscillation, in which PER/CRY complexes inhibit the transcriptional activity of the CLOCK/BMAL1 heterodimer to constitute a negative feedback loop. In this study, we identified the type II protein arginine methyltransferase 5 (PRMT5 as an interacting molecule of CRY1. Although the Prmt5 gene was constitutively expressed, increased interaction of PRMT5 with CRY1 was observed when the Per1 gene was repressed both in synchronized mouse liver and NIH3T3 cells. Moreover, rhythmic recruitment of PRMT5 and CRY1 to the Per1 gene promoter was found to be associated with an increased level of histone H4R3 dimethylation and Per1 gene repression. Consistently, decreased histone H4R3 dimethylation and altered rhythmic Per1 gene expression were observed in Prmt5-depleted cells. Taken together, these findings provide an insight into the link between histone arginine methylation by PRMT5 and transcriptional regulation of the circadian Per1 gene.

Rhythmic expression of Nocturnin mRNA in multiple tissues of the mouse

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Green Carla B

2001-05-01

Full Text Available Abstract Background Nocturnin was originally identified by differential display as a circadian clock regulated gene with high expression at night in photoreceptors of the African clawed frog, Xenopus laevis. Although encoding a novel protein, the nocturnin cDNA had strong sequence similarity with a C-terminal domain of the yeast transcription factor CCR4, and with mouse and human ESTs. Since its original identification others have cloned mouse and human homologues of nocturnin/CCR4, and we have cloned a full-length cDNA from mouse retina, along with partial cDNAs from human, cow and chicken. The goal of this study was to determine the temporal pattern of nocturnin mRNA expression in multiple tissues of the mouse. Results cDNA sequence analysis revealed a high degree of conservation among vertebrate nocturnin/CCR4 homologues along with a possible homologue in Drosophila. Northern analysis of mRNA in C3H/He and C57/Bl6 mice revealed that the mNoc gene is expressed in a broad range of tissues, with greatest abundance in liver, kidney and testis. mNoc is also expressed in multiple brain regions including suprachiasmatic nucleus and pineal gland. Furthermore, mNoc exhibits circadian rhythmicity of mRNA abundance with peak levels at the time of light offset in the retina, spleen, heart, kidney and liver. Conclusion The widespread expression and rhythmicity of mNoc mRNA parallels the widespread expression of other circadian clock genes in mammalian tissues, and suggests that nocturnin plays an important role in clock function or as a circadian clock effector.

Circadian rhythms and food anticipatory behavior in Wfs1-deficient mice

DEFF Research Database (Denmark)

Luuk, Hendrik; Fahrenkrug, Jan; Hannibal, Jens

2012-01-01

in significantly lower body weight and reduced wheel-running activity. Circadian rhythmicity of behavior was normal in Wfs1-deficient mice under ad libitum feeding apart from elongated free-running period in constant light. The amount of food anticipatory activity induced by restricted feeding...

The role of microRNAs (miRNA) in circadian rhythmicity

Indian Academy of Sciences (India)

2008-12-31

Dec 31, 2008 ... role of miRNAs in diverse fields related to regulation of gene expression. .... miRNA levels after sleep deprivation in the rat's brain also show modest .... Duffield G. E. 2003 DNA microarray analyses of circadian tim- ing: the ...

Maternal circadian rhythms and the programming of adult health and disease.

Science.gov (United States)

Varcoe, Tamara J; Gatford, Kathryn L; Kennaway, David J

2018-02-01

The in utero environment is inherently rhythmic, with the fetus subjected to circadian changes in temperature, substrates, and various maternal hormones. Meanwhile, the fetus is developing an endogenous circadian timing system, preparing for life in an external environment where light, food availability, and other environmental factors change predictably and repeatedly every 24 h. In humans, there are many situations that can disrupt circadian rhythms, including shift work, international travel, insomnias, and circadian rhythm disorders (e.g., advanced/delayed sleep phase disorder), with a growing consensus that this chronodisruption can have deleterious consequences for an individual's health and well-being. However, the impact of chronodisruption during pregnancy on the health of both the mother and fetus is not well understood. In this review, we outline circadian timing system ontogeny in mammals and examine emerging research from animal models demonstrating long-term negative implications for progeny health following maternal chronodisruption during pregnancy.

Circadian disruption and health: Shift work as a harbinger of the toll taken by electric lighting.

Science.gov (United States)

Stevens, Richard G

Electric light is one of the signature inventions of human beings. A problem, however, is that electric light can confuse our endogenous circadian rhythmicity. It has now become apparent that circadian biology is fundamental to the functioning and adaptation of almost all life forms. In the modern world, everyone is exposed to electric light during the day and night, and thereby can experience some level of circadian disruption. Perhaps as a canary in the coal mine, study of people whose work hours include nighttime (shift workers) is beginning to yield insights on the adverse health effects of circadian disruption from electric light.

UNC79 and UNC80, putative auxiliary subunits of the NARROW ABDOMEN ion channel, are indispensable for robust circadian locomotor rhythms in Drosophila.

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Bridget C Lear

Full Text Available In the fruit fly Drosophila melanogaster, a network of circadian pacemaker neurons drives daily rhythms in rest and activity. The ion channel NARROW ABDOMEN (NA, orthologous to the mammalian sodium leak channel NALCN, functions downstream of the molecular circadian clock in pacemaker neurons to promote behavioral rhythmicity. To better understand the function and regulation of the NA channel, we have characterized two putative auxiliary channel subunits in Drosophila, unc79 (aka dunc79 and unc80 (aka CG18437. We have generated novel unc79 and unc80 mutations that represent strong or complete loss-of-function alleles. These mutants display severe defects in circadian locomotor rhythmicity that are indistinguishable from na mutant phenotypes. Tissue-specific RNA interference and rescue analyses indicate that UNC79 and UNC80 likely function within pacemaker neurons, with similar anatomical requirements to NA. We observe an interdependent, post-transcriptional regulatory relationship among the three gene products, as loss of na, unc79, or unc80 gene function leads to decreased expression of all three proteins, with minimal effect on transcript levels. Yet despite this relationship, we find that the requirement for unc79 and unc80 in circadian rhythmicity cannot be bypassed by increasing NA protein expression, nor can these putative auxiliary subunits substitute for each other. These data indicate functional requirements for UNC79 and UNC80 beyond promoting channel subunit expression. Immunoprecipitation experiments also confirm that UNC79 and UNC80 form a complex with NA in the Drosophila brain. Taken together, these data suggest that Drosophila NA, UNC79, and UNC80 function together in circadian clock neurons to promote rhythmic behavior.

Temporal phasing of locomotor activity, heart rate rhythmicity, and core body temperature is disrupted in VIP receptor 2-deficient mice

DEFF Research Database (Denmark)

Hannibal, Jens; Hsiung, Hansen M; Fahrenkrug, Jan

2011-01-01

these observations with observations made from mice examined by wheel-running activity. The study demonstrates that VPAC2 signaling is necessary for a functional circadian clock driving locomotor activity, core body temperature, and heart rate rhythmicity, since VPAC2-deficient mice lose the rhythms in all three...... to that of wild-type mice. The use of telemetric devices to measure circadian locomotor activity, temperature, and heart rate, together with the classical determination of circadian rhythms of wheel-running activity, raises questions about how representative wheel-running activity may be of other behavioral...

DNA damage shifts circadian clock time via Hausp-dependent Cry1 stabilization

OpenAIRE

Papp, Stephanie J; Huber, Anne-Laure; Jordan, Sabine D; Kriebs, Anna; Nguyen, Madelena; Moresco, James J; Yates, John R; Lamia, Katja A

2015-01-01

eLife digest Many aspects of our physiology and behavior, most notably our patterns of sleep and wakefulness, are synchronized with the day?night cycle. These circadian rhythms are generated and maintained by the circadian clock, which consists of positive and negative feedback loops formed by a large number of genes and proteins. The end result is that the rates at which thousands of proteins are produced varies rhythmically over the course of the day?night cycle. It has long been suspected ...

Circadian phase resetting via single and multiple control targets.

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Neda Bagheri

2008-07-01

Full Text Available Circadian entrainment is necessary for rhythmic physiological functions to be appropriately timed over the 24-hour day. Disruption of circadian rhythms has been associated with sleep and neuro-behavioral impairments as well as cancer. To date, light is widely accepted to be the most powerful circadian synchronizer, motivating its use as a key control input for phase resetting. Through sensitivity analysis, we identify additional control targets whose individual and simultaneous manipulation (via a model predictive control algorithm out-perform the open-loop light-based phase recovery dynamics by nearly 3-fold. We further demonstrate the robustness of phase resetting by synchronizing short- and long-period mutant phenotypes to the 24-hour environment; the control algorithm is robust in the presence of model mismatch. These studies prove the efficacy and immediate application of model predictive control in experimental studies and medicine. In particular, maintaining proper circadian regulation may significantly decrease the chance of acquiring chronic illness.

Maternal exercise, season and sex modify the human fetal circadian rhythm.

Science.gov (United States)

Sletten, Julie; Cornelissen, Germaine; Assmus, Jørg; Kiserud, Torvid; Albrechtsen, Susanne; Kessler, Jörg

2018-05-13

The knowledge on circadian rhythmicity is rapidly expanding. We aimed to define the longitudinal development of the circadian heart rate rhythm in the human fetus in an unrestricted, out-of-hospital setting, and to examine the effects of maternal physical activity, season and fetal sex. We recruited 48 women with low-risk singleton pregnancies. Using a portable monitor for continuous fetal electrocardiography, fetal heart rate recordings were obtained around gestational weeks 24, 28, 32 and 36. Circadian rhythmicity in fetal heart rate and fetal heart rate variation was detected by cosinor analysis; developmental trends were calculated by population-mean cosinor and multilevel analysis. For the fetal heart rate and fetal heart rate variation, a significant circadian rhythm was present in 122/123 (99.2%) and 116/121 (95.9%) of the individual recordings, respectively. The rhythms were best described by combining cosine waves with periods of 24 and 8 hours. With increasing gestational age, the magnitude of the fetal heart rate rhythm increased, and the peak of the fetal heart rate variation rhythm shifted from a mean of 14:25 (24 weeks) to 20:52 (36 weeks). With advancing gestation, the rhythm-adjusted mean value of the fetal heart rate decreased linearly in females (prhythm diversity was found in male fetuses, during higher maternal physical activity and during the summer season. The dynamic development of the fetal circadian heart rate rhythm during the second half of pregnancy is modified by fetal sex, maternal physical activity and season. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Circadian rhythms of women with fibromyalgia

Science.gov (United States)

Klerman, E. B.; Goldenberg, D. L.; Brown, E. N.; Maliszewski, A. M.; Adler, G. K.

2001-01-01

Fibromyalgia syndrome is a chronic and debilitating disorder characterized by widespread nonarticular musculoskeletal pain whose etiology is unknown. Many of the symptoms of this syndrome, including difficulty sleeping, fatigue, malaise, myalgias, gastrointestinal complaints, and decreased cognitive function, are similar to those observed in individuals whose circadian pacemaker is abnormally aligned with their sleep-wake schedule or with local environmental time. Abnormalities in melatonin and cortisol, two hormones whose secretion is strongly influenced by the circadian pacemaker, have been reported in women with fibromyalgia. We studied the circadian rhythms of 10 women with fibromyalgia and 12 control healthy women. The protocol controlled factors known to affect markers of the circadian system, including light levels, posture, sleep-wake state, meals, and activity. The timing of the events in the protocol were calculated relative to the habitual sleep-wake schedule of each individual subject. Under these conditions, we found no significant difference between the women with fibromyalgia and control women in the circadian amplitude or phase of rhythms of melatonin, cortisol, and core body temperature. The average circadian phases expressed in hours posthabitual bedtime for women with and without fibromyalgia were 3:43 +/- 0:19 and 3:46 +/- 0:13, respectively, for melatonin; 10:13 +/- 0:23 and 10:32 +/- 0:20, respectively for cortisol; and 5:19 +/- 0:19 and 4:57 +/- 0:33, respectively, for core body temperature phases. Both groups of women had similar circadian rhythms in self-reported alertness. Although pain and stiffness were significantly increased in women with fibromyalgia compared with healthy women, there were no circadian rhythms in either parameter. We suggest that abnormalities in circadian rhythmicity are not a primary cause of fibromyalgia or its symptoms.

Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals

NARCIS (Netherlands)

Kumar Jha, Pawan; Challet, Etienne; Kalsbeek, Andries

2015-01-01

Most aspects of energy metabolism display clear variations during day and night. This daily rhythmicity of metabolic functions, including hormone release, is governed by a circadian system that consists of the master clock in the suprachiasmatic nuclei of the hypothalamus (SCN) and many secondary

Sleep quality and circadian rhythm disruption in the intensive care unit

DEFF Research Database (Denmark)

Boyko, Yuliya; Jennum, Poul; Toft, Palle

2017-01-01

, medication, as well as the critical illness itself have been reported as important sleep disturbing factors. Secretion of sleep hormone, melatonin, expressing circadian rhythmicity was found abolished or phase delayed in critically ill patients. Various interventions have been tested in several studies...... aiming to improve sleep quality and circadian rhythm in the ICU. The results of these studies were inconclusive due to using the sleep assessment methods other than PSG or the absence of a reliable sleep scoring tool for the analysis of the PSG findings in this patient population. Development of a valid...

Radioimmunological analysis of circadian rhythms of cortisol and melatonin in saliva

International Nuclear Information System (INIS)

Demel, A.W.

1990-12-01

Since blood cortisol (F) and melatonin (MLT) display a circadian secretion pattern and since the saliva concentration of this hormones is an excellent indicator of its blood levels the measurement of salivary F and MLT may be user for examining circadian rhythmicity. In this study the relationship between salivary F and MLT was explored. For this purpose it was necessary first to establish and validate a radioimmunoassay for F in saliva: salivary F was determined by a direct radioimmunoassay using cortisol-3-(O-carb oxymethyl) oximino-(2-( 125 I)iodohistamin) as tracer and cortisol-3-CMO-BSA antiserum. The parallel measurement of F levels in saliva and serum of adults gave an excellent correlation (r=0.87, p 0.00956x ). Serum F was assayed on the Abott TDX-System using a radioimmunofluorescence method. Secondly, using this assay the circadian saliva F pattern was determined as well as the pattern of salivary MLT in 9 young, healthy volunteers. For saliva MLT estimations a previously published method was applied (SCHULZ et al 1990). Using a computerized program (RHYTHM) written by EVE v. CAUTER (1979), the hormone data of each individuum were examined for circadian rhythmicity and its acrophase (time of occurence of the maximum of a sinusoid fitted to the data). The F acrophase occured between 7:00 and 12:00 h (Mean: 3:33 h, SD: 104.4 min). The easy stress-free non invasive nature of saliva collection makes saliva to one of the most accessible body fluids and of high value in studying the circadian system in healthy humans as well as in infants, children, pregnant women and anaemic patients. Measurements of salivary F and MLT may help to elucidate not only the circadian rhythms of these hormones under normal and pathological conditions but it may also provide insight in physiology and pathology of the circadian system in general. (author)

Interplay between Dioxin-Mediated Signaling and Circadian Clock: A Possible Determinant in Metabolic Homeostasis

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Chun Wang

2014-07-01

Full Text Available The rotation of the earth on its axis creates the environment of a 24 h solar day, which organisms on earth have used to their evolutionary advantage by integrating this timing information into their genetic make-up in the form of a circadian clock. This intrinsic molecular clock is pivotal for maintenance of synchronized homeostasis between the individual organism and the external environment to allow coordinated rhythmic physiological and behavioral function. Aryl hydrocarbon receptor (AhR is a master regulator of dioxin-mediated toxic effects, and is, therefore, critical in maintaining adaptive responses through regulating the expression of phase I/II drug metabolism enzymes. AhR expression is robustly rhythmic, and physiological cross-talk between AhR signaling and circadian rhythms has been established. Increasing evidence raises a compelling argument that disruption of endogenous circadian rhythms contributes to the development of disease, including sleep disorders, metabolic disorders and cancers. Similarly, exposure to environmental pollutants through air, water and food, is increasingly cited as contributory to these same problems. Thus, a better understanding of interactions between AhR signaling and the circadian clock regulatory network can provide critical new insights into environmentally regulated disease processes. This review highlights recent advances in the understanding of the reciprocal interactions between dioxin-mediated AhR signaling and the circadian clock including how these pathways relate to health and disease, with emphasis on the control of metabolic function.

Gnaz couples the circadian and dopaminergic system to G protein-mediated signaling in mouse photoreceptors.

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Patrick Vancura

Full Text Available The mammalian retina harbors a circadian clockwork that regulates vision and promotes healthiness of retinal neurons, mainly through directing the rhythmic release of the neurohormones dopamine-acting on dopamine D4 receptors-and melatonin-acting on MT1 and MT2 receptors. The gene Gnaz-a unique Gi/o subfamily member-was seen in the present study to be expressed in photoreceptors where its protein product Gαz shows a daily rhythm in its subcellular localization. Apart from subcellular localization, Gnaz displays a daily rhythm in expression-with peak values at night-in preparations of the whole retina, microdissected photoreceptors and photoreceptor-related pinealocytes. In retina, Gnaz rhythmicity was observed to persist under constant darkness and to be abolished in retina deficient for Clock or dopamine D4 receptors. Furthermore, circadian regulation of Gnaz was disturbed in the db/db mouse, a model of diabetic retinopathy. The data of the present study suggest that Gnaz links the circadian clockwork-via dopamine acting on D4 receptors-to G protein-mediated signaling in intact but not diabetic retina.

Daily rhythmicity of clock gene transcripts in atlantic cod fast skeletal muscle.

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Carlo C Lazado

Full Text Available The classical notion of a centralized clock that governs circadian rhythmicity has been challenged with the discovery of peripheral oscillators that enable organisms to cope with daily changes in their environment. The present study aimed to identify the molecular clock components in Atlantic cod (Gadus morhua and to investigate their daily gene expression in fast skeletal muscle. Atlantic cod clock genes were closely related to their orthologs in teleosts and tetrapods. Synteny was conserved to varying degrees in the majority of the 18 clock genes examined. In particular, aryl hydrocarbon receptor nuclear translocator-like 2 (arntl2, RAR-related orphan receptor A (rora and timeless (tim displayed high degrees of conservation. Expression profiling during the early ontogenesis revealed that some transcripts were maternally transferred, namely arntl2, cryptochrome 1b and 2 (cry1b and cry2, and period 2a and 2b (per2a and per2b. Most clock genes were ubiquitously expressed in various tissues, suggesting the possible existence of multiple peripheral clock systems in Atlantic cod. In particular, they were all detected in fast skeletal muscle, with the exception of neuronal PAS (Per-Arnt-Single-minded domain-containing protein (npas1 and rora. Rhythmicity analysis revealed 8 clock genes with daily rhythmic expression, namely arntl2, circadian locomotor output cycles kaput (clock, npas2, cry2, cry3 per2a, nuclear receptor subfamily 1, group D, member 1 (nr1d1, and nr1d2a. Transcript levels of the myogenic genes myogenic factor 5 (myf5 and muscleblind-like 1 (mbnl1 strongly correlated with clock gene expression. This is the first study to unravel the molecular components of peripheral clocks in Atlantic cod. Taken together, our data suggest that the putative clock system in fast skeletal muscle of Atlantic cod has regulatory implications on muscle physiology, particularly in the expression of genes related to myogenesis.

Circadian and seasonal variation of migraine attacks in children.

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Soriani, Stefano; Fiumana, Elisa; Manfredini, Roberto; Boari, Benedetta; Battistella, Pier Antonio; Canetta, Elisabetta; Pedretti, Stefania; Borgna-Pignatti, Caterina

2006-01-01

To investigate the rhythmicity of migraine episodes without aura in a pediatric population. Time of occurrence of 2517 migraine attacks in 115 children was recorded, by means of a diary, both by hourly and monthly intervals. A significant circadian variation, characterized by a peak in the afternoon (P < .001) and one in the early morning (P= .002) was found. A seasonal peak was also observed between November and January, while a nadir was observed in July. The clustering of attacks in the morning and midday and in autumn-winter, with a minimum frequency in July, suggests that school activities may represent an important cause of migraine.

Usual normalization strategies for gene expression studies impair the detection and analysis of circadian patterns.

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Figueredo, Diego de Siqueira; Barbosa, Mayara Rodrigues; Coimbra, Daniel Gomes; Dos Santos, José Luiz Araújo; Costa, Ellyda Fernanda Lopes; Koike, Bruna Del Vechio; Alexandre Moreira, Magna Suzana; de Andrade, Tiago Gomes

2018-03-01

Recent studies have shown that transcriptomes from different tissues present circadian oscillations. Therefore, the endogenous variation of total RNA should be considered as a potential bias in circadian studies of gene expression. However, normalization strategies generally include the equalization of total RNA concentration between samples prior to cDNA synthesis. Moreover, endogenous housekeeping genes (HKGs) frequently used for data normalization may exhibit circadian variation and distort experimental results if not detected or considered. In this study, we controlled experimental conditions from the amount of initial brain tissue samples through extraction steps, cDNA synthesis, and quantitative real time PCR (qPCR) to demonstrate a circadian oscillation of total RNA concentration. We also identified that the normalization of the RNA's yield affected the rhythmic profiles of different genes, including Per1-2 and Bmal1. Five widely used HKGs (Actb, Eif2a, Gapdh, Hprt1, and B2m) also presented rhythmic variations not detected by geNorm algorithm. In addition, the analysis of exogenous microRNAs (Cel-miR-54 and Cel-miR-39) spiked during RNA extraction suggests that the yield was affected by total RNA concentration, which may impact circadian studies of small RNAs. The results indicate that the approach of tissue normalization without total RNA equalization prior to cDNA synthesis can avoid bias from endogenous broad variations in transcript levels. Also, the circadian analysis of 2 -Cycle threshold (Ct) data, without HKGs, may be an alternative for chronobiological studies under controlled experimental conditions.

Rhythmic Behavior Is Controlled by the SRm160 Splicing Factor in Drosophila melanogaster.

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Beckwith, Esteban J; Hernando, Carlos E; Polcowñuk, Sofía; Bertolin, Agustina P; Mancini, Estefania; Ceriani, M Fernanda; Yanovsky, Marcelo J

2017-10-01

Circadian clocks organize the metabolism, physiology, and behavior of organisms throughout the day-night cycle by controlling daily rhythms in gene expression at the transcriptional and post-transcriptional levels. While many transcription factors underlying circadian oscillations are known, the splicing factors that modulate these rhythms remain largely unexplored. A genome-wide assessment of the alterations of gene expression in a null mutant of the alternative splicing regulator SR-related matrix protein of 160 kDa (SRm160) revealed the extent to which alternative splicing impacts on behavior-related genes. We show that SRm160 affects gene expression in pacemaker neurons of the Drosophila brain to ensure proper oscillations of the molecular clock. A reduced level of SRm160 in adult pacemaker neurons impairs circadian rhythms in locomotor behavior, and this phenotype is caused, at least in part, by a marked reduction in period ( per ) levels. Moreover, rhythmic accumulation of the neuropeptide PIGMENT DISPERSING FACTOR in the dorsal projections of these neurons is abolished after SRm160 depletion. The lack of rhythmicity in SRm160-downregulated flies is reversed by a fully spliced per construct, but not by an extra copy of the endogenous locus, showing that SRm160 positively regulates per levels in a splicing-dependent manner. Our findings highlight the significant effect of alternative splicing on the nervous system and particularly on brain function in an in vivo model. Copyright © 2017 by the Genetics Society of America.

Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Depression

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Roberto Salgado-Delgado

2011-01-01

Full Text Available Circadian factors might play a crucial role in the etiology of depression. It has been demonstrated that the disruption of circadian rhythms by lighting conditions and lifestyle predisposes individuals to a wide range of mood disorders, including impulsivity, mania and depression. Also, associated with depression, there is the impairment of circadian rhythmicity of behavioral, endocrine, and metabolic functions. Inspite of this close relationship between both processes, the complex relationship between the biological clock and the incidence of depressive symptoms is far from being understood. The efficiency and the timing of treatments based on chronotherapy (e.g., light treatment, sleep deprivation, and scheduled medication indicate that the circadian system is an essential target in the therapy of depression. The aim of the present review is to analyze the biological and clinical data that link depression with the disruption of circadian rhythms, emphasizing the contribution of circadian desynchrony. Therefore, we examine the conditions that may lead to circadian disruption of physiology and behavior as described in depressive states, and, according to this approach, we discuss therapeutic strategies aimed at treating the circadian system and depression.

Dim light at night disrupts molecular circadian rhythms and increases body weight.

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Fonken, Laura K; Aubrecht, Taryn G; Meléndez-Fernández, O Hecmarie; Weil, Zachary M; Nelson, Randy J

2013-08-01

With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms that are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electric lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however, the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to dim light at night and investigated changes in the circadian system and metabolism. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night altered core circadian clock rhythms in the hypothalamus at both the gene and protein level. Circadian rhythms in clock expression persisted during light at night; however, the amplitude of Per1 and Per2 rhythms was attenuated in the hypothalamus. Circadian oscillations were also altered in peripheral tissues critical for metabolic regulation. Exposure to dimly illuminated, as compared to dark, nights decreased the rhythmic expression in all but one of the core circadian clock genes assessed in the liver. Additionally, mice exposed to dim light at night attenuated Rev-Erb expression in the liver and adipose tissue. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide evidence that mild changes in environmental lighting can alter circadian and metabolic function. Detailed analysis of temporal changes induced by nighttime light exposure may provide insight into the onset and progression of obesity and metabolic syndrome, as well as other disorders involving sleep and circadian rhythm disruption.

Circadian oscillations of molecular clock components in the cerebellar cortex of the rat

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Rath, Martin Fredensborg; Rohde, Kristian; Møller, Morten

2012-01-01

these genes, Per1, Per2, Per3, Cry1, Arntl, Nr1d1, and Dbp were found to exhibit circadian rhythms in a sequential temporal manner similar to that of the SCN, but with several hours of delay. The results of lesion studies indicate that the molecular oscillatory profiles of Per1, Per2, and Cry1......The central circadian clock of the mammalian brain resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. At the molecular level, the circadian clockwork of the SCN constitutes a self-sustained autoregulatory feedback mechanism reflected by the rhythmic expression of clock genes. However...... in the cerebellum are controlled, though possibly indirectly, by the central clock of the SCN. These data support the presence of a circadian oscillator in the cortex of the rat cerebellum....

Circadian Rhythms in Diet-Induced Obesity.

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Engin, Atilla

2017-01-01

The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronizes these with daily cycles, feeding patterns also regulates circadian clocks. The clock genes and adipocytokines show circadian rhythmicity. Dysfunction of these genes are involved in the alteration of these adipokines during the development of obesity. Food availability promotes the stimuli associated with food intake which is a circadian oscillator outside of the suprachiasmatic nucleus (SCN). Its circadian rhythm is arranged with the predictable daily mealtimes. Food anticipatory activity is mediated by a self-sustained circadian timing and its principal component is food entrained oscillator. However, the hypothalamus has a crucial role in the regulation of energy balance rather than food intake. Fatty acids or their metabolites can modulate neuronal activity by brain nutrient-sensing neurons involved in the regulation of energy and glucose homeostasis. The timing of three-meal schedules indicates close association with the plasma levels of insulin and preceding food availability. Desynchronization between the central and peripheral clocks by altered timing of food intake and diet composition can lead to uncoupling of peripheral clocks from the central pacemaker and to the development of metabolic disorders. Metabolic dysfunction is associated with circadian disturbances at both central and peripheral levels and, eventual disruption of circadian clock functioning can lead to obesity. While CLOCK expression levels are increased with high fat diet-induced obesity, peroxisome proliferator-activated receptor (PPAR) alpha increases the transcriptional level of brain and muscle ARNT-like 1 (BMAL1) in obese subjects. Consequently, disruption of clock genes results in dyslipidemia, insulin resistance and obesity. Modifying the time of feeding alone can greatly affect body weight. Changes in the circadian clock are associated with temporal alterations in

System identification of the Arabidopsis plant circadian system

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Foo, Mathias; Somers, David E.; Kim, Pan-Jun

2015-02-01

The circadian system generates an endogenous oscillatory rhythm that governs the daily activities of organisms in nature. It offers adaptive advantages to organisms through a coordination of their biological functions with the optimal time of day. In this paper, a model of the circadian system in the plant Arabidopsis (species thaliana) is built by using system identification techniques. Prior knowledge about the physical interactions of the genes and the proteins in the plant circadian system is incorporated in the model building exercise. The model is built by using primarily experimentally-verified direct interactions between the genes and the proteins with the available data on mRNA and protein abundances from the circadian system. Our analysis reveals a great performance of the model in predicting the dynamics of the plant circadian system through the effect of diverse internal and external perturbations (gene knockouts and day-length changes). Furthermore, we found that the circadian oscillatory rhythm is robust and does not vary much with the biochemical parameters except those of a light-sensitive protein P and a transcription factor TOC1. In other words, the circadian rhythmic profile is largely a consequence of the network's architecture rather than its particular parameters. Our work suggests that the current experimental knowledge of the gene-to-protein interactions in the plant Arabidopsis, without considering any additional hypothetical interactions, seems to suffice for system-level modeling of the circadian system of this plant and to present an exemplary platform for the control of network dynamics in complex living organisms.

Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology.

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Reiter, Russel J; Tan, Dun Xian; Korkmaz, Ahmet; Rosales-Corral, Sergio A

2014-01-01

Research within the last decade has shown melatonin to have previously-unsuspected beneficial actions on the peripheral reproductive organs. Likewise, numerous investigations have documented that stable circadian rhythms are also helpful in maintaining reproductive health. The relationship of melatonin and circadian rhythmicity to maternal and fetal health is summarized in this review. Databases were searched for the related published English literature up to 15 May 2013. The search terms used in various combinations included melatonin, circadian rhythms, biological clock, suprachiasmatic nucleus, ovary, pregnancy, uterus, placenta, fetus, pre-eclampsia, intrauterine growth restriction, ischemia-reperfusion, chronodisruption, antioxidants, oxidative stress and free radicals. The results of the studies uncovered are summarized herein. Both melatonin and circadian rhythms impact reproduction, especially during pregnancy. Melatonin is a multifaceted molecule with direct free radical scavenging and indirect antioxidant activities. Melatonin is produced in both the ovary and in the placenta where it protects against molecular mutilation and cellular dysfunction arising from oxidative/nitrosative stress. The placenta, in particular, is often a site of excessive free radical generation due to less than optimal adhesion to the uterine wall, which leads to either persistent hypoxia or intermittent hypoxia and reoxygenation, processes that cause massive free radical generation and organ dysfunction. This may contribute to pre-eclampsia and other disorders which often complicate pregnancy. Melatonin has ameliorated free radical damage to the placenta and to the fetus in experiments using non-human mammals. Likewise, the maintenance of a regular maternal light/dark and sleep/wake cycle is important to stabilize circadian rhythms generated by the maternal central circadian pacemaker, the suprachiasmatic nuclei. Optimal circadian rhythmicity in the mother is important since her

"Time sweet time": circadian characterization of galectin-1 null mice

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Rabinovich Gabriel A

2010-04-01

Full Text Available Abstract Background Recent evidence suggests a two-way interaction between the immune and circadian systems. Circadian control of immune factors, as well as the effect of immunological variables on circadian rhythms, might be key elements in both physiological and pathological responses to the environment. Among these relevant factors, galectin-1 is a member of a family of evolutionarily-conserved glycan-binding proteins with both extracellular and intracellular effects, playing important roles in immune cell processes and inflammatory responses. Many of these actions have been studied through the use of mice with a null mutation in the galectin-1 (Lgals1 gene. To further analyze the role of endogenous galectin-1 in vivo, we aimed to characterize the circadian behavior of galectin-1 null (Lgals1-/- mice. Methods We analyzed wheel-running activity in light-dark conditions, constant darkness, phase responses to light pulses (LP at circadian time 15, and reentrainment to 6 hour shifts in light-dark schedule in wild-type (WT and Lgals1-/- mice. Results We found significant differences in free-running period, which was longer in mutant than in WT mice (24.02 vs 23.57 h, p alpha (14.88 vs. 12.35 circadian h, p Conclusions Given the effect of a null mutation on circadian period and entrainment, we indicate that galectin-1 could be involved in the regulation of murine circadian rhythmicity. This is the first study implicating galectin-1 in the mammalian circadian system.

Dissection of the couplings between cellular messengers and the circadian clock

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Tong Jian; Edmunds, L.N.

1995-12-01

It has been known in recent years that living cells can exhibit circadian rhythms in totally different physiological processes. Intracellular messengers were demonstrated to mediate the entrained pathways linking rhythmic components between circadian clock and its output signalling. Levels of cyclic AMP and cyclic GMP in synchronized cells, and activities of the two key enzymes (AC and PDE) responsible for the cyclic AMP metabolism were measured by applying the isotopic techniques. Bimodal circadian oscillations of the messenger levels and the enzyme activities were disclosed in LD: 12, 12 cycle and constant darkness, as well as in the dividing and non-dividing cultures of the Euglena ZC mutant. Interference experiments with the enzyme activator and inhibitor such as forskolin, 8-Br-cGMP and LY 83583, and analysis of the cell division cycle (CDC) and coupling messengers suggested that the peak pulse of cyclic AMP, circadian oscillation of the AC-cAMP-PDE system and phase-dependent regulation by cyclic GMP might be important coupling factors in downstream mediation between the circadian clock and the CDC. (7 figs.)

Morning and Evening Oscillators Cooperate to Reset Circadian Behavior in Response to Light Input

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Pallavi Lamba

2014-05-01

Full Text Available Light is a crucial input for circadian clocks. In Drosophila, short light exposure can robustly shift the phase of circadian behavior. The model for this resetting posits that circadian photoreception is cell autonomous: CRYPTOCHROME senses light, binds to TIMELESS (TIM, and promotes its degradation, which is mediated by JETLAG (JET. However, it was recently proposed that interactions between circadian neurons are also required for phase resetting. We identify two groups of neurons critical for circadian photoreception: the morning (M and the evening (E oscillators. These neurons work synergistically to reset rhythmic behavior. JET promotes acute TIM degradation cell autonomously in M and E oscillators but also nonautonomously in E oscillators when expressed in M oscillators. Thus, upon light exposure, the M oscillators communicate with the E oscillators. Because the M oscillators drive circadian behavior, they must also receive inputs from the E oscillators. Hence, although photic TIM degradation is largely cell autonomous, neural cooperation between M and E oscillators is critical for circadian behavioral photoresponses.

Extensive circadian and light regulation of the transcriptome in the malaria mosquito Anopheles gambiae

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2013-01-01

Background Mosquitoes exhibit 24 hr rhythms in flight activity, feeding, reproduction and development. To better understand the molecular basis for these rhythms in the nocturnal malaria vector Anopheles gambiae, we have utilized microarray analysis on time-of-day specific collections of mosquitoes over 48 hr to explore the coregulation of gene expression rhythms by the circadian clock and light, and compare these with the 24 hr rhythmic gene expression in the diurnal Aedes aegypti dengue vector mosquito. Results In time courses from An. gambiae head and body collected under light:dark cycle (LD) and constant dark (DD) conditions, we applied three algorithms that detect sinusoidal patterns and an algorithm that detects spikes in expression. This revealed across four experimental conditions 393 probes newly scored as rhythmic. These genes correspond to functions such as metabolic detoxification, immunity and nutrient sensing. This includes glutathione S-transferase GSTE5, whose expression pattern and chromosomal location are shared with other genes, suggesting shared chromosomal regulation; and pulsatile expression of the gene encoding CYP6M2, a cytochrome P450 that metabolizes pyrethroid insecticides. We explored the interaction of light and the circadian clock and highlight the regulation of odorant binding proteins (OBPs), important components of the olfactory system. We reveal that OBPs have unique expression patterns as mosquitoes make the transition from LD to DD conditions. We compared rhythmic expression between An. gambiae and Ae. aegypti heads collected under LD conditions using a single cosine fitting algorithm, and report distinct similarities and differences in the temporal regulation of genes involved in tRNA priming, the vesicular-type ATPase, olfaction and vision between the two species. Conclusions These data build on our previous analyses of time-of-day specific regulation of the An. gambiae transcriptome to reveal additional rhythmic genes, an

Maternal obesity disrupts circadian rhythms of clock and metabolic genes in the offspring heart and liver.

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Wang, Danfeng; Chen, Siyu; Liu, Mei; Liu, Chang

2015-06-01

Early life nutritional adversity is tightly associated with the development of long-term metabolic disorders. Particularly, maternal obesity and high-fat diets cause high risk of obesity in the offspring. Those offspring are also prone to develop hyperinsulinemia, hepatic steatosis and cardiovascular diseases. However, the precise underlying mechanisms leading to these metabolic dysregulation in the offspring remain unclear. On the other hand, disruptions of diurnal circadian rhythms are known to impair metabolic homeostasis in various tissues including the heart and liver. Therefore, we investigated that whether maternal obesity perturbs the circadian expression rhythms of clock, metabolic and inflammatory genes in offspring heart and liver by using RT-qPCR and Western blotting analysis. Offspring from lean and obese dams were examined on postnatal day 17 and 35, when pups were nursed by their mothers or took food independently. On P17, genes examined in the heart either showed anti-phase oscillations (Cpt1b, Pparα, Per2) or had greater oscillation amplitudes (Bmal1, Tnf-α, Il-6). Such phase abnormalities of these genes were improved on P35, while defects in amplitudes still existed. In the liver of 17-day-old pups exposed to maternal obesity, the oscillation amplitudes of most rhythmic genes examined (except Bmal1) were strongly suppressed. On P35, the oscillations of circadian and inflammatory genes became more robust in the liver, while metabolic genes were still kept non-rhythmic. Maternal obesity also had a profound influence in the protein expression levels of examined genes in offspring heart and liver. Our observations indicate that the circadian clock undergoes nutritional programing, which may contribute to the alternations in energy metabolism associated with the development of metabolic disorders in early life and adulthood.

Radioimmunological analysis of circadian rhythms of cortisol and melatonin in saliva

International Nuclear Information System (INIS)

Demel, A.W.

1990-12-01

Since blood cortisol (F) and melatonin (MTL) display a circadian secretion pattern and since the saliva concentration of these hormones is an excellent indicator of its blood levels the measurement of salivary F and MLT may be used for examining circadian rhythmicity. In these study the relationship between salivary F and MLT was explored. For this purpose it was necessary first to establish and validate a radioimmunoassay for F in saliva: salivary F was determined by a direct radioimmunoassay using cortisol-3-(O-carboxymethyl) oximino-(2- ( 125 I)iodohistamin) as tracer and cortisol-3-CMO-BSA antiserum. The parallel measurement of F levels in saliva and serum of adults gave an excellent correlation (r=0.87, p 0.00956x ). Serum F was assayed on the Abott TDX-System using a radioimmunofluorescence method. Secondly, using this assay the circadian saliva F pattern was determined as well as the pattern of salivary MLT in 9 young, healthy volunteers. For saliva MLT estimations a previously published method was applied (SCHULZ et al 1990). Using a computerized program (RHYTHM) written by EVE v. CAUTER (1979), the hormone data of each individuum were examined for circadian rhythmicity and its acrophases (time of occurrence of the maximum of a sinusoid fitted to the data). The F acrophase occured between 7:00 and 12:00 h (Mean: 8:06 h, SD: 93.8 min). The acrophase for MLT was found between 0:00 and 6:00 h (Mean: 3:33 h, SD: 104.4 min). There was a phase difference between both hormones of 3 to 7 hours (Mean: 292.5 min, SD: 74.7 min). The easy stress-free non-invasive nature of saliva collection makes saliva to one of the most accessible body fluids and of high value in studying the circadian system in healthy humans as well as in infants, children, pregnant women and anaemic patients. Measurements of salivary F and MLT may help to elucidate not only the circadian rhythms of these hormones under normal and pathological conditions but it may also provide insight in

Effects of short-term quetiapine treatment on emotional processing, sleep and circadian rhythms.

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Rock, Philippa L; Goodwin, Guy M; Wulff, Katharina; McTavish, Sarah F B; Harmer, Catherine J

2016-03-01

Quetiapine is an atypical antipsychotic that can stabilise mood from any index episode of bipolar disorder. This study investigated the effects of seven-day quetiapine administration on sleep, circadian rhythms and emotional processing in healthy volunteers. Twenty healthy volunteers received 150 mg quetiapine XL for seven nights and 20 matched controls received placebo. Sleep-wake actigraphy was completed for one week both pre-dose and during drug treatment. On Day 8, participants completed emotional processing tasks. Actigraphy revealed that quetiapine treatment increased sleep duration and efficiency, delayed final wake time and had a tendency to reduce within-day variability. There were no effects of quetiapine on subjective ratings of mood or energy. Quetiapine-treated participants showed diminished bias towards positive words and away from negative words during recognition memory. Quetiapine did not significantly affect facial expression recognition, emotional word categorisation, emotion-potentiated startle or emotional word/faces dot-probe vigilance reaction times. These changes in sleep timing and circadian rhythmicity in healthy volunteers may be relevant to quetiapine's therapeutic actions. Effects on emotional processing did not emulate the effects of antidepressants. The effects of quetiapine on sleep and circadian rhythms in patients with bipolar disorder merit further investigation to elucidate its mechanisms of action. © The Author(s) 2016.

A circadian rhythm regulating hyphal melanization in Cercospora kikuchii.

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Bluhm, Burton H; Burnham, A Michele; Dunkle, Larry D

2010-01-01

Many metabolic and developmental processes in fungi are controlled by biological rhythms. Circadian rhythms approximate a daily (24 h) cycle and have been thoroughly studied in the model fungus, Neurospora crassa. However relatively few examples of true circadian rhythms have been documented among other filamentous fungi. In this study we describe a circadian rhythm underlying hyphal melanization in Cercospora kikuchii, an important pathogen of soybean. After growth in light or light : dark cycles, colonies transferred to darkness produced zonate bands of melanized hyphae interspersed with bands of hyaline hyphae. Rhythmic production of bands was remarkably persistent in the absence of external cues, lasting at least 7 d after transfer to darkness, and was compensated over a range of temperatures. As in N. crassa, blue light but not red light was sufficient to entrain the circadian rhythm in C. kikuchii, and a putative ortholog of white collar-1, one of the genes required for light responses in N. crassa, was identified in C. kikuchii. Circadian regulation of melanization is conserved in other members of the genus: Similar rhythms were identified in another field isolate of C. kikuchii as well as field isolates of C. beticola and C. sorghi, but not in wild-type strains of C. zeae-maydis or C. zeina. This report represents the first documented circadian rhythm among Dothideomycete fungi and provides a new opportunity to dissect the molecular basis of circadian rhythms among filamentous fungi.

Circadian regulation of myocardial sarcomeric Titin-cap (Tcap, telethonin: identification of cardiac clock-controlled genes using open access bioinformatics data.

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Peter S Podobed

Full Text Available Circadian rhythms are important for healthy cardiovascular physiology and are regulated at the molecular level by a circadian clock mechanism. We and others previously demonstrated that 9-13% of the cardiac transcriptome is rhythmic over 24 h daily cycles; the heart is genetically a different organ day versus night. However, which rhythmic mRNAs are regulated by the circadian mechanism is not known. Here, we used open access bioinformatics databases to identify 94 transcripts with expression profiles characteristic of CLOCK and BMAL1 targeted genes, using the CircaDB website and JTK_Cycle. Moreover, 22 were highly expressed in the heart as determined by the BioGPS website. Furthermore, 5 heart-enriched genes had human/mouse conserved CLOCK:BMAL1 promoter binding sites (E-boxes, as determined by UCSC table browser, circadian mammalian promoter/enhancer database PEDB, and the European Bioinformatics Institute alignment tool (EMBOSS. Lastly, we validated findings by demonstrating that Titin cap (Tcap, telethonin was targeted by transcriptional activators CLOCK and BMAL1 by showing 1 Tcap mRNA and TCAP protein had a diurnal rhythm in murine heart; 2 cardiac Tcap mRNA was rhythmic in animals kept in constant darkness; 3 Tcap and control Per2 mRNA expression and cyclic amplitude were blunted in Clock(Δ19/Δ19 hearts; 4 BMAL1 bound to the Tcap promoter by ChIP assay; 5 BMAL1 bound to Tcap promoter E-boxes by biotinylated oligonucleotide assay; and 6 CLOCK and BMAL1 induced tcap expression by luciferase reporter assay. Thus this study identifies circadian regulated genes in silico, with validation of Tcap, a critical regulator of cardiac Z-disc sarcomeric structure and function.

Biochemical genetics of the circadian rhythm in Neurospora crassa: studies on the cel strain

International Nuclear Information System (INIS)

Lakin-Thomas, P.L.

1985-01-01

In Neurospora crassa, the cel mutation lengthens the period of the circadian rhythm when the medium is supplemented with linoleic acid (18:2). Double mutant strains were constructed between cel and the clock mutants prd-1 and four alleles at the frq locus. It was found that: (1) the effect of 18:2 on cel was blocked by prd-1, i.e., prd-1 is epistatic to cel. (2) cel and frq interact such that the percent increase in the period produced by 18:2 was inversely proportional to the period of the frq parent. (3) Data from the literature on period effects in double mutant strains support a multiplicative rather than an additive model. A biochemical interpretation of these interactions is discussed, based on the control of flux through metabolic pathways. Because the cel strain is known to be deficient in the pantothenate derivative normally attached to the fatty acid synthetase (FAS) complex, the possibility that cel may affect other pantothenate-modified proteins was investigated. It was found that in the cel + strain, five proteins of molecular weights (M/sub r/) 9000, 19,000, 22,000, 140,000, and 200,000 were labelled with [ 14 C]pantothenate. In the cel strain, only the 200 k (FAS) label was reduced in amount. Therefore, there is no evidence that cel affects circadian rhythmicity through any deficiency other than FAS. A biochemical model for circadian rhythmicity in Neurospora is presented. Oscillations in cytoplasmic and mitochondrial Ca 2+ are proposed; clock mutations are postulated to affect Ca 2+ transporters and the mitochondrial membrane; and phase-shifting effects are accounted for by changes in Ca 2+ or ATP levels

Diurnal oscillations of soybean circadian clock and drought responsive genes.

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Juliana Marcolino-Gomes

Full Text Available Rhythms produced by the endogenous circadian clock play a critical role in allowing plants to respond and adapt to the environment. While there is a well-established regulatory link between the circadian clock and responses to abiotic stress in model plants, little is known of the circadian system in crop species like soybean. This study examines how drought impacts diurnal oscillation of both drought responsive and circadian clock genes in soybean. Drought stress induced marked changes in gene expression of several circadian clock-like components, such as LCL1-, GmELF4- and PRR-like genes, which had reduced expression in stressed plants. The same conditions produced a phase advance of expression for the GmTOC1-like, GmLUX-like and GmPRR7-like genes. Similarly, the rhythmic expression pattern of the soybean drought-responsive genes DREB-, bZIP-, GOLS-, RAB18- and Remorin-like changed significantly after plant exposure to drought. In silico analysis of promoter regions of these genes revealed the presence of cis-elements associated both with stress and circadian clock regulation. Furthermore, some soybean genes with upstream ABRE elements were responsive to abscisic acid treatment. Our results indicate that some connection between the drought response and the circadian clock may exist in soybean since (i drought stress affects gene expression of circadian clock components and (ii several stress responsive genes display diurnal oscillation in soybeans.

Food intake and antiepileptic drugs: evidence for a role of GABA in circadian time keeping.

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Rietveld, W J; van Schravendijk, K

1987-01-01

Long-term application of sodium-valproate was studied while recording food intake of rats. It was found that sodium valproate was able to decrease the period length of free-running circadian rhythmicity. After withdrawal of the drug, the period length returned to the predrug values.

Ischemic stroke destabilizes circadian rhythms

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Borjigin Jimo

2008-10-01

Full Text Available Abstract Background The central circadian pacemaker is a remarkably robust regulator of daily rhythmic variations of cardiovascular, endocrine, and neural physiology. Environmental lighting conditions are powerful modulators of circadian rhythms, but regulation of circadian rhythms by disease states is less clear. Here, we examine the effect of ischemic stroke on circadian rhythms in rats using high-resolution pineal microdialysis. Methods Rats were housed in LD 12:12 h conditions and monitored by pineal microdialysis to determine baseline melatonin timing profiles. After demonstration that the circadian expression of melatonin was at steady state, rats were subjected to experimental stroke using two-hour intralumenal filament occlusion of the middle cerebral artery. The animals were returned to their cages, and melatonin monitoring was resumed. The timing of onset, offset, and duration of melatonin secretion were calculated before and after stroke to determine changes in circadian rhythms of melatonin secretion. At the end of the monitoring period, brains were analyzed to determine infarct volume. Results Rats demonstrated immediate shifts in melatonin timing after stroke. We observed a broad range of perturbations in melatonin timing in subsequent days, with rats exhibiting onset/offset patterns which included: advance/advance, advance/delay, delay/advance, and delay/delay. Melatonin rhythms displayed prolonged instability several days after stroke, with a majority of rats showing a day-to-day alternation between advance and delay in melatonin onset and duration. Duration of melatonin secretion changed in response to stroke, and this change was strongly determined by the shift in melatonin onset time. There was no correlation between infarct size and the direction or amplitude of melatonin phase shifting. Conclusion This is the first demonstration that stroke induces immediate changes in the timing of pineal melatonin secretion, indicating

Circadian control of isoprene emissions from oil palm (Elaeis guineensis).

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Wilkinson, Michael J; Owen, Susan M; Possell, Malcolm; Hartwell, James; Gould, Peter; Hall, Anthony; Vickers, Claudia; Nicholas Hewitt, C

2006-09-01

The emission of isoprene from the biosphere to the atmosphere has a profound effect on the Earth's atmospheric system. Until now, it has been assumed that the primary short-term controls on isoprene emission are photosynthetically active radiation and temperature. Here we show that isoprene emissions from a tropical tree (oil palm, Elaeis guineensis) are under strong circadian control, and that the circadian clock is potentially able to gate light-induced isoprene emissions. These rhythms are robustly temperature compensated with isoprene emissions still under circadian control at 38 degrees C. This is well beyond the acknowledged temperature range of all previously described circadian phenomena in plants. Furthermore, rhythmic expression of LHY/CCA1, a genetic component of the central clock in Arabidopsis thaliana, is still maintained at these elevated temperatures in oil palm. Maintenance of the CCA1/LHY-TOC1 molecular oscillator at these temperatures in oil palm allows for the possibility that this system is involved in the control of isoprene emission rhythms. This study contradicts the accepted theory that isoprene emissions are primarily light-induced.

Diurnal and circadian rhythms in the tomato transcriptome and their modulation by cryptochrome photoreceptors.

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Paolo Facella

Full Text Available BACKGROUND: Circadian clocks are internal molecular time-keeping mechanisms that provide living organisms with the ability to adjust their growth and physiology and to anticipate diurnal environmental changes. Circadian clocks, without exception, respond to light and, in plants, light is the most potent and best characterized entraining stimulus. The capacity of plants to respond to light is achieved through a number of photo-perceptive proteins including cryptochromes and phytochromes. There is considerable experimental evidence demonstrating the roles of photoreceptors in providing light input to the clock. METHODOLOGY: In order to identify genes regulated by diurnal and circadian rhythms, and to establish possible functional relations between photoreceptors and the circadian clock in tomato, we monitored the temporal transcription pattern in plants entrained to long-day conditions, either by large scale comparative profiling, or using a focused approach over a number of photosensory and clock-related genes by QRT-PCR. In parallel, focused transcription analyses were performed in cry1a- and in CRY2-OX tomato genotypes. CONCLUSIONS: We report a large series of transcript oscillations that shed light on the complex network of interactions among tomato photoreceptors and clock-related genes. Alteration of cryptochrome gene expression induced major changes in the rhythmic oscillations of several other gene transcripts. In particular, over-expression of CRY2 had an impact not only on day/night fluctuations but also on rhythmicity under constant light conditions. Evidence was found for widespread diurnal oscillations of transcripts encoding specific enzyme classes (e.g. carotenoid biosynthesis enzymes as well as for post-transcriptional diurnal and circadian regulation of the CRY2 transcript.

Neurobiology of circadian systems.

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Schulz, Pierre; Steimer, Thierry

2009-01-01

Time is a dimension tightly associated with the biology of living species. There are cycles of varied lengths in biological activities, from very short (ultradian) rhythms to rhythms with a period of approximately one day (circadian) and rhythms with longer cycles, of a week, a month, a season, or even longer. These rhythms are generated by endogenous biological clocks, i.e. time-keeping structures, rather than being passive reactions to external fluctuations. In mammals, the suprachiasmatic nucleus (SCN) is the major pacemaker. The pineal gland, which secretes melatonin, is the major pacemaker in other phyla. There also exist biological clocks generating circadian rhythms in peripheral tissues, for example the liver. A series of clock genes generates the rhythm through positive and negative feedback effect of proteins on their own synthesis, and this system oscillates with a circadian period. External factors serve as indicators of the astronomical (solar) time and are called zeitgebers, literally time-givers. Light is the major zeitgeber, which resets daily the SCN circadian clock. In the absence of zeitgebers, the circadian rhythm is said to be free running; it has a period that differs from 24 hours. The SCN, together with peripheral clocks, enables a time-related homeostasis, which can become disorganized in its regulation by external factors (light, social activities, food intake), in the coordination and relative phase position of rhythms, or in other ways. Disturbances of rhythms are found in everyday life (jet lag, shift work), in sleep disorders, and in several psychiatric disorders including affective disorders. As almost all physiological and behavioural functions in humans occur on a rhythmic basis, the possibility that advances, delays or desynchronization of circadian rhythms might participate in neurological and psychiatric disorders has been a theme of research. In affective disorders, a decreased circadian amplitude of several rhythms as well as a

Sleep quality and circadian rhythm disruption in the intensive care unit

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Boyko, Yuliya; Jennum, Poul; Toft, Palle

2017-01-01

Sleep and circadian rhythm are reported to be severely abnormal in critically ill patients. Disturbed sleep can lead to the development of delirium and, as a result, can be associated with prolonged stay in the intensive care unit (ICU) and increased mortality. The standard criterion method...... aiming to improve sleep quality and circadian rhythm in the ICU. The results of these studies were inconclusive due to using the sleep assessment methods other than PSG or the absence of a reliable sleep scoring tool for the analysis of the PSG findings in this patient population. Development of a valid......, medication, as well as the critical illness itself have been reported as important sleep disturbing factors. Secretion of sleep hormone, melatonin, expressing circadian rhythmicity was found abolished or phase delayed in critically ill patients. Various interventions have been tested in several studies...

Genome-wide profiling of 24 hr diel rhythmicity in the water flea, Daphnia pulex: network analysis reveals rhythmic gene expression and enhances functional gene annotation.

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Rund, Samuel S C; Yoo, Boyoung; Alam, Camille; Green, Taryn; Stephens, Melissa T; Zeng, Erliang; George, Gary F; Sheppard, Aaron D; Duffield, Giles E; Milenković, Tijana; Pfrender, Michael E

2016-08-18

Marine and freshwater zooplankton exhibit daily rhythmic patterns of behavior and physiology which may be regulated directly by the light:dark (LD) cycle and/or a molecular circadian clock. One of the best-studied zooplankton taxa, the freshwater crustacean Daphnia, has a 24 h diel vertical migration (DVM) behavior whereby the organism travels up and down through the water column daily. DVM plays a critical role in resource tracking and the behavioral avoidance of predators and damaging ultraviolet radiation. However, there is little information at the transcriptional level linking the expression patterns of genes to the rhythmic physiology/behavior of Daphnia. Here we analyzed genome-wide temporal transcriptional patterns from Daphnia pulex collected over a 44 h time period under a 12:12 LD cycle (diel) conditions using a cosine-fitting algorithm. We used a comprehensive network modeling and analysis approach to identify novel co-regulated rhythmic genes that have similar network topological properties and functional annotations as rhythmic genes identified by the cosine-fitting analyses. Furthermore, we used the network approach to predict with high accuracy novel gene-function associations, thus enhancing current functional annotations available for genes in this ecologically relevant model species. Our results reveal that genes in many functional groupings exhibit 24 h rhythms in their expression patterns under diel conditions. We highlight the rhythmic expression of immunity, oxidative detoxification, and sensory process genes. We discuss differences in the chronobiology of D. pulex from other well-characterized terrestrial arthropods. This research adds to a growing body of literature suggesting the genetic mechanisms governing rhythmicity in crustaceans may be divergent from other arthropod lineages including insects. Lastly, these results highlight the power of using a network analysis approach to identify differential gene expression and provide novel

α1B-Adrenergic receptor signaling controls circadian expression of Tnfrsf11b by regulating clock genes in osteoblasts

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Takao Hirai

2015-11-01

Full Text Available Circadian clocks are endogenous and biological oscillations that occur with a period of <24 h. In mammals, the central circadian pacemaker is localized in the suprachiasmatic nucleus (SCN and is linked to peripheral tissues through neural and hormonal signals. In the present study, we investigated the physiological function of the molecular clock on bone remodeling. The results of loss-of-function and gain-of-function experiments both indicated that the rhythmic expression of Tnfrsf11b, which encodes osteoprotegerin (OPG, was regulated by Bmal1 in MC3T3-E1 cells. We also showed that REV-ERBα negatively regulated Tnfrsf11b as well as Bmal1 in MC3T3-E1 cells. We systematically investigated the relationship between the sympathetic nervous system and the circadian clock in osteoblasts. The administration of phenylephrine, a nonspecific α1-adrenergic receptor (AR agonist, stimulated the expression of Tnfrsf11b, whereas the genetic ablation of α1B-AR signaling led to the alteration of Tnfrsf11b expression concomitant with Bmal1 and Per2 in bone. Thus, this study demonstrated that the circadian regulation of Tnfrsf11b was regulated by the clock genes encoding REV-ERBα (Nr1d1 and Bmal1 (Bmal1, also known as Arntl, which are components of the core loop of the circadian clock in osteoblasts.

Rhythmic expression of miR-27b-3p targets the clock gene Bmal1 at the posttranscriptional level in the mouse liver.

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Zhang, Wenxiang; Wang, Peng; Chen, Siyu; Zhang, Zhao; Liang, Tingming; Liu, Chang

2016-06-01

Circadian clocks orchestrate daily oscillations in mammalian behaviors, physiology, and gene expression. MicroRNAs (miRNAs) play a crucial role in fine-tuning of the circadian system. However, little is known about the direct regulation of the clock genes by specific miRNAs. In this study, we found that miR-27b-3p exhibits rhythmic expression in the metabolic tissues of the mice subjected to constant darkness. MiR-27b-3p's expression is induced in livers of unfed and ob/ob mice. In addition, the oscillation phases of miR-27b-3p can be reversed by restricted feeding, suggesting a role of peripheral clock in regulating its rhythmicity. Bioinformatics analysis indicated that aryl hydrocarbon receptor nuclear translocator-like (also known as Bmal1) may be a direct target of miR-27b-3p. Luciferase reporter assay showed that miR-27b-3p suppressed Bmal1 3' UTR activity in a dose-dependent manner, and mutagenesis of their binding site abolished this suppression. Furthermore, overexpression of miR-27b-3p dose-dependently reduced the protein expression levels of BMAL1 and impaired the endogenous BMAL1 and gluconeogenic protein rhythmicity. Collectively, our results suggest that miR-27b-3p plays an important role in the posttranscriptional regulation of BMAL1 protein in the liver. MiR-27b-3p may serve as a novel node to integrate the circadian clock and energy metabolism.-Zhang, W., Wang, P., Chen, S., Zhang, Z., Liang, T., Liu, C. Rhythmic expression of miR-27b-3p targets the clock gene Bmal1 at the posttranscriptional level in the mouse liver. © FASEB.

Internal ribosomal entry site-mediated translation is important for rhythmic PERIOD1 expression.

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Kyung-Ha Lee

Full Text Available The mouse PERIOD1 (mPER1 plays an important role in the maintenance of circadian rhythm. Translation of mPer1 is directed by both a cap-dependent process and cap-independent translation mediated by an internal ribosomal entry site (IRES in the 5' untranslated region (UTR. Here, we compared mPer1 IRES activity with other cellular IRESs. We also found critical region in mPer1 5'UTR for heterogeneous nuclear ribonucleoprotein Q (HNRNPQ binding. Deletion of HNRNPQ binding region markedly decreased IRES activity and disrupted rhythmicity. A mathematical model also suggests that rhythmic IRES-dependent translation is a key process in mPER1 oscillation. The IRES-mediated translation of mPer1 will help define the post-transcriptional regulation of the core clock genes.

Pronounced between-subject and circadian variability in thymidylate synthase and dihydropyrimidine dehydrogenase enzyme activity in human volunteers

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Jacobs, Bart A W; Deenen, Maarten J; Pluim, Dick; van Hasselt, J G Coen; Krähenbühl, Martin D; van Geel, Robin M J M; de Vries, Niels; Rosing, Hilde; Meulendijks, Didier; Burylo, Artur M; Cats, Annemieke; Beijnen, Jos H; Huitema, Alwin D R; Schellens, Jan H M

AIMS: The enzymatic activity of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are important for the tolerability and efficacy of the fluoropyrimidine drugs. In the present study, we explored between-subject variability (BSV) and circadian rhythmicity in DPD and TS activity in

Life in a dark biosphere: a review of circadian physiology in "arrhythmic" environments.

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Beale, Andrew David; Whitmore, David; Moran, Damian

2016-12-01

Most of the life with which humans interact is exposed to highly rhythmic and extremely predictable changes in illumination that occur with the daily events of sunrise and sunset. However, while the influence of the sun feels omnipotent to surface dwellers such as ourselves, life on earth is dominated, in terms of biomass, by organisms isolated from the direct effects of the sun. A limited understanding of what life is like away from the sun can be inferred from our knowledge of physiology and ecology in the light biosphere, but a full understanding can only be gained by studying animals from the dark biosphere, both in the laboratory and in their natural habitats. One of the least understood aspects of life in the dark biosphere is the rhythmicity of physiology and what it means to live in an environment of low or no rhythmicity. Here we describe methods that may be used to understand rhythmic physiology in the dark and summarise some of the studies of rhythmic physiology in "arrhythmic" environments, such as the poles, deep sea and caves. We review what can be understood about the adaptive value of rhythmic physiology on the Earth's surface from studies of animals from arrhythmic environments and what role a circadian clock may play in the dark.

Nutrigenetics and Nutrimiromics of the Circadian System: The Time for Human Health.

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Micó, Víctor; Díez-Ricote, Laura; Daimiel, Lidia

2016-02-26

Even though the rhythmic oscillations of life have long been known, the precise molecular mechanisms of the biological clock are only recently being explored. Circadian rhythms are found in virtually all organisms and affect our lives. Thus, it is not surprising that the correct running of this clock is essential for cellular functions and health. The circadian system is composed of an intricate network of genes interwined in an intrincated transcriptional/translational feedback loop. The precise oscillation of this clock is controlled by the circadian genes that, in turn, regulate the circadian oscillations of many cellular pathways. Consequently, variations in these genes have been associated with human diseases and metabolic disorders. From a nutrigenetics point of view, some of these variations modify the individual response to the diet and interact with nutrients to modulate such response. This circadian feedback loop is also epigenetically modulated. Among the epigenetic mechanisms that control circadian rhythms, microRNAs are the least studied ones. In this paper, we review the variants of circadian-related genes associated to human disease and nutritional response and discuss the current knowledge about circadian microRNAs. Accumulated evidence on the genetics and epigenetics of the circadian system points to important implications of chronotherapy in the clinical practice, not only in terms of pharmacotherapy, but also for dietary interventions. However, interventional studies (especially nutritional trials) that include chronotherapy are scarce. Given the importance of chronobiology in human health such studies are warranted in the near future.

Association between circadian clock genes and diapause incidence in Drosophila triauraria.

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Hirokazu Yamada

Full Text Available Diapause is an adaptive response triggered by seasonal photoperiodicity to overcome unfavorable seasons. The photoperiodic clock is a system that controls seasonal physiological processes, but our knowledge about its physiological mechanisms and genetic architecture remains incomplete. The circadian clock is another system that controls daily rhythmic physiological phenomena. It has been argued that there is a connection between the two clocks. To examine the genetic connection between them, we analyzed the associations of five circadian clock genes (period, timeless, Clock, cycle and cryptochrome with the occurrence of diapause in Drosophila triauraria, which shows a robust reproductive diapause with clear photoperiodicity. Non-diapause strains found in low latitudes were compared in genetic crosses with the diapause strain, in which the diapause trait is clearly dominant. Single nucleotide polymorphism and deletion analyses of the five circadian clock genes in backcross progeny revealed that allelic differences in timeless and cryptochrome between the strains were additively associated with the differences in the incidence of diapause. This suggests that there is a molecular link between certain circadian clock genes and the occurrence of diapause.

Attenuated food anticipatory activity and abnormal circadian locomotor rhythms in Rgs16 knockdown mice.

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Naoto Hayasaka

Full Text Available Regulators of G protein signaling (RGS are a multi-functional protein family, which functions in part as GTPase-activating proteins (GAPs of G protein α-subunits to terminate G protein signaling. Previous studies have demonstrated that the Rgs16 transcripts exhibit robust circadian rhythms both in the suprachiasmatic nucleus (SCN, the master circadian light-entrainable oscillator (LEO of the hypothalamus, and in the liver. To investigate the role of RGS16 in the circadian clock in vivo, we generated two independent transgenic mouse lines using lentiviral vectors expressing short hairpin RNA (shRNA targeting the Rgs16 mRNA. The knockdown mice demonstrated significantly shorter free-running period of locomotor activity rhythms and reduced total activity as compared to the wild-type siblings. In addition, when feeding was restricted during the daytime, food-entrainable oscillator (FEO-driven elevated food-anticipatory activity (FAA observed prior to the scheduled feeding time was significantly attenuated in the knockdown mice. Whereas the restricted feeding phase-advanced the rhythmic expression of the Per2 clock gene in liver and thalamus in the wild-type animals, the above phase shift was not observed in the knockdown mice. This is the first in vivo demonstration that a common regulator of G protein signaling is involved in the two separate, but interactive circadian timing systems, LEO and FEO. The present study also suggests that liver and/or thalamus regulate the food-entrained circadian behavior through G protein-mediated signal transduction pathway(s.

Circadian Plasticity in the Brain of Insects and Rodents

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Wojciech Krzeptowski

2018-05-01

Full Text Available In both vertebrate and invertebrate brains, neurons, glial cells and synapses are plastic, which means that the physiology and structure of these components are modified in response to internal and external stimuli during development and in mature brains. The term plasticity has been introduced in the last century to describe experience-dependent changes in synapse strength and number. These changes result from local functional and morphological synapse modifications; however, these modifications also occur more commonly in pre- and postsynaptic neurons. As a result, neuron morphology and neuronal networks are constantly modified during the life of animals and humans in response to different stimuli. Nevertheless, it has been discovered in flies and mammals that the number of synapses and size and shape of neurons also oscillate during the day. In most cases, these rhythms are circadian since they are generated by endogenous circadian clocks; however, some rhythmic changes in neuron morphology and synapse number and structure are controlled directly by environmental cues or by both external cues and circadian clocks. When the circadian clock is involved in generating cyclic changes in the nervous system, this type of plasticity is called circadian plasticity. It seems to be important in processing sensory information, in learning and in memory. Disruption of the clock may affect major brain functions.

Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.

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Nicole Purrier

Full Text Available Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods. Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light.

Circadian rhythm genes mediate fenvalerate-induced inhibition of testosterone synthesis in mouse Leydig cells.

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Guo, Yichen; Shen, Ouxi; Han, Jingjing; Duan, Hongyu; Yang, Siyuan; Zhu, Zhenghong; Tong, Jian; Zhang, Jie

2017-01-01

Fenvalerate (Fen), a widely used pesticide, is known to impair male reproductive functions by mechanisms that remain to be elucidated. Recent studies indicated that circadian clock genes may play an important role in successful male reproduction. The aim of this study was to determine the effects of Fen on circadian clock genes involved in the biosynthesis of testosterone using TM3 cells derived from mouse Leydig cells. Data demonstrated that the circadian rhythm of testosterone synthesis in TM3 cells was disturbed following Fen treatment as evidenced by changes in the circadian rhythmicity of core clock genes (Bmal1, Rev-erbα, Rorα). Further, the observed altered rhythms were accompanied by increased intracellular Ca 2+ levels and modified steroidogenic acute regulatory (StAR) mRNA expression. Thus, data suggested that Fen inhibits testosterone synthesis via pathways involving intracellular Ca 2+ and clock genes (Bmal1, Rev-Erbα, Rorα) as well as StAR mRNA expression in TM3 cells.

Clocking In Time to Gate Memory Processes: The Circadian Clock Is Part of the Ins and Outs of Memory

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Oliver Rawashdeh

2018-01-01

Full Text Available Learning, memory consolidation, and retrieval are processes known to be modulated by the circadian (circa: about; dies: day system. The circadian regulation of memory performance is evolutionarily conserved, independent of the type and complexity of the learning paradigm tested, and not specific to crepuscular, nocturnal, or diurnal organisms. In mammals, long-term memory (LTM formation is tightly coupled to de novo gene expression of plasticity-related proteins and posttranslational modifications and relies on intact cAMP/protein kinase A (PKA/protein kinase C (PKC/mitogen-activated protein kinase (MAPK/cyclic adenosine monophosphate response element-binding protein (CREB signaling. These memory-essential signaling components cycle rhythmically in the hippocampus across the day and night and are clearly molded by an intricate interplay between the circadian system and memory. Important components of the circadian timing mechanism and its plasticity are members of the Period clock gene family (Per1, Per2. Interestingly, Per1 is rhythmically expressed in mouse hippocampus. Observations suggest important and largely unexplored roles of the clock gene protein PER1 in synaptic plasticity and in the daytime-dependent modulation of learning and memory. Here, we review the latest findings on the role of the clock gene Period 1 (Per1 as a candidate molecular and mechanistic blueprint for gating the daytime dependency of memory processing.

Melatonin Entrains PER2::LUC Bioluminescence Circadian Rhythm in the Mouse Cornea

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Baba, Kenkichi; Davidson, Alec J.; Tosini, Gianluca

2015-01-01

Purpose Previous studies have reported the presence of a circadian rhythm in PERIOD2::LUCIFERASE (PER2::LUC) bioluminescence in mouse photoreceptors, retina, RPE, and cornea. Melatonin (MLT) modulates many physiological functions in the eye and it is believed to be one of the key circadian signals within the eye. The aim of the present study was to investigate the regulation of the PER2::LUC circadian rhythm in mouse cornea and to determine the role played by MLT. Methods Corneas were obtained from PER2::LUC mice and cultured to measure bioluminescence rhythmicity in isolated tissue using a Lumicycle or CCD camera. To determine the time-dependent resetting of the corneal circadian clocks in response to MLT or IIK7 (a melatonin type 2 receptor, MT2, agonist) was added to the cultured corneas at different times of the day. We also defined the location of the MT2 receptor within different corneal layers using immunohistochemistry. Results A long-lasting bioluminescence rhythm was recorded from cultured PER2::LUC cornea and PER2::LUC signal was localized to the corneal epithelium and endothelium. MLT administration in the early night delayed the cornea rhythm, whereas administration of MLT at late night to early morning advanced the cornea rhythm. Treatment with IIK7 mimicked the MLT phase-shifting effect. Consistent with these results, MT2 immunoreactivity was localized to the corneal epithelium and endothelium. Conclusions Our work demonstrates that MLT entrains the PER2::LUC bioluminescence rhythm in the cornea. Our data indicate that the cornea may represent a model to study the molecular mechanisms by which MLT affects the circadian clock. PMID:26207312

An agent-based model of cellular dynamics and circadian variability in human endotoxemia.

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Tung T Nguyen

Full Text Available As cellular variability and circadian rhythmicity play critical roles in immune and inflammatory responses, we present in this study an agent-based model of human endotoxemia to examine the interplay between circadian controls, cellular variability and stochastic dynamics of inflammatory cytokines. The model is qualitatively validated by its ability to reproduce circadian dynamics of inflammatory mediators and critical inflammatory responses after endotoxin administration in vivo. Novel computational concepts are proposed to characterize the cellular variability and synchronization of inflammatory cytokines in a population of heterogeneous leukocytes. Our results suggest that there is a decrease in cell-to-cell variability of inflammatory cytokines while their synchronization is increased after endotoxin challenge. Model parameters that are responsible for IκB production stimulated by NFκB activation and for the production of anti-inflammatory cytokines have large impacts on system behaviors. Additionally, examining time-dependent systemic responses revealed that the system is least vulnerable to endotoxin in the early morning and most vulnerable around midnight. Although much remains to be explored, proposed computational concepts and the model we have pioneered will provide important insights for future investigations and extensions, especially for single-cell studies to discover how cellular variability contributes to clinical implications.

Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.

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Julian Lippert

Full Text Available From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH in comparison to those of healthy controls (HC. Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG and Multiple Sleep Latency Test (MSLT. Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH.

Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.

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Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Röhr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

2014-01-01

From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH.

There Is No Association Between the Circadian Clock Gene HPER3 and Cognitive Dysfunction After Noncardiac Surgery

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Voigt Hansen, Melissa; Simon Rasmussen, Lars; Jespersgaard, Cathrine

2012-01-01

The specific clock-gene PERIOD3 is important with regard to circadian rhythmicity, sleep homeostasis, and cognitive function. The allele PER3(5/5) has been associated with worse cognitive performance in response to sleep deprivation. We hypothesized that patients with the PER3(5/5) genotype would...

Measuring Relative Coupling Strength in Circadian Systems.

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Schmal, Christoph; Herzog, Erik D; Herzel, Hanspeter

2018-02-01

Modern imaging techniques allow the monitoring of circadian rhythms of single cells. Coupling between these single cellular circadian oscillators can generate coherent periodic signals on the tissue level that subsequently orchestrate physiological outputs. The strength of coupling in such systems of oscillators is often unclear. In particular, effects on coupling strength by varying cell densities, by knockouts, and by inhibitor applications are debated. In this study, we suggest to quantify the relative coupling strength via analyzing period, phase, and amplitude distributions in ensembles of individual circadian oscillators. Simulations of different oscillator networks show that period and phase distributions become narrower with increasing coupling strength. Moreover, amplitudes can increase due to resonance effects. Variances of periods and phases decay monotonically with coupling strength, and can serve therefore as measures of relative coupling strength. Our theoretical predictions are confirmed by studying recently published experimental data from PERIOD2 expression in slices of the suprachiasmatic nucleus during and after the application of tetrodotoxin (TTX). On analyzing the corresponding period, phase, and amplitude distributions, we can show that treatment with TTX can be associated with a reduced coupling strength in the system of coupled oscillators. Analysis of an oscillator network derived directly from the data confirms our conclusions. We suggest that our approach is also applicable to quantify coupling in fibroblast cultures and hepatocyte networks, and for social synchronization of circadian rhythmicity in rodents, flies, and bees.

Circadian rhythms in handwriting kinematics and legibility.

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Jasper, Isabelle; Gordijn, Marijke; Häussler, Andreas; Hermsdörfer, Joachim

2011-08-01

The aim of the present study was to analyze the circadian rhythmicity in handwriting kinematics and legibility and to compare the performance between Dutch and German writers. Two subject groups underwent a 40 h sleep deprivation protocol under Constant Routine conditions either in Groningen (10 Dutch subjects) or in Berlin (9 German subjects). Both groups wrote every 3h a test sentence of similar structure in their native language. Kinematic handwriting performance was assessed with a digitizing tablet and evaluated by writing speed, writing fluency, and script size. Writing speed (frequency of strokes and average velocity) revealed a clear circadian rhythm, with a parallel decline during night and a minimum around 3:00 h in the morning for both groups. Script size and movement fluency did not vary with time of day in neither group. Legibility of handwriting was evaluated by intra-individually ranking handwriting specimens of the 13 sessions by 10 German and 10 Dutch raters. Whereas legibility ratings of the German handwriting specimens deteriorated during night in parallel with slower writing speed, legibility of the Dutch handwriting deteriorated not until the next morning. In conclusion, the circadian rhythm of handwriting kinematics seems to be independent of script language at least among the two tested western countries. Moreover, handwriting legibility is also subject to a circadian rhythm which, however, seems to be influenced by variations in the assessment protocol. Copyright © 2010 Elsevier B.V. All rights reserved.

Classifying Written Texts Through Rhythmic Features

NARCIS (Netherlands)

Balint, Mihaela; Dascalu, Mihai; Trausan-Matu, Stefan

2016-01-01

Rhythm analysis of written texts focuses on literary analysis and it mainly considers poetry. In this paper we investigate the relevance of rhythmic features for categorizing texts in prosaic form pertaining to different genres. Our contribution is threefold. First, we define a set of rhythmic

Insights into the role of the habenular circadian clock in addiction

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Nora L Salaberry

2016-01-01

Full Text Available Drug addiction is a brain disease involving alterations in anatomy and functional neural communication. Drug intake and toxicity show daily rhythms in both humans and rodents. Evidence concerning the role of clock genes in drug intake has been previously reported. However, the implication of a timekeeping brain locus is much less known. The epithalamic lateral habenula (LHb is now emerging as a key nucleus in drug intake and addiction. This brain structure modulates the activity of dopaminergic neurons from the ventral tegmental area, a central part of the reward system. Moreover, the LHb has circadian properties: LHb cellular activity (i.e., firing rate and clock genes expression oscillates in a 24h range, and the nucleus is affected by photic stimulation and has anatomical connections with the main circadian pacemaker, the suprachiasmatic nucleus. Here, we describe the current insights on the role of the LHb as a circadian oscillator and its possible implications on the rhythmic regulation of the dopaminergic activity and drug intake. This data could inspire new strategies to treat drug addiction, considering circadian timing as a principal factor.

Loss of circadian rhythm of circulating insulin concentration induced by high-fat diet intake is associated with disrupted rhythmic expression of circadian clock genes in the liver.

Science.gov (United States)

Honma, Kazue; Hikosaka, Maki; Mochizuki, Kazuki; Goda, Toshinao

2016-04-01

Peripheral clock genes show a circadian rhythm is correlated with the timing of feeding in peripheral tissues. It was reported that these clock genes are strongly regulated by insulin action and that a high-fat diet (HFD) intake in C57BL/6J mice for 21days induced insulin secretion during the dark phase and reduced the circadian rhythm of clock genes. In this study, we examined the circadian expression patterns of these clock genes in insulin-resistant animal models with excess secretion of insulin during the day. We examined whether insulin resistance induced by a HFD intake for 80days altered blood parameters (glucose and insulin concentrations) and expression of mRNA and proteins encoded by clock and functional genes in the liver using male ICR mice. Serum insulin concentrations were continuously higher during the day in mice fed a HFD than control mice. Expression of lipogenesis-related genes (Fas and Accβ) and the transcription factor Chrebp peaked at zeitgeber time (ZT)24 in the liver of control mice. A HFD intake reduced the expression of these genes at ZT24 and disrupted the circadian rhythm. Expression of Bmal1 and Clock, transcription factors that compose the core feedback loop, showed circadian variation and were synchronously associated with Fas gene expression in control mice, but not in those fed a HFD. These results indicate that the disruption of the circadian rhythm of insulin secretion by HFD intake is closely associated with the disappearance of circadian expression of lipogenic and clock genes in the liver of mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Circadian Oscillations within the Hippocampus Support Hippocampus-dependent Memory Processing

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Kristin Lynn Eckel-Mahan

2012-04-01

Full Text Available The ability to sustain memories over long periods of time, sometimes even a lifetime, is one of the most remarkable properties of the brain. Much knowledge has been gained over the past few decades regarding the molecular correlates of memory formation. Once a memory is forged, however, the molecular events that provide permanence are as of yet unclear. Studies in multiple organisms have revealed that circadian rhythmicity is important for the formation, stability, and recall of memories [1]. The neuronal events that provide this link need to be explored further. This article will discuss the findings related to the circadian regulation of memory-dependent processes in the hippocampus. Specifically, the circadian-controlled MAP kinase and cAMP signal transduction pathway plays critical roles in the consolidation of hippocampus-dependent memory. A series of studies have revealed the circadian oscillation of this pathway within the hippocampus, an activity that is absent in memory-deficient, transgenic mice lacking Ca2+-stimulated adenylyl cyclases. Interference with these oscillations proceeding the cellular memory consolidation period impairs the persistence of hippocampus-dependent memory. These data suggest that the persistence of long-term memories may depend upon reactivation of this signal transduction pathway in the hippocampus during the circadian cycle. New data reveals the dependence of hippocampal oscillation in MAPK activity on the SCN, again underscoring the importance of this region in maintaining the circadian physiology of memory. Finally, the downstream ramification of these oscillations in terms of gene expression and epigenetics should be considered, as emerging evidence is pointing strongly to a circadian link between epigenetics and long term synaptic plasticity.

Melatonin promotes circadian rhythm-induced proliferation through Clock/histone deacetylase 3/c-Myc interaction in mouse adipose tissue.

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Liu, Zhenjiang; Gan, Lu; Luo, Dan; Sun, Chao

2017-05-01

Melatonin is synthesized in the pineal gland and controls circadian rhythm of peripheral adipose tissue, resulting in changes in body weight. Although core regulatory components of clock rhythmicity have been defined, insight into the mechanisms of circadian rhythm-mediated proliferation in adipose tissue is still limited. Here, we showed that melatonin (20 mg/kg/d) promoted circadian and proliferation processes in white adipose tissue. The circadian amplitudes of brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1, Pcircadian locomotor output cycles kaput (Clock, Pcircadian disruption and promoted adipocyte proliferation in chronic jet-lagged mice and obese mice. Thus, our study found that melatonin promoted adipocyte proliferation by forming a Clock/HDAC3/c-Myc complex and subsequently driving the circadian amplitudes of proliferation genes. Our data reveal a novel mechanism that links circadian rhythm to cell proliferation in adipose tissue. These findings also identify a new potential means for melatonin to prevent and treat sleep deprivation-caused obesity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Photoperiodism and enzyme activity: towards a model for the control of circadian metabolic rhythms in the crassulacean Acid metabolism.

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Queiroz, O; Morel, C

1974-04-01

Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system.

Regulation of circadian clock transcriptional output by CLOCK:BMAL1

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Trott, Alexandra J.

2018-01-01

The mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of 15% of the transcriptome and control the daily regulation of biological functions. The recent characterization of CLOCK:BMAL1 cistrome revealed that although CLOCK:BMAL1 binds synchronously to all of its target genes, its transcriptional output is highly heterogeneous. By performing a meta-analysis of several independent genome-wide datasets, we found that the binding of other transcription factors at CLOCK:BMAL1 enhancers likely contribute to the heterogeneity of CLOCK:BMAL1 transcriptional output. While CLOCK:BMAL1 rhythmic DNA binding promotes rhythmic nucleosome removal, it is not sufficient to generate transcriptionally active enhancers as assessed by H3K27ac signal, RNA Polymerase II recruitment, and eRNA expression. Instead, the transcriptional activity of CLOCK:BMAL1 enhancers appears to rely on the activity of ubiquitously expressed transcription factors, and not tissue-specific transcription factors, recruited at nearby binding sites. The contribution of other transcription factors is exemplified by how fasting, which effects several transcription factors but not CLOCK:BMAL1, either decreases or increases the amplitude of many rhythmically expressed CLOCK:BMAL1 target genes. Together, our analysis suggests that CLOCK:BMAL1 promotes a transcriptionally permissive chromatin landscape that primes its target genes for transcription activation rather than directly activating transcription, and provides a new framework to explain how environmental or pathological conditions can reprogram the rhythmic expression of clock-controlled genes. PMID:29300726

The circadian clock modulates anti-cancer properties of curcumin

International Nuclear Information System (INIS)

Sarma, Ashapurna; Sharma, Vishal P.; Sarkar, Arindam B.; Sekar, M. Chandra; Samuel, Karunakar; Geusz, Michael E.

2016-01-01

Curcuminoids of the spice turmeric and their enhanced derivatives have much potential as cancer treatments. They act on a wide variety of biological pathways, including those regulating cell division and circadian rhythms. It is known that circadian clocks can modify cancer therapy effectiveness, according to studies aimed at optimizing treatments based on the circadian cycle. It is therefore important to determine whether treatments with curcumin or similar chemotherapeutic agents are regulated by circadian timing. Similarly, it is important to characterize any effects of curcumin on timing abilities of the circadian clocks within cancer cells. We examined the circadian clock’s impact on the timing of cell death and cell division in curcumin-treated C6 rat glioma cells through continuous video microscopy for several days. To evaluate its persistence and distribution in cancer cells, curcumin was localized within cell compartments by imaging its autofluorescence. Finally, HPLC and spectroscopy were used to determine the relative stabilities of the curcumin congeners demethoxycurcumin and bisdemethoxycurcumin that are present in turmeric. Circadian rhythms in cell death were observed in response to low (5 μM) curcumin, reaching a peak several hours before the peak in rhythmic expression of mPER2 protein, a major circadian clock component. These results revealed a sensitive phase of the circadian cycle that could be effectively targeted in patient therapies based on curcumin or its analogs. Curcumin fluorescence was observed in cell compartments at least 24 h after treatment, and the two congeners displayed greater stability than curcumin in cell culture medium. We propose a mechanism whereby curcuminoids act in a sustained manner, over several days, despite their tendency to degrade rapidly in blood and other aqueous media. During cancer therapy, curcumin or its analogs should be delivered to tumor cells at the optimal phase for highest efficacy after identifying

Familial Longevity Is Associated With Higher TSH Secretion and Strong TSH-fT3 Relationship

DEFF Research Database (Denmark)

Jansen, Steffy W; Roelfsema, Ferdinand; van der Spoel, Evie

2015-01-01

and in their partners, ultradian and circadian rhythmicity of TSH, temporal relationship, and feedback and forward interplay between TSH and TH. METHODS: We collected blood samples every 10 minutes for 24 hours for TSH and TH profiles. We used a deconvolution analysis to estimate basal (nonpulsatile), pulsatile......, and other secretion parameters to characterize ultradian rhythmicity and locally weighted polynomial regression of TSH to assess circadian rhythmicity. A cross-correlation analysis was used to investigate the temporal relationship between TSH and TH and cross-approximate entropy to assess feedback...... TSH secretion and a strong temporal relationship between TSH and free T3 but not with differences in ultradian or circadian TSH rhythmicity or feedback and forward interplay between TSH and TH....

Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease.

Science.gov (United States)

Videnovic, Aleksandar; Noble, Charleston; Reid, Kathryn J; Peng, Jie; Turek, Fred W; Marconi, Angelica; Rademaker, Alfred W; Simuni, Tanya; Zadikoff, Cindy; Zee, Phyllis C

2014-04-01

Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD. To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics. A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University. Twenty-four hour monitoring of serum melatonin secretion. Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm. Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm. Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further

Circadian clocks of both plants and pollinators influence flower seeking behavior of the pollinator hawkmoth Manduca sexta.

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Fenske, Myles P; Nguyen, LeAnn P; Horn, Erin K; Riffell, Jeffrey A; Imaizumi, Takato

2018-02-12

Most plant-pollinator interactions occur during specific periods during the day. To facilitate these interactions, many flowers are known to display their attractive qualities, such as scent emission and petal opening, in a daily rhythmic fashion. However, less is known about how the internal timing mechanisms (the circadian clocks) of plants and animals influence their daily interactions. We examine the role of the circadian clock in modulating the interaction between Petunia and one of its pollinators, the hawkmoth Manduca sexta. We find that desynchronization of the Petunia circadian clock affects moth visitation preference for Petunia flowers. Similarly, moths with circadian time aligned to plants show stronger flower-foraging activities than moths that lack this alignment. Moth locomotor activity is circadian clock-regulated, although it is also strongly repressed by light. Moths show a time-dependent burst increase in flight activity during subjective night. In addition, moth antennal responsiveness to the floral scent compounds exhibits a 24-hour rhythm in both continuous light and dark conditions. This study highlights the importance of the circadian clocks in both plants and animals as a crucial factor in initiating specialized plant-pollinator relationships.

CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis.

Science.gov (United States)

Kim, Hyunbae; Zheng, Ze; Walker, Paul D; Kapatos, Gregory; Zhang, Kezhong

2017-07-15

Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. Copyright © 2017 American Society for Microbiology.

Circadian Rhythm Control: Neurophysiological Investigations

Science.gov (United States)

Glotzbach, S. F.

1985-01-01

The suprachiasmatic nucleus (SCN) was implicated as a primary component in central nervous system mechanisms governing circadian rhythms. Disruption of the normal synchronization of temperature, activity, and other rhythms is detrimental to health. Sleep wake disorders, decreases in vigilance and performance, and certain affective disorders may result from or be exacerbated by such desynchronization. To study the basic neurophysiological mechanisms involved in entrainment of circadian systems by the environment, Parylene-coated, etched microwire electrode bundles were used to record extracellular action potentials from the small somata of the SCN and neighboring hypothalamic nuclei in unanesthetized, behaving animals. Male Wistar rats were anesthetized and chronically prepared with EEG ane EMG electrodes in addition to a moveable microdrive assembly. The majority of cells had firing rates 10 Hz and distinct populations of cells which had either the highest firing rate or lowest firing rate during sleep were seen.

Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine.

Science.gov (United States)

Pagel, René; Bär, Florian; Schröder, Torsten; Sünderhauf, Annika; Künstner, Axel; Ibrahim, Saleh M; Autenrieth, Stella E; Kalies, Kathrin; König, Peter; Tsang, Anthony H; Bettenworth, Dominik; Divanovic, Senad; Lehnert, Hendrik; Fellermann, Klaus; Oster, Henrik; Derer, Stefanie; Sina, Christian

2017-11-01

Endogenous circadian clocks regulate 24-h rhythms of physiology and behavior. Circadian rhythm disruption (CRD) is suggested as a risk factor for inflammatory bowel disease. However, the underlying molecular mechanisms remain unknown. Intestinal biopsies from Per1/2 mutant and wild-type (WT) mice were investigated by electron microscopy, immunohistochemistry, and bromodeoxyuridine pulse-chase experiments. TNF-α was injected intraperitoneally, with or without necrostatin-1, into Per1/2 mice or rhythmic and externally desynchronized WT mice to study intestinal epithelial cell death. Experimental chronic colitis was induced by oral administration of dextran sodium sulfate. In vitro , caspase activity was assayed in Per1/2-specific small interfering RNA-transfected cells. Wee1 was overexpressed to study antiapoptosis and the cell cycle. Genetic ablation of circadian clock function or environmental CRD in mice increased susceptibility to severe intestinal inflammation and epithelial dysregulation, accompanied by excessive necroptotic cell death and a reduced number of secretory epithelial cells. Receptor-interacting serine/threonine-protein kinase (RIP)-3-mediated intestinal necroptosis was linked to increased mitotic cell cycle arrest via Per1/2-controlled Wee1, resulting in increased antiapoptosis via cellular inhibitor of apoptosis-2. Together, our data suggest that circadian rhythm stability is pivotal for the maintenance of mucosal barrier function. CRD increases intestinal necroptosis, thus rendering the gut epithelium more susceptible to inflammatory processes.-Pagel, R., Bär, F., Schröder, T., Sünderhauf, A., Künstner, A., Ibrahim, S. M., Autenrieth, S. E., Kalies, K., König, P., Tsang, A. H., Bettenworth, D., Divanovic, S., Lehnert, H., Fellermann, K., Oster, H., Derer, S., Sina, C. Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine. © FASEB.

Interspecific studies of circadian genes period and timeless in Drosophila.

Science.gov (United States)

Noreen, Shumaila; Pegoraro, Mirko; Nouroz, Faisal; Tauber, Eran; Kyriacou, Charalambos P

2018-03-30

The level of rescue of clock function in genetically arrhythmic Drosophila melanogaster hosts using interspecific clock gene transformation was used to study the putative intermolecular coevolution between interacting clock proteins. Among them PER and TIM are the two important negative regulators of the circadian clock feedback loop. We transformed either the D. pseudoobscura per or tim transgenes into the corresponding arrhythmic D. melanogaster mutant (per01 or tim01) and observed >50% rhythmicity but the period of activity rhythm was either longer (D. pseudoobscura-per) or shorter than 24 h (D. pseudoobscura-tim) compared to controls. By introducing both transgenes simultaneously into double mutants, we observed that the period of the activity rhythm was rescued by the pair of hemizygous transgenes (~24 h). These flies also showed a more optimal level of temperature compensation for the period. Under LD 12:12 these flies have a D. pseudoobscura like activity profile with the absence of morning anticipation as well as a very prominent earlier evening peak of activity rhythm. These observation are consistent with the view that TIM and PER form a heterospecific coevolved module at least for the circadian period of activity rhythms. However the strength of rhythmicity was reduced by having both transgenes present, so while evidence for a coevolution between PER and TIM is observed for some characters it is not for others. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Diurnal rhythmicity of the clock genes Per1 and Per2 in the rat ovary.

Science.gov (United States)

Fahrenkrug, Jan; Georg, Birgitte; Hannibal, Jens; Hindersson, Peter; Gräs, Søren

2006-08-01

Circadian rhythms are generated by endogenous clocks in the central brain oscillator, the suprachiasmatic nucleus, and peripheral tissues. The molecular basis for the circadian clock consists of a number of genes and proteins that form transcriptional/translational feedback loops. In the mammalian gonads, clock genes have been reported in the testes, but the expression pattern is developmental rather than circadian. Here we investigated the daily expression of the two core clock genes, Per1 and Per2, in the rat ovary using real-time RT-PCR, in situ hybridization histochemistry, and immunohistochemistry. Both Per1 and Per2 mRNA displayed a statistically significant rhythmic oscillation in the ovary with a period of 24 h in: 1) a group of rats during proestrus and estrus under 12-h light,12-h dark cycles; 2) a second group of rats representing a mixture of all 4 d of the estrous cycle under 12-h light,12-h dark conditions; and 3) a third group of rats representing a mixture of all 4 d of estrous cycle during continuous darkness. Per1 mRNA was low at Zeitgeber time 0-2 and peaked at Zeitgeber time 12-14, whereas Per2 mRNA was delayed by approximately 4 h relative to Per1. By in situ hybridization histochemistry, Per mRNAs were localized to steroidogenic cells in preantral, antral, and preovulatory follicles; corpora lutea; and interstitial glandular tissue. With newly developed antisera, we substantiated the expression of Per1 and Per2 in these cells by single/double immunohistochemistry. Furthermore, we visualized the temporal intracellular movements of PER1 and PER2 proteins. These findings suggest the existence of an ovarian circadian clock, which may play a role both locally and in the hypothalamo-pituitary-ovarian axis.

Circadian Gating of Epithelial-to-Mesenchymal Transition in Breast Cancer Cells Via Melatonin-Regulation of GSK3β

Science.gov (United States)

Mao, Lulu; Dauchy, Robert T.; Blask, David E.; Slakey, Lauren M.; Xiang, Shulin; Yuan, Lin; Dauchy, Erin M.; Shan, Bin; Brainard, George C.; Hanifin, John P.; Duplessis, Tamika T.; Hill, Steven M.

2012-01-01

Disturbed sleep-wake cycle and circadian rhythmicity are associated with cancer, but the underlying mechanisms are unknown. Employing a tissue-isolated human breast xenograft tumor nude rat model, we observed that glycogen synthase kinase 3β (GSK3β), an enzyme critical in metabolism and cell proliferation/survival, exhibits a circadian rhythm of phosphorylation in human breast tumors. Exposure to light-at-night suppresses the nocturnal pineal melatonin synthesis, disrupting the circadian rhythm of GSK3β phosphorylation. Melatonin activates GSK3β by inhibiting the serine-threonine kinase Akt phosphorylation, inducing β-catenin degradation and inhibiting epithelial-to-mesenchymal transition, a fundamental process underlying cancer metastasis. Thus, chronic circadian disruption by light-at-night via occupational exposure or age-related sleep disturbances may contribute to cancer incidence and the metastatic spread of breast cancer by inhibiting GSK3β activity and driving epithelial-to-mesenchymal transition in breast cancer patients. PMID:23002080

Rest-activity circadian rhythms and bone mineral density in elderly men

Directory of Open Access Journals (Sweden)

Tara S. Rogers

2017-12-01

Conclusions: The data demonstrate modest associations between overall circadian rhythmicity of rest and activity (measured by pseudo F-statistic, as well as daytime to nighttime activity ratio (measured by alpha statistic, aBMD and ΔaBMD, but adjustment for covariates related to lifestyle, BMI and comorbidities attenuated most of these associations. These results suggest that RAR patterns are not independently associated with aBMD or four-year ΔaBMD at the total hip or femoral neck in older men, but additional research is needed.

Interactions of Circadian Rhythmicity, Stress and Orexigenic Neuropeptide Systems: Implications for Food Intake Control

OpenAIRE

Blasiak, Anna; Gundlach, Andrew L.; Hess, Grzegorz; Lewandowski, Marian H.

2017-01-01

Many physiological processes fluctuate throughout the day/night and daily fluctuations are observed in brain and peripheral levels of several hormones, neuropeptides and transmitters. In turn, mediators under the “control” of the “master biological clock” reciprocally influence its function. Dysregulation in the rhythmicity of hormone release as well as hormone receptor sensitivity and availability in different tissues, is a common risk-factor for multiple clinical conditions, including psych...

Integration of light and temperature in the regulation of circadian gene expression in Drosophila.

Directory of Open Access Journals (Sweden)

Catharine E Boothroyd

2007-04-01

Full Text Available Circadian clocks are aligned to the environment via synchronizing signals, or Zeitgebers, such as daily light and temperature cycles, food availability, and social behavior. In this study, we found that genome-wide expression profiles from temperature-entrained flies show a dramatic difference in the presence or absence of a thermocycle. Whereas transcript levels appear to be modified broadly by changes in temperature, there is a specific set of temperature-entrained circadian mRNA profiles that continue to oscillate in constant conditions. There are marked differences in the biological functions represented by temperature-driven or circadian regulation. The set of temperature-entrained circadian transcripts overlaps significantly with a previously defined set of transcripts oscillating in response to a photocycle. In follow-up studies, all thermocycle-entrained circadian transcript rhythms also responded to light/dark entrainment, whereas some photocycle-entrained rhythms did not respond to temperature entrainment. Transcripts encoding the clock components Period, Timeless, Clock, Vrille, PAR-domain protein 1, and Cryptochrome were all confirmed to be rhythmic after entrainment to a daily thermocycle, although the presence of a thermocycle resulted in an unexpected phase difference between period and timeless expression rhythms at the transcript but not the protein level. Generally, transcripts that exhibit circadian rhythms both in response to thermocycles and photocycles maintained the same mutual phase relationships after entrainment by temperature or light. Comparison of the collective temperature- and light-entrained circadian phases of these transcripts indicates that natural environmental light and temperature cycles cooperatively entrain the circadian clock. This interpretation is further supported by comparative analysis of the circadian phases observed for temperature-entrained and light-entrained circadian locomotor behavior. Taken

Circadian rhythm of temperature selection in a nocturnal lizard.

Science.gov (United States)

Refinetti, R; Susalka, S J

1997-08-01

We recorded body temperature and locomotor activity of Tokay geckos (Gekko gecko) with free access to a heat source under a 14:10 light-dark cycle and in constant darkness. Under the light-dark cycle, the lizards selected higher temperatures during the light phase, when locomotor activity was less intense. Rhythmicity in temperature selection was transiently disrupted but later resumed when the animals were placed in constant darkness. These results demonstrate the existence of a circadian rhythm of temperature selection in nocturnal ectotherms and extend previous findings of a temporal mismatch between the rhythms of locomotor activity and temperature selection in nocturnal rodents.

Evidence for widespread dysregulation of circadian clock progression in human cancer

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Jarrod Shilts

2018-01-01

Full Text Available The ubiquitous daily rhythms in mammalian physiology are guided by progression of the circadian clock. In mice, systemic disruption of the clock can promote tumor growth. In vitro, multiple oncogenes can disrupt the clock. However, due to the difficulties of studying circadian rhythms in solid tissues in humans, whether the clock is disrupted within human tumors has remained unknown. We sought to determine the state of the circadian clock in human cancer using publicly available transcriptome data. We developed a method, called the clock correlation distance (CCD, to infer circadian clock progression in a group of samples based on the co-expression of 12 clock genes. Our method can be applied to modestly sized datasets in which samples are not labeled with time of day and coverage of the circadian cycle is incomplete. We used the method to define a signature of clock gene co-expression in healthy mouse organs, then validated the signature in healthy human tissues. By then comparing human tumor and non-tumor samples from twenty datasets of a range of cancer types, we discovered that clock gene co-expression in tumors is consistently perturbed. Subsequent analysis of data from clock gene knockouts in mice suggested that perturbed clock gene co-expression in human cancer is not caused solely by the inactivation of clock genes. Furthermore, focusing on lung cancer, we found that human lung tumors showed systematic changes in expression in a large set of genes previously inferred to be rhythmic in healthy lung. Our findings suggest that clock progression is dysregulated in many solid human cancers and that this dysregulation could have broad effects on circadian physiology within tumors. In addition, our approach opens the door to using publicly available data to infer circadian clock progression in a multitude of human phenotypes.

Comparative Circadian Metabolomics Reveal Differential Effects of Nutritional Challenge in the Serum and Liver.

Science.gov (United States)

Abbondante, Serena; Eckel-Mahan, Kristin L; Ceglia, Nicholas J; Baldi, Pierre; Sassone-Corsi, Paolo

2016-02-05

Diagnosis and therapeutic interventions in pathological conditions rely upon clinical monitoring of key metabolites in the serum. Recent studies show that a wide range of metabolic pathways are controlled by circadian rhythms whose oscillation is affected by nutritional challenges, underscoring the importance of assessing a temporal window for clinical testing and thereby questioning the accuracy of the reading of critical pathological markers in circulation. We have been interested in studying the communication between peripheral tissues under metabolic homeostasis perturbation. Here we present a comparative circadian metabolomic analysis on serum and liver in mice under high fat diet. Our data reveal that the nutritional challenge induces a loss of serum metabolite rhythmicity compared with liver, indicating a circadian misalignment between the tissues analyzed. Importantly, our results show that the levels of serum metabolites do not reflect the circadian liver metabolic signature or the effect of nutritional challenge. This notion reveals the possibility that misleading reads of metabolites in circulation may result in misdiagnosis and improper treatments. Our findings also demonstrate a tissue-specific and time-dependent disruption of metabolic homeostasis in response to altered nutrition. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Entrainment to feeding but not to light: circadian phenotype of VPAC2 receptor-null mice.

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Sheward, W John; Maywood, Elizabeth S; French, Karen L; Horn, Jacqueline M; Hastings, Michael H; Seckl, Jonathan R; Holmes, Megan C; Harmar, Anthony J

2007-04-18

The master clock driving mammalian circadian rhythms is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and entrained by daily light/dark cycles. SCN lesions abolish circadian rhythms of behavior and result in a loss of synchronized circadian rhythms of clock gene expression in peripheral organs (e.g., the liver) and of hormone secretion (e.g., corticosterone). We examined rhythms of behavior, hepatic clock gene expression, and corticosterone secretion in VPAC2 receptor-null (Vipr2-/-) mice, which lack a functional SCN clock. Unexpectedly, although Vipr2-/- mice lacked robust circadian rhythms of wheel-running activity and corticosterone secretion, hepatic clock gene expression was strongly rhythmic, but advanced in phase compared with that in wild-type mice. The timing of food availability is thought to be an important entrainment signal for circadian clocks outside the SCN. Vipr2-/- mice consumed food significantly earlier in the 24 h cycle than wild-type mice, consistent with the observed timing of peripheral rhythms of circadian gene expression. When restricted to feeding only during the daytime (RF), mice develop rhythms of activity and of corticosterone secretion in anticipation of feeding time, thought to be driven by a food-entrainable circadian oscillator, located outside the SCN. Under RF, mice of both genotypes developed food-anticipatory rhythms of activity and corticosterone secretion, and hepatic gene expression rhythms also became synchronized to the RF stimulus. Thus, food intake is an effective zeitgeber capable of coordinating circadian rhythms of behavior, peripheral clock gene expression, and hormone secretion, even in the absence of a functional SCN clock.

The expression of the clock gene cycle has rhythmic pattern and is affected by photoperiod in the moth Sesamia nonagrioides.

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Kontogiannatos, Dimitrios; Gkouvitsas, Theodoros; Kourti, Anna

2017-06-01

To obtain clues to the link between the molecular mechanism of circadian and photoperiod clocks, we have cloned the circadian clock gene cycle (Sncyc) in the corn stalk borer, Sesamia nonagrioides, which undergoes facultative diapause controlled by photoperiod. Sequence analysis revealed a high degree of conservation among insects for this gene. SnCYC consists of 667 amino acids and structural analysis showed that it contains a BCTR domain in its C-terminal in addition to the common domains found in Drosophila CYC, i.e. bHLH, PAS-A, PAS-B domains. The results revealed that the sequence of Sncyc showed a similarity to that of its mammalian orthologue, Bmal1. We also investigated the expression patterns of Sncyc in the brain of larvae growing under long-day 16L: 8D (LD), constant darkness (DD) and short-day 10L: 14D (SD) conditions using qRT-PCR assays. The mRNAs of Sncyc expression was rhythmic in LD, DD and SD cycles. Also, it is remarkable that the photoperiodic conditions affect the expression patterns and/or amplitudes of circadian clock gene Sncyc. This gene is associated with diapause in S. nonagrioides, because under SD (diapause conditions) the photoperiodic signal altered mRNA accumulation. Sequence and expression analysis of cyc in S. nonagrioides shows interesting differences compared to Drosophila where this gene does not oscillate or change in expression patterns in response to photoperiod, suggesting that this species is an interesting new model to study the molecular control of insect circadian and photoperiodic clocks. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Chronic Social Defeat Stress on Sleep and Circadian Rhythms Are Mitigated by Kappa-Opioid Receptor Antagonism.

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Wells, Audrey M; Ridener, Elysia; Bourbonais, Clinton A; Kim, Woori; Pantazopoulos, Harry; Carroll, F Ivy; Kim, Kwang-Soo; Cohen, Bruce M; Carlezon, William A

2017-08-09

Stress plays a critical role in the neurobiology of mood and anxiety disorders. Sleep and circadian rhythms are affected in many of these conditions. Here we examined the effects of chronic social defeat stress (CSDS), an ethological form of stress, on sleep and circadian rhythms. We exposed male mice implanted with wireless telemetry transmitters to a 10 day CSDS regimen known to produce anhedonia (a depressive-like effect) and social avoidance (an anxiety-like effect). EEG, EMG, body temperature, and locomotor activity data were collected continuously during the CSDS regimen and a 5 day recovery period. CSDS affected numerous endpoints, including paradoxical sleep (PS) and slow-wave sleep (SWS), as well as the circadian rhythmicity of body temperature and locomotor activity. The magnitude of the effects increased with repeated stress, and some changes (PS bouts, SWS time, body temperature, locomotor activity) persisted after the CSDS regimen had ended. CSDS also altered mRNA levels of the circadian rhythm-related gene mPer2 within brain areas that regulate motivation and emotion. Administration of the κ-opioid receptor (KOR) antagonist JDTic (30 mg/kg, i.p.) before CSDS reduced stress effects on both sleep and circadian rhythms, or hastened their recovery, and attenuated changes in mPer2 Our findings show that CSDS produces persistent disruptions in sleep and circadian rhythmicity, mimicking attributes of stress-related conditions as they appear in humans. The ability of KOR antagonists to mitigate these disruptions is consistent with previously reported antistress effects. Studying homologous endpoints across species may facilitate the development of improved treatments for psychiatric illness. SIGNIFICANCE STATEMENT Stress plays a critical role in the neurobiology of mood and anxiety disorders. We show that chronic social defeat stress in mice produces progressive alterations in sleep and circadian rhythms that resemble features of depression as it appears in

dyschronic, a Drosophila homolog of a deaf-blindness gene, regulates circadian output and Slowpoke channels.

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James E C Jepson

Full Text Available Many aspects of behavior and physiology are under circadian control. In Drosophila, the molecular clock that regulates rhythmic patterns of behavior has been extensively characterized. In contrast, genetic loci involved in linking the clock to alterations in motor activity have remained elusive. In a forward-genetic screen, we uncovered a new component of the circadian output pathway, which we have termed dyschronic (dysc. dysc mutants exhibit arrhythmic locomotor behavior, yet their eclosion rhythms are normal and clock protein cycling remains intact. Intriguingly, dysc is the closest Drosophila homolog of whirlin, a gene linked to type II Usher syndrome, the leading cause of deaf-blindness in humans. Whirlin and other Usher proteins are expressed in the mammalian central nervous system, yet their function in the CNS has not been investigated. We show that DYSC is expressed in major neuronal tracts and regulates expression of the calcium-activated potassium channel SLOWPOKE (SLO, an ion channel also required in the circadian output pathway. SLO and DYSC are co-localized in the brain and control each other's expression post-transcriptionally. Co-immunoprecipitation experiments demonstrate they form a complex, suggesting they regulate each other through protein-protein interaction. Furthermore, electrophysiological recordings of neurons in the adult brain show that SLO-dependent currents are greatly reduced in dysc mutants. Our work identifies a Drosophila homolog of a deaf-blindness gene as a new component of the circadian output pathway and an important regulator of ion channel expression, and suggests novel roles for Usher proteins in the mammalian nervous system.

Effects of task complexity on rhythmic reproduction performance in adults.

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Iannarilli, Flora; Vannozzi, Giuseppe; Iosa, Marco; Pesce, Caterina; Capranica, Laura

2013-02-01

The aim of the present study was to investigate the effect of task complexity on the capability to reproduce rhythmic patterns. Sedentary musically illiterate individuals (age: 34.8±4.2 yrs; M±SD) were administered a rhythmic test including three rhythmic patterns to be reproduced by means of finger-tapping, foot-tapping and walking. For the quantification of subjects' ability in the reproduction of rhythmic patterns, qualitative and quantitative parameters were submitted to analysis. A stereophotogrammetric system was used to reconstruct and evaluate individual performances. The findings indicated a good internal stability of the rhythmic reproduction, suggesting that the present experimental design is suitable to discriminate the participants' rhythmic ability. Qualitative aspects of rhythmic reproduction (i.e., speed of execution and temporal ratios between events) varied as a function of the perceptual-motor requirements of the rhythmic reproduction task, with larger reproduction deviations in the walking task. Copyright © 2013 Elsevier B.V. All rights reserved.

The Circadian System Contributes to Apnea Lengthening across the Night in Obstructive Sleep Apnea.

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Butler, Matthew P; Smales, Carolina; Wu, Huijuan; Hussain, Mohammad V; Mohamed, Yusef A; Morimoto, Miki; Shea, Steven A

2015-11-01

To test the hypothesis that respiratory event duration exhibits an endogenous circadian rhythm. Within-subject and between-subjects. Inpatient intensive physiologic monitoring unit at the Brigham and Women's Hospital. Seven subjects with moderate/severe sleep apnea and four controls, age 48 (SD = 12) years, 7 males. Subjects completed a 5-day inpatient protocol in dim light. Polysomnography was recorded during an initial control 8-h night scheduled at the usual sleep time, then through 10 recurrent cycles of 2 h 40 min sleep and 2 h 40 min wake evenly distributed across all circadian phases, and finally during another 8-h control sleep period. Event durations, desaturations, and apnea-hypopnea index for each sleep opportunity were assessed according to circadian phase (derived from salivary melatonin), time into sleep, and sleep stage. Average respiratory event durations in NREM sleep significantly lengthened across both control nights (21.9 to 28.2 sec and 23.7 to 30.2 sec, respectively). During the circadian protocol, event duration in NREM increased across the circadian phases that corresponded to the usual sleep period, accounting for > 50% of the increase across normal 8-h control nights. AHI and desaturations were also rhythmic: AHI was highest in the biological day while desaturations were greatest in the biological night. The endogenous circadian system plays an important role in the prolongation of respiratory events across the night, and might provide a novel therapeutic target for modulating sleep apnea. © 2015 Associated Professional Sleep Societies, LLC.

The Circadian Clock of the Ant Camponotus floridanus Is Localized in Dorsal and Lateral Neurons of the Brain.

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Kay, Janina; Menegazzi, Pamela; Mildner, Stephanie; Roces, Flavio; Helfrich-Förster, Charlotte

2018-06-01

The circadian clock of social insects has become a focal point of interest for research, as social insects show complex forms of timed behavior and organization within their colonies. These behaviors include brood care, nest maintenance, foraging, swarming, defense, and many other tasks, of which several require social synchronization and accurate timing. Ants of the genus Camponotus have been shown to display a variety of daily timed behaviors such as the emergence of males from the nest, foraging, and relocation of brood. Nevertheless, circadian rhythms of isolated individuals have been studied in few ant species, and the circadian clock network in the brain that governs such behaviors remains completely uncharacterized. Here we show that isolated minor workers of Camponotus floridanus exhibit temperature overcompensated free-running locomotor activity rhythms under constant darkness. Under light-dark cycles, most animals are active during day and night, with a slight preference for the night. On the neurobiological level, we show that distinct cell groups in the lateral and dorsal brain of minor workers of C. floridanus are immunostained with an antibody against the clock protein Period (PER) and a lateral group additionally with an antibody against the neuropeptide pigment-dispersing factor (PDF). PER abundance oscillates in a daily manner, and PDF-positive neurites invade most parts of the brain, suggesting that the PER/PDF-positive neurons are bona fide clock neurons that transfer rhythmic signals into the relevant brain areas controlling rhythmic behavior.

Melanopsin resets circadian rhythms in cells by inducing clock gene Period1

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Yamashita, Shuhei; Uehara, Tomoe; Matsuo, Minako; Kikuchi, Yo; Numano, Rika

2014-02-01

The biochemical, physiological and behavioral processes are under the control of internal clocks with the period of approximately 24 hr, circadian rhythms. The expression of clock gene Period1 (Per1) oscillates autonomously in cells and is induced immediately after a light pulse. Per1 is an indispensable member of the central clock system to maintain the autonomous oscillator and synchronize environmental light cycle. Per1 expression could be detected by Per1∷luc and Per1∷GFP plasmid DNA in which firefly luciferase and Green Fluorescence Protein were rhythmically expressed under the control of the mouse Per1 promoter in order to monitor mammalian circadian rhythms. Membrane protein, MELANOPSIN is activated by blue light in the morning on the retina and lead to signals transduction to induce Per1 expression and to reset the phase of circadian rhythms. In this report Per1 induction was measured by reporter signal assay in Per1∷luc and Per1∷GFP fibroblast cell at the input process of circadian rhythms. To the result all process to reset the rhythms by Melanopsin is completed in single cell like in the retina projected to the central clock in the brain. Moreover, the phase of circadian rhythm in Per1∷luc cells is synchronized by photo-activated Melanopsin, because the definite peak of luciferase activity in one dish was found one day after light illumination. That is an available means that physiological circadian rhythms could be real-time monitor as calculable reporter (bioluminescent and fluorescent) chronological signal in both single and groups of cells.

Aging has the opposite effect on cAMP and cGMP circadian variations in rat Leydig cells.

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Baburski, Aleksandar Z; Sokanovic, Srdjan J; Andric, Silvana A; Kostic, Tatjana S

2017-05-01

The Leydig cell physiology displays a circadian rhythm driven by a complex interaction of the reproductive axis hormones and circadian system. The final output of this regulatory process is circadian pattern of steroidogenic genes expression and testosterone production. Aging gradually decreases robustness of rhythmic testosterone secretion without change in pattern of LH secretion. Here, we analyzed effect of aging on circadian variation of cAMP and cGMP signaling in Leydig cells. Results showed opposite effect of aging on cAMP and cGMP daily variation. Reduced amplitude of cAMP circadian oscillation was probably associated with changed expression of genes involved in cAMP production (increased circadian pattern of Adcy7, Adcy9, Adcy10 and decreased Adcy3); cAMP degradation (increased Pde4a, decreased Pde8b, canceled rhythm of Pde4d, completely reversed circadian pattern of Pde7b and Pde8a); and circadian expression of protein kinase A subunits (Prkac/PRKAC and Prkar2a). Aging stimulates expression of genes responsible for cGMP production (Nos2, Gucy1a3 and Gucy1b3/GUCYB3) and degradation (Pde5a, Pde6a and Pde6h) but the overall net effect is elevation of cGMP circadian oscillations in Leydig cells. In addition, the expression of cGMP-dependent kinase, Prkg1/PRKG1 is up-regulated. It seems that aging potentiate cGMP- and reduce cAMP-signaling in Leydig cells. Since both signaling pathways affect testosterone production and clockwork in the cells, further insights into these signaling pathways will help to unravel disorders linked to the circadian timing system, aging and reproduction.

Vitamin A is a necessary factor for sympathetic-independent rhythmic activation of mitogen-activated protein kinase in the rat pineal gland.

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Guillaumond, F; Giraudet, F; Becquet, D; Sage, D; Laforge-Anglade, G; Bosler, O; François-Bellan, A M

2005-02-01

The circadian clock in the suprachiasmatic nucleus (SCN) controls day-to-day physiology and behavior by sending timing messages to multiple peripheral oscillators. In the pineal gland, a major SCN target, circadian events are believed to be driven exclusively by the rhythmic release of norepinephrine from superior cervical ganglia (SCG) neurons relaying clock messages through a polysynaptic pathway. Here we show in rat an SCN-driven daily rhythm of pineal MAPK activation that is not dependent on the SCG and whose maintenance requires vitamin A as a blood-borne factor. This finding challenges the dogma that SCG-released norepinephrine is an exclusive mediator of SCN-pineal communication and allows the assumption that humoral mechanisms are involved in pineal integration of temporal messages.

Rhythmic Engagement with Music in Early Childhood: A Replication and Extension

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Ilari, Beatriz

2015-01-01

The purpose of this study was to replicate and extend previous findings on spontaneous movement and rhythmic engagement with music in infancy. Using the identical stimuli and procedures from the original study, I investigated spontaneous rhythmic movements in response to music, infant-directed speech, and contrasting rhythmic patterns in 30…

Circadian rhythmicity in AVP secretion and GABAergic synaptic transmission in the rat suprachiasmatic nucleus

Czech Academy of Sciences Publication Activity Database

Kretschmannová, Karla; Svobodová, Irena; Balík, Aleš; Mazna, Petr; Zemková, Hana

2005-01-01

Roč. 1048, - (2005), s. 103-115 ISSN 0077-8923 R&D Projects: GA ČR(CZ) GA309/02/1519; GA AV ČR(CZ) IAA5011103; GA AV ČR(CZ) IAA5011408 Institutional research plan: CEZ:AV0Z5011922 Keywords : circadian rhythms * suprachiasmatic nucleus * melatonin Subject RIV: FH - Neuro logy Impact factor: 1.971, year: 2005

Epigenetic and Posttranslational Modifications in Light Signal Transduction and the Circadian Clock in Neurospora crassa

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Marco Proietto

2015-07-01

Full Text Available Blue light, a key abiotic signal, regulates a wide variety of physiological processes in many organisms. One of these phenomena is the circadian rhythm presents in organisms sensitive to the phase-setting effects of blue light and under control of the daily alternation of light and dark. Circadian clocks consist of autoregulatory alternating negative and positive feedback loops intimately connected with the cellular metabolism and biochemical processes. Neurospora crassa provides an excellent model for studying the molecular mechanisms involved in these phenomena. The White Collar Complex (WCC, a blue-light receptor and transcription factor of the circadian oscillator, and Frequency (FRQ, the circadian clock pacemaker, are at the core of the Neurospora circadian system. The eukaryotic circadian clock relies on transcriptional/translational feedback loops: some proteins rhythmically repress their own synthesis by inhibiting the activity of their transcriptional factors, generating self-sustained oscillations over a period of about 24 h. One of the basic mechanisms that perpetuate self-sustained oscillations is post translation modification (PTM. The acronym PTM generically indicates the addition of acetyl, methyl, sumoyl, or phosphoric groups to various types of proteins. The protein can be regulatory or enzymatic or a component of the chromatin. PTMs influence protein stability, interaction, localization, activity, and chromatin packaging. Chromatin modification and PTMs have been implicated in regulating circadian clock function in Neurospora. Research into the epigenetic control of transcription factors such as WCC has yielded new insights into the temporal modulation of light-dependent gene transcription. Here we report on epigenetic and protein PTMs in the regulation of the Neurospora crassa circadian clock. We also present a model that illustrates the molecular mechanisms at the basis of the blue light control of the circadian clock.

Circadian Clocks and the Interaction between Stress Axis and Adipose Function

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Isa Kolbe

2015-01-01

Full Text Available Many physiological processes and most endocrine functions show fluctuations over the course of the day. These so-called circadian rhythms are governed by an endogenous network of cellular clocks and serve as an adaptation to daily and, thus, predictable changes in the organism’s environment. Circadian clocks have been described in several tissues of the stress axis and in adipose cells where they regulate the rhythmic and stimulated release of stress hormones, such as glucocorticoids, and various adipokine factors. Recent work suggests that both adipose and stress axis clock systems reciprocally influence each other and adrenal-adipose rhythms may be key players in the development and therapy of metabolic disorders. In this review, we summarize our current understanding of adrenal and adipose tissue rhythms and clocks and how they might interact to regulate energy homoeostasis and stress responses under physiological conditions. Potential chronotherapeutic strategies for the treatment of metabolic and stress disorders are discussed.

Direct Repression of Evening Genes by CIRCADIAN CLOCK-ASSOCIATED1 in the Arabidopsis Circadian Clock.

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Kamioka, Mari; Takao, Saori; Suzuki, Takamasa; Taki, Kyomi; Higashiyama, Tetsuya; Kinoshita, Toshinori; Nakamichi, Norihito

2016-03-01

The circadian clock is a biological timekeeping system that provides organisms with the ability to adapt to day-night cycles. Timing of the expression of four members of the Arabidopsis thaliana PSEUDO-RESPONSE REGULATOR(PRR) family is crucial for proper clock function, and transcriptional control of PRRs remains incompletely defined. Here, we demonstrate that direct regulation of PRR5 by CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) determines the repression state of PRR5 in the morning. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) analyses indicated that CCA1 associates with three separate regions upstream of PRR5 CCA1 and its homolog LATE ELONGATED HYPOCOTYL (LHY) suppressed PRR5 promoter activity in a transient assay. The regions bound by CCA1 in the PRR5 promoter gave rhythmic patterns with troughs in the morning, when CCA1 and LHY are at high levels. Furthermore,ChIP-seq revealed that CCA1 associates with at least 449 loci with 863 adjacent genes. Importantly, this gene set contains genes that are repressed but upregulated incca1 lhy double mutants in the morning. This study shows that direct binding by CCA1 in the morning provides strong repression of PRR5, and repression by CCA1 also temporally regulates an evening-expressed gene set that includes PRR5. © 2016 American Society of Plant Biologists. All rights reserved.

Circadian locomotor rhythms in the cricket, Gryllodes sigillatus. II. Interactions between bilaterally paired circadian pacemakers.

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Ushirogawa, H; Abe, Y; Tomioka, K

1997-10-01

The optic lobe is essential for circadian locomotor rhythms in the cricket, Gryllodes sigillatus. We examined potential interactions between the bilaterally paired optic lobes in circadian rhythm generation. When one optic lobe was removed, the free-running period of the locomotor rhythm slightly but significantly lengthened. When exposed to light-dark cycles (LD) with 26 hr period, intact and sham operated animals were clearly entrained to the light cycle, but a large number of animals receiving unilateral optic nerve severance showed rhythm dissociation. In the dissociation, two rhythmic components appeared; one was readily entrained to the given LD and the other free-ran with a period shorter than 24 hr, and activity was expressed only when they were inphase. The period of the free-running component was significantly longer than that of the animals with a single blinded pacemaker kept in LD13:13, suggesting that the pacemaker on the intact side had some influence on the blinded pacemaker even in the dissociated state. The ratio of animals with rhythm dissociation was greater with the lower light intensity of the LD. The results suggest that the bilaterally distributed pacemakers are only weakly coupled to one another but strongly suppress the activity driven by the partner pacemaker during their subjective day. The strong suppression of activity would be advantageous to keep a stable nocturnality for this cricket living indoors.

Effect of photic stimuli disturbing overt circadian rhythms on the dorsomedial and ventrolateral SCN rhythmicity

Czech Academy of Sciences Publication Activity Database

Sumová, Alena; Illnerová, Helena

2005-01-01

Roč. 1048, č. 1-2 (2005), s. 161-169 ISSN 0006-8993 R&D Projects: GA AV ČR(CZ) IAA5011304 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian clock * suprachiasmatic nucleus * photic entrainment Subject RIV: ED - Physiology Impact factor: 2.296, year: 2005

Circadian Rhythm Regulates Development of Enamel in Mouse Mandibular First Molar

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Tao, Jiang; Zhai, Yue; Park, Hyun; Han, Junli; Dong, Jianhui; Xie, Ming; Gu, Ting; Lewi, Keidren; Ji, Fang; Jia, William

2016-01-01

Rhythmic incremental growth lines and the presence of melatonin receptors were discovered in tooth enamel, suggesting possible role of circadian rhythm. We therefore hypothesized that circadian rhythm may regulate enamel formation through melatonin receptors. To test this hypothesis, we examined expression of melatonin receptors (MTs) and amelogenin (AMELX), a maker of enamel formation, during tooth germ development in mouse. Using qRT-PCR and immunocytochemistry, we found that mRNA and protein levels of both MTs and AMELX in normal mandibular first molar tooth germs increased gradually after birth, peaked at 3 or 4 day postnatal, and then decreased. Expression of MTs and AMELX by immunocytochemistry was significantly delayed in neonatal mice raised in all-dark or all-light environment as well as the enamel development. Furthermore, development of tooth enamel was also delayed showing significant immature histology in those animals, especially for newborn mice raised in all daylight condition. Interestingly, disruption in circadian rhythm in pregnant mice also resulted in delayed enamel development in their babies. Treatment with melatonin receptor antagonist 4P-PDOT in pregnant mice caused underexpression of MTs and AMELX associated with long-lasting deficiency in baby enamel tissue. Electromicroscopic evidence demonstrated increased necrosis and poor enamel mineralization in ameloblasts. The above results suggest that circadian rhythm is important for normal enamel development at both pre- and postnatal stages. Melatonin receptors were partly responsible for the regulation. PMID:27494172

The endogenous circadian clock programs animals to eat at certain times of the 24-hour day: What if we ignore the clock?

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Jiang, Peng; Turek, Fred W

2018-04-16

The discovery of the molecular mechanisms underlying the circadian clock, which functions in virtually every cell throughout the body to coordinate biological processes to anticipate and better adapt to daily rhythmic changes in the environment, is one of the major biomedical breakthroughs in the 20th century. Twenty years after this breakthrough, the biomedical community is now at a new frontier to incorporate the circadian clock mechanisms into many areas of biomedical research, as studies continue to reveal an important role of the circadian clock in a wide range of biological functions and diseases. A forefront of this exciting area is the research of interactions between the clock and energy metabolism. In this review, we summarize animal and human studies linking disruptions of the circadian clock, either environmental or genetic, to metabolic dysfunctions associated with obesity, diabetes, and other metabolic disorders. We also discuss how these advances in circadian biology may pave the way to revolutionize clinical practice in the era of precision medicine. Copyright © 2018 Elsevier Inc. All rights reserved.

Circadian Clock Genes Are Essential for Normal Adult Neurogenesis, Differentiation, and Fate Determination.

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Astha Malik

Full Text Available Adult neurogenesis creates new neurons and glia from stem cells in the human brain throughout life. It is best understood in the dentate gyrus (DG of the hippocampus and the subventricular zone (SVZ. Circadian rhythms have been identified in the hippocampus, but the role of any endogenous circadian oscillator cells in hippocampal neurogenesis and their importance in learning or memory remains unclear. Any study of stem cell regulation by intrinsic circadian timing within the DG is complicated by modulation from circadian clocks elsewhere in the brain. To examine circadian oscillators in greater isolation, neurosphere cultures were prepared from the DG of two knockout mouse lines that lack a functional circadian clock and from mPer1::luc mice to identify circadian oscillations in gene expression. Circadian mPer1 gene activity rhythms were recorded in neurospheres maintained in a culture medium that induces neurogenesis but not in one that maintains the stem cell state. Although the differentiating neural stem progenitor cells of spheres were rhythmic, evidence of any mature neurons was extremely sparse. The circadian timing signal originated in undifferentiated cells within the neurosphere. This conclusion was supported by immunocytochemistry for mPER1 protein that was localized to the inner, more stem cell-like neurosphere core. To test for effects of the circadian clock on neurogenesis, media conditions were altered to induce neurospheres from BMAL1 knockout mice to differentiate. These cultures displayed unusually high differentiation into glia rather than neurons according to GFAP and NeuN expression, respectively, and very few BetaIII tubulin-positive, immature neurons were observed. The knockout neurospheres also displayed areas visibly devoid of cells and had overall higher cell death. Neurospheres from arrhythmic mice lacking two other core clock genes, Cry1 and Cry2, showed significantly reduced growth and increased astrocyte

The Aging Clock and Circadian Control of Metabolism and Genome Stability

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Victoria P. Belancio

2015-01-01

Full Text Available It is widely accepted that aging is characterized by a gradual decline in the efficiency and accuracy of biological processes, leading to deterioration of physiological functions and development of age-associated diseases. Age-dependent accumulation of genomic instability and development of metabolic syndrome are well-recognized components of the aging phenotype, both of which have been extensively studied. Existing findings strongly support the view that the integrity of the cellular genome and metabolic function can be influenced by light at night (LAN and associated suppression of circadian melatonin production. While LAN is reported to accelerate aging by promoting age-associated carcinogenesis in several animal models, the specific molecular mechanism(s of its action are not fully understood. Here, we review literature supporting a connection between LAN-induced central circadian disruption of peripheral circadian rhythms and clock function, LINE-1 retrotransposon-associated genomic instability, metabolic deregulation, and aging. We propose that aging is a progressive decline in the stability, continuity and synchronization of multi-frequency oscillations in biological processes to a temporally disorganized state. By extension, healthy aging is the ability to maintain the most consistent, stable and entrainable rhythmicity and coordination of these oscillations, at the molecular, cellular, and systemic levels.

Silencing Nicotiana attenuata LHY and ZTL alters circadian rhythms in flowers.

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Yon, Felipe; Joo, Youngsung; Cortés Llorca, Lucas; Rothe, Eva; Baldwin, Ian T; Kim, Sang-Gyu

2016-02-01

The rhythmic opening/closing and volatile emissions of flowers are known to attract pollinators at specific times. That these rhythms are maintained under constant light or dark conditions suggests a circadian clock involvement. Although a forward and reverse genetic approach has led to the identification of core circadian clock components in Arabidopsis thaliana, the involvement of these clock components in floral rhythms has remained untested, probably because of the weak diurnal rhythms in A. thaliana flowers. Here, we addressed the role of these core clock components in the flowers of the wild tobacco Nicotiana attenuata, whose flowers open at night, emit benzyl acetone (BA) scents and move vertically through a 140° arc. We first measured N. attenuata floral rhythms under constant light conditions. The results suggest that the circadian clock controls flower opening, BA emission and pedicel movement, but not flower closing. We generated transgenic N. attenuata lines silenced in the homologous genes of Arabidopsis LATE ELONGATED HYPOCOTYL (LHY) and ZEITLUPE (ZTL), which are known to be core clock components. Silencing NaLHY and NaZTL strongly altered floral rhythms in different ways, indicating that conserved clock components in N. attenuata coordinate these floral rhythms. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Circadian cycles of gene expression in the coral, Acropora millepora.

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Aisling K Brady

Full Text Available Circadian rhythms regulate many physiological, behavioral and reproductive processes. These rhythms are often controlled by light, and daily cycles of solar illumination entrain many clock regulated processes. In scleractinian corals a number of different processes and behaviors are associated with specific periods of solar illumination or non-illumination--for example, skeletal deposition, feeding and both brooding and broadcast spawning.We have undertaken an analysis of diurnal expression of the whole transcriptome and more focused studies on a number of candidate circadian genes in the coral Acropora millepora using deep RNA sequencing and quantitative PCR. Many examples of diurnal cycles of RNA abundance were identified, some of which are light responsive and damped quickly under constant darkness, for example, cryptochrome 1 and timeless, but others that continue to cycle in a robust manner when kept in constant darkness, for example, clock, cryptochrome 2, cycle and eyes absent, indicating that their transcription is regulated by an endogenous clock entrained to the light-dark cycle. Many other biological processes that varied between day and night were also identified by a clustering analysis of gene ontology annotations.Corals exhibit diurnal patterns of gene expression that may participate in the regulation of circadian biological processes. Rhythmic cycles of gene expression occur under constant darkness in both populations of coral larvae that lack zooxanthellae and in individual adult tissue containing zooxanthellae, indicating that transcription is under the control of a biological clock. In addition to genes potentially involved in regulating circadian processes, many other pathways were found to display diel cycles of transcription.

Stochastic models of cellular circadian rhythms in plants help to understand the impact of noise on robustness and clock structure

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Maria Luisa eGuerriero

2014-10-01

Full Text Available Rhythmic behavior is essential for plants; for example, daily (circadian rhythms control photosynthesis and seasonal rhythms regulate their life cycle. The core of the circadian clock is a genetic network that coordinates the expression of specific clock genes in a circadian rhythm reflecting the 24-hour day/night cycle.Circadian clocks exhibit stochastic noise due to the low copy numbers of clock genes and the consequent cell-to-cell variation: this intrinsic noise plays a major role in circadian clocks by inducing more robust oscillatory behavior. Another source of noise is the environment, which causes variation in temperature and light intensity: this extrinsic noise is part of the requirement for the structural complexity of clock networks.Advances in experimental techniques now permit single-cell measurements and the development of single-cell models. Here we present some modeling studies showing the importance of considering both types of noise in understanding how plants adapt to regular and irregular light variations. Stochastic models have proven useful for understanding the effect of regular variations. By contrast, the impact of irregular variations and the interaction of different noise sources are less studied.

Theory of Inpatient Circadian Care (TICC): A Proposal for a Middle-Range Theory

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Camargo-Sanchez, Andrés; Niño, Carmen L; Sánchez, Leonardo; Echeverri, Sonia; Gutiérrez, Diana P; Duque, Andrés F; Pianeta, Oscar; Jaramillo-Gómez, Jenny A; Pilonieta, Martin A; Cataño, Nhora; Arboleda, Humberto; Agostino, Patricia V; Alvarez-Baron, Claudia P; Vargas, Rafael

2015-01-01

The circadian system controls the daily rhythms of a variety of physiological processes. Most organisms show physiological, metabolic and behavioral rhythms that are coupled to environmental signals. In humans, the main synchronizer is the light/dark cycle, although non-photic cues such as food availability, noise, and work schedules are also involved. In a continuously operating hospital, the lack of rhythmicity in these elements can alter the patient’s biological rhythms and resilience. This paper presents a Theory of Inpatient Circadian Care (TICC) grounded in circadian principles. We conducted a literature search on biological rhythms, chronobiology, nursing care, and middle-range theories in the databases PubMed, SciELO Public Health, and Google Scholar. The search was performed considering a period of 6 decades from 1950 to 2013. Information was analyzed to look for links between chronobiology concepts and characteristics of inpatient care. TICC aims to integrate multidisciplinary knowledge of biomedical sciences and apply it to clinical practice in a formal way. The conceptual points of this theory are supported by abundant literature related to disease and altered biological rhythms. Our theory will be able to enrich current and future professional practice. PMID:25767632

Fish Oil Ameliorates High-Fat Diet Induced Male Mouse Reproductive Dysfunction via Modifying the Rhythmic Expression of Testosterone Synthesis Related Genes

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Hualin Wang

2018-04-01

Full Text Available The present study aims to investigate the protective effects of ω-3 polyunsaturated fatty acids (ω-3PUFAs against high-fat diet induced male mouse reproductive dysfunction and to explore circadian regulation mechanisms. Male C57BL/6 mice were randomly divided into three groups and fed a normal chow diet (control group, CON, a high-fat diet (HFD group or a HFD supplemented with fish oil (FO group for 12 weeks. After 12 weeks of feeding, the body weight and the ratio of perinephric and epididymal fat weight to body weight were significantly higher in the HFD group compared with the CON group. The supplement of fish oil rich in ω-3PUFAs only slightly reduced the HFD-induced obesity but remarkably ameliorated HFD-induced dyslipidemia, sexual hormones disorder, testicle lesions and germ cell apoptosis. Fish oil supplementation restored the expression of steroid synthesis associated genes in HFD fed mouse and flattened the HFD-induced oscillations in circadian genes’ expression. Fish oil supplementation prevented HFD-induced male mouse reproductive dysfunction and modified the rhythmic expression of testosterone synthesis related genes.

An allele of the crm gene blocks cyanobacterial circadian rhythms.

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Boyd, Joseph S; Bordowitz, Juliana R; Bree, Anna C; Golden, Susan S

2013-08-20

The SasA-RpaA two-component system constitutes a key output pathway of the cyanobacterial Kai circadian oscillator. To date, rhythm of phycobilisome associated (rpaA) is the only gene other than kaiA, kaiB, and kaiC, which encode the oscillator itself, whose mutation causes completely arrhythmic gene expression. Here we report a unique transposon insertion allele in a small ORF located immediately upstream of rpaA in Synechococcus elongatus PCC 7942 termed crm (for circadian rhythmicity modulator), which results in arrhythmic promoter activity but does not affect steady-state levels of RpaA. The crm ORF complements the defect when expressed in trans, but only if it can be translated, suggesting that crm encodes a small protein. The crm1 insertion allele phenotypes are distinct from those of an rpaA null; crm1 mutants are able to grow in a light:dark cycle and have no detectable oscillations of KaiC phosphorylation, whereas low-amplitude KaiC phosphorylation rhythms persist in the absence of RpaA. Levels of phosphorylated RpaA in vivo measured over time are significantly altered compared with WT in the crm1 mutant as well as in the absence of KaiC. Taken together, these results are consistent with the hypothesis that the Crm polypeptide modulates a circadian-specific activity of RpaA.

Food and the circadian activity of the hypothalamic-pituitary-adrenal axis

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A.M.O. Leal

1997-12-01

Full Text Available Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or" zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states

Rapid Adjustment of Circadian Clocks to Simulated Travel to Time Zones across the Globe.

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Harrison, Elizabeth M; Gorman, Michael R

2015-12-01

Daily rhythms in mammalian physiology and behavior are generated by a central pacemaker located in the hypothalamic suprachiasmatic nuclei (SCN), the timing of which is set by light from the environment. When the ambient light-dark cycle is shifted, as occurs with travel across time zones, the SCN and its output rhythms must reset or re-entrain their phases to match the new schedule-a sluggish process requiring about 1 day per hour shift. Using a global assay of circadian resetting to 6 equidistant time-zone meridians, we document this characteristically slow and distance-dependent resetting of Syrian hamsters under typical laboratory lighting conditions, which mimic summer day lengths. The circadian pacemaker, however, is additionally entrainable with respect to its waveform (i.e., the shape of the 24-h oscillation) allowing for tracking of seasonally varying day lengths. We here demonstrate an unprecedented, light exposure-based acceleration in phase resetting following 2 manipulations of circadian waveform. Adaptation of circadian waveforms to long winter nights (8 h light, 16 h dark) doubled the shift response in the first 3 days after the shift. Moreover, a bifurcated waveform induced by exposure to a novel 24-h light-dark-light-dark cycle permitted nearly instant resetting to phase shifts from 4 to 12 h in magnitude, representing a 71% reduction in the mismatch between the activity rhythm and the new photocycle. Thus, a marked enhancement of phase shifting can be induced via nonpharmacological, noninvasive manipulation of the circadian pacemaker waveform in a model species for mammalian circadian rhythmicity. Given the evidence of conserved flexibility in the human pacemaker waveform, these findings raise the promise of flexible resetting applicable to circadian disruption in shift workers, frequent time-zone travelers, and any individual forced to adjust to challenging schedules. © 2015 The Author(s).

Perturbed rhythmic activation of signaling pathways in mice deficient for Sterol Carrier Protein 2-dependent diurnal lipid transport and metabolism.

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Jouffe, Céline; Gobet, Cédric; Martin, Eva; Métairon, Sylviane; Morin-Rivron, Delphine; Masoodi, Mojgan; Gachon, Frédéric

2016-04-21

Through evolution, most of the living species have acquired a time keeping system to anticipate daily changes caused by the rotation of the Earth. In all of the systems this pacemaker is based on a molecular transcriptional/translational negative feedback loop able to generate rhythmic gene expression with a period close to 24 hours. Recent evidences suggest that post-transcriptional regulations activated mostly by systemic cues play a fundamental role in the process, fine tuning the time keeping system and linking it to animal physiology. Among these signals, we consider the role of lipid transport and metabolism regulated by SCP2. Mice harboring a deletion of the Scp2 locus present a modulated diurnal accumulation of lipids in the liver and a perturbed activation of several signaling pathways including PPARα, SREBP, LRH-1, TORC1 and its upstream regulators. This defect in signaling pathways activation feedbacks upon the clock by lengthening the circadian period of animals through post-translational regulation of core clock regulators, showing that rhythmic lipid transport is a major player in the establishment of rhythmic mRNA and protein expression landscape.

Social memory in the rat: circadian variation and effect of circadian rhythm disruption

NARCIS (Netherlands)

Reijmers, L.G.J.E.; Leus, I.E.; Burbach, J.P.H.; Spruijt, B.M.; Ree, van J.M.

2001-01-01

Disruption of circadian rhythm can impair long-term passive avoidance memory of rats and mice. The present study investigated whether disruption of circadian rhythm can also impair social memory of male rats. Social memory was assessed using the social discrimination test, in which a short-term

Rhythmic entrainment source separation: Optimizing analyses of neural responses to rhythmic sensory stimulation

OpenAIRE

Cohen, M.S.; Gulbinaite, R.

2017-01-01

Steady-state evoked potentials (SSEPs) are rhythmic brain responses to rhythmic sensory stimulation, and are often used to study perceptual and attentional processes. We present a data analysis method for maximizing the signal-to-noise ratio of the narrow-band steady-state response in the frequency and time-frequency domains. The method, termed rhythmic entrainment source separation (RESS), is based on denoising source separation approaches that take advantage of the simultaneous but differen...

Cryptochrome mediates light-dependent magnetosensitivity of Drosophila's circadian clock.

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Taishi Yoshii

2009-04-01

Full Text Available Since 1960, magnetic fields have been discussed as Zeitgebers for circadian clocks, but the mechanism by which clocks perceive and process magnetic information has remained unknown. Recently, the radical-pair model involving light-activated photoreceptors as magnetic field sensors has gained considerable support, and the blue-light photoreceptor cryptochrome (CRY has been proposed as a suitable molecule to mediate such magnetosensitivity. Since CRY is expressed in the circadian clock neurons and acts as a critical photoreceptor of Drosophila's clock, we aimed to test the role of CRY in magnetosensitivity of the circadian clock. In response to light, CRY causes slowing of the clock, ultimately leading to arrhythmic behavior. We expected that in the presence of applied magnetic fields, the impact of CRY on clock rhythmicity should be altered. Furthermore, according to the radical-pair hypothesis this response should be dependent on wavelength and on the field strength applied. We tested the effect of applied static magnetic fields on the circadian clock and found that flies exposed to these fields indeed showed enhanced slowing of clock rhythms. This effect was maximal at 300 muT, and reduced at both higher and lower field strengths. Clock response to magnetic fields was present in blue light, but absent under red-light illumination, which does not activate CRY. Furthermore, cry(b and cry(OUT mutants did not show any response, and flies overexpressing CRY in the clock neurons exhibited an enhanced response to the field. We conclude that Drosophila's circadian clock is sensitive to magnetic fields and that this sensitivity depends on light activation of CRY and on the applied field strength, consistent with the radical pair mechanism. CRY is widespread throughout biological systems and has been suggested as receptor for magnetic compass orientation in migratory birds. The present data establish the circadian clock of Drosophila as a model system

TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in behavior and plasticity of L2 interneurons in the brain of Drosophila melanogaster.

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Kijak, Ewelina; Pyza, Elżbieta

2017-01-01

Drosophila melanogaster is a common model used to study circadian rhythms in behavior and circadian clocks. However, numerous circadian rhythms have also been detected in non-clock neurons, especially in the first optic neuropil (lamina) of the fly's visual system. Such rhythms have been observed in the number of synapses and in the structure of interneurons, which exhibit changes in size and shape in a circadian manner. Although the patterns of these changes are known, the mechanism remains unclear. In the present study, we investigated the role of the TOR signaling pathway and autophagy in regulating circadian rhythms based on the behavior and structural plasticity of the lamina L2 monopolar cell dendritic trees. In addition, we examined the cyclic expression of the TOR signaling pathway (Tor, Pi3K class 1, Akt1) and autophagy (Atg5 and Atg7) genes in the fly's brain. We observed that Tor, Atg5 and Atg7 exhibit rhythmic expressions in the brain of wild-type flies in day/night conditions (LD 12:12) that are abolished in per01 clock mutants. The silencing of Tor in per expressing cells shortens a period of the locomotor activity rhythm of flies. In addition, silencing of the Tor and Atg5 genes in L2 cells disrupts the circadian plasticity of the L2 cell dendritic trees measured in the distal lamina. In turn, silencing of the Atg7 gene in L2 cells changes the pattern of this rhythm. Our results indicate that the TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in the behavior and plasticity of neurons in the brain of adult flies.

Circadian Rhythms and Clock Genes in Reproduction: Insights From Behavior and the Female Rabbit’s Brain

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Mario Caba

2018-03-01

Full Text Available Clock gene oscillations are necessary for a successful pregnancy and parturition, but little is known about their function during lactation, a period demanding from the mother multiple physiological and behavioral adaptations to fulfill the requirements of the offspring. First, we will focus on circadian rhythms and clock genes in reproductive tissues mainly in rodents. Disruption of circadian rhythms or proper rhythmic oscillations of clock genes provoke reproductive problems, as found in clock gene knockout mice. Then, we will focus mainly on the rabbit doe as this mammal nurses the young just once a day with circadian periodicity. This daily event synchronizes the behavior and the activity of specific brain regions critical for reproductive neuroendocrinology and maternal behavior, like the preoptic area. This region shows strong rhythms of the PER1 protein (product of the Per1 clock gene associated with circadian nursing. Additionally, neuroendocrine cells related to milk production and ejections are also synchronized to daily nursing. A threshold of suckling is necessary to entrain once a day nursing; this process is independent of milk output as even virgin does (behaving maternally following anosmia can display circadian nursing behavior. A timing motivational mechanism may regulate such behavior as mesolimbic dopaminergic cells are entrained by daily nursing. Finally, we will explore about the clinical importance of circadian rhythms. Indeed, women in chronic shift-work schedules show problems in their menstrual cycles and pregnancies and also have a high risk of preterm delivery, making this an important field of translational research.

An autonomous circadian clock in the inner mouse retina regulated by dopamine and GABA.

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Guo-Xiang Ruan

2008-10-01

Full Text Available The influence of the mammalian retinal circadian clock on retinal physiology and function is widely recognized, yet the cellular elements and neural regulation of retinal circadian pacemaking remain unclear due to the challenge of long-term culture of adult mammalian retina and the lack of an ideal experimental measure of the retinal circadian clock. In the current study, we developed a protocol for long-term culture of intact mouse retinas, which allows retinal circadian rhythms to be monitored in real time as luminescence rhythms from a PERIOD2::LUCIFERASE (PER2::LUC clock gene reporter. With this in vitro assay, we studied the characteristics and location within the retina of circadian PER2::LUC rhythms, the influence of major retinal neurotransmitters, and the resetting of the retinal circadian clock by light. Retinal PER2::LUC rhythms were routinely measured from whole-mount retinal explants for 10 d and for up to 30 d. Imaging of vertical retinal slices demonstrated that the rhythmic luminescence signals were concentrated in the inner nuclear layer. Interruption of cell communication via the major neurotransmitter systems of photoreceptors and ganglion cells (melatonin and glutamate and the inner nuclear layer (dopamine, acetylcholine, GABA, glycine, and glutamate did not disrupt generation of retinal circadian PER2::LUC rhythms, nor did interruption of intercellular communication through sodium-dependent action potentials or connexin 36 (cx36-containing gap junctions, indicating that PER2::LUC rhythms generation in the inner nuclear layer is likely cell autonomous. However, dopamine, acting through D1 receptors, and GABA, acting through membrane hyperpolarization and casein kinase, set the phase and amplitude of retinal PER2::LUC rhythms, respectively. Light pulses reset the phase of the in vitro retinal oscillator and dopamine D1 receptor antagonists attenuated these phase shifts. Thus, dopamine and GABA act at the molecular level of PER

Circadian clocks, epigenetics, and cancer

KAUST Repository

Masri, Selma; Kinouchi, Kenichiro; Sassone-Corsi, Paolo

2015-01-01

The interplay between circadian rhythm and cancer has been suggested for more than a decade based on the observations that shift work and cancer incidence are linked. Accumulating evidence implicates the circadian clock in cancer survival and proliferation pathways. At the molecular level, multiple control mechanisms have been proposed to link circadian transcription and cell-cycle control to tumorigenesis.The circadian gating of the cell cycle and subsequent control of cell proliferation is an area of active investigation. Moreover, the circadian clock is a transcriptional system that is intricately regulated at the epigenetic level. Interestingly, the epigenetic landscape at the level of histone modifications, DNA methylation, and small regulatory RNAs are differentially controlled in cancer cells. This concept raises the possibility that epigenetic control is a common thread linking the clock with cancer, though little scientific evidence is known to date.This review focuses on the link between circadian clock and cancer, and speculates on the possible connections at the epigenetic level that could further link the circadian clock to tumor initiation or progression.

Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells

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Adolf M. Sandbichler

2018-04-01

Full Text Available Background/Aims: Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. Methods: For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts. Circadian oscillations of core clock gene mRNA´s were assessed using realtime qPCR with subsequent cosine wave fit analysis. Results: Here we show that under normoxia primary metabolic activity of cells predominately occurs during day time and that after acute hypoxia of two hours, administrated immediately before each sampling point, steady state concentrations of glycolytic key metabolites such as glucose and lactate reveal to be highly rhythmic, following a circadian pattern with highest levels during the night periods and reflecting the circadian variation of the cellular response to hypoxia. Remarkably, rhythms in glycolysis are transferred to cellular energy states under normoxic conditions, so that ADP/ATP ratios oscillate as well, which is the first evidence for cycling ADP/ATP pools in a metazoan cell line to our knowledge. Furthermore, the hypoxia induced alterations in rhythms of glycolysis lead to the alignment of three major cellular redox systems, namely the circadian oscillations of NAD+/NADH and NADP+/NADPH ratios and of increased nocturnal levels

Circadian dysregulation in Parkinson's disease

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Aleksandar Videnovic

2017-01-01

Full Text Available Parkinson's disease (PD is the second most common neurodegenerative disorder that affects over one million individuals in the US alone. PD is characterized by a plethora of motor and non-motor manifestations, resulting from a progressive degeneration of dopaminergic neurons and disbalance of several other neurotransmitters. A growing body of evidence points to significant alterations of the circadian system in PD. This is not surprising given the pivotal role that dopamine plays in circadian regulation as well as the role of circadian influences in dopamine metabolism. In this review we present basic and clinical investigations that examined the function of the circadian system in PD.

Discrete gene replication events drive coupling between the cell cycle and circadian clocks.

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Paijmans, Joris; Bosman, Mark; Ten Wolde, Pieter Rein; Lubensky, David K

2016-04-12

Many organisms possess both a cell cycle to control DNA replication and a circadian clock to anticipate changes between day and night. In some cases, these two rhythmic systems are known to be coupled by specific, cross-regulatory interactions. Here, we use mathematical modeling to show that, additionally, the cell cycle generically influences circadian clocks in a nonspecific fashion: The regular, discrete jumps in gene-copy number arising from DNA replication during the cell cycle cause a periodic driving of the circadian clock, which can dramatically alter its behavior and impair its function. A clock built on negative transcriptional feedback either phase-locks to the cell cycle, so that the clock period tracks the cell division time, or exhibits erratic behavior. We argue that the cyanobacterium Synechococcus elongatus has evolved two features that protect its clock from such disturbances, both of which are needed to fully insulate it from the cell cycle and give it its observed robustness: a phosphorylation-based protein modification oscillator, together with its accompanying push-pull read-out circuit that responds primarily to the ratios of different phosphoform concentrations, makes the clock less susceptible to perturbations in protein synthesis; the presence of multiple, asynchronously replicating copies of the same chromosome diminishes the effect of replicating any single copy of a gene.

Circadian mechanisms of 24-hour blood pressure regulation and patterning.

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Smolensky, Michael H; Hermida, Ramón C; Portaluppi, Francesco

2017-06-01

In most persons, blood pressure (BP) rises slowly during late sleep, increases rapidly upon morning awakening and commencement of diurnal activity, exhibits two - morning and afternoon/early evening - daytime peaks, shows a minor midday nadir, and undergoes a decline during nighttime sleep by 10-20% in systolic BP and somewhat lesser amount in diastolic BP relative to wake-time means. Nyctohemeral cycles of ambient temperature, light, noise and behaviorally driven temporal patterns in food, liquid, salt, and stimulant consumption, mental/emotional stress, posture, and physical activity intensity plus circadian rhythms of wake/sleep, pineal gland melatonin synthesis, autonomic and central nervous, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, renin-angiotensin-aldosterone, renal hemodynamic, endothelial, vasoactive peptide, and opioid systems constitute the key regulators and determinants of the BP 24 h profile. Environmental and behavioral cycles are believed to be far more influential than circadian ones. However, the facts that the: i) BP 24 h pattern of secondary hypertension, e.g., diabetes and renal disease, is characterized by absence of BP fall during sleep, and ii) scheduling of conventional long-acting medications at bedtime, rather than morning, results in much better hypertension control and vascular risk reduction, presumably because highest drug concentration coincides closely with the peak of most key circadian determinants of the BP 24 h profile, indicate endogenous rhythmic influences are of greater importance than previously appreciated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rhythmic expression of circadian clock genes in the preovulatory ovarian follicles of the laying hen.

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Zhichao Zhang

Full Text Available The circadian clock is reported to play a role in the ovaries in a variety of vertebrate species, including the domestic hen. However, the ovary is an organ that changes daily, and the laying hen maintains a strict follicular hierarchy. The aim of this study was to examine the spatial-temporal expression of several known canonical clock genes in the granulosa and theca layers of six hierarchy follicles. We demonstrated that the granulosa cells (GCs of the F1-F3 follicles harbored intrinsic oscillatory mechanisms in vivo. In addition, cultured granulosa cells (GCs from F1 follicles exposed to luteinizing hormone (LH synchronization displayed Per2 mRNA oscillations, whereas, the less mature GCs (F5 plus F6 displayed no circadian change in Per2 mRNA levels. Cultures containing follicle-stimulating hormone (FSH combined with LH expressed levels of Per2 mRNA that were 2.5-fold higher than those in cultures with LH or FSH alone. These results show that there is spatial specificity in the localization of clock cells in hen preovulatory follicles. In addition, our results support the hypothesis that gonadotropins provide a cue for the development of the functional cellular clock in immature GCs.

REV-ERBalpha participates in circadian SREBP signaling and bile acid homeostasis.

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Gwendal Le Martelot

2009-09-01

Full Text Available In mammals, many aspects of behavior and physiology, and in particular cellular metabolism, are coordinated by the circadian timing system. Molecular clocks are thought to rely on negative feedback loops in clock gene expression that engender oscillations in the accumulation of transcriptional regulatory proteins, such as the orphan receptor REV-ERBalpha. Circadian transcription factors then drive daily rhythms in the expression of clock-controlled output genes, for example genes encoding enzymes and regulators of cellular metabolism. To gain insight into clock output functions of REV-ERBalpha, we carried out genome-wide transcriptome profiling experiments with liver RNA from wild-type mice, Rev-erbalpha knock-out mice, or REV-ERBalpha overexpressing mice. On the basis of these genetic loss- and gain-of-function experiments, we concluded that REV-ERBalpha participates in the circadian modulation of sterol regulatory element-binding protein (SREBP activity, and thereby in the daily expression of SREBP target genes involved in cholesterol and lipid metabolism. This control is exerted via the cyclic transcription of Insig2, encoding a trans-membrane protein that sequesters SREBP proteins to the endoplasmic reticulum membranes and thereby interferes with the proteolytic activation of SREBPs in Golgi membranes. REV-ERBalpha also participates in the cyclic expression of cholesterol-7alpha-hydroxylase (CYP7A1, the rate-limiting enzyme in converting cholesterol to bile acids. Our findings suggest that this control acts via the stimulation of LXR nuclear receptors by cyclically produced oxysterols. In conclusion, our study suggests that rhythmic cholesterol and bile acid metabolism is not just driven by alternating feeding-fasting cycles, but also by REV-ERBalpha, a component of the circadian clockwork circuitry.

Sample preparation for phosphoproteomic analysis of circadian time series in Arabidopsis thaliana.

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Krahmer, Johanna; Hindle, Matthew M; Martin, Sarah F; Le Bihan, Thierry; Millar, Andrew J

2015-01-01

Systems biological approaches to study the Arabidopsis thaliana circadian clock have mainly focused on transcriptomics while little is known about the proteome, and even less about posttranslational modifications. Evidence has emerged that posttranslational protein modifications, in particular phosphorylation, play an important role for the clock and its output. Phosphoproteomics is the method of choice for a large-scale approach to gain more knowledge about rhythmic protein phosphorylation. Recent plant phosphoproteomics publications have identified several thousand phosphopeptides. However, the methods used in these studies are very labor-intensive and therefore not suitable to apply to a well-replicated circadian time series. To address this issue, we present and compare different strategies for sample preparation for phosphoproteomics that are compatible with large numbers of samples. Methods are compared regarding number of identifications, variability of quantitation, and functional categorization. We focus on the type of detergent used for protein extraction as well as methods for its removal. We also test a simple two-fraction separation of the protein extract. © 2015 Elsevier Inc. All rights reserved.

Rhythmic speech and stuttering reduction in a syllable-timed language.

Science.gov (United States)

Law, Thomas; Packman, Ann; Onslow, Mark; To, Carol K-S; Tong, Michael C-F; Lee, Kathy Y-S

2018-06-06

Speaking rhythmically, also known as syllable-timed speech (STS), has been known for centuries to be a fluency-inducing condition for people who stutter. Cantonese is a tonal syllable-timed language and it has been shown that, of all languages, Cantonese is the most rhythmic (Mok, 2009). However, it is not known if STS reduces stuttering in Cantonese as it does in English. This is the first study to investigate the effects of STS on stuttering in a syllable-timed language. Nineteen native Cantonese-speaking adults who stutter were engaged in conversational tasks in Cantonese under two conditions: one in their usual speaking style and one using STS. The speakers' percentage syllables stuttered (%SS) and speech rhythmicity were rated. The rhythmicity ratings were used to estimate the extent to which speakers were using STS in the syllable-timed condition. Results revealed a statistically significant reduction in %SS in the STS condition; however, this reduction was not as large as in previous studies in other languages and the amount of stuttering reduction varied across speakers. The rhythmicity ratings showed that some speakers were perceived to be speaking more rhythmically than others and that the perceived rhythmicity correlated positively with reductions in stuttering. The findings were unexpected, as it was anticipated that speakers of a highly rhythmic language such as Cantonese would find STS easy to use and that the consequent reductions in stuttering would be great, even greater perhaps than in a stress-timed language such as English. The theoretical and clinical implications of the findings are discussed.

Rhythmic walking interaction with auditory feedback

DEFF Research Database (Denmark)

Maculewicz, Justyna; Jylhä, Antti; Serafin, Stefania

2015-01-01

We present an interactive auditory display for walking with sinusoidal tones or ecological, physically-based synthetic walking sounds. The feedback is either step-based or rhythmic, with constant or adaptive tempo. In a tempo-following experiment, we investigate different interaction modes...

Different corticospinal control between discrete and rhythmic movement of the ankle.

Science.gov (United States)

Goto, Yumeno; Jono, Yasutomo; Hatanaka, Ryota; Nomura, Yoshifumi; Tani, Keisuke; Chujo, Yuta; Hiraoka, Koichi

2014-01-01

We investigated differences in corticospinal and spinal control between discrete and rhythmic ankle movements. Motor evoked potentials (MEPs) in the tibialis anterior and soleus muscles and soleus H-reflex were elicited in the middle of the plantar flexion phase during discrete ankle movement or in the initial or later cycles of rhythmic ankle movement. The H-reflex was evoked at an intensity eliciting a small M-wave and MEPs were elicited at an intensity of 1.2 times the motor threshold of the soleus MEPs. Only trials in which background EMG level, ankle angle, and ankle velocity were similar among the movement conditions were included for data analysis. In addition, only trials with a similar M-wave were included for data analysis in the experiment evoking H-reflexes. Results showed that H reflex and MEP amplitudes in the soleus muscle during discrete movement were not significantly different from those during rhythmic movement. MEP amplitude in the tibialis anterior muscle during the later cycles of rhythmic movement was significantly larger than that during the initial cycle of the rhythmic movement or during discrete movement. Higher corticospinal excitability in the tibialis anterior muscle during the later cycles of rhythmic movement may reflect changes in corticospinal control from the initial cycle to the later cycles of rhythmic movement.

MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

Energy Technology Data Exchange (ETDEWEB)

Balakrishnan, Anita, E-mail: anita.balakrishnan@doctors.org.uk [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); School of Clinical Sciences, Division of Gastroenterology, University of Liverpool, Liverpool L69 3GE (United Kingdom); Stearns, Adam T. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 2JD (United Kingdom); Park, Peter J. [Department of Medicine, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Harvard Medical School, Center for Biomedical Informatics, Boston, MA 02115 (United States); Dreyfuss, Jonathan M. [Department of Medicine, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Ashley, Stanley W. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Rhoads, David B. [Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Pediatric Endocrine Unit, MassGeneral Hospital for Children, Boston, MA 02114 (United States); Tavakkolizadeh, Ali, E-mail: atavakkoli@partners.org [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States)

2010-12-10

Background and aims: The intestine exhibits profound diurnal rhythms in function and morphology, in part due to changes in enterocyte proliferation. The regulatory mechanisms behind these rhythms remain largely unknown. We hypothesized that microRNAs are involved in mediating these rhythms, and studied the role of microRNAs specifically in modulating intestinal proliferation. Methods: Diurnal rhythmicity of microRNAs in rat jejunum was analyzed by microarrays and validated by qPCR. Temporal expression of diurnally rhythmic mir-16 was further quantified in intestinal crypts, villi, and smooth muscle using laser capture microdissection and qPCR. Morphological changes in rat jejunum were assessed by histology and proliferation by immunostaining for bromodeoxyuridine. In IEC-6 cells stably overexpressing mir-16, proliferation was assessed by cell counting and MTS assay, cell cycle progression and apoptosis by flow cytometry, and cell cycle gene expression by qPCR and immunoblotting. Results: mir-16 peaked 6 hours after light onset (HALO 6) with diurnal changes restricted to crypts. Crypt depth and villus height peaked at HALO 13-14 in antiphase to mir-16. Overexpression of mir-16 in IEC-6 cells suppressed specific G1/S regulators (cyclins D1-3, cyclin E1 and cyclin-dependent kinase 6) and produced G1 arrest. Protein expression of these genes exhibited diurnal rhythmicity in rat jejunum, peaking between HALO 11 and 17 in antiphase to mir-16. Conclusions: This is the first report of circadian rhythmicity of specific microRNAs in rat jejunum. Our data provide a link between anti-proliferative mir-16 and the intestinal proliferation rhythm and point to mir-16 as an important regulator of proliferation in jejunal crypts. This function may be essential to match proliferation and absorptive capacity with nutrient availability.

MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

International Nuclear Information System (INIS)

Balakrishnan, Anita; Stearns, Adam T.; Park, Peter J.; Dreyfuss, Jonathan M.; Ashley, Stanley W.; Rhoads, David B.; Tavakkolizadeh, Ali

2010-01-01

Background and aims: The intestine exhibits profound diurnal rhythms in function and morphology, in part due to changes in enterocyte proliferation. The regulatory mechanisms behind these rhythms remain largely unknown. We hypothesized that microRNAs are involved in mediating these rhythms, and studied the role of microRNAs specifically in modulating intestinal proliferation. Methods: Diurnal rhythmicity of microRNAs in rat jejunum was analyzed by microarrays and validated by qPCR. Temporal expression of diurnally rhythmic mir-16 was further quantified in intestinal crypts, villi, and smooth muscle using laser capture microdissection and qPCR. Morphological changes in rat jejunum were assessed by histology and proliferation by immunostaining for bromodeoxyuridine. In IEC-6 cells stably overexpressing mir-16, proliferation was assessed by cell counting and MTS assay, cell cycle progression and apoptosis by flow cytometry, and cell cycle gene expression by qPCR and immunoblotting. Results: mir-16 peaked 6 hours after light onset (HALO 6) with diurnal changes restricted to crypts. Crypt depth and villus height peaked at HALO 13-14 in antiphase to mir-16. Overexpression of mir-16 in IEC-6 cells suppressed specific G1/S regulators (cyclins D1-3, cyclin E1 and cyclin-dependent kinase 6) and produced G1 arrest. Protein expression of these genes exhibited diurnal rhythmicity in rat jejunum, peaking between HALO 11 and 17 in antiphase to mir-16. Conclusions: This is the first report of circadian rhythmicity of specific microRNAs in rat jejunum. Our data provide a link between anti-proliferative mir-16 and the intestinal proliferation rhythm and point to mir-16 as an important regulator of proliferation in jejunal crypts. This function may be essential to match proliferation and absorptive capacity with nutrient availability.

Rhythmic entrainment source separation: Optimizing analyses of neural responses to rhythmic sensory stimulation

NARCIS (Netherlands)

Cohen, M.S.; Gulbinaite, R.

2017-01-01

Steady-state evoked potentials (SSEPs) are rhythmic brain responses to rhythmic sensory stimulation, and are often used to study perceptual and attentional processes. We present a data analysis method for maximizing the signal-to-noise ratio of the narrow-band steady-state response in the frequency

Effects of Rhythmic and Melodic Alterations and Selected Musical Experiences on Rhythmic Processing.

Science.gov (United States)

Sink, Patricia E.

1984-01-01

Study showed that music listening habits and preferences and instrument training may affect ways an individual processes the multiple dimensions of rhythm. Apparent alterations in tempo, duration and pitch characteristics, rhythmic and melodic phrase patterning, and monotony may serve as organizers of rhythmic processing. (Author/RM)

Daily rhythms of blood pressure, heart rate, and body temperature in fed and fasted male dogs.

Science.gov (United States)

Piccione, G; Caola, G; Refinetti, R

2005-10-01

Daily or circadian rhythmicity in physiological processes has been described in a large number of species of birds and mammals. However, in dogs, most studies have either failed to detect rhythmicity or have found that rhythmicity reflects merely an acute exogenous effect of feeding rather than an autonomous rhythmic process. In the present study, we investigated the rhythmicity of body temperature, blood pressure, and heart rate in dogs fed daily as well as in dogs deprived of food for 60 h. Our results document clear rhythmicity in all three parameters and demonstrate that the rhythmicity is independent of the feeding schedule. The failure of various previous investigations to document daily rhythmicity in dogs is probably due to lack of experimental rigour rather than to weakness of daily rhythmicity in dogs.

Neural correlates of rhythmic expectancy

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Theodore P. Zanto

2006-01-01

Full Text Available Temporal expectancy is thought to play a fundamental role in the perception of rhythm. This review summarizes recent studies that investigated rhythmic expectancy by recording neuroelectric activity with high temporal resolution during the presentation of rhythmic patterns. Prior event-related brain potential (ERP studies have uncovered auditory evoked responses that reflect detection of onsets, offsets, sustains,and abrupt changes in acoustic properties such as frequency, intensity, and spectrum, in addition to indexing higher-order processes such as auditory sensory memory and the violation of expectancy. In our studies of rhythmic expectancy, we measured emitted responses - a type of ERP that occurs when an expected event is omitted from a regular series of stimulus events - in simple rhythms with temporal structures typical of music. Our observations suggest that middle-latency gamma band (20-60 Hz activity (GBA plays an essential role in auditory rhythm processing. Evoked (phase-locked GBA occurs in the presence of physically presented auditory events and reflects the degree of accent. Induced (non-phase-locked GBA reflects temporally precise expectancies for strongly and weakly accented events in sound patterns. Thus far, these findings support theories of rhythm perception that posit temporal expectancies generated by active neural processes.

Role of Inflammatory Signaling in the Differential Effects of Saturated and Poly-unsaturated Fatty Acids on Peripheral Circadian Clocks

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Sam-Moon Kim

2016-05-01

Full Text Available Inflammatory signaling may play a role in high-fat diet (HFD-related circadian clock disturbances that contribute to systemic metabolic dysregulation. Therefore, palmitate, the prevalent proinflammatory saturated fatty acid (SFA in HFD and the anti-inflammatory, poly-unsaturated fatty acid (PUFA, docosahexaenoic acid (DHA, were analyzed for effects on circadian timekeeping and inflammatory responses in peripheral clocks. Prolonged palmitate, but not DHA, exposure increased the period of fibroblast Bmal1-dLuc rhythms. Acute palmitate treatment produced phase shifts of the Bmal1-dLuc rhythm that were larger in amplitude as compared to DHA. These phase-shifting effects were time-dependent and contemporaneous with rhythmic changes in palmitate-induced inflammatory responses. Fibroblast and differentiated adipocyte clocks exhibited cell-specific differences in the time-dependent nature of palmitate-induced shifts and inflammation. DHA and other inhibitors of inflammatory signaling (AICAR, cardamonin repressed palmitate-induced proinflammatory responses and phase shifts of the fibroblast clock, suggesting that SFA-mediated inflammatory signaling may feed back to modulate circadian timekeeping in peripheral clocks.

Distinct functions of Period2 and Period3 in the mouse circadian system revealed by in vitro analysis.

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Julie S Pendergast

2010-01-01

Full Text Available The mammalian circadian system, which is composed of a master pacemaker in the suprachiasmatic nuclei (SCN as well as other oscillators in the brain and peripheral tissues, controls daily rhythms of behavior and physiology. Lesions of the SCN abolish circadian rhythms of locomotor activity and transplants of fetal SCN tissue restore rhythmic behavior with the periodicity of the donor's genotype, suggesting that the SCN determines the period of the circadian behavioral rhythm. According to the model of timekeeping in the SCN, the Period (Per genes are important elements of the transcriptional/translational feedback loops that generate the endogenous circadian rhythm. Previous studies have investigated the functions of the Per genes by examining locomotor activity in mice lacking functional PERIOD proteins. Variable behavioral phenotypes were observed depending on the line and genetic background of the mice. In the current study we assessed both wheel-running activity and Per1-promoter-driven luciferase expression (Per1-luc in cultured SCN, pituitary, and lung explants from Per2(-/- and Per3(-/- mice congenic with the C57BL/6J strain. We found that the Per2(-/- phenotype is enhanced in vitro compared to in vivo, such that the period of Per1-luc expression in Per2(-/- SCN explants is 1.5 hours shorter than in Per2+/+ SCN, while the free-running period of wheel-running activity is only 11 minutes shorter in Per2(-/- compared to Per2+/+ mice. In contrast, circadian rhythms in SCN explants from Per3(-/- mice do not differ from Per3+/+ mice. Instead, the period and phase of Per1-luc expression are significantly altered in Per3(-/- pituitary and lung explants compared to Per3+/+ mice. Taken together these data suggest that the function of each Per gene may differ between tissues. Per2 appears to be important for period determination in the SCN, while Per3 participates in timekeeping in the pituitary and lung.

Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells.

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Sandbichler, Adolf M; Jansen, Bianca; Peer, Bettina A; Paulitsch, Monika; Pelster, Bernd; Egg, Margit

2018-01-01

Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts. Circadian oscillations of core clock gene mRNA´s were assessed using realtime qPCR with subsequent cosine wave fit analysis. Here we show that under normoxia primary metabolic activity of cells predominately occurs during day time and that after acute hypoxia of two hours, administrated immediately before each sampling point, steady state concentrations of glycolytic key metabolites such as glucose and lactate reveal to be highly rhythmic, following a circadian pattern with highest levels during the night periods and reflecting the circadian variation of the cellular response to hypoxia. Remarkably, rhythms in glycolysis are transferred to cellular energy states under normoxic conditions, so that ADP/ATP ratios oscillate as well, which is the first evidence for cycling ADP/ATP pools in a metazoan cell line to our knowledge. Furthermore, the hypoxia induced alterations in rhythms of glycolysis lead to the alignment of three major cellular redox systems, namely the circadian oscillations of NAD+/NADH and NADP+/NADPH ratios and of increased nocturnal levels of oxidized peroxiredoxins, resulting in a highly

Jazz drummers recruit language-specific areas for the processing of rhythmic structure.

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Herdener, Marcus; Humbel, Thierry; Esposito, Fabrizio; Habermeyer, Benedikt; Cattapan-Ludewig, Katja; Seifritz, Erich

2014-03-01

Rhythm is a central characteristic of music and speech, the most important domains of human communication using acoustic signals. Here, we investigated how rhythmical patterns in music are processed in the human brain, and, in addition, evaluated the impact of musical training on rhythm processing. Using fMRI, we found that deviations from a rule-based regular rhythmic structure activated the left planum temporale together with Broca's area and its right-hemispheric homolog across subjects, that is, a network also crucially involved in the processing of harmonic structure in music and the syntactic analysis of language. Comparing the BOLD responses to rhythmic variations between professional jazz drummers and musical laypersons, we found that only highly trained rhythmic experts show additional activity in left-hemispheric supramarginal gyrus, a higher-order region involved in processing of linguistic syntax. This suggests an additional functional recruitment of brain areas usually dedicated to complex linguistic syntax processing for the analysis of rhythmical patterns only in professional jazz drummers, who are especially trained to use rhythmical cues for communication.

Rhythmic Effects of Syntax Processing in Music and Language.

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Jung, Harim; Sontag, Samuel; Park, YeBin S; Loui, Psyche

2015-01-01

Music and language are human cognitive and neural functions that share many structural similarities. Past theories posit a sharing of neural resources between syntax processing in music and language (Patel, 2003), and a dynamic attention network that governs general temporal processing (Large and Jones, 1999). Both make predictions about music and language processing over time. Experiment 1 of this study investigates the relationship between rhythmic expectancy and musical and linguistic syntax in a reading time paradigm. Stimuli (adapted from Slevc et al., 2009) were sentences broken down into segments; each sentence segment was paired with a musical chord and presented at a fixed inter-onset interval. Linguistic syntax violations appeared in a garden-path design. During the critical region of the garden-path sentence, i.e., the particular segment in which the syntactic unexpectedness was processed, expectancy violations for language, music, and rhythm were each independently manipulated: musical expectation was manipulated by presenting out-of-key chords and rhythmic expectancy was manipulated by perturbing the fixed inter-onset interval such that the sentence segments and musical chords appeared either early or late. Reading times were recorded for each sentence segment and compared for linguistic, musical, and rhythmic expectancy. Results showed main effects of rhythmic expectancy and linguistic syntax expectancy on reading time. There was also an effect of rhythm on the interaction between musical and linguistic syntax: effects of violations in musical and linguistic syntax showed significant interaction only during rhythmically expected trials. To test the effects of our experimental design on rhythmic and linguistic expectancies, independently of musical syntax, Experiment 2 used the same experimental paradigm, but the musical factor was eliminated-linguistic stimuli were simply presented silently, and rhythmic expectancy was manipulated at the critical

Circadian variations of adenosine and of its metabolism. Could adenosine be a molecular oscillator for circadian rhythms?

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Chagoya de Sánchez, V

1995-03-01

The present review describes the biological implications of the periodic changes of adenosine concentrations in different tissues of the rat. Adenosine is a purine molecule that could have been formed in the prebiotic chemical evolution and has been preserved. The rhythmicity of this molecule, as well as its metabolism and even the presence of specific receptors, suggests a regulatory role in eukaryotic cells and in multicellular organisms. Adenosine may be considered a chemical messenger and its action could take place at the level of the same cell (autocrine), the same tissue (paracrine), or on separate organs (endocrine). Exploration of the circadian variations of adenosine was planned considering the liver as an important tissue for purine formation, the blood as a vehicle among tissues, and the brain as the possible acceptor for hepatic adenosine or its metabolites. The rats used in these studies were adapted to a dark-light cycle of 12 h with an unrestrained feeding and drinking schedule. The metabolic control of adenosine concentration in the different tissues studied through the 24-h cycle is related to the activity of adenosine-metabolizing enzyme: 5'-nucleotidase adenosine deaminase, adenosine kinase, and S-adenosylhomocysteine hydrolase. Some possibilities of the factors modulating the activity of these enzymes are commented upon. The multiphysiological action of adenosine could be mediated by several actions: (i) by interaction with extracellular and intracellular receptors and (ii) through its metabolism modulating the methylation pathway, possibly inducing physiological lipoperoxidation, or participating in the energetic homeostasis of the cell. The physiological meaning of the circadian variations of adenosine and its metabolism was focused on: maintenance of the energetic homeostasis of the tissues, modulation of membrane structure and function, regulation of fasting and feeding metabolic pattern, and its participation in the sleep-wake cycle. From

Temporal modification in cardiac rhythmicity of Nephrops norvegicus (Crustacea: Decapoda in relation to trawl capture stress

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Jacopo Aguzzi

2005-09-01

Full Text Available The effects of trawling on cardiac rhythmicity of Nephrops norvegicus (L. are still mostly unknown. Ultradian rhythms reported in previous studies may result from trawling capture stress, thus disappearing following acclimatisation to laboratory conditions. To test this hypothesis, 34 time series of cardiac activity data recorded in constant darkness were studied by Fourier analysis. Spectral decomposition of time series was obtained by defining the fundamental or circadian harmonic (CH in 24-h together with 9 submultiples of this period. The power content (PC of each harmonic was estimated in data segments of 24-h duration (days, giving graphic matrices of PC values over consecutive days. Values of PC for 9 submultiples were summed and studied in a block named ultradian band (UB. The modification in the PC of the CH and of the UB was evaluated during laboratory acclimatisation. A significant increase in the PC of the circadian harmonic component (CH over consecutive days of testing was observed. These findings suggest that, rather than being a product of dim light environmental fluctuations experienced by the animals from the deep waters of the continental slope, ultradian periodicity could well be caused by the stress of capture.

Distinguishing rhythmic from non-rhythmic brain activity during rest in healthy neurocognitive aging.

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Caplan, Jeremy B; Bottomley, Monica; Kang, Pardeep; Dixon, Roger A

2015-05-15

Rhythmic brain activity at low frequencies (healthy neurocognitive aging are mixed. Here we address two reasons conventional spectral analyses may have led to inconsistent results. First, spectral-power measures are compared to a baseline condition; when resting activity is the signal of interest, it is unclear what the baseline should be. Second, conventional methods do not clearly differentiate power due to rhythmic versus non-rhythmic activity. The Better OSCillation detection method (BOSC; Caplan et al., 2001; Whitten et al., 2011) avoids these problems by using the signal's own spectral characteristics as a reference to detect elevations in power lasting a few cycles. We recorded electroencephalographic (EEG) signal during rest, alternating eyes open and closed, in healthy younger (18-25 years) and older (60-74 years) participants. Topographic plots suggested the conventional and BOSC analyses measured different sources of activity, particularly at frequencies, like delta (1-4Hz), at which rhythms are sporadic; topographies were more similar in the 8-12Hz alpha band. There was little theta-band activity meeting the BOSC method's criteria, suggesting prior findings of theta power in healthy aging may reflect non-rhythmic signal. In contrast, delta oscillations were present at higher levels than theta in both age groups. In summary, applying strict and standardized criteria for rhythmicity, slow rhythms appear present in the resting brain at delta and alpha, but not theta frequencies, and appear unchanged in healthy aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Circadian light

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Bierman Andrew

2010-02-01

Full Text Available Abstract The present paper reflects a work in progress toward a definition of circadian light, one that should be informed by the thoughtful, century-old evolution of our present definition of light as a stimulus for the human visual system. This work in progress is based upon the functional relationship between optical radiation and its effects on nocturnal melatonin suppression, in large part because the basic data are available in the literature. Discussed here are the fundamental differences between responses by the visual and circadian systems to optical radiation. Brief reviews of photometry, colorimetry, and brightness perception are presented as a foundation for the discussion of circadian light. Finally, circadian light (CLA and circadian stimulus (CS calculation procedures based on a published mathematical model of human circadian phototransduction are presented with an example.

Rhythmic complexity and predictive coding

DEFF Research Database (Denmark)

Vuust, Peter; Witek, Maria A G

2014-01-01

Musical rhythm, consisting of apparently abstract intervals of accented temporal events,has a remarkable capacity to move our minds and bodies. How does the cognitive systemenable our experiences of rhythmically complex music? In this paper, we describe somecommon forms of rhythmic complexity...

Rhythmic Cognition in Humans and Animals: Distinguishing Meter and Pulse Perception

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W Tecumseh eFitch

2013-10-01

Full Text Available This paper outlines a cognitive and comparative perspective on human rhythmic cognition that emphasizes a key distinction between pulse perception and meter perception. Pulse perception involves the extraction of a regular pulse or 'tactus' from a stream of events. Meter perception involves grouping of events into hierarchical trees with differing levels of 'strength', or perceptual prominence. I argue that metrically-structured rhythms are required to either perform or move appropriately to music (e.g. to dance. Rhythms, from this metrical perspective, constitute 'trees in time'. Rhythmic syntax represents a neglected form of musical syntax, and warrants more thorough neuroscientific investigation. The recent literature on animal entrainment clearly demonstrates the capacity to extract the pulse from rhythmic music, and to entrain periodic movements to this pulse, in several parrot species and a California sea lion, and a more limited ability to do so in one chimpanzee. However, the ability of these or other species to infer hierarchical rhythmic trees remains, for the most part, unexplored (with some apparent negative results from macaques. The results from this new animal comparative research, combined with new methods to explore rhythmic cognition neurally, provide exciting new routes for understanding not just rhythmic cognition, but hierarchical cognition more generally, from a biological and neural perspective.

Intergeneric complementation of a circadian rhythmicity defect : phylogenetic conservation of structure and function of the clock gene frequency

NARCIS (Netherlands)

Merrow, Martha W.; Dunlap, Jay C.; Dover, G.

1994-01-01

The Neurospora crassa frequency locus encodes a 989 amino acid protein that is a central component, a state variable, of the circadian biological clock. We have determined the sequence of all or part of this protein and surrounding regulatory regions from additional fungi representing three genera

Sex-Specific Diurnal Immobility Induced by Forced Swim Test in Wild Type and Clock Gene Deficient Mice

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Ningyue Li

2015-03-01

Full Text Available Objective: The link between alterations in circadian rhythms and depression are well established, but the underlying mechanisms are far less elucidated. We investigated the circadian characteristics of immobility behavior in wild type (WT mice and mice with mutations in core Clock genes. Methods: All mice were tested with forced swim test (FST at 4 h intervals. Results: These experiments revealed significant diurnal rhythms associated with immobility behavior in both male and female WT mice with sex-different circadian properties. In addition, male mice showed significantly less immobility during the night phase in comparison to female mice. Female Per1Brdm1 mice also showed significant rhythmicity. However, the timing of rhythmicity was very different from that observed in female wild type mice. Male Per1Brdm1 mice showed a pattern of rhythmicity similar to that of wild type mice. Furthermore, female Per1Brdm1 mice showed higher duration of immobility in comparison to male Per1Brdm1 mice in both daytime and early night phases. Neither Per2Brdm1 nor ClockΔ19 mice showed significant rhythmicity, but both female Per2Brdm1 and ClockΔ19 mice had lower levels of immobility, compared to males. Conclusions: This study highlights the differences in the circadian characteristics of immobility induced by FST in WT, ClockΔ19, Per1, and Per2 deficient mice.

Circadian rhythms in sports performance--an update.

Science.gov (United States)

Drust, B; Waterhouse, J; Atkinson, G; Edwards, B; Reilly, T

2005-01-01

We discuss current knowledge on the description, impact, and underlying causes of circadian rhythmicity in sports performance. We argue that there is a wealth of information from both applied and experimental work, which, when considered together, suggests that sports performance is affected by time of day in normal entrained conditions and that the variation has at least some input from endogenous mechanisms. Nevertheless, precise information on the relative importance of endogenous and exogenous factors is lacking. No single study can answer both the applied and basic research questions that are relevant to this topic, but an appropriate mixture of real-world research on rhythm disturbances and tightly controlled experiments involving forced desynchronization protocols is needed. Important issues, which should be considered by any chronobiologist interested in sports and exercise, include how representative the study sample and the selected performance tests are, test-retest reliability, as well as overall design of the experiment.

Strength Recovery Following Rhythmic or Sustained Exercise as a Function of Time.

Science.gov (United States)

Kearney, Jay T.

The relative rates of strength recovery subsequent to bouts of rhythmic or sustained isometric exercise were investigated. The 72 undergraduates who served as subjects were tested seven times within the framework of a repeated measures design. Each testing session involved two bouts of either rhythmic or sustained isometric exercise separated by a…

Photoperiodism and circadian rhythms in relation to the hazards of environmental pollutants

International Nuclear Information System (INIS)

Attia, A.M.; Ali, M.M.; Abdou, M.M.

1999-01-01

The duration, intensity and wavelengths of light to which vertebrates and invertebrates are exposed vary widely over a 24-hour period as well as throughout the year. Species, by means of their behavioral patterns, differentially control in part the photoperiodic environment to which they are exposed. It is essential that mammals, probably including humans, adjust their physiology with changes in the makeup of the photoperiod. Numerous body functions undergo variations recurring at about 24-hour intervals in the presence or absence of known environmental changes with similar periods. This applies to continuos but rhythmic phenomena, with a peak and trough repeating itself every 24-hours, as well as to discrete events occurring about once a day. The time intervals separating these consecutive periodic events are similar but often not identical. Such periods are called circadian. Rhythms have been reported in cell growth, hormonal levels, and so on. Rhythms are generally resistant to a variety of chemical substances including stimulants and depressants. photoperiodism and circadian rhythms, in relation to the hazardous effects of environmental pollutants, as pesticides; which may directly or indirectly affect or alter physiologocal processes in living things, are summarized

Daily rhythm of circulating fat soluble vitamin concentration (A, D, E and K in the horse

Directory of Open Access Journals (Sweden)

Caola Giovanni

2004-07-01

Full Text Available Abstract Background Many physiological processes of mammalian species exhibit daily rhythmicity. An intrinsic relationship exists between fat soluble vitamins (A, D, E and K and several body functions. Few investigations on the rhythmic pattern of vitamins in domestic animals have been carried out. The present study evaluated the circadian rhythmicity of fat soluble vitamins in the horse. Methods Blood samples from 5 Thoroughbred mares were collected at four-hour intervals over a 48-hour period (starting at 8:00 hours on day 1 and finishing at 4:00 on day 2 via an intravenous cannula inserted into the jugular vein. Fat soluble vitamin concentration in the serum (A, D, E and K was measured by HPLC. One-way repeated measures analysis of variance (ANOVA was used to determine significant differences. p values Results ANOVA showed a highly significant effect of time in all the horses for the vitamins studied (p Conclusion Fat soluble vitamins exhibit daily rhythmicity with diurnal peak. Further investigations could help optimize the use of these substances according to their circadian (or other rhythms.

Feedback Signal from Motoneurons Influences a Rhythmic Pattern Generator.

Science.gov (United States)

Rotstein, Horacio G; Schneider, Elisa; Szczupak, Lidia

2017-09-20

the actual rhythmic pattern of movements. We have investigated whether motoneurons are limited to function as output units. Analysis of the network that controls crawling behavior in the leech has clearly indicated that motoneurons, in addition to controlling muscle activity, send signals to the pattern generator. Physiological and modeling studies on the role of specific motoneurons suggest that these feedback signals modulate the phase relationship of the rhythmic activity. Copyright © 2017 the authors 0270-6474/17/379149-11$15.00/0.

Entrainment of the Circadian Rhythm in Egg Hatching of the Crab Dyspanopeus sayi by Chemical Cues from Ovigerous Females.

Science.gov (United States)

Forward, Richard B; Sanchez, Kevin G; Riley, Paul P

2016-02-01

The subtidal crab Dyspanopeus sayi has a circadian rhythm in larval release with a free-running period of 24.1 h. Under constant conditions, eggs hatch primarily in the 4-h interval after the time of sunset. The study tested the new model for entrainment in subtidal crabs, which proposes that the female perceives the environmental cycles and entrains the endogenous rhythm in the embryos. Results verified the model for D. sayi. Hatching by embryos collected from the field when they had not yet developed eye pigments, and were kept in constant conditions attached to their mother, exhibited the circadian hatching rhythm. Attached embryos could also be entrained to a new photoperiod in the laboratory before they developed eye pigments. Further, mature embryos removed from the female hatched rhythmically, indicating that a circadian rhythm resides in the embryos. However, if mature embryos with eye pigments were removed from the female and exposed to a new light-dark cycle, they could not be entrained to the new cycle; rather, they hatched according to the timing of the original light-dark cycle. Nevertheless, detached, mature embryos would entrain to a new light-dark cycle if they were in chemical, but not physical, contact with the female. Thus, the female perceives the light-dark cycle, and uses chemical cues to entrain the circadian rhythm of hatching by the embryos. © 2016 Marine Biological Laboratory.

Analysis of a Gene Regulatory Cascade Mediating Circadian Rhythm in Zebrafish

Science.gov (United States)

Wang, Haifang; Du, Jiulin; Yan, Jun

2013-01-01

In the study of circadian rhythms, it has been a puzzle how a limited number of circadian clock genes can control diverse aspects of physiology. Here we investigate circadian gene expression genome-wide using larval zebrafish as a model system. We made use of a spatial gene expression atlas to investigate the expression of circadian genes in various tissues and cell types. Comparison of genome-wide circadian gene expression data between zebrafish and mouse revealed a nearly anti-phase relationship and allowed us to detect novel evolutionarily conserved circadian genes in vertebrates. We identified three groups of zebrafish genes with distinct responses to light entrainment: fast light-induced genes, slow light-induced genes, and dark-induced genes. Our computational analysis of the circadian gene regulatory network revealed several transcription factors (TFs) involved in diverse aspects of circadian physiology through transcriptional cascade. Of these, microphthalmia-associated transcription factor a (mitfa), a dark-induced TF, mediates a circadian rhythm of melanin synthesis, which may be involved in zebrafish's adaptation to daily light cycling. Our study describes a systematic method to discover previously unidentified TFs involved in circadian physiology in complex organisms. PMID:23468616

Genetic Analysis of Daily Activity in Humans and Mice

National Research Council Canada - National Science Library

Takahashi, Joseph

1999-01-01

.... We have characterized variation in five circadian phenotypes: free-running circadian period, phase angle of entrainment, amplitude of the circadian rhythm, circadian activity level, and dissociation of rhythmicity...

Circadian Rhythm Neuropeptides in Drosophila: Signals for Normal Circadian Function and Circadian Neurodegenerative Disease.

Science.gov (United States)

He, Qiankun; Wu, Binbin; Price, Jeffrey L; Zhao, Zhangwu

2017-04-21

Circadian rhythm is a ubiquitous phenomenon in many organisms ranging from prokaryotes to eukaryotes. During more than four decades, the intrinsic and exogenous regulations of circadian rhythm have been studied. This review summarizes the core endogenous oscillation in Drosophila and then focuses on the neuropeptides, neurotransmitters and hormones that mediate its outputs and integration in Drosophila and the links between several of these (pigment dispersing factor (PDF) and insulin-like peptides) and neurodegenerative disease. These signaling molecules convey important network connectivity and signaling information for normal circadian function, but PDF and insulin-like peptides can also convey signals that lead to apoptosis, enhanced neurodegeneration and cognitive decline in flies carrying circadian mutations or in a senescent state.

Circadian variations of interferon-induced enhancement of human natural killer (NK) cell activity.

Science.gov (United States)

Gatti, G; Cavallo, R; Sartori, M L; Carignola, R; Masera, R; Delponte, D; Salvadori, A; Angeli, A

1988-01-01

We searched for circadian changes in the enhancement of the NK activity after exposure to IFN-gamma of peripheral blood mononuclear (PBM) cells obtained serially throughout the 24-h cycle. In August-October 1986, blood was drawn from 7 healthy, diurnally active and nocturnally resting male volunteers (22-34 yr) at 4-h intervals for 24 h starting at 08:00. PBM cells were immediately separated and assayed for NK cell activity, using K 562 cultured cells as a target in a 4-h 51Cr release assay after prior incubation for 20 h with buffer or 300 IU rIFN-gamma. Circadian variations of the spontaneous NK cell cytotoxicity were apparent; the activity was at its maximum at the end of the night or in the early morning and then declined in the afternoon. The 24-h rhythmic pattern was validated with statistical significance by the Cosinor method (p less than 0.02; acrophase 04:22). Maximum enhancement by IFN-gamma was attained in the second part of the night or in the early morning, i.e. in phase with the peak of the spontaneous NK cell activity. A significant circadian rhythm of the percent increase above control levels was validated by the Cosinor method (p less than 0.01; acrophase 04:03). Our findings may be of relevance to a better understanding of the mechanisms of control of human NK activity and warrant consideration as an approach to improve the effectiveness of time-qualified immunotherapy.

The impact of circadian rhythms on medical imaging and radiotherapy regimes for the paediatric patient

International Nuclear Information System (INIS)

Forssell-Aronsson, E.; Quinlan, R.A.

2017-01-01

Daily rhythmic changes are found in cellular events in cell cycle, DNA repair, apoptosis and angiogenesis in both normal and tumour tissue, as well as in enzymatic activity and drug metabolism. In this paper, we hypothesize that circadian rhythms need to be considered in radiation protection and optimization in personalized medicine, especially for paediatric care. The sensitivity of the eye lens to ionizing radiation makes the case for limiting damage to the lens epithelium by planning medical radio-imaging procedures for the afternoon, rather than the morning. Equally, the tumour and normal tissue response to radiotherapy is also subject to diurnal variation enabling optimization of time of treatment. (authors)

Vertebrate-like CRYPTOCHROME 2 from monarch regulates circadian transcription via independent repression of CLOCK and BMAL1 activity.

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Zhang, Ying; Markert, Matthew J; Groves, Shayna C; Hardin, Paul E; Merlin, Christine

2017-09-05

Circadian repression of CLOCK-BMAL1 by PERIOD and CRYPTOCHROME (CRY) in mammals lies at the core of the circadian timekeeping mechanism. CRY repression of CLOCK-BMAL1 and regulation of circadian period are proposed to rely primarily on competition for binding with coactivators on an α-helix located within the transactivation domain (TAD) of the BMAL1 C terminus. This model has, however, not been tested in vivo. Here, we applied CRISPR/Cas9-mediated mutagenesis in the monarch butterfly ( Danaus plexippus ), which possesses a vertebrate-like CRY (dpCRY2) and an ortholog of BMAL1, to show that insect CRY2 regulates circadian repression through TAD α-helix-dependent and -independent mechanisms. Monarch mutants lacking the BMAL1 C terminus including the TAD exhibited arrhythmic eclosion behavior. In contrast, mutants lacking the TAD α-helix but retaining the most distal C-terminal residues exhibited robust rhythms during the first day of constant darkness (DD1), albeit with a delayed peak of eclosion. Phase delay in this mutant on DD1 was exacerbated in the presence of a single functional allele of dpCry2 , and rhythmicity was abolished in the absence of dpCRY2. Reporter assays in Drosophila S2 cells further revealed that dpCRY2 represses through two distinct mechanisms: a TAD-dependent mechanism that involves the dpBMAL1 TAD α-helix and dpCLK W328 and a TAD-independent mechanism involving dpCLK E333. Together, our results provide evidence for independent mechanisms of vertebrate-like CRY circadian regulation on the BMAL1 C terminus and the CLK PAS-B domain and demonstrate the importance of a BMAL1 TAD-independent mechanism for generating circadian rhythms in vivo.

Body weight gain in rats by a high-fat diet produces chronodisruption in activity/inactivity circadian rhythm.

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Bravo, Rafael; Cubero, Javier; Franco, Lourdes; Mesa, Mónica; Galán, Carmen; Rodríguez, Ana Beatriz; Jarne, Carlos; Barriga, Carmen

2014-04-01

In the last few decades, obesity has become one of the most important public health problems. Adipose tissue is an active endocrine tissue which follows a rhythmic pattern in its functions and may produce alterations in certain circadian rhythms. Our aim was to evaluate whether the locomotor activity circadian rhythm could be modified by a hypercaloric diet in rodents. Two groups were considered in the experiment: 16 rats were used as a control group and were fed standard chow; the other group comprised 16 rats fed a high-fat diet (35.8% fat, 35% glucides). The trial lasted 16 weeks. Body weight was measured every week, and a blood sample was extracted every two weeks to quantify triglyceride levels. The activity/inactivity circadian rhythm was logged through actimetry throughout the trial, and analysed using the DAS 24© software package. At the end of the experiment, the high-fat fed rats had obese-like body weights and high plasma triglyceride levels, and, compared with the control group, increased diurnal activity, decreased nocturnal activity, reductions in amplitude, midline estimating statistic of rhythm, acrophase and interdaily stability, and increases in intradaily variability of their activity rhythms. The results thus show how obesity can lead to symptoms of chronodisruption in the body similar to those of ageing.

Decoding magnetoencephalographic rhythmic activity using spectrospatial information.

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Kauppi, Jukka-Pekka; Parkkonen, Lauri; Hari, Riitta; Hyvärinen, Aapo

2013-12-01

We propose a new data-driven decoding method called Spectral Linear Discriminant Analysis (Spectral LDA) for the analysis of magnetoencephalography (MEG). The method allows investigation of changes in rhythmic neural activity as a result of different stimuli and tasks. The introduced classification model only assumes that each "brain state" can be characterized as a combination of neural sources, each of which shows rhythmic activity at one or several frequency bands. Furthermore, the model allows the oscillation frequencies to be different for each such state. We present decoding results from 9 subjects in a four-category classification problem defined by an experiment involving randomly alternating epochs of auditory, visual and tactile stimuli interspersed with rest periods. The performance of Spectral LDA was very competitive compared with four alternative classifiers based on different assumptions concerning the organization of rhythmic brain activity. In addition, the spectral and spatial patterns extracted automatically on the basis of trained classifiers showed that Spectral LDA offers a novel and interesting way of analyzing spectrospatial oscillatory neural activity across the brain. All the presented classification methods and visualization tools are freely available as a Matlab toolbox. © 2013.

Rhythmicity in mice selected for extremes in stress reactivity: behavioural, endocrine and sleep changes resembling endophenotypes of major depression.

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Chadi Touma

Full Text Available Dysregulation of the hypothalamic-pituitary-adrenal (HPA axis, including hyper- or hypo-activity of the stress hormone system, plays a critical role in the pathophysiology of mood disorders such as major depression (MD. Further biological hallmarks of MD are disturbances in circadian rhythms and sleep architecture. Applying a translational approach, an animal model has recently been developed, focusing on the deviation in sensitivity to stressful encounters. This so-called 'stress reactivity' (SR mouse model consists of three separate breeding lines selected for either high (HR, intermediate (IR, or low (LR corticosterone increase in response to stressors.In order to contribute to the validation of the SR mouse model, our study combined the analysis of behavioural and HPA axis rhythmicity with sleep-EEG recordings in the HR/IR/LR mouse lines. We found that hyper-responsiveness to stressors was associated with psychomotor alterations (increased locomotor activity and exploration towards the end of the resting period, resembling symptoms like restlessness, sleep continuity disturbances and early awakenings that are commonly observed in melancholic depression. Additionally, HR mice also showed neuroendocrine abnormalities similar to symptoms of MD patients such as reduced amplitude of the circadian glucocorticoid rhythm and elevated trough levels. The sleep-EEG analyses, furthermore, revealed changes in rapid eye movement (REM and non-REM sleep as well as slow wave activity, indicative of reduced sleep efficacy and REM sleep disinhibition in HR mice.Thus, we could show that by selectively breeding mice for extremes in stress reactivity, clinically relevant endophenotypes of MD can be modelled. Given the importance of rhythmicity and sleep disturbances as biomarkers of MD, both animal and clinical studies on the interaction of behavioural, neuroendocrine and sleep parameters may reveal molecular pathways that ultimately lead to the discovery of new

Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on: data derived from a randomized clinical trial

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Lone Baandrup

2016-10-01

Full Text Available Abstract Background Patients with severe mental illness often suffer from disruptions in circadian rest-activity cycles, which might partly be attributed to ongoing psychopharmacological medication. Benzodiazepines are frequently prescribed for prolonged periods despite recommendations of only short-term usage. Melatonin, a naturally occurring nocturnal hormone, has the potential to stabilize disrupted circadian rhythmicity. Our aim was to investigate how prolonged-release melatonin affects rest-activity patterns in medicated patients with severe mental illness and if benzodiazepine dose reduction is associated with changes in circadian rhythm parameters. Method Data were derived from a randomized, double-blinded clinical trial with 24 weeks follow-up. Participants were randomized to add-on treatment with prolonged-release melatonin (2 mg or matching placebo, and usual benzodiazepine dosage was gradually tapered. Here we report the results of 72 h of actigraphic assessment of activity-rest cycles performed pre and post tapering. Changes in rest-activity rhythm parameters between the melatonin and placebo group were analyzed using the univariate general linear model. Change in activity counts per 6 h, from baseline to follow-up, in the whole sample was analyzed using paired samples t-test. Results A subsample of 48 patients participated in the actigraphic assessment: 20 in the melatonin group and 28 in the placebo group. Rest-activity cycles varied from regular to highly disrupted. Melatonin significantly increased the interdaily stability and at a trend level decreased the intradaily variability compared with placebo. Benzodiazepine dose reduction was not associated with these circadian rhythm parameters. Activity counts were generally higher after benzodiazepine dose reduction compared with pre tapering, but differences did not reach statistical significance. Conclusion Our data suggest melatonin as an aid during benzodiazepine withdrawal for

Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain

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Goldstein-Kral Lauren

2011-01-01

Full Text Available Abstract Background The mammalian suprachiasmatic nucleus (SCN, located in the ventral hypothalamus, is a major regulator of circadian rhythms in mammals and birds. However, the role of the SCN in lower vertebrates remains poorly understood. Zebrafish cyclops (cyc mutants lack ventral brain, including the region that gives rise to the SCN. We have used cyc embryos to define the function of the zebrafish SCN in regulating circadian rhythms in the developing pineal organ. The pineal organ is the major source of the circadian hormone melatonin, which regulates rhythms such as daily rest/activity cycles. Mammalian pineal rhythms are controlled almost exclusively by the SCN. In zebrafish and many other lower vertebrates, the pineal has an endogenous clock that is responsible in part for cyclic melatonin biosynthesis and gene expression. Results We find that pineal rhythms are present in cyc mutants despite the absence of an SCN. The arginine vasopressin-like protein (Avpl, formerly called Vasotocin is a peptide hormone expressed in and around the SCN. We find avpl mRNA is absent in cyc mutants, supporting previous work suggesting the SCN is missing. In contrast, expression of the putative circadian clock genes, cryptochrome 1b (cry1b and cryptochrome 3 (cry3, in the brain of the developing fish is unaltered. Expression of two pineal rhythmic genes, exo-rhodopsin (exorh and serotonin-N-acetyltransferase (aanat2, involved in photoreception and melatonin synthesis, respectively, is also similar between cyc embryos and their wildtype (WT siblings. The timing of the peaks and troughs of expression are the same, although the amplitude of expression is slightly decreased in the mutants. Cyclic gene expression persists for two days in cyc embryos transferred to constant light or constant dark, suggesting a circadian clock is driving the rhythms. However, the amplitude of rhythms in cyc mutants kept in constant conditions decreased more quickly than in their

[Role of rhythmicity in infant development].

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Ciccone, A

2015-09-01

This article deals with rhythm in the experiences of infants, focusing in particular on the function of rhythmicity in the baby's sense of being and its continuity. Infants are inevitably subjected to experiences of discontinuity. These experiences are necessary to development, but they expose the child to chaotic experiences when a basic rhythmicity is not ensured. The rhythmicity of childcare experiences gives the illusion of permanence and enables anticipation. This nourishes the basic feeling of security and supports the development of thought. Interactive and intersubjective exchanges must be rhythmic and must be in keeping with the rhythm of the baby, who needs to withdraw regularly from the interaction to internalize the experience of the exchange. Without this retreat, the interaction is over-stimulating and prevents internalization. Object presence/ absence must also be rhythmic, to enable the infant to keep the object alive inside him/ herself. Observation of babies has demonstrated their ability to manage experiences of discontinuity: they are able to sustain a continuous link via their gaze, look for clues indicating the presence of a lost object, search for support in sensations, and fabricate rhythmicity to remain open to the self and the world. The author gives some examples of infant observations that provide evidence of these capacities. One observation shows how a baby defends itself against a discontinuity by actively maintaining a link via his/her gaze. Another example shows an infant holding on to "hard sensations" in order to stay away from "soft" ones, which represent the fragility of the separation experience. This example pertains to a seven-month-old's prelanguage and "prosodic tonicity". The author takes this opportunity to propose the notion of "psychic bisensuality" to describe these two sensation poles, which must be harmoniously articulated to guarantee an inner sense of security. Such repairs of discontinuity are only possible if the

Protein phosphatase dependent circadian regulation of intermediate-term associative memory

OpenAIRE

Michel, Maximilian; Gardner, Jacob S.; Green, Charity L.; Organ, Chelsea L.; Lyons, Lisa C.

2013-01-01

The endogenous circadian clock is a principal factor modulating memory across species. Determining the processes through which the circadian clock modulates memory formation is a key issue in understanding and identifying mechanisms to improve memory. We used the marine mollusk Aplysia californica to investigate circadian modulation of intermediate-term memory (ITM) and the mechanisms through which the circadian clock phase specifically suppresses memory using the operant learning paradigm, l...

The rhythm of feeding : Effect of nutrients on metabolism and the molecular clock

NARCIS (Netherlands)

Oosterman, J.E.

2017-01-01

This thesis describes studies we performed to assess the relationship between nutrients and the circadian clock. We assessed the effects of sugar and fatty acids on the daily rhythmicity of hepatic clock genes and whole-body metabolism in vivo, and on circadian rhythmicity of clock genes in vitro.

Long-term Levodopa Treatment Accelerates the Circadian Rhythm Dysfunction in a 6-hydroxydopamine Rat Model of Parkinson's Disease

Institute of Scientific and Technical Information of China (English)

Si-Yue Li; Ya-Li Wang; Wen-Wen Liu; Dong-Jun Lyu; Fen Wang; Cheng-Jie Mao; Ya-Ping Yang; Li-Fang Hu; Chun-Feng Liu

2017-01-01

Background:Parkinson's disease (PD) patients with long-term levodopa (L-DOPA) treatment are suffering from severe circadian dysfunction.However,it is hard to distinguish that the circadian disturbance in patients is due to the disease progression itself,or is affected by L-DOPA replacement therapy.This study was to investigate the role of L-DOPA on the circadian dysfunction in a rat model of PD.Methods:The rat model of PD was constructed by a bilateral striatal injection with 6-hydroxydopamine (6-OHDA),followed by administration of saline or 25 mg/kg L-DOPA for 21 consecutive days.Rotarod test,footprint test,and open-field test were carried out to evaluate the motor function.Striatum,suprachiasmatic nucleus (SCN),liver,and plasma were collected at 6:00,12:00,18:00,and 24:00.Quantitative real-time polymerase chain reaction was used to examine the expression of clock genes.Enzyme-linked immunosorbent assay was used to determine the secretion level of cortisol and melatonin.High-performance liquid chromatography was used to measure the neurotransmitters.Analysis of variance was used for data analysis.Results:L-DOPA alleviated the motor deficits induced by 6-OHDA lesions in the footprint and open-field test (P ＜ 0.01,P ＜ 0.001,respectively).After L-DOPA treatment,Bmal1 decreased in the SCN compared with 6-OHDA group at 12:00 (P ＜ 0.01) and 24:00 (P ＜ 0.001).In the striatum,the expression ofBmal1,Rorα was lower than that in the 6-OHDA group at 18:00 (P ＜ 0.05) and L-DOPA seemed to delay the peak of Per2 to 24:00.In liver,L-DOPA did not affect the rhythmicity and expression of these clock genes (P ＞ 0.05).In addition,the cortisol secretion was increased (P ＞ 0.05),but melatonin was further inhibited after L-DOPA treatment at 6:00 (P ＜ 0.01).Conclusions:In the circadian system of advanced PD rat models,circadian dysfunction is not only contributed by the degeneration of the disease itself but also long-term L-DOPA therapy may further aggravate it.

Circadian expression profiles of chromatin remodeling factor genes in Arabidopsis.

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Lee, Hong Gil; Lee, Kyounghee; Jang, Kiyoung; Seo, Pil Joon

2015-01-01

The circadian clock is a biological time keeper mechanism that regulates biological rhythms to a period of approximately 24 h. The circadian clock enables organisms to anticipate environmental cycles and coordinates internal cellular physiology with external environmental cues. In plants, correct matching of the clock with the environment confers fitness advantages to plant survival and reproduction. Therefore, circadian clock components are regulated at multiple layers to fine-tune the circadian oscillation. Epigenetic regulation provides an additional layer of circadian control. However, little is known about which chromatin remodeling factors are responsible for circadian control. In this work, we analyzed circadian expression of 109 chromatin remodeling factor genes and identified 17 genes that display circadian oscillation. In addition, we also found that a candidate interacts with a core clock component, supporting that clock activity is regulated in part by chromatin modification. As an initial attempt to elucidate the relationship between chromatin modification and circadian oscillation, we identified novel regulatory candidates that provide a platform for future investigations of chromatin regulation of the circadian clock.

The bZIP transcription factor HY5 interacts with the promoter of the monoterpene synthase gene QH6 in modulating its rhythmic expression.

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Zhou, Fei; Sun, Tian-Hu; Zhao, Lei; Pan, Xi-Wu; Lu, Shan

2015-01-01

The Artemisia annua L. β-pinene synthase QH6 was previously determined to be circadian-regulated at the transcriptional level, showing a rhythmic fluctuation of steady-state transcript abundances. Here we isolated both the genomic sequence and upstream promoter region of QH6. Different regulatory elements, such as G-box (TGACACGTGGCA, -421 bp from the translation initiation site) which might have effects on rhythmic gene expression, were found. Using the yeast one-hybrid and electrophoretic mobility shift assay (EMSA), we confirmed that the bZIP transcription factor HY5 binds to this motif of QH6. Studies with promoter truncations before and after this motif suggested that this G-box was important for the diurnal fluctuation of the transgenic β-glucuronidase gene (GUS) transcript abundance in Arabidopsis thaliana. GUS gene driven by the promoter region immediately after G-box showed an arrhythmic expression in both light/dark (LD) and constant dark (DD) conditions, whereas the control with G-box retained its fluctuation in both LD and DD. We further transformed A. thaliana with the luciferase gene (LUC) driven by an 1400 bp fragment upstream QH6 with its G-box intact or mutated, respectively. The luciferase activity assay showed that a peak in the early morning disappeared in the mutant. Gene expression analysis also demonstrated that the rhythmic expression of LUC was abolished in the hy5-1 mutant.

Processing rhythmic pattern during Chinese sentence reading: An eye movement study

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Yingyi eLuo

2015-12-01

Full Text Available Prosodic constraints play a fundamental role during both spoken sentence comprehension and silent reading. In Chinese, the rhythmic pattern of the verb-object (V-O combination has been found to rapidly affect the semantic access/integration process during sentence reading (Luo and Zhou, 2010. Rhythmic pattern refers to the combination of words with different syllabic lengths, with certain combinations disallowed (e.g., [2+1]; numbers standing for the number of syllables of the verb and the noun respectively and certain combinations preferred (e.g., [1+1] or [2+2]. This constraint extends to the situation in which the combination is used to modify other words. A V-O phrase could modify a noun by simply preceding it, forming a V-O-N compound; when the verb is disyllabic, however, the word order has to be O-V-N and the object is preferred to be disyllabic. In this study, we investigated how the reader processes the rhythmic pattern and word order information by recording the reader’s eye-movements. We created four types of sentences by crossing rhythmic pattern and word order in compounding. The compound, embedding a disyllabic verb, could be in the correct O-V-N or the incorrect V-O-N order; the object could be disyllabic or monosyllabic. We found that the reader spent more time and made more regressions on and after the compounds when either type of anomaly was detected during the first pass reading. However, during re-reading (after all the words in the sentence have been viewed, less regressive eye movements were found for the anomalous rhythmic pattern, relative to the correct pattern; moreover, only the abnormal rhythmic pattern, not the violated word order, influenced the regressive eye movements. These results suggest that while the processing of rhythmic pattern and word order information occurs rapidly during the initial reading of the sentence, the process of recovering from the rhythmic pattern anomaly may ease the reanalysis

Processing Rhythmic Pattern during Chinese Sentence Reading: An Eye Movement Study.

Science.gov (United States)

Luo, Yingyi; Duan, Yunyan; Zhou, Xiaolin

2015-01-01

Prosodic constraints play a fundamental role during both spoken sentence comprehension and silent reading. In Chinese, the rhythmic pattern of the verb-object (V-O) combination has been found to rapidly affect the semantic access/integration process during sentence reading (Luo and Zhou, 2010). Rhythmic pattern refers to the combination of words with different syllabic lengths, with certain combinations disallowed (e.g., [2 + 1]; numbers standing for the number of syllables of the verb and the noun respectively) and certain combinations preferred (e.g., [1 + 1] or [2 + 2]). This constraint extends to the situation in which the combination is used to modify other words. A V-O phrase could modify a noun by simply preceding it, forming a V-O-N compound; when the verb is disyllabic, however, the word order has to be O-V-N and the object is preferred to be disyllabic. In this study, we investigated how the reader processes the rhythmic pattern and word order information by recording the reader's eye-movements. We created four types of sentences by crossing rhythmic pattern and word order in compounding. The compound, embedding a disyllabic verb, could be in the correct O-V-N or the incorrect V-O-N order; the object could be disyllabic or monosyllabic. We found that the reader spent more time and made more regressions on and after the compounds when either type of anomaly was detected during the first pass reading. However, during re-reading (after all the words in the sentence have been viewed), less regressive eye movements were found for the anomalous rhythmic pattern, relative to the correct pattern; moreover, only the abnormal rhythmic pattern, not the violated word order, influenced the regressive eye movements. These results suggest that while the processing of rhythmic pattern and word order information occurs rapidly during the initial reading of the sentence, the process of recovering from the rhythmic pattern anomaly may ease the reanalysis processing at the

Effects of Partial and Acute Total Sleep Deprivation on Performance across Cognitive Domains, Individuals and Circadian Phase

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Lo, June C.; Groeger, John A.; Santhi, Nayantara; Arbon, Emma L.; Lazar, Alpar S.; Hasan, Sibah; von Schantz, Malcolm; Archer, Simon N.; Dijk, Derk-Jan

2012-01-01

Background Cognitive performance deteriorates during extended wakefulness and circadian phase misalignment, and some individuals are more affected than others. Whether performance is affected similarly across cognitive domains, or whether cognitive processes involving Executive Functions are more sensitive to sleep and circadian misalignment than Alertness and Sustained Attention, is a matter of debate. Methodology/Principal Findings We conducted a 2 × 12-day laboratory protocol to characterize the interaction of repeated partial and acute total sleep deprivation and circadian phase on performance across seven cognitive domains in 36 individuals (18 males; mean ± SD of age = 27.6±4.0 years). The sample was stratified for the rs57875989 polymorphism in PER3, which confers cognitive susceptibility to total sleep deprivation. We observed a deterioration of performance during both repeated partial and acute total sleep deprivation. Furthermore, prior partial sleep deprivation led to poorer cognitive performance in a subsequent total sleep deprivation period, but its effect was modulated by circadian phase such that it was virtually absent in the evening wake maintenance zone, and most prominent during early morning hours. A significant effect of PER3 genotype was observed for Subjective Alertness during partial sleep deprivation and on n-back tasks with a high executive load when assessed in the morning hours during total sleep deprivation after partial sleep loss. Overall, however, Subjective Alertness and Sustained Attention were more affected by both partial and total sleep deprivation than other cognitive domains and tasks including n-back tasks of Working Memory, even when implemented with a high executive load. Conclusions/Significance Sleep loss has a primary effect on Sleepiness and Sustained Attention with much smaller effects on challenging Working Memory tasks. These findings have implications for understanding how sleep debt and circadian rhythmicity

Rhythmic diel pattern of gene expression in juvenile maize leaf.

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Maciej Jończyk

Full Text Available BACKGROUND: Numerous biochemical and physiological parameters of living organisms follow a circadian rhythm. Although such rhythmic behavior is particularly pronounced in plants, which are strictly dependent on the daily photoperiod, data on the molecular aspects of the diurnal cycle in plants is scarce and mostly concerns the model species Arabidopsis thaliana. Here we studied the leaf transcriptome in seedlings of maize, an important C4 crop only distantly related to A. thaliana, throughout a cycle of 10 h darkness and 14 h light to look for rhythmic patterns of gene expression. RESULTS: Using DNA microarrays comprising ca. 43,000 maize-specific probes we found that ca. 12% of all genes showed clear-cut diel rhythms of expression. Cluster analysis identified 35 groups containing from four to ca. 1,000 genes, each comprising genes of similar expression patterns. Perhaps unexpectedly, the most pronounced and most common (concerning the highest number of genes expression maxima were observed towards and during the dark phase. Using Gene Ontology classification several meaningful functional associations were found among genes showing similar diel expression patterns, including massive induction of expression of genes related to gene expression, translation, protein modification and folding at dusk and night. Additionally, we found a clear-cut tendency among genes belonging to individual clusters to share defined transcription factor-binding sequences. CONCLUSIONS: Co-expressed genes belonging to individual clusters are likely to be regulated by common mechanisms. The nocturnal phase of the diurnal cycle involves gross induction of fundamental biochemical processes and should be studied more thoroughly than was appreciated in most earlier physiological studies. Although some general mechanisms responsible for the diel regulation of gene expression might be shared among plants, details of the diurnal regulation of gene expression seem to differ

[Circadian markers and genes in bipolar disorder].

Science.gov (United States)

Yeim, S; Boudebesse, C; Etain, B; Belliviera, F

2015-09-01

Bipolar disorder is a severe and complex multifactorial disease, characterized by alternance of acute episodes of depression and mania/hypomania, interspaced by euthymic periods. The etiological determinants of bipolar disorder yet, are still poorly understood. For the last 30 years, chronobiology is an important field of investigation to better understand the pathophysiology of bipolar disorder. We conducted a review using Medline, ISI Database, EMBase, PsyInfo up to January 2015, using the following keywords combinations: "mood disorder", "bipolar disorder", "depression", "unipolar disorder", "major depressive disorder", "affective disorder", for psychiatric conditions; and "circadian rhythms", "circadian markers", "circadian gene", "clock gene", "melatonin" for circadian rhythms. The search critera was presence of word in any field of the article. Quantitative and qualitative circadian abnormalities are associated with bipolar disorders both during acute episodes and euthymic periods, suggesting that these altered circadian rhythms may represent biological trait markers of the disorder. These circadian dysfunctions were assessed by various validated tools including polysomnography, actigraphy, sleep diaries, chronotype assessments and blood melatonin/cortisol measures. Other altered endogenous circadian activities have also been reported in bipolar patients, such as hormones secretion, core body temperature or fibroblasts activity. Moreover, these markers were also altered in healthy relatives of bipolar patients, suggesting a degree of heritability. Several genetic association studies have also showed associations between multiple circadian genes and bipolar disorder, such as CLOCK, ARTNL1, GSK3β, PER3, NPAS2, NR1D1, TIMELESS, RORA, RORB, and CSNK1ε. Thus, these circadian gene variants may contribute to the genetic susceptibility of the disease. Furthermore, the study of the clock system may help to better understand some phenotypic aspects like the

Different corticospinal control between discrete and rhythmic movement of the ankle

OpenAIRE

Goto, Yumeno; Jono, Yasutomo; Hatanaka, Ryota; Nomura, Yoshifumi; Tani, Keisuke; Chujo, Yuta; Hiraoka, Koichi

2014-01-01

We investigated differences in corticospinal and spinal control between discrete and rhythmic ankle movements. Motor evoked potentials (MEPs) in the tibialis anterior and soleus muscles and soleus H-reflex were elicited in the middle of the plantar flexion phase during discrete ankle movement or in the initial or later cycles of rhythmic ankle movement. The H-reflex was evoked at an intensity eliciting a small M-wave and MEPs were elicited at an intensity of 1.2 times the motor threshold of t...

Time-frequency analysis of human motion during rhythmic exercises.

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Omkar, S N; Vyas, Khushi; Vikranth, H N

2011-01-01

Biomechanical signals due to human movements during exercise are represented in time-frequency domain using Wigner Distribution Function (WDF). Analysis based on WDF reveals instantaneous spectral and power changes during a rhythmic exercise. Investigations were carried out on 11 healthy subjects who performed 5 cycles of sun salutation, with a body-mounted Inertial Measurement Unit (IMU) as a motion sensor. Variance of Instantaneous Frequency (I.F) and Instantaneous Power (I.P) for performance analysis of the subject is estimated using one-way ANOVA model. Results reveal that joint Time-Frequency analysis of biomechanical signals during motion facilitates a better understanding of grace and consistency during rhythmic exercise.

Effects of exercise on circadian rhythms and mobility in aging Drosophila melanogaster

OpenAIRE

Rakshit, Kuntol; Wambua, Rebecca; Giebultowicz, Tomasz M.; Giebultowicz, Jadwiga M.

2013-01-01

Daily life functions such as sleep and feeding oscillate with circa 24 h period due to endogenous circadian rhythms generated by circadian clocks. Genetic or environmental disruption of circadian rhythms is associated with various aging-related phenotypes. Circadian rhythms decay during normal aging, and there is a need to explore strategies that could avert age-related changes in the circadian system. Exercise was reported to delay aging in mammals. Here, we investigated whether daily exerci...

Evidence for Multiple Rhythmic Skills

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Tierney, Adam; Kraus, Nina

2015-01-01

Rhythms, or patterns in time, play a vital role in both speech and music. Proficiency in a number of rhythm skills has been linked to language ability, suggesting that certain rhythmic processes in music and language rely on overlapping resources. However, a lack of understanding about how rhythm skills relate to each other has impeded progress in understanding how language relies on rhythm processing. In particular, it is unknown whether all rhythm skills are linked together, forming a single broad rhythmic competence, or whether there are multiple dissociable rhythm skills. We hypothesized that beat tapping and rhythm memory/sequencing form two separate clusters of rhythm skills. This hypothesis was tested with a battery of two beat tapping and two rhythm memory tests. Here we show that tapping to a metronome and the ability to adjust to a changing tempo while tapping to a metronome are related skills. The ability to remember rhythms and to drum along to repeating rhythmic sequences are also related. However, we found no relationship between beat tapping skills and rhythm memory skills. Thus, beat tapping and rhythm memory are dissociable rhythmic aptitudes. This discovery may inform future research disambiguating how distinct rhythm competencies track with specific language functions. PMID:26376489

Evidence for Multiple Rhythmic Skills.

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Adam Tierney

Full Text Available Rhythms, or patterns in time, play a vital role in both speech and music. Proficiency in a number of rhythm skills has been linked to language ability, suggesting that certain rhythmic processes in music and language rely on overlapping resources. However, a lack of understanding about how rhythm skills relate to each other has impeded progress in understanding how language relies on rhythm processing. In particular, it is unknown whether all rhythm skills are linked together, forming a single broad rhythmic competence, or whether there are multiple dissociable rhythm skills. We hypothesized that beat tapping and rhythm memory/sequencing form two separate clusters of rhythm skills. This hypothesis was tested with a battery of two beat tapping and two rhythm memory tests. Here we show that tapping to a metronome and the ability to adjust to a changing tempo while tapping to a metronome are related skills. The ability to remember rhythms and to drum along to repeating rhythmic sequences are also related. However, we found no relationship between beat tapping skills and rhythm memory skills. Thus, beat tapping and rhythm memory are dissociable rhythmic aptitudes. This discovery may inform future research disambiguating how distinct rhythm competencies track with specific language functions.

Rhythmic entrainment source separation: Optimizing analyses of neural responses to rhythmic sensory stimulation.

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Cohen, Michael X; Gulbinaite, Rasa

2017-02-15

Steady-state evoked potentials (SSEPs) are rhythmic brain responses to rhythmic sensory stimulation, and are often used to study perceptual and attentional processes. We present a data analysis method for maximizing the signal-to-noise ratio of the narrow-band steady-state response in the frequency and time-frequency domains. The method, termed rhythmic entrainment source separation (RESS), is based on denoising source separation approaches that take advantage of the simultaneous but differential projection of neural activity to multiple electrodes or sensors. Our approach is a combination and extension of existing multivariate source separation methods. We demonstrate that RESS performs well on both simulated and empirical data, and outperforms conventional SSEP analysis methods based on selecting electrodes with the strongest SSEP response, as well as several other linear spatial filters. We also discuss the potential confound of overfitting, whereby the filter captures noise in absence of a signal. Matlab scripts are available to replicate and extend our simulations and methods. We conclude with some practical advice for optimizing SSEP data analyses and interpreting the results. Copyright © 2016 Elsevier Inc. All rights reserved.

Individualization of music-based rhythmic auditory cueing in Parkinson's disease.

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Bella, Simone Dalla; Dotov, Dobromir; Bardy, Benoît; de Cock, Valérie Cochen

2018-06-04

Gait dysfunctions in Parkinson's disease can be partly relieved by rhythmic auditory cueing. This consists in asking patients to walk with a rhythmic auditory stimulus such as a metronome or music. The effect on gait is visible immediately in terms of increased speed and stride length. Moreover, training programs based on rhythmic cueing can have long-term benefits. The effect of rhythmic cueing, however, varies from one patient to the other. Patients' response to the stimulation may depend on rhythmic abilities, often deteriorating with the disease. Relatively spared abilities to track the beat favor a positive response to rhythmic cueing. On the other hand, most patients with poor rhythmic abilities either do not respond to the cues or experience gait worsening when walking with cues. An individualized approach to rhythmic auditory cueing with music is proposed to cope with this variability in patients' response. This approach calls for using assistive mobile technologies capable of delivering cues that adapt in real time to patients' gait kinematics, thus affording step synchronization to the beat. Individualized rhythmic cueing can provide a safe and cost-effective alternative to standard cueing that patients may want to use in their everyday lives. © 2018 New York Academy of Sciences.

Coordination of the maize transcriptome by a conserved circadian clock

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Harmon Frank G

2010-06-01

Full Text Available Abstract Background The plant circadian clock orchestrates 24-hour rhythms in internal physiological processes to coordinate these activities with daily and seasonal changes in the environment. The circadian clock has a profound impact on many aspects of plant growth and development, including biomass accumulation and flowering time. Despite recent advances in understanding the circadian system of the model plant Arabidopsis thaliana, the contribution of the circadian oscillator to important agronomic traits in Zea mays and other cereals remains poorly defined. To address this deficit, this study investigated the transcriptional landscape of the maize circadian system. Results Since transcriptional regulation is a fundamental aspect of circadian systems, genes exhibiting circadian expression were identified in the sequenced maize inbred B73. Of the over 13,000 transcripts examined, approximately 10 percent displayed circadian expression patterns. The majority of cycling genes had peak expression at subjective dawn and dusk, similar to other plant circadian systems. The maize circadian clock organized co-regulation of genes participating in fundamental physiological processes, including photosynthesis, carbohydrate metabolism, cell wall biogenesis, and phytohormone biosynthesis pathways. Conclusions Circadian regulation of the maize genome was widespread and key genes in several major metabolic pathways had circadian expression waveforms. The maize circadian clock coordinated transcription to be coincident with oncoming day or night, which was consistent with the circadian oscillator acting to prepare the plant for these major recurring environmental changes. These findings highlighted the multiple processes in maize plants under circadian regulation and, as a result, provided insight into the important contribution this regulatory system makes to agronomic traits in maize and potentially other C4 plant species.

Circadian modulation of short-term memory in Drosophila.

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Lyons, Lisa C; Roman, Gregg

2009-01-01

Endogenous biological clocks are widespread regulators of behavior and physiology, allowing for a more efficient allocation of efforts and resources over the course of a day. The extent that different processes are regulated by circadian oscillators, however, is not fully understood. We investigated the role of the circadian clock on short-term associative memory formation using a negatively reinforced olfactory-learning paradigm in Drosophila melanogaster. We found that memory formation was regulated in a circadian manner. The peak performance in short-term memory (STM) occurred during the early subjective night with a twofold performance amplitude after a single pairing of conditioned and unconditioned stimuli. This rhythm in memory is eliminated in both timeless and period mutants and is absent during constant light conditions. Circadian gating of sensory perception does not appear to underlie the rhythm in short-term memory as evidenced by the nonrhythmic shock avoidance and olfactory avoidance behaviors. Moreover, central brain oscillators appear to be responsible for the modulation as cryptochrome mutants, in which the antennal circadian oscillators are nonfunctional, demonstrate robust circadian rhythms in short-term memory. Together these data suggest that central, rather than peripheral, circadian oscillators modulate the formation of short-term associative memory and not the perception of the stimuli.

Circadian Modulation of Short-Term Memory in "Drosophila"

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Lyons, Lisa C.; Roman, Gregg

2009-01-01

Endogenous biological clocks are widespread regulators of behavior and physiology, allowing for a more efficient allocation of efforts and resources over the course of a day. The extent that different processes are regulated by circadian oscillators, however, is not fully understood. We investigated the role of the circadian clock on short-term…

Circadian Rhythms, Sleep Deprivation, and Human Performance

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Goel, Namni; Basner, Mathias; Rao, Hengyi; Dinges, David F.

2014-01-01

Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep–wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance. Endogenous circadian rhythms in neurobehavioral functions, including physiological alertness and cognitive performance, have been demonstrated using special laboratory protocols that reveal the interaction of the biological clock with the sleep homeostatic drive. Individual differences in circadian rhythms and genetic and other components underlying such differences also influence waking neurobehavioral functions. Both acute total sleep deprivation and chronic sleep restriction increase homeostatic sleep drive and degrade waking neurobehavioral functions as reflected in sleepiness, attention, cognitive speed, and memory. Recent evidence indicating a high degree of stability in neurobehavioral responses to sleep loss suggests that these trait-like individual differences are phenotypic and likely involve genetic components, including circadian genes. Recent experiments have revealed both sleep homeostatic and circadian effects on brain metabolism and neural activation. Investigation of the neural and genetic mechanisms underlying the dynamically complex interaction between sleep homeostasis and circadian systems is beginning. A key goal of this work is to identify biomarkers that accurately predict human performance in situations in which the circadian and sleep homeostatic systems are perturbed. PMID:23899598

Sympathetic network drive during water deprivation does not increase respiratory or cardiac rhythmic sympathetic nerve activity.

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Holbein, Walter W; Toney, Glenn M

2013-06-15

Effects of water deprivation on rhythmic bursting of sympathetic nerve activity (SNA) were investigated in anesthetized, bilaterally vagotomized, euhydrated (control) and 48-h water-deprived (WD) rats (n = 8/group). Control and WD rats had similar baseline values of mean arterial pressure, heart rate, end-tidal CO2, and central respiratory drive. Although integrated splanchnic SNA (sSNA) was greater in WD rats than controls (P analysis of respiratory rhythmic bursting of sSNA revealed that inspiratory rhythmic burst amplitude was actually smaller (P analysis revealed that water deprivation had no effect on either the amplitude or periodicity of the cardiac rhythmic oscillation of sSNA. Collectively, these data indicate that the increase of sSNA produced by water deprivation is not attributable to either increased respiratory or cardiac rhythmic burst discharge. Thus the sympathetic network response to acute water deprivation appears to differ from that of chronic sympathoexcitation in neurogenic forms of arterial hypertension, where increased respiratory rhythmic bursting of SNA and baroreflex adaptations have been reported.

Enhanced musical rhythmic perception in Turkish early and late learners of German

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Maria Paula eRoncaglia-Denissen

2013-09-01

Full Text Available As language rhythm relies partly on general acoustic properties, such as intensity and duration, mastering two languages with distinct rhythmic properties (i.e., stress position may enhance musical rhythm perception. We investigated whether second language (L2 competence affects musical rhythm aptitude in Turkish early (TELG and late learners (TLLG of German in comparison to German monolingual speakers (GMC. To account for inter-individual differences, we measured participants’ short-term and working memory capacity, melodic aptitude, and time they spent listening to music. Both L2 speaker groups perceived rhythmic variations significantly better than monolinguals. No differences were found between early and late learners’ performances. Our findings suggest that mastering two languages with different rhythmic properties enhances musical rhythm perception, providing further evidence of cognitive share between language and music.

The bZIP transcription factor HY5 interacts with the promoter of the monoterpene synthase gene QH6 in modulating its rhythmic expression

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Fei eZhou

2015-04-01

Full Text Available The Artemisia annua L. β-pinene synthase QH6 was previously determined to be circadian-regulated at the transcriptional level, showing a rhythmic fluctuation of steady-state transcript abundances. Here we isolated both the genomic sequence and upstream promoter region of QH6. Different regulatory elements, such as G-box (TGACACGTGGCA, -421 bp from the translation initiation site which might have effects on rhythmic gene expression, were found. Using the yeast one-hybrid and electrophoretic mobility shift assay (EMSA, we confirmed that the bZIP transcription factor HY5 binds to this motif of QH6. Studies with promoter truncations before and after this motif suggested that this G-box was important for the diurnal fluctuation of the transgenic β-glucuronidase gene (GUS transcript abundance in Arabidopsis thaliana. GUS gene driven by the promoter region immediately after G-box showed an arrhythmic expression in both light/dark (LD and constant dark (DD conditions, whereas the control with G-box retained its fluctuation in both LD and DD. We further transformed A. thaliana with the luciferase gene (LUC driven by an 1400 bp fragment upstream QH6 with its G-box intact or mutated, respectively. The luciferase activity assay showed that a peak in the early morning disappeared in the mutant. Gene expression analysis also demonstrated that the rhythmic expression of LUC was abolished in the hy5-1 mutant.

Circadian Clock Proteins and Melatonin Receptors in Neurons and Glia of the Sapajus apella Cerebellum

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Leila M. Guissoni Campos

2018-02-01

Full Text Available Oscillations of brain proteins in circadian rhythms are important for determining several cellular and physiological processes in anticipation of daily and seasonal environmental rhythms. In addition to the suprachiasmatic nucleus, the primary central oscillator, the cerebellum shows oscillations in gene and protein expression. The variety of local circuit rhythms that the cerebellar cortex contains influences functions such as motivational processes, regulation of feeding, food anticipation, language, and working memory. The molecular basis of the cerebellar oscillator has been demonstrated by “clock gene” expression within cells of the cerebellar layers. Genetic and epidemiological evidence suggests that disruption of circadian rhythms in humans can lead to many pathological conditions. Despite this importance, data about clock gene and protein expression in the cerebellum of diurnal (day-active species, specifically primates, is currently poorly explored, mainly in regard to cellular identity, as well as the relationship with other molecules also involved in cerebellar functions. These studies could contribute to clarification of the possible mechanisms behind cerebellar rhythmicity. Considering that calcium binding proteins (CaBPs play crucial roles in preserving and modulating cerebellar functions and that clock gene expression can be controlled by afferent projections or paracrine circadian signals such as the hormone melatonin, the present study aimed to describe cellular identities, distribution patterns and day/night expression changes in PER1, PER2, CaBPs, and MT1 and MT2 melatonin receptors in the cerebellar cortex of a diurnal primate using conventional fluorescence and peroxidase-antiperoxidase immunocytochemical techniques. PER1 and PER2 immunoreactive (IR cells were observed in the Purkinje cells of the cerebellum, and MT1 and MT2 receptors were localized around Purkinje cells in the Pj layer in Bergmann cells. This identity

Rhythmic abilities and musical training in Parkinson's disease: do they help?

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Cochen De Cock, V; Dotov, D G; Ihalainen, P; Bégel, V; Galtier, F; Lebrun, C; Picot, M C; Driss, V; Landragin, N; Geny, C; Bardy, B; Dalla Bella, S

2018-01-01

Rhythmic auditory cues can immediately improve gait in Parkinson's disease. However, this effect varies considerably across patients. The factors associated with this individual variability are not known to date. Patients' rhythmic abilities and musicality (e.g., perceptual and singing abilities, emotional response to music, and musical training) may foster a positive response to rhythmic cues. To examine this hypothesis, we measured gait at baseline and with rhythmic cues in 39 non-demented patients with Parkinson's disease and 39 matched healthy controls. Cognition, rhythmic abilities and general musicality were assessed. A response to cueing was qualified as positive when the stimulation led to a clinically meaningful increase in gait speed. We observed that patients with positive response to cueing ( n  = 17) were more musically trained, aligned more often their steps to the rhythmic cues while walking, and showed better music perception as well as poorer cognitive flexibility than patients with non-positive response ( n  = 22). Gait performance with rhythmic cues worsened in six patients. We concluded that rhythmic and musical skills, which can be modulated by musical training, may increase beneficial effects of rhythmic auditory cueing in Parkinson's disease. Screening patients in terms of musical/rhythmic abilities and musical training may allow teasing apart patients who are likely to benefit from cueing from those who may worsen their performance due to the stimulation.

Symptom clusters in cancer patients and their relation to EGFR ligand modulation of the circadian axis.

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Rich, Tyvin A

2007-04-01

Recent studies in chronobiology and the neurosciences have led to rapid growth in our understanding of the molecular biology of the human timekeeping apparatus and the neuroanatomic sites involved in signaling between the "master clock" in the hypothalamus and other parts of the brain. The circadian axis comprises a central clock mechanism and a downstream network of hypothalamic relay stations that modulate arousal, feeding, and sleeping behavior. Communication between the clock and these hypothalamic signaling centers is mediated, in part, by diffusible substances that include ligands of the epidermal growth factor receptor (EGFR). Preclinical studies reveal that EGFR ligands such as transforming growth factor-alpha (TGF-alpha) inhibit hypothalamic signaling of rhythmic behavior; clinical observations show that elevated levels of TGF-alpha are associated with fatigue, flattened circadian rhythms, and loss of appetite in patients with metastatic colorectal cancer. These data support the hypothesis that a symptom cluster of fatigue, appetite loss, and sleep disruption commonly seen in cancer patients may be related to EGFR ligands, released either by the cancer itself or by the host in response to the stress of cancer, and suggest that further examination of their role in the production of symptom clustering is warranted.

Circadian response of annual weeds to glyphosate and glufosinate.

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Martinson, Krishona B; Sothern, Robert B; Koukkari, Willard L; Durgan, Beverly R; Gunsolus, Jeffrey L

2002-03-01

Five field experiments were conducted in 1998 and 1999 in Minnesota to examine the influence of time of day efficacy of glyphosate [N-(phosphonomethyl)glycine] and glufosinate [2-amino-4-(hydroxymethyl-phosphinyl)butanoic acid] applications on the control of annual weeds. Each experiment was designed to be a randomized complete block with four replications using plot sizes of 3 x 9 m. Glyphosate and glufosinate were applied at rates of 0.421 kg ae/ha and 0.292 kg ai/ha, respectively, with and without an additional adjuvant that consisted of 20% nonionic surfactant and 80% ammonium sulfate. All treatments were applied with water at 94 L/ha. Times of day for the application of herbicide were 06:00h, 09:00h, 12:00h, 15:00h, 18:00h, 21:00h, and 24:00h. Efficacy was evaluated 14 d after application by visual ratings. At 14 d, a circadian response to each herbicide was found, with greatest annual weed control observed with an application occurring between 09:00h and 18:00h and significantly less weed control observed with an application at 06:00h, 21:00h, or 24:00h. The addition of an adjuvant to both herbicides increased overall efficacy, but did not overcome the rhythmic time of day effect. Results of the multiple regression analysis showed that after environmental temperature, time of day was the second most important predictor of percent weed kill. Thus, circadian timing of herbicide application significantly influenced weed control with both glyphosate and glufosinate.

Genome-wide analysis of SREBP1 activity around the clock reveals its combined dependency on nutrient and circadian signals.

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Federica Gilardi

2014-03-01

Full Text Available In mammals, the circadian clock allows them to anticipate and adapt physiology around the 24 hours. Conversely, metabolism and food consumption regulate the internal clock, pointing the existence of an intricate relationship between nutrient state and circadian homeostasis that is far from being understood. The Sterol Regulatory Element Binding Protein 1 (SREBP1 is a key regulator of lipid homeostasis. Hepatic SREBP1 function is influenced by the nutrient-response cycle, but also by the circadian machinery. To systematically understand how the interplay of circadian clock and nutrient-driven rhythm regulates SREBP1 activity, we evaluated the genome-wide binding of SREBP1 to its targets throughout the day in C57BL/6 mice. The recruitment of SREBP1 to the DNA showed a highly circadian behaviour, with a maximum during the fed status. However, the temporal expression of SREBP1 targets was not always synchronized with its binding pattern. In particular, different expression phases were observed for SREBP1 target genes depending on their function, suggesting the involvement of other transcription factors in their regulation. Binding sites for Hepatocyte Nuclear Factor 4 (HNF4 were specifically enriched in the close proximity of SREBP1 peaks of genes, whose expression was shifted by about 8 hours with respect to SREBP1 binding. Thus, the cross-talk between hepatic HNF4 and SREBP1 may underlie the expression timing of this subgroup of SREBP1 targets. Interestingly, the proper temporal expression profile of these genes was dramatically changed in Bmal1-/- mice upon time-restricted feeding, for which a rhythmic, but slightly delayed, binding of SREBP1 was maintained. Collectively, our results show that besides the nutrient-driven regulation of SREBP1 nuclear translocation, a second layer of modulation of SREBP1 transcriptional activity, strongly dependent from the circadian clock, exists. This system allows us to fine tune the expression timing of SREBP1

Genome-Wide Analysis of SREBP1 Activity around the Clock Reveals Its Combined Dependency on Nutrient and Circadian Signals

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Naldi, Aurélien; Baruchet, Michaël; Canella, Donatella; Le Martelot, Gwendal; Guex, Nicolas; Desvergne, Béatrice; Delorenzi, Mauro; Deplancke, Bart; Desvergne, Béatrice; Guex, Nicolas; Herr, Winship; Naef, Felix; Rougemont, Jacques; Schibler, Ueli; Deplancke, Bart; Guex, Nicolas; Herr, Winship; Guex, Nicolas; Andersin, Teemu; Cousin, Pascal; Gilardi, Federica; Gos, Pascal; Martelot, Gwendal Le; Lammers, Fabienne; Canella, Donatella; Gilardi, Federica; Raghav, Sunil; Fabbretti, Roberto; Fortier, Arnaud; Long, Li; Vlegel, Volker; Xenarios, Ioannis; Migliavacca, Eugenia; Praz, Viviane; Guex, Nicolas; Naef, Felix; Rougemont, Jacques; David, Fabrice; Jarosz, Yohan; Kuznetsov, Dmitry; Liechti, Robin; Martin, Olivier; Delafontaine, Julien; Sinclair, Lucas; Cajan, Julia; Krier, Irina; Leleu, Marion; Migliavacca, Eugenia; Molina, Nacho; Naldi, Aurélien; Rey, Guillaume; Symul, Laura; Guex, Nicolas; Naef, Felix; Rougemont, Jacques; Bernasconi, David; Delorenzi, Mauro; Andersin, Teemu; Canella, Donatella; Gilardi, Federica; Martelot, Gwendal Le; Lammers, Fabienne; Baruchet, Michaël; Raghav, Sunil

2014-01-01

In mammals, the circadian clock allows them to anticipate and adapt physiology around the 24 hours. Conversely, metabolism and food consumption regulate the internal clock, pointing the existence of an intricate relationship between nutrient state and circadian homeostasis that is far from being understood. The Sterol Regulatory Element Binding Protein 1 (SREBP1) is a key regulator of lipid homeostasis. Hepatic SREBP1 function is influenced by the nutrient-response cycle, but also by the circadian machinery. To systematically understand how the interplay of circadian clock and nutrient-driven rhythm regulates SREBP1 activity, we evaluated the genome-wide binding of SREBP1 to its targets throughout the day in C57BL/6 mice. The recruitment of SREBP1 to the DNA showed a highly circadian behaviour, with a maximum during the fed status. However, the temporal expression of SREBP1 targets was not always synchronized with its binding pattern. In particular, different expression phases were observed for SREBP1 target genes depending on their function, suggesting the involvement of other transcription factors in their regulation. Binding sites for Hepatocyte Nuclear Factor 4 (HNF4) were specifically enriched in the close proximity of SREBP1 peaks of genes, whose expression was shifted by about 8 hours with respect to SREBP1 binding. Thus, the cross-talk between hepatic HNF4 and SREBP1 may underlie the expression timing of this subgroup of SREBP1 targets. Interestingly, the proper temporal expression profile of these genes was dramatically changed in Bmal1 −/− mice upon time-restricted feeding, for which a rhythmic, but slightly delayed, binding of SREBP1 was maintained. Collectively, our results show that besides the nutrient-driven regulation of SREBP1 nuclear translocation, a second layer of modulation of SREBP1 transcriptional activity, strongly dependent from the circadian clock, exists. This system allows us to fine tune the expression timing of SREBP1 target genes

Age-Related Changes in the Expression of the Circadian Clock Protein PERIOD in Drosophila Glial Cells

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Dani M. Long

2018-01-01

Full Text Available Circadian clocks consist of molecular negative feedback loops that coordinate physiological, neurological, and behavioral variables into “circa” 24-h rhythms. Rhythms in behavioral and other circadian outputs tend to weaken during aging, as evident in progressive disruptions of sleep-wake cycles in aging organisms. However, less is known about the molecular changes in the expression of clock genes and proteins that may lead to the weakening of circadian outputs. Western blot studies have demonstrated that the expression of the core clock protein PERIOD (PER declines in the heads of aged Drosophila melanogaster flies. This age-related decline in PER does not occur in the central pacemaker neurons but has been demonstrated so far in retinal photoreceptors. Besides photoreceptors, clock proteins are also expressed in fly glia, which play important roles in neuronal homeostasis and are further categorized into subtypes based on morphology and function. While previous studies of mammalian glial cells have demonstrated the presence of functional clocks in astrocytes and microglia, it is not known which glial cell types in Drosophila express clock proteins and how their expression may change in aged individuals. Here, we conducted immunocytochemistry experiments to identify which glial subtypes express PER protein suggestive of functional circadian clocks. Glial cell subtypes that showed night-time accumulation and day-time absence in PER consistent with oscillations reported in the pacemaker neurons were selected to compare the level of PER protein between young and old flies. Our data demonstrate that some glial subtypes show rhythmic PER expression and the relative PER levels become dampened with advanced age. Identification of glial cell types that display age-related dampening of PER levels may help to understand the cellular changes that contribute to the loss of homeostasis in the aging brain.

The role of alternative Polyadenylation in regulation of rhythmic gene expression.

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Ptitsyna, Natalia; Boughorbel, Sabri; El Anbari, Mohammed; Ptitsyn, Andrey

2017-08-04

Alternative transcription is common in eukaryotic cells and plays important role in regulation of cellular processes. Alternative polyadenylation results from ambiguous PolyA signals in 3' untranslated region (UTR) of a gene. Such alternative transcripts share the same coding part, but differ by a stretch of UTR that may contain important functional sites. The methodoogy of this study is based on mathematical modeling, analytical solution, and subsequent validation by datamining in multiple independent experimental data from previously published studies. In this study we propose a mathematical model that describes the population dynamics of alternatively polyadenylated transcripts in conjunction with rhythmic expression such as transcription oscillation driven by circadian or metabolic oscillators. Analysis of the model shows that alternative transcripts with different turnover rates acquire a phase shift if the transcript decay rate is different. Difference in decay rate is one of the consequences of alternative polyadenylation. Phase shift can reach values equal to half the period of oscillation, which makes alternative transcripts oscillate in abundance in counter-phase to each other. Since counter-phased transcripts share the coding part, the rate of translation becomes constant. We have analyzed a few data sets collected in circadian timeline for the occurrence of transcript behavior that fits the mathematical model. Alternative transcripts with different turnover rate create the effect of rectifier. This "molecular diode" moderates or completely eliminates oscillation of individual transcripts and stabilizes overall protein production rate. In our observation this phenomenon is very common in different tissues in plants, mice, and humans. The occurrence of counter-phased alternative transcripts is also tissue-specific and affects functions of multiple biological pathways. Accounting for this mechanism is important for understanding the natural and engineering

Situational influences on rhythmicity in speech, music, and their interaction.

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Hawkins, Sarah

2014-12-19

Brain processes underlying the production and perception of rhythm indicate considerable flexibility in how physical signals are interpreted. This paper explores how that flexibility might play out in rhythmicity in speech and music. There is much in common across the two domains, but there are also significant differences. Interpretations are explored that reconcile some of the differences, particularly with respect to how functional properties modify the rhythmicity of speech, within limits imposed by its structural constraints. Functional and structural differences mean that music is typically more rhythmic than speech, and that speech will be more rhythmic when the emotions are more strongly engaged, or intended to be engaged. The influence of rhythmicity on attention is acknowledged, and it is suggested that local increases in rhythmicity occur at times when attention is required to coordinate joint action, whether in talking or music-making. Evidence is presented which suggests that while these short phases of heightened rhythmical behaviour are crucial to the success of transitions in communicative interaction, their modality is immaterial: they all function to enhance precise temporal prediction and hence tightly coordinated joint action. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Situational influences on rhythmicity in speech, music, and their interaction

Science.gov (United States)

Hawkins, Sarah

2014-01-01

Brain processes underlying the production and perception of rhythm indicate considerable flexibility in how physical signals are interpreted. This paper explores how that flexibility might play out in rhythmicity in speech and music. There is much in common across the two domains, but there are also significant differences. Interpretations are explored that reconcile some of the differences, particularly with respect to how functional properties modify the rhythmicity of speech, within limits imposed by its structural constraints. Functional and structural differences mean that music is typically more rhythmic than speech, and that speech will be more rhythmic when the emotions are more strongly engaged, or intended to be engaged. The influence of rhythmicity on attention is acknowledged, and it is suggested that local increases in rhythmicity occur at times when attention is required to coordinate joint action, whether in talking or music-making. Evidence is presented which suggests that while these short phases of heightened rhythmical behaviour are crucial to the success of transitions in communicative interaction, their modality is immaterial: they all function to enhance precise temporal prediction and hence tightly coordinated joint action. PMID:25385776

Comparison of rhythmic masticatory muscle activity during non-rapid eye movement sleep in guinea pigs and humans.

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Kato, Takafumi; Toyota, Risa; Haraki, Shingo; Yano, Hiroyuki; Higashiyama, Makoto; Ueno, Yoshio; Yano, Hiroshi; Sato, Fumihiko; Yatani, Hirofumi; Yoshida, Atsushi

2017-09-27

Rhythmic masticatory muscle activity can be a normal variant of oromotor activity, which can be exaggerated in patients with sleep bruxism. However, few studies have tested the possibility in naturally sleeping animals to study the neurophysiological mechanisms of rhythmic masticatory muscle activity. This study aimed to investigate the similarity of cortical, cardiac and electromyographic manifestations of rhythmic masticatory muscle activity occurring during non-rapid eye movement sleep between guinea pigs and human subjects. Polysomnographic recordings were made in 30 freely moving guinea pigs and in eight healthy human subjects. Burst cycle length, duration and activity of rhythmic masticatory muscle activity were compared with those for chewing. The time between R-waves in the electrocardiogram (RR interval) and electroencephalogram power spectrum were calculated to assess time-course changes in cardiac and cortical activities in relation to rhythmic masticatory muscle activity. In animals, in comparison with chewing, rhythmic masticatory muscle activity had a lower burst activity, longer burst duration and longer cycle length (P motor activation in comparison to human subjects. © 2017 European Sleep Research Society.

Obesity Disrupts the Rhythmic Profiles of Maternal and Fetal Progesterone in Rat Pregnancy.

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Crew, Rachael C; Mark, Peter J; Clarke, Michael W; Waddell, Brendan J

2016-09-01

Maternal obesity increases the risk of abnormal fetal growth, but the underlying mechanisms remain unclear. Because steroid hormones regulate fetal growth, and both pregnancy and obesity markedly alter circadian biology, we hypothesized that maternal obesity disrupts the normal rhythmic profiles of steroid hormones in rat pregnancy. Obesity was established by cafeteria (CAF) feeding for 8 wk prior to mating and throughout pregnancy. Control (CON) animals had ad libitum access to chow. Daily profiles of plasma corticosterone, 11-dehydrocorticosterone, progesterone, and testosterone were measured at Days 15 and 21 of gestation (term = 23 days) in maternal (both days) and fetal (Day 21) plasma. CAF mothers exhibited increased adiposity relative to CON and showed fetal and placental growth restriction. There was no change, however, in total fetal or placental mass due to slightly larger litter sizes in CAF. Nocturnal declines in progesterone were observed in maternal (39% lower) and fetal (45% lower) plasma in CON animals, but these were absent in CAF animals. CAF mothers were hyperlipidemic at both days of gestation, but this effect was isolated to the dark period at Day 21. CAF maternal testosterone was slightly lower at Day 15 (8%) but increased above CON by Day 21 (16%). Despite elevated maternal testosterone, male fetal testosterone was suppressed by obesity on Day 21. Neither maternal nor fetal glucocorticoid profiles were affected by obesity. In conclusion, obesity disrupts rhythmic profiles of maternal and fetal progesterone, preventing the normal nocturnal decline. Obesity subtly changed testosterone profiles but did not alter maternal and fetal glucocorticoids. © 2016 by the Society for the Study of Reproduction, Inc.

Circadian Dynamics of the Cone-Rod Homeobox (CRX) Transcription Factor in the Rat Pineal Gland and Its Role in Regulation of Arylalkylamine N-Acetyltransferase (AANAT)

DEFF Research Database (Denmark)

Rohde, Kristian; Rovsing, Louise; Ho, Anthony K

2014-01-01

that intact levels of Crx mRNA are required to obtain high levels of Aanat expression, whereas overexpression of Crx induces Aanat transcription in vitro. This regulatory function of Crx is further supported by circadian analysis of Aanat in the pineal gland of the Crx-knockout mouse. Our data indicate...... that the rhythmic nature of pineal CRX protein may directly modulate the daily profile of Aanat expression by inducing nighttime expression of this enzyme, thus facilitating nocturnal melatonin synthesis in addition to its role in ensuring a correct tissue distribution of Aanat expression....

Music Games: Potential Application and Considerations for Rhythmic Training.

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Bégel, Valentin; Di Loreto, Ines; Seilles, Antoine; Dalla Bella, Simone

2017-01-01

Rhythmic skills are natural and widespread in the general population. The majority can track the beat of music and move along with it. These abilities are meaningful from a cognitive standpoint given their tight links with prominent motor and cognitive functions such as language and memory. When rhythmic skills are challenged by brain damage or neurodevelopmental disorders, remediation strategies based on rhythm can be considered. For example, rhythmic training can be used to improve motor performance (e.g., gait) as well as cognitive and language skills. Here, we review the games readily available in the market and assess whether they are well-suited for rhythmic training. Games that train rhythm skills may serve as useful tools for retraining motor and cognitive functions in patients with motor or neurodevelopmental disorders (e.g., Parkinson's disease, dyslexia, or ADHD). Our criteria were the peripheral used to capture and record the response, the type of response and the output measure. None of the existing games provides sufficient temporal precision in stimulus presentation and/or data acquisition. In addition, games do not train selectively rhythmic skills. Hence, the available music games, in their present form, are not satisfying for training rhythmic skills. Yet, some features such as the device used, the interface or the game scenario provide good indications for devising efficient training protocols. Guidelines are provided for devising serious music games targeting rhythmic training in the future.

Music Games: Potential Application and Considerations for Rhythmic Training

Directory of Open Access Journals (Sweden)

Valentin Bégel

2017-05-01

Full Text Available Rhythmic skills are natural and widespread in the general population. The majority can track the beat of music and move along with it. These abilities are meaningful from a cognitive standpoint given their tight links with prominent motor and cognitive functions such as language and memory. When rhythmic skills are challenged by brain damage or neurodevelopmental disorders, remediation strategies based on rhythm can be considered. For example, rhythmic training can be used to improve motor performance (e.g., gait as well as cognitive and language skills. Here, we review the games readily available in the market and assess whether they are well-suited for rhythmic training. Games that train rhythm skills may serve as useful tools for retraining motor and cognitive functions in patients with motor or neurodevelopmental disorders (e.g., Parkinson’s disease, dyslexia, or ADHD. Our criteria were the peripheral used to capture and record the response, the type of response and the output measure. None of the existing games provides sufficient temporal precision in stimulus presentation and/or data acquisition. In addition, games do not train selectively rhythmic skills. Hence, the available music games, in their present form, are not satisfying for training rhythmic skills. Yet, some features such as the device used, the interface or the game scenario provide good indications for devising efficient training protocols. Guidelines are provided for devising serious music games targeting rhythmic training in the future.

The evolution of locomotor rhythmicity in tetrapods.

Science.gov (United States)

Ross, Callum F; Blob, Richard W; Carrier, David R; Daley, Monica A; Deban, Stephen M; Demes, Brigitte; Gripper, Janaya L; Iriarte-Diaz, Jose; Kilbourne, Brandon M; Landberg, Tobias; Polk, John D; Schilling, Nadja; Vanhooydonck, Bieke

2013-04-01

Differences in rhythmicity (relative variance in cycle period) among mammal, fish, and lizard feeding systems have been hypothesized to be associated with differences in their sensorimotor control systems. We tested this hypothesis by examining whether the locomotion of tachymetabolic tetrapods (birds and mammals) is more rhythmic than that of bradymetabolic tetrapods (lizards, alligators, turtles, salamanders). Species averages of intraindividual coefficients of variation in cycle period were compared while controlling for gait and substrate. Variance in locomotor cycle periods is significantly lower in tachymetabolic than in bradymetabolic animals for datasets that include treadmill locomotion, non-treadmill locomotion, or both. When phylogenetic relationships are taken into account the pooled analyses remain significant, whereas the non-treadmill and the treadmill analyses become nonsignificant. The co-occurrence of relatively high rhythmicity in both feeding and locomotor systems of tachymetabolic tetrapods suggests that the anatomical substrate of rhythmicity is in the motor control system, not in the musculoskeletal components. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Understanding Epileptiform After-Discharges as Rhythmic Oscillatory Transients.

Science.gov (United States)

Baier, Gerold; Taylor, Peter N; Wang, Yujiang

2017-01-01

Electro-cortical activity in patients with epilepsy may show abnormal rhythmic transients in response to stimulation. Even when using the same stimulation parameters in the same patient, wide variability in the duration of transient response has been reported. These transients have long been considered important for the mapping of the excitability levels in the epileptic brain but their dynamic mechanism is still not well understood. To investigate the occurrence of abnormal transients dynamically, we use a thalamo-cortical neural population model of epileptic spike-wave activity and study the interaction between slow and fast subsystems. In a reduced version of the thalamo-cortical model, slow wave oscillations arise from a fold of cycles (FoC) bifurcation. This marks the onset of a region of bistability between a high amplitude oscillatory rhythm and the background state. In vicinity of the bistability in parameter space, the model has excitable dynamics, showing prolonged rhythmic transients in response to suprathreshold pulse stimulation. We analyse the state space geometry of the bistable and excitable states, and find that the rhythmic transient arises when the impending FoC bifurcation deforms the state space and creates an area of locally reduced attraction to the fixed point. This area essentially allows trajectories to dwell there before escaping to the stable steady state, thus creating rhythmic transients. In the full thalamo-cortical model, we find a similar FoC bifurcation structure. Based on the analysis, we propose an explanation of why stimulation induced epileptiform activity may vary between trials, and predict how the variability could be related to ongoing oscillatory background activity. We compare our dynamic mechanism with other mechanisms (such as a slow parameter change) to generate excitable transients, and we discuss the proposed excitability mechanism in the context of stimulation responses in the epileptic cortex.

Circadian rhythms, food timing and obesity.

Science.gov (United States)

Lopez-Minguez, J; Gómez-Abellán, P; Garaulet, M

2016-11-01

It is known that our physiology changes throughout the day and that several physiological hormones display circadian rhythmicity. The alteration of this normal pattern is called chronodisruption (CD). In recent years, it has been demonstrated that CD is related to obesity. Although several factors may be causing CD, one important aspect to consider is the failure in our internal clock. Indeed, studies performed in mutant animals have demonstrated that mutations in clock genes are related to obesity. In human subjects, mutations are rare (obesity and weight loss. Taking into account that genetics is behind CD, as has already been demonstrated in twins' models, the question is: Are we predestinated? We will see along these lines that nutrigenetics and epigenetics answer: 'No, we are not predestinated'. Through nutrigenetics we know that our behaviours may interact with our genes and may decrease the deleterious effect of one specific risk variant. From epigenetics the message is even more positive: it is demonstrated that by changing our behaviours we can change our genome. Herein, we propose modifying 'what, how, and when we eat' as an effective tool to decrease our genetic risk, and as a consequence to diminish CD and decrease obesity. This is a novel and very promising area in obesity prevention and treatment.

Relationships between early literacy and nonlinguistic rhythmic processes in kindergarteners.

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Ozernov-Palchik, Ola; Wolf, Maryanne; Patel, Aniruddh D

2018-03-01

A growing number of studies report links between nonlinguistic rhythmic abilities and certain linguistic abilities, particularly phonological skills. The current study investigated the relationship between nonlinguistic rhythmic processing, phonological abilities, and early literacy abilities in kindergarteners. A distinctive aspect of the current work was the exploration of whether processing of different types of rhythmic patterns is differentially related to kindergarteners' phonological and reading-related abilities. Specifically, we examined the processing of metrical versus nonmetrical rhythmic patterns, that is, patterns capable of being subdivided into equal temporal intervals or not (Povel & Essens, 1985). This is an important comparison because most music involves metrical sequences, in which rhythm often has an underlying temporal grid of isochronous units. In contrast, nonmetrical sequences are arguably more typical to speech rhythm, which is temporally structured but does not involve an underlying grid of equal temporal units. A rhythm discrimination app with metrical and nonmetrical patterns was administered to 74 kindergarteners in conjunction with cognitive and preliteracy measures. Findings support a relationship among rhythm perception, phonological awareness, and letter-sound knowledge (an essential precursor of reading). A mediation analysis revealed that the association between rhythm perception and letter-sound knowledge is mediated through phonological awareness. Furthermore, metrical perception accounted for unique variance in letter-sound knowledge above all other language and cognitive measures. These results point to a unique role for temporal regularity processing in the association between musical rhythm and literacy in young children. Copyright © 2017 Elsevier Inc. All rights reserved.

Rhythmic Auditory Cueing in Motor Rehabilitation for Stroke Patients: Systematic Review and Meta-Analysis.

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Yoo, Ga Eul; Kim, Soo Ji

2016-01-01

Given the increasing evidence demonstrating the effects of rhythmic auditory cueing for motor rehabilitation of stroke patients, this synthesized analysis is needed in order to improve rehabilitative practice and maximize clinical effectiveness. This study aimed to systematically analyze the literature on rhythmic auditory cueing for motor rehabilitation of stroke patients by highlighting the outcome variables, type of cueing, and stage of stroke. A systematic review with meta-analysis of randomized controlled or clinically controlled trials was conducted. Electronic databases and music therapy journals were searched for studies including stroke, the use of rhythmic auditory cueing, and motor outcomes, such as gait and upper-extremity function. A total of 10 studies (RCT or CCT) with 356 individuals were included for meta-analysis. There were large effect sizes (Hedges's g = 0.984 for walking velocity; Hedges's g = 0.840 for cadence; Hedges's g = 0.760 for stride length; and Hedges's g = 0.456 for Fugl-Meyer test scores) in the use of rhythmic auditory cueing. Additional subgroup analysis demonstrated that although the type of rhythmic cueing and stage of stroke did not lead to statistically substantial group differences, the effect sizes and heterogeneity values in each subgroup implied possible differences in treatment effect. This study corroborates the beneficial effects of rhythmic auditory cueing, supporting its expanded application to broadened areas of rehabilitation for stroke patients. Also, it suggests the future investigation of the differential outcomes depending on how rhythmic auditory cueing is provided in terms of type and intensity implemented. © the American Music Therapy Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian Circadian Clock.

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Teruya Tamaru

Full Text Available Intracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we established a pivotal role for casein kinase (CK-2-mediated circadian BMAL1-Ser90 phosphorylation (BMAL1-P in regulating central and peripheral core clocks. Subsequent analysis of the underlying mechanism showed a novel role of CRY as a repressor for protein kinase. Co-immunoprecipitation experiments and real-time monitoring of protein-protein interactions revealed that CRY-mediated periodic binding of CK2β to BMAL1 inhibits BMAL1-Ser90 phosphorylation by CK2α. The FAD binding domain of CRY1, two C-terminal BMAL1 domains, and particularly BMAL1-Lys537 acetylation/deacetylation by CLOCK/SIRT1, were shown to be critical for CRY-mediated BMAL1-CK2β binding. Reciprocally, BMAL1-Ser90 phosphorylation is prerequisite for BMAL1-Lys537 acetylation. We propose a dual negative-feedback model in which a CRY-dependent CK2-driven posttranslational BMAL1-P-BMAL1 loop is an integral part of the core clock oscillator.

Redox rhythm reinforces the circadian clock to gate immune response.

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Zhou, Mian; Wang, Wei; Karapetyan, Sargis; Mwimba, Musoki; Marqués, Jorge; Buchler, Nicolas E; Dong, Xinnian

2015-07-23

Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant's redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism.

Differences between the sexes in technical mastery of rhythmic gymnastics.

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Bozanic, Ana; Miletic, Durdica

2011-02-01

The aims of this study were to determine possible differences between the sexes in specific rhythmic gymnastics techniques, and to examine the influence of various aspects of technique on rhythmic composition performance. Seventy-five students aged 21 ± 2 years (45 males, 30 female) undertook four test sessions to determine: coefficients of asymmetry, stability, versatility, and the two rhythmic compositions (without apparatus and with rope). An independent-sample t-test revealed sex-based differences in technique acquisition: stability for ball (P rhythmic composition without apparatus (P analysis revealed that the variables for assessing stability (beta = 0.44; P rhythmic composition performance of females, and the variables for assessing asymmetry (beta = -0.38; P rhythmic composition performance of males. The results suggest that female students dominate in body skill technique, while male students have the advantage with apparatus. There was a lack of an expressive aesthetic component in performance for males. The need for ambidexterity should be considered in the planning of training programmes.

Intermittent Exposure to Social Defeat and Open-field Test in Rats : Acute and Long-term Effects on ECG, Body Temperature and Physical Activity

NARCIS (Netherlands)

Sgoifo, Andrea; Pozzato, Chiara; Meerlo, Peter; Costoli, Tania; Manghi, Massimo; Stilli, Donatella; Olivetti, Giorgio; Musso, Ezio

2002-01-01

This study investigated the effects of exposure to an intermittent homotypic stressor on: (i) habituation of acute autonomic responsivity (i.e. cardiac sympathovagal balance and susceptibility to arrhythmias), and (ii) circadian rhythmicity of heart rate, body temperature, and physical activity.

Danish music education and the 'rhythmic music' concept

DEFF Research Database (Denmark)

Pedersen, Peder Kaj

2014-01-01

' was avoided and the Danish phrase 'rytmisk musik' (rhythmic music) was created to emphasize the educational and pedagogical content. The aim was also to prevent the prejudicious idea associated with jazz, especially by opponents. The article intends to evaluate the situation of 'rhythmic music' in the context......The article reflects on Danish music education and the concept of 'rhythmic music'. It highligths the so-called "jazz-oratorio", a unique genre, created by the composer Bernhard Christensen (1906-2004) and the librettist Sven Møller Kristensen (1909-91). The article shows that the term 'jazz...... of Danish music education....

Inter-limb coupling in bimanual rhythmic coordination in Parkinson's disease

NARCIS (Netherlands)

Verheul, M.H.G.; Geuze, RH

2004-01-01

Recently, it has been shown that rhythmic inter-limb coordination is disturbed in patients with Parkinson's disease (PD). The present study aims to investigate whether this coordination deficit is primarily the result of an impaired coupling, related to hypoactivation of the supplementary motor area

Music Games: Potential Application and Considerations for Rhythmic Training

OpenAIRE

Valentin Bégel; Valentin Bégel; Ines Di Loreto; Antoine Seilles; Simone Dalla Bella; Simone Dalla Bella; Simone Dalla Bella; Simone Dalla Bella

2017-01-01

Rhythmic skills are natural and widespread in the general population. The majority can track the beat of music and move along with it. These abilities are meaningful from a cognitive standpoint given their tight links with prominent motor and cognitive functions such as language and memory. When rhythmic skills are challenged by brain damage or neurodevelopmental disorders, remediation strategies based on rhythm can be considered. For example, rhythmic training can be used to improve motor pe...

Associations between circadian and stress response cortisol in children.

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Simons, Sterre S H; Cillessen, Antonius H N; de Weerth, Carolina

2017-01-01

Hypothalamic-pituitary-adrenal (HPA) axis functioning is characterized by the baseline production of cortisol following a circadian rhythm, as well as by the superimposed production of cortisol in response to a stressor. However, it is relatively unknown whether the basal cortisol circadian rhythm is associated with the cortisol stress response in children. Since alterations in cortisol stress responses have been associated with mental and physical health, this study investigated whether the cortisol circadian rhythm is associated with cortisol stress responses in 6-year-old children. To this end, 149 normally developing children (M age  = 6.09 years; 70 girls) participated in an innovative social evaluative stress test that effectively provoked increases in cortisol. To determine the cortisol stress response, six cortisol saliva samples were collected and two cortisol stress response indices were calculated: total stress cortisol and cortisol stress reactivity. To determine children's cortisol circadian rhythm eight cortisol circadian samples were collected during two days. Total diurnal cortisol and diurnal cortisol decline scores were calculated as indices of the cortisol circadian rhythm. Hierarchical regression analyses indicated that higher total diurnal cortisol as well as a smaller diurnal cortisol decline, were both uniquely associated with higher total stress cortisol. No associations were found between the cortisol circadian rhythm indices and cortisol stress reactivity. Possible explanations for the patterns found are links with children's self-regulatory capacities and parenting quality.

RNAi of the circadian clock gene period disrupts the circadian rhythm but not the circatidal rhythm in the mangrove cricket

OpenAIRE

Takekata, Hiroki; Matsuura, Yu; Goto, Shin G.; Satoh, Aya; Numata, Hideharu

2012-01-01

The clock mechanism for circatidal rhythm has long been controversial, and its molecular basis is completely unknown. The mangrove cricket, Apteronemobius asahinai, shows two rhythms simultaneously in its locomotor activity: a circatidal rhythm producing active and inactive phases as well as a circadian rhythm modifying the activity intensity of circatidal active phases. The role of the clock gene period (per), one of the key components of the circadian clock in insects, was investigated in t...

Retention of a 24-hour time memory in Syrian hamsters carrying the 20-hour short circadian period mutation in casein kinase-1ε (ck1εtau/tau).

Science.gov (United States)

Cain, Sean W; Yoon, Jeena; Shrestha, Tenjin C; Ralph, Martin R

2014-10-01

Circadian rhythmic expression of conditioned place avoidance (CPA) was produced in Syrian hamsters homozygous for the circadian short period mutation, tau. In constant dim red light neither the 20 h endogenous period, nor a 20 h place conditioning schedule eliminated the 24 h modulation of CPA behavior described previously for wild type (wt) hamsters and other species. Tau mutants exhibited a 20 h rhythm superimposed on the 24 h modulation. The 20 h component was removed selectively with lesions of the suprachiasmatic nucleus. Wt animals conditioned on a 20 h schedule did not produce a 20 h rhythm, but still expressed the 24 h modulation. The results show that the context entrainable oscillator (CEO) underlying memory for the timing of an unconditioned stimulus, retains a period of about 24 h regardless of clock gene background (tau mutation) and/or the conditioning schedule (24 vs 20 h). Therefore the CEO responsible for time memory is distinct from the biological clock controlling activity; the underlying circadian molecular mechanisms may differ from the ubiquitous transcription-translation feedback oscillator; and time memory itself is not classically conditioned. Copyright © 2014 Elsevier Inc. All rights reserved.

Setting the pace: host rhythmic behaviour and gene expression patterns in the facultatively symbiotic cnidarian Aiptasia are determined largely by Symbiodinium.

Science.gov (United States)

Sorek, Michal; Schnytzer, Yisrael; Ben-Asher, Hiba Waldman; Caspi, Vered Chalifa; Chen, Chii-Shiarng; Miller, David J; Levy, Oren

2018-05-09

All organisms employ biological clocks to anticipate physical changes in the environment; however, the integration of biological clocks in symbiotic systems has received limited attention. In corals, the interpretation of rhythmic behaviours is complicated by the daily oscillations in tissue oxygen tension resulting from the photosynthetic and respiratory activities of the associated algal endosymbiont Symbiodinium. In order to better understand the integration of biological clocks in cnidarian hosts of Symbiodinium, daily rhythms of behaviour and gene expression were studied in symbiotic and aposymbiotic morphs of the sea-anemone Aiptasia diaphana. The results showed that whereas circatidal (approx. 12-h) cycles of activity and gene expression predominated in aposymbiotic morphs, circadian (approx. 24-h) patterns were the more common in symbiotic morphs, where the expression of a significant number of genes shifted from a 12- to 24-h rhythm. The behavioural experiments on symbiotic A. diaphana displayed diel (24-h) rhythmicity in body and tentacle contraction under the light/dark cycles, whereas aposymbiotic morphs showed approximately 12-h (circatidal) rhythmicity. Reinfection experiments represent an important step in understanding the hierarchy of endogenous clocks in symbiotic associations, where the aposymbiotic Aiptasia morphs returned to a 24-h behavioural rhythm after repopulation with algae. Whilst some modification of host metabolism is to be expected, the extent to which the presence of the algae modified host endogenous behavioural and transcriptional rhythms implies that it is the symbionts that influence the pace. Our results clearly demonstrate the importance of the endosymbiotic algae in determining the timing and the duration of the extension and contraction of the body and tentacles and temporal gene expression.

Circadian Rhythm Sleep Disorders

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Erhan Akinci

2016-06-01

Full Text Available The circadian rhythm sleep disorders define the clinical conditions where sleep and ndash;wake rhythm is disrupted despite optimum environmental and social conditions. They occur as a result of the changes in endogenous circadian hours or non-compatibility of environmental factors or social life with endogenous circadian rhythm. The sleep and ndash;wake rhythm is disrupted continuously or in repeating phases depending on lack of balance between internal and external cycles. This condition leads to functional impairments which cause insomnia, excessive sleepiness or both in people. Application of detailed sleep anamnesis and sleep diary with actigraphy record, if possible, will be sufficient for diagnosis. The treatment aims to align endogenous circadian rhythm with environmental conditions. The purpose of this article is to review pathology, clinical characteristics, diagnosis and treatment of circadian rhythm disorder. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(2: 178-189

Altered time structure of neuro-endocrine-immune system function in lung cancer patients

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Carughi Stefano

2010-06-01

Full Text Available Abstract Background The onset and the development of neoplastic disease may be influenced by many physiological, biological and immunological factors. The nervous, endocrine and immune system might act as an integrated unit to mantain body defense against this pathological process and reciprocal influences have been evidenced among hypothalamus, pituitary, thyroid, adrenal, pineal gland and immune system. In this study we evaluated differences among healthy subjects and subjects suffering from lung cancer in the 24-hour secretory profile of melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 and circadian variations of lymphocyte subpopulations. Methods In ten healthy male volunteers (age range 45-66 and ten male patients with untreated non small cell lung cancer (age range 46-65 we measured melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 serum levels and percentages of lymphocyte subpopulations on blood samples collected every four hours for 24 hours. One-way ANOVA between the timepoints for each variable and each group was performed to look for a time-effect, the presence of circadian rhythmicity was evaluated, MESOR, amplitude and acrophase values, mean diurnal levels and mean nocturnal levels were compared. Results A clear circadian rhythm was validated in the control group for hormone serum level and for lymphocyte subsets variation. Melatonin, TRH, TSH, GH, CD3, CD4, HLA-DR, CD20 and CD25 expressing cells presented circadian rhythmicity with acrophase during the night. Cortisol, CD8, CD8bright, CD8dim, CD16, TcRδ1 and δTcS1 presented circadian rhythmicity with acrophase in the morning/at noon. FT4, IGF-1 and IL-2 variation did not show circadian rhythmicity. In lung cancer patients cortisol, TRH, TSH and GH serum level and all the lymphocyte subsubsets variation (except for CD4 showed loss of circadian rhythmicity. MESOR of cortisol, TRH, GH, IL-2 and CD16 was increased, whereas MESOR of TSH, IGF-1, CD8, CD8bright, TcRδ1 and �

Aging and Circadian Rhythms

Science.gov (United States)

Duffy, Jeanne F.; Zitting, Kirsi-Marja; Chinoy, Evan D.

2015-01-01

Aging is associated with numerous changes, including changes in sleep timing, duration, and quality. The circadian timing system interacts with a sleep-wake homeostatic system to regulate human sleep, including sleep timing and structure. Here, we review key features of the human circadian timing system, age-related changes in the circadian timing system, and how those changes may contribute to the observed alterations in sleep. PMID:26568120

Rhythmic Haptic Stimuli Improve Short-Term Attention.

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Zhang, Shusheng; Wang, Dangxiao; Afzal, Naqash; Zhang, Yuru; Wu, Ruilin

2016-01-01

Brainwave entrainment using rhythmic visual and/or auditory stimulation has shown its efficacy in modulating neural activities and cognitive ability. In the presented study, we aim to investigate whether rhythmic haptic stimulation could enhance short-term attention. An experiment with sensorimotor rhythm (SMR) increasing protocol was performed in which participants were presented sinusoidal vibrotactile stimulus of 15 Hz on their palm. Test of Variables of Attention (T.O.V.A.) was performed before and after the stimulating session. Electroencephalograph (EEG) was recorded across the stimulating session and the two attention test sessions. SMR band power manifested a significant increase after stimulation. Results of T.O.V.A. tests indicated an improvement in the attention of participants who had received the stimulation compared to the control group who had not received the stimulation. The D prime score of T.O.V.A. reveals that participants performed better in perceptual sensitivity and sustaining attention level compared to their baseline performance before the stimulating session. These findings highlight the potential value of using haptics-based brainwave entrainment for cognitive training.

Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function.

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Alexandra Vaccaro

2017-01-01

Full Text Available Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration. Here we examined the effects of clock disruptions on locomotor aging and longevity in Drosophila. We found that lifespan was similarly reduced in three arrhythmic mutants (ClkAR, cyc0 and tim0 and in wild-type flies under constant light, which stops the clock. In contrast, ClkAR mutants showed significantly faster age-related locomotor deficits (as monitored by startle-induced climbing than cyc0 and tim0, or than control flies under constant light. Reactive oxygen species accumulated more with age in ClkAR mutant brains, but this did not appear to contribute to the accelerated locomotor decline of the mutant. Clk, but not Cyc, inactivation by RNA interference in the pigment-dispersing factor (PDF-expressing central pacemaker neurons led to similar loss of climbing performance as ClkAR. Conversely, restoring Clk function in these cells was sufficient to rescue the ClkAR locomotor phenotype, independently of behavioral rhythmicity. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the posterior protocerebral lateral 1 (PPL1 clusters. This neuronal loss was rescued when the ClkAR mutation was placed in an apoptosis-deficient background. Impairing dopamine synthesis in a single pair of PPL1 neurons that innervate the mushroom bodies accelerated locomotor decline in otherwise wild-type flies. Our results therefore reveal a novel circadian-independent requirement for Clk in brain circadian neurons to maintain a subset of dopaminergic cells and avoid premature locomotor aging in Drosophila.

Circadian physiology of metabolism.

Science.gov (United States)

Panda, Satchidananda

2016-11-25

A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark. Copyright © 2016, American Association for the Advancement of Science.

Regulation of behavioral circadian rhythms and clock protein PER1 by the deubiquitinating enzyme USP2

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Yaoming Yang

2012-06-01

Endogenous 24-hour rhythms are generated by circadian clocks located in most tissues. The molecular clock mechanism is based on feedback loops involving clock genes and their protein products. Post-translational modifications, including ubiquitination, are important for regulating the clock feedback mechanism. Previous work has focused on the role of ubiquitin ligases in the clock mechanism. Here we show a role for the rhythmically-expressed deubiquitinating enzyme ubiquitin specific peptidase 2 (USP2 in clock function. Mice with a deletion of the Usp2 gene (Usp2 KO display a longer free-running period of locomotor activity rhythms and altered responses of the clock to light. This was associated with altered expression of clock genes in synchronized Usp2 KO mouse embryonic fibroblasts and increased levels of clock protein PERIOD1 (PER1. USP2 can be coimmunoprecipitated with several clock proteins but directly interacts specifically with PER1 and deubiquitinates it. Interestingly, this deubiquitination does not alter PER1 stability. Taken together, our results identify USP2 as a new core component of the clock machinery and demonstrate a role for deubiquitination in the regulation of the circadian clock, both at the level of the core pacemaker and its response to external cues.

Circadian disorganization alters intestinal microbiota.

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Robin M Voigt

Full Text Available Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases.

Light and the human circadian clock.

Science.gov (United States)

Roenneberg, Till; Kantermann, Thomas; Juda, Myriam; Vetter, Céline; Allebrandt, Karla V

2013-01-01

The circadian clock can only reliably fulfil its function if it is stably entrained. Most clocks use the light-dark cycle as environmental signal (zeitgeber) for this active synchronisation. How we think about clock function and entrainment has been strongly influenced by the early concepts of the field's pioneers, and the astonishing finding that circadian rhythms continue a self-sustained oscillation in constant conditions has become central to our understanding of entrainment.Here, we argue that we have to rethink these initial circadian dogmas to fully understand the circadian programme and how it entrains. Light is also the prominent zeitgeber for the human clock, as has been shown experimentally in the laboratory and in large-scale epidemiological studies in real life, and we hypothesise that social zeitgebers act through light entrainment via behavioural feedback loops (zeitnehmer). We show that human entrainment can be investigated in detail outside of the laboratory, by using the many 'experimental' conditions provided by the real world, such as daylight savings time, the 'forced synchrony' imposed by the introduction of time zones, or the fact that humans increasingly create their own light environment. The conditions of human entrainment have changed drastically over the past 100 years and have led to an increasing discrepancy between biological and social time (social jetlag). The increasing evidence that social jetlag has detrimental consequences for health suggests that shift-work is only an extreme form of circadian misalignment, and that the majority of the population in the industrialised world suffers from a similarly 'forced synchrony'.

Treatment guidelines for Circadian Rhythm Sleep-Wake Disorders of the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association. Part I. Physiology, assessment and therapeutic methods.

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Wichniak, Adam; Jankowski, Konrad S; Skalski, Michal; Skwarło-Sońta, Krystyna; Zawilska, Jolanta B; Żarowski, Marcin; Poradowska, Ewa; Jernajczyk, Wojciech

2017-10-29

Majority of the physiological processes in the human organism are rhythmic. The most common are the diurnal changes that repeat roughly every 24 hours, called circadian rhythms. Circadian rhythms disorders have negative influence on human functioning. The aim of this article is to present the current understanding of the circadian rhythms physiological role, with particular emphasis on the circadian rhythm sleep-wake disorders (CRSWD), principles of their diagnosis and chronobiological therapy. The guidelines are based on the review of recommendations from the scientific societies involved in sleep medicine and the clinical experiences of the authors. Researchers participating in the preparation of guidelines were invited by the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association, based on their significant contributions in circadian rhythm research and/or clinical experience in the treatment of such disorders. Finally, the guidelines were adjusted to the questions and comments given by the members of both Societies. CRSWD have a significant negative impact on human health and functioning. Standard methods used to assess CRSWD are sleep diaries and sleep logs, while the actigraphy, when available, should be also used. The most effective methods of CRSWD treatment are melatonin administration and light therapy. Behavioral interventions are also recommended. Afourteen-day period of sleep-wake rhythm assessment in CRSWD enables accurate diagnosis, adequate selection of chronobiological interventions, and planning adequate diurnal timing of their application. This type of assessment is quite easy, low-cost, and provides valuable indications how to adjust the therapeutic approach to the circadian phase of the particular patient.

Differential effects of rhythmic auditory stimulation and neurodevelopmental treatment/Bobath on gait patterns in adults with cerebral palsy: a randomized controlled trial.

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Kim, Soo Ji; Kwak, Eunmi E; Park, Eun Sook; Cho, Sung-Rae

2012-10-01

To investigate the effects of rhythmic auditory stimulation (RAS) on gait patterns in comparison with changes after neurodevelopmental treatment (NDT/Bobath) in adults with cerebral palsy. A repeated-measures analysis between the pretreatment and posttreatment tests and a comparison study between groups. Human gait analysis laboratory. Twenty-eight cerebral palsy patients with bilateral spasticity participated in this study. The subjects were randomly allocated to either neurodevelopmental treatment (n = 13) or rhythmic auditory stimulation (n = 15). Gait training with rhythmic auditory stimulation or neurodevelopmental treatment was performed three sessions per week for three weeks. Temporal and kinematic data were analysed before and after the intervention. Rhythmic auditory stimulation was provided using a combination of a metronome beat set to the individual's cadence and rhythmic cueing from a live keyboard, while neurodevelopmental treatment was implemented following the traditional method. Temporal data, kinematic parameters and gait deviation index as a measure of overall gait pathology were assessed. Temporal gait measures revealed that rhythmic auditory stimulation significantly increased cadence, walking velocity, stride length, and step length (P rhythmic auditory stimulation (P rhythmic auditory stimulation (P rhythmic auditory stimulation showed aggravated maximal internal rotation in the transverse plane (P rhythmic auditory stimulation or neurodevelopmental treatment elicited differential effects on gait patterns in adults with cerebral palsy.

Time-varying spectral analysis revealing differential effects of sevoflurane anaesthesia: non-rhythmic-to-rhythmic ratio.

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Lin, Y-T; Wu, H-T; Tsao, J; Yien, H-W; Hseu, S-S

2014-02-01

Heart rate variability (HRV) may reflect various physiological dynamics. In particular, variation of R-R peak interval (RRI) of electrocardiography appears regularly oscillatory in deeper levels of anaesthesia and less regular in lighter levels of anaesthesia. We proposed a new index, non-rhythmic-to-rhythmic ratio (NRR), to quantify this feature and investigated its potential to estimate depth of anaesthesia. Thirty-one female patients were enrolled in this prospective study. The oscillatory pattern transition of RRI was visualised by the time-varying power spectrum and quantified by NRR. The prediction of anaesthetic events, including skin incision, first reaction of motor movement during emergence period, loss of consciousness (LOC) and return of consciousness (ROC) by NRR were evaluated by serial prediction probability (PK ) analysis; the ability to predict the decrease of effect-site sevoflurane concentration was also evaluated. The results were compared with Bispectral Index (BIS). NRR well-predicted first reaction (PK  > 0.90) 30 s ahead, earlier than BIS and significantly better than HRV indices. NRR well-correlated with sevoflurane concentration, although its correlation was inferior to BIS, while HRV indices had no such correlation. BIS indicated LOC and ROC best. Our findings suggest that NRR provides complementary information to BIS regarding the differential effects of anaesthetics on the brain, especially the subcortical motor activity. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Sleep- and circadian rhythm-associated pathways as therapeutic targets in bipolar disorder.

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Bellivier, Frank; Geoffroy, Pierre-Alexis; Etain, Bruno; Scott, Jan

2015-06-01

Disruptions in sleep and circadian rhythms are observed in individuals with bipolar disorders (BD), both during acute mood episodes and remission. Such abnormalities may relate to dysfunction of the molecular circadian clock and could offer a target for new drugs. This review focuses on clinical, actigraphic, biochemical and genetic biomarkers of BDs, as well as animal and cellular models, and highlights that sleep and circadian rhythm disturbances are closely linked to the susceptibility to BDs and vulnerability to mood relapses. As lithium is likely to act as a synchronizer and stabilizer of circadian rhythms, we will review pharmacogenetic studies testing circadian gene polymorphisms and prophylactic response to lithium. Interventions such as sleep deprivation, light therapy and psychological therapies may also target sleep and circadian disruptions in BDs efficiently for treatment and prevention of bipolar depression. We suggest that future research should clarify the associations between sleep and circadian rhythm disturbances and alterations of the molecular clock in order to identify critical targets within the circadian pathway. The investigation of such targets using human cellular models or animal models combined with 'omics' approaches are crucial steps for new drug development.

Visual cortex responses reflect temporal structure of continuous quasi-rhythmic sensory stimulation.

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Keitel, Christian; Thut, Gregor; Gross, Joachim

2017-02-01

Neural processing of dynamic continuous visual input, and cognitive influences thereon, are frequently studied in paradigms employing strictly rhythmic stimulation. However, the temporal structure of natural stimuli is hardly ever fully rhythmic but possesses certain spectral bandwidths (e.g. lip movements in speech, gestures). Examining periodic brain responses elicited by strictly rhythmic stimulation might thus represent ideal, yet isolated cases. Here, we tested how the visual system reflects quasi-rhythmic stimulation with frequencies continuously varying within ranges of classical theta (4-7Hz), alpha (8-13Hz) and beta bands (14-20Hz) using EEG. Our findings substantiate a systematic and sustained neural phase-locking to stimulation in all three frequency ranges. Further, we found that allocation of spatial attention enhances EEG-stimulus locking to theta- and alpha-band stimulation. Our results bridge recent findings regarding phase locking ("entrainment") to quasi-rhythmic visual input and "frequency-tagging" experiments employing strictly rhythmic stimulation. We propose that sustained EEG-stimulus locking can be considered as a continuous neural signature of processing dynamic sensory input in early visual cortices. Accordingly, EEG-stimulus locking serves to trace the temporal evolution of rhythmic as well as quasi-rhythmic visual input and is subject to attentional bias. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Circadian rhythm phase shifts and endogenous free-running circadian period differ between African-Americans and European-Americans.

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Eastman, Charmane I; Suh, Christina; Tomaka, Victoria A; Crowley, Stephanie J

2015-02-11

Successful adaptation to modern civilization requires the internal circadian clock to make large phase shifts in response to circumstances (e.g., jet travel and shift work) that were not encountered during most of our evolution. We found that the magnitude and direction of the circadian clock's phase shift after the light/dark and sleep/wake/meal schedule was phase-advanced (made earlier) by 9 hours differed in European-Americans compared to African-Americans. European-Americans had larger phase shifts, but were more likely to phase-delay after the 9-hour advance (to phase shift in the wrong direction). The magnitude and direction of the phase shift was related to the free-running circadian period, and European-Americans had a longer circadian period than African-Americans. Circadian period was related to the percent Sub-Saharan African and European ancestry from DNA samples. We speculate that a short circadian period was advantageous during our evolution in Africa and lengthened with northern migrations out of Africa. The differences in circadian rhythms remaining today are relevant for understanding and treating the modern circadian-rhythm-based disorders which are due to a misalignment between the internal circadian rhythms and the times for sleep, work, school and meals.

Circadian rhythm and its role in malignancy

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Mahmood Saqib

2010-03-01

Full Text Available Abstract Circadian rhythms are daily oscillations of multiple biological processes directed by endogenous clocks. The circadian timing system comprises peripheral oscillators located in most tissues of the body and a central pacemaker located in the suprachiasmatic nucleus (SCN of the hypothalamus. Circadian genes and the proteins produced by these genes constitute the molecular components of the circadian oscillator which form positive/negative feedback loops and generate circadian rhythms. The circadian regulation extends beyond clock genes to involve various clock-controlled genes (CCGs including various cell cycle genes. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis. This may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. Different lines of evidence in mice and humans suggest that cancer may be a circadian-related disorder. The genetic or functional disruption of the molecular circadian clock has been found in various cancers including breast, ovarian, endometrial, prostate and hematological cancers. The acquisition of current data in circadian clock mechanism may help chronotherapy, which takes into consideration the biological time to improve treatments by devising new therapeutic approaches for treating circadian-related disorders, especially cancer.

Model-based investigation of the circadian clock and cell cycle coupling in mouse embryonic fibroblasts: Prediction of RevErb-α up-regulation during mitosis.

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Traynard, Pauline; Feillet, Céline; Soliman, Sylvain; Delaunay, Franck; Fages, François

2016-11-01

Experimental observations have put in evidence autonomous self-sustained circadian oscillators in most mammalian cells, and proved the existence of molecular links between the circadian clock and the cell cycle. Some mathematical models have also been built to assess conditions of control of the cell cycle by the circadian clock. However, recent studies in individual NIH3T3 fibroblasts have shown an unexpected acceleration of the circadian clock together with the cell cycle when the culture medium is enriched with growth factors, and the absence of such acceleration in confluent cells. In order to explain these observations, we study a possible entrainment of the circadian clock by the cell cycle through a regulation of clock genes around the mitosis phase. We develop a computational model and a formal specification of the observed behavior to investigate the conditions of entrainment in period and phase. We show that either the selective activation of RevErb-α or the selective inhibition of Bmal1 transcription during the mitosis phase, allow us to fit the experimental data on both period and phase, while a uniform inhibition of transcription during mitosis seems incompatible with the phase data. We conclude on the arguments favoring the RevErb-α up-regulation hypothesis and on some further predictions of the model. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Uncoupling the Mitogenic and Metabolic Functions of FGF1 by Tuning FGF1-FGF Receptor Dimer Stability

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Zhifeng Huang

2017-08-01

Full Text Available Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is therefore highly relevant in the context of circadian biology, but its characterization on the proteome-wide scale and its circadian clock dependence are still poorly described. Here, we provide a comprehensive and rhythmic acetylome map of the mouse liver. Rhythmic acetylated proteins showed subcellular localization-specific phases that correlated with the related metabolites in the regulated pathways. Mitochondrial proteins were over-represented among the rhythmically acetylated proteins and were highly correlated with SIRT3-dependent deacetylation. SIRT3 activity being nicotinamide adenine dinucleotide (NAD+ level-dependent, we show that NAD+ is orchestrated by both feeding rhythms and the circadian clock through the NAD+ salvage pathway but also via the nicotinamide riboside pathway. Hence, the diurnal acetylome relies on a functional circadian clock and affects important diurnal metabolic pathways in the mouse liver.

Circadian rhythms and obesity in mammals.

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Froy, Oren

2012-01-01

Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating the circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabolism. Moreover, disruption of circadian rhythms leads to obesity and metabolic disorders. Therefore, it is plausible that resetting of the circadian clock can be used as a new approach to attenuate obesity. Feeding regimens, such as restricted feeding (RF), calorie restriction (CR), and intermittent fasting (IF), provide a time cue and reset the circadian clock and lead to better health. In contrast, high-fat (HF) diet leads to disrupted circadian expression of metabolic factors and obesity. This paper focuses on circadian rhythms and their link to obesity.

Circadian Rhythm Disruption Promotes Lung Tumorigenesis.

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Papagiannakopoulos, Thales; Bauer, Matthew R; Davidson, Shawn M; Heimann, Megan; Subbaraj, Lakshmipriya; Bhutkar, Arjun; Bartlebaugh, Jordan; Vander Heiden, Matthew G; Jacks, Tyler

2016-08-09

Circadian rhythms are 24-hr oscillations that control a variety of biological processes in living systems, including two hallmarks of cancer, cell division and metabolism. Circadian rhythm disruption by shift work is associated with greater risk for cancer development and poor prognosis, suggesting a putative tumor-suppressive role for circadian rhythm homeostasis. Using a genetically engineered mouse model of lung adenocarcinoma, we have characterized the effects of circadian rhythm disruption on lung tumorigenesis. We demonstrate that both physiologic perturbation (jet lag) and genetic mutation of the central circadian clock components decreased survival and promoted lung tumor growth and progression. The core circadian genes Per2 and Bmal1 were shown to have cell-autonomous tumor-suppressive roles in transformation and lung tumor progression. Loss of the central clock components led to increased c-Myc expression, enhanced proliferation, and metabolic dysregulation. Our findings demonstrate that both systemic and somatic disruption of circadian rhythms contribute to cancer progression. Copyright © 2016 Elsevier Inc. All rights reserved.

Manipulating the Cellular Circadian Period of Arginine Vasopressin Neurons Alters the Behavioral Circadian Period.

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Mieda, Michihiro; Okamoto, Hitoshi; Sakurai, Takeshi

2016-09-26

As the central pacemaker in mammals, the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is a heterogeneous structure consisting of multiple types of GABAergic neurons with distinct chemical identities [1, 2]. Although individual cells have a cellular clock driven by autoregulatory transcriptional/translational feedback loops of clock genes, interneuronal communication among SCN clock neurons is likely essential for the SCN to generate a highly robust, coherent circadian rhythm [1]. However, neuronal mechanisms that determine circadian period length remain unclear. The SCN is composed of two subdivisions: a ventral core region containing vasoactive intestinal peptide (VIP)-producing neurons and a dorsal shell region characterized by arginine vasopressin (AVP)-producing neurons. Here we examined whether AVP neurons act as pacemaker cells that regulate the circadian period of behavior rhythm in mice. The deletion of casein kinase 1 delta (CK1δ) specific to AVP neurons, which was expected to lengthen the period of cellular clocks [3-6], lengthened the free-running period of circadian behavior as well. Conversely, the overexpression of CK1δ specific to SCN AVP neurons shortened the free-running period. PER2::LUC imaging in slices confirmed that cellular circadian periods of the SCN shell were lengthened in mice without CK1δ in AVP neurons. Thus, AVP neurons may be an essential component of circadian pacemaker cells in the SCN. Remarkably, the alteration of the shell-core phase relationship in the SCN of these mice did not impair the generation per se of circadian behavior rhythm, thereby underscoring the robustness of the SCN network. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effect of Haptic Guidance on Learning a Hybrid Rhythmic-Discrete Motor Task.

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Marchal-Crespo, Laura; Bannwart, Mathias; Riener, Robert; Vallery, Heike

2015-01-01

Bouncing a ball with a racket is a hybrid rhythmic-discrete motor task, combining continuous rhythmic racket movements with discrete impact events. Rhythmicity is exceptionally important in motor learning, because it underlies fundamental movements such as walking. Studies suggested that rhythmic and discrete movements are governed by different control mechanisms at different levels of the Central Nervous System. The aim of this study is to evaluate the effect of fixed/fading haptic guidance on learning to bounce a ball to a desired apex in virtual reality with varying gravity. Changing gravity changes dominance of rhythmic versus discrete control: The higher the value of gravity, the more rhythmic the task; lower values reduce the bouncing frequency and increase dwell times, eventually leading to a repetitive discrete task that requires initiation and termination, resembling target-oriented reaching. Although motor learning in the ball-bouncing task with varying gravity has been studied, the effect of haptic guidance on learning such a hybrid rhythmic-discrete motor task has not been addressed. We performed an experiment with thirty healthy subjects and found that the most effective training condition depended on the degree of rhythmicity: Haptic guidance seems to hamper learning of continuous rhythmic tasks, but it seems to promote learning for repetitive tasks that resemble discrete movements.

[Circadian rhythm : Influence on Epworth Sleepiness Scale score].

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Herzog, M; Bedorf, A; Rohrmeier, C; Kühnel, T; Herzog, B; Bremert, T; Plontke, S; Plößl, S

2017-02-01

The Epworth Sleepiness Scale (ESS) is frequently used to determine daytime sleepiness in patients with sleep-disordered breathing. It is still unclear whether different levels of alertness induced by the circadian rhythm influence ESS score. The aim of this study is to investigate the influence of circadian rhythm-dependent alertness on ESS performance. In a monocentric prospective noninterventional observation study, 97 patients with suspected sleep-disordered breathing were investigated with respect to daytime sleepiness in temporal relationship to polysomnographic examination and treatment. The Karolinska Sleepiness Scale (KSS) and the Stanford Sleepiness Scale (SSS) served as references for the detection of present sleepiness at three different measurement times (morning, noon, evening), prior to and following a diagnostic polysomnography night as well as after a continuous positive airway pressure (CPAP) titration night (9 measurements in total). The KSS, SSS, and ESS were performed at these times in a randomized order. The KSS and SSS scores revealed a circadian rhythm-dependent curve with increased sleepiness at noon and in the evening. Following a diagnostic polysomnography night, the scores were increased compared to the measurements prior to the night. After the CPAP titration night, sleepiness in the morning was reduced. KSS and SSS reflect the changes in alertness induced by the circadian rhythm. The ESS score war neither altered by the intra-daily nor by the inter-daily changes in the level of alertness. According to the present data, the ESS serves as a reliable instrument to detect the level of daytime sleepiness independently of the circadian rhythm-dependent level of alertness.

The Acoustic Reality of the Kachruvian Circles: A Rhythmic Perspective

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Low, Ee Ling

2010-01-01

This paper investigates whether the rhythmic properties of varieties of English found in each of the concentric circles of Kachru's model can, in any way, be elucidated by the "Three Circles" model. A measurement and comparison of the rhythm of three varieties of English: British English (from the Inner Circle), Singapore English (from…

Associations between circadian and stress response cortisol in children

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Simons, S.S.H.; Cillessen, A.H.N.; Weerth, C. de

2017-01-01

Hypothalamic-pituitary-adrenal (HPA) axis functioning is characterized by the baseline production of cortisol following a circadian rhythm, as well as by the superimposed production of cortisol in response to a stressor. However, it is relatively unknown whether the basal cortisol circadian rhythm is associated with the cortisol stress response in children. Since alterations in cortisol stress responses have been associated with mental and physical health, this study investigated whether the ...

Speak on time! Effects of a musical rhythmic training on children with hearing loss.

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Hidalgo, Céline; Falk, Simone; Schön, Daniele

2017-08-01

This study investigates temporal adaptation in speech interaction in children with normal hearing and in children with cochlear implants (CIs) and/or hearing aids (HAs). We also address the question of whether musical rhythmic training can improve these skills in children with hearing loss (HL). Children named pictures presented on the screen in alternation with a virtual partner. Alternation rate (fast or slow) and the temporal predictability (match vs mismatch of stress occurrences) were manipulated. One group of children with normal hearing (NH) and one with HL were tested. The latter group was tested twice: once after 30 min of speech therapy and once after 30 min of musical rhythmic training. Both groups of children (NH and with HL) can adjust their speech production to the rate of alternation of the virtual partner. Moreover, while children with normal hearing benefit from the temporal regularity of stress occurrences, children with HL become sensitive to this manipulation only after rhythmic training. Rhythmic training may help children with HL to structure the temporal flow of their verbal interactions. Copyright © 2017 Elsevier B.V. All rights reserved.

Rhythmic patterning in Malaysian and Singapore English.

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Tan, Rachel Siew Kuang; Low, Ee-Ling

2014-06-01

Previous work on the rhythm of Malaysian English has been based on impressionistic observations. This paper utilizes acoustic analysis to measure the rhythmic patterns of Malaysian English. Recordings of the read speech and spontaneous speech of 10 Malaysian English speakers were analyzed and compared with recordings of an equivalent sample of Singaporean English speakers. Analysis was done using two rhythmic indexes, the PVI and VarcoV. It was found that although the rhythm of read speech of the Singaporean speakers was syllable-based as described by previous studies, the rhythm of the Malaysian speakers was even more syllable-based. Analysis of the syllables in specific utterances showed that Malaysian speakers did not reduce vowels as much as Singaporean speakers in cases of syllables in utterances. Results of the spontaneous speech confirmed the findings for the read speech; that is, the same rhythmic patterning was found which normally triggers vowel reductions.

RHYTHMIC MUSIC PEDAGOGY: A SCANDINAVIAN APPROACH TO MUSIC EDUCATION

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Hauge Torunn Bakken

2012-06-01

Full Text Available Rhythmic music pedagogy is a relatively new Scandinavian approach to classroom music education that offers a variety of methods and strategies for teaching and learning music, especially within the performance of improvised and rhythmic music. This article is based on two earlier projects published in Norwegian, in which the concept of rytmisk musikkpedagogikk (or “rhythmic music pedagogy” as well as its applications and implications were thoroughly described. This research confirms that rhythmic music pedagogy may be an effective strategy for learning music in general, but most especially for learning skills associated with ensemble musicianship and playing by ear. In a multicultural and fluid society in which there are tendencies toward passivity and fragmentation, it may be more important than ever to maintain the idea of music as a collaborative creative process that extends across borders; in this context, rhythmic music pedagogy can play a central role in children’s social development. As a social medium, ensemble playing requires the participant to decentralize socially, since the perspectives of the other participants are necessary for a successful performance. The activity’s general potential for re-structuring social settings and moving boundaries in a positive way should not be underestimated.

Circadian Rhythm Sleep-Wake Disorders.

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Abbott, Sabra M; Reid, Kathryn J; Zee, Phyllis C

2015-12-01

The circadian system regulates the timing and expression of nearly all biological processes, most notably, the sleep-wake cycle, and disruption of this system can result in adverse effects on both physical and mental health. The circadian rhythm sleep-wake disorders (CRSWDs) consist of 5 disorders that are due primarily to pathology of the circadian clock or to a misalignment of the timing of the endogenous circadian rhythm with the environment. This article outlines the nature of these disorders, the association of many of these disorders with psychiatric illness, and available treatment options. Copyright © 2015 Elsevier Inc. All rights reserved.

Transtornos alimentares e padrão circadiano alimentar: uma revisão Eating disorders and circadian eating pattern: a review

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Fabiana Bernardi

2009-12-01

food intake, which seems to increase such disorders. Circadian rhythm can influence eating behavior. However, more studies and knowledge about food rhythmicity might contribute to better understanding the current eating behavior, acting in prevention and/or treatment of eating disorders.

The development of rhythmic preferences by Dutch-learning infants

NARCIS (Netherlands)

Keij, B.M.; Kager, R.W.J.

2016-01-01

In this chapter the early acquisition of word stress is discussed. This study is aimed at examining rhythmic preferences for either strong-weak or weak-strong stress patterns of Dutch-learning infants between 4 and 8 months of age. It is complementary to previous rhythmic preference studies

The development of rhythmic preferences by Dutch-learning infants

NARCIS (Netherlands)

Keij, B.M.|info:eu-repo/dai/nl/374786097; Kager, R.W.J.|info:eu-repo/dai/nl/072294124

In this chapter the early acquisition of word stress is discussed. This study is aimed at examining rhythmic preferences for either strong-weak or weak-strong stress patterns of Dutch-learning infants between 4 and 8 months of age. It is complementary to previous rhythmic preference studies

Circadian secretion patterns of ß-endorphin and leucine enkephalin

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E. H. de Wet

1992-07-01

Full Text Available ß-endorphin and leucine enkephalin are neuropeptides with potent opioid activity. In a study to investigate the circadian secretion patterns of the above-mentioned, blood samples were collected hourly from 12 healthy males who were subjected to the experiment for 24 hours. Radioimmunoassays were used in the analysis of plasma samples for ß-endorphin and leucine enkephalin. Peak concentrations of ß-endorphin were demonstrated from 08:00-09:00, while peak concentrations of leucine enkephalin occured from 23:00-07:00. Trough concentrations of ß-endorphin occurred from 24:00-05:00, while trough con­centrations of leucine enkephalin were demonstrated from 09:00-12:00. The illustrated circadian secretion pattern for ß-endorphin simulates the well-known circadian rhythm of cortisol. The answer to this may be in the fact that ß-endorphin and corticotropin stem from the same precursor. The illustrated circadian secretion pattern for leucine enkephalin simulates that of melatonin. The reason for this is unclear.

Effects of exercise on circadian rhythms and mobility in aging Drosophila melanogaster.

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Rakshit, Kuntol; Wambua, Rebecca; Giebultowicz, Tomasz M; Giebultowicz, Jadwiga M

2013-11-01

Daily life functions such as sleep and feeding oscillate with circa 24 h period due to endogenous circadian rhythms generated by circadian clocks. Genetic or environmental disruption of circadian rhythms is associated with various aging-related phenotypes. Circadian rhythms decay during normal aging, and there is a need to explore strategies that could avert age-related changes in the circadian system. Exercise was reported to delay aging in mammals. Here, we investigated whether daily exercise via stimulation of upward climbing movement could improve circadian rest/activity rhythms in aging Drosophila melanogaster. We found that repeated exercise regimen did not strengthen circadian locomotor activity rhythms in aging flies and had no effect on their lifespan. We also tested the effects of exercise on mobility and determined that regular exercise lowered age-specific climbing ability in both wild type and clock mutant flies. Interestingly, the climbing ability was most significantly reduced in flies carrying a null mutation in the core clock gene period, while rescue of this gene significantly improved climbing to wild type levels. Our work highlights the importance of period in sustaining endurance in aging flies exposed to physical challenge. © 2013.

A tapping device for recording and quantitative characterization of rhythmic/auditory sequences.

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Piazza, Caterina; Cesareo, Ambra; Caccia, Martina; Reni, Gianluigi; Lorusso, Maria L

2017-07-01

The processing of auditory stimuli is essential for the correct perception of language and deficits in this ability are often related to the presence or development of language disorders. The motor imitation (e.g. tapping or beating) of rhythmic sequences can be a very sensitive correlate of deficits in auditory processing. Thus, the study of the tapping performance, with the investigation of both temporal and intensity information, might be very useful. The present work is aimed at the development and preliminary testing of a tapping device to be used for the imitation and/or the production of rhythmic sequences, allowing the recording of both tapping duration and intensity. The device is essentially made up of a Force Sensing Resistor and an Arduino UNO board. It was validated using different sampling frequencies (f s ) in a group of 10 young healthy adults investigating its efficacy in terms of touch and intensity detection by means of two testing procedures. Results demonstrated a good performance of the device when programmed with fs equal to 50 and 100Hz. Moreover, both temporal and intensity parameters were extracted, thus supporting the potential use of the device for the analysis of the imitation or production of rhythmic sequences. This work represents a first step for the development of a useful, low cost tool to support the diagnosis, training and rehabilitation of language disorders.

Metabolic rate changes proportionally to circadian frequency in tau mutant Syrian hamsters

NARCIS (Netherlands)

Oklejewicz, M; Hut, RA; Daan, S; Loudon, ASI; Stirland, AJ; Loudon, Andrew S.I.; Stirland, Anne J.

1997-01-01

The tau mutation in Syrian hamsters (Mesocricetus auratus) is phenotypically expressed in a period of the circadian rhythm of about 20 h in homozygotes (SS) and about 22 h in heterozygotes (S+). The authors investigate whether this well-defined model for variation in circadian period exhibits

Circadian rhythm disruption as a link between Attention-Deficit/Hyperactivity Disorder and obesity?

NARCIS (Netherlands)

Vogel, S.W.; Bijlenga, D.; Tanke, M.; Bron, T.I.; van der Heijden, K.B.; Swaab, H.; Beekman, A.T.; Kooij, J.

2015-01-01

Objective: Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) have a high prevalence of obesity. This is the first study to investigate whether circadian rhythmdisruption is a mechanismlinking ADHD symptoms to obesity. Methods: ADHD symptoms and two manifestations of circadian

Effect of Spaceflight on the Circadian Rhythm, Lifespan and Gene Expression of Drosophila melanogaster

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Xu, Kanyan

2015-01-01

Space travelers are reported to experience circadian rhythm disruption during spaceflight. However, how the space environment affects circadian rhythm is yet to be determined. The major focus of this study was to investigate the effect of spaceflight on the Drosophila circadian clock at both the behavioral and molecular level. We used China’s Shenzhou-9 spaceship to carry Drosophila. After 13 days of spaceflight, behavior tests showed that the flies maintained normal locomotor activity rhythm and sleep pattern. The expression level and rhythm of major clock genes were also unaffected. However, expression profiling showed differentially regulated output genes of the circadian clock system between space flown and control flies, suggesting that spaceflight affected the circadian output pathway. We also investigated other physiological effects of spaceflight such as lipid metabolism and lifespan, and searched genes significantly affected by spaceflight using microarray analysis. These results provide new information on the effects of spaceflight on circadian rhythm, lipid metabolism and lifespan. Furthermore, we showed that studying the effect of spaceflight on gene expression using samples collected at different Zeitgeber time could obtain different results, suggesting the importance of appropriate sampling procedures in studies on the effects of spaceflight. PMID:25798821

Effect of spaceflight on the circadian rhythm, lifespan and gene expression of Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Lingling Ma

Full Text Available Space travelers are reported to experience circadian rhythm disruption during spaceflight. However, how the space environment affects circadian rhythm is yet to be determined. The major focus of this study was to investigate the effect of spaceflight on the Drosophila circadian clock at both the behavioral and molecular level. We used China's Shenzhou-9 spaceship to carry Drosophila. After 13 days of spaceflight, behavior tests showed that the flies maintained normal locomotor activity rhythm and sleep pattern. The expression level and rhythm of major clock genes were also unaffected. However, expression profiling showed differentially regulated output genes of the circadian clock system between space flown and control flies, suggesting that spaceflight affected the circadian output pathway. We also investigated other physiological effects of spaceflight such as lipid metabolism and lifespan, and searched genes significantly affected by spaceflight using microarray analysis. These results provide new information on the effects of spaceflight on circadian rhythm, lipid metabolism and lifespan. Furthermore, we showed that studying the effect of spaceflight on gene expression using samples collected at different Zeitgeber time could obtain different results, suggesting the importance of appropriate sampling procedures in studies on the effects of spaceflight.

Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

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Zhu Zhu

2016-01-01

Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

Enhanced musical rhythmic perception in Turkish early and late learners of German

NARCIS (Netherlands)

Roncaglia-Denissen, M.P.; Schmidt-Kassow, M.; Heine, A.; Vuust, P.; Kotz, S.A.

2013-01-01

As language rhythm relies partly on general acoustic properties, such as intensity and duration, mastering two languages with distinct rhythmic properties (i.e., stress position) may enhance musical rhythm perception. We investigated whether competence in a second language (L2) with different

Dim Light at Night Disrupts Molecular Circadian Rhythms and Affects Metabolism

Science.gov (United States)

Fonken, Laura K.; Aubrecht, Taryn G.; Meléndez-Fernández, O. Hecmarie; Weil, Zachary M.; Nelson, Randy J.

2014-01-01

With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms which are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electrical lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to nighttime light and investigated changes in the circadian system and body weight. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night attenuate core circadian clock rhythms in the SCN at both the gene and protein level. Moreover, circadian clock rhythms were perturbed in the liver by nighttime light exposure. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide mechanistic evidence for how mild changes in environmental lighting can alter circadian and metabolic function. PMID:23929553

The Edit Distance as a Measure of Perceived Rhythmic Similarity

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Olaf Post

2012-07-01

Full Text Available The ‘edit distance’ (or ‘Levenshtein distance’ measure of distance between two data sets is defined as the minimum number of editing operations – insertions, deletions, and substitutions – that are required to transform one data set to the other (Orpen and Huron, 1992. This measure of distance has been applied frequently and successfully in music information retrieval, but rarely in predicting human perception of distance. In this study, we investigate the effectiveness of the edit distance as a predictor of perceived rhythmic dissimilarity under simple rhythmic alterations. Approaching rhythms as a set of pulses that are either onsets or silences, we study two types of alterations. The first experiment is designed to test the model’s accuracy for rhythms that are relatively similar; whether rhythmic variations with the same edit distance to a source rhythm are also perceived as relatively similar by human subjects. In addition, we observe whether the salience of an edit operation is affected by its metric placement in the rhythm. Instead of using a rhythm that regularly subdivides a 4/4 meter, our source rhythm is a syncopated 16-pulse rhythm, the son. Results show a high correlation between the predictions by the edit distance model and human similarity judgments (r = 0.87; a higher correlation than for the well-known generative theory of tonal music (r = 0.64. In the second experiment, we seek to assess the accuracy of the edit distance model in predicting relatively dissimilar rhythms. The stimuli used are random permutations of the son’s inter-onset intervals: 3-3-4-2-4. The results again indicate that the edit distance correlates well with the perceived rhythmic dissimilarity judgments of the subjects (r = 0.76. To gain insight in the relationships between the individual rhythms, the results are also presented by means of graphic phylogenetic trees.

Control of the Estradiol-Induced Prolactin Surge by the Suprachiasmatic Nucleus

NARCIS (Netherlands)

Palm, Inge F.; van der Beek, Eline M.; Swarts, Hans J. M.; van der Vliet, Jan; Wiegant, Victor M.; Buijs, Ruud M.; Kalsbeek, Andries

2001-01-01

In the present study we investigated how the suprachiasmatic nucleus (SCN) controls the E(2)-induced PRL surge in female rats. First, the role of vasopressin (VP), a SCN transmitter present in medial preoptic area (MPO) projections and rhythmically released by SCN neurons, as a circadian signal for

Differential processing of melodic, rhythmic and simple tone deviations in musicians--an MEG study.

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Lappe, Claudia; Lappe, Markus; Pantev, Christo

2016-01-01

Rhythm and melody are two basic characteristics of music. Performing musicians have to pay attention to both, and avoid errors in either aspect of their performance. To investigate the neural processes involved in detecting melodic and rhythmic errors from auditory input we tested musicians on both kinds of deviations in a mismatch negativity (MMN) design. We found that MMN responses to a rhythmic deviation occurred at shorter latencies than MMN responses to a melodic deviation. Beamformer source analysis showed that the melodic deviation activated superior temporal, inferior frontal and superior frontal areas whereas the activation pattern of the rhythmic deviation focused more strongly on inferior and superior parietal areas, in addition to superior temporal cortex. Activation in the supplementary motor area occurred for both types of deviations. We also recorded responses to similar pitch and tempo deviations in a simple, non-musical repetitive tone pattern. In this case, there was no latency difference between the MMNs and cortical activation was smaller and mostly limited to auditory cortex. The results suggest that prediction and error detection of musical stimuli in trained musicians involve a broad cortical network and that rhythmic and melodic errors are processed in partially different cortical streams. Copyright © 2015 Elsevier Inc. All rights reserved.

Body composition and cardiac dimensions in elite rhythmic gymnasts.

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Galetta, F; Franzoni, F; D'alessandro, C; Piazza, M; Tocchini, L; Fallahi, P; Antonelli, A; Cupisti, F; Santoro, G

2015-09-01

Rhythmic gymnasts are often believed to be a population at risk of malnutrition because of their tendency to keep a low weight and a lean appearance for better athletic performance, and because they start intensive training at a very young age. The purpose of this study was to evaluate in adolescent elite gymnasts the effects of physical activity on body composition and cardiac morphology and function. Sixteen national level rhythmic gymnasts and 16 control adolescent female underwent anthropometric measurements, bioelectric impedance and echocardiography to assess body composition and cardiac morphology and function. As compared to controls, gymnasts had lower body mass index (16.9±1.1 vs. 18.7±1.0, Panalysis showed a lower percentage of body fat in the gymnasts, together with a higher percentage of fat-free mass. Echocardiographic findings indicate that elite rhythmic gymnastics present left ventricular remodeling as training-induced cardiac adaptation. Intensive training, dietary attitude and evident leanness of rhythmic gymnasts are not associated with cardiac abnormalities, as it is the case of pathological leanness.

The 1993 Gordon Research Conference on Chronobiology

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Schwartz, William J.

1993-01-01

The study of biological timekeeping is now at a particularly fertile stage, encompassing multiple levels of biological organization, recruiting a wide array of disciplines and methodologies and uniting a host of investigators. This report summarizes a research conference on Chronobiology. Some of the topics focused on transcriptional and translational mechanisms of circadian rhythmicity, with discussions of putative 'clock genes' in cyanobacteria, algae, fungi, fruitflies, and hamsters. Cellular analysis, with emphasis on photoreceptors in frogs, neurons in molluscs, and testis in moths was addressed. New methods for investigating the circadian clock in the suprachiasmatic nucleus were introduced.

Rhythmic synchronization tapping to an audio–visual metronome in budgerigars

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Hasegawa, Ai; Okanoya, Kazuo; Hasegawa, Toshikazu; Seki, Yoshimasa

2011-01-01

In all ages and countries, music and dance have constituted a central part in human culture and communication. Recently, vocal-learning animals such as parrots and elephants have been found to share rhythmic ability with humans. Thus, we investigated the rhythmic synchronization of budgerigars, a vocal-mimicking parrot species, under controlled conditions and a systematically designed experimental paradigm as a first step in understanding the evolution of musical entrainment. We trained eight budgerigars to perform isochronous tapping tasks in which they pecked a key to the rhythm of audio–visual metronome-like stimuli. The budgerigars showed evidence of entrainment to external stimuli over a wide range of tempos. They seemed to be inherently inclined to tap at fast tempos, which have a similar time scale to the rhythm of budgerigars' natural vocalizations. We suggest that vocal learning might have contributed to their performance, which resembled that of humans. PMID:22355637

Rhythmic synchronization tapping to an audio-visual metronome in budgerigars.

Science.gov (United States)

Hasegawa, Ai; Okanoya, Kazuo; Hasegawa, Toshikazu; Seki, Yoshimasa

2011-01-01

In all ages and countries, music and dance have constituted a central part in human culture and communication. Recently, vocal-learning animals such as parrots and elephants have been found to share rhythmic ability with humans. Thus, we investigated the rhythmic synchronization of budgerigars, a vocal-mimicking parrot species, under controlled conditions and a systematically designed experimental paradigm as a first step in understanding the evolution of musical entrainment. We trained eight budgerigars to perform isochronous tapping tasks in which they pecked a key to the rhythm of audio-visual metronome-like stimuli. The budgerigars showed evidence of entrainment to external stimuli over a wide range of tempos. They seemed to be inherently inclined to tap at fast tempos, which have a similar time scale to the rhythm of budgerigars' natural vocalizations. We suggest that vocal learning might have contributed to their performance, which resembled that of humans.

Intensive gait training with rhythmic auditory stimulation in individuals with chronic hemiparetic stroke: a pilot randomized controlled study.

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Cha, Yuri; Kim, Young; Hwang, Sujin; Chung, Yijung

2014-01-01

Motor relearning protocols should involve task-oriented movement, focused attention, and repetition of desired movements. To investigate the effect of intensive gait training with rhythmic auditory stimulation on postural control and gait performance in individuals with chronic hemiparetic stroke. Twenty patients with chronic hemiparetic stroke participated in this study. Subjects in the Rhythmic auditory stimulation training group (10 subjects) underwent intensive gait training with rhythmic auditory stimulation for a period of 6 weeks (30 min/day, five days/week), while those in the control group (10 subjects) underwent intensive gait training for the same duration. Two clinical measures, Berg balance scale and stroke specific quality of life scale, and a 2-demensional gait analysis system, were used as outcome measure. To provide rhythmic auditory stimulation during gait training, the MIDI Cuebase musical instrument digital interface program and a KM Player version 3.3 was utilized for this study. Intensive gait training with rhythmic auditory stimulation resulted in significant improvement in scores on the Berg balance scale, gait velocity, cadence, stride length and double support period in affected side, and stroke specific quality of life scale compared with the control group after training. Findings of this study suggest that intensive gait training with rhythmic auditory stimulation improves balance and gait performance as well as quality of life, in individuals with chronic hemiparetic stroke.

A comparison of high-throughput techniques for assaying circadian rhythms in plants.

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Tindall, Andrew J; Waller, Jade; Greenwood, Mark; Gould, Peter D; Hartwell, James; Hall, Anthony

2015-01-01

Over the last two decades, the development of high-throughput techniques has enabled us to probe the plant circadian clock, a key coordinator of vital biological processes, in ways previously impossible. With the circadian clock increasingly implicated in key fitness and signalling pathways, this has opened up new avenues for understanding plant development and signalling. Our tool-kit has been constantly improving through continual development and novel techniques that increase throughput, reduce costs and allow higher resolution on the cellular and subcellular levels. With circadian assays becoming more accessible and relevant than ever to researchers, in this paper we offer a review of the techniques currently available before considering the horizons in circadian investigation at ever higher throughputs and resolutions.

Integrating circadian activity and gene expression profiles to predict chronotoxicity of Drosophila suzukii response to insecticides.

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Hamby, Kelly A; Kwok, Rosanna S; Zalom, Frank G; Chiu, Joanna C

2013-01-01

Native to Southeast Asia, Drosophila suzukii (Matsumura) is a recent invader that infests intact ripe and ripening fruit, leading to significant crop losses in the U.S., Canada, and Europe. Since current D. suzukii management strategies rely heavily on insecticide usage and insecticide detoxification gene expression is under circadian regulation in the closely related Drosophila melanogaster, we set out to determine if integrative analysis of daily activity patterns and detoxification gene expression can predict chronotoxicity of D. suzukii to insecticides. Locomotor assays were performed under conditions that approximate a typical summer or winter day in Watsonville, California, where D. suzukii was first detected in North America. As expected, daily activity patterns of D. suzukii appeared quite different between 'summer' and 'winter' conditions due to differences in photoperiod and temperature. In the 'summer', D. suzukii assumed a more bimodal activity pattern, with maximum activity occurring at dawn and dusk. In the 'winter', activity was unimodal and restricted to the warmest part of the circadian cycle. Expression analysis of six detoxification genes and acute contact bioassays were performed at multiple circadian times, but only in conditions approximating Watsonville summer, the cropping season, when most insecticide applications occur. Five of the genes tested exhibited rhythmic expression, with the majority showing peak expression at dawn (ZT0, 6am). We observed significant differences in the chronotoxicity of D. suzukii towards malathion, with highest susceptibility at ZT0 (6am), corresponding to peak expression of cytochrome P450s that may be involved in bioactivation of malathion. High activity levels were not found to correlate with high insecticide susceptibility as initially hypothesized. Chronobiology and chronotoxicity of D. suzukii provide valuable insights for monitoring and control efforts, because insect activity as well as insecticide timing

Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression

KAUST Repository

Rossetti, Clara

2017-12-06

Obesity and depression are major public health concerns, and there is increasing evidence that they share etiological mechanisms. CREB-regulated transcription coactivator 1 (CRTC1) participates in neurobiological pathways involved in both mood and energy balance regulation. Crtc1 -/- mice rapidly develop a depressive-like and obese phenotype in early adulthood, and are therefore a relevant animal model to explore possible common mechanisms underlying mood disorders and obesity. Here, the obese phenotype of male and female Crtc1 -/- mice was further characterized by investigating CRTC1\\'s role in the homeostatic and hedonic regulation of food intake, as well as its influence on daily locomotor activity. Crtc1 -/- mice showed a strong gender difference in the homeostatic regulation of energy balance. Mutant males were hyperphagic and rapidly developed obesity on normal chow diet, whereas Crtc1 -/- females exhibited mild late-onset obesity without hyperphagia. Overeating of mutant males was accompanied by alterations in the expression of several orexigenic and anorexigenic hypothalamic genes, thus confirming a key role of CRTC1 in the central regulation of food intake. No alteration in preference and conditioned response for saccharine was observed in Crtc1 -/- mice, suggesting that mutant males\\' hyperphagia was not due to an altered hedonic regulation of food intake. Intriguingly, mutant males exhibited a hyperphagic behavior only during the resting (diurnal) phase of the light cycle. This abnormal feeding behavior was associated with a higher diurnal locomotor activity indicating that the lack of CRTC1 may affect circadian rhythmicity. Collectively, these findings highlight the male-specific involvement of CRTC1 in the central control of energy balance and circadian locomotor activity.

Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression

KAUST Repository

Rossetti, Clara; Sciarra, Daniel; Petit, Jean-Marie; Eap, Chin B.; Halfon, Olivier; Magistretti, Pierre J.; Boutrel, Benjamin; Cardinaux, Jean-René

2017-01-01

Obesity and depression are major public health concerns, and there is increasing evidence that they share etiological mechanisms. CREB-regulated transcription coactivator 1 (CRTC1) participates in neurobiological pathways involved in both mood and energy balance regulation. Crtc1 -/- mice rapidly develop a depressive-like and obese phenotype in early adulthood, and are therefore a relevant animal model to explore possible common mechanisms underlying mood disorders and obesity. Here, the obese phenotype of male and female Crtc1 -/- mice was further characterized by investigating CRTC1's role in the homeostatic and hedonic regulation of food intake, as well as its influence on daily locomotor activity. Crtc1 -/- mice showed a strong gender difference in the homeostatic regulation of energy balance. Mutant males were hyperphagic and rapidly developed obesity on normal chow diet, whereas Crtc1 -/- females exhibited mild late-onset obesity without hyperphagia. Overeating of mutant males was accompanied by alterations in the expression of several orexigenic and anorexigenic hypothalamic genes, thus confirming a key role of CRTC1 in the central regulation of food intake. No alteration in preference and conditioned response for saccharine was observed in Crtc1 -/- mice, suggesting that mutant males' hyperphagia was not due to an altered hedonic regulation of food intake. Intriguingly, mutant males exhibited a hyperphagic behavior only during the resting (diurnal) phase of the light cycle. This abnormal feeding behavior was associated with a higher diurnal locomotor activity indicating that the lack of CRTC1 may affect circadian rhythmicity. Collectively, these findings highlight the male-specific involvement of CRTC1 in the central control of energy balance and circadian locomotor activity.

The Effect of Cataract Surgery on Circadian Photoentrainment

DEFF Research Database (Denmark)

Brøndsted, Adam Elias; Sander, Birgit; Haargaard, Birgitte

2015-01-01

of cataract surgery on circadian photoentrainment and to determine any difference between blue-blocking and neutral intraocular lenses (IOLs). DESIGN: The study was a single-center, investigator-driven, double-masked, block-randomized clinical trial. PARTICIPANTS: One eye in 76 patients with bilateral age......PURPOSE: Cataract decreases blue light transmission. Because of the selective blue light sensitivity of the retinal ganglion cells governing circadian photoentrainment, cataract may interfere with normal sleep-wake regulation and cause sleep disturbances. The purpose was to investigate the effect......-related cataract eligible for cataract surgery was included. METHODS: Intervention was cataract surgery by phacoemulsification. Patients were randomized to receive a blue-blocking or neutral IOL. MAIN OUTCOME MEASURES: Primary outcome was activation of intrinsic photosensitive ganglion cells using post...

An analysis of rhythmic ratios in scores of various kinds of music

NARCIS (Netherlands)

Sadakata, M.; Desain, P.W.M.; Honing, H.J.; Lipscomb, S.D.; Ashley, R.; Gjerdignen, R.O.; Webster, P.

2004-01-01

The aim of this study is to investigate our daily experience of rhythm. The frequency of occurrence of rhythmic patterns consisting of two intervals was counted in different music corpora. Only subdivisions of metrical units were considered. A very large corpus of diverse kinds of music (western

Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential

Science.gov (United States)

Hurley, Jennifer M.; Dasgupta, Arko; Emerson, Jillian M.; Zhou, Xiaoying; Ringelberg, Carol S.; Knabe, Nicole; Lipzen, Anna M.; Lindquist, Erika A.; Daum, Christopher G.; Barry, Kerrie W.; Grigoriev, Igor V.; Smith, Kristina M.; Galagan, James E.; Bell-Pedersen, Deborah; Freitag, Michael; Cheng, Chao; Loros, Jennifer J.; Dunlap, Jay C.

2014-01-01

Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation–based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset of ccg promoters, including those of many transcription factors. High temporal resolution (2-h) sampling over 48 h using RNA sequencing (RNA-Seq) identified circadianly expressed genes in Neurospora, revealing that from ∼10% to as much 40% of the transcriptome can be expressed under circadian control. Functional classifications of these genes revealed strong enrichment in pathways involving metabolism, protein synthesis, and stress responses; in broad terms, daytime metabolic potential favors catabolism, energy production, and precursor assembly, whereas night activities favor biosynthesis of cellular components and growth. Discriminative regular expression motif elicitation (DREME) identified key promoter motifs highly correlated with the temporal regulation of ccgs. Correlations between ccg abundance from RNA-Seq, the degree of ccg-promoter activation as reported by ccg-promoter–luciferase fusions, and binding of WCC as measured by ChIP-Seq, are not strong. Therefore, although circadian activation is critical to ccg rhythmicity, posttranscriptional regulation plays a major role in determining rhythmicity at the mRNA level. PMID:25362047

Group Rhythmic Synchrony and Attention in Children

Directory of Open Access Journals (Sweden)

Alexander K Khalil

2013-09-01

Full Text Available Synchrony, or the coordinated processing of time, is an often-overlooked yet critical context for human interaction. This study tests the relationship between the ability to synchronize rhythmically in a group setting with the ability to attend in 102 elementary schoolchildren. Impairments in temporal processing have frequently been shown to exist in clinical populations with learning disorders, particularly those with Attention Deficit Hyperactivity Disorder (ADHD. Based on this evidence, we hypothesized that the ability to synchronize rhythmically in a group setting—an instance of the type of temporal processing necessary for successful interaction and learning—would be correlated with the ability to attend across the continuum of the population. A music class is an ideal setting for the study of interpersonal timing. In order to measure synchrony in this context, we constructed instruments that allowed the recording and measurement of individual rhythmic performance. The SWAN teacher questionnaire was used as a measurement of attentional behavior. We find that the ability to synchronize with others in a group music class can predict a child’s attentional behavior.

Molecular Mechanisms of Circadian Regulation During Spaceflight

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Zanello, S. B.; Boyle, R.

2012-01-01

The physiology of both vertebrates and invertebrates follows internal rhythms coordinated in phase with the 24-hour daily light cycle. This circadian clock is governed by a central pacemaker, the suprachiasmatic nucleus (SCN) in the brain. However, peripheral circadian clocks or oscillators have been identified in most tissues. How the central and peripheral oscillators are synchronized is still being elucidated. Light is the main environmental cue that entrains the circadian clock. Under the absence of a light stimulus, the clock continues its oscillation in a free-running condition. In general, three functional compartments of the circadian clock are defined. The vertebrate retina contains endogenous clocks that control many aspects of retinal physiology, including retinal sensitivity to light, neurohormone synthesis (melatonin and dopamine), rod disk shedding, signalling pathways and gene expression. Neurons with putative local circadian rhythm generation are found among all the major neuron populations in the mammalian retina. In the mouse, clock genes and function are more localized to the inner retinal and ganglion cell layers. The photoreceptor, however, secrete melatonin which may still serve a an important circadian signal. The reception and transmission of the non-visual photic stimulus resides in a small subpopulation (1-3%) or retinal ganglion cells (RGC) that express the pigment melanopsin (Opn4) and are called intrisically photoreceptive RGC (ipRGC). Melanopsin peak absorption is at 420 nm and all the axons of the ipRGC reach the SCN. A common countermeasure for circadian re-entrainment utilizes blue-green light to entrain the circadian clock and mitigate the risk of fatigue and health and performance decrement due to circadian rhythm disruption. However, an effective countermeasure targeting the photoreceptor system requires that the basic circadian molecular machinery remains intact during spaceflight. We hypothesize that spaceflight may affect ip

The Importance of Stochastic Effects for Explaining Entrainment in the Zebrafish Circadian Clock

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Raphaela Heussen

2015-01-01

Full Text Available The circadian clock plays a pivotal role in modulating physiological processes and has been implicated, either directly or indirectly, in a range of pathological states including cancer. Here we investigate how the circadian clock is entrained by external cues such as light. Working with zebrafish cell lines and combining light pulse experiments with simulation efforts focused on the role of synchronization effects, we find that even very modest doses of light exposure are sufficient to trigger some entrainment, whereby a higher light intensity or duration correlates with strength of the circadian signal. Moreover, we observe in the simulations that stochastic effects may be considered an essential feature of the circadian clock in order to explain the circadian signal decay in prolonged darkness, as well as light initiated resynchronization as a strong component of entrainment.

Evolution of circadian organization in vertebrates

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M. Menaker

1997-03-01

Full Text Available Circadian organization means the way in which the entire circadian system above the cellular level is put together physically and the principles and rules that determine the interactions among its component parts which produce overt rhythms of physiology and behavior. Understanding this organization and its evolution is of practical importance as well as of basic interest. The first major problem that we face is the difficulty of making sense of the apparently great diversity that we observe in circadian organization of diverse vertebrates. Some of this diversity falls neatly into place along phylogenetic lines leading to firm generalizations: i in all vertebrates there is a "circadian axis" consisting of the retinas, the pineal gland and the suprachiasmatic nucleus (SCN, ii in many non-mammalian vertebrates of all classes (but not in any mammals the pineal gland is both a photoreceptor and a circadian oscillator, and iii in all non-mammalian vertebrates (but not in any mammals there are extraretinal (and extrapineal circadian photoreceptors. An interesting explanation of some of these facts, especially the differences between mammals and other vertebrates, can be constructed on the assumption that early in their evolution mammals passed through a "nocturnal bottleneck". On the other hand, a good deal of the diversity among the circadian systems of vertebrates does not fall neatly into place along phylogenetic lines. In the present review we will consider how we might better understand such "phylogenetically incoherent" diversity and what sorts of new information may help to further our understanding of the evolution of circadian organization in vertebrates

Circadian monitoring of ECG findings and central hemodynamics in cancer patients at radiotherapy planning

International Nuclear Information System (INIS)

Tolkachov, Yu.A.; Vasil'jev, L.Ya.; Svinarenko, A.V.

2003-01-01

Fifty-seven patients aged 34-67 were examined. Considerable circadian fluctuations of main hemodynamic and ECG parameters, which can suggest disorders of circadian rhythms or limit chemoradiotherapy were not noticed in different cancers. Functional criteria of biorhythm state require further investigation

Synthesis of asymmetric movement trajectories in timed rhythmic behaviour by means of frequency modulation.

Science.gov (United States)

Waadeland, Carl Haakon

2017-01-01

Results from different empirical investigations on gestural aspects of timed rhythmic movements indicate that the production of asymmetric movement trajectories is a feature that seems to be a common characteristic of various performances of repetitive rhythmic patterns. The behavioural or neural origin of these asymmetrical trajectories is, however, not identified. In the present study we outline a theoretical model that is capable of producing syntheses of asymmetric movement trajectories documented in empirical investigations by Balasubramaniam et al. (2004). Characteristic qualities of the extension/flexion profiles in the observed asymmetric trajectories are reproduced, and we conduct an experiment similar to Balasubramaniam et al. (2004) to show that the empirically documented movement trajectories and our modelled approximations share the same spectral components. The model is based on an application of frequency modulated movements, and a theoretical interpretation offered by the model is to view paced rhythmic movements as a result of an unpaced movement being "stretched" and "compressed", caused by the presence of a metronome. We discuss our model construction within the framework of event-based and emergent timing, and argue that a change between these timing modes might be reflected by the strength of the modulation in our model. Copyright © 2016 Elsevier B.V. All rights reserved.

Genomic Analysis Reveals Contrasting PIFq Contribution to Diurnal Rhythmic Gene Expression in PIF-Induced and -Repressed Genes.

Science.gov (United States)

Martin, Guiomar; Soy, Judit; Monte, Elena

2016-01-01

Members of the PIF quartet (PIFq; PIF1, PIF3, PIF4, and PIF5) collectively contribute to induce growth in Arabidopsis seedlings under short day (SD) conditions, specifically promoting elongation at dawn. Their action involves the direct regulation of growth-related and hormone-associated genes. However, a comprehensive definition of the PIFq-regulated transcriptome under SD is still lacking. We have recently shown that SD and free-running (LL) conditions correspond to "growth" and "no growth" conditions, respectively, correlating with greater abundance of PIF protein in SD. Here, we present a genomic analysis whereby we first define SD-regulated genes at dawn compared to LL in the wild type, followed by identification of those SD-regulated genes whose expression depends on the presence of PIFq. By using this sequential strategy, we have identified 349 PIF/SD-regulated genes, approximately 55% induced and 42% repressed by both SD and PIFq. Comparison with available databases indicates that PIF/SD-induced and PIF/SD-repressed sets are differently phased at dawn and mid-morning, respectively. In addition, we found that whereas rhythmicity of the PIF/SD-induced gene set is lost in LL, most PIF/SD-repressed genes keep their rhythmicity in LL, suggesting differential regulation of both gene sets by the circadian clock. Moreover, we also uncovered distinct overrepresented functions in the induced and repressed gene sets, in accord with previous studies in other examined PIF-regulated processes. Interestingly, promoter analyses showed that, whereas PIF/SD-induced genes are enriched in direct PIF targets, PIF/SD-repressed genes are mostly indirectly regulated by the PIFs and might be more enriched in ABA-regulated genes.

Rate control and quality assurance during rhythmic force tracking.

Science.gov (United States)

Huang, Cheng-Ya; Su, Jyong-Huei; Hwang, Ing-Shiou

2014-02-01

Movement characteristics can be coded in the single neurons or in the summed activity of neural populations. However, whether neural oscillations are conditional to the frequency demand and task quality of rhythmic force regulation is still unclear. This study was undertaken to investigate EEG dynamics and behavior correlates during force-tracking at different target rates. Fourteen healthy volunteers conducted load-varying isometric abduction of the index finger by coupling the force output to sinusoidal targets at 0.5 Hz, 1.0 Hz, and 2.0 Hz. Our results showed that frequency demand significantly affected EEG delta oscillation (1-4 Hz) in the C3, CP3, CPz, and CP4 electrodes, with the greatest delta power and lowest delta peak around 1.5 Hz for slower tracking at 0.5 Hz. Those who had superior tracking congruency also manifested enhanced alpha oscillation (8-12 Hz). Alpha rhythms of the skilled performers during slow tracking spread through the whole target cycle, except for the phase of direction changes. However, the alpha rhythms centered at the mid phase of a target cycle with increasing target rate. In conclusion, our findings clearly suggest two advanced roles of cortical oscillation in rhythmic force regulation. Rate-dependent delta oscillation involves a paradigm shift in force control under different time scales. Phasic organization of alpha rhythms during rhythmic force tracking is related to behavioral success underlying the selective use of bimodal controls (feedback and feedforward processes) and the timing of attentional focus on the target's peak velocity. Copyright © 2013 Elsevier B.V. All rights reserved.

Calculating activation energies for temperature compensation in circadian rhythms

International Nuclear Information System (INIS)

Bodenstein, C; Heiland, I; Schuster, S

2011-01-01

Many biological species possess a circadian clock, which helps them anticipate daily variations in the environment. In the absence of external stimuli, the rhythm persists autonomously with a period of approximately 24 h. However, single pulses of light, nutrients, chemicals or temperature can shift the clock phase. In the case of light- and temperature-cycles, this allows entrainment of the clock to cycles of exactly 24 h. Circadian clocks have the remarkable property of temperature compensation, that is, the period of the circadian rhythm remains relatively constant within a physiological range of temperatures. For several organisms, temperature-regulated processes within the circadian clock have been identified in recent years. However, how these processes contribute to temperature compensation is not fully understood. Here, we theoretically investigate temperature compensation in general oscillatory systems. It is known that every oscillator can be locally temperature compensated around a reference temperature, if reactions are appropriately balanced. A balancing is always possible if the control coefficient with respect to the oscillation period of at least one reaction in the oscillator network is positive. However, for global temperature compensation, the whole physiological temperature range is relevant. Here, we use an approach which leads to an optimization problem subject to the local balancing principle. We use this approach to analyse different circadian clock models proposed in the literature and calculate activation energies that lead to temperature compensation

Rhythmic Density Affects Listeners' Emotional Response to Microtiming

Directory of Open Access Journals (Sweden)

Olivier Senn

2017-10-01

– Study A investigates the effect of fixed time displacements within and between the parts played by different musicians. Listeners (n = 160 reacted negatively to irregularities within the drum track, but the mutual displacement of bass vs. drums did not have an effect.– Study B develops three metrics to calculate the average microtiming magnitude in a musical excerpt. The experiment showed that listeners' (n = 160 emotional responses to expert performance microtiming aligned with each other across styles, when microtiming magnitude was adjusted for rhythmic density. This indicates that rhythmic density is a unifying moderator for listeners' emotional response to microtiming in swing and funk.– Study C used the data from both experiments in order to compare the effect of fixed microtiming displacements (from Study A with scaled versions of the originally performed microtiming patterns (from Study B. It showed that fixed snare drum displacements irritated expert listeners more than the more flexible deviations occurring in the original performances. This provides some evidence that listeners' emotional response to microtiming deviations not only depends on the magnitude of the deviations, but also on the kind and origin of the microtiming patterns (fixed lab displacements vs. flexible performance microtiming.

Alpha-Band Rhythms in Visual Task Performance: Phase-Locking by Rhythmic Sensory Stimulation

Science.gov (United States)

de Graaf, Tom A.; Gross, Joachim; Paterson, Gavin; Rusch, Tessa; Sack, Alexander T.; Thut, Gregor

2013-01-01

Oscillations are an important aspect of neuronal activity. Interestingly, oscillatory patterns are also observed in behaviour, such as in visual performance measures after the presentation of a brief sensory event in the visual or another modality. These oscillations in visual performance cycle at the typical frequencies of brain rhythms, suggesting that perception may be closely linked to brain oscillations. We here investigated this link for a prominent rhythm of the visual system (the alpha-rhythm, 8–12 Hz) by applying rhythmic visual stimulation at alpha-frequency (10.6 Hz), known to lead to a resonance response in visual areas, and testing its effects on subsequent visual target discrimination. Our data show that rhythmic visual stimulation at 10.6 Hz: 1) has specific behavioral consequences, relative to stimulation at control frequencies (3.9 Hz, 7.1 Hz, 14.2 Hz), and 2) leads to alpha-band oscillations in visual performance measures, that 3) correlate in precise frequency across individuals with resting alpha-rhythms recorded over parieto-occipital areas. The most parsimonious explanation for these three findings is entrainment (phase-locking) of ongoing perceptually relevant alpha-band brain oscillations by rhythmic sensory events. These findings are in line with occipital alpha-oscillations underlying periodicity in visual performance, and suggest that rhythmic stimulation at frequencies of intrinsic brain-rhythms can be used to reveal influences of these rhythms on task performance to study their functional roles. PMID:23555873

Circadian behaviour in neuroglobin deficient mice

DEFF Research Database (Denmark)

Hundahl, Christian A; Fahrenkrug, Jan; Hay-Schmidt, Anders

2012-01-01

on circadian behavior. Ngb-deficient and wild-type (wt) mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1) and the immediate early gene Fos was determined after light...

Chronotype and circadian rhythm in bipolar disorder: A systematic review.

Science.gov (United States)

Melo, Matias C A; Abreu, Rafael L C; Linhares Neto, Vicente B; de Bruin, Pedro F C; de Bruin, Veralice M S

2017-08-01

Despite a complex relationship between mood, sleep and rhythm, the impact of circadian disruptions on bipolar disorder (BD) has not been clarified. The purpose of this systematic review was to define current evidence regarding chronotype and circadian rhythm patterns in BD patients. 42 studies were included, involving 3432 BD patients. Disruption of the biological rhythm was identified, even in drug-naïve BD patients and independently of mood status. Daily profiles of melatonin levels and cortisol indicated a delayed phase. Depression was more frequently associated with circadian alterations than euthymia. Few studies evaluated mania, demonstrating irregular rhythms. Evening type was more common in BD adults. Studies about the influence of chronotype on depressive symptoms showed conflicting results. Only one investigation observed the influences of chronotype in mania, revealing no significant association. Effects of psychoeducation and lithium on rhythm in BD patients were poorly studied, demonstrating no improvement of rhythm parameters. Studies about genetics are incipient. In conclusion, disruption in circadian rhythm and eveningness are common in BD. Prospective research evaluating the impact of circadian disruption on mood symptoms, metabolism, seasonality, the influence of age and the effects of mood stabilizers are needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of mRNA markers for estimating blood deposition time: Towards alibi testing from human forensic stains with rhythmic biomarkers.

Science.gov (United States)

Lech, Karolina; Liu, Fan; Ackermann, Katrin; Revell, Victoria L; Lao, Oscar; Skene, Debra J; Kayser, Manfred

2016-03-01

Determining the time a biological trace was left at a scene of crime reflects a crucial aspect of forensic investigations as - if possible - it would permit testing the sample donor's alibi directly from the trace evidence, helping to link (or not) the DNA-identified sample donor with the crime event. However, reliable and robust methodology is lacking thus far. In this study, we assessed the suitability of mRNA for the purpose of estimating blood deposition time, and its added value relative to melatonin and cortisol, two circadian hormones we previously introduced for this purpose. By analysing 21 candidate mRNA markers in blood samples from 12 individuals collected around the clock at 2h intervals for 36h under real-life, controlled conditions, we identified 11 mRNAs with statistically significant expression rhythms. We then used these 11 significantly rhythmic mRNA markers, with and without melatonin and cortisol also analysed in these samples, to establish statistical models for predicting day/night time categories. We found that although in general mRNA-based estimation of time categories was less accurate than hormone-based estimation, the use of three mRNA markers HSPA1B, MKNK2 and PER3 together with melatonin and cortisol generally enhanced the time prediction accuracy relative to the use of the two hormones alone. Our data best support a model that by using these five molecular biomarkers estimates three time categories, i.e. night/early morning, morning/noon, and afternoon/evening with prediction accuracies expressed as AUC values of 0.88, 0.88, and 0.95, respectively. For the first time, we demonstrate the value of mRNA for blood deposition timing and introduce a statistical model for estimating day/night time categories based on molecular biomarkers, which shall be further validated with additional samples in the future. Moreover, our work provides new leads for molecular approaches on time of death estimation using the significantly rhythmic m

Age-Related Changes in Bimanual Instrument Playing with Rhythmic Cueing

Directory of Open Access Journals (Sweden)

Soo Ji Kim

2017-09-01

Full Text Available Deficits in bimanual coordination of older adults have been demonstrated to significantly limit their functioning in daily life. As a bimanual sensorimotor task, instrument playing has great potential for motor and cognitive training in advanced age. While the process of matching a person’s repetitive movements to auditory rhythmic cueing during instrument playing was documented to involve motor and attentional control, investigation into whether the level of cognitive functioning influences the ability to rhythmically coordinate movement to an external beat in older populations is relatively limited. Therefore, the current study aimed to examine how timing accuracy during bimanual instrument playing with rhythmic cueing differed depending on the degree of participants’ cognitive aging. Twenty one young adults, 20 healthy older adults, and 17 older adults with mild dementia participated in this study. Each participant tapped an electronic drum in time to the rhythmic cueing provided using both hands simultaneously and in alternation. During bimanual instrument playing with rhythmic cueing, mean and variability of synchronization errors were measured and compared across the groups and the tempo of cueing during each type of tapping task. Correlations of such timing parameters with cognitive measures were also analyzed. The results showed that the group factor resulted in significant differences in the synchronization errors-related parameters. During bimanual tapping tasks, cognitive decline resulted in differences in synchronization errors between younger adults and older adults with mild dimentia. Also, in terms of variability of synchronization errors, younger adults showed significant differences in maintaining timing performance from older adults with and without mild dementia, which may be attributed to decreased processing time for bimanual coordination due to aging. Significant correlations were observed between variability of

Model of rhythmic ball bouncing using a visually controlled neural oscillator.

Science.gov (United States)

Avrin, Guillaume; Siegler, Isabelle A; Makarov, Maria; Rodriguez-Ayerbe, Pedro

2017-10-01

The present paper investigates the sensory-driven modulations of central pattern generator dynamics that can be expected to reproduce human behavior during rhythmic hybrid tasks. We propose a theoretical model of human sensorimotor behavior able to account for the observed data from the ball-bouncing task. The novel control architecture is composed of a Matsuoka neural oscillator coupled with the environment through visual sensory feedback. The architecture's ability to reproduce human-like performance during the ball-bouncing task in the presence of perturbations is quantified by comparison of simulated and recorded trials. The results suggest that human visual control of the task is achieved online. The adaptive behavior is made possible by a parametric and state control of the limit cycle emerging from the interaction of the rhythmic pattern generator, the musculoskeletal system, and the environment. NEW & NOTEWORTHY The study demonstrates that a behavioral model based on a neural oscillator controlled by visual information is able to accurately reproduce human modulations in a motor action with respect to sensory information during the rhythmic ball-bouncing task. The model attractor dynamics emerging from the interaction between the neuromusculoskeletal system and the environment met task requirements, environmental constraints, and human behavioral choices without relying on movement planning and explicit internal models of the environment. Copyright © 2017 the American Physiological Society.

Modeling discrete and rhythmic movements through motor primitives: a review.

Science.gov (United States)

Degallier, Sarah; Ijspeert, Auke

2010-10-01

Rhythmic and discrete movements are frequently considered separately in motor control, probably because different techniques are commonly used to study and model them. Yet the increasing interest in finding a comprehensive model for movement generation requires bridging the different perspectives arising from the study of those two types of movements. In this article, we consider discrete and rhythmic movements within the framework of motor primitives, i.e., of modular generation of movements. In this way we hope to gain an insight into the functional relationships between discrete and rhythmic movements and thus into a suitable representation for both of them. Within this framework we can define four possible categories of modeling for discrete and rhythmic movements depending on the required command signals and on the spinal processes involved in the generation of the movements. These categories are first discussed in terms of biological concepts such as force fields and central pattern generators and then illustrated by several mathematical models based on dynamical system theory. A discussion on the plausibility of theses models concludes the work.

Temperature compensation and entrainment in circadian rhythms

International Nuclear Information System (INIS)

Bodenstein, C; Heiland, I; Schuster, S

2012-01-01

To anticipate daily variations in the environment and coordinate biological activities into a daily cycle many organisms possess a circadian clock. In the absence of external time cues the circadian rhythm persists with a period of approximately 24 h. The clock phase can be shifted by single pulses of light, darkness, chemicals, or temperature and this allows entrainment of the clock to exactly 24 h by cycles of these zeitgebers. On the other hand, the period of the circadian rhythm is kept relatively constant within a physiological range of constant temperatures, which means that the oscillator is temperature compensated. The mechanisms behind temperature compensation and temperature entrainment are not fully understood, neither biochemically nor mathematically. Here, we theoretically investigate the interplay of temperature compensation and entrainment in general oscillatory systems. We first give an analytical treatment for small temperature shifts and derive that every temperature-compensated oscillator is entrainable to external small-amplitude temperature cycles. Temperature compensation ensures that this entrainment region is always centered at the endogenous period regardless of possible seasonal temperature differences. Moreover, for small temperature cycles the entrainment region of the oscillator is potentially larger for rectangular pulses. For large temperature shifts we numerically analyze different circadian clock models proposed in the literature with respect to these properties. We observe that for such large temperature shifts sinusoidal or gradual temperature cycles allow a larger entrainment region than rectangular cycles. (paper)

The development of rhythmic abilities among of secondary school age pupils

Directory of Open Access Journals (Sweden)

Chaskina O. V.

2016-07-01

Full Text Available this article is aimed to examine the system of development of rhythmic abilities. It is also studied and analyzed systems of development of rhythmicity of Jacques Dalcroze, V.A. Griner. The definition of the concept «rhythm» is revealed.

Circadian Pacemaker – Temperature Compensation

NARCIS (Netherlands)

Gerkema, Menno P.; Binder, Marc D.; Hirokawa, Nobutaka; Windhorst, Uwe

2009-01-01

One of the defining characteristics of circadian pacemakers and indicates the independence of the speed of circadian clock processes of environmental temperature. Mechanisms involved, so far not elucidated in full detail, entail at least two processes that are similarly affected by temperature

Slowed EEG rhythmicity in patients with chronic pancreatitis: evidence of abnormal cerebral pain processing?

DEFF Research Database (Denmark)

Olesen, Søren Schou; Hansen, Tine Maria; Gravesen, Carina

2011-01-01

Intractable pain usually dominates the clinical presentation of chronic pancreatitis (CP). Slowing of electroencephalogram (EEG) rhythmicity has been associated with abnormal cortical pain processing in other chronic pain disorders. The aim of this study was to investigate the spectral distribution...

Later endogenous circadian temperature nadir relative to an earlier wake time in older people

Science.gov (United States)

Duffy, J. F.; Dijk, D. J.; Klerman, E. B.; Czeisler, C. A.

1998-01-01

The contribution of the circadian timing system to the age-related advance of sleep-wake timing was investigated in two experiments. In a constant routine protocol, we found that the average wake time and endogenous circadian phase of 44 older subjects were earlier than that of 101 young men. However, the earlier circadian phase of the older subjects actually occurred later relative to their habitual wake time than it did in young men. These results indicate that an age-related advance of circadian phase cannot fully account for the high prevalence of early morning awakening in healthy older people. In a second study, 13 older subjects and 10 young men were scheduled to a 28-h day, such that they were scheduled to sleep at many circadian phases. Self-reported awakening from scheduled sleep episodes and cognitive throughput during the second half of the wake episode varied markedly as a function of circadian phase in both groups. The rising phase of both rhythms was advanced in the older subjects, suggesting an age-related change in the circadian regulation of sleep-wake propensity. We hypothesize that under entrained conditions, these age-related changes in the relationship between circadian phase and wake time are likely associated with self-selected light exposure at an earlier circadian phase. This earlier exposure to light could account for the earlier clock hour to which the endogenous circadian pacemaker is entrained in older people and thereby further increase their propensity to awaken at an even earlier time.

Model-based investigation of the circadian clock and cell cycle coupling in mouse embryonic fibroblasts: Prediction of RevErb-α up-regulation during mitosis

OpenAIRE

Traynard , Pauline; Feillet , Céline; Soliman , Sylvain; Delaunay , Franck; Fages , François

2016-01-01

International audience; Experimental observations have put in evidence autonomous self-sustained circadian oscillators in most mammalian cells, and proved the existence of molecular links between the circadian clock and the cell cycle. Some mathematical models have also been built to assess conditions of control of the cell cycle by the circadian clock. However, recent studies in individual NIH3T3 fibroblasts have shown an unexpected acceleration of the circadian clock together with the cell ...

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

... functions, althoughhow interaction between sexes affects the circadian timing of male singing is not understood yet. It is suggested thatsocial cues rendered by a conspecific female could improve the circadian performance by restoring rhythmicity in thebiological functions of the cohabiting arrhythmic male partner.

Hypophysectomy abolishes rhythms in rat thyroid hormones but not in the thyroid clock

DEFF Research Database (Denmark)

Fahrenkrug, J; Georg, B; Hannibal, J

2017-01-01

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 bra...

Comparison between treadmill training with rhythmic auditory stimulation and ground walking with rhythmic auditory stimulation on gait ability in chronic stroke patients: A pilot study.

Science.gov (United States)

Park, Jin; Park, So-yeon; Kim, Yong-wook; Woo, Youngkeun

2015-01-01

Generally, treadmill training is very effective intervention, and rhythmic auditory stimulation is designed to feedback during gait training in stroke patients. The purpose of this study was to compare the gait abilities in chronic stroke patients following either treadmill walking training with rhythmic auditory stimulation (TRAS) or over ground walking training with rhythmic auditory stimulation (ORAS). Nineteen subjects were divided into two groups: a TRAS group (9 subjects) and an ORAS group (10 subjects). Temporal and spatial gait parameters and motor recovery ability were measured before and after the training period. Gait ability was measured by the Biodex Gait trainer treadmill system, Timed up and go test (TUG), 6 meter walking distance (6MWD) and Functional gait assessment (FGA). After the training periods, the TRAS group showed a significant improvement in walking speed, step cycle, step length of the unaffected limb, coefficient of variation, 6MWD, and, FGA when compared to the ORAS group (p <  0.05). Treadmill walking training during the rhythmic auditory stimulation may be useful for rehabilitation of patients with chronic stroke.

A New Perspective for Parkinson's Disease: Circadian Rhythm.

Science.gov (United States)

Li, Siyue; Wang, Yali; Wang, Fen; Hu, Li-Fang; Liu, Chun-Feng

2017-02-01

Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson's disease (PD) exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative consequences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.

Nocturia: The circadian voiding disorder

Directory of Open Access Journals (Sweden)

Jin Wook Kim

2016-05-01

Full Text Available Nocturia is a prevalent condition of waking to void during the night. The concept of nocturia has evolved from being a symptomatic aspect of disease associated with the prostate or bladder to a form of lower urinary tract disorder. However, recent advances in circadian biology and sleep science suggest that it might be important to consider nocturia as a form of circadian dysfunction. In the current review, nocturia is reexamined with an introduction to sleep disorders and recent findings in circadian biology in an attempt to highlight the importance of rediscovering nocturia as a problem of chronobiology.

Identification of circadian clock modulators from existing drugs.

Science.gov (United States)

Tamai, T Katherine; Nakane, Yusuke; Ota, Wataru; Kobayashi, Akane; Ishiguro, Masateru; Kadofusa, Naoya; Ikegami, Keisuke; Yagita, Kazuhiro; Shigeyoshi, Yasufumi; Sudo, Masaki; Nishiwaki-Ohkawa, Taeko; Sato, Ayato; Yoshimura, Takashi

2018-04-17

Chronic circadian disruption due to shift work or frequent travel across time zones leads to jet-lag and an increased risk of diabetes, cardiovascular disease, and cancer. The development of new pharmaceuticals to treat circadian disorders, however, is costly and hugely time-consuming. We therefore performed a high-throughput chemical screen of existing drugs for circadian clock modulators in human U2OS cells, with the aim of repurposing known bioactive compounds. Approximately 5% of the drugs screened altered circadian period, including the period-shortening compound dehydroepiandrosterone (DHEA; also known as prasterone). DHEA is one of the most abundant circulating steroid hormones in humans and is available as a dietary supplement in the USA Dietary administration of DHEA to mice shortened free-running circadian period and accelerated re-entrainment to advanced light-dark (LD) cycles, thereby reducing jet-lag. Our drug screen also revealed the involvement of tyrosine kinases, ABL1 and ABL2, and the BCR serine/threonine kinase in regulating circadian period. Thus, drug repurposing is a useful approach to identify new circadian clock modulators and potential therapies for circadian disorders. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Peripheral Skin Temperature and Circadian Biological Clock in Shift Nurses after a Day off

Directory of Open Access Journals (Sweden)

Massimo Bracci

2016-04-01

Full Text Available The circadian biological clock is essentially based on the light/dark cycle. Some people working with shift schedules cannot adjust their sleep/wake cycle to the light/dark cycle, and this may result in alterations of the circadian biological clock. This study explored the circadian biological clock of shift and daytime nurses using non-invasive methods. Peripheral skin temperature, cortisol and melatonin levels in saliva, and Per2 expression in pubic hair follicle cells were investigated for 24 h after a day off. Significant differences were observed in peripheral skin temperature and cortisol levels between shift and daytime nurses. No differences in melatonin levels were obtained. Per2 maximum values were significantly different between the two groups. Shift nurses exhibited lower circadian variations compared to daytime nurses, and this may indicate an adjustment of the circadian biological clock to continuous shift schedules. Non-invasive procedures, such as peripheral skin temperature measurement, determination of cortisol and melatonin in saliva, and analysis of clock genes in hair follicle cells, may be effective approaches to extensively study the circadian clock in shift workers.

Tempo discrimination of musical patterns: effects due to pitch and rhythmic structure.

Science.gov (United States)

Boltz, M G

1998-11-01

The purpose of this research was to investigate a set of factors that may influence the perceived rate of an auditory event. In a paired-comparison task, subjects were presented with a set of music-like patterns that differed in their relative number of contour changes and in the magnitude of pitch skips (Experiment 1) as well as in the compatibility of rhythmic accent structure with the arrangement of pitch relations (Experiment 2) Results indicated that, relative to their standard referents, comparison melodies were judged to unfold more slowly when they displayed more changes in pitch direction, greater pitch distances, and an incompatible rhythmic accent structure. These findings are suggested to stem from an imputed velocity hypothesis, in which people overgeneralize certain invariant relations that typically occur between melodic and temporal accent structure within Western music.

Simple neural substrate predicts complex rhythmic structure in duetting birds

Science.gov (United States)

Amador, Ana; Trevisan, M. A.; Mindlin, G. B.

2005-09-01

Horneros (Furnarius Rufus) are South American birds well known for their oven-looking nests and their ability to sing in couples. Previous work has analyzed the rhythmic organization of the duets, unveiling a mathematical structure behind the songs. In this work we analyze in detail an extended database of duets. The rhythms of the songs are compatible with the dynamics presented by a wide class of dynamical systems: forced excitable systems. Compatible with this nonlinear rule, we build a biologically inspired model for how the neural and the anatomical elements may interact to produce the observed rhythmic patterns. This model allows us to synthesize songs presenting the acoustic and rhythmic features observed in real songs. We also make testable predictions in order to support our hypothesis.

Predictive coding of music--brain responses to rhythmic incongruity.

Science.gov (United States)

Vuust, Peter; Ostergaard, Leif; Pallesen, Karen Johanne; Bailey, Christopher; Roepstorff, Andreas

2009-01-01

During the last decades, models of music processing in the brain have mainly discussed the specificity of brain modules involved in processing different musical components. We argue that predictive coding offers an explanatory framework for functional integration in musical processing. Further, we provide empirical evidence for such a network in the analysis of event-related MEG-components to rhythmic incongruence in the context of strong metric anticipation. This is seen in a mismatch negativity (MMNm) and a subsequent P3am component, which have the properties of an error term and a subsequent evaluation in a predictive coding framework. There were both quantitative and qualitative differences in the evoked responses in expert jazz musicians compared with rhythmically unskilled non-musicians. We propose that these differences trace a functional adaptation and/or a genetic pre-disposition in experts which allows for a more precise rhythmic prediction.

The Role of the Mammalian Prion Protein in the Control of Sleep

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Amber Roguski

2017-11-01

Full Text Available Sleep disruption is a prevalent clinical feature in many neurodegenerative disorders, including human prion diseases where it can be the defining dysfunction, as in the case of the “eponymous” fatal familial insomnia, or an early-stage symptom as in certain types of Creutzfeldt-Jakob disease. It is important to establish the role of the cellular prion protein (PrPC, the key molecule involved in prion pathogenesis, within the sleep-wake system in order to understand fully the mechanisms underlying its contribution to both healthy circadian rhythmicity and sleep dysfunction during disease. Although severe disruption to the circadian rhythm and melatonin release is evident during the pathogenic phases of some prion diseases, untangling whether PrPC plays a role in circadian rhythmicity, as suggested in mice deficient for PrPC expression, is challenging given the lack of basic experimental research. We provide a short review of the small amount of direct literature focused on the role of PrPC in melatonin and circadian rhythm regulation, as well as suggesting mechanisms by which PrPC might exert influence upon noradrenergic and dopaminergic signaling and melatonin synthesis. Future research in this area should focus upon isolating the points of dysfunction within the retino-pineal pathway and further investigate PrPC mediation of pinealocyte GPCR activity.

Primate beta oscillations and rhythmic behaviors.

Science.gov (United States)

Merchant, Hugo; Bartolo, Ramón

2018-03-01

The study of non-human primates in complex behaviors such as rhythm perception and entrainment is critical to understand the neurophysiological basis of human cognition. Next to reviewing the role of beta oscillations in human beat perception, here we discuss the role of primate putaminal oscillatory activity in the control of rhythmic movements that are guided by a sensory metronome or internally gated. The analysis of the local field potentials of the behaving macaques showed that gamma-oscillations reflect local computations associated with stimulus processing of the metronome, whereas beta-activity involves the entrainment of large putaminal circuits, probably in conjunction with other elements of cortico-basal ganglia-thalamo-cortical circuit, during internally driven rhythmic tapping. Thus, this review emphasizes the need of parametric neurophysiological observations in non-human primates that display a well-controlled behavior during high-level cognitive processes.

Sleep and circadian rhythm disturbance in bipolar disorder.

Science.gov (United States)

Bradley, A J; Webb-Mitchell, R; Hazu, A; Slater, N; Middleton, B; Gallagher, P; McAllister-Williams, H; Anderson, K N

2017-07-01

Subjective reports of insomnia and hypersomnia are common in bipolar disorder (BD). It is unclear to what extent these relate to underlying circadian rhythm disturbance (CRD). In this study we aimed to objectively assess sleep and circadian rhythm in a cohort of patients with BD compared to matched controls. Forty-six patients with BD and 42 controls had comprehensive sleep/circadian rhythm assessment with respiratory sleep studies, prolonged accelerometry over 3 weeks, sleep questionnaires and diaries, melatonin levels, alongside mood, psychosocial functioning and quality of life (QoL) questionnaires. Twenty-three (50%) patients with BD had abnormal sleep, of whom 12 (52%) had CRD and 29% had obstructive sleep apnoea. Patients with abnormal sleep had lower 24-h melatonin secretion compared to controls and patients with normal sleep. Abnormal sleep/CRD in BD was associated with impaired functioning and worse QoL. BD is associated with high rates of abnormal sleep and CRD. The association between these disorders, mood and functioning, and the direction of causality, warrants further investigation.

Short-Wavelength Countermeasures for Circadian Desynchrony

National Research Council Canada - National Science Library

Heller, H. C; Smith, Mark

2008-01-01

.... Exposure of humans to bright light for an hour or more at the right phase of the circadian cycle produces significant phase shifts of circadian rhythms speeding recovery from jet-lag, and optimizing...

NONO couples the circadian clock to the cell cycle.

Science.gov (United States)

Kowalska, Elzbieta; Ripperger, Juergen A; Hoegger, Dominik C; Bruegger, Pascal; Buch, Thorsten; Birchler, Thomas; Mueller, Anke; Albrecht, Urs; Contaldo, Claudio; Brown, Steven A

2013-01-29

Mammalian circadian clocks restrict cell proliferation to defined time windows, but the mechanism and consequences of this interrelationship are not fully understood. Previously we identified the multifunctional nuclear protein NONO as a partner of circadian PERIOD (PER) proteins. Here we show that it also conveys circadian gating to the cell cycle, a connection surprisingly important for wound healing in mice. Specifically, although fibroblasts from NONO-deficient mice showed approximately normal circadian cycles, they displayed elevated cell doubling and lower cellular senescence. At a molecular level, NONO bound to the p16-Ink4A cell cycle checkpoint gene and potentiated its circadian activation in a PER protein-dependent fashion. Loss of either NONO or PER abolished this activation and circadian expression of p16-Ink4A and eliminated circadian cell cycle gating. In vivo, lack of NONO resulted in defective wound repair. Because wound healing defects were also seen in multiple circadian clock-deficient mouse lines, our results therefore suggest that coupling of the cell cycle to the circadian clock via NONO may be useful to segregate in temporal fashion cell proliferation from tissue organization.

Circadian Rhythm Sleep-Wake Disorders in Older Adults.

Science.gov (United States)

Kim, Jee Hyun; Duffy, Jeanne F

2018-03-01

The timing, duration, and consolidation of sleep result from the interaction of the circadian timing system with a sleep-wake homeostatic process. When aligned and functioning optimally, this allows wakefulness throughout the day and a long consolidated sleep episode at night. Mismatch between the desired timing of sleep and the ability to fall and remain asleep is a hallmark of the circadian rhythm sleep-wake disorders. This article discusses changes in circadian regulation of sleep with aging; how age influences the prevalence, diagnosis, and treatment of circadian rhythm sleep-wake disorders; and how neurologic diseases in older patients affect circadian rhythms and sleep. Copyright © 2017 Elsevier Inc. All rights reserved.

Circadian Rhythm Shapes the Gut Microbiota Affecting Host Radiosensitivity.

Science.gov (United States)

Cui, Ming; Xiao, Huiwen; Luo, Dan; Zhang, Xin; Zhao, Shuyi; Zheng, Qisheng; Li, Yuan; Zhao, Yu; Dong, Jiali; Li, Hang; Wang, Haichao; Fan, Saijun

2016-10-26

Modern lifestyles, such as shift work, nocturnal social activities, and jet lag, disturb the circadian rhythm. The interaction between mammals and the co-evolved intestinal microbiota modulates host physiopathological processes. Radiotherapy is a cornerstone of modern management of malignancies; however, it was previously unknown whether circadian rhythm disorder impairs prognosis after radiotherapy. To investigate the effect of circadian rhythm on radiotherapy, C57BL/6 mice were housed in different dark/light cycles, and their intestinal bacterial compositions were compared using high throughput sequencing. The survival rate, body weight, and food intake of mice in diverse cohorts were measured following irradiation exposure. Finally, the enteric bacterial composition of irradiated mice that experienced different dark/light cycles was assessed using 16S RNA sequencing. Intriguingly, mice housed in aberrant light cycles harbored a reduction of observed intestinal bacterial species and shifts of gut bacterial composition compared with those of the mice kept under 12 h dark/12 h light cycles, resulting in a decrease of host radioresistance. Moreover, the alteration of enteric bacterial composition of mice in different groups was dissimilar. Our findings provide novel insights into the effects of biological clocks on the gut bacterial composition, and underpin that the circadian rhythm influences the prognosis of patients after radiotherapy in a preclinical setting.

Disturbances in the circadian pattern of activity and sleep after laparoscopic versus open abdominal surgery

DEFF Research Database (Denmark)

Gögenur, Ismail; Bisgaard, Thue; Burgdorf, Stefan

2008-01-01

BACKGROUND: Studies on the circadian variation in bodily functions and sleep are important for understanding the pathophysiological processes in the postoperative period. We aimed to investigate changes in the circadian variation in activity after minimally invasive surgery (laparoscopic...... scale (sleep quality, general well-being and pain) and fatigue was measured by a ten-point fatigue scale. The activity levels of the patients were monitored by actigraphy (a wrist-worn device measuring patient activity). Measures of circadian activity level [interday stability (IS), intraday variability...

Robustness from flexibility in the fungal circadian clock

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Akman Ozgur E

2010-06-01

Full Text Available Abstract Background Robustness is a central property of living systems, enabling function to be maintained against environmental perturbations. A key challenge is to identify the structures in biological circuits that confer system-level properties such as robustness. Circadian clocks allow organisms to adapt to the predictable changes of the 24-hour day/night cycle by generating endogenous rhythms that can be entrained to the external cycle. In all organisms, the clock circuits typically comprise multiple interlocked feedback loops controlling the rhythmic expression of key genes. Previously, we showed that such architectures increase the flexibility of the clock's rhythmic behaviour. We now test the relationship between flexibility and robustness, using a mathematical model of the circuit controlling conidiation in the fungus Neurospora crassa. Results The circuit modelled in this work consists of a central negative feedback loop, in which the frequency (frq gene inhibits its transcriptional activator white collar-1 (wc-1, interlocked with a positive feedback loop in which FRQ protein upregulates WC-1 production. Importantly, our model reproduces the observed entrainment of this circuit under light/dark cycles with varying photoperiod and cycle duration. Our simulations show that whilst the level of frq mRNA is driven directly by the light input, the falling phase of FRQ protein, a molecular correlate of conidiation, maintains a constant phase that is uncoupled from the times of dawn and dusk. The model predicts the behaviour of mutants that uncouple WC-1 production from FRQ's positive feedback, and shows that the positive loop enhances the buffering of conidiation phase against seasonal photoperiod changes. This property is quantified using Kitano's measure for the overall robustness of a regulated system output. Further analysis demonstrates that this functional robustness is a consequence of the greater evolutionary flexibility conferred on

Implications of Circadian Rhythm in Dopamine and Mood Regulation.

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Kim, Jeongah; Jang, Sangwon; Choe, Han Kyoung; Chung, Sooyoung; Son, Gi Hoon; Kim, Kyungjin

2017-07-31

Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-erbα induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

A multiresolution model of rhythmic expectancy

NARCIS (Netherlands)

Smith, L.M.; Honing, H.; Miyazaki, K.; Hiraga, Y.; Adachi, M.; Nakajima, Y.; Tsuzaki, M.

2008-01-01

We describe a computational model of rhythmic cognition that predicts expected onset times. A dynamic representation of musical rhythm, the multiresolution analysis using the continuous wavelet transform is used. This representation decomposes the temporal structure of a musical rhythm into time

Metabolic influences on circadian rhythmicity in Siberian and Syrian hamsters exposed to long photoperiods.

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Challet, E; Kolker, D E; Turek, F W

2000-01-01

Calorie restriction and other situations of reduced glucose availability in rodents alter the entraining effects of light on the circadian pacemaker located in the suprachiasmatic nuclei. Siberian and Syrian hamsters are photoperiodic species that are sexually active when exposed to long summer-like photoperiods, while both species show opposite changes in body mass when transferred from long to short or short to long days. Because metabolic cues may fine tune the photoperiodic responses via the suprachiasmatic nuclei, we tested whether timed calorie restriction can alter the photic synchronization of the light-entrainable pacemaker in these two hamster species exposed to long photoperiods. Siberian and Syrian hamsters were exposed to 16 h:8 h light:dark cycles and received daily hypocaloric (75% of daily food intake) or normocaloric diet (100% of daily food intake) 4 h after light onset. Four weeks later, hamsters were transferred to constant darkness and fed ad libitum. The onset of the nocturnal pattern of locomotor activity was phase advanced by 1.5 h in calorie-restricted Siberian hamsters, but not in Syrian hamsters. The lack of phase change in calorie-restricted Syrian hamsters was also observed in individuals exposed to 14 h:10 h dim light:dark cycles and fed with lower hypocaloric food (i.e. 60% of daily food intake) 2 h after light onset. Moreover, in hamsters housed in constant darkness and fed ad lib., light-induced phase shifts of the locomotor activity in Siberian hamsters, but not in Syrian hamsters were significantly reduced when glucose utilization was blocked by pretreatment with 500 mg/kg i.p. 2-deoxy-D-glucose. Taken together, these results show that the photic synchronization of the light-entrainable pacemaker can be modulated by metabolic cues in Siberian hamsters, but not in Syrian hamsters maintained on long days.

Circadian rhythm in melatonin release as a mechanism to reinforce the temporal organization of the circadian system in crayfish.

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Mendoza-Vargas, Leonor; Báez-Saldaña, Armida; Alvarado, Ramón; Fuentes-Pardo, Beatriz; Flores-Soto, Edgar; Solís-Chagoyán, Héctor

2017-06-01

Melatonin (MEL) is a conserved molecule with respect to its synthesis pathway and functions. In crayfish, MEL content in eyestalks (Ey) increases at night under the photoperiod, and this indoleamine synchronizes the circadian rhythm of electroretinogram amplitude, which is expressed by retinas and controlled by the cerebroid ganglion (CG). The aim of this study was to determine whether MEL content in eyestalks and CG or circulating MEL in hemolymph (He) follows a circadian rhythm under a free-running condition; in addition, it was tested whether MEL might directly influence the spontaneous electrical activity of the CG. Crayfish were maintained under constant darkness and temperature, a condition suitable for studying the intrinsic properties of circadian systems. MEL was quantified in samples obtained from He, Ey, and CG by means of an enzyme-linked immunosorbent assay, and the effect of exogenous MEL on CG spontaneous activity was evaluated by electrophysiological recording. Variation of MEL content in He, Ey, and CG followed a circadian rhythm that peaked at the same circadian time (CT). In addition, a single dose of MEL injected into the crayfish at different CTs reduced the level of spontaneous electrical activity in the CG. Results suggest that the circadian increase in MEL content directly affects the CG, reducing its spontaneous electrical activity, and that MEL might act as a periodical signal to reinforce the organization of the circadian system in crayfish.

Diurnal Variations of Human Circulating Cell-Free Micro-RNA.

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Niels H H Heegaard

Full Text Available A 24-hour light and dark cycle-dependent rhythmicity pervades physiological processes in virtually all living organisms including humans. These regular oscillations are caused by external cues to endogenous, independent biological time-keeping systems (clocks. The rhythm is reflected by gene expression that varies in a circadian and specific fashion in different organs and tissues and is regulated largely by dynamic epigenetic and post-transcriptional mechanisms. This leads to well-documented oscillations of specific electrolytes, hormones, metabolites, and plasma proteins in blood samples. An emerging, important class of gene regulators is short single-stranded RNA (micro-RNA, miRNA that interferes post-transcriptionally with gene expression and thus may play a role in the circadian variation of gene expression. MiRNAs are promising biomarkers by virtue of their disease-specific tissue expression and because of their presence as stable entities in the circulation. However, no studies have addressed the putative circadian rhythmicity of circulating, cell-free miRNAs. This question is important both for using miRNAs as biological markers and for clues to miRNA function in the regulation of circadian gene expression. Here, we investigate 92 miRNAs in plasma samples from 24 young male, healthy volunteers repeatedly sampled 9 times during a 24-hour stay in a regulated environment. We demonstrate that a third (26/79 of the measurable plasma miRNAs (using RT-qPCR on a microfluidic system exhibit a rhythmic behavior and are distributed in two main phase patterns. Some of these miRNAs weakly target known clock genes and many have strong targets in intracellular MAPK signaling pathways. These novel findings highlight the importance of considering bio-oscillations in miRNA biomarker studies and suggest the further study of a set of specific circulating miRNAs in the regulation and functioning of biological clocks.

Individual differences in circadian locomotor parameters correlate with anxiety- and depression-like behavior.

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Jeffrey Anyan

Full Text Available Disrupted circadian rhythms are a core feature of mood and anxiety disorders. Circadian rhythms are coordinated by a light-entrainable master clock located in the suprachiasmatic nucleus. Animal models of mood and anxiety disorders often exhibit blunted rhythms in locomotor activity and clock gene expression. Interestingly, the changes in circadian rhythms correlate with mood-related behaviours. Although animal models of depression and anxiety exhibit aberrant circadian rhythms in physiology and behavior, it is possible that the methodology being used to induce the behavioral phenotype (e.g., brain lesions, chronic stress, global gene deletion affect behavior independently of circadian system. This study investigates the relationship between individual differences in circadian locomotor parameters and mood-related behaviors in healthy rats. The circadian phenotype of male Lewis rats was characterized by analyzing wheel running behavior under standard 12h:12h LD conditions, constant dark, constant light, and rate of re-entrainment to a phase advance. Rats were then tested on a battery of behavioral tests: activity box, restricted feeding, elevated plus maze, forced swim test, and fear conditioning. Under 12h:12h LD conditions, percent of daily activity in the light phase and variability in activity onset were associated with longer latency to immobility in the forced swim test. Variability in onset also correlated positively with anxiety-like behavior in the elevated plus maze. Rate of re-entrainment correlated positively with measures of anxiety in the activity box and elevated plus maze. Lastly, we found that free running period under constant dark was associated with anxiety-like behaviors in the activity box and elevated plus maze. Our results provide a previously uncharacterized relationship between circadian locomotor parameters and mood-related behaviors in healthy rats and provide a basis for future examination into circadian clock

How does healthy aging impact on the circadian clock?

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Popa-Wagner, Aurel; Buga, Ana-Maria; Dumitrascu, Dinu Iuliu; Uzoni, Adriana; Thome, Johannes; Coogan, Andrew N

2017-02-01

Circadian rhythms are recurring patterns in a host of physiological and other parameters that recur with periods of near 24 h. These rhythms reflect the temporal organization of an organism's homeostatic control systems and as such are key processes in ensuring optimal physiological performance. Dysfunction of circadian processes is linked with adverse health conditions. In this review we highlight the evidence that normal, healthy aging is associated with changes in the circadian system; we examine the molecular mechanisms through which such changes may arise, discuss whether more robust circadian function is a predictor of longevity and highlight the role of circadian rhythms in age-related diseases. Overall, the literature shows that aging is associated with marked changes in circadian processes, both at the behavioral and molecular levels, and the molecular mechanisms through which such changes arise remain to be elucidated, but may involve inflammatory process, redox homeostasis and epigenetic modifications. Understanding the nature of age-related circadian dysfunction will allow for the design of chronotherapeutic intervention strategies to attenuate circadian dysfunction and thus improve health and quality of life.

Environmental Disruption of Circadian Rhythm Predisposes Mice to Osteoarthritis-Like Changes in Knee Joint

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Voigt, Robin M; Ellman, Michael B; Summa, Keith C; Vitaterna, Martha Hotz; Keshavarizian, Ali; Turek, Fred W; Meng, Qing-Jun; Stein, Gary S.; van Wijnen, Andre J.; Chen, Di; Forsyth, Christopher B; Im, Hee-Jeong

2015-01-01

Circadian rhythm dysfunction is linked to many diseases, yet pathophysiological roles in articular cartilage homeostasis and degenerative joint disease including osteoarthritis (OA) remains to be investigated in vivo. Here, we tested whether environmental or genetic disruption of circadian homeostasis predisposes to OA-like pathological changes. Male mice were examined for circadian locomotor activity upon changes in the light:dark (LD) cycle or genetic disruption of circadian rhythms. Wild-type (WT) mice were maintained on a constant 12 hour:12 hour LD cycle (12:12 LD) or exposed to weekly 12 hour phase shifts. Alternatively, male circadian mutant mice (ClockΔ19 or Csnk1etau mutants) were compared with age-matched WT littermates that were maintained on a constant 12:12 LD cycle. Disruption of circadian rhythms promoted osteoarthritic changes by suppressing proteoglycan accumulation, upregulating matrix-degrading enzymes and downregulating anabolic mediators in the mouse knee joint. Mechanistically, these effects involved activation of the PKCδ-ERK-RUNX2/NFκB and β-catenin signaling pathways, stimulation of MMP-13 and ADAMTS-5, as well as suppression of the anabolic mediators SOX9 and TIMP-3 in articular chondrocytes of phase-shifted mice. Genetic disruption of circadian homeostasis does not predispose to OA-like pathological changes in joints. Our results, for the first time, provide compelling in vivo evidence that environmental disruption of circadian rhythms is a risk factor for the development of OA-like pathological changes in the mouse knee joint. PMID:25655021

Immunity's fourth dimension: approaching the circadian-immune connection.

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Arjona, Alvaro; Silver, Adam C; Walker, Wendy E; Fikrig, Erol

2012-12-01

The circadian system ensures the generation and maintenance of self-sustained ~24-h rhythms in physiology that are linked to internal and environmental changes. In mammals, daily variations in light intensity and other cues are integrated by a hypothalamic master clock that conveys circadian information to peripheral molecular clocks that orchestrate physiology. Multiple immune parameters also vary throughout the day and disruption of circadian homeostasis is associated with immune-related disease. Here, we discuss the molecular links between the circadian and immune systems and examine their outputs and disease implications. Understanding the mechanisms that underlie circadian-immune crosstalk may prove valuable for devising novel prophylactic and therapeutic interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rhythmic ganglion cell activity in bleached and blind adult mouse retinas.

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Menzler, Jacob; Channappa, Lakshmi; Zeck, Guenther

2014-01-01

In retinitis pigmentosa--a degenerative disease which often leads to incurable blindness--the loss of photoreceptors deprives the retina from a continuous excitatory input, the so-called dark current. In rodent models of this disease this deprivation leads to oscillatory electrical activity in the remaining circuitry, which is reflected in the rhythmic spiking of retinal ganglion cells (RGCs). It remained unclear, however, if the rhythmic RGC activity is attributed to circuit alterations occurring during photoreceptor degeneration or if rhythmic activity is an intrinsic property of healthy retinal circuitry which is masked by the photoreceptor's dark current. Here we tested these hypotheses by inducing and analysing oscillatory activity in adult healthy (C57/Bl6) and blind mouse retinas (rd10 and rd1). Rhythmic RGC activity in healthy retinas was detected upon partial photoreceptor bleaching using an extracellular high-density multi-transistor-array. The mean fundamental spiking frequency in bleached retinas was 4.3 Hz; close to the RGC rhythm detected in blind rd10 mouse retinas (6.5 Hz). Crosscorrelation analysis of neighbouring wild-type and rd10 RGCs (separation distance rhythmic RGC spiking in these retinas is driven by a network of presynaptic neurons. The inhibition of glutamatergic ganglion cell input or the inhibition of gap junctional coupling abolished the rhythmic pattern. In rd10 and rd1 retinas the presynaptic network leads to local field potentials, whereas in bleached retinas additional pharmacological disinhibition is required to achieve detectable field potentials. Our results demonstrate that photoreceptor bleaching unmasks oscillatory activity in healthy retinas which shares many features with the functional phenotype detected in rd10 retinas. The quantitative physiological differences advance the understanding of the degeneration process and may guide future rescue strategies.

Now you hear it: a predictive coding model for understanding rhythmic incongruity

DEFF Research Database (Denmark)

Vuust, Peter; Dietz, Martin; Witek, Maria

2018-01-01

Rhythmic incongruity in the form of syncopation is a prominent feature of many contemporary musical styles. Syncopations afford incongruity between rhythmic patterns and the meter, giving rise to mental models of differently accented isochronous beats. Syncopations occur either in isolation or as...

Circadian Stress Regimes Affect the Circadian Clock and Cause Jasmonic Acid-Dependent Cell Death in Cytokinin-Deficient Arabidopsis Plants[OPEN

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Nitschke, Silvia; Cortleven, Anne; Iven, Tim; Havaux, Michel; Schmülling, Thomas

2016-01-01

The circadian clock helps plants measure daylength and adapt to changes in the day-night rhythm. We found that changes in the light-dark regime triggered stress responses, eventually leading to cell death, in leaves of Arabidopsis thaliana plants with reduced cytokinin levels or defective cytokinin signaling. Prolonged light treatment followed by a dark period induced stress and cell death marker genes while reducing photosynthetic efficiency. This response, called circadian stress, is also characterized by altered expression of clock and clock output genes. In particular, this treatment strongly reduced the expression of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Intriguingly, similar changes in gene expression and cell death were observed in clock mutants lacking proper CCA1 and LHY function. Circadian stress caused strong changes in reactive oxygen species- and jasmonic acid (JA)-related gene expression. The activation of the JA pathway, involving the accumulation of JA metabolites, was crucial for the induction of cell death, since the cell death phenotype was strongly reduced in the jasmonate resistant1 mutant background. We propose that adaptation to circadian stress regimes requires a normal cytokinin status which, acting primarily through the AHK3 receptor, supports circadian clock function to guard against the detrimental effects of circadian stress. PMID:27354555

Circadian Metabolomics in Time and Space

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Kenneth A. Dyar

2017-07-01

Full Text Available Circadian rhythms are widely known to govern human health and disease, but specific pathogenic mechanisms linking circadian disruption to metabolic diseases are just beginning to come to light. This is thanks in part to the development and application of various “omics”-based tools in biology and medicine. Current high-throughput technologies allow for the simultaneous monitoring of multiple dynamic cellular events over time, ranging from gene expression to metabolite abundance and sub-cellular localization. These fundamental temporal and spatial perspectives have allowed for a more comprehensive understanding of how various dynamic cellular events and biochemical processes are related in health and disease. With advances in technology, metabolomics has become a more routine “omics” approach for studying metabolism, and “circadian metabolomics” (i.e., studying the 24-h metabolome has recently been undertaken by several groups. To date, circadian metabolomes have been reported for human serum, saliva, breath, and urine, as well as tissues from several species under specific disease or mutagenesis conditions. Importantly, these studies have consistently revealed that 24-h rhythms are prevalent in almost every tissue and metabolic pathway. Furthermore, these circadian rhythms in tissue metabolism are ultimately linked to and directed by internal 24-h biological clocks. In this review, we will attempt to put these data-rich circadian metabolomics experiments into perspective to find out what they can tell us about metabolic health and disease, and what additional biomarker potential they may reveal.

Numerical study of entrainment of the human circadian system and recovery by light treatment.

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Kim, Soon Ho; Goh, Segun; Han, Kyungreem; Kim, Jong Won; Choi, MooYoung

2018-05-09

While the effects of light as a zeitgeber are well known, the way the effects are modulated by features of the sleep-wake system still remains to be studied in detail. A mathematical model for disturbance and recovery of the human circadian system is presented. The model combines a circadian oscillator and a sleep-wake switch that includes the effects of orexin. By means of simulations, we characterize the period-locking zone of the model, where a stable 24-hour circadian rhythm exists, and the occurrence of circadian disruption due to both insufficient light and imbalance in orexin. We also investigate how daily bright light treatments of short duration can recover the normal circadian rhythm. It is found that the system exhibits continuous phase advance/delay at lower/higher orexin levels. Bright light treatment simulations disclose two optimal time windows, corresponding to morning and evening light treatments. Among the two, the morning light treatment is found effective in a wider range of parameter values, with shorter recovery time. This approach offers a systematic way to determine the conditions under which circadian disruption occurs, and to evaluate the effects of light treatment. In particular, it could potentially offer a way to optimize light treatments for patients with circadian disruption, e.g., sleep and mood disorders, in clinical settings.

Estimation of Circadian Body Temperature Rhythm Based on Heart Rate in Healthy, Ambulatory Subjects.

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Sim, Soo Young; Joo, Kwang Min; Kim, Han Byul; Jang, Seungjin; Kim, Beomoh; Hong, Seungbum; Kim, Sungwan; Park, Kwang Suk

2017-03-01

Core body temperature is a reliable marker for circadian rhythm. As characteristics of the circadian body temperature rhythm change during diverse health problems, such as sleep disorder and depression, body temperature monitoring is often used in clinical diagnosis and treatment. However, the use of current thermometers in circadian rhythm monitoring is impractical in daily life. As heart rate is a physiological signal relevant to thermoregulation, we investigated the feasibility of heart rate monitoring in estimating circadian body temperature rhythm. Various heart rate parameters and core body temperature were simultaneously acquired in 21 healthy, ambulatory subjects during their routine life. The performance of regression analysis and the extended Kalman filter on daily body temperature and circadian indicator (mesor, amplitude, and acrophase) estimation were evaluated. For daily body temperature estimation, mean R-R interval (RRI), mean heart rate (MHR), or normalized MHR provided a mean root mean square error of approximately 0.40 °C in both techniques. The mesor estimation regression analysis showed better performance than the extended Kalman filter. However, the extended Kalman filter, combined with RRI or MHR, provided better accuracy in terms of amplitude and acrophase estimation. We suggest that this noninvasive and convenient method for estimating the circadian body temperature rhythm could reduce discomfort during body temperature monitoring in daily life. This, in turn, could facilitate more clinical studies based on circadian body temperature rhythm.

Somatotype of top-level serbian rhythmic gymnasts.

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Purenović-Ivanović, Tijana; Popović, Ružena

2014-03-27

Body size and build influence performance in many sports, especially in those belonging to the group of female aesthetic sports (rhythmic gymnastics, artistic gymnastics, and figure skating). These sports pose high specific demands upon the functional, energy, motor and psychological capacities of athletes, but also upon the size, body build and composition of the performers, particularly of the top-level female athletes. The study of the top athletes (rhythmic gymnasts, in this case) may provide valuable information on the morphological requirements for achieving success in this sport. Therefore, the main objective of this research was to analyze the somatotype of 40 Serbian top-level rhythmic gymnasts, aged 13.04±2.79, and to form the five age group categories. The anthropometric variables included body height, body mass, the selected diameters, girths and skinfolds, and the Heath-Carter anthropometric somatotype. All of the anthropometric data were collected according to International Biological Programme, and then processed in the Somatotype 1.2. The applied analysis of variance indicated an increase in endomorphic component with age. The obtained results show that the balanced ectomorph is a dominant somatotype, being similar for all of the athletes that took part in the research (3.54-3.24-4.5). These results are in line with the ones obtained in previous studies.

The Drosophila melanogaster circadian pacemaker circuit

Indian Academy of Sciences (India)

2016-08-26

Aug 26, 2016 ... Keywords. circadian rhythm; neuronal network; ion channel; behaviour; neurotransmitter; electrophysiology; Drosophila. Abstract. As an experimental model system, the fruit fly Drosophila melanogaster has been seminal in shaping our understanding of the circadian clockwork. The wealth of genetic tools ...

l-Serine Enhances Light-Induced Circadian Phase Resetting in Mice and Humans.

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Yasuo, Shinobu; Iwamoto, Ayaka; Lee, Sang-Il; Ochiai, Shotaro; Hitachi, Rina; Shibata, Satomi; Uotsu, Nobuo; Tarumizu, Chie; Matsuoka, Sayuri; Furuse, Mitsuhiro; Higuchi, Shigekazu

2017-12-01

Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood. Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans. Methods: Male CBA/N mice were orally administered 1 of 20 l-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before l-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of l-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase. Results: l-Serine administration enhanced light-induced phase shifts in mice (1.86-fold; P light-dark cycle by 6 h, l-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, l-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-l-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances. © 2017 American Society for Nutrition.

Photoperiodic plasticity in circadian clock neurons in insects

Directory of Open Access Journals (Sweden)

Sakiko eShiga

2013-08-01

Full Text Available Since Bünning’s observation of circadian rhythms and photoperiodism in the runner bean Phaseolus multiflorus in 1936, many studies have shown that photoperiodism is based on the circadian clock system. In insects, involvement of circadian clock genes or neurons has been recently shown in the photoperiodic control of developmental arrests, diapause. Based on molecular and neuronal studies in Drosophila melanogaster, photoperiodic changes have been reported for expression patterns of the circadian clock genes, subcellular distribution of clock proteins, fiber distribution, or the number of plausible clock neurons in different species. Photoperiod sets peaks of per or tim mRNA abundance at lights-off in Sarcophaga crassipalpis, Chymomyza costata and Protophormia terraenovae. Abundance of per and Clock mRNA changes by photoperiod in Pyrrhocoris apterus. Subcellular Per distribution in circadian clock neurons changes with photoperiod in P. terraenovae. Although photoperiodism is not known in Leucophaea maderae, under longer day length, more stomata and longer commissural fibers of circadian clock neurons have been found. These plastic changes in the circadian clock neurons could be an important constituent for photoperiodic clock mechanisms to integrate repetitive photoperiodic information and produce different outputs based on day length.

Sleep, circadian rhythm and body weight: parallel developments.

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Westerterp-Plantenga, Margriet S

2016-11-01

Circadian alignment is crucial for body-weight management, and for metabolic health. In this context, circadian alignment consists of alignment of sleep, meal patterns and physical activity. During puberty a significant reduction in sleep duration occurs, and pubertal status is inversely associated with sleep duration. A consistent inverse association between habitual sleep duration and body-weight development occurs, independent of possible confounders. Research on misalignment reveals that circadian misalignment affects sleep-architecture and subsequently disturbs glucose-insulin metabolism, substrate oxidation, leptin- and ghrelin concentrations, appetite, food reward, hypothalamic-pituitary-adrenal-axis activity and gut-peptide concentrations enhancing positive energy balance and metabolic disturbance. Not only aligning meals and sleep in a circadian way is crucial, also regular physical activity during the day strongly promotes the stability and amplitude of circadian rhythm, and thus may serve as an instrument to restore poor circadian rhythms. Endogenicity may play a role in interaction of these environmental variables with a genetic predisposition. In conclusion, notwithstanding the separate favourable effects of sufficient daily physical activity, regular meal patterns, sufficient sleep duration and quality sleep on energy balance, the overall effect of the amplitude and stability of the circadian rhythm, perhaps including genetic predisposition, may integrate the separate effects in an additive way.

Rhythmic interaction in VR

DEFF Research Database (Denmark)

Erkut, Cumhur

2017-01-01

Cinematic virtual reality is a new and relatively unexplored area in academia. While research in guiding the spectator's attention in this new medium has been conducted for some time, a focus on editing in conjunction with spectator orientation is only currently emerging. In this paper, we consid...... in rhythm perception, and complement it with applications in traditional editing. Through the notion of multimodal listening we provide guidelines that can be used in rhythmic and sonic interaction design in VR....

Insulin resistance and circadian rhythm of cardiac autonomic modulation

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Cai Jianwen

2010-12-01

Full Text Available Abstract Background Insulin resistance (IR has been associated with cardiovascular diseases (CVD. Heart rate variability (HRV, an index of cardiac autonomic modulation (CAM, is also associated with CVD mortality and CVD morbidity. Currently, there are limited data about the impairment of IR on the circadian pattern of CAM. Therefore, we conducted this investigation to exam the association between IR and the circadian oscillations of CAM in a community-dwelling middle-aged sample. Method Homeostasis models of IR (HOMA-IR, insulin, and glucose were used to assess IR. CAM was measured by HRV analysis from a 24-hour electrocardiogram. Two stage modeling was used in the analysis. In stage one, for each individual we fit a cosine periodic model based on the 48 segments of HRV data. We obtained three individual-level cosine parameters that quantity the circadian pattern: mean (M, measures the overall average of a HRV index; amplitude (Â, measures the amplitude of the oscillation of a HRV index; and acrophase time (θ, measures the timing of the highest oscillation. At the second stage, we used a random-effects-meta-analysis to summarize the effects of IR variables on the three circadian parameters of HRV indices obtained in stage one of the analysis. Results In persons without type diabetes, the multivariate adjusted β (SE of log HOMA-IR and M variable for HRV were -0.251 (0.093, -0.245 (0.078, -0.19 (0.06, -4.89 (1.76, -3.35 (1.31, and 2.14 (0.995, for log HF, log LF, log VLF, SDNN, RMSSD and HR, respectively (all P Conclusion Elevated IR, among non-diabetics significantly impairs the overall mean levels of CAM. However, the  or θ of CAM were not significantly affected by IR, suggesting that the circadian mechanisms of CAM are not impaired. However, among persons with type 2 diabetes, a group clinically has more severe form of IR, the adverse effects of increased IR on all three HRV circadian parameters are much larger.

Redundancy of stomatal control for the circadian photosynthetic rhythm in Kalanchoë daigremontiana Hamet et Perrier.

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Wyka, T P; Duarte, H M; Lüttge, U E

2005-03-01

In continuous light, the Crassulacean acid metabolism plant Kalanchoe daigremontiana Hamet et Perrier has a circadian rhythm of gas exchange with peaks occurring during the subjective night. The rhythm of gas exchange is coupled to a weak, reverse phased rhythm of quantum yield of photosystem II (Phi (PSII)). To test if the rhythm of Phi (PSII) persists in the absence of stomatal control, leaves were coated with a thin layer of translucent silicone grease which prevented CO2 and H2O exchange. In spite of this treatment, the rhythm of Phi (PSII) occurred with close to normal phase timing and with a much larger amplitude than in uncoated leaves. The mechanism underlying the Phi (PSII) rhythm in coated leaves can be explained by a circadian activity of phosphoenolpyruvate carboxylase (PEPC). At peaks of PEPC activity, the small amount of CO2 contained in the coated leaf could have become depleted, preventing the carboxylase activity of Rubisco and causing decreases in electron transport rates (observed as deep troughs of Phi (PSII) at 23-h in LL and at ca. 24-h intervals afterwards). Peaks of Phi (PSII) would be caused by a downregulation of PEPC leading to improved supply of CO2 to Rubisco. Substrate limitation of photochemistry at 23 h (trough of Phi (PSII)) was also suggested by the weak response of ETR in coated leaves to stepwise light enhancement. These results show that photosynthetic rhythmicity in K. daigremontiana is independent of stomatal regulation and may originate in the mesophyll.

Circadian clock gene LATE ELONGATED HYPOCOTYL directly regulates the timing of floral scent emission in Petunia.

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Fenske, Myles P; Hewett Hazelton, Kristen D; Hempton, Andrew K; Shim, Jae Sung; Yamamoto, Breanne M; Riffell, Jeffrey A; Imaizumi, Takato

2015-08-04

Flowers present a complex display of signals to attract pollinators, including the emission of floral volatiles. Volatile emission is highly regulated, and many species restrict emissions to specific times of the day. This rhythmic emission of scent is regulated by the circadian clock; however, the mechanisms have remained unknown. In Petunia hybrida, volatile emissions are dominated by products of the floral volatile benzenoid/phenylpropanoid (FVBP) metabolic pathway. Here we demonstrate that the circadian clock gene P. hybrida LATE ELONGATED HYPOCOTYL (LHY; PhLHY) regulates the daily expression patterns of the FVBP pathway genes and floral volatile production. PhLHY expression peaks in the morning, antiphasic to the expression of P. hybrida GIGANTEA (PhGI), the master scent regulator ODORANT1 (ODO1), and many other evening-expressed FVBP genes. Overexpression phenotypes of PhLHY in Arabidopsis caused an arrhythmic clock phenotype, which resembles those of LHY overexpressors. In Petunia, constitutive expression of PhLHY depressed the expression levels of PhGI, ODO1, evening-expressed FVBP pathway genes, and FVBP emission in flowers. Additionally, in the Petunia lines in which PhLHY expression was reduced, the timing of peak expression of PhGI, ODO1, and the FVBP pathway genes advanced to the morning. Moreover, PhLHY protein binds to cis-regulatory elements called evening elements that exist in promoters of ODO1 and other FVBP genes. Thus, our results imply that PhLHY directly sets the timing of floral volatile emission by restricting the expression of ODO1 and other FVBP genes to the evening in Petunia.

Recent Advances in Circadian Rhythms in Cardiovascular System

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Lihong eChen

2015-04-01

Full Text Available Growing evidence shows that intrinsic circadian clocks are tightly related to cardiovascular functions. The diurnal changes in blood pressure and heart rate are well known circadian rhythms. Endothelial function, platelet aggregation and thrombus formation exhibit circadian changes as well. The onset of many cardiovascular diseases (CVDs or events, such as myocardial infarction, stroke, arrhythmia, and sudden cardiac death, also exhibits temporal trends. Furthermore, there is strong evidence from animal models and epidemiological studies showing that disruption of circadian rhythms is a significant risk factor for many CVDs, and the intervention of CVDs may have a time dependent effect. In this mini review, we summarized recent advances in our understanding of the relationship between circadian rhythm and cardiovascular physiology and diseases including blood pressure regulation and myocardial infarction.

Rhythmic EEG patterns in extremely preterm infants: Classification and association with brain injury and outcome.

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Weeke, Lauren C; van Ooijen, Inge M; Groenendaal, Floris; van Huffelen, Alexander C; van Haastert, Ingrid C; van Stam, Carolien; Benders, Manon J; Toet, Mona C; Hellström-Westas, Lena; de Vries, Linda S

2017-12-01

Classify rhythmic EEG patterns in extremely preterm infants and relate these to brain injury and outcome. Retrospective analysis of 77 infants born Rhythmic patterns were observed in 62.3% (ictal 1.3%, PEDs 44%, other waveforms 86.3%) with multiple patterns in 36.4%. Ictal discharges were only observed in one and excluded from further analyses. The EEG location of the other waveforms (pRhythmic waveforms related to head position are likely artefacts. Rhythmic EEG patterns may have a different significance in extremely preterm infants. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Circadian Rhythms, Sleep, and Disorders of Aging.

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Mattis, Joanna; Sehgal, Amita

2016-04-01

Sleep-wake cycles are known to be disrupted in people with neurodegenerative disorders. These findings are now supported by data from animal models for some of these disorders, raising the question of whether the disrupted sleep/circadian regulation contributes to the loss of neural function. As circadian rhythms and sleep consolidation also break down with normal aging, changes in these may be part of what makes aging a risk factor for disorders like Alzheimer's disease (AD). Mechanisms underlying the connection between circadian/sleep dysregulation and neurodegeneration remain unclear, but several recent studies provide interesting possibilities. While mechanistic analysis is under way, it is worth considering treatment of circadian/sleep disruption as a means to alleviate symptoms of neurodegenerative disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Circadian Clock-controlled Transcriptome of Developing Soybean Seeds

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Karen A. Hudson

2010-07-01

Full Text Available A number of metabolic and physiological processes in plants are controlled by the circadian clock, which enables a plant to anticipate daily changes in the environment. Relatively little is known about circadian rhythms in developing seeds, which may be important for determining the extent and timing of nutrient storage in grain. Microarray expression profiling was used to identify genes expressed in developing soybean ( seeds that are controlled by the circadian clock. Genes with predicted functions in protein synthesis, fatty acid metabolism, and photosynthesis totaling 1.8% of the mRNAs detected in seed were found to be expressed in a circadian rhythm. Known circadian and light-controlled promoter elements were identified as over-represented in the promoters of clock-controlled seed genes, with the over-represented elements varying according to the phase of circadian expression. A subset of circadian-regulated genes were found to be expressed in different phases in developing seeds with respect to leaves from the same plants, many of which have roles in photosynthesis and carbon metabolism. These results help to characterize the genes and processes in seeds that may be regulated by the circadian clock, and provide some insight into organ-specific phasing of clock controlled gene expression.

Transitions between discrete and rhythmic primitives in a unimanual task

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Sternad, Dagmar; Marino, Hamal; Charles, Steven K.; Duarte, Marcos; Dipietro, Laura; Hogan, Neville

2013-01-01

Given the vast complexity of human actions and interactions with objects, we proposed that control of sensorimotor behavior may utilize dynamic primitives. However, greater computational simplicity may come at the cost of reduced versatility. Evidence for primitives may be garnered by revealing such limitations. This study tested subjects performing a sequence of progressively faster discrete movements in order to “stress” the system. We hypothesized that the increasing pace would elicit a transition to rhythmic movements, assumed to be computationally and neurally more efficient. Abrupt transitions between the two types of movements would support the hypothesis that rhythmic and discrete movements are distinct primitives. Ten subjects performed planar point-to-point arm movements paced by a metronome: starting at 2 s, the metronome intervals decreased by 36 ms per cycle to 200 ms, stayed at 200 ms for several cycles, then increased by similar increments. Instructions emphasized to insert explicit stops between each movement with a duration that equaled the movement time. The experiment was performed with eyes open and closed, and with short and long metronome sounds, the latter explicitly specifying the dwell duration. Results showed that subjects matched instructed movement times but did not preserve the dwell times. Rather, they progressively reduced dwell time to zero, transitioning to continuous rhythmic movements before movement times reached their minimum. The acceleration profiles showed an abrupt change between discrete and rhythmic profiles. The loss of dwell time occurred earlier with long auditory specification, when subjects also showed evidence of predictive control. While evidence for hysteresis was weak, taken together, the results clearly indicated a transition between discrete and rhythmic movements, supporting the proposal that representation is based on primitives rather than on veridical internal models. PMID:23888139

Transitions between Discrete and Rhythmic Primitives in a Unimanual Task

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Dagmar eSternad

2013-07-01

Full Text Available Given the vast complexity of human actions and interactions with objects, we proposed that control of sensorimotor behavior may utilize dynamic primitives. However, greater computational simplicity may come at the cost of reduced versatility. Evidence for primitives may be garnered by revealing such limitations. This study tested subjects performing a sequence of progressively faster discrete movements, in order to stress the system. We hypothesized that the increasing pace would elicit a transition to rhythmic movements, assumed to be computationally and neurally more efficient. Abrupt transitions between the two types of movements would support the hypothesis that rhythmic and discrete movements are distinct primitives. Ten subjects performed planar point-to-point arm movements paced by a metronome: Starting at 2s the metronome intervals decreased by 36ms per cycle to 200ms, stayed at 200ms for several cycles, then increased by similar increments. Instructions emphasized to insert explicit stops between each movement with a duration that equaled the movement time. The experiment was performed with eyes open and closed, and with short and long metronome sounds, the latter explicitly specifying the dwell duration. Results showed that subjects matched instructed movement times but did not preserve the dwell times. Rather, they progressively reduced dwell time to zero, transitioning to continuous rhythmic movements before movement times reached their minimum. The acceleration profiles showed an abrupt change between discrete and rhythmic profiles. The loss of dwell time occurred earlier with long auditory specification, when subjects also showed evidence of predictive control. While evidence for hysteresis was weak, taken together, the results clearly indicated a transition between discrete and rhythmic movements, supporting the proposal that representation is based on primitives rather than on veridical internal models.

The impact of the perception of rhythmic music on self-paced oscillatory movements.

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Peckel, Mathieu; Pozzo, Thierry; Bigand, Emmanuel

2014-01-01

Inspired by theories of perception-action coupling and embodied music cognition, we investigated how rhythmic music perception impacts self-paced oscillatory movements. In a pilot study, we examined the kinematic parameters of self-paced oscillatory movements, walking and finger tapping using optical motion capture. In accordance with biomechanical constraints accounts of motion, we found that movements followed a hierarchical organization depending on the proximal/distal characteristic of the limb used. Based on these findings, we were interested in knowing how and when the perception of rhythmic music could resonate with the motor system in the context of these constrained oscillatory movements. In order to test this, we conducted an experiment where participants performed four different effector-specific movements (lower leg, whole arm and forearm oscillation and finger tapping) while rhythmic music was playing in the background. Musical stimuli consisted of computer-generated MIDI musical pieces with a 4/4 metrical structure. The musical tempo of each song increased from 60 BPM to 120 BPM by 6 BPM increments. A specific tempo was maintained for 20 s before a 2 s transition to the higher tempo. The task of the participant was to maintain a comfortable pace for the four movements (self-paced) while not paying attention to the music. No instruction on whether to synchronize with the music was given. Results showed that participants were distinctively influenced by the background music depending on the movement used with the tapping task being consistently the most influenced. Furthermore, eight strategies put in place by participants to cope with the task were unveiled. Despite not instructed to do so, participants also occasionally synchronized with music. Results are discussed in terms of the link between perception and action (i.e., motor/perceptual resonance). In general, our results give support to the notion that rhythmic music is processed in a motoric

The impact of the perception of rhythmic music on oscillatory self-paced movements

Directory of Open Access Journals (Sweden)

Mathieu ePeckel

2014-09-01

Full Text Available Inspired by theories of perception-action coupling and embodied music cognition, we investigated how rhythmic music perception impacts self-paced oscillatory movements. In a pilot study, we examined the kinematic parameters of self-paced oscillatory movements, walking and finger tapping using optical motion capture. In accordance with biomechanical constraints accounts of motion, we found that movements followed a hierarchical organization depending on the proximal/distal characteristic of the limb used. Based on these findings, we were interested in knowing how and when the perception of rhythmic music could resonate with the motor system in the context of these constrained oscillatory movements. In order to test this, we conducted an experiment where participants performed four different effector-specific movements (lower leg, whole arm and forearm oscillation and finger tapping while rhythmic music was playing in the background. Musical stimuli consisted of computer-generated MIDI musical pieces with a 4/4 metrical structure. The musical tempo of each song increased from 60 BPM to 120 BPM by 6 BPM increments. A specific tempo was maintained for 20s before a 2s transition to the higher tempo. The task of the participant was to maintain a comfortable pace for the four movements (self-paced while not paying attention to the music. No instruction on whether to synchronize with the music was given. Results showed that participants were distinctively influenced by the background music depending on the movement used with the tapping task being consistently the most influenced. Furthermore, eight strategies put in place by participants to cope with task were unveiled. Despite not instructed to do so, participants also occasionally synchronized with music. Results are discussed in terms of the link between perception and action (i.e. motor/perceptual resonance. In general, our results give support to the notion that rhythmic music is processed in a

The effect of lens aging and cataract surgery on circadian rhythm.

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Yan, Shen-Shen; Wang, Wei

2016-01-01

Many organisms have evolved an approximately 24-hour circadian rhythm that allows them to achieve internal physiological homeostasis with external environment. Suprachiasmatic nucleus (SCN) is the central pacemaker of circadian rhythm, and its activity is entrained to the external light-dark cycle. The SCN controls circadian rhythm through regulating the synthesis of melatonin by pineal gland via a multisynaptic pathway. Light, especially short-wavelength blue light, is the most potent environmental time cue in circadian photoentrainment. Recently, the discovery of a novel type of retinal photoreceptors, intrinsically photosensitive retinal ganglion cells, sheds light on the mechanism of circadian photoentrainment and raises concerns about the effect of ocular diseases on circadian system. With age, light transmittance is significantly decreased due to the aging of crystalline lens, thus possibly resulting in progressive loss of circadian photoreception. In the current review, we summarize the circadian physiology, highlight the important role of light in circadian rhythm regulation, discuss about the correlation between age-related cataract and sleep disorders, and compare the effect of blue light- filtering intraocular lenses (IOLs) and ultraviolet only filtering IOLs on circadian rhythm.

Rhythmic Patterns in Ragtime and Jazz

NARCIS (Netherlands)

Odekerken, Daphne; Volk, A.; Koops, Hendrik Vincent

2017-01-01

This paper presents a corpus-based study on rhythmic patterns in ragtime and jazz. Ragtime and jazz are related genres, but there are open questions on what specifies the two genres. Earlier studies revealed that variations of a particular syncopation pattern, referred to as 121, are among the most

Circadian rhythm in QT interval is preserved in mice deficient of potassium channel interacting protein 2

DEFF Research Database (Denmark)

Gottlieb, Lisa A; Lubberding, Anniek; Larsen, Anders Peter

2017-01-01

Potassium Channel Interacting Protein 2 (KChIP2) is suggested to be responsible for the circadian rhythm in repolarization duration, ventricular arrhythmias, and sudden cardiac death. We investigated the hypothesis that there is no circadian rhythm in QT interval in the absence of KChIP2. Implanted...... cardiac deaths were observed. We find similar diurnal (light:dark) and circadian (darkness) rhythms of RR intervals in WT and KChIP2(-/-) mice. Circadian rhythms in QT100 intervals are present in both groups, but at physiological small amplitudes: 1.6 ± 0.2 and 1.0 ± 0.3 ms in WT and KChIP2......(-/-), respectively (p = 0.15). A diurnal rhythm in QT100 intervals was only found in WT mice. QTmean-RR intervals display clear diurnal and circadian rhythms in both WT and KChIP2(-/-). The amplitude of the circadian rhythm in QTmean-RR is 4.0 ± 0.3 and 3.1 ± 0.5 ms in WT and KChIP2(-/-), respectively (p = 0...

Pilot investigation of the circadian plasma melatonin rhythm across the menstrual cycle in a small group of women with premenstrual dysphoric disorder.

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Ari Shechter

Full Text Available Women with premenstrual dysphoric disorder (PMDD experience mood deterioration and altered circadian rhythms during the luteal phase (LP of their menstrual cycles. Disturbed circadian rhythms may be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP and LP of the menstrual cycle, consisting of intensive physiological monitoring under "unmasked", time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P≤.03 worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P = .025 increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (P<.05 decreased melatonin at circadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed.

Circadian behaviour in neuroglobin deficient mice.

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Christian A Hundahl

Full Text Available Neuroglobin (Ngb, a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN. The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1 and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night.

Circadian Rhythms

Indian Academy of Sciences (India)

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Early studies on circadian rhythms focussed on unravelling the fundamental .... careful analysis revealed that deaths of most arrhythmic indi- viduals were due to .... is no more a sci-fi movie script and is achievable through a technique called ...

Circadian polymorphisms associated with affective disorders

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Shekhtman Tatyana

2009-01-01

Full Text Available Abstract Background Clinical symptoms of affective disorders, their response to light treatment, and sensitivity to other circadian interventions indicate that the circadian system has a role in mood disorders. Possibly the mechanisms involve circadian seasonal and photoperiodic mechanisms. Since genetic susceptibilities contribute a strong component to affective disorders, we explored whether circadian gene polymorphisms were associated with affective disorders in four complementary studies. Methods Four groups of subjects were recruited from several sources: 1 bipolar proband-parent trios or sib-pair-parent nuclear families, 2 unrelated bipolar participants who had completed the BALM morningness-eveningness questionnaire, 3 sib pairs from the GenRed Project having at least one sib with early-onset recurrent unipolar depression, and 4 a sleep clinic patient group who frequently suffered from depression. Working mainly with the SNPlex assay system, from 2 to 198 polymorphisms in genes related to circadian function were genotyped in the participant groups. Associations with affective disorders were examined with TDT statistics for within-family comparisons. Quantitative trait associations were examined within the unrelated samples. Results In NR1D1, rs2314339 was associated with bipolar disorder (P = 0.0005. Among the unrelated bipolar participants, 3 SNPs in PER3 and CSNK1E were associated with the BALM score. A PPARGC1B coding SNP, rs7732671, was associated with affective disorder with nominal significance in bipolar family groups and independently in unipolar sib pairs. In TEF, rs738499 was associated with unipolar depression; in a replication study, rs738499 was also associated with the QIDS-SR depression scale in the sleep clinic patient sample. Conclusion Along with anti-manic effects of lithium and the antidepressant effects of bright light, these findings suggest that perturbations of the circadian gene network at several levels may

A little elastic for a better performance: kinesiotaping of the motor effector modulates neural mechanisms for rhythmic movements.

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Bravi, Riccardo; Quarta, Eros; Cohen, Erez J; Gottard, Anna; Minciacchi, Diego

2014-01-01

A rhythmic motor performance is brought about by an integration of timing information with movements. Investigations on the millisecond time scale distinguish two forms of time control, event-based timing and emergent timing. While event-based timing asserts the existence of a central internal timekeeper for the control of repetitive movements, the emergent timing perspective claims that timing emerges from dynamic control of nontemporal movements parameters. We have recently demonstrated that the precision of an isochronous performance, defined as performance of repeated movements having a uniform duration, was insensible to auditory stimuli of various characteristics (Bravi et al., 2014). Such finding has led us to investigate whether the application of an elastic therapeutic tape (Kinesio® Tex taping; KTT) used for treating athletic injuries and a variety of physical disorders, is able to reduce the timing variability of repetitive rhythmic movement. Young healthy subjects, tested with and without KTT, have participated in sessions in which sets of repeated isochronous wrist's flexion-extensions (IWFEs) were performed under various auditory conditions and during their recall. Kinematics was recorded and temporal parameters were extracted and analyzed. Our results show that the application of KTT decreases the variability of rhythmic movements by a 2-fold effect: on the one hand KTT provides extra proprioceptive information activating cutaneous mechanoreceptors, on the other KTT biases toward the emergent timing thus modulating the processes for rhythmic movements. Therefore, KTT appears able to render movements less audio dependent by relieving, at least partially, the central structures from time control and making available more resources for an augmented performance.

A little elastic for a better performance: kinesiotaping of the motor effector modulates neural mechanisms for rhythmic movements

Directory of Open Access Journals (Sweden)

Riccardo eBravi

2014-09-01

Full Text Available A rhythmic motor performance is brought about by an integration of timing information with movements. Investigations on the millisecond time scale distinguish two forms of time control, event-based timing and emergent timing. While event-based timing asserts the existence of a central internal timekeeper for the control of repetitive movements, the emergent timing perspective claims that timing emerges from dynamic control of nontemporal movements parameters. We have recently demonstrated that the precision of an isochronous performance, defined as performance of repeated movements having a uniform duration, was insensible to auditory stimuli of various characteristics (Bravi et al., 2014. Such finding has led us to investigate whether the application of an elastic therapeutic tape (Kinesio® Tex taping; KTT used for treating athletic injuries and a variety of physical disorders, is able to reduce the timing variability of repetitive rhythmic movement. Young healthy subjects, tested with and without KTT, have participated in sessions in which sets of repeated isochronous wrist's flexion-extensions (IWFEs were performed under various auditory conditions and during their recall. Kinematics was recorded and temporal parameters were extracted and analyzed. Our results show that the application of KTT decreases the variability of rhythmic movements by a twofold effect: on the one hand KTT provides extra proprioceptive information activating cutaneous mechanoreceptors, on the other KTT biases toward the emergent timing thus modulating the processes for rhythmic movements. Therefore, KTT appears able to render movements less audio dependent by relieving, at least partially, the central structures from time control and making available more resources for an augmented performance.

Phase coupling of a circadian neuropeptide with rest/activity rhythms detected using a membrane-tethered spider toxin.

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Ying Wu

2008-11-01

induces rhythmic action potential bursts and depolarized plateau potentials. These in vitro and in vivo electrophysiological effects of membrane-tethered delta-ACTX-Hv1a are consistent with the effects of soluble delta-ACTX-Hv1a purified from venom on Na(+ channel physiological and biophysical properties in cockroach neurons. Membrane-tethered delta-ACTX-Hv1a expression in the PDF-secreting subset of clock neurons induces an approximately 4-h phase advance of the rhythm of PDF accumulation in their terminals relative to both the phase of the day:night cycle and the phase of the circadian transcriptional feedback loops. As a consequence, the morning anticipatory peak of locomotor activity preceding dawn, which has been shown to be driven by the clocks of the PDF-secreting subset of clock neurons, phase advances coordinately with the phase of the PDF rhythm of the PDF-secreting clock neurons, rather than maintaining its phase relationship with the day:night cycle and circadian transcriptional feedback loops. These results (1 validate the tethered-toxin technology for cell-autonomous modulation of ion channel biophysical properties in vivo in transgenic Drosophila, (2 demonstrate that the kinetics of para Na(+ channel inactivation is a key parameter for determining the phase relationship between circadian transcriptional feedback oscillation and PDF secretion, and (3 provide experimental support for the hypothesis that PDF-secreting clock neurons entrain the phase of organismal rhythms via the temporal patterning of secreted PDF signals.

Rhythmic Rituals and Emergent Listening: Intra-Activity, Sonic Sounds and Digital Composing with Young Children

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