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Sample records for generating circadian rhythms

  1. Brief Communication Circadian Rhythm Generation and Entrainment

    E-print Network

    Newman, Eric A.

    Brief Communication Circadian Rhythm Generation and Entrainment in Astrocytes Laura M. Prolo,1 into an SCN- lesioned animal restores circadian rhythms with the donor's pe- riod (Ralph et al., 1990,themastercircadianpacemakerisconsideredthesuprachiasmaticnucleus(SCN)ofthehypothalamus.TheSCNconsistsof aheterogeneouspopulationofneuronsandrelativelyunderstudiedglia.Weinvestigatedwhetherglia,likeneurons,rhythmicallyexpress circadian genes. We generated pure

  2. Circadian Rhythms

    MedlinePLUS

    ... NIGMS Home > Science Education > Circadian Rhythms Fact Sheet Circadian Rhythms Fact Sheet Tagline (Optional) Middle/Main Content Area En español What are circadian rhythms? Circadian rhythms are physical, mental and behavioral changes ...

  3. A Mathematical Model for the Intracellular Circadian Rhythm Generator

    E-print Network

    van Pelt, Jaap

    A Mathematical Model for the Intracellular Circadian Rhythm Generator Tjeerd olde Scheper,1 Don for the intracellular circadian rhythm generator has been studied, based on a negative feedback of protein products. Key words: SCN; circadian rhythm; molecular clock; entrain- ment; phase­response curves; models Free

  4. Circadian Rhythms

    MedlinePLUS

    ... chronobiology. Are circadian rhythms the same thing as biological clocks? No, but they are related. Our biological clocks drive our circadian rhythms. What are biological clocks? The biological clocks that control circadian rhythms ...

  5. Biological Clocks & Circadian Rhythms

    ERIC Educational Resources Information Center

    Robertson, Laura; Jones, M. Gail

    2009-01-01

    The study of biological clocks and circadian rhythms is an excellent way to address the inquiry strand in the National Science Education Standards (NSES) (NRC 1996). Students can study these everyday phenomena by designing experiments, gathering and analyzing data, and generating new experiments. As students explore biological clocks and circadian

  6. Sleep and circadian rhythms

    NASA Technical Reports Server (NTRS)

    Monk, Timothy H.

    1991-01-01

    Three interacting processes are involved in the preservation of circadian rhythms: (1) endogenous rhythm generation mechanisms, (2) entrainment mechanisms to keep these rhythms 'on track', and (3) exogenous masking processes stemming from changes in environment and bahavior. These processes, particularly the latter two, can be dramatically affected in individuals of advanced age and in space travelers, with a consequent disruption in sleep and daytime functioning. This paper presents results of a phase-shift experiment investigating the age-related effects of the exogeneous component of circadian rhythms in various physiological and psychological functions by comparing these functions in middle aged and old subjects. Dramatic differences were found between the two age groups in measures of sleep, mood, activation, and performance efficiency.

  7. Circadian Rhythms in Cyanobacteria.

    PubMed

    Cohen, Susan E; Golden, Susan S

    2015-12-01

    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

  8. CHAPTER SEVEN Circadian Rhythms, Sleep

    E-print Network

    Pennsylvania, University of

    CHAPTER SEVEN Circadian Rhythms, Sleep Deprivation, and Human Performance Namni Goel*, Mathias-Process Model 157 3. Circadian Rhythms of Performance 162 3.1 Subjective measures of sleepiness and alertness. Interindividual Variability in Circadian Rhythms 166 5.1 Chronotype (morningness­eveningness) 167 5.2 Genetics

  9. Robustness of circadian rhythms with respect to molecular noise

    E-print Network

    Goldbeter, Albert

    Robustness of circadian rhythms with respect to molecular noise Didier Gonze, Jose´ Halloy molecular model capable of generating circadian rhythms to assess the robustness of circadian oscillations stochastic simulations model Drosophila Neurospora Circadian rhythms characterized by a period close to 24 h

  10. Circadian Rhythm Sleep Disorders

    PubMed Central

    Kim, Min Ju; Lee, Jung Hie; Duffy, Jeanne F.

    2014-01-01

    Objective To review circadian rhythm sleep disorders, including underlying causes, diagnostic considerations, and typical treatments. Methods Literature review and discussion of specific cases. Results Survey studies 1,2 suggest that up to 3% of the adult population suffers from a circadian rhythm sleep disorder (CRSD). However, these sleep disorders are often confused with insomnia, and an estimated 10% of adult and 16% of adolescent sleep disorders patients may have a CRSD 3-6. While some CRSD (such as jet lag) can be self-limiting, others when untreated can lead to adverse medical, psychological, and social consequences. The International Classification of Sleep Disorders classifies CRSD as dyssomnias, with six subtypes: Advanced Sleep Phase Type, Delayed Sleep Phase Type, Irregular Sleep Wake Type, Free Running Type, Jet Lag Type, and Shift Work Type. The primary clinical characteristic of all CRSD is an inability to fall asleep and wake at the desired time. It is believed that CRSD arise from a problem with the internal biological clock (circadian timing system) and/or misalignment between the circadian timing system and the external 24-hour environment. This misalignment can be the result of biological and/or behavioral factors. CRSD can be confused with other sleep or medical disorders. Conclusions Circadian rhythm sleep disorders are a distinct class of sleep disorders characterized by a mismatch between the desired timing of sleep and the ability to fall asleep and remain asleep. If untreated, CRSD can lead to insomnia and excessive daytime sleepiness, with negative medical, psychological, and social consequences. It is important for physicians to recognize potential circadian rhythm sleep disorders so that appropriate diagnosis, treatment, and referral can be made. PMID:25368503

  11. Genetics of Circadian Rhythms.

    PubMed

    Andreani, Tomas S; Itoh, Taichi Q; Yildirim, Evrim; Hwangbo, Dae-Sung; Allada, Ravi

    2015-12-01

    Nearly all organisms exhibit time-dependent behavior and physiology across a 24-hour day known as circadian rhythms. These outputs are manifestations of endogenous cyclic gene expression patterns driven by the activity of a core transcription/translation feedback loop. Cyclic gene expression determines highly tissue-specific functional activity regulating such processes as metabolic state, endocrine activity, and neural excitability. Entrainment of these cellular clocks is achieved through exogenous daily inputs, such as light and food. Dysregulation of the transcription/translation feedback loop has been shown to result in a wide range of disorders and diseases driving increased interest in circadian therapies. PMID:26568119

  12. Gonadectomy reveals sex differences in circadian rhythms and suprachiasmatic nucleus androgen receptors in mice

    E-print Network

    Silver, Rae

    Gonadectomy reveals sex differences in circadian rhythms and suprachiasmatic nucleus androgen rights reserved. Keywords: Circadian rhythms; Mouse; Gonadal hormones; Dihydrotestosterone; Testosterone is necessary for the generation and maintenance of circadian rhythms (Klein et al., 1991). In proof, lesions

  13. Circadian Rhythms Regulate Amelogenesis

    PubMed Central

    Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A.; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

    2013-01-01

    Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24h) intervals both at RNA and protein levels. This study also reveals that two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stage of amelogenesis might be under circadian control. Changes in clock genes expression patterns might result in significant alterations of enamel apposition and mineralization. PMID:23486183

  14. 244 Dispatch Circadian rhythms: Partners in time

    E-print Network

    Krasnow, Mark A.

    244 Dispatch Circadian rhythms: Partners in time Russell N. Van Gelder* and Mark A. Krasnow of the rhythms he discovered. Circadian rhythms -- self- sustained, nearly 24 hour rhythms of behavior in insects. Despite intensive analysis of the physiological properties of circadian rhythms, no clear insight

  15. Circadian rhythm and its role in malignancy

    PubMed Central

    2010-01-01

    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. PMID:20353609

  16. Studying circadian rhythms in Drosophila melanogaster

    PubMed Central

    Tataroglu, Ozgur; Emery, Patrick

    2014-01-01

    Circadian rhythms have a profound influence on most bodily functions: from metabolism to complex behaviors. They ensure that all these biological processes are optimized with the time-of-day. They are generated by endogenous molecular oscillators that have a period that closely, but not exactly, matches day length. These molecular clocks are synchronized by environmental cycles such as light intensity and temperature. Drosophila melanogaster has been a model organism of choice to understand genetically, molecularly and at the level of neural circuits how circadian rhythms are generated, how they are synchronized by environmental cues, and how they drive behavioral cycles such as locomotor rhythms. This review will cover a wide range of techniques that have been instrumental to our understanding of Drosophila circadian rhythms, and that are essential for current and future research. PMID:24412370

  17. CIRCADIAN RHYTHM DISTURBANCES IN DEPRESSION

    PubMed Central

    Germain, Anne; Kupfer, David J.

    2008-01-01

    Objective The aim of this article is to review progress in understanding the mechanisms that underlie circadian and sleep rhythms, and their role in the pathogenesis and treatment of depression. Methods Literature was selected principally by Medline searches, and additional reports were identified based on ongoing research activities in the authors’ laboratory. Results Many physiological processes show circadian rhythms of activity. Sleep and waking are the most obvious circadian rhythms in mammals. There is considerable evidence that circadian and sleep disturbances are important in the pathophysiology of mood disorders. Depressed patients often show altered circadian rhythms, sleep disturbances, and diurnal mood variation. Chronotherapies, including bright light exposure, sleep deprivation, and social rhythm therapies, may be useful adjuncts in non-seasonal and seasonal depression. Antidepressant drugs have marked effects on circadian processes and sleep. Conclusions Recent progress in understanding chronobiological and sleep regulation mechanisms may provide novel insights and avenues into the development of new pharmacological and behavioral treatment strategies for mood disorders. PMID:18680211

  18. The Neurobiology of Circadian Rhythms.

    PubMed

    Sollars, Patricia J; Pickard, Gary E

    2015-12-01

    There is a growing recognition that the coordinated timing of behavioral, physiologic, and metabolic circadian rhythms is a requirement for a healthy body and mind. In mammals, the primary circadian oscillator is the hypothalamic suprachiasmatic nucleus (SCN), which is responsible for circadian coordination throughout the organism. Temporal homeostasis is recognized as a complex interplay between rhythmic clock gene expression in brain regions outside the SCN and in peripheral organs. Abnormalities in this intricate circadian orchestration may alter sleep patterns and contribute to the pathophysiology of affective disorders. PMID:26600101

  19. Aging and Circadian Rhythms.

    PubMed

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

    2015-12-01

    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. This article reviews 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

  20. Phenotyping Circadian Rhythms in Mice.

    PubMed

    Eckel-Mahan, Kristin; Sassone-Corsi, Paolo

    2015-01-01

    Circadian rhythms take place with a periodicity of 24 hr, temporally following the rotation of the earth around its axis. Examples of circadian rhythms are the sleep/wake cycle, feeding, and hormone secretion. Light powerfully entrains the mammalian clock and assists in keeping animals synchronized to the 24-hour cycle of the earth by activating specific neurons in the "central pacemaker" of the brain, the suprachiasmatic nucleus. Absolute periodicity of an animal can deviate slightly from 24 hr as manifest when an animal is placed into constant dark or "free-running" conditions. Simple measurements of an organism's activity in free-running conditions reveal its intrinsic circadian period. Mice are a particularly useful model for studying circadian rhythmicity due to the ease of genetic manipulation, thus identifying molecular contributors to rhythmicity. Furthermore, their small size allows for monitoring locomotion or activity in their homecage environment with relative ease. Several tasks commonly used to analyze circadian periodicity and plasticity in mice are presented here including the process of entrainment, determination of tau (period length) in free-running conditions, determination of circadian periodicity in response to light disruption (e.g., jet lag studies), and evaluation of clock plasticity in non-24-hour conditions (T-cycles). Studying the properties of circadian periods such as their phase, amplitude, and length in response to photic perturbation, can be particularly useful in understanding how humans respond to jet lag, night shifts, rotating shifts, or other transient or chronic disruption of environmental surroundings. PMID:26331760

  1. Circadian Rhythm Control: Neurophysiological Investigations

    NASA Technical Reports Server (NTRS)

    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.

  2. Circadian Rhythm Disruption in Cancer Biology

    PubMed Central

    Savvidis, Christos; Koutsilieris, Michael

    2012-01-01

    Circadian rhythms show universally a 24-h oscillation pattern in metabolic, physiological and behavioral functions of almost all species. This pattern is due to a fundamental adaptation to the rotation of Earth around its own axis. Molecular mechanisms of generation of circadian rhythms organize a biochemical network in suprachiasmatic nucleus and peripheral tissues, building cell autonomous clock pacemakers. Rhythmicity is observed in transcriptional expression of a wide range of clock-controlled genes that regulate a variety of normal cell functions, such as cell division and proliferation. Desynchrony of this rhythmicity seems to be implicated in several pathologic conditions, including tumorigenesis and progression of cancer. In 2007, the International Agency for Research on Cancer (IARC) categorized “shiftwork that involves circadian disruption [as] probably carcinogenic to humans” (Group 2A in the IARC classification system of carcinogenic potency of an agentagent) (Painting, Firefighting, and Shiftwork; IARC; 2007). This review discusses the potential relation between disruptions of normal circadian rhythms with genetic driving machinery of cancer. Elucidation of the role of clockwork disruption, such as exposure to light at night and sleep disruption, in cancer biology could be important in developing new targeted anticancer therapies, optimizing individualized chronotherapy and modifying lighting environment in workplaces or homes. PMID:22811066

  3. Neurobiology of Circadian Rhythm Regulation.

    PubMed

    Rosenwasser, Alan M; Turek, Fred W

    2015-12-01

    Over the past few decades, multilevel research has elucidated the basic neuroanatomy, neurochemistry, and molecular neurobiology of the master circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). The circadian timing system is composed of a large number of cellular oscillators located in the SCN, in non-SCN brain structures, and throughout the body. Cellular-level oscillations are generated by a molecular feedback loop in which circadian clock genes rhythmically regulate their own transcription, as well as that of hundreds of clock-controlled genes. The maintenance of proper coordination within this network of cellular- and tissue-level clocks is essential for health and well-being. PMID:26568118

  4. Circadian rhythms in myocardial metabolism and function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythms in myocardial function and dysfunction are firmly established in both animal models and humans. For example, the incidence of arrhythmias and sudden cardiac death increases when organisms awaken. Such observations have classically been explained by circadian rhythms in neurohumoral...

  5. Endogenous circadian rhythm in human motor activity uncoupled from circadian influences

    E-print Network

    Stanley, H. Eugene

    Endogenous circadian rhythm in human motor activity uncoupled from circadian influences on cardiac significant circadian rhythms with a peak at the circadian phase corresponding to 5­9 p.m. ( 9 h later than a circadian rhythm. These findings suggest that endogenous circadian-mediated activity vari- ations

  6. Circadian Rhythm Sleep-Wake Disorders.

    PubMed

    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. PMID:26600110

  7. Circadian rhythms of women with fibromyalgia

    NASA Technical Reports Server (NTRS)

    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.

  8. From circadian rhythms to cancer chronotherapeutics.

    PubMed

    Lévi, Francis

    2002-01-01

    Mammalian circadian rhythms result from a complex organization involving molecular clocks within nearly all "normal" cells and a dedicated neuroanatomical system, which coordinates the so-called "peripheral oscillators." The core of the central clock system is constituted by the suprachiasmatic nuclei that are located on the floor of the hypothalamus. Our understanding of the mechanisms of circadian rhythm generation and coordination processes has grown rapidly over the past few years. In parallel, we have learnt how to use the predictable changes in cellular metabolism or proliferation along the 24h time scale in order to improve treatment outcome for a variety of diseases, including cancer. The chronotherapeutics of malignant diseases has emerged as a result of a consistent development ranging from experimental, clinical, and technological prerequisites to multicenter clinical trials of chronomodulated delivery schedules. Indeed large dosing-time dependencies characterize the tolerability of anticancer agents in mice or rats, a better efficacy usually results from treatment administration near the least toxic circadian time in rodent tumor models. Programmable in time multichannel pumps have allowed to test the chronotherapy concepts in cancer patients and to implement chronomodulated delivery schedules in current practice. Clinical phase I and II trials have established the feasibility, the safety, and the activity of the chronotherapy schedules, so that this treatment method has undergone further evaluation in international multicenter phase III trials. Overall, more than 2,000 patients with metastatic disease have been registered in chronotherapy trials. Improved tolerability and/or better antitumor activity have been demonstrated in randomized multicenter studies involving large patient cohorts. The relation between circadian rhythmicity and quality of life and even survival has also been a puzzling finding over the recent years. An essential step toward further developments of circadian-timed therapy has been the recent constitution of a Chronotherapy cooperative group within the European Organization for Research and Treatment of Cancer. This group now involves over 40 institutions in 12 countries. It is conducting currently six trials and preparing four new studies. The 19 contributions in this special issue reflect the current status and perspectives of the several components of cancer chronotherapeutics. PMID:11962669

  9. Modeling the molecular regulatory mechanism of circadian rhythms

    E-print Network

    Goldbeter, Albert

    Modeling the molecular regulatory mechanism of circadian rhythms in Drosophila Jean mechanism of circadian rhythms in Drosoph- ila, theoretical models closely related to experimental a second to years.(1,2) Among these rhythms, circadian oscillations, which occur with a period of about 24

  10. Cellular and biochemical mechanisms underlying circadian rhythms in vertebrates

    E-print Network

    Gillette, Martha U.

    797 Cellular and biochemical mechanisms underlying circadian rhythms in vertebrates Martha U some behavioral rhythms. Consensus is emerging that circadian mechanisms are conserved across phylogeny with near Z-l-hour periods. Thus, these daily oscillations in behaviors are termed `circadian rhythms

  11. Development of Heart Rate Circadian Rhythm in Chickens *, R. Akiyamab

    E-print Network

    Burggren, Warren

    Development of Heart Rate Circadian Rhythm in Chickens K. Moriyaa *, R. Akiyamab , E.M. Dzialowskic such as a circadian rhythm. The present report reviews measurements of embryonic and hatchling HR fluctua- tions and examine development of HR circadian rhythms during the late stages of incubation and after hatching

  12. Circadian Synchrony in Networks of Protein Rhythm Driven Neurons

    E-print Network

    Siegelmann , Hava T

    Circadian Synchrony in Networks of Protein Rhythm Driven Neurons WILLIAM S. BUSH AND HAVA T; suprachiasmatic nucleus; protein expression; circadian rhythms INTRODUCTION S yncronicity has been examined M P L E X I T Y 67 DOI 10.1002/cplx.20145 #12;circadian rhythms, such as the sleep­wake cycle

  13. Circadian rhythms and molecular noise Didier Gonze and Albert Goldbeter

    E-print Network

    Goldbeter, Albert

    Circadian rhythms and molecular noise Didier Gonze and Albert Goldbeter Faculté des Sciences; accepted 17 May 2006; published online 30 June 2006 Circadian rhythms, characterized by a period of about to be crucial for the coherence of circadian rhythms is the binding/unbinding rate of the inhibitory protein

  14. Shape Invariant Modelling of Circadian Rhythms with Random Effects and

    E-print Network

    Wang, Yuedong

    Shape Invariant Modelling of Circadian Rhythms with Random Effects and Smoothing Spline ANOVA dynamics such as circadian rhythms. Under the assumption that the expected response functions of all methods to a real data set to investigate disease effects on circadian rhythms of cortisol, a hormone

  15. Circadian rhythms in Macaca mulatta monkeys during Bion 11 flight

    NASA Technical Reports Server (NTRS)

    Alpatov, A. M.; Hoban-Higgins, T. M.; Klimovitsky, V. Y.; Tumurova, E. G.; Fuller, C. A.

    2000-01-01

    Circadian rhythms of primate brain temperature, head and ankle skin temperature, motor activity, and heart rate were studied during spaceflight and on the ground. In space, the circadian rhythms of all the parameters were synchronized with diurnal Zeitgebers. However, in space the brain temperature rhythm showed a significantly more delayed phase angle, which may be ascribed to an increase of the endogenous circadian period.

  16. Circadian Rhythms of Ethylene Emission in Arabidopsis1[w

    E-print Network

    Tobin, Elaine

    Circadian Rhythms of Ethylene Emission in Arabidopsis1[w] Simon C. Thain2,3 , Filip Vandenbussche2 are critical for all circadian rhythms yet tested in Arabidopsis. Mutation of ethylene signaling pathways did not alter the phase or period of circadian rhythms. Mutants with altered ethylene production or signaling

  17. Circadian Rhythms, Sleep, and Substance Abuse

    PubMed Central

    Hasler, Brant P.; Smith, Leisha J.; Cousins, Jennifer C.; Bootzin, Richard R.

    2011-01-01

    Substance abuse is linked to numerous mental and physical health problems, including disturbed sleep. The association between substance use and sleep appears to be bidirectional, in that substance use may directly cause sleep disturbances, and difficulty sleeping may be a risk factor for relapse to substance use. Growing evidence similarly links substance use to disturbances in circadian rhythms, although many gaps in knowledge persist, particularly regarding whether circadian disturbance leads to substance abuse or dependence. Given the integral role circadian rhythms play in regulating sleep, circadian mechanisms may account in part for sleep-substance abuse interactions. Furthermore, a burgeoning research base supports a role for the circadian system in regulating reward processing, indicating that circadian mechanisms may be directly linked to substance abuse independently of sleep pathways. More work in this area is needed, particularly in elucidating how sleep and circadian disturbance may contribute to initiation of, and/or relapse to, substance use. Sleep and circadian-based interventions could play a critical role in the prevention and treatment of substance use disorders. PMID:21620743

  18. Circadian rhythms of performance: new trends

    NASA Technical Reports Server (NTRS)

    Carrier, J.; Monk, T. H.

    2000-01-01

    This brief review is concerned with how human performance efficiency changes as a function of time of day. It presents an overview of some of the research paradigms and conceptual models that have been used to investigate circadian performance rhythms. The influence of homeostatic and circadian processes on performance regulation is discussed. The review also briefly presents recent mathematical models of alertness that have been used to predict cognitive performance. Related topics such as interindividual differences and the postlunch dip are presented.

  19. Circadian Rhythms, Sleep Deprivation, and Human Performance

    PubMed Central

    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

  20. JOURNAL OF BIOLOGICAL RHYTHMS / December 1999Leloup et al. / LIMIT CYCLE MODELS FOR CIRCADIAN RHYTHMS Limit Cycle Models for Circadian Rhythms

    E-print Network

    Goldbeter, Albert

    JOURNAL OF BIOLOGICAL RHYTHMS / December 1999Leloup et al. / LIMIT CYCLE MODELS FOR CIRCADIAN RHYTHMS Limit Cycle Models for Circadian Rhythms Based on Transcriptional Regulation in Drosophila, in the form of limit cycle oscillations. The effect of light on circadian rhythms is taken into account

  1. Procedures for numerical analysis of circadian rhythms

    PubMed Central

    REFINETTI, ROBERTO; LISSEN, GERMAINE CORNÉ; HALBERG, FRANZ

    2010-01-01

    This article reviews various procedures used in the analysis of circadian rhythms at the populational, organismal, cellular and molecular levels. The procedures range from visual inspection of time plots and actograms to several mathematical methods of time series analysis. Computational steps are described in some detail, and additional bibliographic resources and computer programs are listed. PMID:23710111

  2. A circadian rhythm of conidiation in Neurospora crassa (L-12)

    NASA Technical Reports Server (NTRS)

    Miyoshi, Yashuhiro

    1993-01-01

    Two fungi growth chambers containing six growth tubes each are used in this experiment. One chamber is for the space experiment; the other is for the simultaneous ground control experiment. The hyphae of Neurospora crassa band A mutant are inoculated at one end of each tube. Both the chambers are kept at 3 C plus or minus 1.5 C to stop hyphae growth until the Spacelab is activated. After the activation, each chamber is transferred simultaneously to the Spacelab and a phytotron in KSC and kept in continuous light at the same temperature. After about 24 hours of light exposure, each chamber is inserted into a growth chamber bag to keep it in constant darkness. The circadian rhythm of conidiation is initiated by this light to dark transition. After the dark incubation for 5 days at room temperature, both the growth chambers are kept at 3 C plus or minus 1.5 C to stop growth of the hyphae. After the space shuttle lands, both conidiation patterns are compared and analyzed. It has been known that numerous physiological phenomena show circadian rhythms. They are characterized by the fact that the oscillation can persist under constant conditions of light and temperature. Therefore, it has been accepted by most investigators that the generation mechanism of the circadian rhythm is endogeneous. However, one cannot reject the possibility that these rhythms are caused by some geophysical exogeneous factor having a 24-hour period, such as atmospheric pressure, gravity, or electromagnetic radiation. We use Neurospora crassa band A mutual which shows an obvious circadian rhythm in its spore-forming (conidiation) on the ground, and we intend to attempt the conidation of this mutant in the Spacelab where 24-hour periodicity is severely attenuated and to elucidate the effect of the geophysical exogeneous factor in the generation mechanism of the circadian rhythm.

  3. Circadian rhythms, alcohol and gut interactions.

    PubMed

    Forsyth, Christopher B; Voigt, Robin M; Burgess, Helen J; Swanson, Garth R; Keshavarzian, Ali

    2015-06-01

    The circadian clock establishes rhythms throughout the body with an approximately 24 hour period that affect expression of hundreds of genes. Epidemiological data reveal chronic circadian misalignment, common in our society, significantly increases the risk for a myriad of diseases, including cardiovascular disease, diabetes, cancer, infertility and gastrointestinal disease. Disruption of intestinal barrier function, also known as gut leakiness, is especially important in alcoholic liver disease (ALD). Several studies have shown that alcohol causes ALD in only a 20-30% subset of alcoholics. Thus, a better understanding is needed of why only a subset of alcoholics develops ALD. Compelling evidence shows that increased gut leakiness to microbial products and especially LPS play a critical role in the pathogenesis of ALD. Clock and other circadian clock genes have been shown to regulate lipid transport, motility and other gut functions. We hypothesized that one possible mechanism for alcohol-induced intestinal hyperpermeability is through disruption of central or peripheral (intestinal) circadian regulation. In support of this hypothesis, our recent data shows that disruption of circadian rhythms makes the gut more susceptible to injury. Our in vitro data show that alcohol stimulates increased Clock and Per2 circadian clock proteins and that siRNA knockdown of these proteins prevents alcohol-induced permeability. We also show that intestinal Cyp2e1-mediated oxidative stress is required for alcohol-induced upregulation of Clock and Per2 and intestinal hyperpermeability. Our mouse model of chronic alcohol feeding shows that circadian disruption through genetics (in Clock(?19) mice) or environmental disruption by weekly 12h phase shifting results in gut leakiness alone and exacerbates alcohol-induced gut leakiness and liver pathology. Our data in human alcoholics show they exhibit abnormal melatonin profiles characteristic of circadian disruption. Taken together our data support circadian mechanisms for alcohol-induced gut leakiness that could provide new therapeutic targets for ALD. PMID:25499101

  4. Flexible and waterproof micro-sensors to uncover zebrafish circadian rhythms: The next generation of cardiac monitoring for drug screening.

    PubMed

    Zhang, Xiaoxiao; Beebe, Tyler; Jen, Nelson; Lee, Chia-An; Tai, Yuchong; Hsiai, Tzung K

    2015-09-15

    Flexible electronics are the next generation of sensors for mobile health and implantation. Zebrafish (Danio rerio) is an emergent strategy for pre-clinical drug development and toxicity testing. To address the confounding effects from sedation of fish and removal from the aquatic habitat for micro-electrocardiogram (µECG) measurements, we developed waterproof and wearable sensors to uncover the circadian variation in heart rate (HR) and heart rate variability (HRV) (Massin et al., 2000). The parylene-C based ECG sensor consisted of an ultra-soft silicone integrated jacket designed to wrap around the fish during swimming. The Young's modulus of this silicone jacket matched with the fish surface, and an extended parylene cable connected the underwater chest electrodes with the out-of water electronics. In addition, embedded micro-glass spheres in the silicone effectively reduced the effective density of the jacket to ~1 g cm(-3). These innovations enabled physiological ECG telemetry in the fish's natural habitat without the need for sedation. Furthermore, a set of non-linear signal processing techniques filtered out the breathing and electromagnetic artifacts from the recorded signals. We observed a reduction in mean HR and an increase in HRV over 24h at 10 dpa, accompanied by QT prolongation as well as diurnal variations, followed by normalization in mean HR and QT intervals at 26 days post ventricular amputation (dpa). We revealed Amiodarone-mediated QTc prolongation, HR reduction and HRV increase otherwise masked by sedation. The novel features of the flexible silicon jacket for µECG telemetry unraveled the biological clock and normalization of QT intervals at 26 dpa, providing the first evidence of new physiological phenomena during cardiac injury and repair as well as cardiac drug-mediated aberrant rhythms. Thus, the light weight and waterproof design holds promise to advance the next generation of mobile health and drug discovery. PMID:25909335

  5. A novel animal model linking adiposity to altered circadian rhythms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Researchers have provided evidence for a link between obesity and altered circadian rhythms (e.g., shift work, disrupted sleep), but the mechanism for this association is still unknown. Adipocytes possess an intrinsic circadian clock, and circadian rhythms in adipocytokines and adipose tissue metab...

  6. Environmental synchronizers of squirrel monkey circadian rhythms

    NASA Technical Reports Server (NTRS)

    Sulzman, F. M.; Fuller, C. A.; Moore-Ede, M. C.

    1977-01-01

    Various temporal signals in the environment were tested to determine if they could synchronize the circadian timing system of the squirrel monkey (Saimiri sciureus). The influence of cycles of light and dark, eating and fasting, water availability and deprivation, warm and cool temperature, sound and quiet, and social interaction and isolation on the drinking and activity rhythms of unrestrained monkeys was examined. In the absence of other time cues, 24-hr cycles of each of these potential synchronizers were applied for up to 3 wk, and the periods of the monkey's circadian rhythms were examined. Only light-dark cycles and cycles of food availability were shown to be entraining agents, since they were effective in determining the period and phase of the rhythmic variables. In the presence of each of the other environmental cycles, the monkey's circadian rhythms exhibited free-running periods which were significantly different from 24 hr with all possible phase relationships between the rhythms and the environmental cycles being examined.

  7. Quantification of human performance circadian rhythms.

    PubMed

    Freivalds, A; Chaffin, D B; Langolf, G D

    1983-09-01

    The quantification of worker performance changes during a shift is critical to establishing worker productivity. This investigation examined the existence of circadian rhythms in response variables that relate most meaningfully to the physiological and neurological state of the body for three subjects maintaining a resting posture for 25 hours on five separate occasions. Significant circadian variation ranging from 3% to 11% of the mean value was detected for elbow flexion strength, physiological tremor, simple reaction time, information processing rate and critical eye-hand tracking capacity. PMID:6637808

  8. Circadian rhythms have broad implications for understanding brain and behavior

    PubMed Central

    Silver, Rae; Kriegsfeld, Lance J.

    2015-01-01

    Circadian rhythms are generated by an endogenously organized timing system that drives daily rhythms in behavior, physiology and metabolism. In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is the locus of a master circadian clock. The SCN is synchronized to environmental changes in the light:dark cycle by direct, monosynaptic innervation via the retino-hypothalamic tract. In turn, the SCN coordinates the rhythmic activities of innumerable subordinate clocks in virtually all bodily tissues and organs. The core molecular clockwork is composed of a transcriptional/post-translational feedback loop in which clock genes and their protein products periodically suppress their own transcription. This primary loop connects to downstream output genes by additional, interlocked transcriptional feedback loops to create tissue-specific ‘circadian transcriptomes’. Signals from peripheral tissues inform the SCN of the internal state of the organism and the brain’s master clock is modified accordingly. A consequence of this hierarchical, multilevel feedback system is that there are ubiquitous effects of circadian timing on genetic and metabolic responses throughout the body. This overview examines landmark studies in the history of the study of circadian timing system, and highlights our current understanding of the operation of circadian clocks with a focus on topics of interest to the neuroscience community. PMID:24799154

  9. Drugs of abuse can entrain circadian rhythms.

    PubMed

    Kosobud, Ann E K; Gillman, Andrea G; Leffel, Joseph K; Pecoraro, Norman C; Rebec, G V; Timberlake, William

    2007-01-01

    Circadian rhythms prepare organisms for predictable events in the 24 h day. These rhythms are entrained by a variety of stimuli. Light is the most ubiquitous and best known zeitgeber, but a number of others have been identified, including food, social cues, locomotor activity, and, most recently drugs of abuse. Given the diversity of zeitgebers, it is probably not surprising that genes capable of clock functions are located throughout almost all organs and tissues. Recent evidence suggests that drugs of abuse can directly entrain some circadian rhythms. We have report here that entrainment by drugs of abuse is independent of the suprachiasmatic nucleus and the light/dark cycle, is not dependent on direct locomotor stimulation, and is shared by a variety of classes of drugs of abuse. We suggest that drug-entrained rhythms reflect variations in underlying neurophysiological states. This could be the basis for known daily variations in drug metabolism, tolerance, and sensitivity to drug reward. These rhythms could also take the form of daily periods of increased motivation to seek and take drugs, and thus contribute to abuse, addiction and relapse. PMID:17982594

  10. Circadian rhythm asynchrony in man during hypokinesis.

    NASA Technical Reports Server (NTRS)

    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.

  11. Circadian rhythm and cell population growth

    E-print Network

    Clairambault, Jean; Lepoutre, Thomas

    2010-01-01

    Molecular circadian clocks, that are found in all nucleated cells of mammals, are known to dictate rhythms of approximately 24 hours (circa diem) to many physiological processes. This includes metabolism (e.g., temperature, hormonal blood levels) and cell proliferation. It has been observed in tumor-bearing laboratory rodents that a severe disruption of these physiological rhythms results in accelerated tumor growth. The question of accurately representing the control exerted by circadian clocks on healthy and tumour tissue proliferation to explain this phenomenon has given rise to mathematical developments, which we review. The main goal of these previous works was to examine the influence of a periodic control on the cell division cycle in physiologically structured cell populations, comparing the effects of periodic control with no control, and of different periodic controls between them. We state here a general convexity result that may give a theoretical justification to the concept of cancer chronothera...

  12. Circadian rhythms, athletic performance, and jet lag.

    PubMed

    Manfredini, R; Manfredini, F; Fersini, C; Conconi, F

    1998-06-01

    Rapid air travel across several time zones exposes the traveller to a shift in his/her internal biological clock. The result is a transient desynchronisation of the circadian rhythm, called jet lag, lasting until the rhythm is rephased to the new environmental conditions. The most commonly experienced symptoms are sleep disorders, difficulties with concentrating, irritability, depression, fatigue, disorientation, loss of appetite, and gastrointestinal disturbance. Apart from the decrements in mental and physical performance directly consequent on such symptoms, competitive athletes are also exposed to the additional negative consequences of a shift from the optimal circadian window of performance. A brief summary of the possible negative effects of jet lag on athletic performance and potentially alleviating strategies is given. PMID:9631214

  13. Sleep, circadian rhythms, and athletic performance.

    PubMed

    Thun, Eirunn; Bjorvatn, Bjørn; Flo, Elisabeth; Harris, Anette; Pallesen, Ståle

    2015-10-01

    Sleep deprivation and time of day are both known to influence performance. A growing body of research has focused on how sleep and circadian rhythms impact athletic performance. This review provides a systematic overview of this research. We searched three different databases for articles on these issues and inspected relevant reference lists. In all, 113 articles met our inclusion criteria. The most robust result is that athletic performance seems to be best in the evening around the time when the core body temperature typically is at its peak. Sleep deprivation was negatively associated with performance whereas sleep extension seems to improve performance. The effects of desynchronization of circadian rhythms depend on the local time at which performance occurs. The review includes a discussion of differences regarding types of skills involved as well as methodological issues. PMID:25645125

  14. Space environment, electromagnetic fields, and circadian rhythm.

    PubMed

    Izumi, R; Ishioka, N; Mizuno, K; Goka, T

    2001-01-01

    Human space activity began in 1961. About 400 persons have gone to space since then, and about 70 of them have stayed more than 1 month. Circadian rhythm and sleep in space have been investigated several times, though the effect of longer stays in space has not been adequately clarified. Electromagnetic fields are different in the space environment, especially in deeper space missions, such as the Moon or Mars, but their effects on human health have rarely been studied. In this article, we summarize the current status of the International Space Station project, study circadian rhythm and sleep in space, investigate electromagnetic fields, and state the necessity for investigating this research field. PMID:11774866

  15. Sleep, Circadian Rhythms, and Anxious Traits.

    PubMed

    Coles, Meredith E; Schubert, Jessica R; Nota, Jacob A

    2015-09-01

    Anxiety is adaptive and plays an important role in keeping us safe. However, when anxiety becomes too extreme, it can cause significant disruptions and distress. Understanding the mechanisms underlying excessive anxiety and how to best treat it is a priority for researchers and clinicians. There is increasing recognition that disruptions in the amount and timing of sleep are associated with anxiety symptoms and characteristics. In the current paper, we explore the intersections between sleep, circadian rhythms, and anxiety. First, we review accumulating evidence that anxiety is associated with disruptions in sleep and circadian rhythms in both clinical and nonclinical samples and across ages. Next, we discuss the data linking sleep disruptions with anxiety-related traits (anxiety sensitivity, neuroticism, and perfectionism) and patterns of cognition and emotion. Finally, potential treatment implications are highlighted. Overall, these data suggest that delineating the role of disruptions in the amount and timing of sleep holds promise for improving the lives of individuals with heightened anxiety. PMID:26216591

  16. INTRINSIC CIRCADIAN RHYTHMS IN THE CARDIOMYOCYTE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cardiomyocyte possesses a fully functional circadian clock. Circadian clocks are a set of proteins that generate self-sustained transcriptional positive and negative feedback loops with a free-running period of 24 hours. These intracellular molecular mechanisms confer the selective advantage of ...

  17. Temperature compensation and entrainment in circadian rhythms

    NASA Astrophysics Data System (ADS)

    Bodenstein, C.; Heiland, I.; Schuster, S.

    2012-06-01

    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.

  18. Circadian rhythms. A protein fold switch joins the circadian oscillator to clock output in cyanobacteria.

    PubMed

    Chang, Yong-Gang; Cohen, Susan E; Phong, Connie; Myers, William K; Kim, Yong-Ick; Tseng, Roger; Lin, Jenny; Zhang, Li; Boyd, Joseph S; Lee, Yvonne; Kang, Shannon; Lee, David; Li, Sheng; Britt, R David; Rust, Michael J; Golden, Susan S; LiWang, Andy

    2015-07-17

    Organisms are adapted to the relentless cycles of day and night, because they evolved timekeeping systems called circadian clocks, which regulate biological activities with ~24-hour rhythms. The clock of cyanobacteria is driven by a three-protein oscillator composed of KaiA, KaiB, and KaiC, which together generate a circadian rhythm of KaiC phosphorylation. We show that KaiB flips between two distinct three-dimensional folds, and its rare transition to an active state provides a time delay that is required to match the timing of the oscillator to that of Earth's rotation. Once KaiB switches folds, it binds phosphorylated KaiC and captures KaiA, which initiates a phase transition of the circadian cycle, and it regulates components of the clock-output pathway, which provides the link that joins the timekeeping and signaling functions of the oscillator. PMID:26113641

  19. Circadian rhythms originate from intertwined feedback processes in genetic regulatory net-works. Computational models of increasing complexity have been proposed for the molec-

    E-print Network

    Goldbeter, Albert

    ABSTRACT Circadian rhythms originate from intertwined feedback processes in genetic regulatory net for circadian rhythms in Drosophila account for a variety of dynamical properties, such as phase shifting: THE COMPUTATIONAL BIOLOGY OF CIRCADIAN RHYTHMS Most living organisms have developed the capability of generating

  20. N-nitrosomelatonin enhances photic synchronization of mammalian circadian rhythms.

    PubMed

    Baidanoff, Fernando M; Plano, Santiago A; Doctorovich, Fabio; Suárez, Sebastián A; Golombek, Diego A; Chiesa, Juan J

    2014-04-01

    Most physiological processes in mammals are synchronized to the daily light:dark cycle by a circadian clock located in the hypothalamic suprachiasmatic nucleus. Signal transduction of light-induced phase advances of the clock is mediated through a neuronal nitric oxide synthase-guanilyl cyclase pathway. We have employed a novel nitric oxide-donor, N-nitrosomelatonin, to enhance the photic synchronization of circadian rhythms in hamsters. The intraperitoneal administration of this drug before a sub-saturating light pulse at circadian time 18 generated a twofold increase of locomotor rhythm phase-advances, having no effect over saturating light pulses. This potentiation was also obtained even when inhibiting suprachiasmatic nitric oxide synthase activity. However, N-nitrosomelatonin had no effect on light-induced phase delays at circadian time 14. The photic-enhancing effects were correlated with an increased suprachiasmatic immunoreactivity of FBJ murine osteosarcoma viral oncogene and period1. Moreover, in vivo nitric oxide release by N-nitrosomelatonin was verified by measuring nitrate and nitrite levels in suprachiasmatic nuclei homogenates. The compound also accelerated resynchronization to an abrupt 6-h advance in the light:dark cycle (but not resynchronization to a 6-h delay). Here, we demonstrate the chronobiotic properties of N-nitrosomelatonin, emphasizing the importance of nitric oxide-mediated transduction for circadian phase advances. PMID:24261470

  1. Circadian rhythms, sleep, and performance in space

    NASA Technical Reports Server (NTRS)

    Mallis, M. M.; DeRoshia, C. W.

    2005-01-01

    Maintaining optimal alertness and neurobehavioral functioning during space operations is critical to enable the National Aeronautics and Space Administration's (NASA's) vision "to extend humanity's reach to the Moon, Mars and beyond" to become a reality. Field data have demonstrated that sleep times and performance of crewmembers can be compromised by extended duty days, irregular work schedules, high workload, and varying environmental factors. This paper documents evidence of significant sleep loss and disruption of circadian rhythms in astronauts and associated performance decrements during several space missions, which demonstrates the need to develop effective countermeasures. Both sleep and circadian disruptions have been identified in the Behavioral Health and Performance (BH&P) area and the Advanced Human Support Technology (AHST) area of NASA's Bioastronautics Critical Path Roadmap. Such disruptions could have serious consequences on the effectiveness, health, and safety of astronaut crews, thus reducing the safety margin and increasing the chances of an accident or incident. These decrements oftentimes can be difficult to detect and counter effectively in restrictive operational environments. NASA is focusing research on the development of optimal sleep/wake schedules and countermeasure timing and application to help mitigate the cumulative effects of sleep and circadian disruption and enhance operational performance. Investing research in humans is one of NASA's building blocks that will allow for both short- and long-duration space missions and help NASA in developing approaches to manage and overcome the human limitations of space travel. In addition to reviewing the current state of knowledge concerning sleep and circadian disruptions during space operations, this paper provides an overview of NASA's broad research goals. Also, NASA-funded research, designed to evaluate the relationships between sleep quality, circadian rhythm stability, and performance proficiency in both ground-based simulations and space mission studies, as described in the 2003 NASA Task Book, will be reviewed.

  2. Circadian rhythms, sleep, and performance in space.

    PubMed

    Mallis, M M; DeRoshia, C W

    2005-06-01

    Maintaining optimal alertness and neurobehavioral functioning during space operations is critical to enable the National Aeronautics and Space Administration's (NASA's) vision "to extend humanity's reach to the Moon, Mars and beyond" to become a reality. Field data have demonstrated that sleep times and performance of crewmembers can be compromised by extended duty days, irregular work schedules, high workload, and varying environmental factors. This paper documents evidence of significant sleep loss and disruption of circadian rhythms in astronauts and associated performance decrements during several space missions, which demonstrates the need to develop effective countermeasures. Both sleep and circadian disruptions have been identified in the Behavioral Health and Performance (BH&P) area and the Advanced Human Support Technology (AHST) area of NASA's Bioastronautics Critical Path Roadmap. Such disruptions could have serious consequences on the effectiveness, health, and safety of astronaut crews, thus reducing the safety margin and increasing the chances of an accident or incident. These decrements oftentimes can be difficult to detect and counter effectively in restrictive operational environments. NASA is focusing research on the development of optimal sleep/wake schedules and countermeasure timing and application to help mitigate the cumulative effects of sleep and circadian disruption and enhance operational performance. Investing research in humans is one of NASA's building blocks that will allow for both short- and long-duration space missions and help NASA in developing approaches to manage and overcome the human limitations of space travel. In addition to reviewing the current state of knowledge concerning sleep and circadian disruptions during space operations, this paper provides an overview of NASA's broad research goals. Also, NASA-funded research, designed to evaluate the relationships between sleep quality, circadian rhythm stability, and performance proficiency in both ground-based simulations and space mission studies, as described in the 2003 NASA Task Book, will be reviewed. PMID:15943202

  3. Circadian rhythms in healthy aging--effects downstream from the pacemaker

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Kupfer, D. J.

    2000-01-01

    Using both previously published findings and entirely new data, we present evidence in support of the argument that the circadian dysfunction of advancing age in the healthy human is primarily one of failing to transduce the circadian signal from the circadian timing system (CTS) to rhythms "downstream" from the pacemaker rather than one of failing to generate the circadian signal itself. Two downstream rhythms are considered: subjective alertness and objective performance. For subjective alertness, we show that in both normal nychthemeral (24 h routine, sleeping at night) and unmasking (36 h of constant wakeful bed rest) conditions, advancing age, especially in men, leads to flattening of subjective alertness rhythms, even when circadian temperature rhythms are relatively robust. For objective performance, an unmasking experiment involving manual dexterity, visual search, and visual vigilance tasks was used to demonstrate that the relationship between temperature and performance is strong in the young, but not in older subjects (and especially not in older men).

  4. [The kidney and circadian rhythms: a whole new world?].

    PubMed

    Manfredini, Roberto; Sasso, Ferdinando Carlo; Pala, Marco; De Giorgi, Alfredo; Fabbian, Fabio

    2013-01-01

    Chronobiology is a branch of biomedical sciences devoted to the study of biological rhythms. Biological rhythms exist at any level of living organisms and, according to their cycle length, may be divided into three main types: circadian, ultradian, and infradian rhythms. Circadian rhythms are the most commonly and widely studied. The principal circadian clock is located in the suprachiasmatic nucleus of the hypothalamus, and is supposed to regulate peripheral clocks via neurohumoral modulation. Circadian clocks have been identified within almost all mammalian cell types, and circadian clock genes seem to be essential for cardiovascular health. Disturbance of the renal circadian rhythms is increasingly recognized as a risk factor for hypertension, polyuria, and other diseases and may contribute to renal fibrosis. The origin of these rhythms has been attributed to the reactive response of the kidney to circadian changes in volume and/or in the composition of extracellular fluids regulated by rest/activity and feeding/fasting cycles. However, most of the renal excretory rhythms persist for long periods of time, even in the absence of periodic environmental cues. These observations led to the hypothesis of the existence of a self-sustained mechanism, enabling the kidney to anticipate various predictable circadian challenges to homeostasis. The molecular basis of this mechanism remained unknown until the recent discovery of the mammalian circadian clock, comprising a system of autoregulatory transcriptional/translational feedback loops, which have also been found in the kidney. PMID:24403200

  5. Circadian Activity Rhythms, Time Urgency, and Achievement Concerns.

    ERIC Educational Resources Information Center

    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…

  6. Drosophila Circadian Rhythms: Stability Robustness Analysis and Model Reduction

    E-print Network

    Cambridge, University of

    Drosophila Circadian Rhythms: Stability Robustness Analysis and Model Reduction Jorge M. Gonc investigates two models of circadian rhythms in Drosophila: one by Gonze et al. and a more generic model by Vilar et al. that describes the biological clock in Drosophila as well as other organisms. For both

  7. A Circadian Rhythm Regulating Hyphal Melanization in Cercospora Kikuchii

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythms, biochemical or developmental processes with a period length of approximately 24 hours, are thoroughly documented in plants and animals. However, virtually all of what is currently known about circadian rhythms in fungi is derived from the model fungus, Neurospora crassa, including...

  8. Circadian temperature rhythms of older people

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Buysse, D. J.; Reynolds, C. F. 3rd; Kupfer, D. J.; Houck, P. R.

    1995-01-01

    This collection of studies had the aim of exploring whether older (77+ years) men and women have circadian body temperature rhythms different from those of younger adults. A total of 20 older men and 28 older women were compared with either 22 young men or 14 middle-aged men in four protocols; all but the first protocol using a subset of the sample. The four protocols were: 1) 24 h, and 2) 72 h data collections on a normal laboratory routine (sleeping at night); 3) between 36 h and 153 h of field data collection at home; and 4) 36 h of a constant conditions routine (wakeful bedrest under temporal isolation) in the laboratory. There was some evidence for an age-related phase advance in temperature rhythm, especially for the older men on a normal routine, though this was not present in the constant conditions protocol, where 5 of the older subjects showed major delays in the timing of the body temperature trough (10:00 or later). There was no statistically significant evidence from any of the protocols that older subjects generally had lower temperature rhythm amplitudes than younger adults. Only when older men were compared with younger men in 24-h rhythm amplitude by simple t-test did any comparison involving amplitude achieve statistical significance (p < 0.05).

  9. Characterization of neurospora circadian rhythms in space

    NASA Technical Reports Server (NTRS)

    Ferraro, James S.

    1987-01-01

    To determine whether the circadian rhythm of conidiation in neurospora crassa is endogenously derived or is driven by some geophysical time cue, an experiment was conducted on space shuttle flight STS-9, where inoculated race tubes were exposed to the microgravity environment of space. The results demonstated that the rhythm can persist in space. However, there were several minor alterations noted; an increase in the period of the oscillation and the variability of the growth rate and a diminished rhythm amplitude, which eventually damped out in 25% of the flight tubes. On day seven of the flight, the tubes were exposed to light while their growth fronts were marked. It appears that some aspects of this marking process reinstated a robust rhythm in all the tubes which continued throughout the remainder of the flight. It was hypothesized that the damping found prior to the marking procedure on STS-9 may have been a result of the hypergravity pulse of launch and not due to the microgravity of the orbital lab; furthermore, that the marking procedure, by exposing the samples to light, had reinstated rhythmicity. To test this, an investigation was conducted into the effects of acute and chronic exposure to hypergravity.

  10. JOURNAL OF BIOLOGICAL RHYTHMS / June 1999Olde Scheper et al. / MOLECULAR CIRCADIAN CLOCKS A Model of Molecular Circadian Clocks

    E-print Network

    van Pelt, Jaap

    JOURNAL OF BIOLOGICAL RHYTHMS / June 1999Olde Scheper et al. / MOLECULAR CIRCADIAN CLOCKS A Model, the Netherlands Abstract A fundamental question in the field of circadian rhythms concerns the biochemical of the intricate molecu- lar interactions governing circadian rhythmogenesis. Key words circadian rhythm

  11. Circadian rhythms in rheumatology - a glucocorticoid perspective

    PubMed Central

    2014-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in regulating and controlling immune responses. Dysfunction of the HPA axis has been implicated in the pathogenesis of rheumatoid arthritis (RA) and other rheumatic diseases. The impact of glucocorticoid (GC) therapy on HPA axis function also remains a matter of concern, particularly for longer treatment duration. Knowledge of circadian rhythms and the influence of GC in rheumatology is important: on the one hand we aim for optimal treatment of the daily undulating inflammatory symptoms, for example morning stiffness and swelling; on the other, we wish to disturb the HPA axis as little as possible. This review describes circadian rhythms in RA and other chronic inflammatory diseases, dysfunction of the HPA axis in RA and other rheumatic diseases and the recent concept of the hepato-hypothalamic-pituitary-adrenal-renal axis, the problem of adrenal suppression by GC therapy and how it can be avoided, and evidence that chronotherapy with modified release prednisone effective at 02:00 a.m. can inhibit proinflammatory sequelae of nocturnal inflammation better compared with GC administration in the morning but does not increase the risk of HPA axis insufficiency in RA. PMID:25608777

  12. Jean-Jacques d'Ortous de Mairan, 1729 WHY CIRCADIAN RHYTHM?

    E-print Network

    South Bohemia, University of

    #12;Jean-Jacques d'Ortous de Mairan, 1729 #12;WHY CIRCADIAN RHYTHM? #12;#12;NON-CIRCADIAN RHYTHM · Geneticly determined #12;#12;Circadian rhythms (David Dolezel - BCAV CR) david.dolezel@entu.cas.cz You #12;#12;#12;#12;ENTRAINMENT #12;#12;Circadian rhythms (David Dolezel - BCAV CR) david

  13. A ticking clock: Performance analysis of a Circadian rhythm with stochastic process

    E-print Network

    Imperial College, London

    A ticking clock: Performance analysis of a Circadian rhythm with stochastic process algebra Jeremy problem, that of capturing and reproducing the Circadian rhythm. A Circadian rhythm provides cells us to simulate resource starvation and observe its effect on the Circadian rhythm. #12;Recent

  14. A ticking clock: Performance analysis of a Circadian rhythm with stochastic process

    E-print Network

    Imperial College, London

    A ticking clock: Performance analysis of a Circadian rhythm with stochastic process algebra Jeremy problem, that of capturing and reproducing the Circadian rhythm. A Circadian rhythm provides cells us to simulate resource starvation and observe its e#ect on the Circadian rhythm. #12; Recent

  15. Preliminary characterization of persisting circadian rhythms during space flight: Neurospora as a model system

    NASA Technical Reports Server (NTRS)

    Sulzman, F. W.

    1981-01-01

    The effects of the Spacelab environment on the circadian rhythms in microorganisms are investigated. Neurospora is chosen because of its well characterized circadian rhythm of growth. Growth rate, banding patterns, and circadian period and phase information are studied.

  16. Circadian rhythms and addiction: Mechanistic insights and future directions

    PubMed Central

    Logan, Ryan W.; Williams, Wilbur P.; McClung, Colleen A.

    2014-01-01

    Circadian rhythms are prominent in many physiological and behavioral functions. Circadian disruptions either by environmental or molecular perturbation can have profound health consequences, including the development and progression of addiction. Both animal and humans studies indicate extensive bidirectional relationships between the circadian system and drugs of abuse. Addicted individuals display disrupted rhythms, and chronic disruption or particular chronotypes, may increase the risk for substance abuse and relapse. Moreover, polymorphisms in circadian genes and an evening chronotype have been linked to mood and addiction disorders, and recent efforts suggest an association with the function of reward neurocircuitry. Animal studies are beginning to determine how altered circadian gene function results in drug induced neuroplasticity and behaviors. Many studies suggest a critical role for circadian rhythms in reward-related pathways in the brain and indicate that drugs of abuse directly affect the central circadian pacemaker. In this review, we highlight key findings demonstrating the importance of circadian rhythms in addiction, and how future studies will reveal important mechanistic insights into the involvement of circadian rhythms in drug addiction. PMID:24731209

  17. Barley Hv CIRCADIAN CLOCK ASSOCIATED 1 and Hv PHOTOPERIOD H1 Are Circadian Regulators That Can Affect Circadian Rhythms in Arabidopsis

    PubMed Central

    Martí, María C.; Laurie, David A.; Greenland, Andy J.; Hall, Anthony; Webb, Alex A. R.

    2015-01-01

    Circadian clocks regulate many aspects of plant physiology and development that contribute to essential agronomic traits. Circadian clocks contain transcriptional feedback loops that are thought to generate circadian timing. There is considerable similarity in the genes that comprise the transcriptional and translational feedback loops of the circadian clock in the plant Kingdom. Functional characterisation of circadian clock genes has been restricted to a few model species. Here we provide a functional characterisation of the Hordeum vulgare (barley) circadian clock genes Hv CIRCADIAN CLOCK ASSOCIATED 1 (HvCCA1) and Hv PHOTOPERIODH1, which are respectively most similar to Arabidopsis thaliana CIRCADIAN CLOCK ASSOCIATED 1 (AtCCA1) and PSEUDO RESPONSE REGULATOR 7 (AtPRR7). This provides insight into the circadian regulation of one of the major crop species of Northern Europe. Through a combination of physiological assays of circadian rhythms in barley and heterologous expression in wild type and mutant strains of A. thaliana we demonstrate that HvCCA1 has a conserved function to AtCCA1. We find that Hv PHOTOPERIOD H1 has AtPRR7-like functionality in A. thaliana and that the effects of the Hv photoperiod h1 mutation on photoperiodism and circadian rhythms are genetically separable. PMID:26076005

  18. Circadian rhythm in Alzheimer disease after trazodone use.

    PubMed

    Grippe, Talyta C; Gonçalves, Bruno S B; Louzada, Luciana L; Quintas, Juliana L; Naves, Janeth O S; Camargos, Einstein F; Nóbrega, Otávio T

    2015-11-01

    A circadian rhythm is a cycle of approximately 24?h, responsible for many physiological adjustments, and ageing of the circadian clock contributes to cognitive decline. Rhythmicity is severely impaired in Alzheimer disease (AD) and few therapeutic attempts succeeded in improving sleep disorders in such context. This study evaluated sleep parameters by actigraphy in 30 AD patients before and after trazodone use for 2 weeks, and we show a significant improvement in relative rhythm amplitude (RRA), compatible with a more stable daytime behavioral pattern. So, trazodone appears to produce a stabilization of the circadian rhythms in individuals with AD. PMID:26376345

  19. Activity in the ferret: oestradiol effects and circadian rhythms

    NASA Technical Reports Server (NTRS)

    Stockman, E. R.; Albers, H. E.; Baum, M. J.; Wurtman, R. J. (Principal Investigator)

    1985-01-01

    The present study was conducted to determine whether oestradiol increases activity in the European ferret (Mustela furo), whether this effect is sexually dimorphic, and whether a 24-h rhythm is present in the ferret's daily activity. The activity of male and female adult, postpubertally gonadectomized ferrets was monitored while they were maintained singly on a 13:11 light-dark cycle, before and after implantation with oestradiol-17 beta. Gonadectomized male and female ferrets exhibited equal levels of activity, and neither sex exhibited a significant change in activity following oestradiol implantation. None of the ferrets exhibited a strong circadian rhythm, although weak 24-h rhythms and shorter harmonic rhythms were present. Golden hamsters (Mesocricetus auratus), monitored in an identical manner, exhibited strong circadian rhythms. It was concluded that oestradiol administration may not cause an increase in activity in the ferret, and that this species lacks a strong circadian activity rhythm.

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

    PubMed Central

    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 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. PMID:23916842

  1. Preliminary characterization of persisting circadian rhythms during space flight

    NASA Technical Reports Server (NTRS)

    Sultzman, F. M.

    1984-01-01

    In order to evaluate the function of the circadian timing system in space, the circadian rhythm of conidiation of the fungus Neurospora crassa was monitored in constant darkness on the STS 9 flight of the Space Shuttle Columbia. During the first 7 days of spaceflight many tubes showed a marked reduction in the apparent amplitude of the conidiation rhythm, and some cultures appeared arrhythmic. There was more variability in the growth rate and circadian rhythms of individual cultures in space than is usually seen on earth. The results of this experiment indicate that while the circadian rhythm of Neurospora conidiation can persist outside of the earth's environment, either the timekeeping process or its expression is altered in space.

  2. Theoretical models for circadian rhythms in Neurospora and Drosophila

    E-print Network

    Goldbeter, Albert

    Theoretical models for circadian rhythms in Neurospora and Drosophila Didier Gonzea , Jean-Christophe protéines PER et TIM et de leurs ARN messagers; ces oscillations entre- tenues sont du type cycle limite. Le

  3. Preliminary characterization of persisting circadian rhythms during space flight

    NASA Astrophysics Data System (ADS)

    Sulzman, Frank M.

    In order to evaluate the function of the circadian timing system in space, the circadian rhythm of conidiation of the fungus Neurospora crassa was monitored in constant darkness on the STS 9 flight of the Space Shuttle Columbia. During the first 7 days of spaceflight many tubes showed a marked reduction in the apparent amplitude of the conidiation rhythm, and some cultures appeared arrhythmic. There was more variability in the growth rate and circadian rhythms of individual cultures in space than is usually seen on earth. The results of this experiment indicate that while the circadian rhythm of Neurospora conidiation can persist outside of the earth's environment, either the timekeeping process or its expression is altered in space.

  4. Recent advances in circadian rhythms in cardiovascular system

    PubMed Central

    Chen, Lihong; Yang, Guangrui

    2015-01-01

    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. PMID:25883568

  5. Endogenous circadian rhythm in an index of cardiac vulnerability independent of changes in behavior

    E-print Network

    Stanley, H. Eugene

    Endogenous circadian rhythm in an index of cardiac vulnerability independent of changes in behavior features of the healthy human heartbeat have an endogenous circadian rhythm that brings the features closer circadian rhythm (with a sharp peak at the circadian phase corre- sponding to 10 a.m.), which is independent

  6. Circadian rhythms in electric waveform structure and rate in the electric fish Brachyhypopomus pinnicaudatus

    E-print Network

    Stoddard, Philip

    Circadian rhythms in electric waveform structure and rate in the electric fish Brachyhypopomus regulation of circadian rhythm expression. Previous studies asserting that these oscillations are circadian and magnitude, a difference consistent with proposals by others that declines of behavioral circadian rhythms

  7. Dynamics of three coupled van der Pol oscillators with application to circadian rhythms

    E-print Network

    Rand, Richard H.

    Dynamics of three coupled van der Pol oscillators with application to circadian rhythms Kevin this system comes from the presence of circadian rhythms in the chemistry of the eyes. We model the circadian.elsevier.com/locate/cnsns #12;Our motivation for studying this system comes from the presence of circadian rhythms

  8. Dynamical Analysis of bantam-Regulated Drosophila Circadian Rhythm Model

    NASA Astrophysics Data System (ADS)

    Li, Ying; Liu, Zengrong

    MicroRNAs (miRNAs) interact with 3?untranslated region (UTR) elements of target genes to regulate mRNA stability or translation, and play a crucial role in regulating many different biological processes. bantam, a conserved miRNA, is involved in several functions, such as regulating Drosophila growth and circadian rhythm. Recently, it has been discovered that bantam plays a crucial role in the core circadian pacemaker. In this paper, based on experimental observations, a detailed dynamical model of bantam-regulated circadian clock system is developed to show the post-transcriptional behaviors in the modulation of Drosophila circadian rhythm, in which the regulation of bantam is incorporated into a classical model. The dynamical behaviors of the model are consistent with the experimental observations, which shows that bantam is an important regulator of Drosophila circadian rhythm. The sensitivity analysis of parameters demonstrates that with the regulation of bantam the system is more sensitive to perturbations, indicating that bantam regulation makes it easier for the organism to modulate its period against the environmental perturbations. The effectiveness in rescuing locomotor activity rhythms of mutated flies shows that bantam is necessary for strong and sustained rhythms. In addition, the biological mechanisms of bantam regulation are analyzed, which may help us more clearly understand Drosophila circadian rhythm regulated by other miRNAs.

  9. A qualitative model of a motor circadian rhythm.

    PubMed

    Fuentes-Pardo, Beatriz; Guzmán-Gómez, Ana M; Lara-Aparicio, Miguel; López de Medrano, Santiago

    2003-09-01

    In Nature it is possible to observe diverse rhythms. Because of their adaptive characteristics, the circadian rhythms are of major importance and have been the subject of numerous experimental and theoretical studies. In this article, we give a presentation of the main results we have obtained about the motor circadian rhythm along some years of collaboration between biologists and mathematicians. We present a mathematical model simulating changes in frequency, synchronization and amplitude of the circadian oscillation during two developmental stages of the crayfish, namely, the juvenile and the adult stages. We report also some work in progress on the simulation of the phase response curve and on a simplified model of the rhythm. PMID:14568207

  10. JO URN ALOF BIO LOGI CAL RHYTHMS / February 1998Leloup, Goldbeter /MODELFO RCIRCADIAN RHYTHMS A Model for Circadian Rhythms in Drosophila

    E-print Network

    Goldbeter, Albert

    A Model for Circadian Rhythms in Drosophila Incorporating the Formation of a Complex between the PER obtained experi- mentally in the wild type and pers mutant of Drosophila. Key words circadian rhythms the molecular bases of circadian rhythms (Konopka and Benzer, 1971; Hall and Rosbash, 1988; Baylies et al., 1993

  11. Circadian rhythms in urinary functions: possible roles of circadian clocks?

    PubMed

    Noh, Jong-Yun; Han, Dong-Hee; Yoon, Ji-Ae; Kim, Mi-Hee; Kim, Sung-Eun; Ko, Il-Gyu; Kim, Khae-Hawn; Kim, Chang-Ju; Cho, Sehyung

    2011-06-01

    Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In this review, we briefly introduce circadian clocks and their organization in mammals. We then summarize known daily or circadian variations in urinary function. Importantly, recent findings by others as well as results obtained by us suggest an active role of circadian clock genes in various urinary functions. Finally, we discuss possible research avenues for the circadian control of urinary function. PMID:21811695

  12. Circadian Rhythms in Urinary Functions: Possible Roles of Circadian Clocks?

    PubMed Central

    Noh, Jong-Yun; Han, Dong-Hee; Yoon, Ji-Ae; Kim, Mi-Hee; Kim, Sung-Eun; Ko, Il-Gyu; Kim, Khae-Hawn; Kim, Chang-Ju

    2011-01-01

    Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In this review, we briefly introduce circadian clocks and their organization in mammals. We then summarize known daily or circadian variations in urinary function. Importantly, recent findings by others as well as results obtained by us suggest an active role of circadian clock genes in various urinary functions. Finally, we discuss possible research avenues for the circadian control of urinary function. PMID:21811695

  13. ‘The clocks that time us’—circadian rhythms in neurodegenerative disorders

    PubMed Central

    Videnovic, Aleksandar; Lazar, Alpar S.; Barker, Roger A.; Overeem, Sebastiaan

    2015-01-01

    Circadian rhythms are physiological and behavioural cycles generated by an endogenous biological clock, the suprachiasmatic nucleus. The circadian system influences the majority of physiological processes, including sleep–wake homeostasis. Impaired sleep and alertness are common symptoms of neurodegenerative disorders, and circadian dysfunction might exacerbate the disease process. The pathophysiology of sleep–wake disturbances in these disorders remains largely unknown, and is presumably multifactorial. Circadian rhythm dysfunction is often observed in patients with Alzheimer disease, in whom it has a major impact on quality of life and represents one of the most important factors leading to institutionalization of patients. Similarly, sleep and circadian problems represent common nonmotor features of Parkinson disease and Huntington disease. Clinical studies and experiments in animal models of neurodegenerative disorders have revealed the progressive nature of circadian dysfunction throughout the course of neurodegeneration, and suggest strategies for the restoration of circadian rhythmicity involving behavioural and pharmacological interventions that target the sleep–wake cycle. In this Review, we discuss the role of the circadian system in the regulation of the sleep–wake cycle, and outline the implications of disrupted circadian timekeeping in neurodegenerative diseases. PMID:25385339

  14. Systematic individual differences in sleep homeostatic and circadian rhythm contributions to neurobehavioral impairment

    E-print Network

    Pennsylvania, University of

    Systematic individual differences in sleep homeostatic and circadian rhythm contributions are considerable and represent a neurobiological trait. Genetic polymorphisms reported to be predictors have processes. Keywords Sleep homeostasis; Circadian rhythm; Inter-individual differences; Psychomotor vigilance

  15. Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

    PubMed Central

    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

  16. Redox rhythm reinforces the circadian clock to gate immune response.

    PubMed

    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. PMID:26098366

  17. Circadian Rhythms in Stomatal Responsiveness to Red and Blue Light.

    PubMed Central

    Gorton, H. L.; Williams, W. E.; Assmann, S. M.

    1993-01-01

    Stomata of many plants have circadian rhythms in responsiveness to environmental cues as well as circadian rhythms in aperture. Stomatal responses to red light and blue light are mediated by photosynthetic photoreceptors; responses to blue light are additionally controlled by a specific blue-light photoreceptor. This paper describes circadian rhythmic aspects of stomatal responsiveness to red and blue light in Vicia faba. Plants were exposed to a repeated light:dark regime of 1.5:2.5 h for a total of 48 h, and because the plants could not entrain to this short light:dark cycle, circadian rhythms were able to "free run" as if in continuous light. The rhythm in the stomatal conductance established during the 1.5-h light periods was caused both by a rhythm in sensitivity to light and by a rhythm in the stomatal conductance established during the preceding 2.5-h dark periods. Both rhythms peaked during the middle of the subjective day. Although the stomatal response to blue light is greater than the response to red light at all times of day, there was no discernible difference in period, phase, or amplitude of the rhythm in sensitivity to the two light qualities. We observed no circadian rhythmicity in net carbon assimilation with the 1.5:2.5 h light regime for either red or blue light. In continuous white light, small rhythmic changes in photosynthetic assimilation were observed, but at relatively high light levels, and these appeared to be attributable largely to changes in internal CO2 availability governed by stomatal conductance. PMID:12231947

  18. Behavioural Processes 64 (2003) 161175 Circadian rhythms of locomotor activity in Drosophila

    E-print Network

    Rouyer, Francois

    2003-01-01

    Behavioural Processes 64 (2003) 161­175 Circadian rhythms of locomotor activity in Drosophila André that clockwatchers have to face when using Drosophila activity rhythms to understand the multiple facets of circadian function. © 2003 Elsevier B.V. All rights reserved. Keywords: Drosophila; Circadian clock; Activity rhythms

  19. Circadian Rhythms Confer a Higher Level of Fitness to Arabidopsis Plants1

    E-print Network

    Tobin, Elaine

    Circadian Rhythms Confer a Higher Level of Fitness to Arabidopsis Plants1 Rachel M. Green, Sonia, P.O. Box 160606, University of California, Los Angeles, California 90095­1606 Circadian rhythms have circadian rhythm mutants, LHY-ox and elf3, have low-viability phenotypes. Our findings demonstrate

  20. Circadian rhythms constrain leaf and canopy gas exchange in an Amazonian forest

    E-print Network

    Goulden, Michael L.

    Circadian rhythms constrain leaf and canopy gas exchange in an Amazonian forest Christopher E circadian rhythms constrain the rates of leaf and canopy gas exchange in an Amazonian forest over a day of the day. We attribute these cycles to circadian rhythms that are analogous to ones that have been reported

  1. Cellular/Molecular Cellular Location and Circadian Rhythm of Expression of the

    E-print Network

    Silver, Rae

    Cellular/Molecular Cellular Location and Circadian Rhythm of Expression of the Biological Clock and circadian rhythms were found for the fraction of neurons showing strong GFP-IR, with peak expression between mouse; biological clock genes; retina; amacrine cell; melanopsin; circadian rhythm Introduction

  2. Food-entrained circadian rhythms are sustained in arrhythmic Clk/Clk mutant mice

    E-print Network

    Silver, Rae

    Food-entrained circadian rhythms are sustained in arrhythmic Clk/Clk mutant mice SiNae Pitts,1 of the suprachiasmatic nucleus (SCN). Circadian rhythms within the SCN depend on transcription- translation feedback). Light- and food- entrainable circadian rhythms share many properties, including limits of entrainment

  3. Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists

    E-print Network

    Gillette, Martha U.

    Review Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin Circadian rhythm sleep disorders (CRSDs), whether chronic or transient, affect a broad range of individuals-running circadian rhythms. Furthermore, studies have reported beneficial effects of melatonin for treatment

  4. The protein kinase CK2 is involved in regulation of circadian rhythms in Arabidopsis

    E-print Network

    Tobin, Elaine

    The protein kinase CK2 is involved in regulation of circadian rhythms in Arabidopsis Shoji Sugano by endogenous circadian rhythms. The circa- dian clock-associated 1 (CCA1) and the late elongated hypocotyl (LHY. Finally, we found that the photoperiodic flow- ering response, which is influenced by circadian rhythms

  5. Circadian rhythms in Neurospora crassa: Dynamics of the clock component frequency visualized using a fluorescent reporter

    E-print Network

    Hasty, Jeff

    Circadian rhythms in Neurospora crassa: Dynamics of the clock component frequency visualized using August 2009 Accepted 30 December 2009 Available online 4 January 2010 Keywords: Circadian rhythm m essential to the function of this organism's circadian rhythm. Increasingly, deciphering the coupling

  6. Shape Invariant Modelling of Circadian Rhythms with Random E#ects and

    E-print Network

    Wang, Yuedong

    Shape Invariant Modelling of Circadian Rhythms with Random E#ects and Smoothing Spline ANOVA dynamics such as circadian rhythms. Under the assumption that the expected response functions of all methods to a real data set to investigate disease e#ects on circadian rhythms of cortisol, a hormone

  7. Employing Circadian Rhythms to Enhance Power and Reliability Saket Gupta, Broadcom Corporation

    E-print Network

    Sapatnekar, Sachin

    A Employing Circadian Rhythms to Enhance Power and Reliability Saket Gupta, Broadcom Corporation (BTI), inspired by the notion of human circadian rhythms. The method works in two alternating phases. and Sapatnekar, S. S. 2012. Employing Circadian Rhythms to Enhance Power and Reliability. ACM Trans. Des. Autom

  8. Inositols affect the mating circadian rhythm of Drosophila melanogaster

    PubMed Central

    Sakata, Kazuki; Kawasaki, Haruhisa; Suzuki, Takahiro; Ito, Kumpei; Negishi, Osamu; Tsuno, Takuo; Tsuno, Hiromi; Yamazaki, Youta; Ishida, Norio

    2015-01-01

    Accumulating evidence indicates that the molecular circadian clock underlies the mating behavior of Drosophila melanogaster. However, information about which food components affect circadian mating behavior is scant. The ice plant, Mesembryanthemum crystallinum has recently become a popular functional food. Here, we showed that the close-proximity (CP) rhythm of D. melanogaster courtship behavior was damped under low-nutrient conditions, but significantly enhanced by feeding the flies with powdered ice plant. Among various components of ice plants, we found that myo-inositol increased the amplitude and slightly shortened the period of the CP rhythm. Real-time reporter assays showed that myo-inositol and D-pinitol shortened the period of the circadian reporter gene Per2-luc in NIH 3T3 cells. These data suggest that the ice plant is a useful functional food and that the ability of inositols to shorten rhythms is a general phenomenon in insects as well as mammals. PMID:26097456

  9. [Clock genes, circadian rhythms and food intake].

    PubMed

    Challet, E

    2007-01-01

    The molecular clockwork in mammals involves various clock genes with specific temporal patterns of expression. Synchronization of the master circadian clock located in the suprachiasmatic nuclei is accomplished mainly via daily resetting of the phase of the clock by light stimuli. Phase shifting responses to light are correlated with induction of Per1 and Per2 within the suprachiasmatic cells. The timing of peripheral oscillators is controlled by the suprachiasmatic clock when food is available ad libitum. Time of feeding, as modulated by temporal restricted feeding, is a potent Zeitgeber (synchronizer) for peripheral oscillators with no clear synchronizing influence on the suprachiasmatic clockwork. However, a timed calorie restriction (i.e. when only a hypocaloric diet is given each day at the same time) can modify the temporal organization generated by the suprachiasmatic nuclei and reset by the light-dark cycle. Such a situation of conflict between photic and feeding synchronizers alters timing of clock gene expression within the suprachiasmatic nuclei and timing of circadian outputs, indicating that the suprachiasmatic clock is sensitive to nutritional cues. PMID:17412526

  10. Sleep, circadian rhythms, and the pathogenesis of Alzheimer Disease

    PubMed Central

    Musiek, Erik S; Xiong, David D; Holtzman, David M

    2015-01-01

    Disturbances in the sleep–wake cycle and circadian rhythms are common symptoms of Alzheimer Disease (AD), and they have generally been considered as late consequences of the neurodegenerative processes. Recent evidence demonstrates that sleep–wake and circadian disruption often occur early in the course of the disease and may even precede the development of cognitive symptoms. Furthermore, the sleep–wake cycle appears to regulate levels of the pathogenic amyloid-beta peptide in the brain, and manipulating sleep can influence AD-related pathology in mouse models via multiple mechanisms. Finally, the circadian clock system, which controls the sleep–wake cycle and other diurnal oscillations in mice and humans, may also have a role in the neurodegenerative process. In this review, we examine the current literature related to the mechanisms by which sleep and circadian rhythms might impact AD pathogenesis, and we discuss potential therapeutic strategies targeting these systems for the prevention of AD. PMID:25766617

  11. Circadian rhythms and risk for substance use disorders in adolescence

    PubMed Central

    Hasler, Brant P.; Soehner, Adriane M.; Clark, Duncan B.

    2014-01-01

    Purpose of the review This article explores recent research in adolescent circadian rhythms, neurobiological changes influencing affective regulation and reward responding, and the emergence of substance use and related problems. Recent findings Recent findings have confirmed that adolescents with drug and alcohol problems are also beset by sleep problems, and have advanced our understanding of the relationship between sleep problems and substance involvement in this developmental period. During adolescence, a shift to later preferred sleep times interacts with early school start times to cause sleep loss and circadian misalignment. Sleep loss and circadian misalignment may disrupt reward-related brain function and impair inhibitory control. Deficits or delays in mature reward and inhibitory functions may contribute to adolescent alcohol use and other substance involvement. Summary An integration of the available research literature suggests that changes in sleep and circadian rhythms during adolescence may contribute to accelerated substance use and related problems. PMID:25247459

  12. Sleep, Circadian Rhythms, and Performance During Space Shuttle Missions

    NASA Technical Reports Server (NTRS)

    Neri, David F.; Czeisler, Charles A.; Dijk, Derk-Jan; Wyatt, James K.; Ronda, Joseph M.; Hughes, Rod J.

    2003-01-01

    Sleep and circadian rhythms may be disturbed during spaceflight, and these disturbances can affect crewmembers' performance during waking hours. The mechanisms underlying sleep and circadian rhythm disturbances in space are not well understood, and effective countermeasures are not yet available. We investigated sleep, circadian rhythms, cognitive performance, and light-dark cycles in five astronauts prior to, during, and after the 16-day STS-90 mission and the IO-day STS-95 mission. The efficacy of low-dose, alternative-night, oral melatonin administration as a countermeasure for sleep disturbances was evaluated. During these missions, scheduled rest activity cycles were 20-35 minutes shorter than 24 hours. Light levels on the middeck and in the Spacelab were very low; whereas on the flight deck (which has several windows), they were highly variable. Circadian rhythm abnormalities were observed. During the second half of the missions, the rhythm of urinary cortisol appeared to be delayed relative to the sleep-wake schedule. Performance during wakefulness was impaired. Astronauts slept only about 6.5 hours per day, and subjective sleep quality was lower in space. No beneficial effects of melatonin (0.3 mg administered prior to sleep episodes on alternate nights) were observed. A surprising finding was a marked increase in rapid eye movement (REM) sleep upon return to Earth. We conclude that these Space Shuttle missions were associated with circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and alterations in REM sleep homeostasis. Shorter than 24-hour rest-activity schedules and exposure to light-dark cycles inadequate for optimal circadian synchronization may have contributed to these disturbances.

  13. Mood Disorders, Circadian Rhythms, Melatonin and Melatonin Agonists

    PubMed Central

    Quera Salva, M.A.; Hartley, S.

    2012-01-01

    Recent advances in the understanding of circadian rhythms have led to an interest in the treatment of major depressive disorder with chronobiotic agents. Many tissues have autonomous circadian rhythms, which are orchestrated by the master clock, situated in the suprachiasmatic nucleus (SNC). Melatonin (N-acetyl-5-hydroxytryptamine) is secreted from the pineal gland during darkness. Melatonin acts mainly on MT1 and MT2 receptors, which are present in the SNC, regulating physiological and neuroendocrine functions, including circadian entrainment, referred to as the chronobiotic effet. Circadian rhythms has been shown to be either misaligned or phase shifted or decreased in amplitude in both acute episodes and relapse of major depressive disorder (MDD) and bipolar disorder. Manipulation of circadian rhythms either using physical treatments (such as high intensity light) or behavioral therapy has shown promise in improving symptoms. Pharmacotherapy using melatonin and pure melatonin receptor agonists, while improving sleep, has not been shown to improve symptoms of depression. A novel antidepressant, agomelatine, combines 5HT2c antagonist and melatonin agonist action, and has shown promise in both acute treatment of MDD and in preventing relapse. PMID:23650464

  14. Circadian rhythms of temperature and activity in obese and lean Zucker rats

    NASA Technical Reports Server (NTRS)

    Murakami, D. M.; Horwitz, B. A.; Fuller, C. A.

    1995-01-01

    The circadian timing system is important in the regulation of feeding and metabolism, both of which are aberrant in the obese Zucker rat. This study tested the hypothesis that these abnormalities involve a deficit in circadian regulation by examining the circadian rhythms of body temperature and activity in lean and obese Zucker rats exposed to normal light-dark cycles, constant light, and constant dark. Significant deficits in both daily mean and circadian amplitude of temperature and activity were found in obese Zucker female rats relative to lean controls in all lighting conditions. However, the circadian period of obese Zucker rats did not exhibit differences relative to lean controls in either of the constant lighting conditions. These results indicate that although the circadian regulation of temperature and activity in obese Zucker female rats is in fact depressed, obese rats do exhibit normal entrainment and pacemaker functions in the circadian timing system. The results suggest a deficit in the process that generates the amplitude of the circadian rhythm.

  15. Multiparameter data acquisition systems for studies of circadian rhythms

    SciTech Connect

    Groh, K.R.; Ehret, C.F.; Eisler, W.J. Jr.; LeBuis, D.A.

    1985-01-01

    Long-term, simultaneous monitoring of multiple metabolic circadian cycles such as energy metabolism, animal activity, and body temperature together have revealed ultradian fine-structure rhythms which are dependent on circadian phase and the perturbations of environmental influences. Because of the variation between individual animals, these experiments need to have large sample sizes for each experimental condition. To this end we have designed, constructed and used four microcomputer controlled data acquisition systems to collect circadian data from individually housed rats and mice. 11 refs., 6 figs.

  16. Circadian rhythms in anesthesia and critical care medicine: potential importance of circadian disruptions.

    PubMed

    Brainard, Jason; Gobel, Merit; Bartels, Karsten; Scott, Benjamin; Koeppen, Michael; Eckle, Tobias

    2015-03-01

    The rotation of the earth and associated alternating cycles of light and dark--the basis of our circadian rhythms--are fundamental to human biology and culture. However, it was not until 1971 that researchers first began to describe the molecular mechanisms for the circadian system. During the past few years, groundbreaking research has revealed a multitude of circadian genes affecting a variety of clinical diseases, including diabetes, obesity, sepsis, cardiac ischemia, and sudden cardiac death. Anesthesiologists, in the operating room and intensive care units, manage these diseases on a daily basis as they significantly affect patient outcomes. Intriguingly, sedatives, anesthetics, and the intensive care unit environment have all been shown to disrupt the circadian system in patients. In the current review, we will discuss how newly acquired knowledge of circadian rhythms could lead to changes in clinical practice and new therapeutic concepts. PMID:25294583

  17. Absence of Circadian Rhythms of Gonadotropin Secretion in Women

    PubMed Central

    Klingman, Kara M.; Marsh, Erica E.; Klerman, Elizabeth B.; Anderson, Ellen J.

    2011-01-01

    Context: Diurnal rhythms of LH and FSH have been reported in normal women, but it is unclear whether these reflect underlying circadian control from the suprachiasmatic nucleus and/or external influences. Objective: The aim of this study was to determine whether endogenous circadian rhythms of LH, FSH, and the glycoprotein free ?-subunit (FAS) are present in reproductive-aged women. Design and Setting: Subjects were studied in the early follicular phase using a constant routine protocol in a Clinical Research Center at an academic medical center. Subjects: Subjects were healthy, normal-cycling women aged 23–29 yr (n = 11). Main Outcome Measures: Temperature data were collected, and blood samples were assayed for LH, FSH, FAS, and TSH. Results: Core body temperature and TSH were best fit by a sinusoid model, indicating that known circadian rhythms were present in this population. However, the patterns of FSH, LH, and FAS over 24 h were best fit by a linear model. Furthermore, there were no differences in LH and FAS interpulse intervals or pulse amplitudes between evening, night, and morning. Conclusions: Under conditions that control for sleep/wake, light/dark, activity, position, and nutritional cues, there is no circadian rhythm of LH, FSH, or FAS in women during the early follicular phase despite the presence of endogenous rhythms of TSH and core body temperature. These studies indicate that endogenous circadian control does not contribute to previously reported diurnal rhythms in reproductive-aged women and emphasizes the importance of environmental cues in controlling normal reproductive function. PMID:21346063

  18. PPAR{alpha} is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders

    SciTech Connect

    Shirai, Hidenori; Oishi, Katsutaka; Kudo, Takashi; Shibata, Shigenobu; Ishida, Norio . E-mail: n.ishida@aist.go.jp

    2007-06-08

    Recent progress at the molecular level has revealed that nuclear receptors play an important role in the generation of mammalian circadian rhythms. To examine whether peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is involved in the regulation of circadian behavioral rhythms in mammals, we evaluated the locomotor activity of mice administered with the hypolipidemic PPAR{alpha} ligand, bezafibrate. Circadian locomotor activity was phase-advanced about 3 h in mice given bezafibrate under light-dark (LD) conditions. Transfer from LD to constant darkness did not change the onset of activity in these mice, suggesting that bezafibrate advanced the phase of the endogenous clock. Surprisingly, bezafibrate also advanced the phase in mice with lesions of the suprachiasmatic nucleus (SCN; the central clock in mammals). The circadian expression of clock genes such as period2, BMAL1, and Rev-erb{alpha} was also phase-advanced in various tissues (cortex, liver, and fat) without affecting the SCN. Bezafibrate also phase-advanced the activity phase that is delayed in model mice with delayed sleep phase syndrome (DSPS) due to a Clock gene mutation. Our results indicated that PPAR{alpha} is involved in circadian clock control independently of the SCN and that PPAR{alpha} could be a potent target of drugs to treat circadian rhythm sleep disorders including DSPS.

  19. Circadian rhythms in human performance and mood under constant conditions

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Buysse, D. J.; Reynolds, C. F. 3rd; Berga, S. L.; Jarrett, D. B.; Begley, A. E.; Kupfer, D. J.

    1997-01-01

    This study explored the relationship between circadian performance rhythms and rhythms in rectal temperature, plasma cortisol, plasma melatonin, subjective alertness and well-being. Seventeen healthy young adults were studied under 36 h of 'unmasking' conditions (constant wakeful bedrest, temporal isolation, homogenized 'meals') during which rectal temperatures were measured every minute, and plasma cortisol and plasma melatonin measured every 20 min. Hourly subjective ratings of global vigour (alertness) and affect (well-being) were obtained followed by one of two performance batteries. On odd-numbered hours performance (speed and accuracy) of serial search, verbal reasoning and manual dexterity tasks was assessed. On even-numbered hours, performance (% hits, response speed) was measured at a 25-30 min visual vigilance task. Performance of all tasks (except search accuracy) showed a significant time of day variation usually with a nocturnal trough close to the trough in rectal temperature. Performance rhythms appeared not to reliably differ with working memory load. Within subjects, predominantly positive correlations emerged between good performance and higher temperatures and better subjective alertness; predominantly negative correlations between good performance and higher plasma levels of cortisol and melatonin. Temperature and cortisol rhythms correlated with slightly more performance measures (5/7) than did melatonin rhythms (4/7). Global vigour correlated about as well with performance (5/7) as did temperature, and considerably better than global affect (1/7). In conclusion: (1) between-task heterogeneity in circadian performance rhythms appeared to be absent when the sleep/wake cycle was suspended; (2) temperature (positively), cortisol and melatonin (negatively) appeared equally good as circadian correlates of performance, and (3) subjective alertness correlated with performance rhythms as well as (but not better than) body temperature, suggesting that performance rhythms were not directly mediated by rhythms in subjective alertness.

  20. ANIMAL RESPONSES TO CIRCADIAN RHYTHMS IN FORAGE QUALITY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Net photosynthesis and respiration in growing plants cause a circadian rhythm in forage quality. Soluble sugar concentrations increase in plants during the day causing a dilution in ADF and NDF. Herbivores show a strong preference for afternoon (PM) vs morning (AM) harvested forage. Cattle, sheep, g...

  1. Renal electrolyte circadian rhythms - Independence from feeding and activity patterns

    NASA Technical Reports Server (NTRS)

    Moore-Ede, M. C.; Herd, J. A.

    1977-01-01

    Experiments were conducted on six unanesthetized chair-acclimatized adult male squirrel monkeys (Saimiri sciureus) weighing 600-900 g to determine whether internal synchronization is the result of simple passive dependence of renal excretory rhythms on endogenous rhythms of those variable that influence electrolyte excretion such as dietary intake and muscular activity. Independence of the urinary rhythms from diurnal variations in feeding, drinking, and activity was secured by depriving the animals of food, water, and training them to perform a two-hourly schedule of feeding, drinking, and activity throughout day and night. Results indicate that the internal synchronization which is normally observed between the behavioral and urinary rhythms cannot be explained by any direct dependence of renal function on behavioral patterns. The most probable mechanism for circadian internal synchronization is that the various behavioral and renal rhythms are controlled by potentially independent separate oscillators which are normally kept in synchrony with one another.

  2. Wavelet analysis of circadian and ultradian behavioral rhythms.

    PubMed

    Leise, Tanya L

    2013-01-01

    : We review time-frequency methods that can be useful in quantifying circadian and ultradian patterns in behavioral records. These records typically exhibit details that may not be captured through commonly used measures such as activity onset and so may require alternative approaches. For instance, activity may involve multiple bouts that vary in duration and magnitude within a day, or may exhibit day-to-day changes in period and in ultradian activity patterns. The discrete Fourier transform and other types of periodograms can estimate the period of a circadian rhythm, but we show that they can fail to correctly assess ultradian periods. In addition, such methods cannot detect changes in the period over time. Time-frequency methods that can localize frequency estimates in time are more appropriate for analysis of ultradian periods and of fluctuations in the period. The continuous wavelet transform offers a method for determining instantaneous frequency with good resolution in both time and frequency, capable of detecting changes in circadian period over the course of several days and in ultradian period within a given day. The discrete wavelet transform decomposes a time series into components associated with distinct frequency bands, thereby facilitating the removal of noise and trend or the isolation of a particular frequency band of interest. To demonstrate the wavelet-based analysis, we apply the transforms to a numerically-generated example and also to a variety of hamster behavioral records. When used appropriately, wavelet transforms can reveal patterns that are not easily extracted using other methods of analysis in common use, but they must be applied and interpreted with care. PMID:23816159

  3. Circadian rhythms and fractal fluctuations in forearm motion

    NASA Astrophysics Data System (ADS)

    Hu, Kun; Hilton, Michael F.

    2005-03-01

    Recent studies have shown that the circadian pacemaker --- an internal body clock located in the brain which is normally synchronized with the sleep/wake behavioral cycles --- influences key physiologic functions such as the body temperature, hormone secretion and heart rate. Surprisingly, no previous studies have investigated whether the circadian pacemaker impacts human motor activity --- a fundamental physiologic function. We investigate high-frequency actigraph recordings of forearm motion from a group of young and healthy subjects during a forced desynchrony protocol which allows to decouple the sleep/wake cycles from the endogenous circadian cycle while controlling scheduled behaviors. We investigate both static properties (mean value, standard deviation), dynamical characteristics (long-range correlations), and nonlinear features (magnitude and Fourier-phase correlations) in the fluctuations of forearm acceleration across different circadian phases. We demonstrate that while the static properties exhibit significant circadian rhythms with a broad peak in the afternoon, the dynamical and nonlinear characteristics remain invariant with circadian phase. This finding suggests an intrinsic multi-scale dynamic regulation of forearm motion the mechanism of which is not influenced by the circadian pacemaker, thus suggesting that increased cardiac risk in the early morning hours is not related to circadian-mediated influences on motor activity.

  4. Circadian Clock Proteins in Prokaryotes: Hidden Rhythms?

    PubMed Central

    Loza-Correa, Maria; Gomez-Valero, Laura; Buchrieser, Carmen

    2010-01-01

    Circadian clock genes are vital features of eukaryotes that have evolved such that organisms can adapt to our planet's rotation in order to anticipate the coming day or night as well as unfavorable seasons. This circadian clock uses oscillation as a timekeeping element. However, circadian clock mechanisms exist also in prokaryotes. The circadian clock of Cyanobacteria is well studied. It is regulated by a cluster of three genes: kaiA, kaiB, and kaiC. In this review, we will discuss the circadian system in cyanobacteria, and provide an overview and updated phylogenetic analysis of prokaryotic organisms that contain the main circadian genes. It is evident that the evolution of the kai genes has been influenced by lateral transfers but further and deeper studies are needed to get an in depth understanding of the exact evolutionary history of these genes. Interestingly, Legionella pneumophila an environmental bacterium and opportunistic human pathogen that parasitizes protozoa in fresh water environments also contains kaiB and kaiC, but their functions are not known. All of the residues described for the biochemical functions of the main pacemaker KaiC in Synechococcus elongatus are also conserved in the L. pneumophila KaiC protein. PMID:21687756

  5. Light and Gravity Effects on Circadian Rhythms of Rhesus Macaques

    NASA Technical Reports Server (NTRS)

    Fuller, Charles

    1997-01-01

    Temporal integration of a biological organism's physiological, behavioral and biochemical systems depends upon its circadian timing system. The endogenous period of this timing system is typically synchronized to the 24- hour day by environmental cues. The daily alternation of light and dark has long been known as one of the most potent environmental synchronizers influencing the circadian timing system. Alterations in the lighting environment (length or intensity of light exposure) can also affect the homeostatic state of the organism. A series of experiments was performed using rhesus monkeys with the objective of defining the fundamental properties of the circadian rhythm of body temperature. Three major experiments were performed in addition to several preliminary studies. These experiments explored 1.) the response of the rhesus body temperature rhythm to varying day length and light intensity; 2.) the response of the body temperature rhythm to light exposure as a function of time of day; and 3.) the characteristics of the metabolic heat production rhythm which is responsible for the daily cycle in body temperature. Results of these three completed experiments will be reported here. In addition, preliminary experiments were also performed in social entrainment of rhesus circadian rhythms and the properties of rhesus body temperature rhythms in constant conditions, where no external time cues were provided. Four adult male rhesus monkeys served as subjects in all experiments. All experiments were performed at the California Regional Primate Research Center. Each animal was implanted with a biotelemetry unit that measured deep body temperature. All surgeries were performed by a board certified veterinary surgeon under sterile conditions. The biotelemetry implants also provided an index of activity level in each animal. For metabolic heat production measurements, oxygen consumption and carbon dioxide production were measured and the caloric equivalent of these was calculated. Specific methodologies are described in detail.

  6. Role of mutation of the circadian clock gene Per2 in cardiovascular circadian rhythms.

    PubMed

    Vukolic, Ana; Antic, Vladan; Van Vliet, Bruce N; Yang, Zhihong; Albrecht, Urs; Montani, Jean-Pierre

    2010-03-01

    Alterations in the circadian blood pressure pattern are frequently observed in hypertension and lead to increased cardiovascular morbidity. However, there are no studies that have investigated a possible implication of the Period2 gene, a key component of the molecular circadian clock, on the circadian rhythms of blood pressure and heart rate. To address this question, we monitored blood pressure, heart rate, and locomotor activity 24 h a day by telemetry in mice carrying a mutation in the Period2 gene and in wild-type control mice. Under a standard 12:12-h light-dark cycle, mutant mice showed a mild cardiovascular phenotype with an elevated 24-h heart rate, a decreased 24-h diastolic blood pressure, and an attenuation of the dark-light difference in blood pressure and heart rate. Locomotor activity was similar in both groups and did not appear to explain the observed hemodynamic differences. When mice were placed under constant darkness during eight consecutive days, wild-type mice maintained 24-h rhythms, whereas there was an apparent progressive loss of 24-h rhythm of blood pressure, heart rate, and locomotor activity in mutant mice. However, a chi square periodogram revealed that circadian rhythms were preserved under complete absence of any light cue, but with shorter periods by approximately 40 min, leading to a cumulative phase shift toward earlier times of approximately 5 h and 20 min by the end of the 8th day. When heart rate, mean arterial pressure, and activity were recalculated according to the endogenous circadian periods of each individual mouse, the amplitudes of the circadian rhythms ("subjective night"-"subjective day" differences) were maintained for all variables studied. Our data show that mutation of the Period2 gene results in an attenuated dipping of blood pressure and heart rate during both light-dark cycles and constant darkness, and in shorter circadian periods during constant darkness. PMID:20053965

  7. A Novel Bmal1 Mutant Mouse Reveals Essential Roles of the C-Terminal Domain on Circadian Rhythms

    PubMed Central

    Cheon, Solmi; Row, Hansang; Lee, Jiyeon; Han, Dong-Hee; Cho, Sehyung; Kim, Kyungjin

    2015-01-01

    The mammalian circadian clock is an endogenous biological timer comprised of transcriptional/translational feedback loops of clock genes. Bmal1 encodes an indispensable transcription factor for the generation of circadian rhythms. Here, we report a new circadian mutant mouse from gene-trapped embryonic stem cells harboring a C-terminus truncated Bmal1 (Bmal1GT?C) allele. The homozygous mutant (Bmal1GT?C/GT?C) mice immediately lost circadian behavioral rhythms under constant darkness. The heterozygous (Bmal1+/GT?C) mice displayed a gradual loss of rhythms, in contrast to Bmal1+/- mice where rhythms were sustained. Bmal1GT?C/GT?C mice also showed arrhythmic mRNA and protein expression in the SCN and liver. Lack of circadian reporter oscillation was also observed in cultured fibroblast cells, indicating that the arrhythmicity of Bmal1GT?C/GT?C mice resulted from impaired molecular clock machinery. Expression of clock genes exhibited distinct responses to the mutant allele in Bmal1+/GT?C and Bmal1GT?C/GT?C mice. Despite normal cellular localization and heterodimerization with CLOCK, overexpressed BMAL1GT?C was unable to activate transcription of Per1 promoter and BMAL1-dependent CLOCK degradation. These results indicate that the C-terminal region of Bmal1 has pivotal roles in the regulation of circadian rhythms and the Bmal1GT?C mice constitute a novel model system to evaluate circadian functional mechanism of BMAL1. PMID:26394143

  8. Circadian Rhythms and Mood Disorders: Are the Phenomena and Mechanisms Causally Related?

    PubMed Central

    Bechtel, William

    2015-01-01

    This paper reviews some of the compelling evidence of disrupted circadian rhythms in individuals with mood disorders (major depressive disorder, seasonal affective disorder, and bipolar disorder) and that treatments such as bright light, designed to alter circadian rhythms, are effective in treating these disorders. Neurotransmitters in brain regions implicated in mood regulation exhibit circadian rhythms. A mouse model originally employed to identify a circadian gene has proven a potent model for mania. While this evidence is suggestive of an etiological role for altered circadian rhythms in mood disorders, it is compatible with other explanations, including that disrupted circadian rhythms and mood disorders are effects of a common cause and that genes and proteins implicated in both simply have pleiotropic effects. In light of this, the paper advances a proposal as to what evidence would be needed to establish a direct causal link between disruption of circadian rhythms and mood disorders. PMID:26379559

  9. Circadian and ultradian rhythms of clock gene expression in the suprachiasmatic nucleus of freely moving mice

    PubMed Central

    Ono, Daisuke; Honma, Ken-ichi; Honma, Sato

    2015-01-01

    In mammals, the temporal order of physiology and behavior is primarily regulated by the circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). Rhythms are generated in cells by an auto-regulatory transcription/translation feedback loop, composed of several clock genes and their protein products. Taking advantage of bioluminescence reporters, we have succeeded in continuously monitoring the expression of clock gene reporters Per1-luc, PER2::LUC and Bmal1-ELuc in the SCN of freely moving mice for up to 3 weeks in constant darkness. Bioluminescence emitted from the SCN was collected with an implanted plastic optical fiber which was connected to a cooled photomultiplier tube. We found robust circadian rhythms in the clock gene expression, the phase-relation of which were the same as those observed ex vivo. The circadian rhythms were superimposed by episodic bursts which had ultradian periods of approximately 3.0?h. Episodic bursts often accompanied activity bouts, but stoichiometric as well as temporal analyses revealed no causality between them. Clock gene expression in the SCN in vivo is regulated by the circadian pacemaker and ultradian rhythms of unknown origin. PMID:26194231

  10. A Flexible Model For Human Circadian Rhythms Yuedong Wang and Morton B. Brown

    E-print Network

    Wang, Yuedong

    A Flexible Model For Human Circadian Rhythms Yuedong Wang and Morton B. Brown Department. In this paper we describe a semi­parametric periodic spline function that can be fit to circadian rhythms physiological processes vary in a circadian pattern. Although a sine/cosine function can be used to model

  11. Circadian Rhythms, the Molecular Clock, and Skeletal Muscle

    PubMed Central

    Lefta, Mellani; Wolff, Gretchen; Esser, Karyn A.

    2015-01-01

    Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock mechanism found in most, if not all, cell types including skeletal muscle. The mammalian molecular clock is a complex of multiple oscillating networks that are regulated through transcriptional mechanisms, timed protein turnover, and input from small molecules. At this time, very little is known about circadian aspects of skeletal muscle function/metabolism but some progress has been made on understanding the molecular clock in skeletal muscle. The goal of this chapter is to provide the basic terminology and concepts of circadian rhythms with a more detailed review of the current state of knowledge of the molecular clock, with reference to what is known in skeletal muscle. Research has demonstrated that the molecular clock is active in skeletal muscles and that the muscle-specific transcription factor, MyoD, is a direct target of the molecular clock. Skeletal muscle of clock-compromised mice, Bmal1?/? and Clock?19 mice, are weak and exhibit significant disruptions in expression of many genes required for adult muscle structure and metabolism. We suggest that the interaction between the molecular clock, MyoD, and metabolic factors, such as PGC-1, provide a potential system of feedback loops that may be critical for both maintenance and adaptation of skeletal muscle. PMID:21621073

  12. Calculating activation energies for temperature compensation in circadian rhythms

    NASA Astrophysics Data System (ADS)

    Bodenstein, C.; Heiland, I.; Schuster, S.

    2011-10-01

    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.

  13. Sleep and Circadian Rhythms in Four Orbiting Astronauts

    NASA Technical Reports Server (NTRS)

    Monk, Timothy H.; Buysse, Daniel J.; Billy, Bart D.; Kennedy, Kathy S.; Willrich, Linda M.

    1999-01-01

    INTRODUCTION The study of human sleep and circadian rhythms in space has both operational and scientific significance. Operationally, U.S. Spaceflight is moving away from brief missions with durations of less than one week. Most space shuttle missions now last two weeks or more, and future plans involving space stations, lunar bases and interplanetary missions all presume that people will be living away from the gravity and time cues of earth for months at a time. Thus, missions are moving away from situations where astronauts can "tough it out" for comparatively brief durations, to situations where sleep and circadian disruptions are likely to become chronic, and thus resistant to short term pharmacological or behavioral manipulations. As well as the operational significance, there is a strong theoretical imperative for studying the sleep and circadian rhythms of people who are removed from the gravity and time cues of earth. Like other animals, in humans, the Circadian Timekeeping System (CTS) is entrained to the correct period (24h) and temporal orientation by various time cues ("zeitgebers"), the most powerful of which is the alternation of daylight and darkness. In leaving Earth, astronauts are removing themselves from the prime zeitgeber of their circadian system -- the 24h alternation of daylight and darkness.

  14. Age, circadian rhythms, and sleep loss in flight crews

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.; Nguyen, DE; Rosekind, Mark R.; Connell, Linda J.

    1993-01-01

    Age-related changes in trip-induced sleep loss, personality, and the preduty temperature rhythm were analyzed in crews from various flight operations. Eveningness decreased with age. The minimum of the baseline temperature rhythm occurred earlier with age. The amplitude of the baseline temperature rhythm declined with age. Average daily percentage sleep loss during trips increased with age. Among crewmembers flying longhaul flight operations, subjects aged 50-60 averaged 3.5 times more sleep loss per day than subjects aged 20-30. These studies support previous findings that evening types and subjects with later peaking temperature rhythms adapt better to shift work and time zone changes. Age and circadian type may be important considerations for duty schedules and fatigue countermeasures.

  15. Circadian rhythms in liver metabolism and disease

    PubMed Central

    Ferrell, Jessica M.; Chiang, John Y.L.

    2015-01-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease. PMID:26579436

  16. Recording and analysis of circadian rhythms in running-wheel activity in rodents.

    PubMed

    Verwey, Michael; Robinson, Barry; Amir, Shimon

    2013-01-01

    When rodents have free access to a running wheel in their home cage, voluntary use of this wheel will depend on the time of day. Nocturnal rodents, including rats, hamsters, and mice, are active during the night and relatively inactive during the day. Many other behavioral and physiological measures also exhibit daily rhythms, but in rodents, running-wheel activity serves as a particularly reliable and convenient measure of the output of the master circadian clock, the suprachiasmatic nucleus (SCN) of the hypothalamus. In general, through a process called entrainment, the daily pattern of running-wheel activity will naturally align with the environmental light-dark cycle (LD cycle; e.g. 12 hr-light:12 hr-dark). However circadian rhythms are endogenously generated patterns in behavior that exhibit a ~24 hr period, and persist in constant darkness. Thus, in the absence of an LD cycle, the recording and analysis of running-wheel activity can be used to determine the subjective time-of-day. Because these rhythms are directed by the circadian clock the subjective time-of-day is referred to as the circadian time (CT). In contrast, when an LD cycle is present, the time-of-day that is determined by the environmental LD cycle is called the zeitgeber time (ZT). Although circadian rhythms in running-wheel activity are typically linked to the SCN clock, circadian oscillators in many other regions of the brain and body could also be involved in the regulation of daily activity rhythms. For instance, daily rhythms in food-anticipatory activity do not require the SCN and instead, are correlated with changes in the activity of extra-SCN oscillators. Thus, running-wheel activity recordings can provide important behavioral information not only about the output of the master SCN clock, but also on the activity of extra-SCN oscillators. Below we describe the equipment and methods used to record, analyze and display circadian locomotor activity rhythms in laboratory rodents. PMID:23380887

  17. KaiC CII Ring Flexibility Governs the Rhythm of the Circadian Clock of Cyanobacteria 

    E-print Network

    Kuo, Nai-Wei

    2012-07-16

    The circadian clock orchestrates metabolism and cell division and imposes important consequences to health and diseases, such as obesity, diabetes, and cancer. It is well established that phosphorylation-dependent circadian rhythms are the result...

  18. Circadian rhythms affect electroretinogram, compound eye color, striking behavior and locomotion of the praying mantis Hierodula patellifera.

    PubMed

    Schirmer, Aaron E; Prete, Frederick R; Mantes, Edgar S; Urdiales, Andrew F; Bogue, Wil

    2014-11-01

    Many behaviors and physiological processes oscillate with circadian rhythms that are synchronized to environmental cues (e.g. light onset), but persist with periods of ~24 h in the absence of such cues. We used a multilevel experimental approach to assess whether circadian rhythms modulate several aspects of the visual physiology and behavior of the praying mantis Hierodula patellifera. We used electroretinograms (ERGs) to assess compound eye sensitivity, colorimetric photographic analyses to assess compound eye color changes (screening pigment migration), behavioral assays of responsiveness to computer-generated prey-like visual stimuli and analyses of locomotor activity patterns on a modified treadmill apparatus. Our results indicate that circadian clocks control and/or modulate each of the target behaviors. Strong rhythms, persisting under constant conditions, with periods of ~24 h were evident in photoreceptor sensitivity to light, appetitive responsiveness to prey-like stimuli and gross locomotor activity. In the first two cases, responsiveness was highest during the subjective night and lowest during the subjective day. Locomotor activity was strongly clustered around the transition time from day to night. In addition, pigment migration and locomotor behavior responded strongly to light:dark cycles and anticipated the light-dark transition, suggesting that the circadian clocks modulating both were entrained to environmental light cues. Together, these data indicate that circadian rhythms operate at the cellular, cellular systems and organismal level in H. patellifera. Our results represent an intriguing first step in uncovering the complexities of circadian rhythms in the Mantodea. PMID:25214491

  19. Suprachiasmatic neuron numbers and rest-activity circadian rhythms in older humans.

    PubMed

    Wang, Joshua L; Lim, Andrew S; Chiang, Wei-Yin; Hsieh, Wan-Hsin; Lo, Men-Tzung; Schneider, Julie A; Buchman, Aron S; Bennett, David A; Hu, Kun; Saper, Clifford B

    2015-08-01

    The suprachiasmatic nucleus (SCN) of the hypothalamus, the master mammalian circadian pacemaker, synchronizes endogenous rhythms with the external day-night cycle. Older humans, particularly those with Alzheimer disease (AD), often have difficulty maintaining normal circadian rhythms compared to younger adults, but the basis of this change is unknown. We report that the circadian rhythm amplitude of motor activity in both AD subjects and age-matched controls is correlated with the number of vasoactive intestinal peptide-expressing SCN neurons. AD was additionally associated with delayed circadian phase compared to cognitively healthy subjects, suggesting distinct pathologies and strategies for treating aging- and AD-related circadian disturbances. PMID:25921596

  20. Circadian rhythm dissociation in an environment with conflicting temporal information

    NASA Technical Reports Server (NTRS)

    Sulzman, F. M.; Fuller, C. A.; Hiles, L. G.; Moore-Ede, M. C.

    1978-01-01

    The relative contributions of light-dark (LD) cycles and eating-fasting (EF) cycles in providing temporal information to the circadian time-keeping system were examined in chair-acclimatized squirrel monkeys (Saimiri sciureus). The circadian rhythms of drinking, colonic temperature, urine volume, and urinary potassium excretion were measured with the LD and EF cycles providing either conflicting phases or periods. In conflicting phase experiments, animals were exposed to 24-hr LD cycles consisting of 12 hr of 600 lx followed by 12 hr of less than 1 lx and concurrent 24-hr EF cycles in which the animals ate for 3 hr and then fasted for 21 hr. One group had food available at the beginning and a second group at the end of the light period. In conflicting period experiments, monkeys were exposed to 23-hr LD cycles and 24-hr EF cycles. Analysis of the rhythms showed that both phase and period information were conveyed to the drinking and urinary rhythms by the EF cycle, and to the temperature rhythm by the LD cycle.

  1. cap alpha. -Methyl-p-tyrosine shifts circadian temperature rhythms

    SciTech Connect

    Cahill, A.L.; Ehret, C.F.

    1982-09-01

    ..cap alpha..-Methyl-p-tyrosine shifts the acrophase (time of highest temperature) of the circadian temperature rhythm of the rat to earlier or later times of day depending on the phase of the cicadian cycle at which the drug is administered. When ..cap alpha..-methyl-p-tyrosine methyl ester HCl is injected intraperitoneally at a dose of 100 mg/kg late in the projected 8-h light phase, the acrophase of the intraperitoneal temperature rhythm is delayed by up to 3 h.However, when the same dose of drug is given 9-10 h into the projected 16-h dark phase of the daily cycle, the acrophase of the temperature rhythm occurs about 2 h earlier than expected. The times of ..cap alpha..-methyl-p-tyrosine administration leading to maximal phase delays or advances are correlated with the times of minimal and maximal turnover of norepinephrine in the hypothalamus. These results suggest that changing rates of norepinephrine turnover in the hypothalamus may regulate the circadian temperature rhythm in rats. The results also emphasize the fact that the effects of drugs may vary as a function of the time of administration. This fact must be taken into account in pharmacologic testing.

  2. JO URN ALOF BIO LOGI CAL RHYTHMS / February 1999Krieg sf eld et al. /CIRCADIAN LOCOMOTOR ANALYSIS Circadian Locomotor Analysis of

    E-print Network

    Demas, Greg

    JO URN ALOF BIO LOGI CAL RHYTHMS / February 1999Krieg sf eld et al. /CIRCADIAN LOCOMOTOR ANALYSIS revealed that NO might be necessary for photic entrainment of circadian rhythms; general NOS inhibitors the specific role of nNOS in mediating entrainment of circadian rhythms, mice with targeted deletion

  3. Neuromedin s-producing neurons act as essential pacemakers in the suprachiasmatic nucleus to couple clock neurons and dictate circadian rhythms.

    PubMed

    Lee, Ivan T; Chang, Alexander S; Manandhar, Manabu; Shan, Yongli; Fan, Junmei; Izumo, Mariko; Ikeda, Yuichi; Motoike, Toshiyuki; Dixon, Shelley; Seinfeld, Jeffrey E; Takahashi, Joseph S; Yanagisawa, Masashi

    2015-03-01

    Circadian behavior in mammals is orchestrated by neurons within the suprachiasmatic nucleus (SCN), yet the neuronal population necessary for the generation of timekeeping remains unknown. We show that a subset of SCN neurons expressing the neuropeptide neuromedin S (NMS) plays an essential role in the generation of daily rhythms in behavior. We demonstrate that lengthening period within Nms neurons is sufficient to lengthen period of the SCN and behavioral circadian rhythms. Conversely, mice without a functional molecular clock within Nms neurons lack synchronous molecular oscillations and coherent behavioral daily rhythms. Interestingly, we found that mice lacking Nms and its closely related paralog, Nmu, do not lose in vivo circadian rhythms. However, blocking vesicular transmission from Nms neurons with intact cell-autonomous clocks disrupts the timing mechanisms of the SCN, revealing that Nms neurons define a subpopulation of pacemakers that control SCN network synchrony and in vivo circadian rhythms through intercellular synaptic transmission. PMID:25741729

  4. Implicit Associations Have a Circadian Rhythm

    PubMed Central

    Zadra, Jonathan R.; Proffitt, Dennis R.

    2014-01-01

    The current study shows that people's ability to inhibit implicit associations that run counter to their explicit views varies in a circadian pattern. The presence of this rhythmic variation suggests the involvement of a biological process in regulating automatic associations—specifically, with the current data, associations that form undesirable social biases. In 1998, Greenwald, McGhee, and Schwartz introduced the Implicit Association Test as a means of measuring individual differences in implicit cognition. The IAT is a powerful tool that has become widely used. Perhaps most visibly, studies employing the IAT demonstrate that people generally hold implicit biases against social groups, which often conflict with their explicitly held views. The IAT engages inhibitory processes similar to those inherent in self-control tasks. Because the latter processes are known to be resource-limited, we considered whether IAT scores might likewise be resource dependent. Analyzing IAT performance from over a million participants across all times of day, we found a clear circadian pattern in scores. This finding suggests that the IAT measures not only the strength of implicit associations, but also the effect of variations in the physiological resources available to inhibit their undesirable influences on explicit behavior. PMID:25365254

  5. Sundowning and circadian rhythm disorders in dementia.

    PubMed

    Klaffke, S; Staedt, J

    2006-12-01

    Sleep disorders and disruptive nocturnal behaviours are commonly reported in people with senile dementia and present both a significant clinical problem and a cause of increased stress for caregivers. Neuronal degeneration of cholinergic Nucleus basalis Meynert (NBM) neurons promote rest-activity disturbance and Sundowning in Alzheimer's disease. NBM neurons modulate the activity of the mainly cholinergic suprachiasmatic nucleus (SCN) and the induction of NONREM sleep. Sundowning might be explained as a syndrome occurring when arousal is to be processed while the neocortex is already turned "off" to (NONREM) sleep. The therapeutic measures should thus primarily be aimed at the stimulation of the circadian system and enforcing "external Zeitgebers". Pharmacologically, application of cholinergic enhancers i.e. cholinesterase inhibitors and melatonin supports and should stabilize the weakened structures. PMID:17323834

  6. An allele of the crm gene blocks cyanobacterial circadian rhythms.

    PubMed

    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. PMID:23918383

  7. An allele of the crm gene blocks cyanobacterial circadian rhythms

    PubMed Central

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

    2013-01-01

    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. PMID:23918383

  8. Respiratory Rhythm Generation In Vivo

    PubMed Central

    Richter, Diethelm W.; Smith, Jeffrey C.

    2014-01-01

    The cellular and circuit mechanisms generating the rhythm of breathing in mammals have been under intense investigation for decades. Here, we try to integrate the key discoveries into an updated description of the basic neural processes generating respiratory rhythm under in vivo conditions. PMID:24382872

  9. Circadian rhythms in myocardial metabolism and contractile function; influence of workload and oleate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiple extra-cardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its ...

  10. Genetics of Circadian Rhythms in Mammalian Model Organisms

    PubMed Central

    Lowrey, Phillip L.; Takahashi, Joseph S.

    2013-01-01

    The mammalian circadian system is a complex hierarchical temporal network which is organized around an ensemble of uniquely coupled cells comprising the principal circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus. This central pacemaker is entrained each day by the environmental light/dark cycle and transmits synchronizing cues to cell-autonomous oscillators in tissues throughout the body. Within cells of the central pacemaker and the peripheral tissues, the underlying molecular mechanism by which oscillations in gene expression occur involves interconnected feedback loops of transcription and translation. Over the past 10 years we have learned much regarding the genetics of this system, including how it is particularly resilient when challenged by single-gene mutations, how accessory transcriptional loops enhance the robustness of oscillations, how epigenetic mechanisms contribute to the control of circadian gene expression, and how, from coupled neuronal networks, emergent clock properties arise. Here we will explore the genetics of the mammalian circadian system from cell-autonomous molecular oscillations, to interactions among central and peripheral oscillators and ultimately, to the daily rhythms of behavior observed in the animal. PMID:21924978

  11. Therapeutic applications of circadian rhythms for the cardiovascular system

    PubMed Central

    Tsimakouridze, Elena V.; Alibhai, Faisal J.; Martino, Tami A.

    2015-01-01

    The cardiovascular system exhibits dramatic time-of-day dependent rhythms, for example the diurnal variation of heart rate, blood pressure, and timing of onset of adverse cardiovascular events such as heart attack and sudden cardiac death. Over the past decade, the circadian clock mechanism has emerged as a crucial factor regulating these daily fluctuations. Most recently, these studies have led to a growing clinical appreciation that targeting circadian biology offers a novel therapeutic approach toward cardiovascular (and other) diseases. Here we describe leading-edge therapeutic applications of circadian biology including (1) timing of therapy to maximize efficacy in treating heart disease (chronotherapy); (2) novel biomarkers discovered by testing for genomic, proteomic, metabolomic, or other factors at different times of day and night (chronobiomarkers); and (3) novel pharmacologic compounds that target the circadian mechanism with potential clinical applications (new chronobiology drugs). Cardiovascular disease remains a leading cause of death worldwide and new approaches in the management and treatment of heart disease are clearly warranted and can benefit patients clinically. PMID:25941487

  12. Comparison of circadian rhythms in male and female humans

    NASA Technical Reports Server (NTRS)

    Winget, C. M.; Deroshia, C. W.; Vernikos-Danellis, J.; Rosenblatt, W. S.; Hetherington, N. W.

    1977-01-01

    Heart rate (HR) and rectal temperature (RT) data were obtained from 12 female and 27 male subjects. The subjects were housed in a facility where the environment was controlled. Human male and female RT and HR exhibit a circadian rhythm with an excursion of about 1.2 C and 30 beats/min, respectively. The acrophases, amplitudes, and level crossings are only slightly different between the sexes. The male HR and RT circadian wave forms are more stable than those of the females. However, the actual RT and HR of males were always lower than that of females at all time points around the clock. The HR during sleep in females is 15 per cent below the daily mean heart rate and in males, 22 per cent.

  13. A molecular explanation for the long-term suppression of circadian rhythms by a single light pulse

    E-print Network

    Goldbeter, Albert

    A molecular explanation for the long-term suppression of circadian rhythms by a single light pulse explanation for the long-term suppression of circadian rhythms by a single light pulse. Am J Physiol-term suppression of circadian rhythms observed in a variety of organisms in response to a single light pulse

  14. The influence of circadian rhythms on pre-and post-prandial metabolism in the snake Lamprophis fuliginosus

    E-print Network

    Hopkins, William A.

    The influence of circadian rhythms on pre- and post-prandial metabolism in the snake Lamprophis energy cost of circadian rhythms. To estimate SMR, SDA, and identify metabolic variation associated% of their body mass. Circadian rhythms in metabolism were perceptible in the V O2 data during fasting and after

  15. Circadian rhythm disorders among adolescents: assessment and treatment options.

    PubMed

    Bartlett, Delwyn J; Biggs, Sarah N; Armstrong, Stuart M

    2013-10-21

    Delayed sleep phase disorder (DSPD) - a circadian rhythm sleep disorder - is most commonly seen in adolescents. The differential diagnosis between DSPD and conventional psychophysiological insomnia is important for correct therapeutic intervention. Adolescent DSPD sleep duration is commonly 9 hours or more. Depression may be comorbid with DSPD. DSPD has a negative impact on adolescent academic performance. DSPD treatments include bright light therapy, chronotherapeutic regimens, and administration of melatonin as a chronobiotic (as distinct from a soporific). Attention to non-photic and extrinsic factors including healthy sleep parameters is also important to enable better sleep and mood outcomes in adolescents. PMID:24138360

  16. Aging human circadian rhythms: conventional wisdom may not always be right

    NASA Technical Reports Server (NTRS)

    Monk, Timothy H.

    2005-01-01

    This review discusses the ways in which the circadian rhythms of older people are different from those of younger adults. After a brief discussion of clinical issues, the review describes the conventional wisdom regarding age-related changes in circadian rhythms. These can be summarized as four assertions regarding what happens to people as they get older: 1) the amplitude of their circadian rhythms reduces, 2) the phase of their circadian rhythms becomes earlier, 3) their natural free-running period (tau) shortens, and 4) their ability to tolerate abrupt phase shifts (e.g., from jet travel or night work) worsens. The review then discusses the empirical evidence for and against these assertions and discusses some alternative explanations. The conclusions are that although older people undoubtedly have earlier circadian phases than younger adults, and have more trouble coping with shift work and jet lag, evidence for the assertions about rhythm amplitude and tau are, at best, mixed.

  17. Effect of hypergravity on the circadian rhythms of white rats.

    NASA Technical Reports Server (NTRS)

    Lafferty, J. F.

    1972-01-01

    The effects of artificial gravity on the circadian rhythm of white rats was observed by comparing feeding activity at 1.0 and 1.75 g. The feeding cycle data were obtained by observing the number of feeding switch responses, as well as the amount of food obtained, as a function of time. One of the three subjects clearly established a free-running cycle with a period of 24.742 hr. During a 40-day exposure to the 1.75 g environment, the subjects maintained the same feeding cycle period which was established at 1.0 g. While the results of this study indicate that the activity rhythms of rats are insensitive to gravity levels between 1.0 and 1.75 g, the effects of gravity levels below 1.0 g are yet to be determined.

  18. A neural theory of circadian rhythms: Aschoff s rule in diurnal and nocturnal mammals

    E-print Network

    Grossberg, Stephen

    "" , - , ,\\i', (-\\' A neural theory of circadian rhythms: Aschoff s rule in diurnal and nocturnal- theory of circadian rhythms: A~choff's rule in diurnal and nr:c- mals, including the "dead zone" of phase.lcnuclelsuggest~h°v.:beha":lor~lac~lvIty,rest, of the pacemaker by high light intensities (3,11). Due to and circadian period depend on light intensity In diurnal

  19. Experiment K-7-35: Circadian Rhythms and Temperature Regulation During Spaceflight. Part 1; Circadian Rhythms and Temperature Regulation

    NASA Technical Reports Server (NTRS)

    Fuller, C. A.; Alpatov, A. M.; Hoban-Higgins, T. M.; Klimovitsky, V. Y.

    1994-01-01

    Mammals have developed the ability to adapt to most variations encountered in their everyday environment. For example, homeotherms have developed the ability to maintain the internal cellular environment at a relatively constant temperature. Also, in order to compensate for temporal variations in the terrestrial environment, the circadian timing system has evolved. However, throughout the evolution of life on earth, living organisms have been exposed to the influence of an unvarying level of earth's gravity. As a result changes in gravity produce adaptive responses which are not completely understood. In particular, spaceflight has pronounced effects on various physiological and behavioral systems. Such systems include body temperature regulation and circadian rhythms. This program has examined the influence of microgravity on temperature regulation and circadian timekeeping systems in Rhesus monkeys. Animals flown on the Soviet Biosatellite, COSMOS 2044, were exposed to 14 days of microgravity while constantly monitoring the circadian patterns temperature regulation, heart rate and activity. This experiment has extended our previous observations from COSMOS 1514, as well as providing insights into the physiological mechanisms that produce these changes.

  20. Effect of circadian rhythm on CNS oxygen toxicity.

    NASA Technical Reports Server (NTRS)

    Hof, D. G.; Dexter, J. D.; Mengel, C. E.

    1971-01-01

    The circadian rhythm in susceptibility to oxygen toxicity seizures was investigated by using six groups of 20 male Sprague-Dawley rats (101-196 gm.). The animals were given standard chow, exposed to standard diurnal conditions of light (0700-1900 hr) and dark (1900-0700 hr), and fasted for 15-16 hr prior to exposure to hyperbaric oxygen. The animals were placed in a previously oxygen flushed chamber and raised to 60 psi (gauge) oxygen at a rate of 3 psi/min. Time of exposure started with attainment of 60 psi. End point was first convulsion. The animals' weights were equally distributed within the groups, and the groups were defined by hour of exposure. Time of exposure in minutes prior to seizure was significantly longer in those exposed at 0700-0800 hr and 1000-1100 hr than in four other groups. There was no relationship between animals' weights and time of exposure to seizures. All R values were negative, and the highest R value was -035. These data suggest a definite circadian rhythm in susceptibility to oxygen toxicity seizures.

  1. Protecting the melatonin rhythm through circadian healthy light exposure.

    PubMed

    Bonmati-Carrion, Maria Angeles; Arguelles-Prieto, Raquel; Martinez-Madrid, Maria Jose; Reiter, Russel; Hardeland, Ruediger; Rol, Maria Angeles; Madrid, Juan Antonio

    2014-01-01

    Currently, in developed countries, nights are excessively illuminated (light at night), whereas daytime is mainly spent indoors, and thus people are exposed to much lower light intensities than under natural conditions. In spite of the positive impact of artificial light, we pay a price for the easy access to light during the night: disorganization of our circadian system or chronodisruption (CD), including perturbations in melatonin rhythm. Epidemiological studies show that CD is associated with an increased incidence of diabetes, obesity, heart disease, cognitive and affective impairment, premature aging and some types of cancer. Knowledge of retinal photoreceptors and the discovery of melanopsin in some ganglion cells demonstrate that light intensity, timing and spectrum must be considered to keep the biological clock properly entrained. Importantly, not all wavelengths of light are equally chronodisrupting. Blue light, which is particularly beneficial during the daytime, seems to be more disruptive at night, and induces the strongest melatonin inhibition. Nocturnal blue light exposure is currently increasing, due to the proliferation of energy-efficient lighting (LEDs) and electronic devices. Thus, the development of lighting systems that preserve the melatonin rhythm could reduce the health risks induced by chronodisruption. This review addresses the state of the art regarding the crosstalk between light and the circadian system. PMID:25526564

  2. Wavelet-based analysis of circadian behavioral rhythms.

    PubMed

    Leise, Tanya L

    2015-01-01

    The challenging problems presented by noisy biological oscillators have led to the development of a great variety of methods for accurately estimating rhythmic parameters such as period and amplitude. This chapter focuses on wavelet-based methods, which can be quite effective for assessing how rhythms change over time, particularly if time series are at least a week in length. These methods can offer alternative views to complement more traditional methods of evaluating behavioral records. The analytic wavelet transform can estimate the instantaneous period and amplitude, as well as the phase of the rhythm at each time point, while the discrete wavelet transform can extract the circadian component of activity and measure the relative strength of that circadian component compared to those in other frequency bands. Wavelet transforms do not require the removal of noise or trend, and can, in fact, be effective at removing noise and trend from oscillatory time series. The Fourier periodogram and spectrogram are reviewed, followed by descriptions of the analytic and discrete wavelet transforms. Examples illustrate application of each method and their prior use in chronobiology is surveyed. Issues such as edge effects, frequency leakage, and implications of the uncertainty principle are also addressed. PMID:25662453

  3. Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

    PubMed Central

    Bonmati-Carrion, Maria Angeles; Arguelles-Prieto, Raquel; Martinez-Madrid, Maria Jose; Reiter, Russel; Hardeland, Ruediger; Rol, Maria Angeles; Madrid, Juan Antonio

    2014-01-01

    Currently, in developed countries, nights are excessively illuminated (light at night), whereas daytime is mainly spent indoors, and thus people are exposed to much lower light intensities than under natural conditions. In spite of the positive impact of artificial light, we pay a price for the easy access to light during the night: disorganization of our circadian system or chronodisruption (CD), including perturbations in melatonin rhythm. Epidemiological studies show that CD is associated with an increased incidence of diabetes, obesity, heart disease, cognitive and affective impairment, premature aging and some types of cancer. Knowledge of retinal photoreceptors and the discovery of melanopsin in some ganglion cells demonstrate that light intensity, timing and spectrum must be considered to keep the biological clock properly entrained. Importantly, not all wavelengths of light are equally chronodisrupting. Blue light, which is particularly beneficial during the daytime, seems to be more disruptive at night, and induces the strongest melatonin inhibition. Nocturnal blue light exposure is currently increasing, due to the proliferation of energy-efficient lighting (LEDs) and electronic devices. Thus, the development of lighting systems that preserve the melatonin rhythm could reduce the health risks induced by chronodisruption. This review addresses the state of the art regarding the crosstalk between light and the circadian system. PMID:25526564

  4. Circadian Sleep-Wake Rhythm of Older Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Maaskant, Marijke; van de Wouw, Ellen; van Wijck, Ruud; Evenhuis, Heleen M.; Echteld, Michael A.

    2013-01-01

    The circadian sleep-wake rhythm changes with aging, resulting in a more fragmented sleep-wake pattern. In individuals with intellectual disabilities (ID), brain structures regulating the sleep-wake rhythm might be affected. The aims of this study were to compare the sleep-wake rhythm of older adults with ID to that of older adults in the general…

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

    PubMed Central

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

    2015-01-01

    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. PMID:25670162

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

    PubMed

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

    2015-01-01

    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. PMID:25670162

  7. Effects of 24-hour shift work with nighttime napping on circadian rhythm characteristics in ambulance personnel.

    PubMed

    Motohashi, Y; Takano, T

    1993-12-01

    Forty-two ambulance personnel engaged in a 24-h shift system participated in a chronobiological field study to study the effects of 24-h shift work on circadian rhythm characteristics. Autorhythmometry of circadian rhythms of oral temperature, right and left grip strengths, and heart rate plus subjective assessment of drowsiness, fatigue, and attention was performed every approximately 4 h except during sleep for 7 days. Cosinor and power spectral analyses were applied to the longitudinal data of each individual. Changes in circadian period different from 24 h of oral temperature, grip strengths, and heart rate plus subjective drowsiness, fatigue, and attention were observed in ambulance personnel. The incidence of circadian periodicity different from 24 h in oral temperature and right and left grip strength was 28.6%, 35.7%, and 47.6%, respectively. The incidence was relatively lower than that of shift workers engaged in a discontinuous 8-h shift system we reported on previously. Working conditions allowing ambulance personnel to nap when not called for emergency (for > 4 h) might contribute to a stabilization of circadian rhythms. Furthermore, long nighttime ambulance service amounting to > 100 min was significantly associated with a high incidence of at least one prominent circadian period among oral temperature and right and left grip strength rhythms different from 24 h. In conclusion, 24-h shift work altered the characteristics of circadian rhythms of ambulance personnel; nighttime naps seemed to have a favorable effect on averting changes in circadian rhythms. PMID:8111871

  8. Hippocampal activity mediates the relationship between circadian activity rhythms and memory in older adults.

    PubMed

    Sherman, Stephanie M; Mumford, Jeanette A; Schnyer, David M

    2015-08-01

    Older adults experience parallel changes in sleep, circadian rhythms, and episodic memory. These processes appear to be linked such that disruptions in sleep contribute to deficits in memory. Although more variability in circadian patterns is a common feature of aging and predicts pathology, little is known about how alterations in circadian activity rhythms within older adults influence new episodic learning. Following 10 days of recording sleep-wake patterns using actigraphy, healthy older adults underwent fMRI while performing an associative memory task. The results revealed better associative memory was related to more consistent circadian activity rhythms, independent of total sleep time, sleep efficiency, and level of physical activity. Moreover, hippocampal activity during successful memory retrieval events was positively correlated with associative memory accuracy and circadian activity rhythm (CAR) consistency. We demonstrated that the link between consistent rhythms and associative memory performance was mediated by hippocampal activity. These findings provide novel insight into how the circadian rhythm of sleep-wake cycles are associated with memory in older adults and encourage further examination of circadian activity rhythms as a biomarker of cognitive functioning. PMID:26205911

  9. Environmental Progestins Progesterone and Drospirenone Alter the Circadian Rhythm Network in Zebrafish (Danio rerio).

    PubMed

    Zhao, Yanbin; Castiglioni, Sara; Fent, Karl

    2015-08-18

    Progestins alter hormone homeostasis and may result in reproductive effects in humans and animals. Thus far, studies in fish have focused on the hypothalamic-pituitary-gonadal (HPG)-axis and reproduction, but other effects have little been investigated. Here we report that progesterone (P4) and drospirenone (DRS) interfere with regulation of the circadian rhythm in fish. Breeding pairs of adult zebrafish were exposed to P4 and DRS at concentrations between 7 and 13?650 ng/L for 21 days. Transcriptional analysis revealed significant and dose-dependent alterations of the circadian rhythm network in the brain with little effects in the gonads. Significant alterations of many target transcripts occurred even at environmental relevant concentrations of 7 ng/L P4 and at 99 ng/L DRS. They were fully consistent with the well-described circadian rhythm negative/positive feedback loops. Transcriptional alterations of the circadian rhythm network were correlated with those in the HPG-Liver-axis. Fecundity was decreased at 742 (P4) and 2763 (DRS) ng/L. Dose-dependent alterations in the circadian rhythm network were also observed in F1 eleuthero-embryos. Our results suggest a potential target of environmental progestins, the circadian rhythm network, in addition to the adverse reproductive effects. Forthcoming studies should show whether the transcriptional alterations in circadian rhythm translate into physiological effects. PMID:26161812

  10. Barley Hv CIRCADIAN CLOCK ASSOCIATED 1 and Hv PHOTOPERIOD H1 are circadian regulators that can affect circadian rhythms in Arabidopsis

    E-print Network

    Kusakina, Jelena; Rutterford, Zoe; Cotter, Sean; Martí, María C.; Laurie, David; Greenland, Andrew; Hall, Anthony; Webb, Alex

    2015-06-01

    RESPONSE REGULATOR 7 (AtPRR7). This provides insight in to the circadian regulation of one of the major crop species of Northern Europe. Through a combination of physiological assays of circadian rhythms in barley and heterologous expression in wild type...

  11. Circadian rhythms in fatty acid-induced depression of myocardial contractile function: Potential mediation by the circadian clock within the cardiomyocyte

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythms in susceptibility to cardiovascular (CV) pathologic events (e.g., arrhythmias, myocardial infarction) are well established. These phenomena have been explained largely by diurnal variations in neurohumoral influences, such as sympathetic activity. Circadian clocks are intracellular...

  12. Circadian rhythm disturbances in patients with Alzheimer's disease: a review.

    PubMed

    Weldemichael, Dawit A; Grossberg, George T

    2010-01-01

    Circadian Rhythm Disturbances (CRDs) affect as many as a quarter of Alzheimer's disease (AD) patients during some stage of their illness. Alterations in the suprachiasmatic nucleus and melatonin secretion are the major factors linked with the cause of CRDs. As a result, the normal physiology of sleep, the biological clock, and core body temperature are affected. This paper systematically discusses some of the causative factors, typical symptoms, and treatment options for CRDs in patients with AD. This paper also emphasizes the implementation of behavioral and environmental therapies before embarking on medications to treat CRDs. Pharmacotherapeutic options are summarized to provide symptomatic benefits for the patient and relieve stress on their families and professional care providers. As of today, there are few studies relative to CRDs in AD. Large randomized trials are warranted to evaluate the effects of treatments such as bright light therapy and engaging activities in the reduction of CRDs in AD patients. PMID:20862344

  13. The Interplay of cis-Regulatory Elements Rules Circadian Rhythms in Mouse Liver

    PubMed Central

    Koren?i?, Anja; Bordyugov, Grigory; Košir, Rok; Rozman, Damjana; Goli?nik, Marko; Herzel, Hanspeter

    2012-01-01

    The mammalian circadian clock is driven by cell-autonomous transcriptional feedback loops that involve E-boxes, D-boxes, and ROR-elements. In peripheral organs, circadian rhythms are additionally affected by systemic factors. We show that intrinsic combinatorial gene regulation governs the liver clock. With a temporal resolution of 2 h, we measured the expression of 21 clock genes in mouse liver under constant darkness and equinoctial light-dark cycles. Based on these data and known transcription factor binding sites, we develop a six-variable gene regulatory network. The transcriptional feedback loops are represented by equations with time-delayed variables, which substantially simplifies modelling of intermediate protein dynamics. Our model accurately reproduces measured phases, amplitudes, and waveforms of clock genes. Analysis of the network reveals properties of the clock: overcritical delays generate oscillations; synergy of inhibition and activation enhances amplitudes; and combinatorial modulation of transcription controls the phases. The agreement of measurements and simulations suggests that the intrinsic gene regulatory network primarily determines the circadian clock in liver, whereas systemic cues such as light-dark cycles serve to fine-tune the rhythms. PMID:23144788

  14. Electrochemical Detection of Circadian Redox Rhythm in Cyanobacterial Cells via Extracellular Electron Transfer.

    PubMed

    Nishio, Koichi; Pornpitra, Tunanunkul; Izawa, Seiichiro; Nishiwaki-Ohkawa, Taeko; Kato, Souichiro; Hashimoto, Kazuhito; Nakanishi, Shuji

    2015-06-01

    Recent research on cellular circadian rhythms suggests that the coupling of transcription-translation feedback loops and intracellular redox oscillations is essential for robust circadian timekeeping. For clarification of the molecular mechanism underlying the circadian rhythm, methods that allow for the dynamic and simultaneous detection of transcription/translation and redox oscillations in living cells are needed. Herein, we report that the cyanobacterial circadian redox rhythm can be electrochemically detected based on extracellular electron transfer (EET), a process in which intracellular electrons are exchanged with an extracellular electrode. As the EET-based method is non-destructive, concurrent detection with transcription/translation rhythm using bioluminescent reporter strains becomes possible. An EET pathway that electrochemically connected the intracellular region of cyanobacterial cells with an extracellular electrode was constructed via a newly synthesized electron mediator with cell membrane permeability. In the presence of the mediator, the open circuit potential of the culture medium exhibited temperature-compensated rhythm with approximately 24 h periodicity. Importantly, such circadian rhythm of the open circuit potential was not observed in the absence of the electron mediator, indicating that the EET process conveys the dynamic information regarding the intracellular redox state to the extracellular electrode. These findings represent the first direct demonstration of the intracellular circadian redox rhythm of cyanobacterial cells. PMID:25975263

  15. Neurospora circadian rhythms in space - A reexamination of the endogenous-exogenous question

    NASA Technical Reports Server (NTRS)

    Sulzman, F. M.; Ellman, D.; Wassmer, G.; Fuller, C. A.; Moore-Ede, M.

    1984-01-01

    To test the functioning of circadian rhythms removed from periodicities of the earth's 24-hour rotation, the conidiation rhythm of the fungus Neurospora crassa was monitored in constant darkness during spaceflight. The free-running period of the rhythm was the same in space as on the earth, but there was a marked reduction in the clarity of the rhythm, and apparent arrhythmicity in some tubes. At the current stage of analysis of the results there is insufficient evidence to determine whether the effect seen in space was related to removal from 24-hour periodicities and whether the circadian timekeeping mechanism, or merely its expression, was affected.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. Gravity and thermoregulation: metabolic changes and circadian rhythms

    NASA Technical Reports Server (NTRS)

    Robinson, E. L.; Fuller, C. A.

    2000-01-01

    Gravity appears to alter thermoregulation through changes in both the regulated level of body temperature and the rhythmic organization of temperature regulation. Gravity has been hypothesized to have an associated metabolic cost. Increased resting energy expenditure and dietary intake have been observed in animals during centrifuge experiments at hypergravity. Thus far, only animals have shown a corresponding reduction in metabolism in microgravity. Altered heat loss has been proposed as a response to altered gravitational environments, but remains documented only as changes in skin temperature. Changes in circadian timing, including the body temperature rhythm, have been shown in both hypergravity and microgravity, and probably contribute to alterations in sleep and performance. Changes in body temperature regulation may result from circadian disturbance, from the direct or indirect actions of gravity on the regulated temperature, or from changes in thermoregulatory effectors (heat production and heat loss) due to altered gravitational load and convective changes. To date, however, we have little data on the underlying thermoregulatory changes in altered gravity, and thus the precise mechanisms by which gravity alters temperature regulation remain largely unknown.

  18. Sleep and Circadian Rhythm Regulation in Early Parkinson Disease

    PubMed Central

    Nawarathna, Upekshani; Fisher, Kate; Shneerson, John M.; Reddy, Akhilesh B.; Barker, Roger A.

    2014-01-01

    IMPORTANCE Sleep disturbances are recognized as a common nonmotor complaint in Parkinson disease but their etiology is poorly understood. OBJECTIVE To define the sleep and circadian phenotype of patients with early-stage Parkinson disease. DESIGN, SETTING, AND PARTICIPANTS Initial assessment of sleep characteristics in a large population-representative incident Parkinson disease cohort (N=239) at the University of Cambridge, England, followed by further comprehensive case-control sleep assessments in a subgroup of these patients (n=30) and matched controls (n=15). MAIN OUTCOMES AND MEASURES Sleep diagnoses and sleep architecture based on polysomnography studies, actigraphy assessment, and 24-hour analyses of serum cortisol, melatonin, and peripheral clock gene expression (Bmal1, Per2, and Rev-Erb?). RESULTS Subjective sleep complaints were present in almost half of newly diagnosed patients and correlated significantly with poorer quality of life. Patients with Parkinson disease exhibited increased sleep latency (P = .04), reduced sleep efficiency (P = .008), and reduced rapid eye movement sleep (P = .02). In addition, there was a sustained elevation of serum cortisol levels, reduced circulating melatonin levels, and altered Bmal1 expression in patients with Parkinson disease compared with controls. CONCLUSIONS AND RELEVANCE Sleep dysfunction seen in early Parkinson disease may reflect a more fundamental pathology in the molecular clock underlying circadian rhythms. PMID:24687146

  19. Treatment of a Circadian Rhythm Disturbance in a 2-Year-Old Blind Child.

    ERIC Educational Resources Information Center

    Mindell, J. A.; And Others

    1996-01-01

    The use of sleep scheduling and a daytime routine for the treatment of circadian rhythm disorder was found helpful in decreasing a blind 2-year old's nighttime wake periods and daytime sleepiness. (DB)

  20. Circadian, or near-24-h, rhythms of biological processes that persist in the absence of environmental cues, have been

    E-print Network

    Beltz, Barbara S.

    3765 Circadian, or near-24-h, rhythms of biological processes that persist in the absence subjective dusk and a trough before subjective dawn. This persistent circadian rhythm in constant darkness. The molecular clocks that control these rhythms are highly conserved across a broad range of species (King et al

  1. Circadian rhythm characteristics of oral squamous cell carcinoma growth in an orthotopic xenograft model

    PubMed Central

    Zhao, Ningbo; Tang, Hong; Yang, Kai; Chen, Dan

    2013-01-01

    Background Recent studies show that circadian rhythm changes are closely related to the occurrence and development of various tumors, such as breast, liver, and prostate. However, there are significant differences in circadian rhythm between different tumors. At present, the circadian rhythm characteristics of oral cancer remain unknown. The purpose of this study is to investigate the circadian rhythm characteristics of the in vivo growth of oral squamous cell carcinoma (OSCC). Materials and methods Thirty-two nude mice were placed under 12-hour light/12-hour dark cycles. The human OSCC cell line BcaCD885 was inoculated in the cheek of nude mice. After 3 weeks, eight mice were sacrificed at four time points, including 4 hours after light onset (HALO), 10 HALO, 16 HALO, and 22 HALO, during a period of 24 hours. The volume of excised tumors was measured and the proliferative index (PI) and apoptotic index (AI) of tumor cells were determined by flow cytometry. A cosine analysis method was used to determine whether the tumor volume, PI, and AI obeyed a circadian rhythm. Results There was a significant circadian rhythm in the tumor volume and PI of OSCC cells. For the tumor volume, there were significant differences between the four time points. The peak and trough values of the tumor volume appeared at 3.23 HALO and 15.23 HALO, whereas the peak and trough values of PI appeared at 6.60 HALO and 18.16 HALO, respectively. However, there was no circadian rhythm in the AI of tumor cells, despite significant differences between the four time points. Conclusion This study demonstrates, for the first time, that the tumor volume and PI of in vivo growing OSCC undergo circadian rhythms. These results support the assertion that time factor should be considered in the occurrence, development, treatment, efficacy evaluation and pathophysiology of OSCC. PMID:23378773

  2. Rhythm and blues. Neurochemical, neuropharmacological and neuropsychological implications of a hypothesis of circadian rhythm dysfunction in the affective disorders.

    PubMed

    Healy, D

    1987-01-01

    Current views on the organisation and functions of the circadian rhythm system are outlined. Evidence is presented supportive of the notion that the pathophysiology of the affective disorders involves a disruption of circadian rhythms and that the primary locus of action of agents effective in the affective disorders is on the circadian rhythm system. Potential disruptions of this system are enumerated. Such a hypothesis, it is argued, might potentially unite the disparate neurochemical and neuroendocrinological findings emerging in both depression and mania. There are in addition neuropsychological and nosological implications of such a framework, which may help bridge the divide between molecular and behavioural approaches to research on the affective disorders which are outlined. PMID:3124158

  3. Non-Circadian Expression Masking Clock-Driven Weak Transcription Rhythms in U2OS Cells

    PubMed Central

    Hoffmann, Julia; Symul, Laura; Shostak, Anton; Fischer, Tamás; Naef, Felix; Brunner, Michael

    2014-01-01

    U2OS cells harbor a circadian clock but express only a few rhythmic genes in constant conditions. We identified 3040 binding sites of the circadian regulators BMAL1, CLOCK and CRY1 in the U2OS genome. Most binding sites even in promoters do not correlate with detectable rhythmic transcript levels. Luciferase fusions reveal that the circadian clock supports robust but low amplitude transcription rhythms of representative promoters. However, rhythmic transcription of these potentially clock-controlled genes is masked by non-circadian transcription that overwrites the weaker contribution of the clock in constant conditions. Our data suggest that U2OS cells harbor an intrinsically rather weak circadian oscillator. The oscillator has the potential to regulate a large number of genes. The contribution of circadian versus non-circadian transcription is dependent on the metabolic state of the cell and may determine the apparent complexity of the circadian transcriptome. PMID:25007071

  4. Circadian-Rhythm Sleep Disorders in Persons Who Are Totally Blind.

    ERIC Educational Resources Information Center

    Sack, R. L.; Blood, M. L.; Hughes, R. J.; Lewy, A. J.

    1998-01-01

    Discusses the diagnosis and management of "non-24-hour sleep-wake syndrome," a form of cyclic insomnia to which people who are totally blind are prone. Covered are incidence and clinical features, formal diagnostic criteria, the biological basis of circadian sleep disorders, circadian rhythms in blind people, pharmacological entrainment, and the…

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

    PubMed Central

    2011-01-01

    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 WT siblings. Conclusion Our data suggests that circadian rhythms can be initiated and maintained in the absence of SCN and other tissues in the ventral brain. However, the SCN may have a role in regulating the amplitude of rhythms when environmental cues are absent. This provides some of the first evidence that the SCN of teleosts is not essential for establishing circadian rhythms during development. Several SCN-independent circadian rhythms have also been found in mammalian species. Thus, zebrafish may serve as a model system for understanding how vertebrate embryos coordinate rhythms that are controlled by different circadian clocks. PMID:21232144

  6. Photocontrol of Dark Circadian Rhythms in Stomata of Phaseolus vulgaris L

    PubMed Central

    Holmes, M. Geoffrey; Klein, William H.

    1986-01-01

    Stomatal diffusion resistance in primary leaves of Phaseolus vulgaris L. which had been grown in light:dark cycles followed a marked circadian rhythm when the plants were transferred to continuous darkness. Reentrainment of the rhythm required more than one inductive change in photoperiod. The phasing of the rhythm of dark stomatal opening was contolled primarily by the light-on (dawn) signal, whereas the rhythm of dark closure was related to the light-off (dusk) signal. The evidence points to a dual control of the circadian clock in which a product of photosynthesis plays a major role. No evidence for phytochrome involvement in the phasing of the rhythm was found. An influence of phytochrome on the amplitude of the stomatal rhythm was observed in which removal of phytochrome-far-red absorbing form caused rapid damping. PMID:16665006

  7. Individual variation in circadian rhythms of sleep, EEG, temperature, and activity among monkeys - Implications for regulatory mechanisms.

    NASA Technical Reports Server (NTRS)

    Crowley, T. J.; Halberg, F.; Kripke, D. F.; Pegram, G. V.

    1971-01-01

    Investigation of circadian rhythms in a number of variables related to sleep, EEG, temperature, and motor activity in rhesus monkeys on an LD 12:12 schedule. Circadian rhythms were found to appear in each of 15 variables investigated. Statistical procedures assessed the variables for evidence of common regulation in these aspects of their circadian rhythms: acrophase (timing), amplitude (extent of change), and level (24-hr mean value). Patterns appearing in the data suggested that the circadian rhythms of certain variables are regulated in common. The circadian modulation of activity in the beta and sigma frequency bands of the EEG was correlated with statistical significance in acrophase, level, and amplitude. The delta frequency band appeared to be under circadian rhythm regulation distinct from that of the other bands. The circadian rhythm of REM stage sleep was like that of beta activity in level and amplitude. The data indicate that REM stage may share some common regulation of circadian timing with both stage 3-4 sleep and with temperature. Generally, however, the circadian rhythm of temperature appeared to bear little relation to the circadian rhythms of motor activity, EEG, or sleep.

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

    PubMed Central

    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

  9. Circadian rhythms synchronise intracellular calcium dynamics and ATP production for facilitating Arabidopsis pollen tube growth

    PubMed Central

    Yue, Xun; Gao, Xin-Qi; Zhang, Xian Sheng

    2015-01-01

    Experimental evidences support that the circadian rhythm regulates the transcription levels of genes encoding the enzymes involved in plant metabolism. However, there is no paper to refer the correlation of the circadian rhythms and the metabolic processes for facilitating pollen tube growth. In this study, we found that many central components of the circadian clock were highly enriched and specifically present in the in vivo grown Arabidopsis pollen tubes. Our analysis also identified the significant differentially expressed genes encoding co-expressed enzymes in the consecutive steps of fatty acid ?-oxidation II, pentose phosphate pathway (oxidative branch) and phosphatidic acid biosynthesis pathway in the in vivo grown Arabidopsis pollen tubes during pollination. Thus, it is implicated that the circadian rhythms of pollen tube may be adjusted and have a greater probability of the direct or indirect functional relationship with enhanced intracellular Ca2+ dynamics and ATP production for facilitating pollen tube growth in vivo. PMID:26039479

  10. Analysis of a Gene Regulatory Cascade Mediating Circadian Rhythm in Zebrafish

    PubMed Central

    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

  11. Bidirectional communication between sleep and circadian rhythms and its implications for depression: lessons from agomelatine.

    PubMed

    Pandi-Perumal, Seithikurippu R; Moscovitch, Adam; Srinivasan, Venkatramanujam; Spence, David Warren; Cardinali, Daniel P; Brown, Gregory M

    2009-08-01

    Depression is a family of complex and multifactorial illnesses that are characterized by disruptions in the functioning of a number of physiological, neuroendocrine and behavioral processes. Of these, sleep disturbance and circadian rhythm abnormalities constitute the most prevalent signs of depressive illness. Difficulty in falling asleep, decreases in total sleep time and sleep efficiency, early morning awakenings, and rapid eye movement sleep alterations are all commonly seen in depressed patients. Advances or delays in the phase of circadian rhythms have been documented in patients with major depressive disorder (MDD), bipolar disorder and patients with seasonal affective disorder (SAD). The disturbances in the amplitude and rhythm of melatonin secretion that occur in patients with depression resemble those seen in subjects with chronobiological disorders. The finding that insomnia and circadian rhythm abnormalities are prominent features in depression suggests that a close link exists between melatonin secretion disturbance and depressed mood. This inference has been further strengthened by the finding that agomelatine, a recently introduced melatonergic agent with a novel mechanism of action, has beneficial effects in patients with MDD, bipolar disorder or SAD. Among agomelatine's characteristics are a rapid onset of action and a pronounced effectiveness for improving sleep efficiency and correcting circadian rhythm abnormalities. Disruptions in melatonin secretion or availability may be the common factor, which underlies depressive disorder and its prominent signs and symptoms such as sleep and circadian rhythm abnormalities. PMID:19454302

  12. Comparison of hormone and electrolyte circadian rhythms in male and female humans

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.; Winget, C. M.; Goodwin, A. E.; Reilly, T.

    1977-01-01

    Circadian rhythm characteristics in healthy male and female humans were studied at 4-hour intervals for urine volume, cortisol, 5-hydroxyindoleacetic acid (5-HIAA), Na, K, Na/K ratios in the urine, as well as plasma cortisol. While plasma and urinary cortisol rhythms were very similar in both sexes, the described rhythms in urine volume, electrolyte, and 5-HIAA excretion differ for the two sexes. The results suggest that sex differences exist in the circadian patterns of important hormone and metabolic functions and that the internal synchrony of circadian rhythms differs for the two sexes. The results seem to indicate that the rhythmical secretion of cortisol does not account for the pattern of Na and K excretion.

  13. The social zeitgeber theory, circadian rhythms, and mood disorders: review and evaluation.

    PubMed

    Grandin, Louisa D; Alloy, Lauren B; Abramson, Lyn Y

    2006-10-01

    The social zeitgeber theory [Ehlers, C. L., Frank, E., & Kupfer, D. J. (1988). Social zeitgebers and biological rhythms. Archives of General Psychiatry, 45, 948-952] offers an explanation of how life events trigger depressive episodes. According to this theory, life stress leads to mood episodes by causing disruptions in individuals' social routines and, in turn, their biological circadian rhythms. In this article, we review the literature pertaining to the social zeitgeber theory, as well as evidence that this theory may be applied to (hypo)manic episodes. Given the limited data supporting the social zeitgeber theory to date, we also evaluate whether circadian rhythm disruptions are triggered by an internal mechanism, such as an abnormality in one's pacemaker (the suprachiasmatic nucleus; SCN). We review these two theories in an attempt to understand the potential causes of circadian rhythm disruptions and affective episodes in individuals with unipolar and bipolar disorders. We also propose several areas of future research. PMID:16904251

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

    PubMed

    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. PMID:23929553

  15. Simulation of Drosophila Circadian Oscillations, Mutations, and Light Responses by a Model with VRI, PDP-1, and CLK

    E-print Network

    Byrne, John H.

    , University of Houston, Houston, Texas ABSTRACT A model of Drosophila circadian rhythm generation could be tested in transgenic Drosophila. INTRODUCTION Circadian rhythms in physiology and behavior that represents the mechanisms of circadian transcriptional regulation as currently understood in Drosophila. Fig

  16. Circadian rhythm of aldosterone in dairy cattle during the summer

    NASA Astrophysics Data System (ADS)

    Aranas, T. J.; Roussel, J. D.; Seybt, S. H.

    1987-09-01

    Twelve Holstein heifers, pregnant from 120 150 days were used to study the circadian rhythm of aldosterone, cortisol, progesterone, sodium and potassium in dairy cattle during the summer in Louisiana. Cortisol was not significantly influenced by time (time 1 = 06.00 h). Aldosterone, sodium, potassium and progesterone changed significantly (P<.01) with time. Aldosterone peaked (116.5±17.2 pg/ml) at 08.00 h and then generally declined to 16.00 h (26.7±2.0 pg/ml). Sodium generally increased from 06.00 h (320.1±7.3 mg%) to 18.00 h (377.9±6.1 mg%), and then declined. Potassium generally increased from 06.00 h (20.9±0.5 mg%) to 22.00 h (23.0±0.3 mg%). Progesterone generally increased from 07.00 h (2.8±0.4 mg/ml) to 24.00 h (7.5±1.4 mg/ml). Aldosterone was significantly related to temperature associated with the time of the day samples were taken (r = 0.66, P<.02).

  17. [Circadian rhythm of skin temperature of children during puberty].

    PubMed

    Pronina, T S; Orlova, N I; Rybakov, V P

    2015-01-01

    Results of long-term research of becoming circadian rhythm of temperature (CRT) of human skin of shoulder during puberty are presented. For this purpose, 48-hour monitoring T at children, teenagers and mature young men and female from 8 till 22-th years with application of a method "Thermochron iButton" has been led. Age dynamics of mesor, reflecting process of becoming thermoregulation of organism during puberty, has wave character. The first wave with maximum T was observed at children of 10-11 years, second maximum T--at teenagers of 14-15 years. And at persons man's and female dynamics of mesor is synchronous, however, at girls from 8 till 17 years mesor authentically above. At adult people mesoris above at young men. Dynamics of amplitude CRT does not vary till 12-13 years, in 14-15 years at boys the size of amplitude decreases, and at girls increases. In 16-17 years at children amplitude sharply increases with the subsequent significant decrease by the period of a maturity (20-22 years). At boys, amplitude of CRT it is authentic more, than at girls, at adult people this parameter does not differ. At research of a cycle a dream-wakefulness periods in which changes daily thermoregulation are revealed: at boys in the age of 10-11 years, and at girls at 10-11 and in 16-17 years. During these periods T at night is above, than in the afternoon. PMID:26027336

  18. A Long Noncoding RNA Perturbs the Circadian Rhythm of Hepatoma Cells to Facilitate Hepatocarcinogenesis12

    PubMed Central

    Cui, Ming; Zheng, Minying; Sun, Baodi; Wang, Yue; Ye, Lihong; Zhang, Xiaodong

    2015-01-01

    Clock circadian regulator (CLOCK)/brain and muscle arnt-like protein-1 (BMAL1) complex governs the regulation of circadian rhythm through triggering periodic alterations of gene expression. However, the underlying mechanism of circadian clock disruption in hepatocellular carcinoma (HCC) remains unclear. Here, we report that a long noncoding RNA (lncRNA), highly upregulated in liver cancer (HULC), contributes to the perturbations in circadian rhythm of hepatoma cells. Our observations showed that HULC was able to heighten the expression levels of CLOCK and its downstream circadian oscillators, such as period circadian clock 1 and cryptochrome circadian clock 1, in hepatoma cells. Strikingly, HULC altered the expression pattern and prolonged the periodic expression of CLOCK in hepatoma cells. Mechanistically, the complementary base pairing between HULC and the 5' untranslated region of CLOCK mRNA underlay the HULC-modulated expression of CLOCK, and the mutants in the complementary region failed to achieve the event. Moreover, immunohistochemistry staining and quantitative real-time polymerase chain reaction validated that the levels of CLOCK were elevated in HCC tissues, and the expression levels of HULC were positively associated with those of CLOCK in clinical HCC samples. In functional experiments, our data exhibited that CLOCK was implicated in the HULC-accelerated proliferation of hepatoma cells in vitro and in vivo. Taken together, our data show that an lncRNA, HULC, is responsible for the perturbations in circadian rhythm through upregulating circadian oscillator CLOCK in hepatoma cells, resulting in the promotion of hepatocarcinogenesis. Thus, our finding provides new insights into the mechanism by which lncRNA accelerates hepatocarcinogenesis through disturbing circadian rhythm of HCC. PMID:25622901

  19. An ecdysone-responsive nuclear receptor regulates circadian rhythms in Drosophila

    PubMed Central

    Kumar, Shailesh; Chen, Dechun; Jang, Christopher; Nall, Alexandra; Zheng, Xiangzhong; Sehgal, Amita

    2014-01-01

    Summary Little is known about molecular links between circadian clocks and steroid hormone signaling although both are important for normal physiology. Here we report a circadian function for a nuclear receptor, Ecdysone Induced Protein 75 (Eip75/E75), which we identify through a gain-of-function screen for circadian genes in Drosophila melanogaster. Overexpression or knockdown of E75 in clock neurons disrupts rest:activity rhythms and dampens molecular oscillations. E75 represses expression of the gene encoding the transcriptional activator, CLOCK (CLK), and may also affect circadian output. PER inhibits the activity of E75 on the Clk promoter, thereby providing a mechanism for a previously proposed de-repressor effect of PER on Clk transcription. The ecdysone receptor is also expressed in central clock cells and manipulations of its expression produce effects similar to those of E75 on circadian rhythms. We find that E75 protects rhythms under stressful conditions, suggesting a function for steroid signaling in the maintenance of circadian rhythms in Drosophila. PMID:25511299

  20. Lighting, sleep and circadian rhythm: An intervention study in the intensive care unit.

    PubMed

    Engwall, Marie; Fridh, Isabell; Johansson, Lotta; Bergbom, Ingegerd; Lindahl, Berit

    2015-12-01

    Patients in an intensive care unit (ICU) may risk disruption of their circadian rhythm. In an intervention research project a cycled lighting system was set up in an ICU room to support patients' circadian rhythm. Part I aimed to compare experiences of the lighting environment in two rooms with different lighting environments by lighting experiences questionnaire. The results indicated differences in advantage for the patients in the intervention room (n=48), in perception of daytime brightness (p=0.004). In nighttime, greater lighting variation (p=0.005) was found in the ordinary room (n=52). Part II aimed to describe experiences of lighting in the room equipped with the cycled lighting environment. Patients (n=19) were interviewed and the results were presented in categories: "A dynamic lighting environment", "Impact of lighting on patients' sleep", "The impact of lighting/lights on circadian rhythm" and "The lighting calms". Most had experiences from sleep disorders and half had nightmares/sights and circadian rhythm disruption. Nearly all were pleased with the cycled lighting environment, which together with daylight supported their circadian rhythm. In night's actual lighting levels helped patients and staff to connect which engendered feelings of calm. PMID:26215384

  1. Disruption of Circadian Rhythms and Sleep in Critical Illness and its Impact on Innate Immunity.

    PubMed

    Dengler, Viola; Westphalen, Kristin; Koeppen, Michael

    2015-01-01

    The earth rotates on its axis around the sun, creating a day and night cycle, that caused the development of circadian rhythms. The circadian rhythm is primarily entrained by light, which is detected by the retina. Retinal ganglion cells project to a part of the hypothalamus termed suprachiasmatic nucleus. Here, we find the master molecular clock, composed of a transcription-translation-loop at its core. The master clock indirectly influences the innate immune system via different biological systems. Also, the master clock controls the peripheral clocks, which are present in innate immune cells. Here, circadian rhythm proteins influence the response of immune cells to pathogens. Furthermore, the master clock influences our sleep-pattern, the most important restorative physiological function. In critically ill patients the circadian rhythm is substantially altered, supporting a dysfunctional innate immune response. This review discusses recent basic science findings on the interaction of the circadian rhythm and the innate immune system. Furthermore we give an outlook on potential future therapeutic strategies. PMID:26144943

  2. Wheel-running activity modulates circadian organization and the daily rhythm of eating behavior

    PubMed Central

    Pendergast, Julie S.; Branecky, Katrina L.; Huang, Roya; Niswender, Kevin D.; Yamazaki, Shin

    2014-01-01

    Consumption of high-fat diet acutely alters the daily rhythm of eating behavior and circadian organization (the phase relationship between oscillators in central and peripheral tissues) in mice. Voluntary wheel-running activity counteracts the obesogenic effects of high-fat diet and also modulates circadian rhythms in mice. In this study, we sought to determine whether voluntary wheel-running activity could prevent the proximate effects of high-fat diet consumption on circadian organization and behavioral rhythms in mice. Mice were housed with locked or freely rotating running wheels and fed chow or high-fat diet for 1 week and rhythms of locomotor activity, eating behavior, and molecular timekeeping (PERIOD2::LUCIFERASE luminescence rhythms) in ex vivo tissues were measured. Wheel-running activity delayed the phase of the liver rhythm by 4 h in both chow- and high-fat diet-fed mice. The delayed liver phase was specific to wheel-running activity since an enriched environment without the running wheel did not alter the phase of the liver rhythm. In addition, wheel-running activity modulated the effect of high-fat diet consumption on the daily rhythm of eating behavior. While high-fat diet consumption caused eating events to be more evenly dispersed across the 24 h-day in both locked-wheel and wheel-running mice, the effect of high-fat diet was much less pronounced in wheel-running mice. Together these data demonstrate that wheel-running activity is a salient factor that modulates liver phase and eating behavior rhythms in both chow- and high-fat-diet fed mice. Wheel-running activity in mice is both a source of exercise and a self-motivating, rewarding behavior. Understanding the putative reward-related mechanisms whereby wheel-running activity alters circadian rhythms could have implications for human obesity since palatable food and exercise may modulate similar reward circuits. PMID:24624109

  3. Non-peptide oxytocin receptor ligands and hamster circadian wheel running rhythms.

    PubMed

    Gannon, Robert L

    2014-10-17

    The synchronization of circadian rhythms in sleep, endocrine and metabolic functions with the environmental light cycle is essential for health, and dysfunction of this synchrony is thought to play a part in the development of many neurological disorders. There is a demonstrable need to develop new therapeutics for the treatment of neurological disorders such as depression and schizophrenia, and oxytocin is currently being investigated for this purpose. There are no published reports describing activity of oxytocin receptor ligands on mammalian circadian rhythms and that, then, is the purpose of this study. Non-peptide oxytocin receptor ligands that cross the blood brain barrier were systemically injected in hamsters to determine their ability to modulate light-induced phase advances and delays of circadian wheel running rhythms. The oxytocin receptor agonist WAY267464 (10 mg/kg) inhibited light induced phase advances of wheel running rhythms by 55%, but had no effect on light-induced phase delays. In contrast, the oxytocin receptor antagonist WAY162720 (10 mg/kg) inhibited light-induced phase delays by nearly 75%, but had no effect on light-induced phase advances. Additionally, WAY162720 was able to antagonize the inhibitory effects of WAY267464 on light-induced phase advances. These results are consistent for a role of oxytocin in the phase-delaying effects of light on circadian activity rhythms early in the night. Therefore, oxytocin may prove to be useful in developing therapeutics for the treatment of mood disorders with a concomitant dysfunction in circadian rhythms. Investigators should also be cognizant that oxytocin ligands may negatively affect circadian rhythms during clinical trials for other conditions. PMID:25148710

  4. Melanopsin resets circadian rhythms in cells by inducing clock gene Period1

    NASA Astrophysics Data System (ADS)

    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.

  5. Development of Salivary Cortisol Circadian Rhythm and Reference Intervals in Full-Term Infants

    PubMed Central

    Ivars, Katrin; Nelson, Nina; Theodorsson, Annette; Theodorsson, Elvar; Ström, Jakob O.; Mörelius, Evalotte

    2015-01-01

    Background Cortisol concentrations in plasma display a circadian rhythm in adults and children older than one year. Earlier studies report divergent results regarding when cortisol circadian rhythm is established. The present study aims to investigate at what age infants develop a circadian rhythm, as well as the possible influences of behavioral regularity and daily life trauma on when the rhythm is established. Furthermore, we determine age-related reference intervals for cortisol concentrations in saliva during the first year of life. Methods 130 healthy full-term infants were included in a prospective, longitudinal study with saliva sampling on two consecutive days, in the morning (07:30-09:30), noon (10:00-12:00) and evening (19:30-21:30), each month from birth until the infant was twelve months old. Information about development of behavioral regularity and potential exposure to trauma was obtained from the parents through the Baby Behavior Questionnaire and the Life Incidence of Traumatic Events checklist. Results A significant group-level circadian rhythm of salivary cortisol secretion was established at one month, and remained throughout the first year of life, although there was considerable individual variability. No correlation was found between development of cortisol circadian rhythm and the results from either the Baby Behavior Questionnaire or the Life Incidence of Traumatic Events checklist. The study presents salivary cortisol reference intervals for infants during the first twelve months of life. Conclusions Cortisol circadian rhythm in infants is already established by one month of age, earlier than previous studies have shown. The current study also provides first year age-related reference intervals for salivary cortisol levels in healthy, full-term infants. PMID:26086734

  6. Development of the cortisol circadian rhythm in the light of stress early in life.

    PubMed

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

    2015-12-01

    The secretion of the stress hormone cortisol follows a diurnal circadian rhythm. There are indications that this rhythm is affected by stress early in life. This paper addresses the development of the cortisol circadian rhythm between 1 and 6 years of age, and the role of maternal stress and anxiety early in the child's life on this (developing) rhythm. Participants were 193 healthy mother-child dyads from a community sample. Self-reported maternal stress and anxiety and physiological stress (saliva cortisol), were assessed prenatally (gestational week 37). Postnatally, self-reported maternal stress and anxiety were measured at 3, 6, 12, 30, and 72 months. Saliva cortisol samples from the children were collected on two days (four times each day) at 12, 30, and 72 months of age. The total amount of cortisol during the day and the cortisol decline over the day were determined to indicate children's cortisol circadian rhythm. Multilevel analyses showed that the total amount of cortisol decreased between 1 and 6 years. Furthermore, more maternal pregnancy-specific stress was related to higher total amounts of cortisol in the child. Higher levels of early postnatal maternal anxiety were associated with flatter cortisol declines in children. Higher levels of early postnatal maternal daily hassles were associated with steeper child cortisol declines over the day. These results indicated developmental change in children's cortisol secretion from 1 to 6 years and associations between maternal stress and anxiety early in children's lives and children's cortisol circadian rhythm in early childhood. PMID:26352482

  7. Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson’s disease

    PubMed Central

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

    2014-01-01

    Importance Diurnal fluctuations of motor and non-motor symptoms and high prevalence of sleep/wake disturbances in Parkinson’s disease (PD) suggest a role of the circadian system in the modulation of these symptoms. Yet, surprisingly little is known regarding circadian function in PD, and whether circadian dysfunction is involved in the development of sleep/wake disturbances in PD. Objective The objective of this study was 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. Design A cross-sectional study, (2009–2012). Setting PD and Movement Disorders Center, Northwestern University, Chicago. Participants Twenty PD patients on stable dopaminergic therapy and 15 age-matched controls underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions. Main Outcome Measure(s) Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index (PSQI)) and daytime sleepiness (Epworth Sleepiness Scale (ESS)), circadian markers of the melatonin rhythm, including the amplitude, area-under-the-curve (AUC), and phase of the 24-hour rhythm. Results Participants with PD had a blunted circadian rhythms of melatonin secretion compared to controls; both the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD participants compared with controls (p<0.001). Markers of circadian phase were not significantly different between the two groups. Among PD participants, those with excessive daytime sleepiness (ESS score ?10) had a significantly lower amplitude of the melatonin rhythm and the 24-hour melatonin AUC compared with PD participants without excessive sleepiness (p=0.001). Disease duration, UPDRS scores, levodopa equivalent dose and global PSQI scores in the PD group were not significantly related to measures of the melatonin circadian rhythm. Conclusion and Relevance These results indicate that circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be further explored in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed bright light and exercise, might potentially serve as complementary therapies for the non-motor manifestations of PD. PMID:24566763

  8. Analysis of Circadian Rhythms in the Basal Filamentous Ascomycete Pyronema confluens

    PubMed Central

    Traeger, Stefanie; Nowrousian, Minou

    2015-01-01

    Many organisms use circadian clocks to adapt to daily changes in the environment. Major insights into the molecular mechanisms of circadian oscillators have been gained through studies of the model organism Neurospora crassa; however, little is known about molecular components of circadian clocks in other fungi. An important part of the N. crassa circadian clock is the frequency (frq) gene, homologs of which can be found in Sordariomycetes, Dothideomycetes, and Leotiomycetes, but not Eurotiomycetes. Recently, we identified a frq homolog in Pyronema confluens, a member of the early-diverging Pezizomycete lineage of filamentous ascomycetes. The P. confluens FRQ shares many conserved domains with the N. crassa FRQ. However, there is no known morphological phenotype showing overt circadian rhythmicity in P. confluens. To investigate whether a molecular clock is present, we analyzed frq transcription in constant darkness, and found circadian oscillation of frq with a peak in the subjective morning. This rhythm was temperature compensated. To identify additional clock-controlled genes, we performed RNA sequencing of two time points (subjective morning and evening). Circadian expression of two morning-specific genes was verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) over a full time course, whereas expression of two putative morning-specific and five putative evening-specific genes could not be verified as circadian. frq expression was synchronized, but not entrained by light. In summary, we have found evidence for two of the three main properties of circadian rhythms (free-running rhythm, temperature compensation) in P. confluens, suggesting that a circadian clock with rhythmically expressed frq is present in this basal filamentous ascomycete. PMID:26254031

  9. Disturbed mouse circadian rhythm before the Kobe EQ in 1995

    NASA Astrophysics Data System (ADS)

    Yokoi, Sayoko

    2013-04-01

    Legends of macro-anomalies before large earthquakes have been passed down for generations in Asia. Most of the statements on earthquake precursors are considered unreliable afterthoughts by traditional scientists. However, disturbed biological rhythms in mice were observed before the Kobe EQ in 1995 (Yokoi et al, 2003). The records of unusual mouse behavior before the earthquake were obtained to study biological clock at Institute for Protein Research, Osaka University. It is clarified that the disturbance was very rare phenomena statistically. Similar phenomenon was observed before the Wenchuan earthquake in 2008, too (Li et al, 2009). In the presentation, I will discuss the phenomena as one example of preseismic unusual animal behaviors.

  10. September 26, 2007 22:2 WSPC -Proceedings Trim Size: 9in x 6in agarwal EFFICIENT MULTISCALE SIMULATION OF CIRCADIAN RHYTHMS USING

    E-print Network

    Roychowdhury, Jaijeet

    SIMULATION OF CIRCADIAN RHYTHMS USING AUTOMATED PHASE MACROMODELLING TECHNIQUES SHATAM AGARWAL Indian jr@umn.edu Circadian rhythm mechanisms involve multi-scale interactions between endogenous DNA-extracted macromodels. 1. Introduction Circadian rhythms are amongst the most fundamental of physiological processes

  11. differentially control circadian rhythms and synchrony in clock neuronsi/oGABA and G Sara J. Aton, James E. Huettner, Martin Straume, and Erik D. Herzog

    E-print Network

    Huettner, James E.

    differentially control circadian rhythms and synchrony in clock neuronsi/oGABA and G Sara J. Aton, see: Notes: #12;GABA and Gi/o differentially control circadian rhythms and synchrony in clock neurons. GABAA and GABAB antagonism increased circadian peak firing rates and rhythm precision of cultured SCN

  12. Reduction of translation rate stabilizes circadian rhythm and reduces the magnitude of phase shift.

    PubMed

    Nakajima, Masato; Koinuma, Satoshi; Shigeyoshi, Yasufumi

    2015-08-14

    In the intracellular environment, the circadian oscillator is exposed to molecular noise. Nevertheless, cellular rhythms are robust and show almost constant period length for several weeks. To find which molecular processes modulate the stability, we examined the effects of a sublethal dose of inhibitors for processes in the molecular clock. Inhibition of PER1/2 phosphorylation by CKI?/? led to reduced amplitude and enhancement of damping, suggesting that inhibition of this process destabilized oscillation. In contrast, moderate inhibition of translation led to stabilization of the circadian oscillation. Moreover, inhibition of translation also reduced magnitude of phase shift. These results suggest that some specific molecular processes are crucial for stabilizing the circadian rhythm, and that the molecular clock may be stabilized by optimizing parameters of some crucial processes in the primary negative feedback loop. Moreover, our findings also suggested that rhythm stability is closely associated with phase stability against stimuli. PMID:26141234

  13. Controlling Circadian Rhythms by Dark-Pulse Perturbations in Arabidopsis thaliana

    PubMed Central

    Fukuda, Hirokazu; Murase, Haruhiko; Tokuda, Isao T.

    2013-01-01

    Plant circadian systems are composed of a large number of self-sustained cellular circadian oscillators. Although the light-dark signal in the natural environment is known to be the most powerful Zeitgeber for the entrainment of cellular oscillators, its effect is too strong to control the plant rhythm into various forms of synchrony. Here, we show that the application of pulse perturbations, i.e., short-term injections of darkness under constant light, provides a novel technique for controlling the synchronized behavior of plant rhythm in Arabidopsis thaliana. By destroying the synchronized cellular activities, circadian singularity was experimentally induced. The present technique is based upon the theory of phase oscillators, which does not require prior knowledge of the detailed dynamics of the plant system but only knowledge of its phase and amplitude responses to the pulse perturbation. Our approach can be applied to diverse problems of controlling biological rhythms in living systems. PMID:23524981

  14. Resetting of circadian melatonin and cortisol rhythms in humans by ordinary room light

    NASA Technical Reports Server (NTRS)

    Boivin, D. B.; Czeisler, C. A.

    1998-01-01

    The present study was designed to investigate whether a weak photic stimulus can reset the endogenous circadian rhythms of plasma melatonin and plasma cortisol in human subjects. A stimulus consisting of three cycles of 5 h exposures to ordinary room light (approximately 180 lux), centered 1.5 h after the endogenous temperature nadir, significantly phase-advanced the plasma melatonin rhythm in eight healthy young men compared with the phase delays observed in eight control subjects who underwent the same protocol but were exposed to darkness (p < or = 0.003). After light-induced phase advances, the circadian rhythms of plasma melatonin and plasma cortisol maintained stable temporal relationships with the endogenous core body temperature cycle, consistent with the conclusion that exposure to ordinary indoor room light had shifted a master circadian pacemaker.

  15. A circadian rhythm in optic nerve impulses from an isolated eye in darkness.

    NASA Technical Reports Server (NTRS)

    Jacklet, J. W.

    1971-01-01

    Study of the circadian rhythm of optic nerve potentials recorded from the isolated eye of the sea hare Aplysia. The optic nerve activity in constant conditions is found to be clearly circadian and to obey the circadian rule for diurnal animals. In addition, the period length depends on the in vitro culturing solution. In seawater it is about 22 hr, but in culture medium it is 27 hr. The rhythm can be completely phase-shifted in one trial if the phase of the LD 12:12 Zeitgeber is advanced or delayed 4 hr. The rhythm in one eye can be phase-shifted in vivo independently of the other eye and in vitro independently of the rest of the animal. Thus, in the animal, the eye oscillators are, at most, only slightly influenced by each other or by other oscillators in the animal.

  16. Adaptation of sleep and circadian rhythms to the Antarctic summer - A question of zeitgeber strength

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.; Macdonald, John A.; Montgomery, John C.; Paulin, Michael G.

    1991-01-01

    Adaptation of sleep and circadian rhythms was examined in three temperate zone dwellers arriving in Antarctica during summer. Rectal temperature, wrist activity, and heart rate were monitored continuously, sleep timing and quality noted on awakening, and mood and fatigue rated every 2 h while awake. Sleep was poorer in 2/3 subjects in Antarctica, where all subjects reported more difficulty rising. Sleep occurred at the same clock times in New Zealand and Antarctica, however, the rhythms of temperature, activity, and heart rate underwent a delay of about of 2 h. The subject with the most Antarctic experience had the least difficulty adapting to sleeping during constant daylight. The subject with the most delayed circadian rhythms had the most difficulty. The delay in the circadian system with respect to sleep and clock time is hypothesized to be due to differences in zeitgeber strength and/or zeitgeber exposure between Antarctica and New Zealand.

  17. Therapeutic strategies for circadian rhythm and sleep disturbances in Huntington disease.

    PubMed

    van Wamelen, Daniel J; Roos, Raymund Ac; Aziz, Nasir A

    2015-12-01

    Aside from the well-known motor, cognitive and psychiatric signs and symptoms, Huntington disease (HD) is also frequently complicated by circadian rhythm and sleep disturbances. Despite the observation that these disturbances often precede motor onset and have a high prevalence, no studies are available in HD patients which assess potential treatments. In this review, we will briefly outline the nature of circadian rhythm and sleep disturbances in HD and subsequently focus on potential treatments based on findings in other neurodegenerative diseases with similarities to HD, such as Parkinson and Alzheimer disease. The most promising treatment options to date for circadian rhythm and sleep disruption in HD include melatonin (agonists) and bright light therapy, although further corroboration in clinical trials is warranted. PMID:26621387

  18. The possible long-term effects of early-life circadian rhythm disturbance on social behavior.

    PubMed

    Kohyama, Jun

    2014-07-01

    Sleep loss impairs brain function. As late sleep onset can reduce sleep, this sleep/circadian rhythm disturbance may cause brain impairment. Specific data on the long-term effects of sleep/circadian rhythm disturbance on subsequent brain function are lacking. Japan, a sleep-deprived society from infancy to adulthood, provides an ideal platform to investigate the association of these disturbances in early life with subsequent functioning. In this article, several current problematic behaviors among youth in Japan (dropping out from high school, school absenteeism, early resignation from employment, and suicide) are discussed in relation to early life sleep/circadian rhythm patterns. We hypothesize that daily habits of modern society during early stages of life produce unfavorable effects on brain function resulting in problematic behaviors in subsequent years. PMID:24902476

  19. [Circadian rhythms and temperature homeostasis in monkeys during a flight on the Kosmos 1514 biosatellite

    NASA Technical Reports Server (NTRS)

    Klimovitskui, V. Ia; Alpatov, A. M.; Salzman, F. M.; Fuller, C. A.; Moore-Ede, M. S.

    1987-01-01

    In the course of a 5-day space flight of two rhesus-monkeys the following parameters were recorded at an interval of 16 min: core body temperature (Tc), skin temperature (Ts), and motor activity (MA). The telemetric Tc sensor was implanted subcutaneously in the right axilla, Ts thermistor was attached to the right ankle, and the MA piezotape was fixed to the inner side of the vest. Circadian rhythms of Tc varied with a period of 24 hours in one monkey and 25 hours in the other. The daily Tc decreased on the average by 0.5 degrees C, Ts fell immediately after launch and remained close to the lower limit throughout the flight. The Ts amplitude decreased 5-fold. Phases of the circadian rhythms of Ts changed and circadian rhythms of MA remained unchanged and equal to 24 hours.

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

    PubMed Central

    Salgado-Delgado, Roberto; Tapia Osorio, Araceli; Saderi, Nadia; Escobar, Carolina

    2011-01-01

    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. PMID:21845223

  1. Circadian regulation gene polymorphisms are associated with sleep disruption and duration, and circadian phase and rhythm in adults with HIV.

    PubMed

    Lee, Kathryn A; Gay, Caryl; Byun, Eeeseung; Lerdal, Anners; Pullinger, Clive R; Aouizerat, Bradley E

    2015-11-01

    Genes involved in circadian regulation, such as circadian locomotor output cycles kaput [CLOCK], cryptochrome [CRY1] and period [PER], have been associated with sleep outcomes in prior animal and human research. However, it is unclear whether polymorphisms in these genes are associated with the sleep disturbances commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Thus, the purpose of this study was to describe polymorphisms in selected circadian genes that are associated with sleep duration or disruption as well as the sleep-wake rhythm strength and phase timing among adults living with HIV/AIDS. A convenience sample of 289 adults with HIV/AIDS was recruited from HIV clinics and community sites in the San Francisco Bay Area. A wrist actigraph was worn for 72?h on weekdays to estimate sleep duration or total sleep time (TST), sleep disruption or percentage of wake after sleep onset (WASO) and several circadian rhythm parameters: mesor, amplitude, the ratio of mesor to amplitude (circadian quotient), and 24-h autocorrelation. Circadian phase measures included clock time for peak activity (acrophase) from actigraphy movement data, and bed time and final wake time from actigraphy and self-report. Genotyping was conducted for polymorphisms in five candidate genes involved in circadian regulation: CLOCK, CRY1, PER1, PER2 and PER3. Demographic and clinical variables were evaluated as potential covariates. Interactions between genotype and HIV variables (i.e. viral load, years since HIV diagnosis) were also evaluated. Controlling for potentially confounding variables (e.g. race, gender, CD4+ T-cell count, waist circumference, medication use, smoking and depressive symptoms), CLOCK was associated with WASO, 24-h autocorrelation and objectively-measured bed time; CRY1 was associated with circadian quotient; PER1 was associated with mesor and self-reported habitual wake time; PER2 was associated with TST, mesor, circadian quotient, 24-h autocorrelation and bed and wake times; PER3 was associated with amplitude, 24-h autocorrelation, acrophase and bed and wake times. Most of the observed associations involved a significant interaction between genotype and HIV. In this chronic illness population, polymorphisms in several circadian genes were associated with measures of sleep disruption and timing. These findings extend the evidence for an association between genetic variability in circadian regulation and sleep outcomes to include the sleep-wake patterns experienced by adults living with HIV/AIDS. These results provide direction for future intervention research related to circadian sleep-wake behavior patterns. PMID:26512752

  2. Assaying Locomotor Activity to Study Circadian Rhythms and Sleep Parameters in Drosophila

    PubMed Central

    Chiu, Joanna C.; Low, Kwang Huei; Pike, Douglas H.; Yildirim, Evrim; Edery, Isaac

    2010-01-01

    Most life forms exhibit daily rhythms in cellular, physiological and behavioral phenomena that are driven by endogenous circadian (?24 hr) pacemakers or clocks. Malfunctions in the human circadian system are associated with numerous diseases or disorders. Much progress towards our understanding of the mechanisms underlying circadian rhythms has emerged from genetic screens whereby an easily measured behavioral rhythm is used as a read-out of clock function. Studies using Drosophila have made seminal contributions to our understanding of the cellular and biochemical bases underlying circadian rhythms. The standard circadian behavioral read-out measured in Drosophila is locomotor activity. In general, the monitoring system involves specially designed devices that can measure the locomotor movement of Drosophila. These devices are housed in environmentally controlled incubators located in a darkroom and are based on using the interruption of a beam of infrared light to record the locomotor activity of individual flies contained inside small tubes. When measured over many days, Drosophila exhibit daily cycles of activity and inactivity, a behavioral rhythm that is governed by the animal's endogenous circadian system. The overall procedure has been simplified with the advent of commercially available locomotor activity monitoring devices and the development of software programs for data analysis. We use the system from Trikinetics Inc., which is the procedure described here and is currently the most popular system used worldwide. More recently, the same monitoring devices have been used to study sleep behavior in Drosophila. Because the daily wake-sleep cycles of many flies can be measured simultaneously and only 1 to 2 weeks worth of continuous locomotor activity data is usually sufficient, this system is ideal for large-scale screens to identify Drosophila manifesting altered circadian or sleep properties. PMID:20972399

  3. Circadian rhythms. Atomic-scale origins of slowness in the cyanobacterial circadian clock.

    PubMed

    Abe, Jun; Hiyama, Takuya B; Mukaiyama, Atsushi; Son, Seyoung; Mori, Toshifumi; Saito, Shinji; Osako, Masato; Wolanin, Julie; Yamashita, Eiki; Kondo, Takao; Akiyama, Shuji

    2015-07-17

    Circadian clocks generate slow and ordered cellular dynamics but consist of fast-moving bio-macromolecules; consequently, the origins of the overall slowness remain unclear. We identified the adenosine triphosphate (ATP) catalytic region [adenosine triphosphatase (ATPase)] in the amino-terminal half of the clock protein KaiC as the minimal pacemaker that controls the in vivo frequency of the cyanobacterial clock. Crystal structures of the ATPase revealed that the slowness of this ATPase arises from sequestration of a lytic water molecule in an unfavorable position and coupling of ATP hydrolysis to a peptide isomerization with high activation energy. The slow ATPase is coupled with another ATPase catalyzing autodephosphorylation in the carboxyl-terminal half of KaiC, yielding the circadian response frequency of intermolecular interactions with other clock-related proteins that influences the transcription and translation cycle. PMID:26113637

  4. Self-arrangement of cellular circadian rhythms through phase-resetting in plant roots

    NASA Astrophysics Data System (ADS)

    Fukuda, Hirokazu; Ukai, Kazuya; Oyama, Tokitaka

    2012-10-01

    We discovered a striped pattern of gene expression with circadian rhythms in growing plant roots using bioluminescent imaging of gene expression. Our experimental analysis revealed that the stripe wave in the bioluminescent image originated at the root tip and was caused by a continuous phase resetting of circadian oscillations. Some complex stripe waves containing arrhythmic regions were also observed. We succeeded in describing the formation mechanisms of these patterns using a growing phase oscillator network with a phase-resetting boundary condition.

  5. Circadian rhythms of crawling and swimming in the nudibranch mollusc Melibe leonina.

    PubMed

    Newcomb, James M; Kirouac, Lauren E; Naimie, Amanda A; Bixby, Kimberly A; Lee, Colin; Malanga, Stephanie; Raubach, Maureen; Watson, Winsor H

    2014-12-01

    Daily rhythms of activity driven by circadian clocks are expressed by many organisms, including molluscs. We initiated this study, with the nudibranch Melibe leonina, with four goals in mind: (1) determine which behaviors are expressed with a daily rhythm; (2) investigate which of these rhythmic behaviors are controlled by a circadian clock; (3) determine if a circadian clock is associated with the eyes or optic ganglia of Melibe, as it is in several other gastropods; and (4) test the hypothesis that Melibe can use extraocular photoreceptors to synchronize its daily rhythms to natural light-dark cycles. To address these goals, we analyzed the behavior of 55 animals exposed to either artificial or natural light-dark cycles, followed by constant darkness. We also repeated this experiment using 10 animals that had their eyes removed. Individuals did not express daily rhythms of feeding, but they swam and crawled more at night. This pattern of locomotion persisted in constant darkness, indicating the presence of a circadian clock. Eyeless animals also expressed a daily rhythm of locomotion, with more locomotion at night. The fact that eyeless animals synchronized their locomotion to the light-dark cycle suggests that they can detect light using extraocular photoreceptors. However, in constant darkness, these rhythms deteriorated, suggesting that the clock neurons that influence locomotion may be located in, or near, the eyes. Thus, locomotion in Melibe appears to be influenced by both ocular and extraocular photoreceptors, although the former appear to have a greater influence on the expression of circadian rhythms. PMID:25572214

  6. Circadian rhythm of leaf movement in Capsicum annuum observed during centrifugation

    NASA Technical Reports Server (NTRS)

    Chapman, D. K.; Brown, A. H.; Dahl, A. O.

    1975-01-01

    Plant circadian rhythms of leaf movement in seedlings of the pepper plant (Capsicum annuum L., var. Yolo Wonder) were observed at different g-levels by means of a centrifuge. Except for the chronically imposed g-force all environmental conditions to which the plants were exposed were held constant. The circadian period, rate of change of amplitude of successive oscillations, symmetry of the cycles, and phase of the rhythm all were found not to be significantly correlated with the magnitude of the sustained g-force.

  7. Dim Light at Night Disrupts Molecular Circadian Rhythms and Affects Metabolism

    PubMed Central

    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

  8. Cortisol-mediated synchronization of circadian rhythm in urinary potassium excretion

    NASA Technical Reports Server (NTRS)

    Moore-Ede, M. C.; Schmelzer, W. S.; Kass, D. A.; Herd, J. A.

    1977-01-01

    Conscious chair-acclimatized squirrel monkeys (Saimiri sciureus) studied with lights on (600 lx) from 0800 to 2000 hr daily (LD 12:12) display a prominent circadian rhythm in renal potassium excretion. The characteristics of this rhythm were reproduced in adrenalectomized monkeys by infusing 5 mg cortisol and 0.001 mg aldosterone, or 5 mg cortisol alone, between 0800 and 0900 kr daily. When the timing of cortisol administration (with or without aldosterone) was phase-delayed by 8 hr, the urinary potassium rhythm resynchronized by 80% of the cortisol phase shift, but only after a transient response lasting 3-4 days. With the same daily dose of adrenal steroids given as a continuous infusion throughout each 24 hr, urinary potassium excretion showed free-running oscillations no longer synchronized to the light-dark cycle. These results indicate that the circadian rhythm of plasma cortisol concentration acts as an internal mediator in the circadian timing system, synchronizing a potentially autonomous oscillation in renal potassium excretion to environmental time cues and to other circadian rhythms within the animal.

  9. No time to lose: workshop on circadian rhythms and metabolic disease

    PubMed Central

    Silva, Corinne M.; Sato, Sheryl; Margolis, Ronald N.

    2010-01-01

    The objective of the workshop was to gain a better understanding of the link between circadian rhythms and human health and disease. The impacts of circadian rhythms on metabolic gene regulation, as well as the effect of nutrient uptake and balance on the molecular components of the clock, were discussed. Topics included the neural circuitry underlying the central clock; the effect of the environment and diet on the central clock as well as peripheral, tissue-specific clocks; and the transcriptional, post-transcriptional, and post-translational (e.g., epigenomic) mechanisms through which these signals are transduced. Evidence presented during the meeting demonstrated that circadian rhythms and metabolism are intricately linked, and that disruption in these rhythms have profound consequences—many times leading to metabolic disease. The mechanisms by which circadian rhythms are maintained and the cross-talk with metabolic signaling are just beginning to be elucidated. However, the interactions between these fields and the knowledge learned will clearly have a profound impact on our understanding of metabolic disease and lead to novel therapeutic approaches in the future PMID:20634312

  10. Circadian foraging rhythms of bumblebees monitored by radio-frequency identification.

    PubMed

    Jürgen Stelzer, Ralph; Stanewsky, Ralf; Chittka, Lars

    2010-08-01

    Circadian clocks enable organisms to anticipate changes of environmental conditions. In social insects, the colony as a superorganism has a foraging rhythm aligned to the diurnal patterns of resource availability. Within this colony rhythm, the diurnal patterns of individuals are embedded, and various tasks within the colony are performed at different times by different individuals to best serve the colony as a whole. Recent studies have shown that social cues influence the traits of the circadian clock in social insects, but keeping track of the activity of individual workers is not an easy task. Here the authors use fully automatic radio-frequency identification (RFID) to analyze the circadian rhythms of bumblebee foragers (Bombus terrestris) in the normal social context of their nest. They monitored their foraging patterns under different light conditions in the laboratory, including light:dark cycles (LD) as well as constant darkness (DD) and constant light conditions (LL). Their results show that the majority of bumblebee foragers exhibit robust circadian rhythms in LD under laboratory conditions, while they show free-running rhythms both in DD and LL, with free-running periods being significantly shorter in LL conditions. The authors also found that bumblebee workers show an increased level of arrhythmic activity ("death dance") in the hours or days before their death. PMID:20679495

  11. Comparison of synchronization of primate circadian rhythms by light and food

    NASA Technical Reports Server (NTRS)

    Sulzman, F. M.; Fuller, C. A.; Moore-Ede, M. C.

    1978-01-01

    It is a well-documented fact that cycles of light and dark (LD) are the major entraining agent or 'zeitgeber' for circadian rhythms and that cycles of eating and fasting (EF) are capable of synchronizing a few circadian rhythms in the squirrel monkey. In this paper, by contrasting how these rhythms are timed by LD and EF cycles, the differential coupling to the oscillating system within adult male squirrel monkeys is examined. The variables measured are the rhythms of drinking, colonic temperature, and urinary potassium and water excretion. Attention is given to a comparison of the reproducibility of the averaged waveforms of the rhythms, the stability of the timing of a phase reference point, and the rate of resynchronization of these rhythms following an abrupt 8-hr phase delay in the zeitgeber. It is shown that the colonic temperature rhythm is more tightly controlled by LD than EF cycles, and that the drinking and urinary rhythms are more tightly coupled to EF than LD cycles.

  12. Modulation of metabolic and clock gene mRNA rhythms by pineal and retinal circadian oscillators.

    PubMed

    Karaganis, Stephen P; Bartell, Paul A; Shende, Vikram R; Moore, Ashli F; Cassone, Vincent M

    2009-04-01

    Avian circadian organization involves interactions between three neural pacemakers: the suprachiasmatic nuclei (SCN), pineal, and retina. Each of these structures is linked within a neuroendocrine loop to influence downstream processes and peripheral oscillations. However, the contribution of each structure to drive or synchronize peripheral oscillators or circadian outputs in avian species is largely unknown. To explore these interactions in the chick, we measured 2-deoxy[(14)C]-glucose (2DG) uptake and mRNA expression of the chick clock genes bmal1, cry1, and per3 in three brain areas and in two peripheral organs in chicks that underwent pinealectomy, enucleation, or sham surgery. We found that 2DG uptake rhythms damp under constant darkness in intact animals, while clock gene mRNA levels continue to cycle, demonstrating that metabolic rhythms are not directly driven by clock gene transcription. Moreover, 2DG rhythms are not phase-locked to rhythms of clock gene mRNA. However, pinealectomy and enucleation had similar disruptive effects on both metabolic and clock gene rhythms, suggesting that both of these oscillators act similarly to reinforce molecular and physiological rhythms in the chicken. Finally, we show that the relative phasing of at least one clock gene, cry1, varies between central and peripheral oscillators in a tissue specific manner. These data point to a complex, differential orchestration of central and peripheral oscillators in the chick, and, importantly, indicate a disconnect between canonical clock gene regulation and circadian control of metabolism. PMID:19136000

  13. Influence of the circadian rhythm in cell division on radiation-induced mitotic delay in vivo

    SciTech Connect

    Rubin, N.H.

    1982-01-01

    Mitotic delay is described as a classical response to radiation; however, circadian rhythmicity in cell division in vivo has not been considered by many authors. The present study investigated the relation between fluctuations reported as mitotic delay and recovery in vivo and circadian oscillations in mitotic index in mouse corneal epithelium. One aspect involved single doses (approximately 600 rad) given to mice at different circadian stages. The normal circadian rhythm in cell division was never obliterated. Inhibition of mitosis was evident but unpredictable, ranging from 6 to 15 hr after irradiation. Recovery was evident only during the daily increase in mitotic index of controls. The classical interpretation of recovery from mitotic delay may be in an in vitro phenomenon not reflecting in vivo responses, which are apparently strongly circadian stage dependent. The second portion of the study demonstrated a dose-response effect on length of mitotic delay and, to a lesser extent, degree of recovery.

  14. Changes in Circadian Rhythms during Puberty in Rattus Norvegicus: Developmental Time Course and Gonadal Dependency

    PubMed Central

    Hagenauer, Megan Hastings; King, Andrea F.; Possidente, Bernard; McGinnis, Marilyn Y.; Lumia, Augustus R.; Peckham, Elizabeth M.; Lee, Theresa M.

    2011-01-01

    During puberty, humans develop a later chronotype, exhibiting a phase-delayed daily rest/activity rhythm. The purpose of this study was to determine: 1) whether similar changes in chronotype occur during puberty in a laboratory rodent species, 2) whether these changes are due to pubertal hormones affecting the circadian timekeeping system. We tracked the phasing and distribution of wheel-running activity rhythms during post-weaning development in rats that were gonadectomized before puberty or left intact. We found that intact peripubertal rats had activity rhythms that were phase-delayed relative to adults. Young rats also exhibited a bimodal nocturnal activity distribution. As puberty progressed, bimodality diminished and late-night activity phase-advanced until it consolidated with early-night activity. By late puberty, intact rats showed a strong, unimodal rhythm that peaked at the beginning of the night. These pubertal changes in circadian phase were more pronounced in males than females. Increases in gonadal hormones during puberty partially accounted for these changes, as rats that were gonadectomized before puberty demonstrated smaller phase changes than intact rats and maintained ultradian rhythms into adulthood. We investigated the role of photic entrainment by comparing circadian development under constant and entrained conditions. We found that the period(?) of free-running rhythms developed sex differences during puberty. These changes in ? did not account for pubertal changes in entrained circadian phase, as the consolidation of activity at the beginning of the subjective night persisted under constant conditions in both sexes. We conclude that the circadian system continues to develop in a hormone-sensitive manner during puberty. PMID:21397604

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

    PubMed Central

    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

  16. Circadian regulation of prion protein messenger RNA in the rat forebrain: a widespread and synchronous rhythm.

    PubMed

    Cagampang, F R; Whatley, S A; Mitchell, A L; Powell, J F; Campbell, I C; Coen, C W

    1999-01-01

    Although the expression of the normal prion protein in the host is critical to the development of transmissible spongiform encephalopathies, the physiological role of this protein and the processes regulating its expression remain obscure. We now report that the messenger RNA for the prion protein is regulated in the rat brain in a marked circadian manner not only in the suprachiasmatic nuclei, the principal site for the generation of mammalian circadian rhythms, but also in other forebrain regions. The data show a remarkable consistency in the concurrence of a single peak of prion protein messenger RNA at each of the sites early in the animal's phase of increased locomotor activity; behavioural arousal does not, however, appear to affect this expression. We believe this to be the first study demonstrating that the expression of prion protein messenger RNA can change over a relatively short period in vivo. The results are discussed with reference to the range of recently discovered "clock-related" transcripts which also have widespread tissue expression; these include the messenger RNAs for D-box binding protein and thyroid embryonic factor, transcription factors which bind to the prion protein promoter. PMID:10391428

  17. CIRCADIAN RHYTHMS OF FEEDING, OVIPOSITION, AND EMERGENCE OF THE BOLL WEEVIL (COLEOPTERA: CURCULIONIDAE)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythm of feeding, oviposition, and emergence of boll weevil adults were determined at 5 different photophases (24, 14, 12, 10 and 0 hours) and a constant 27 deg C temperature, 65% RH in the laboratory. Squares from petri dishes, where they were exposed to boll weevil females, were remove...

  18. A Comparative Study of Circadian Rhythm Functioning and Sleep in People with Asperger Syndrome

    ERIC Educational Resources Information Center

    Hare, Dougal Julian; Jones, Steven; Evershed, Kate

    2006-01-01

    The circadian rhythm functioning and sleep patterns of 10 adults with Asperger syndrome were investigated using actigraphy. When compared with data from neurotypical adults, both statistical and clinically significant differences were found between the two groups, with the adults with Asperger syndrome showing marked abnormalities in both the…

  19. Urinary Cortisol Circadian Rhythm in a Group of High-Functioning Children with Autism.

    ERIC Educational Resources Information Center

    Richdale, Amanda L.; Prior, Margot R.

    1992-01-01

    This study found no evidence for abnormal temporal placement of the basal urinary cortisol circadian rhythm in a group of 18 high-functioning children (ages 4-14) with autism. There was a tendency toward cortisol hypersecretion during the day, predominantly in autistic children who were integrated into the normal school system. (Author/JDD)

  20. The Suprachiasmatic Nucleus Is Essential for Circadian Body Temperature Rhythms in Hibernating Ground Squirrels

    E-print Network

    Zucker, Irving

    The Suprachiasmatic Nucleus Is Essential for Circadian Body Temperature Rhythms in Hibernating in constant light, suggest that light can reach the retina of hibernating ground squirrels maintained in the laboratory and affect hibernation via an SCN-independent mechanism. Key words: suprachiasmatic nucleus

  1. Darwin, Earthworms & Circadian Rhythms: A Fertile Field for Science Fair Experiments

    ERIC Educational Resources Information Center

    Burns, John T.; Scurti, Paul J.; Furda, Amy M.

    2009-01-01

    This article discusses why the study of earthworms has fascinated many scientists, and why earthworms make ideal experimental animals for students to test in the laboratory. Although earthworms may appear to be primitive, they are governed by both circadian and seasonal rhythms, just as more advanced organisms are. They possess an intelligence…

  2. New light on an old paradox: Site-dependent effects of carbachol on circadian rhythms

    E-print Network

    Gillette, Martha U.

    resetting at night, similar to nocturnal light exposure. However, the retinohypothalamic tract connecting slice, cholinergic stimulation during subjective night did not cause the light-like response, but ratherNew light on an old paradox: Site-dependent effects of carbachol on circadian rhythms Gordon F

  3. Maternal obesity and post-natal high fat diet disrupt hepatic circadian rhythm in rat offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Offspring of obese (Ob) rat dams gain greater body wt and fat mass when fed high-fat diet (HFD) as compared to controls. Alterations of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver. We sought to determine if maternal obesity (MOb) leads to p...

  4. Circadian rhythms and mood regulation: insights from pre-clinical models.

    PubMed

    McClung, Colleen A

    2011-09-01

    Affective disorders such as major depression, bipolar disorder, and seasonal affective disorder are associated with major disruptions in circadian rhythms. Indeed, altered sleep/wake cycles are a critical feature for diagnosis in the DSM IV and several of the therapies used to treat these disorders have profound effects on rhythm length and stabilization in human populations. Furthermore, multiple human genetic studies have identified polymorphisms in specific circadian genes associated with these disorders. Thus, there appears to be a strong association between the circadian system and mood regulation, although the mechanisms that underlie this association are unclear. Recently, a number of studies in animal models have begun to shed light on the complex interactions between circadian genes and mood-related neurotransmitter systems, the effects of light manipulation on brain circuitry, the impact of chronic stress on rhythms, and the ways in which antidepressant and mood-stabilizing drugs alter the clock. This review will focus on the recent advances that have been gleaned from the use of pre-clinical models to further our understanding of how the circadian system regulates mood. PMID:21835596

  5. Circadian Rhythms and Mood Regulation: Insights from Pre-Clinical Models

    PubMed Central

    McClung, Colleen A.

    2011-01-01

    Affective disorders such as major depression, bipolar disorder, and seasonal affective disorder are associated with major disruptions in circadian rhythms. Indeed, altered sleep/wake cycles are a critical feature for diagnosis in the DSM IV and several of the therapies used to treat these disorders have profound effects on rhythm length and stabilization in human populations. Furthermore, multiple human genetic studies have identified polymorphisms in specific circadian genes that associate with these disorders. Thus, there appears to be a strong association between the circadian system and mood regulation, although the mechanisms that underlie this association are unclear. Recently, a number of studies in animal models have begun to shed light on the complex interactions between circadian genes and mood-related neurotransmitter systems, the effects of light manipulation on brain circuitry, the impact of chronic stress on rhythms, and the ways in which antidepressant and mood-stabilizing drugs alter the clock. This review will focus on the recent advances that have been gleaned from the use of pre-clinical models to further our understanding of how the circadian system regulates mood. PMID:21835596

  6. Effect of feeding regimens on circadian rhythms: Implications for aging and longevity

    PubMed Central

    Froy, Oren; Miskin, Ruth

    2010-01-01

    Increased longevity and improved health can be achieved in mammals by two feeding regimens, caloric restriction (CR), which limits the amount of daily calorie intake, and intermittent fasting (IF), which allows the food to be availablead libitum every other day. The precise mechanisms mediating these beneficial effects are still unresolved. Resetting the circadian clock is another intervention that can lead to increased life span and well being, while clock disruption is associated with aging and morbidity. Currently, a large body of evidence links circadian rhythms with metabolism and feeding regimens. In particular, CR, and possibly also IF, can entrain the master clock located in the suprachiasmatic nuclei (SCN) of the brain hypothalamus. These findings raise the hypothesis that the beneficial effects exerted by these feeding regimens could be mediated, at least in part, through resetting of the circadian clock, thus leading to synchrony in metabolism and physiology. This hypothesis is reinforced by a transgenic mouse model showing spontaneously reduced eating alongside robust circadian rhythms and increased life span. This review will summarize recent findings concerning the relationships between feeding regimens, circadian rhythms, and metabolism with implications for ageing attenuation and life span extension. PMID:20228939

  7. Time-Specific Fear Acts as a Non-Photic Entraining Stimulus of Circadian Rhythms in Rats

    PubMed Central

    Pellman, Blake A.; Kim, Earnest; Reilly, Melissa; Kashima, James; Motch, Oleksiy; de la Iglesia, Horacio O.; Kim, Jeansok J.

    2015-01-01

    Virtually all animals have endogenous clock mechanisms that “entrain” to the light-dark (LD) cycle and synchronize psychophysiological functions to optimal times for exploring resources and avoiding dangers in the environment. Such circadian rhythms are vital to human mental health, but it is unknown whether circadian rhythms “entrained” to the LD cycle can be overridden by entrainment to daily recurring threats. We show that unsignaled nocturnal footshock caused rats living in an “ethological” apparatus to switch their natural foraging behavior from the dark to the light phase and that this switch was maintained as a free-running circadian rhythm upon removal of light cues and footshocks. Furthermore, this fear-entrained circadian behavior was dependent on an intact amygdala and suprachiasmatic nucleus. Thus, time-specific fear can act as a non-photic entraining stimulus for the circadian system, and limbic centers encoding aversive information are likely part of the circadian oscillator network that temporally organizes behavior. PMID:26468624

  8. Time-Specific Fear Acts as a Non-Photic Entraining Stimulus of Circadian Rhythms in Rats.

    PubMed

    Pellman, Blake A; Kim, Earnest; Reilly, Melissa; Kashima, James; Motch, Oleksiy; de la Iglesia, Horacio O; Kim, Jeansok J

    2015-01-01

    Virtually all animals have endogenous clock mechanisms that "entrain" to the light-dark (LD) cycle and synchronize psychophysiological functions to optimal times for exploring resources and avoiding dangers in the environment. Such circadian rhythms are vital to human mental health, but it is unknown whether circadian rhythms "entrained" to the LD cycle can be overridden by entrainment to daily recurring threats. We show that unsignaled nocturnal footshock caused rats living in an "ethological" apparatus to switch their natural foraging behavior from the dark to the light phase and that this switch was maintained as a free-running circadian rhythm upon removal of light cues and footshocks. Furthermore, this fear-entrained circadian behavior was dependent on an intact amygdala and suprachiasmatic nucleus. Thus, time-specific fear can act as a non-photic entraining stimulus for the circadian system, and limbic centers encoding aversive information are likely part of the circadian oscillator network that temporally organizes behavior. PMID:26468624

  9. The circadian cycle: daily rhythms from behaviour to genes

    PubMed Central

    Merrow, Martha; Spoelstra, Kamiel; Roenneberg, Till

    2005-01-01

    The daily recurrence of activity and rest are so common as to seem trivial. However, they reflect a ubiquitous temporal programme called the circadian clock. In the absence of either anatomical clock structures or clock genes, the timing of sleep and wakefulness is disrupted. The complex nature of circadian behaviour is evident in the fact that phasing of the cycle during the day varies widely for individuals, resulting in extremes colloquially called 'larks' and 'owls'. These behavioural oscillations are mirrored in the levels of physiology and gene expression. Deciphering the underlying mechanisms will provide important insights into how the circadian clock affects health and disease. PMID:16222241

  10. Circadian Mechanisms of Food Anticipatory Rhythms in Rats Fed Once or Twice Daily: Clock Gene and Endocrine Correlates

    PubMed Central

    Patton, Danica F.; Katsuyama, Ângela M.; Pavlovski, Ilya; Michalik, Mateusz; Patterson, Zachary; Parfyonov, Maksim; Smit, Andrea N.; Marchant, Elliott G.; Chung, John; Abizaid, Alfonso; Storch, Kai-Florian; de la Iglesia, Horacio; Mistlberger, Ralph E.

    2014-01-01

    Circadian clocks in many brain regions and peripheral tissues are entrained by the daily rhythm of food intake. Clocks in one or more of these locations generate a daily rhythm of locomotor activity that anticipates a regular mealtime. Rats and mice can also anticipate two daily meals. Whether this involves 1 or 2 circadian clocks is unknown. To gain insight into how the circadian system adjusts to 2 daily mealtimes, male rats in a 12?12 light-dark cycle were fed a 2 h meal either 4 h after lights-on or 4 h after lights-off, or a 1 h meal at both times. After 30 days, brain, blood, adrenal and stomach tissue were collected at 6 time points. Multiple clock genes from adrenals and stomachs were assayed by RT-PCR. Blood was assayed for corticosterone and ghrelin. Bmal1 expression was quantified in 14 brain regions by in situ hybridization. Clock gene rhythms in adrenal and stomach from day-fed rats oscillated in antiphase with the rhythms in night-fed rats, and at an intermediate phase in rats fed twice daily. Corticosterone and ghrelin in 1-meal rats peaked at or prior to the expected mealtime. In 2-meal rats, corticosterone peaked only prior the nighttime meal, while ghrelin peaked prior to the daytime meal and then remained elevated. The olfactory bulb, nucleus accumbens, dorsal striatum, cerebellum and arcuate nucleus exhibited significant daily rhythms of Bmal1 in the night-fed groups that were approximately in antiphase in the day-fed groups, and at intermediate levels (arrhythmic) in rats anticipating 2 daily meals. The dissociations between anticipatory activity and the peripheral clocks and hormones in rats anticipating 2 daily meals argue against a role for these signals in the timing of behavioral rhythms. The absence of rhythmicity at the tissue level in brain regions from rats anticipating 2 daily meals support behavioral evidence that circadian clock cells in these tissues may reorganize into two populations coupled to different meals. PMID:25502949

  11. The genetic background of individual variations of circadian-rhythm periods in healthy human adults.

    PubMed Central

    Ashkenazi, I E; Reinberg, A; Bicakova-Rocher, A; Ticher, A

    1993-01-01

    As a group phenomenon, human variables exhibit a rhythm with a period (tau) equal to 24 h. However, healthy human adults may differ from one another with regard to the persistence of the 24-h periods of a set of variables' rhythms within a given individual. Such an internal desynchronization (or individual circadian dyschronism) was documented during isolation experiments without time cues, both in the present study involving 78 male shift workers and in 20 males and 19 females living in a natural setting. Circadian rhythms of sleep-wake cycles, oral temperature, grip strength of both hands, and heart rate were recorded, and power-spectra analyses of individual time series of about 15 days were used to quantify the rhythm period of each variable. The period of the sleep-wake cycle seldom differed from 24 h, while rhythm periods of the other variables exhibited a trimodal distribution (tau = 24 h, tau > 24 h, tau < 24 h). Among the temperature rhythm periods which were either < 24 h or > 24 h, none was detected between 23.2 and 24 h or between 24 and 24.8 h. Furthermore, the deviations from the 24-h period were predominantly grouped in multiples of +/- 0.8 h. Similar results were obtained when the rhythm periods of hand grip strength were analyzed (for each hand separately). In addition, the distribution of grip strength rhythm periods of the left hand exhibited a gender-related difference. These results suggested the presence of genetically controlled variability. Consequently, the distribution pattern of the periods was analyzed to elucidate its compatibility with a genetic control consisting of either a two-allele system, a multiple-allele system, or a polygenic system. The analysis resulted in structuring a model which integrates the function of a constitutive (essential) gene which produces the exact 24-h period (the Dian domain) with a set of (inducible) polygenes, the alleles of which, contribute identical time entities to the period. The time entities which affected the rhythm periods of the variables examined were in the magnitude of +/- 0.8 h. Such an assembly of genes may create periods ranging from 20 to 28 h (the Circadian domain). The model was termed by us "The Dian-Circadian Model." This model can also be used to explain the beat phenomena in biological rhythms, the presence of 7-d and 30-d periods, and interindividual differences in sensitivity of rhythm characteristics (phase shifts, synchronization, etc.) to external (and environmental) factors. PMID:8503453

  12. Pregnancy-induced changes in ultradian rhythms persist in circadian arrhythmic Siberian hamsters.

    PubMed

    Wang, Z Yan; Cable, Erin J; Zucker, Irving; Prendergast, Brian J

    2014-07-01

    The impact of pregnancy and lactation on ultradian rhythms (URs) and circadian rhythms (CRs) of locomotor activity was assessed in circadian rhythmic and arrhythmic Siberian hamsters maintained in a long-day photoperiod (16h light/day). Progressive decrements in CR robustness and amplitude over the course of gestation were accompanied by enhanced URs. Dark-phase UR period and amplitude increased during early gestation and complexity and robustness increased during late gestation. The persistence of pregnancy-associated enhancements of URs in circadian arrhythmic (ARR) hamsters suggests that reproductive modulation of the UR waveform is not dependent on coherent circadian organization. The increased incidence of dark-phase URs appeared more rapidly in ARR dams than entrained (ENTR) dams. Throughout gestation, the percentage of dams with dark-phase URs was significantly greater in the ARR group. Gestational increases in UR complexity and robustness emerged earlier and were greater in ARR than ENTR dams. The attenuation of CRs during lactation is correlated with increased expression of URs. Relaxation of circadian control of the dam's behavior may increase fitness by permitting more efficient interactions with circadian arrhythmic pups. PMID:24798705

  13. The Circadian Clock in the Regulation of Renal Rhythms.

    PubMed

    Solocinski, Kristen; Gumz, Michelle L

    2015-12-01

    Since the kidney is integral to maintenance of fluid and ion homeostasis, and therefore blood pressure regulation, its proper function is paramount. Circadian fluctuations in blood pressure, renal blood flow, glomerular filtration rate, and sodium and water excretion have been documented for decades, if not longer. Recent studies on the role of circadian clock proteins in the regulation of a variety of renal transport genes suggest that the molecular clock in the kidney controls circadian fluctuations in renal function. The circadian clock appears to be a critical regulator of renal function with important implications for the treatment of renal pathologies, which include chronic kidney disease and hypertension. The development, regulation, and mechanism of the kidney clock are reviewed here. PMID:26527094

  14. Alteration of Daily and Circadian Rhythms following Dopamine Depletion in MPTP Treated Non-Human Primates

    PubMed Central

    Fifel, Karim; Vezoli, Julien; Dzahini, Kwamivi; Claustrat, Bruno; Leviel, Vincent; Kennedy, Henry; Procyk, Emmanuel; Dkhissi-Benyahya, Ouria; Gronfier, Claude; Cooper, Howard M.

    2014-01-01

    Disturbances of the daily sleep/wake cycle are common non-motor symptoms of Parkinson's disease (PD). However, the impact of dopamine (DA) depletion on circadian rhythms in PD patients or non-human primate (NHP) models of the disorder have not been investigated. We evaluated alterations of circadian rhythms in NHP following MPTP lesion of the dopaminergic nigro-striatal system. DA degeneration was assessed by in vivo PET ([11C]-PE2I) and post-mortem TH and DAT quantification. In a light?dark cycle, control and MPTP-treated NHP both exhibit rest-wake locomotor rhythms, although DA-depleted NHP show reduced amplitude, decreased stability and increased fragmentation. In all animals, 6-sulphatoxymelatonin peaks at night and cortisol in early morning. When the circadian system is challenged by exposure to constant light, controls retain locomotor rest-wake and hormonal rhythms that free-run with stable phase relationships whereas in the DA-depleted NHP, locomotor rhythms are severely disturbed or completely abolished. The amplitude and phase relations of hormonal rhythms nevertheless remain unaltered. Use of a light-dark masking paradigm shows that expression of daily rest-wake activity in MPTP monkeys requires the stimulatory and inhibitory effects of light and darkness. These results suggest that following DA lesion, the central clock in the SCN remains intact but, in the absence of environmental timing cues, is unable to drive downstream rhythmic processes of striatal clock gene and dopaminergic functions that control locomotor output. These findings suggest that the circadian component of the sleep-wake disturbances in PD is more profoundly affected than previously assumed. PMID:24465981

  15. Circadian rhythms of visual accommodation responses and physiological correlations.

    NASA Technical Reports Server (NTRS)

    Murphy, M. R.; Randle, R. J.; Williams, B. A.

    1972-01-01

    Use of a recently developed servocontrolled infrared optometer to continuously record the state of monocular focus while subjects viewed a visual target for which the stimulus to focus was systematically varied. Calculated parameters form recorded data - e.g., speeds of accommodation to approaching and receding targets, magnitude of accommodation to step changes in target distance, and amplitude and phase lag of response to sinusoidally varying stimuli were submitted to periodicity analyses. Ear canal temperature (ECT) and heart rate (HR) rhythms were also recorded for physiological correlation with accommodation rhythms. HR demonstrated a 24-hr rhythm, but ECT data did not.

  16. Coupling circadian rhythms of metabolism and chromatin remodelling.

    PubMed

    Masri, S; Orozco-Solis, R; Aguilar-Arnal, L; Cervantes, M; Sassone-Corsi, P

    2015-09-01

    The circadian clock controls a large variety of neuronal, endocrine, behavioural and physiological responses in mammals. This control is exerted in large part at the transcriptional level on genes expressed in a cyclic manner. A highly specialized transcriptional machinery based on clock regulatory factors organized in feedback autoregulatory loops governs a significant portion of the genome. These oscillations in gene expression are paralleled by critical events of chromatin remodelling that appear to provide plasticity to circadian regulation. Specifically, the nicotinamide adenine dinucleotide (NAD)(+) -dependent deacetylases SIRT1 and SIRT6 have been linked to circadian control of gene expression. This, and additional accumulating evidence, shows that the circadian epigenome appears to share intimate links with cellular metabolic processes and has remarkable plasticity showing reprogramming in response to nutritional challenges. In addition to SIRT1 and SIRT6, a number of chromatin remodellers have been implicated in clock control, including the histone H3K4 tri-methyltransferase MLL1. Deciphering the molecular mechanisms that link metabolism, epigenetic control and circadian responses will provide valuable insights towards innovative strategies of therapeutic intervention. PMID:26332964

  17. The circadian rhythm and its interaction with human epilepsy: a review of literature.

    PubMed

    Hofstra, Wytske Aelig; de Weerd, Al Wytze

    2009-12-01

    Knowledge on the interaction between circadian rhythm and human epilepsy is relatively poor, although if it exists, this interaction may be of value for better knowledge of pathophysiology and for timing of diagnostic procedures and therapy. It appears that human seizure occurrence may have 24-h rhythmicity, depending on the origin. These findings are endorsed by animal studies. Rats placed in constant darkness showed spontaneous limbic seizures occurring in an endogenously mediated circadian pattern. More studies are available on the influence of epilepsy on circadian rhythms. Significant differences in chronotypes between patients with different epilepsy syndromes have been found and numerous studies have described influences of epilepsy and seizures on sleep. In contrast, knowledge on (core) body temperature and clock genes in patients is minimal. Reduced heart rate variability and changed hormone levels, which are under the influence of the biological clock, have been observed in people with epilepsy. In short, large gaps in the knowledge about the interaction of circadian rhythm and human epilepsy still remain. Proposals for studies in this borderline area between the biological clock and epilepsy will be discussed. PMID:19398353

  18. Animal activity around the clock with no overt circadian rhythms: patterns, mechanisms and adaptive value

    PubMed Central

    Bloch, Guy; Barnes, Brian M.; Gerkema, Menno P.; Helm, Barbara

    2013-01-01

    Circadian rhythms are ubiquitous in many organisms. Animals that are forced to be active around the clock typically show reduced performance, health and survival. Nevertheless, we review evidence of animals showing prolonged intervals of activity with attenuated or nil overt circadian rhythms and no apparent ill effects. We show that around-the-clock and ultradian activity patterns are more common than is generally appreciated, particularly in herbivores, in animals inhabiting polar regions and habitats with constant physical environments, in animals during specific life-history stages (such as migration or reproduction), and in highly social animals. The underlying mechanisms are diverse, but studies suggest that some circadian pacemakers continue to measure time in animals active around the clock. The prevalence of around-the-clock activity in diverse animals and habitats, and an apparent diversity of underlying mechanisms, are consistent with convergent evolution. We suggest that the basic organizational principles of the circadian system and its complexity encompass the potential for chronobiological plasticity. There may be trade-offs between benefits of persistent daily rhythms versus plasticity, which for reasons still poorly understood make overt daily arrhythmicity functionally adaptive only in selected habitats and for selected lifestyles. PMID:23825202

  19. / www.sciencemag.org/content/early/recent / XX Month 2014 / Page 1 / 10.1126/science.xxxxxx Endogenous circadian (~24 hour) rhythms are found in

    E-print Network

    Napp, Nils

    .xxxxxx Endogenous circadian (~24 hour) rhythms are found in diverse organisms, arising as an adaptation to the Earth S. elongatus (denoted by se ), the standard model for investigating in vivo circadian rhythms (16's persistent cycles of night and day (1). To uncover the molec- ular mechanism of a circadian clock, we chose

  20. Circadian rhythm of maternal blood pressure and fetal growth.

    PubMed

    Maggioni, C; Cornélissen, G; Otsuka, K; Halberg, F; Consonni, D; Nicolini, U

    2005-10-01

    This study aimed at examining any relation between the circadian variation in blood pressure (BP) in human pregnancy and fetal growth. A prospective study included 52 pregnant women monitored during the third trimester of pregnancy. There were 33 uncomplicated pregnancies with normal fetal growth (Group 1) and 19 pregnancies complicated by intrauterine growth retardation (IUGR), confirmed at birth (Group 2). Ten women (five in each group) had pregnancy-induced hypertension. All women were hospitalized and followed a similar daily routine. BP was recorded with an automatic wearable device. Measurements were obtained every 20 min for 24 +/- 1 h. BP profiles were analyzed by conventional statistical methods and by cosinor, involving the least squares fit of cosine curves with an anticipated period (24 h) to the data. BP parameters, fetal outcome, demographic and obstetric characteristics were compared between the two groups. Logistic regression and multivariate analyses were used to assess factors putatively associated with fetal outcome. The circadian amplitude of diastolic BP was found to be larger in normotensive women with IUGR. As gauged by odds ratios (OR), the circadian amplitude of diastolic BP (OR = 1.7, 95% CI: 1.1-2.8; P = 0.03) and hematocrit (OR = 1.4, 95% CI: 1.0-1.9; P = 0.04) were the only variables positively and independently associated with IUGR. In the presence of maternal hypertension, the circadian amplitude of systolic BP was negatively associated with IUGR (OR = 0.7, 95% CI: 0.5-1.0; P = 0.03). A larger circadian variation in diastolic BP, rather than a difference in the mean value of systolic or diastolic BP, was found to be statistically significantly associated with IUGR. This study adds another condition in which the circadian BP amplitude constitutes a harbinger of elevated risk, apart from an association with a shortened lifespan in the absence or presence of malignant hypertension and with an increased risk of stroke and nephropathy reported earlier. PMID:16275513

  1. Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights

    NASA Technical Reports Server (NTRS)

    Dijk, D. J.; Neri, D. F.; Wyatt, J. K.; Ronda, J. M.; Riel, E.; Ritz-De Cecco, A.; Hughes, R. J.; Elliott, A. R.; Prisk, G. K.; West, J. B.; Czeisler, C. A.

    2001-01-01

    Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.

  2. Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights.

    PubMed

    Dijk, D J; Neri, D F; Wyatt, J K; Ronda, J M; Riel, E; Ritz-De Cecco, A; Hughes, R J; Elliott, A R; Prisk, G K; West, J B; Czeisler, C A

    2001-11-01

    Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep. PMID:11641138

  3. Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver.

    PubMed

    Atger, Florian; Gobet, Cédric; Marquis, Julien; Martin, Eva; Wang, Jingkui; Weger, Benjamin; Lefebvre, Grégory; Descombes, Patrick; Naef, Felix; Gachon, Frédéric

    2015-11-24

    Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5'-Terminal Oligo Pyrimidine tract (5'-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5'-UTR (TISU) motif. The increased translation efficiency of 5'-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. PMID:26554015

  4. Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

    PubMed Central

    Atger, Florian; Gobet, Cédric; Marquis, Julien; Martin, Eva; Wang, Jingkui; Weger, Benjamin; Lefebvre, Grégory; Descombes, Patrick; Naef, Felix; Gachon, Frédéric

    2015-01-01

    Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light–dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5?-Terminal Oligo Pyrimidine tract (5?-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5?-UTR (TISU) motif. The increased translation efficiency of 5?-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. PMID:26554015

  5. Circadian rhythm of salivary cortisol in infants with congenital heart disease

    PubMed Central

    Caprirolo, Giovanna; Ghanayem, Nancy S.; Murkowski, Kathy; Nugent, Melodee L.; Simpson, Pippa M.; Raff, Hershel

    2015-01-01

    Children with congenital heart disease (CHD) have associated extracardiac co-morbidities at the time of surgery and during ongoing growth and development. Perioperative events include disrupted glucose homeostasis, capillary leak, and fluid retention. The hypothalamic-pituitary-adrenal (HPA) axis has an important role in homeostasis in that the secretion of cortisol contributes to the response to stress, glucose regulation, blood volume control and immune regulation. We investigated the diurnal rhythm of the HPA axis in infants with CHD by measuring salivary cortisol in the morning (0600–0900 hr – circadian peak) and evening (2100–2400 hr – circadian nadir). Twenty-nine infants aged 12 weeks to 1 year were included: 16 with acyanotic disease (SpO2?90%) and 13 with cyanotic disease (SpO2<90%). Morning salivary cortisol was similar between the two groups [acyanotic 7.0 nmol/L (1.8–23.1); cyanotic 9.7 nmol/L (0.9–15.6); p=0.68]. Evening salivary cortisol was similar between the two groups [acyanotic 0.9 nmol/L (0.2–8.5); cyanotic 1.4 nmol/L (0.5–14.9); p=0.32]. Both cyanotic and acyanotic groups demonstrated an intact diurnal rhythm. In conclusion, chronic hypoxia secondary to cyanotic CHD does not affect the circadian rhythm of the HPA axis. By twelve weeks of age, infants with hypoxia secondary to cyanotic CHD have a normal cortisol diurnal rhythm. PMID:22976914

  6. The Effect of Disrupted Circadian Rhythm and Associated microRNA on Biliary Injury and Malignant Transformation 

    E-print Network

    Han, Yuyan

    2014-12-12

    Cholangiocarcinoma (CCA) is a devastating tumor characterized by late presentation of symptoms with limited treatment options. Disruption of circadian rhythm is associated with cancer development and progression. MicroRNAs ...

  7. Analysis of Circadian Rhythm Gene Expression With Reference to Diurnal Pattern of Intraocular Pressure in Mice

    PubMed Central

    Dalvin, Lauren A.; Fautsch, Michael P.

    2015-01-01

    Purpose. To determine the expression of circadian rhythm clock genes in the iris–ciliary body complex of mice and their association with the diurnal pattern of intraocular pressure (IOP). Methods. Thirty wild-type C57BL/6 mice were acclimated to a 12-hour light–dark cycle. Intraocular pressure was measured with a rebound tonometer at six time points daily (circadian time [CT] 2, 6, 10, 14, 18, and 22 hours) for five consecutive days. On day 6, mice were euthanized at CT 2, 6, 10, 14, 18, and 22. Eyes were flash-frozen or fixed in 4% phosphate-buffered paraformaldehyde. Total RNA was extracted from the iris–ciliary body complex, and RNA expression of circadian rhythm genes Bmal1, Clock, Cry1, Cry2, Per1, and Per2 was assessed by quantitative real-time PCR. Fixed eyes were paraffin embedded, and immunohistochemistry was performed to localize corresponding proteins (BMAL1, CLOCK, CRY1, CRY2, PER1, and PER2). Linear regression analysis was performed to correlate gene expression with IOP. Results. Intraocular pressure demonstrated a consistent circadian pattern. The clock genes Bmal1, Clock, Cry1, Cry2, Per1, and Per2 showed a circadian pattern of expression in the iris–ciliary body complex of mice. Bmal1, Clock, Cry1, Per1, and Per2 gene expression demonstrated statistically significant correlations with diurnal variations of IOP. BMAL1, CLOCK, CRY1, CRY2, PER1, and PER2 proteins were found to be expressed locally in the nonpigmented epithelium of the ciliary body. Conclusions. Expression patterns of candidate circadian rhythm genes correlates with the diurnal pattern variation of IOP in mouse eyes, indicating a possible mechanism of IOP regulation through these genes. PMID:25813988

  8. Involvement of the Circadian Rhythm and Inflammatory Cytokines in the Pathogenesis of Rheumatoid Arthritis

    PubMed Central

    Yoshida, Kohsuke; Hashimoto, Teppei; Sakai, Yoshitada; Hashiramoto, Akira

    2014-01-01

    Among the symptoms of patients with rheumatoid arthritis (RA), joint stiffness is influenced by diurnal rhythm and reaches peak in the morning, which is a common complaint and reflects the circadian nature of disease manifestation. In addition, inflammatory cytokines, which reach peak secretion early in the morning are major players causing the morning stiffness. In this review, we explore the link between the circadian clock and inflammation, focusing on the interactions of various clock genes with the immune-pathways underlying the pathology of rheumatoid arthritis. PMID:24901009

  9. Circadian Rhythms in Cognitive Processes: Implications for School Learning

    ERIC Educational Resources Information Center

    Valdez, Pablo; Ramírez, Candelaria; García, Aída

    2014-01-01

    Circadian variations have been found in cognitive processes, such as attention, working memory, and executive functions, which may explain oscillations in the performance of many tasks. These cognitive processes improve during the day and decrease during the night and early hours of the morning. Sleep deprivation further decreases these cognitive…

  10. Robust and tunable circadian rhythms from differentially sensitive catalytic domains

    E-print Network

    Lee, Ka Yee C.

    are ubiquitous biological oscillators that coordi- nate an organism's behavior with the daily cycling, in a reconstituted circadian system from cyanobacteria, these con- flicting requirements are satisfied by distinct functions for two domains of the central clock protein KaiC: the C-terminal autoki- nase domain integrates

  11. On the Role of Histamine Receptors in the Regulation of Circadian Rhythms

    PubMed Central

    Rozov, Stanislav V.; Porkka-Heiskanen, Tarja; Panula, Pertti

    2015-01-01

    Several lines of evidence suggest a regulatory role of histamine in circadian rhythms, but little is known about signaling pathways that would be involved in such a putative role. The aim of this study was to examine whether histamine mediates its effects on the circadian system through Hrh1 or Hrh3 receptors. We assessed both diurnal and free-running locomotor activity rhythms of Hrh1-/- and Hrh3-/- mice. We also determined the expression of Per1, Per2 and Bmal1 genes in the suprachiasmatic nuclei, several areas of the cerebral cortex and striatum under symmetric 24 h light-dark cycle at zeitgeber times 14 and 6 by using radioactive in situ hybridization. We found no differences between Hrh1-/- and wild type mice in the length, amplitude and mesor of diurnal and free-running activity rhythms as well as in expression of Per1, Per2 and Bmal1 genes in any of the examined brain structures. The amplitude of free-running activity rhythm of the Hrh3-/- mice was significantly flattened, whereas the expression of the clock genes in Hrh3-/- mice was similar to the wild type animals in all of the assessed brain structures. Therefore, the knockout of Hrh1 receptor had no effects on the circadian rhythm of spontaneous locomotion, and a knockout of Hrh3 receptor caused a substantial reduction of free-running activity rhythm amplitude, but none of these knockout models affected the expression patterns of the core clock genes in any of the studied brain structures. PMID:26660098

  12. Predicted Role of NAD Utilization in the Control of Circadian Rhythms during DNA Damage Response

    PubMed Central

    Luna, Augustin; McFadden, Geoffrey B.; Aladjem, Mirit I.; Kohn, Kurt W.

    2015-01-01

    The circadian clock is a set of regulatory steps that oscillate with a period of approximately 24 hours influencing many biological processes. These oscillations are robust to external stresses, and in the case of genotoxic stress (i.e. DNA damage), the circadian clock responds through phase shifting with primarily phase advancements. The effect of DNA damage on the circadian clock and the mechanism through which this effect operates remains to be thoroughly investigated. Here we build an in silico model to examine damage-induced circadian phase shifts by investigating a possible mechanism linking circadian rhythms to metabolism. The proposed model involves two DNA damage response proteins, SIRT1 and PARP1, that are each consumers of nicotinamide adenine dinucleotide (NAD), a metabolite involved in oxidation-reduction reactions and in ATP synthesis. This model builds on two key findings: 1) that SIRT1 (a protein deacetylase) is involved in both the positive (i.e. transcriptional activation) and negative (i.e. transcriptional repression) arms of the circadian regulation and 2) that PARP1 is a major consumer of NAD during the DNA damage response. In our simulations, we observe that increased PARP1 activity may be able to trigger SIRT1-induced circadian phase advancements by decreasing SIRT1 activity through competition for NAD supplies. We show how this competitive inhibition may operate through protein acetylation in conjunction with phosphorylation, consistent with reported observations. These findings suggest a possible mechanism through which multiple perturbations, each dominant during different points of the circadian cycle, may result in the phase advancement of the circadian clock seen during DNA damage. PMID:26020938

  13. Synchronization of Biological Clock Neurons by Light and Peripheral Feedback Systems Promotes Circadian Rhythms and Health

    PubMed Central

    Ramkisoensing, Ashna; Meijer, Johanna H.

    2015-01-01

    In mammals, the suprachiasmatic nucleus (SCN) functions as a circadian clock that drives 24-h rhythms in both physiology and behavior. The SCN is a multicellular oscillator in which individual neurons function as cell-autonomous oscillators. The production of a coherent output rhythm is dependent upon mutual synchronization among single cells and requires both synaptic communication and gap junctions. Changes in phase-synchronization between individual cells have consequences on the amplitude of the SCN’s electrical activity rhythm, and these changes play a major role in the ability to adapt to seasonal changes. Both aging and sleep deprivation negatively affect the circadian amplitude of the SCN, whereas behavioral activity (i.e., exercise) has a positive effect on amplitude. Given that the amplitude of the SCN’s electrical activity rhythm is essential for achieving robust rhythmicity in physiology and behavior, the mechanisms that underlie neuronal synchronization warrant further study. A growing body of evidence suggests that the functional integrity of the SCN contributes to health, well-being, cognitive performance, and alertness; in contrast, deterioration of the 24-h rhythm is a risk factor for neurodegenerative disease, cancer, depression, and sleep disorders. PMID:26097465

  14. A statistical model of the human core-temperature circadian rhythm

    NASA Technical Reports Server (NTRS)

    Brown, E. N.; Choe, Y.; Luithardt, H.; Czeisler, C. A.

    2000-01-01

    We formulate a statistical model of the human core-temperature circadian rhythm in which the circadian signal is modeled as a van der Pol oscillator, the thermoregulatory response is represented as a first-order autoregressive process, and the evoked effect of activity is modeled with a function specific for each circadian protocol. The new model directly links differential equation-based simulation models and harmonic regression analysis methods and permits statistical analysis of both static and dynamical properties of the circadian pacemaker from experimental data. We estimate the model parameters by using numerically efficient maximum likelihood algorithms and analyze human core-temperature data from forced desynchrony, free-run, and constant-routine protocols. By representing explicitly the dynamical effects of ambient light input to the human circadian pacemaker, the new model can estimate with high precision the correct intrinsic period of this oscillator ( approximately 24 h) from both free-run and forced desynchrony studies. Although the van der Pol model approximates well the dynamical features of the circadian pacemaker, the optimal dynamical model of the human biological clock may have a harmonic structure different from that of the van der Pol oscillator.

  15. Profiling molecular and behavioral circadian rhythms in the non-symbiotic sea anemone Nematostella vectensis

    PubMed Central

    Oren, Matan; Tarrant, Ann M.; Alon, Shahar; Simon-Blecher, Noa; Elbaz, Idan; Appelbaum, Lior; Levy, Oren

    2015-01-01

    Endogenous circadian clocks are poorly understood within early-diverging animal lineages. We have characterized circadian behavioral patterns and identified potential components of the circadian clock in the starlet sea anemone, Nematostella vectensis: a model cnidarian which lacks algal symbionts. Using automatic video tracking we showed that Nematostella exhibits rhythmic circadian locomotor activity, which is persistent in constant dark, shifted or disrupted by external dark/light cues and maintained the same rate at two different temperatures. This activity was inhibited by a casein kinase 1?/? inhibitor, suggesting a role for CK1 homologue(s) in Nematostella clock. Using high-throughput sequencing we profiled Nematostella transcriptomes over 48?hours under a light-dark cycle. We identified 180 Nematostella diurnally-oscillated transcripts and compared them with previously established databases of adult and larvae of the symbiotic coral Acropora millepora, revealing both shared homologues and unique rhythmic genes. Taken together, this study further establishes Nematostella as a non-symbiotic model organism to study circadian rhythms and increases our understanding about the fundamental elements of circadian regulation and their evolution within the Metazoa PMID:26081482

  16. ATAXIN-2 activates PERIOD translation to sustain circadian rhythms in Drosophila.

    PubMed

    Lim, Chunghun; Allada, Ravi

    2013-05-17

    Evidence for transcriptional feedback in circadian timekeeping is abundant, yet little is known about the mechanisms underlying translational control. We found that ATAXIN-2 (ATX2), an RNA-associated protein involved in neurodegenerative disease, is a translational activator of the rate-limiting clock component PERIOD (PER) in Drosophila. ATX2 specifically interacted with TWENTY-FOUR (TYF), an activator of PER translation. RNA interference-mediated depletion of Atx2 or the expression of a mutant ATX2 protein that does not associate with polyadenylate-binding protein (PABP) suppressed behavioral rhythms and decreased abundance of PER. Although ATX2 can repress translation, depletion of Atx2 from Drosophila S2 cells inhibited translational activation by RNA-tethered TYF and disrupted the association between TYF and PABP. Thus, ATX2 coordinates an active translation complex important for PER expression and circadian rhythms. PMID:23687047

  17. Edinburgh Research Explorer Peroxiredoxins are conserved markers of circadian rhythms

    E-print Network

    Millar, Andrew J.

    that users recognise and abide by the legal requirements associated with these rights. Take down policy organisms have evolved under predictable daily cycles due to the Earth's rotation. The advantage conferred of mechanisms driving these rhythms has been difficult to dissect because identified clock genes and proteins

  18. Effects of microgravity on circadian rhythms in insects

    NASA Technical Reports Server (NTRS)

    Alpatov, A. M.; Hoban-Higgins, T. M.; Fuller, C. A.; Lazarev, A. O.; Rietveld, W. J.; Tschernyshev, V. B.; Tumurova, E. G.; Wassmer, G.; Zotov, V. A.

    1998-01-01

    The desert beetle Trigonoscelis gigas Reitt. was used as a biological model in studies that examined the effects of space flight on the circadian timing system. Results from studies aboard the Bion-10, Bion-11, and Photon-11 missions are reported. The control study is an ongoing Mir experiment. The studies indicate that the free-running period in beetles may be longer during space flight.

  19. Phase-shifting human circadian rhythms: influence of sleep timing, social contact and light exposure

    NASA Technical Reports Server (NTRS)

    Duffy, J. F.; Kronauer, R. E.; Czeisler, C. A.

    1996-01-01

    1. Both the timing of behavioural events (activity, sleep and social interactions) and the environmental light-dark cycle have been reported to contribute to entrainment of human circadian rhythms to the 24 h day. Yet, the relative contribution of those putative behavioural synchronizers to that of light exposure remains unclear. 2. To investigate this, we inverted the schedule of rest, sedentary activity and social contact of thirty-two young men either with or without exposure to bright light. 3. On this inverted schedule, the endogenous component of the core temperature rhythm of subjects who were exposed to bright light showed a significant phase shift, demonstrating that they were adapting to the new schedule. In contrast, the core temperature rhythm of subjects who were not exposed to bright light moved on average 0.2 h later per day and after 10 days had not significantly adapted to the new schedule. 4. The direction of phase shift in the groups exposed to bright light was dependent on the time of bright light exposure, while control subjects drifted to a later hour regardless of the timing of their schedule of sleep timing, social contact and meals. 5. These results support the concept that the light-dark cycle is the most important synchronizer of the human circadian system. They suggest that inversion of the sleep-wake, rest-activity and social contact cycles provides relatively minimal drive for resetting the human circadian pacemaker. 6. These data indicate that interventions designed to phase shift human circadian rhythms for adjustment to time zone changes or altered work schedules should focus on properly timed light exposure.

  20. [Smith-Magenis syndrome is an association of behavioral and sleep/wake circadian rhythm disorders].

    PubMed

    Poisson, A; Nicolas, A; Sanlaville, D; Cochat, P; De Leersnyder, H; Rigard, C; Franco, P; des Portes, V; Edery, P; Demily, C

    2015-06-01

    Smith-Magenis syndrome (SMS) is a genetic disorder characterized by the association of facial dysmorphism, oral speech delay, as well as behavioral and sleep/wake circadian rhythm disorders. Most SMS cases (90%) are due to a 17p11.2 deletion encompassing the RAI1 gene; other cases stem from mutations of the RAI1 gene. Behavioral issues may include frequent outbursts, attention deficit/hyperactivity disorders, self-injuries with onychotillomania and polyembolokoilamania (insertion of objects into bodily orifices), etc. It is noteworthy that the longer the speech delay and the more severe the sleep disorders, the more severe the behavioral issues are. Typical sleep/wake circadian rhythm disorders associate excessive daytime sleepiness with nocturnal agitation. They are related to an inversion of the physiological melatonin secretion cycle. Yet, with an adapted therapeutic strategy, circadian rhythm disorders can radically improve. Usually an association of beta-blockers in the morning (stops daily melatonin secretion) and melatonin in the evening (mimics the evening deficient peak) is used. Once the sleep disorders are controlled, effective treatment of the remaining psychiatric features is needed. Unfortunately, as for many orphan diseases, objective guidelines have not been drawn up. However, efforts should be focused on improving communication skills. In the same vein, attention deficit/hyperactivity disorders, aggressiveness, and anxiety should be identified and specifically treated. This whole appropriate medical management is underpinned by the diagnosis of SMS. Diagnostic strategies include fluorescent in situ hybridization (FISH) or array comparative genomic hybridization (array CGH) when a microdeletion is sought and Sanger sequencing when a point mutation is suspected. Thus, the diagnosis of SMS can be made from a simple blood sample and should be questioned in subjects of any age presenting with an association of facial dysmorphism, speech delay with behavioral and sleep/wake circadian rhythm disorders, and other anomalies including short stature and mild dysmorphic features. PMID:25934608

  1. Sleep and circadian rhythms in long duration space flight - Antarctica as an analogue environment

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.

    1992-01-01

    The feasibility of using Antarctica as an environment for studying the impact of unusual 24 h environmental cycles (zeitgebers) on the circadian system is discussed. Adaptation of circadian rhythms and sleep of three scientists travelling from New Zealand to Antarctica during summer (which is analogous to arrival at a lunar base during the lunar day) has been studied. Data obtained indicate that sleep occurred at the same clock time, but sleep quality was poorer in Antarctica, which can be explained by the fact that the circadian system delayed by about 2 h in Antarctica, as would be expected in a weaker zeitgeber environment. It is suggested that sleep could be improved by altering patterns of exposure to the available zeitgebers to increase their effective strength.

  2. Lipids around the Clock: Focus on Circadian Rhythms and Lipid Metabolism

    PubMed Central

    Gnocchi, Davide; Pedrelli, Matteo; Hurt-Camejo, Eva; Parini, Paolo

    2015-01-01

    Disorders of lipid and lipoprotein metabolism and transport are responsible for the development of a large spectrum of pathologies, ranging from cardiovascular diseases, to metabolic syndrome, even to tumour development. Recently, a deeper knowledge of the molecular mechanisms that control our biological clock and circadian rhythms has been achieved. From these studies it has clearly emerged how the molecular clock tightly regulates every aspect of our lives, including our metabolism. This review analyses the organisation and functioning of the circadian clock and its relevance in the regulation of physiological processes. We also describe metabolism and transport of lipids and lipoproteins as an essential aspect for our health, and we will focus on how the circadian clock and lipid metabolism are greatly interconnected. Finally, we discuss how a deeper knowledge of this relationship might be useful to improve the recent spread of metabolic diseases. PMID:25665169

  3. Cognitive Performance as a Zeitgeber: Cognitive Oscillators and Cholinergic Modulation of the SCN Entrain Circadian Rhythms

    PubMed Central

    Gritton, Howard J.; Stasiak, Ashley M.; Sarter, Martin; Lee, Theresa M.

    2013-01-01

    The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals that can synchronize or entrain to environmental cues. Although light exerts powerful influences on SCN output, other non-photic stimuli can modulate the SCN as well. We recently demonstrated that daily performance of a cognitive task requiring sustained periods of attentional effort that relies upon basal forebrain (BF) cholinergic activity dramatically alters circadian rhythms in rats. In particular, normally nocturnal rats adopt a robust diurnal activity pattern that persists for several days in the absence of cognitive training. Although anatomical and pharmacological data from non-performing animals support a relationship between cholinergic signaling and circadian rhythms, little is known about how endogenous cholinergic signaling influences SCN function in behaving animals. Here we report that BF cholinergic projections to the SCN provide the principal signal allowing for the expression of cognitive entrainment in light-phase trained animals. We also reveal that oscillator(s) outside of the SCN drive cognitive entrainment as daily timed cognitive training robustly entrains SCN-lesioned arrhythmic animals. Ablation of the SCN, however, resulted in significant impairments in task acquisition, indicating that SCN-mediated timekeeping benefits new learning and cognitive performance. Taken together, we conclude that cognition entrains non-photic oscillators, and cholinergic signaling to the SCN serves as a temporal timestamp attenuating SCN photic-driven rhythms, thereby permitting cognitive demands to modulate behavior. PMID:23441168

  4. Demonstration of Circadian Rhythm in Heart Rate Turbulence using Novel Application of Correlator Functions

    E-print Network

    Watanabe, M; Barthel, P; Bauer, A; Schmidt, G; Schneider, R; Stein, P; Alford, Mark; Barthel, Petra; Bauer, Axel; Schmidt, Georg; Schneider, Raphael; Stein, Phyllis; Watanabe, Mari

    2006-01-01

    Background: It has been difficult to demonstrate circadian rhythm in the two parameters of heart rate turbulence, turbulence onset (TO) and turbulence slope (TS). Objective: To devise a new method for detecting circadian rhythm in noisy data, and apply it to selected Holter recordings from two post-myocardial infarction databases, Cardiac Arrhythmia Suppression Trial (CAST, n=684) and Innovative Stratification of Arrhythmic Risk (ISAR, n=327). Methods: For each patient, TS and TO were calculated for each hour with >4 VPCs. An autocorrelation function Corr(Delta t) = was then calculated, and averaged over all patients. Positive Corr(Delta t) indicates that TS at a given hour and Delta t hours later are similar. TO was treated likewise. Simulations and mathematical analysis showed that circadian rhythm required Corr(Delta t) to have a U-shape consisting of positive values near Delta t=0 and 23, and negative values for intermediate Delta t. Significant deviation of Corr(Delta t) from the correlator function of ...

  5. The Development and Course of Bipolar Spectrum Disorders: An Integrated Reward and Circadian Rhythm Dysregulation Model

    PubMed Central

    Alloy, Lauren B.; Nusslock, Robin; Boland, Elaine M.

    2014-01-01

    In this article, we present and review the evidence for two major biopsychosocial theories of the onset and course of bipolar spectrum disorders (BSDs) that integrate behavioral, environmental, and neurobiological mechanisms: the reward hypersensitivity and the social and circadian rhythm disruption models. We describe the clinical features, spectrum, age of onset, and course of BSDs. We then discuss research designs relevant to demonstrating whether a hypothesized mechanism represents a correlate, vulnerability, or predictor of the course of BSDs, as well as important methodological issues. We next present the reward hypersensitivity model of BSD, followed by the social/circadian rhythm disruption model of BSD. For each model, we review evidence regarding whether the proposed underlying mechanism is associated with BSDs, provides vulnerability to the onset of BSDs, and predicts the course of BSDs. We then present a new integrated reward/circadian rhythm (RCR) dysregulation model of BSD and discuss how the RCR model explains the symptoms, onset, and course of BSDs. We end with recommendations for future research directions. PMID:25581235

  6. Eyeless Mexican Cavefish Save Energy by Eliminating the Circadian Rhythm in Metabolism

    PubMed Central

    Moran, Damian; Softley, Rowan; Warrant, Eric J.

    2014-01-01

    The eyed surface form and eyeless cave form of the Mexican tetra Astyanax mexicanus experience stark differences in the daily periodicities of light, food and predation, factors which are likely to have a profound influence on metabolism. We measured the metabolic rate of Pachón cave and surface fish at a fixed swimming speed under light/dark and constant dark photoperiods. In constant darkness surface forms exhibited a circadian rhythm in metabolism with an increase in oxygen demand during the subjective daytime, whereas cave forms did not. The lack of circadian rhythm in metabolism leads to a 27% energy savings for Pachón cave fish compared to surface fish when comparing both forms in their natural photoperiods. When surface forms were tested under constant dark conditions they expended 38% more energy than cave forms under equivalent conditions. Elimination of the circadian rhythm in metabolism may be a general feature of animals that live in perpetually dark food-limited environments such as caves or the deep sea. PMID:25251018

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

    PubMed

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

    2015-12-15

    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 clocks in the brain and peripheral organs. The SCN control peripheral timing via the autonomic and neuroendocrine system, as well as via behavioral outputs. The sleep-wake cycle, the feeding/fasting rhythm and most hormonal rhythms, including that of leptin, ghrelin and glucocorticoids, usually show an opposite phase (relative to the light-dark cycle) in diurnal and nocturnal species. By contrast, the SCN clock is most active at the same astronomical times in these two categories of mammals. Moreover, in both species, pineal melatonin is secreted only at night. In this review we describe the current knowledge on the regulation of glucose and lipid metabolism by central and peripheral clock mechanisms. Most experimental knowledge comes from studies in nocturnal laboratory rodents. Nevertheless, we will also mention some relevant findings in diurnal mammals, including humans. It will become clear that as a consequence of the tight connections between the circadian clock system and energy metabolism, circadian clock impairments (e.g., mutations or knock-out of clock genes) and circadian clock misalignments (such as during shift work and chronic jet-lag) have an adverse effect on energy metabolism, that may trigger or enhancing obese and diabetic symptoms. PMID:25662277

  8. Nondestructive and intuitive determination of circadian chlorophyll rhythms in soybean leaves using multispectral imaging

    NASA Astrophysics Data System (ADS)

    Pan, Wen-Juan; Wang, Xia; Deng, Yong-Ren; Li, Jia-Hang; Chen, Wei; Chiang, John Y.; Yang, Jian-Bo; Zheng, Lei

    2015-06-01

    The circadian clock, synchronized by daily cyclic environmental cues, regulates diverse aspects of plant growth and development and increases plant fitness. Even though much is known regarding the molecular mechanism of circadian clock, it remains challenging to quantify the temporal variation of major photosynthesis products as well as their metabolic output in higher plants in a real-time, nondestructive and intuitive manner. In order to reveal the spatial-temporal scenarios of photosynthesis and yield formation regulated by circadian clock, multispectral imaging technique has been employed for nondestructive determination of circadian chlorophyll rhythms in soybean leaves. By utilizing partial least square regression analysis, the determination coefficients R2, 0.9483 for chlorophyll a and 0.8906 for chlorophyll b, were reached, respectively. The predicted chlorophyll contents extracted from multispectral data showed an approximately 24-h rhythm which could be entrained by external light conditions, consistent with the chlorophyll contents measured by chemical analyses. Visualization of chlorophyll map in each pixel offers an effective way to analyse spatial-temporal distribution of chlorophyll. Our results revealed the potentiality of multispectral imaging as a feasible nondestructive universal assay for examining clock function and robustness, as well as monitoring chlorophyll a and b and other biochemical components in plants.

  9. Nonentrained circadian rhythms of melatonin in submariners scheduled to an 18-hour day.

    PubMed

    Kelly, T L; Neri, D F; Grill, J T; Ryman, D; Hunt, P D; Dijk, D J; Shanahan, T L; Czeisler, C A

    1999-06-01

    The human circadian timing system has previously been shown to free run with a period slightly longer than 24 h in subjects living in the laboratory under conditions of forced desynchrony. In forced desynchrony, subjects are shielded from bright light and periodic time cues and are required to live on a day length outside the range of circadian entrainment. The work schedule used for most personnel aboard American submarines is 6 h on duty alternating with 12 h off duty. This imposed 18-h cycle is too short for human circadian synchronization, especially given that there is no bright-light exposure aboard submarines. However, crew members are exposed to 24-h stimuli that could mediate synchronization, such as clocks and social contacts with personnel who are living on a 24-h schedule. The authors investigated circadian rhythms of salivary melatonin in 20 crew members during a prolonged voyage on a Trident nuclear submarine. The authors found that in crew members living on the 18-h duty cycle, the endogenous rhythm of melatonin showed an average period of 24.35 h (n = 12, SD = 0.18 h). These data indicate that social contacts and knowledge of clock time are insufficient for entrainment to a 24-h period in personnel living by an 18-h rest-activity cycle aboard a submarine. PMID:10452330

  10. Nondestructive and intuitive determination of circadian chlorophyll rhythms in soybean leaves using multispectral imaging.

    PubMed

    Pan, Wen-Juan; Wang, Xia; Deng, Yong-Ren; Li, Jia-Hang; Chen, Wei; Chiang, John Y; Yang, Jian-Bo; Zheng, Lei

    2015-01-01

    The circadian clock, synchronized by daily cyclic environmental cues, regulates diverse aspects of plant growth and development and increases plant fitness. Even though much is known regarding the molecular mechanism of circadian clock, it remains challenging to quantify the temporal variation of major photosynthesis products as well as their metabolic output in higher plants in a real-time, nondestructive and intuitive manner. In order to reveal the spatial-temporal scenarios of photosynthesis and yield formation regulated by circadian clock, multispectral imaging technique has been employed for nondestructive determination of circadian chlorophyll rhythms in soybean leaves. By utilizing partial least square regression analysis, the determination coefficients R(2), 0.9483 for chlorophyll a and 0.8906 for chlorophyll b, were reached, respectively. The predicted chlorophyll contents extracted from multispectral data showed an approximately 24-h rhythm which could be entrained by external light conditions, consistent with the chlorophyll contents measured by chemical analyses. Visualization of chlorophyll map in each pixel offers an effective way to analyse spatial-temporal distribution of chlorophyll. Our results revealed the potentiality of multispectral imaging as a feasible nondestructive universal assay for examining clock function and robustness, as well as monitoring chlorophyll a and b and other biochemical components in plants. PMID:26059057

  11. Nondestructive and intuitive determination of circadian chlorophyll rhythms in soybean leaves using multispectral imaging

    PubMed Central

    Pan, Wen-Juan; Wang, Xia; Deng, Yong-Ren; Li, Jia-Hang; Chen, Wei; Chiang, John Y.; Yang, Jian-Bo; Zheng, Lei

    2015-01-01

    The circadian clock, synchronized by daily cyclic environmental cues, regulates diverse aspects of plant growth and development and increases plant fitness. Even though much is known regarding the molecular mechanism of circadian clock, it remains challenging to quantify the temporal variation of major photosynthesis products as well as their metabolic output in higher plants in a real-time, nondestructive and intuitive manner. In order to reveal the spatial-temporal scenarios of photosynthesis and yield formation regulated by circadian clock, multispectral imaging technique has been employed for nondestructive determination of circadian chlorophyll rhythms in soybean leaves. By utilizing partial least square regression analysis, the determination coefficients R2, 0.9483 for chlorophyll a and 0.8906 for chlorophyll b, were reached, respectively. The predicted chlorophyll contents extracted from multispectral data showed an approximately 24-h rhythm which could be entrained by external light conditions, consistent with the chlorophyll contents measured by chemical analyses. Visualization of chlorophyll map in each pixel offers an effective way to analyse spatial-temporal distribution of chlorophyll. Our results revealed the potentiality of multispectral imaging as a feasible nondestructive universal assay for examining clock function and robustness, as well as monitoring chlorophyll a and b and other biochemical components in plants. PMID:26059057

  12. Light as a central modulator of circadian rhythms, sleep and affect

    PubMed Central

    LeGates, T.A.; Fernandez, D.C.; Hattar, S

    2014-01-01

    Light has profoundly influenced the evolution of life on earth. As widely appreciated, light allows us to generate images of our environment. However, light, through the atypical intrinsically photosensitive retinal ganglion cells (ipRGCs; Box 1), also influences behaviors that are essential for our health and quality of life, yet are independent of image formation. These include the synchronization of the circadian clock to the solar day, tracking of seasonal changes, and regulation of sleep. Irregular light environments lead to problems in circadian rhythms and sleep, which eventually cause mood and learning deficits. Recently, it was found that irregular light can also directly impact mood and learning without producing major disruptions in circadian rhythms and sleep. Here, we will discuss the indirect and direct influence of light on mood and learning and provide a model for how light, the circadian clock, and sleep interact to influence mood and cognitive functions. Box 1Intrinsically photosensitive retinal ganglion cells (ipRGCs)Retinal photoreceptors transduce light energy into electrical signals that initiate vision. The classical photoreceptors, rods and cones, possess modified cilia that consist of stacks of membranes in which photopigments (rhodopsin and cone opsins) are concentrated. Rods are exquisitely sensitive and are able to detect even a few photons. Rods are therefore used for night vision. Cones are less sensitive than rods and are used for day and color vision. Color vision is mediated by cone photoreceptors that express cone-opsins with sensitivity peaks at different wavelengths (colors) of light. Humans have three cone types: short, mid and long wavelength sensitive cones (for simplicity, we will refer to these as blue, green and red cones, respectively). Rods and cones relay photic information through multisynaptic pathways to retinal ganglion cells (RGCs), which innervate different areas in the brain for complex visual processing13.A surprising discovery showed that a subpopulation of RGCs is intrinsically photosensitive and express the photopigment melanopsin. These cells were thus termed ipRGCs17–19. The melanopsin gene (Opn4) was originally cloned from Xenopus laevis dermal melanophores, and was shown to have orthologs in many mammalian species, including humans141. Sequence analysis shows that melanopsin shares more homology with invertebrate opsins than with vertebrate opsins, suggesting that melanopsin may use a different mechanism for light signaling than that used by the photopigments present in the rods and cones of vertebrates142. ipRGCs do not have modified membranes in which the photopigment can be concentrated: thus, melanopsin protein is expressed uniformly throughout the soma, dendrites, and the initial segment of the axon143. The lack of membrane specialization makes ipRGCs less sensitive to light than rods and cones. However, ipRGCs are able to incorporate light signals over extended period of time, resulting in an increase in their sensitivity during prolonged light stimulation. ipRGCs are most sensitive to wavelengths of light that are in the blue region of the light spectrum144, 145. As ganglion cells, ipRGCs also convey light information from rods and cones in addition to their intrinsic melanopsin-dependent pathway and can control a variety of light-mediated behaviors30.Originally, ipRGCs were thought to comprise a uniform population, however, recent discoveries revealed that ipRGCs are highly diverse, comprising at least five distinct subtypes (M1-M5) in rodents based on morphological and electrophysiological analyses22–29. The originally identified population is now known as M1 ipRGCs and project predominantly to brain regions involved in non-image forming visual functions, whereas the non-M1 ipRGCs show widespread projections to areas in the brain important for image formation. ipRGC subtypes express varying levels of the melanopsin protein and have different patterns of dendrite stratification in the inner plexiform layer (IPL)27, 28, 146, 147, indicating

  13. Scheduled daily mating induces circadian anticipatory activity rhythms in the male rat.

    PubMed

    Landry, Glenn J; Opiol, Hanna; Marchant, Elliott G; Pavlovski, Ilya; Mear, Rhiannon J; Hamson, Dwayne K; Mistlberger, Ralph E

    2012-01-01

    Daily schedules of limited access to food, palatable high calorie snacks, water and salt can induce circadian rhythms of anticipatory locomotor activity in rats and mice. All of these stimuli are rewarding, but whether anticipation can be induced by neural correlates of reward independent of metabolic perturbations associated with manipulations of food and hydration is unclear. Three experiments were conducted to determine whether mating, a non-ingestive behavior that is potently rewarding, can induce circadian anticipatory activity rhythms in male rats provided scheduled daily access to steroid-primed estrous female rats. In Experiment 1, rats anticipated access to estrous females in the mid-light period, but also exhibited post-coital eating and running. In Experiment 2, post-coital eating and running were prevented and only a minority of rats exhibited anticipation. Rats allowed to see and smell estrous females showed no anticipation. In both experiments, all rats exhibited sustained behavioral arousal and multiple mounts and intromissions during every session, but ejaculated only every 2-3 days. In Experiment 3, the rats were given more time with individual females, late at night for 28 days, and then in the midday for 28 days. Ejaculation rates increased and anticipation was robust to night sessions and significant although weaker to day sessions. The anticipation rhythm persisted during 3 days of constant dark without mating. During anticipation of nocturnal mating, the rats exhibited a significant preference for a tube to the mating cage over a tube to a locked cage with mating cage litter. This apparent place preference was absent during anticipation of midday mating, which may reflect a daily rhythm of sexual reward. The results establish mating as a reward stimulus capable of inducing circadian rhythms of anticipatory behavior in the male rat, and reveal a critical role for ejaculation, a modulatory role for time of day, and a potential confound role for uncontrolled food intake. PMID:22848408

  14. Pinealectomy shortens resynchronisation times of house sparrow ( Passer domesticus) circadian rhythms

    NASA Astrophysics Data System (ADS)

    Kumar, Vinod; Gwinner, Eberhard

    2005-09-01

    In many birds periodic melatonin secretion by the pineal organ is essential for the high-amplitude self-sustained output of the circadian pacemaker, and thus for the persistence of rhythmicity in 24 h oscillations controlled by it. The elimination of the pineal melatonin rhythm, or a reduction of its amplitude, renders the circadian pacemaker a less self-sustained, often highly damped, oscillatory system. A reduction in the degree of self-sustainment of a rhythm should not only increase its range of entrainment but also shorten the resynchronization times following phase-shifts of the zeitgeber. This hypothesis has not yet been directly tested. We therefore carried out the present study in which house sparrows (Passer domesticus) were subjected to both 6-h advance and 6-h delay phase-shifts of the light-dark cycle before and after the pinealectomy, and the rhythms in locomotion and feeding were recorded. The results indicate that following the delay, but not the advance, phase shift, resynchronization times were significantly shorter after pinealectomy. The dependence of resynchronization times on the presence or absence of the pineal organ is not only of theoretical interest but might also be of functional significance in the natural life of birds. A reduction or elimination of the amplitude of the melatonin secretion rhythm by the pineal organ might be responsible for faster adjustment to changes in zeitgeber conditions in nature.

  15. Masking of the circadian rhythms of heart rate and core temperature by the rest-activity cycle in man

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.; Connell, Linda J.; Graeber, R. Curtis

    1986-01-01

    Experiments were conducted to estimate the magnitude of the masking effect produced in humans by alternate periods of physical activity and rest or sleep on the circadian rhythms of heart rate and core temperature. The heart rate, rectal temperature, and nondominant wrist activity were monitored in 12 male subjects during 6 days of normal routine at home and during 6 days of controlled bed-rest regimen. The comparisons of averaged waveforms for the activity, heart rate, and temperature indicated that about 45 percent of the range of the circadian heart rate rhythm during normal routine and about 14 percent of the range of the circadian temperature rhythm were attributable to the effects of activity. The smaller effect of activity on the temperature rhythm may be partially attributable to the fact that core temperature is being more rigorously conserved than heart rate, at least during moderate exercise.

  16. Nonlinear dynamics of the CAM circadian rhythm in response to environmental forcing.

    PubMed

    Hartzell, Samantha; Bartlett, Mark S; Virgin, Lawrence; Porporato, Amilcare

    2015-03-01

    Crassulacean acid metabolism (CAM) photosynthesis functions as an endogenous circadian rhythm coupled to external environmental forcings of energy and water availability. This paper explores the nonlinear dynamics of a new CAM photosynthesis model (Bartlett et al., 2014) and investigates the responses of CAM plant carbon assimilation to different combinations of environmental conditions. The CAM model (Bartlett et al., 2014) consists of a Calvin cycle typical of C3 plants coupled to an oscillator of the type employed in the Van der Pol and FitzHugh-Nagumo systems. This coupled system is a function of environmental variables including leaf temperature, leaf moisture potential, and irradiance. Here, we explore the qualitative response of the system and the expected carbon assimilation under constant and periodically forced environmental conditions. The model results show how the diurnal evolution of these variables entrains the CAM cycle with prevailing environmental conditions. While constant environmental conditions generate either steady-state or periodically oscillating responses in malic acid uptake and release, forcing the CAM system with periodic daily fluctuations in light exposure and leaf temperature results in quasi-periodicity and possible chaos for certain ranges of these variables. This analysis is a first step in quantifying changes in CAM plant productivity with variables such as the mean temperature, daily temperature range, irradiance, and leaf moisture potential. Results may also be used to inform model parametrization based on the observed fluctuating regime. PMID:25542971

  17. Human circadian rhythms: physiological and therapeutic relevance of light and melatonin.

    PubMed

    Skene, Debra J; Arendt, Josephine

    2006-09-01

    Ocular light plays a key role in human physiology by transmitting time of day information. The production of the pineal gland hormone melatonin is under the control of the light-dark cycle. Its profile of secretion defines biological night and it has been called the 'darkness hormone'. Light mediates a number of non-visual responses, such as phase shifting the internal circadian clock, increasing alertness, heart rate and pupil constriction. Both exogenous melatonin and light, if appropriately timed, can phase shift the human circadian system. These 'chronobiotic' effects of light and melatonin have been used successfully to alleviate and correct circadian rhythm disorders, such as those experienced following travel across time zones, in night shift work and in circadian sleep disorders. The effectiveness of melatonin and light are currently being optimized in terms of time of administration, light intensity, duration and wavelength, and melatonin dose and formulation. The aim of this review is not to replicate information that has been reported in a number of reviews of the human circadian timing system and the role of melatonin and light, but rather to extract findings relevant to the field of clinical biochemistry. PMID:17022876

  18. Manipulating the sleep-wake cycle and circadian rhythms to improve clinical management of major depression

    PubMed Central

    2013-01-01

    Background Clinical psychiatry has always been limited by the lack of objective tests to substantiate diagnoses and a lack of specific treatments that target underlying pathophysiology. One area in which these twin failures has been most frustrating is major depression. Due to very considerable progress in the basic and clinical neurosciences of sleep-wake cycles and underlying circadian systems this situation is now rapidly changing. Discussion The development of specific behavioral or pharmacological strategies that target these basic regulatory systems is driving renewed clinical interest. Here, we explore the extent to which objective tests of sleep-wake cycles and circadian function - namely, those that measure timing or synchrony of circadian-dependent physiology as well as daytime activity and nighttime sleep patterns - can be used to identify a sub-class of patients with major depression who have disturbed circadian profiles. Summary Once this unique pathophysiology is characterized, a highly personalized treatment plan can be proposed and monitored. New treatments will now be designed and old treatments re-evaluated on the basis of their effects on objective measures of sleep-wake cycles, circadian rhythms and related metabolic systems. PMID:23521808

  19. The Transcription Factor DBP Affects Circadian Sleep Consolidation and Rhythmic EEG Activity

    E-print Network

    Halazonetis, Thanos

    of the molecular basis of circadian rhythm generation in mice. Thus, several clock elements have been identified; Fonjallaz et al., 1996), DBP mRNA also displays a strong circadian rhythm in the SCN, and the lack of DBP results in a shortening of the period of the circadian free-running rhythm and in a reduction of locomo

  20. The Effects of Hydrogen Peroxide on the Circadian Rhythms of Microcystis aeruginosa

    PubMed Central

    Yu, Shuqiong; Pan, Xiangjie; Wu, Tao; Fu, Zhengwei

    2012-01-01

    Background The cyanobacterium Microcystis aeruginosa is one of the principal bloom-forming cyanobacteria present in a wide range of freshwater ecosystems. M. aeruginosa produces cyanotoxins, which can harm human and animal health. Many metabolic pathways in M. aeruginosa, including photosynthesis and microcystin synthesis, are controlled by its circadian rhythms. However, whether xenobiotics affect the cyanobacterial circadian system and change its growth, physiology and biochemistry is unknown. We used real-time PCR to study the effect of hydrogen peroxide (H2O2) on the expression of clock genes and some circadian genes in M. aeruginosa during the light/dark (LD) cycle. Results The results revealed that H2O2 changes the expression patterns of clock genes (kaiA, kaiB, kaiC and sasA) and significantly decreases the transcript levels of kaiB, kaiC and sasA. H2O2 treatment also decreased the transcription of circadian genes, such as photosynthesis-related genes (psaB, psbD1 and rbcL) and microcystin-related genes (mcyA, mcyD and mcyH), and changed their circadian expression patterns. Moreover, the physiological functions of M. aeruginosa, including its growth and microcystin synthesis, were greatly influenced by H2O2 treatment during LD. These results indicate that changes in the cyanobacterial circadian system can affect its physiological and metabolic pathways. Conclusion Our findings show that a xenobiotic can change the circadian expression patterns of its clock genes to influence clock-controlled gene regulation, and these influences are evident at the level of cellular physiology. PMID:22413018

  1. Circadian Disruption Alters the Effects of Lipopolysaccharide Treatment on Circadian and Ultradian Locomotor Activity and Body Temperature Rhythms of Female Siberian Hamsters.

    PubMed

    Prendergast, Brian J; Cable, Erin J; Stevenson, Tyler J; Onishi, Kenneth G; Zucker, Irving; Kay, Leslie M

    2015-12-01

    The effect of circadian rhythm (CR) disruption on immune function depends on the method by which CRs are disrupted. Behavioral and thermoregulatory responses induced by lipopolysaccharide (LPS) treatment were assessed in female Siberian hamsters in which circadian locomotor activity (LMA) rhythms were eliminated by exposure to a disruptive phase-shifting protocol (DPS) that sustains arrhythmicity even when hamsters are housed in a light-dark cycle. This noninvasive treatment avoids genome manipulations and neurological damage associated with other models of CR disruption. Circadian rhythmic (RHYTH) and arrhythmic (ARR) hamsters housed in a 16L:8D photocycle were injected with bacterial LPS near the onset of the light (zeitgeber time 1; ZT1) or dark (ZT16) phase. LPS injections at ZT16 and ZT1 elicited febrile responses in both RHYTH and ARR hamsters, but the effect was attenuated in the arrhythmic females. In ZT16, LPS inhibited LMA in the dark phase immediately after injection but not on subsequent nights in both chronotypes; in contrast, LPS at ZT1 elicited more enduring (~4 day) locomotor hypoactivity in ARR than in RHYTH hamsters. Power and period of dark-phase ultradian rhythms (URs) in LMA and Tb were markedly altered by LPS treatment, as was the power in the circadian waveform. Disrupted circadian rhythms in this model system attenuated responses to LPS in a trait- and ZT-specific manner; changes in UR period and power are novel components of the acute-phase response to infection that may affect energy conservation. PMID:26566981

  2. Circadian rhythm. Dysrhythmia in the suprachiasmatic nucleus inhibits memory processing.

    PubMed

    Fernandez, Fabian; Lu, Derek; Ha, Phong; Costacurta, Patricia; Chavez, Renee; Heller, H Craig; Ruby, Norman F

    2014-11-14

    Chronic circadian dysfunction impairs declarative memory in humans but has little effect in common rodent models of arrhythmia caused by clock gene knockouts or surgical ablation of the suprachiasmatic nucleus (SCN). An important problem overlooked in these translational models is that human dysrhythmia occurs while SCN circuitry is genetically and neurologically intact. Siberian hamsters (Phodopus sungorus) are particularly well suited for translational studies because they can be made arrhythmic by a one-time photic treatment that severely impairs spatial and recognition memory. We found that once animals are made arrhythmic, subsequent SCN ablation completely rescues memory processing. These data suggest that the inhibitory effects of a malfunctioning SCN on cognition require preservation of circuitry between the SCN and downstream targets that are lost when these connections are severed. PMID:25395537

  3. Circadian rhythm of mechanically mediated differentiation of osteoblasts

    NASA Technical Reports Server (NTRS)

    Roberts, W. E.; Mozsary, P. G.; Klingler, E.

    1984-01-01

    The differential of osteoblasts in response to orthodontic pressure in the periodontal ligament of the maxillary-first-molar periodontal ligaments of 12-h-light/dark-entrained 7-wk-old male Simonsen outbred rats is measured by (H-3)-Thymidine nuclear-volume morphometry (Roberts et al., 1983) at hourly intervals throughout the circadian cycle. The results are presented in graphs and discussed. Preosteoblast large nuclei (D-cells) are found to synthesize DNA mainly in light and to divide in the following dark period, while small-nucleus osteoprogenitors (A-cells) synthesize in darkness and divide in light. These findings are seen as consistent with a model in which the sequence of proliferation and differentiation requires at least 60 h (five 12-h periods) and the shift from A to D cells lasts about 19 h.

  4. Effects of bile acid administration on bile acid synthesis and its circadian rhythm in man

    SciTech Connect

    Pooler, P.A.; Duane, W.C.

    1988-09-01

    In man bile acid synthesis has a distinct circadian rhythm but the relationship of this rhythm to feedback inhibition by bile acid is unknown. We measured bile acid synthesis as release of 14CO2 from (26-14C)cholesterol every 2 hr in three normal volunteers during five separate 24-hr periods. Data were fitted by computer to a cosine curve to estimate amplitude and acrophase of the circadian rhythm. In an additional six volunteers, we measured synthesis every 2 hr from 8:00 a.m. to 4:00 p.m. only. During the control period, amplitude (expressed as percentage of mean synthesis) averaged 52% and acrophase averaged 6:49 a.m. During administration of ursodeoxycholic acid (15 mg per kg per day), synthesis averaged 126% of baseline (p less than 0.1), amplitude averaged 43% and acrophase averaged 6:20 a.m. During administration of chenodeoxycholic acid (15 mg per kg per day), synthesis averaged 43% of baseline (p less than 0.001), amplitude averaged 53% and acrophase averaged 9:04 a.m. Addition of prednisone to this regimen of chenodeoxycholic acid to eliminate release of 14CO2 from corticosteroid hormone synthesis resulted in a mean amplitude of 62% and a mean acrophase of 6:50 a.m., values very similar to those in the baseline period. Administration of prednisone alone also did not significantly alter the baseline amplitude (40%) or acrophase (6:28 a.m.). We conclude that neither chenodeoxycholic acid nor ursodeoxycholic acid significantly alters the circadian rhythm of bile acid synthesis in man.

  5. A Study of Circadian Rhythm and Meteorological Factors Influencing Acute Myocardial Infarction

    E-print Network

    A. M. Selvam; D. Sen; S. M. S. Mody

    1998-12-08

    The circadian rhythm in the occurrence of acute myocardial infarction (AMI) was assessed in three hundred and twenty three patients admitted with AMI during the two-year period June 1992 to May 1994. The influence of the following meteorological, solar-geophysical and cosmic parameters in the causation of an infarct was also considered : (1) surface pressure (2) maximum temperature (3) minimum temperature (4) relative humidity (5) cosmic ray index (6) geomagnetic aa index (7) solar flares and (8) sunspot number. A well pronounced diurnal variability in AMI with a peak in the morning hours (6-12 a.m.) was seen. Further analysis of the data by considering one-hour periods revealed the presence of a smaller evening (10 p.m.) increase in incidence, i.e., the existence of a bimodal circadian rhythm. The simultaneous occurrence of the well documented semi-diurnal rhythm in surface pressure and incidence of acute myocardial infarction were evident. This may be one of the factors involved in the causation of the smaller evening peak-the reasons for which were unclear till now. Month-to-month variation in surface pressure was also found to be significantly correlated with incidence of acute myocardial infarction. Recognition of a circadian rhythm in the onset of AMI suggests the need for enhanced pharmacological protection during the vulnerable periods. Significant correlations were also found between monthly incidence of AMI and month-to-month variation of cosmic ray index and solar flare counts. The pattern of incidence of AMI was seen to be modified by full moon and new moon. There was no association between maximum temperature, minimum temperature or relative humidity and incidence of AMI.

  6. Effects of long-term microgravity exposure in space on circadian rhythms of heart rate variability.

    PubMed

    Yamamoto, Naomune; Otsuka, Kuniaki; Kubo, Yutaka; Hayashi, Mitsutoshi; Mizuno, Koh; Ohshima, Hiroshi; Mukai, Chiaki

    2015-04-01

    We evaluated their circadian rhythms using data from electrocardiographic records and examined the change in circadian period related to normal RR intervals for astronauts who completed a long-term (?6-month) mission in space. The examinees were seven astronauts, five men and two women, from 2009 to 2010. Their mean?±?SD age was 52.0?±?4.2 years (47-59?yr). Each stayed in space for more than 160 days; their average length of stay was 172.6?±?14.6 days (163-199 days). We conducted a 24-h Holter electrocardiography before launch (Pre), at one month after launch (DF1), at two months after launch (DF2), at two weeks before return (DF3), and at three months after landing (Post), comparing each index of frequency-domain analysis and 24-h biological rhythms of the NN intervals (normal RR intervals). Results show that the mean period of Normal Sinus (NN) intervals was within 24?±?4?h at each examination. Inter-individual variability differed among the stages, being significantly smaller at DF3 (Pre versus DF1 versus DF3 versus Post?=?22.36?±?2.50 versus 25.46?±?4.37 versus 22.46?±?1.75 versus 26.16?±?7.18?h, p?circadian rhythms were disturbed until one month had passed in space, well-scheduled sleep and wake rhythms and meal times served as synchronizers. PMID:25392280

  7. [Peculiarities of circadian rhythms in plants from different geographical latitudes].

    PubMed

    Mayer, W

    1966-09-01

    1 Two species of plants (Taraxacum arcticum and Arnica angustifolia), collected in Spitsbergen (geogr. latitude 76-80 degrees) exhibit endogenous circadian leaf movements but also movements with shorter periods. Astragalus frigidus, A. alpinus and Hedysarum hedysaroides, collected in arctic regions of continental Europe, also show endogenous diurnal leaf movements. 2. In most of the species tested, there was no difference in the length of the free running periods of plants from arctic and Central-European regions. This is also the case when individuals of the same species collected in different regions are compared. However, in Taraxacum arcticum the period is shorter than in T. officinale In general, under constant conditions the circadian oscillations of arctic plants persist for a shorter period than those of other plants. 3. The free running periods of several of the investigated species from tropical regions are much longer than 24 hours, i.e., much longer than those of species from Central-European and arctic regions. 4. The free running periods of several tropical species are temperature-independent (Erythrina senegalensis, Albizzia lophanta, Rhynchosia memmonia, Vigna catjang, Phaseolus multiflorus). In other tropical species, however, the periods decrease rather strongly with increasing temperature (Phaseolus mungo, Canavalia obtusifolia, Clitoria ternatea, Dolichos lablab, Vigna sesquipedalis, Dolichos zebra). The temperature does not influence the amplitudes in Phaseolus mungo and Vigna sesquipedalis, but it strongly influences the amplitudes in Erythrina senegalensis, in LD-cycles as well as in continuous light. 5. The arctic plant Astragalus frigidus still shows free running oscillations at 12°C, whereas several tropical species oscillate only at temperatures above 17°C. 6. The differences in the periods of tropical and non-tropical species (see under [3]) disappear if the plants are compared not at the same temperature but at temperatures which are optimal for them. If tropical plants are tested 27°C and Central-European and arctic species at 17°C, the periods always approach the value of 24 hours. PMID:24557984

  8. Altered circadian rhythms of natural killer (NK) cell activity in patients with autoimmune rheumatic diseases.

    PubMed

    Masera, R G; Carignola, R; Staurenghi, A H; Sartori, M L; Lazzero, A; Griot, G; Angeli, A

    1994-01-01

    Natural Killer (NK) cells are a lymphocyte subset actively involved in cytotoxicity against tumor-transformed and virus-infected cells; they are a reliable model for the study of neuroendocrine-immune interactions. In previous works we demonstrated that in healthy subjects NK activity of peripheral blood mononuclear cells (PBMC) and susceptibility to endogenous modifiers display statistically validated circadian rhythms. In rheumatoid arthritis (RA) and in other autoimmune rheumatic diseases abnormalities of the circadian rhythm of serum cortisol and altered levels of NK cell activity have been reported. We evaluated the circadian pattern of NK cell activity in 7 hospitalized patients with autoimmune rheumatic diseases (4 RA, 1 scleroderma, 2 mixed connective tissue disease). Temporal variations of in vitro responses to either positive recombinant (immune interferon, r IFN-gamma IFN-gamma: 650 IU/ml; recombinant interleukin-2, r IL-2 IL-2: 100 IU/ml) or negative (cortisol: 10(-6) M) modifiers were also studied. Blood was drawn at 4h intervals for 24 h, starting at 0800. PBMC preparations were immediately separated and incubated for 20h in the presence or absence of modifiers. NK activity was assessed with a direct non-radiometric 4h cytolytic assay, using K 562 cells as targets. Significant circadian variations of spontaneous NK activity were documented only in women with RA, with a peak in the evening hours and a minimum in the night or in the early morning (p < 0.05, PR 51.5%, phi 1829). Population-mean cosinor analysis did not yield detection of significant circadian variations of in vitro responsiveness to modifiers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7924633

  9. Temporally Relationship between Renal Local Clock System and Circadian Rhythm of the Water Electrolyte Excretion.

    PubMed

    Zhang, Rui-Yu; Mou, Li-Jun; Li, Xue-Mei; Li, Xue-Wang; Qin, Yan

    2015-12-25

    Objective To investigate the relationship of the circadian rhythm of the urine volume and urine electrolytes excretion rate and the daily expression pattern of the clock genes and clock-controlled genes with the water electrolyte transportation circadian pattern in rat kidneys. Methods Male adult SD rats were exposed to in a light:dark (12:12) cycles. We collected two period urine from zeitgeber time (ZT)00:00-ZT12:00 (light time,rest period) and ZT12:00-24:00 (dark time,activity period) and then compared the urinary excretion rates of volume,sodium,potassium,and chloride at light time with those at dark time. Rats were sacrificed every 4 hours throughout a 24-hour day-night cycle. Circadian clock gene CLOCK,BMAL1,Per1,Per2,Cry1,Cry2 and kidney specific clock-controlled gene NHE3,?ENaC?NCC,Ptges,V1aR,V2R expression were profiled by real-time quantitative polymerase chain reaction. Data were analysed by a partial Fourier analysis and a stepwise regression technique. Results Urine volume and urine potassium excretion rate displayed high level at dark time and low at light time in SD rats (P<0.05),and urine sodium and chloride excretion rate also showed the trend(P>0.05).Clock gene CLOCK,BMAL1,Per1,Per2,Cry1,Cry2(P<0.05)and kidney specific clock-controlled gene NHE3,?ENaC,NCC,Ptges,V1aR,V2R (P<0.05)mRNA expression showed circadian pattern,and the peak times of the genes were in the dark time. Conclusion Urine volume and urine electrolyte excretion rate which displayed circadian pattern were temporally coupled with the rhythm of expression of clock and clock-controlled genes associated with water electrolyte transportation in rats kidney. PMID:26725393

  10. Circadian rhythms of clock gene expression in the cerebellum of serotonin-deficient Pet-1 knockout mice.

    PubMed

    Paulus, Erin V; Mintz, Eric M

    2016-01-01

    Serotonin plays an important role in the central regulation of circadian clock function. Serotonin levels are generally higher in the brain during periods of high activity, and these periods are in turn heavily regulated by the circadian clock located in the suprachiasmatic nucleus. However, the role of serotonin as a regulator of circadian rhythms elsewhere in the brain has not been extensively examined. In this study, we examined circadian rhythms of clock gene expression in the cerebellum in mice lacking the Pet-1 transcription factor, which results in a developed brain that is deficient in serotonin neurons. If serotonin helps to synchronize rhythms in brain regions other than the suprachiasmatic nucleus, we would expect to see differences in clock gene expression in these serotonin deficient mice. We found minor differences in the expression of Per1 and Per2 in the knockout mice as compared to wild type, but these differences were small and of questionable functional importance. We also measured the response of cerebellar clocks to injections of the serotonin agonist 8-OH-DPAT during the early part of the night. No effect on clock genes was observed, though the immediate-early gene Fos showed increased expression in wild type mice but not the knockouts. These results suggest that serotonin is not an important mediator of circadian rhythms in the cerebellum in a way that parallels its regulation of the circadian clock in the suprachiasmatic nucleus. PMID:26529643

  11. Disruption of cardiovascular circadian rhythms in mice post myocardial infarction: relationship with central angiotensin II receptor expression

    PubMed Central

    Mousa, Tarek M.; Schiller, Alicia M.; Zucker, Irving H.

    2014-01-01

    Abstract Angiotensin II (Ang II) is well known to participate in the abnormal autonomic cardiovascular control that occurs during the development of chronic heart failure (CHF). Disrupted cardiovascular circadian rhythm in CHF is also well accepted; however, the mechanisms underlying and the role of central Ang II type 1 receptors (AT1R) and oxidative stress in mediating such changes are not clear. In a post myocardial infarction (MI) CHF mouse model we investigated the circadian rhythm for mean arterial pressure (MAP), heart rate (HR), and baroreflex sensitivity (BRS) following MI. The cardiovascular parameters represent the middle 6?h averages during daytime (6:00–18:00) and nighttime (18:00–6:00). HR increased with the severity of CHF reaching its maximum by 12 weeks post?MI; loss of circadian HR and BRS rhythms were observed as early as 4 weeks post?MI in conjunction with a significant blunting of the BRS and an upregulation in the AT1R and gp91phox proteins in the brainstem. Loss of MAP circadian rhythm was observed 8 weeks post?MI. Circadian AT1R expression was demonstrated in sham animals but was lost 8 weeks following MI. Losartan reduced AT1R expression in daytime (1.18 ± 0.1 vs. 0.85 ± 0.1; P < 0.05) with a trend toward a reduction in the AT1R mRNA expression in the nighttime (1.2 ± 0.1 vs. 1.0 ± 0.1; P > 0.05) but failed to restore circadian variability. The disruption of circadian rhythm for HR, MAP and BRS along with the upregulation of AT1 and gp91phox suggests a possible role for central oxidative stress as a mediator of circadian cardiovascular parameters in the post?MI state. PMID:25413327

  12. Altered Circadian Rhythm and Metabolic Gene Profile in Rats Subjected to Advanced Light Phase Shifts

    PubMed Central

    Herrero, Laura; Valcarcel, Lorea; da Silva, Crhistiane Andressa; Albert, Nerea; Diez-Noguera, Antoni; Cambras, Trinitat; Serra, Dolors

    2015-01-01

    The circadian clock regulates metabolic homeostasis and its disruption predisposes to obesity and other metabolic diseases. However, the effect of phase shifts on metabolism is not completely understood. We examined whether alterations in the circadian rhythm caused by phase shifts induce metabolic changes in crucial genes that would predispose to obesity. Three-month-old rats were maintained on a standard diet under lighting conditions with chronic phase shifts consisting of advances, delays or advances plus delays. Serum leptin, insulin and glucose levels decreased only in rats subjected to advances. The expression of the clock gene Bmal 1 increased in the hypothalamus, white adipose tissue (WAT), brown adipose tissue (BAT) and liver of the advanced group compared to control rats. The advanced group showed an increase in hypothalamic AgRP and NPY mRNA, and their lipid metabolism gene profile was altered in liver, WAT and BAT. WAT showed an increase in inflammation and ER stress and brown adipocytes suffered a brown-to-white transformation and decreased UCP-1 expression. Our results indicate that chronic phase advances lead to significant changes in neuropeptides, lipid metabolism, inflammation and ER stress gene profile in metabolically relevant tissues such as the hypothalamus, liver, WAT and BAT. This highlights a link between alteration of the circadian rhythm and metabolism at the transcriptional level. PMID:25837425

  13. Effects of square-wave and simulated natural light-dark cycles on hamster circadian rhythms

    NASA Technical Reports Server (NTRS)

    Tang, I. H.; Murakami, D. M.; Fuller, C. A.

    1999-01-01

    Circadian rhythms of activity (Act) and body temperature (Tb) were recorded from male Syrian hamsters under square-wave (LDSq) and simulated natural (LDSN, with dawn and dusk transitions) light-dark cycles. Light intensity and data sampling were under the synchronized control of a laboratory computer. Changes in reactive and predictive onsets and offsets for the circadian rhythms of Act and Tb were examined in both lighting conditions. The reactive Act onset occurred 1.1 h earlier (P < 0.01) in LDSN than in LDSq and had a longer alpha-period (1.7 h; P < 0.05). The reactive Tb onset was 0.7 h earlier (P < 0.01) in LDSN. In LDSN, the predictive Act onset advanced by 0.3 h (P < 0.05), whereas the Tb predictive onset remained the same as in LDSq. The phase angle difference between Act and Tb predictive onsets decreased by 0.9 h (P < 0.05) in LDSN, but the offsets of both measures remained unchanged. In this study, animals exhibited different circadian entrainment characteristics under LDSq and LDSN, suggesting that gradual and abrupt transitions between light and dark may provide different temporal cues.

  14. Serotonin, a possible intermediate between disturbed circadian rhythms and metabolic disease.

    PubMed

    Versteeg, R I; Serlie, M J; Kalsbeek, A; la Fleur, S E

    2015-08-20

    It is evident that eating in misalignment with the biological clock (such as in shift work, eating late at night and skipping breakfast) is associated with increased risk for obesity and diabetes. The biological clock located in the suprachiasmatic nucleus dictates energy balance including feeding behavior and glucose metabolism. Besides eating and sleeping patterns, glucose metabolism also exhibits clear diurnal variations with higher blood glucose concentrations, glucose tolerance and insulin sensitivity prior to waking up. The daily variation in plasma glucose concentrations in rats, is independent of the rhythm in feeding behavior. On the other hand, feeding itself has profound effects on glucose metabolism, but differential effects occur depending on the time of the day. We here review data showing that a disturbed diurnal eating pattern results in alterations in glucose metabolism induced by a disrupted circadian clock. We first describe the role of central serotonin on feeding behavior and glucose metabolism and subsequently describe the effects of central serotonin on the circadian system. We next explore the interaction between the serotonergic system and the circadian clock in conditions of disrupted diurnal rhythms in feeding and how this might be involved in the metabolic dysregulation that occurs with chronodisruption. PMID:26047725

  15. Improvement of Circadian Rhythm of Heart Rate Variability by Eurythmy Therapy Training

    PubMed Central

    Seifert, Georg; Kanitz, Jenny-Lena; Pretzer, Kim; Henze, Günter; Witt, Katharina; Reulecke, Sina; Voss, Andreas

    2013-01-01

    Background. Impairment of circadian rhythm is associated with various clinical problems. It not only has a negative impact on quality of life but can also be associated with a significantly poorer prognosis. Eurythmy therapy (EYT) is an anthroposophic movement therapy aimed at reducing fatigue symptoms and stress levels. Objective. This analysis of healthy subjects was conducted to examine whether the improvement in fatigue symptoms was accompanied by improvements in the circadian rhythm of heart rate variability (HRV). Design. Twenty-three women performed 10 hours of EYT over six weeks. Electrocardiograms (ECGs) were recorded before and after the EYT trial. HRV was quantified by parameters of the frequency and time domains and the nonlinear parameters of symbolic dynamics. Results. The day-night contrast with predominance of vagal activity at night becomes more pronounced after the EYT training, and with decreased Ultralow and very low frequencies, the HRV shows evidence of calmer sleep. During the night, the complexity of the HRV is significantly increased indicated by nonlinear parameters. Conclusion. The analysis of the circadian patterns of cardiophysiological parameters before and after EYT shows significant improvements in HRV in terms of greater day-night contrast caused by an increase of vagal activity and calmer and more complex HRV patterns during sleep. PMID:23533496

  16. The parathyroid hormone circadian rhythm is truly endogenous--a general clinical research center study

    NASA Technical Reports Server (NTRS)

    el-Hajj Fuleihan, G.; Klerman, E. B.; Brown, E. N.; Choe, Y.; Brown, E. M.; Czeisler, C. A.

    1997-01-01

    While circulating levels of PTH follow a diurnal pattern, it has been unclear whether these changes are truly endogenous or are dictated by external factors that themselves follow a diurnal pattern, such as sleep-wake cycles, light-dark cycles, meals, or posture. We evaluated the diurnal rhythm of PTH in 11 normal healthy male volunteers in our Intensive Physiologic Monitoring Unit. The first 36 h spent under baseline conditions were followed by 28-40 h of constant routine conditions (CR; enforced wakefulness in the strict semirecumbent position, with the consumption of hourly snacks). During baseline conditions, PTH levels followed a bimodal diurnal rhythm with an average amplitude of 4.2 pg/mL. A primary peak (t1max) occurred at 0314 h, and the secondary peak (t2max) occurred at 1726 h, whereas the primary and secondary nadirs (t1min and t2min) took place, on the average, at 1041 and 2103 h, respectively. This rhythm was preserved under CR conditions, albeit with different characteristics, thus confirming its endogenous nature. The serum ionized calcium (Cai) demonstrated a rhythm in 3 of the 5 subjects studied that varied widely between individuals and did not have any apparent relation to PTH. Urinary calcium/creatinine (UCa/Cr), phosphate/Cr (UPO4/Cr), and sodium/Cr (UNa/Cr) ratios all followed a diurnal rhythm during the baseline day. These rhythms persisted during the CR, although with different characteristics for the first two parameters, whereas that of UNa/Cr was unchanged. In general, the temporal pattern for the UCa/Cr curve was a mirror image of the PTH curve, whereas the UPO4/Cr pattern moved in parallel with the PTH curve. In conclusion, PTH levels exhibit a diurnal rhythm that persists during a CR, thereby confirming that a large component of this rhythm is an endogenous circadian rhythm. The clinical relevance of this rhythm is reflected in the associated rhythms of biological markers of PTH effect at the kidney, namely UCa/Cr and UPO4/Cr.

  17. Corkscrews and singularities in fruitflies - Resetting behavior of the circadian eclosion rhythm.

    NASA Technical Reports Server (NTRS)

    Winfree, A. T.

    1971-01-01

    Description of experiments undertaken to define the phase-resetting behavior of the circadian rhythm of pupal eclosion in populations of fruitflies. An attempt is made to determine how and why the resetting response depends on the duration of a standard perturbation as well as on the time at which it is given. Plotting a three-dimensional graph of the measured emergence centroids vs the stimulus variables, the data are found to spiral up around a vertical rotation axis. Using a computer, a smooth surface, called the resetting surface, which approximately fits the helicoidal cloud of data points, is obtained and is shown to be best described as a vertical corkscrew linking together tilted planes. This corkscrew feature of the resetting surface is taken to indicate that there is an isolated perturbation following which there is either no circadian rhythm of emergence in the steady state, or one of unpredictable phase. A hypothesis concerning the clock dynamics underlying the eclosion rhythm is briefly sketched which encompasses the main features of known resetting data using single discrete pulses of any perturbing agent.

  18. The Scorpion An ideal animal model to study long-term microgravity effects on circadian rhythms

    NASA Astrophysics Data System (ADS)

    Riewe, Pascal C.; Horn, Eberhard R.

    2000-01-01

    The temporal pattern of light and darkness is basic for the coordination of circadian rhythms and establishment of homoeostasis. The 24th frequency of zeitgebers is probably a function of the Earth's rotation. The only way to eliminate its influence on organisms is to study their behavior in space because the reduced day length during orbiting the Earth might disrupt synchronizing mechanisms based on the 24th rhythm. The stability of microgravity induced disturbances of synchronization as well as the extent of adaptation of different physiological processes to this novel environment can only be studied during long-term exposures to microgravity, i.e., on the International Space Station. Biological studies within the long-term domain on ISS demand the use of experimental models which can be exposed to automatic handling of measurements and which need less or no nutritional care. Scorpions offer these features. We describe a fully automatic recording device for the simultaneous collection of data regarding the sensorimotor system and homoeostatic mechanisms. In particular, we record sensitivity changes of the eyes, motor activity and heart beat and/or respiratory activity. The advantage of the scorpion model is supported by the fact that data can be recorded preflight, inflight and postflight from the same animal. With this animal model, basic insights will be obtained about the de-coupling of circadian rhythms of multiple oscillators and their adaptation to the entraining zeitgeber periodicity during exposure to microgravity for at least three biological parameters recorded simultaneously. .

  19. Vasopressin deficiency and circadian rhythms during food-restriction stress.

    PubMed

    Murphy, H M; Wideman, C H; Nadzam, G R

    1993-01-01

    Vasopressin-containing, Long-Evans (LE) rats and vasopressin-deficient, Brattleboro (DI) rats were monitored for activity and core body temperature via telemetry. Rats were exposed to a 12-12 light-dark cycle and allowed to habituate with ad lib access to food and water. The habituation period was followed by an experimental period of 23 h of food-restriction stress in which a 1-h feeding period was provided during the light cycle. Although both strains of animals showed nocturnal activity and temperature rhythms during the habituation period, DI rats were more active than LE rats. The DI rats also had a lower body temperature in the dark. During the experimental period, both strains exhibited a phase shift of activity and body temperature correlating with the presentation of food. The DI rats developed a diurnal shift more rapidly than LE rats. The DI animals showed a dramatic increase in activity during the light phase and a marked decrease in body temperature during the dark phase. The LE animals showed a significant attenuation of activity, but maintained both nocturnal and diurnal temperature peaks throughout the food-restricted condition. PMID:8134303

  20. Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome.

    PubMed

    Trenkwalder, C; Hening, W A; Walters, A S; Campbell, S S; Rahman, K; Chokroverty, S

    1999-01-01

    The symptoms of restless legs syndrome (RLS) worsen while patients are sitting or lying and also worsen at night. The current study was designed to determine if the periodic limb movements (PLMs) and sensory symptoms of RLS are modulated by an independent circadian factor. We recorded sleeping and waking PLMs and waking sensory symptoms in eight volunteers with RLS for 3 successive nights and days, starting with a polysomnographic recording of 2 nights, followed by a third night of sleep deprivation and the day after sleep deprivation. This study showed that both the PLMs and sensory symptoms were worst at night with a maximum for both between midnight and 1:00 AM and a minimum between 9:00 and 11:00 AM. Sleep and drowsiness had a tendency to worsen PLMs and sensory symptoms after the night of sleep deprivation. Circadian temperature curves were normal in all four patients with adequate data collection. The highest PLM counts occurred on the falling phase of the circadian temperature curve whereas the lowest PLM counts occurred on the rising phase of the curve. We conclude that the PLM and sensory symptoms in RLS are influenced by a circadian rhythm, and that the "worsening at night" criterion of the RLS Definition Criteria is, at least in part, distinct from the "worsening while lying or sitting" criterion. PMID:9918351

  1. Impacts of shift work on sleep and circadian rhythms.

    PubMed

    Boivin, D B; Boudreau, P

    2014-10-01

    Shift work comprises work schedules that extend beyond the typical "nine-to-five" workday, wherein schedules often comprise early work start, compressed work weeks with 12-hour shifts, and night work. According to recent American and European surveys, between 15 and 30% of adult workers are engaged in some type of shift work, with 19% of the European population reportedly working at least 2 hours between 22:00 and 05:00. The 2005 International Classification of Sleep Disorders estimates that a shift work sleep disorder can be found in 2-5% of workers. This disorder is characterized by excessive sleepiness and/or sleep disruption for at least one month in relation with the atypical work schedule. Individual tolerance to shift work remains a complex problem that is affected by the number of consecutive work hours and shifts, the rest periods, and the predictability of work schedules. Sleepiness usually occurs during night shifts and is maximal at the end of the night. Impaired vigilance and performance occur around times of increased sleepiness and can seriously compromise workers' health and safety. Indeed, workers suffering from a shift work sleep-wake disorder can fall asleep involuntarily at work or while driving back home after a night shift. Working on atypical shifts has important socioeconomic impacts as it leads to an increased risk of accidents, workers' impairment and danger to public safety, especially at night. The aim of the present review is to review the circadian and sleep-wake disturbances associated with shift work as well as their medical impacts. PMID:25246026

  2. Hopf Bifurcations in a Model for Circadian Rhythms in Arabidopsis Thaliana

    NASA Astrophysics Data System (ADS)

    Shindell, Orrin; Tagg, Randall

    2011-03-01

    Arabidopsis thaliana is a plant used for many fundamental studies, including circadian rhythms. Numerically integrating the 7-equation kinetic model of Locke et al. [J. Theor. Bio. 234 (2005) 383], we have mapped regions of parameter space where circadian expression of key mRNA and proteins undergoes limit cycle oscillation. We seek to relate this to the work of Fukuda et al. [Phys. Rev. Lett. 99 (2007) 098102], where a coupled system of cells individually described by Stuart-Landau equations is used phenomenologically to describe experimentally observed spatio-temporal patterns in the plant leaves. To that end we have done a weakly nonlinear analysis of the system of kinetic equations. We also comment on possible experimental directions to further connect the kinetic models to dynamics in this multi-cellular system.

  3. Influences of horizontal hypokinesia on performance and circadian physiological rhythms in female humans

    NASA Technical Reports Server (NTRS)

    Winget, C. M.; Deroshia, C. W.; Sandler, H.

    1982-01-01

    Eight females from 35-45 yr of age were subjected to seven days of ambulatory control, seven days of bed rest, and a five day recovery period, with 30 min of centrifugation on day seven of bedrest to determine the effects of weightlessness on the circadian rhythms of females in that age group. Heart rate and rectal temperature (RT) were monitored and each subject was tested in a flight simulator twice a day in conditions of varying levels of turbulence. The flight simulations were run during the morning and acrophase of the circadian RT and performance errors wery monitored for 6 min. No significant differences were detected in the group performance data pre-, during, and post-bedrest, although better performance in the simulator was observed after the centrifuge exposure. An RT phase shift was statistically significant between pre- and during bedrest stages.

  4. Circadian rhythms and metabolic syndrome: from experimental genetics to human disease.

    PubMed

    Maury, Eleonore; Ramsey, Kathryn Moynihan; Bass, Joseph

    2010-02-19

    The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal clock system, and sleep, constitute risk factors for disorders including obesity, diabetes mellitus, cardiovascular disease, thrombosis and even inflammation. An exciting aspect of the field has been the integration of behavioral and physiological approaches, and the emerging insight into both neural and peripheral tissues in disease pathogenesis. Consideration of the cell and molecular links between disorders of circadian rhythms and sleep with metabolic syndrome has begun to open new opportunities for mechanism-based therapeutics. PMID:20167942

  5. The role of clock genes and circadian rhythm in the development of cardiovascular diseases.

    PubMed

    Takeda, Norihiko; Maemura, Koji

    2015-09-01

    The time of onset of cardiovascular disorders such as myocardial infarctions or ventricular arrhythmias exhibits a circadian rhythm. Diurnal variations in autonomic nervous activity, plasma cortisol level or renin-angiotensin activity underlie the pathogenesis of cardiovascular diseases. Transcriptional-translational feedback loop of the clock genes constitute a molecular clock system. In addition to the central clock in the suprachiasmatic nucleus, clock genes are also expressed in a circadian fashion in each organ to make up the peripheral clock. The peripheral clock seems to be beneficial for anticipating external stimuli and thus contributes to the maintenance of organ homeostasis. Loss of synchronization between the central and peripheral clocks also augments disease progression. Moreover, accumulating evidence shows that clock genes affect inflammatory and intracellular metabolic signaling. Elucidating the roles of the molecular clock in cardiovascular pathology through the identification of clock controlled genes will help to establish a novel therapeutic approach for cardiovascular disorders. PMID:25972277

  6. Dynamics of three coupled van der Pol oscillators with application to circadian rhythms

    NASA Astrophysics Data System (ADS)

    Rompala, Kevin; Rand, Richard; Howland, Howard

    2007-08-01

    In this work we study a system of three van der Pol oscillators. Two of the oscillators are identical, and are not directly coupled to each other, but rather are coupled via the third oscillator. We investigate the existence of the in-phase mode in which the two identical oscillators have the same behavior. To this end we use the two variable expansion perturbation method (also known as multiple scales) to obtain a slow flow, which we then analyze using the computer algebra system MACSYMA and the numerical bifurcation software AUTO. Our motivation for studying this system comes from the presence of circadian rhythms in the chemistry of the eyes. We model the circadian oscillator in each eye as a van der Pol oscillator. Although there is no direct connection between the two eyes, they are both connected to the brain, especially to the pineal gland, which is here represented by a third van der Pol oscillator.

  7. Control mechanisms of circadian rhythms in body composition: Implications for manned spaceflight

    NASA Technical Reports Server (NTRS)

    Ede, M. C. M.

    1975-01-01

    The mechanisms that underlie the circadian variations in electrolyte content in body fluid compartments were investigated, and the mechanisms that control the oscillations were studied in order to investigate what effects internal desynchronization in such a system would have during manned space flight. The studies were performed using volunteer human subjects and squirrel monkeys. The intercompartmental distribution of potassium was examined when dietary intake, activity, and posture are held constant throughout each 24-hour day. A net flux of potassium was observed out of the body cell mass during the day and a reverse flux from the extracellular fluid into the body cell mass during the night, counterbalanced by changes in urinary potassium excretion. Experiments with monkeys provided evidence for the synchronization of renal potassium excretion by the rhythm of cortisol secretion with the light-dark cycle. Three models of the circadian timing system were formalized.

  8. Effect of feeding and temperature on the circadian rhythms of cortisol, thyroxine and triiodothyronine in pigs

    SciTech Connect

    Becker, B.A.; Nienaber, J.A.; Ford, J.J.; Hahn, G.L.

    1986-03-05

    An experiment was conducted to evaluate the circadian rhythms of cortisol, thyroxine (T/sub 4/) and triiodothyronine (T/sub 3/) in pigs under two temperature and feeding regimes. Twenty-eight barrows were randomly assigned to one of the following: 1) ad-libitum fed at 5/sup 0/C(AL-5); 2) ad-libitum fed at 20/sup 0/C(AL-20); 3) meal fed at 5/sup 0/C(M-5); and 4) meal fed at 20/sup 0/C(M-20). M-5 and M-20 animals were fed at 0730 and 1400 hrs. Lights were on from 0600 to 2000 hrs. After 5 wks, blood samples were collected for 27 hrs. Serum cortisol, T/sub 4/ and T/sub 3/ concentrations were determined by RIA. No significant differences were found in the mesors, amplitudes or acrophases for cortisol. The mesors for T/sub 4/ (p<.01) were 60.6 +/- 5.6, 40.2 +/- 5.6, 61.2 +/- 5.6 and 49.1 +/- 5.0 ng/ml for AL-5, AL-20, M-5, and M-20, respectively. The mesors for T/sub 3/ (p<.01) were .85 +/- .06, .69 +/- .06, .92 +/- .06 and .66 +/- .05 ng/ml for AL-5, AL-20, M-5, and M-20 respectively. No differences in the amplitudes or acrophases for T/sub 3/ or T/sub 4/ were found. These data show that temperature and feeding regimes do not entrain the circadian rhythm of cortisol in pigs. The circadian rhythms of T/sub 4/ and T/sub 3/ are also not altered by feeding regimes but are affected by temperature.

  9. Pharmacology of Myopia and Potential Role for Intrinsic Retinal Circadian Rhythms

    PubMed Central

    Stone, Richard A.; Pardue, Machelle T.; Iuvone, P. Michael; Khurana, Tejvir S.

    2013-01-01

    Despite the high prevalence and public health impact of refractive errors, the mechanisms responsible for ametropias are poorly understood. Much evidence now supports the concept that the retina is central to the mechanism(s) regulating emmetropization and underlying refractive errors. Using a variety of pharmacologic methods and well-defined experimental eye growth models in laboratory animals, many retinal neurotransmitters and neuromodulators have been implicated in this process. Nonetheless, an accepted framework for understanding the molecular and/or cellular pathways that govern postnatal eye development is lacking. Here, we review two extensively studied signaling pathways whose general roles in refractive development are supported by both experimental and clinical data: acetylcholine signaling through muscarinic and/or nicotinic acetylcholine receptors and retinal dopamine pharmacology. The muscarinic acetylcholine receptor antagonist atropine was first studied as an anti-myopia drug some two centuries ago, and much subsequent work has continued to connect muscarinic receptors to eye growth regulation. Recent research implicates a potential role of nicotinic acetycholine receptors; and the refractive effects in population surveys of passive exposure to cigarette smoke, of which nicotine is a constituent, support clinical relevance. Reviewed here, many puzzling results inhibit formulating a mechanistic framework that explains acetylcholine’s role in refractive development. How cholinergic receptor mechanisms might be used to develop acceptable approaches to normalize refractive development remains a challenge. Retinal dopamine signaling not only has a putative role in refractive development, its upregulation by light comprises an important component of the retinal clock network and contributes to the regulation of retinal circadian physiology. During postnatal development, the ocular dimensions undergo circadian and/or diurnal fluctuations in magnitude; these rhythms shift in eyes developing experimental ametropia. Long-standing clinical ideas about myopia in particular have postulated a role for ambient lighting, although molecular or cellular mechanisms for these speculations have remained obscure. Experimental myopia induced by the wearing of a concave spectacle lens alters the retinal expression of a significant proportion of intrinsic circadian clock genes, as well as genes encoding a melatonin receptor and the photopigment melanopsin. Together this evidence suggests a hypothesis that the retinal clock and intrinsic retinal circadian rhythms may be fundamental to the mechanism(s) regulating refractive development, and that disruptions in circadian signals may produce refractive errors. Here we review the potential role of biological rhythms in refractive development. While much future research is needed, this hypothesis could unify many of the disparate clinical and laboratory observations addressing the pathogenesis of refractive errors. PMID:23313151

  10. Circadian Rhythms in Rho1 Activity Regulate Neuronal Plasticity and Network Hierarchy.

    PubMed

    Petsakou, Afroditi; Sapsis, Themistoklis P; Blau, Justin

    2015-08-13

    Neuronal plasticity helps animals learn from their environment. However, it is challenging to link specific changes in defined neurons to altered behavior. Here, we focus on circadian rhythms in the structure of the principal s-LNv clock neurons in Drosophila. By quantifying neuronal architecture, we observed that s-LNv structural plasticity changes the amount of axonal material in addition to cycles of fasciculation and defasciculation. We found that this is controlled by rhythmic Rho1 activity that retracts s-LNv axonal termini by increasing myosin phosphorylation and simultaneously changes the balance of pre-synaptic and dendritic markers. This plasticity is required to change clock network hierarchy and allow seasonal adaptation. Rhythms in Rho1 activity are controlled by clock-regulated transcription of Puratrophin-1-like (Pura), a Rho1 GEF. Since spinocerebellar ataxia is associated with mutations in human Puratrophin-1, our data support the idea that defective actin-related plasticity underlies this ataxia. PMID:26234154

  11. The Journal of Neuroscience, January 15, 1996, 16(2):744-751 Cholinergic Regulation of the Suprachiasmatic Nucleus Circadian

    E-print Network

    Gillette, Martha U.

    of the Suprachiasmatic Nucleus Circadian Rhythm via a Muscarinic Mechanism at Night Chen Liul and Martha U. Gillette',2) is responsible for the generation of most circadian rhythms and for their entrainment to environmental cues. Carbachol, an agonist of acetylcholine (ACh), has been shown to shift the phase of circadian rhythms

  12. Circadian rhythm of plasma and urinary angiotensinogen in healthy volunteers and in patients with chronic kidney disease

    PubMed Central

    Nishijima, Yoko; Kobori, Hiroyuki; Kaifu, Kumiko; Mizushige, Tomoko; Hara, Taiga; Nishiyama, Akira; Kohno, Masakazu

    2014-01-01

    The urinary angiotensinogen (AGT) excretion rate could be a novel biomarker for the intrarenal activity of the reninangiotensin system. Little is known about the circadian rhythm of AGT levels in plasma or urine. In this short article, making use of data in plasma and urine of healthy volunteers and patients with chronic kidney diseases, we first report that we were unable to find evidence for a circadian rhythm of AGT under any condition. Next we critically discuss to what degree elevated urinary AGT levels might be considered an independent biomarker that is not simply the non-specific consequence of proteinuria. PMID:25381307

  13. Circadian Rhythms of Sense and Antisense Transcription in Sugarcane, a Highly Polyploid Crop

    PubMed Central

    Hotta, Carlos Takeshi; Nishiyama, Milton Yutaka; Souza, Glaucia Mendes

    2013-01-01

    Commercial sugarcane (Saccharum hybrid) is a highly polyploid and aneuploid grass that stores large amounts of sucrose in its stem. We have measured circadian rhythms of sense and antisense transcription in a commercial cultivar (RB855453) using a custom oligoarray with 14,521 probes that hybridize to sense transcripts (SS) and 7,380 probes that hybridize to antisense transcripts (AS).We estimated that 32% of SS probes and 22% AS probes were rhythmic. This is a higher proportion of rhythmic probes than the usually found in similar experiments in other plant species. Orthologs and inparalogs of Arabidopsis thaliana, sugarcane, rice, maize and sorghum were grouped in ortholog clusters. When ortholog clusters were used to compare probes among different datasets, sugarcane also showed a higher proportion of rhythmic elements than the other species. Thus, it is possible that a higher proportion of transcripts are regulated by the sugarcane circadian clock. Thirty-six percent of the identified AS/SS pairs had significant correlated time courses and 64% had uncorrelated expression patterns. The clustering of transcripts with similar function, the anticipation of daily environmental changes and the temporal compartmentation of metabolic processes were some properties identified in the circadian sugarcane transcriptome. During the day, there was a dominance of transcripts associated with photosynthesis and carbohydrate metabolism, including sucrose and starch synthesis. During the night, there was dominance of transcripts associated with genetic processing, such as histone regulation and RNA polymerase, ribosome and protein synthesis. Finally, the circadian clock also regulated hormone signalling pathways: a large proportion of auxin and ABA signalling components were regulated by the circadian clock in an unusual biphasic distribution. PMID:23936527

  14. Evidence for clock genes circadian rhythms in human full-term placenta.

    PubMed

    Pérez, Silvia; Murias, Lucía; Fernández-Plaza, Catalina; Díaz, Irene; González, Celestino; Otero, Jesús; Díaz, Elena

    2015-12-01

    Biological rhythms are driven by endogenous biological clocks; in mammals, the master clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. This master pacemaker can synchronize other peripheral oscillators in several tissues such as some involved in endocrine or reproductive functions. The presence of an endogenous placental clock has received little attention. In fact, there are no studies in human full-term placentas. To test the existence of an endogenous pacemaker in this tissue we have studied the expression of circadian locomoter output cycles kaput (Clock), brain and muscle arnt-like (Bmal)1, period (Per)2, and cryptochrome (Cry)1 mRNAs at 00, 04, 08, 12, 16, and 20 hours by qPCR. The four clock genes studied are expressed in full-term human placenta. The results obtained allow us to suggest that a peripheral oscillator exists in human placenta. Data were analyzed using Fourier series where only the Clock and Bmal1 expression shows a circadian rhythm. PMID:26247999

  15. Light masking of circadian rhythms of heat production, heat loss, and body temperature in squirrel monkeys

    NASA Technical Reports Server (NTRS)

    Robinson, E. L.; Fuller, C. A.

    1999-01-01

    Whole body heat production (HP) and heat loss (HL) were examined to determine their relative contributions to light masking of the circadian rhythm in body temperature (Tb). Squirrel monkey metabolism (n = 6) was monitored by both indirect and direct calorimetry, with telemetered measurement of body temperature and activity. Feeding was also measured. Responses to an entraining light-dark (LD) cycle (LD 12:12) and a masking LD cycle (LD 2:2) were compared. HP and HL contributed to both the daily rhythm and the masking changes in Tb. All variables showed phase-dependent masking responses. Masking transients at L or D transitions were generally greater during subjective day; however, L masking resulted in sustained elevation of Tb, HP, and HL during subjective night. Parallel, apparently compensatory, changes of HL and HP suggest action by both the circadian timing system and light masking on Tb set point. Furthermore, transient HL increases during subjective night suggest that gain change may supplement set point regulation of Tb.

  16. Single-cell resolution fluorescence imaging of circadian rhythms detected with a Nipkow spinning disk confocal system.

    PubMed

    Enoki, Ryosuke; Ono, Daisuke; Hasan, Mazahir T; Honma, Sato; Honma, Ken-Ichi

    2012-05-30

    Single-point laser scanning confocal imaging produces signals with high spatial resolution in living organisms. However, photo-induced toxicity, bleaching, and focus drift remain challenges, especially when recording over several days for monitoring circadian rhythms. Bioluminescence imaging is a tool widely used for this purpose, and does not cause photo-induced difficulties. However, bioluminescence signals are dimmer than fluorescence signals, and are potentially affected by levels of cofactors, including ATP, O(2), and the substrate, luciferin. Here we describe a novel time-lapse confocal imaging technique to monitor circadian rhythms in living tissues. The imaging system comprises a multipoint scanning Nipkow spinning disk confocal unit and a high-sensitivity EM-CCD camera mounted on an inverted microscope with auto-focusing function. Brain slices of the suprachiasmatic nucleus (SCN), the central circadian clock, were prepared from transgenic mice expressing a clock gene, Period 1 (Per1), and fluorescence reporter protein (Per1::d2EGFP). The SCN slices were cut out together with membrane, flipped over, and transferred to the collagen-coated glass dishes to obtain signals with a high signal-to-noise ratio and to minimize focus drift. The imaging technique and improved culture method enabled us to monitor the circadian rhythm of Per1::d2EGFP from optically confirmed single SCN neurons without noticeable photo-induced effects or focus drift. Using recombinant adeno-associated virus carrying a genetically encoded calcium indicator, we also monitored calcium circadian rhythms at a single-cell level in a large population of SCN neurons. Thus, the Nipkow spinning disk confocal imaging system developed here facilitates long-term visualization of circadian rhythms in living cells. PMID:22480987

  17. Chronotype influences activity circadian rhythm and sleep: differences in sleep quality between weekdays and weekend.

    PubMed

    Vitale, Jacopo A; Roveda, Eliana; Montaruli, Angela; Galasso, Letizia; Weydahl, Andi; Caumo, Andrea; Carandente, Franca

    2015-04-01

    Several studies have shown the differences among chronotypes in the circadian rhythm of different physiological variables. Individuals show variation in their preference for the daily timing of activity; additionally, there is an association between chronotype and sleep duration/sleep complaints. Few studies have investigated sleep quality during the week days and weekends in relation to the circadian typology using self-assessment questionnaires or actigraphy. The purpose of this study was to use actigraphy to assess the relationship between the three chronotypes and the circadian rhythm of activity levels and to determine whether sleep parameters respond differently with respect to time (weekdays versus the weekend) in Morning-types (M-types), Neither-types (N-types) and Evening-types (E-types). The morningness-eveningness questionnaire (MEQ) was administered to 502 college students to determine their chronotypes. Fifty subjects (16?M-types, 15?N-types and 19?E-types) were recruited to undergo a 7-days monitoring period with an actigraph (Actiwacth® actometers, CNT, Cambridge, UK) to evaluate their sleep parameters and the circadian rhythm of their activity levels. To compare the amplitude and the acrophase among the three chronotypes, we used a one-way ANOVA followed by the Tukey-Kramer post-hoc test. To compare the Midline Estimating Statistic of Rhythm (MESOR) among the three chronotypes, we used a Kruskal-Wallis non-parametric test followed by pairwise comparisons that were performed using Dunn's procedure with a Bonferroni correction for multiple comparisons. The analysis of each sleep parameter was conducted using the mixed ANOVA procedure. The results showed that the chronotype was influenced by sex (?(2) with p?=?0.011) and the photoperiod at birth (?(2) with p?circadian rhythm of activity levels was influenced by the chronotype; second, the chronotype had a significant effect on sleep parameters: the E-types had a reduced sleep quality and quantity compared with the M- and N-types during weekdays, whereas the E-types reached the same levels as the other chronotypes during the weekends. These findings suggest that E-types accumulate a sleep deficit during weekdays due to social and academic commitments and that they recover from this deficit during "free days" on the weekend. PMID:25469597

  18. Weaker Circadian Activity Rhythms are Associated with Poorer Executive Function in Older Women

    PubMed Central

    Walsh, Christine M.; Blackwell, Terri; Tranah, Gregory J.; Stone, Katie L.; Ancoli-Israel, Sonia; Redline, Susan; Paudel, Misti; Kramer, Joel H.; Yaffe, Kristine

    2014-01-01

    Study Objectives: Older adults and patients with dementia often have disrupted circadian activity rhythms (CARs). Disrupted CARs are associated with health declines and could affect cognitive aging. We hypothesized that among older women, weaker CARs would be associated with poorer cognitive function 5 y later. Design: Prospective observational study. Setting: Three US clinical sites. Participants: There were 1,287 community-dwelling older women (82.8 ± 3.1 y) participating in an ongoing prospective study who were free of dementia at the baseline visit. Measurements and Results: Baseline actigraphy was used to determine CAR measures (amplitude, mesor, and rhythm robustness, analyzed as quartiles; acrophase analyzed by peak activity time < 13:34 and > 15:51). Five years later, cognitive performance was assessed with the Modified Mini-Mental Status Examination (3MS), California Verbal Learning Task (CVLT), digit span, Trail Making Test B (Trails B), categorical fluency, and letter fluency. We compared cognitive performance with CARs using analyses of covariance adjusted for a number of health factors and comorbidities. Women in the lowest quartile for CAR amplitude performed worse on Trails B and categorical fluency compared to women in the highest quartile (group difference (d) = 30.42 sec, d = -1.01 words respectively, P < 0.05). Women in the lowest quartile for mesor performed worse on categorical fluency (d = -0.86 words, P < 0.05). Women with a later acrophase performed worse on categorical fluency (d = -0.69 words, P < 0.05). Controlling for baseline Mini-Mental State Examination and sleep factors had little effect on our results. Conclusions: Weaker circadian activity rhythm patterns are associated with worse cognitive function, especially executive function, in older women without dementia. Further investigation is required to determine the etiology of these relationships. Citation: Walsh CM, Blackwell T, Tranah GJ, Stone KL, Ancoli-Israel S, Redline S, Paudel M, Kramer JH, Yaffe K. Weaker circadian activity rhythms are associated with poorer executive function in older women. SLEEP 2014;37(12):2009-2016. PMID:25337947

  19. Coordinated regulation of circadian rhythms and homeostasis by the suprachiasmatic nucleus

    PubMed Central

    Nakagawa, Hachiro; Okumura, Nobuaki

    2010-01-01

    We have demonstrated that in rats activities of various enzymes related to gluconeogenesis and amino acid metabolism show circadian rhythms. Based on these results, we have explored the molecular mechanisms underlying circadian oscillation and phase response to light of the master clock located in the dorsomedial subdivision of the suprachiasmatic nucleus (SCN) and found various proteins closely related to phase response such as BIT/SHPS-1 and those of circadian oscillation, some of which are involved in protein-tyrosine phosphorylation. On the other hand, we have presented several lines of evidence that the ventrolateral subdivision of the SCN includes not only the control center of energy supply to the brain, but also that of homeostasis such as blood glucose, blood pressure, water balance, and body temperature. We have also shown that besides these functions, the latter subdivision is involved in the regulations of hormone secretions such as insulin, glucagon, corticosterone and vasopressin. It has been also shown by electrophysiological means that light exposure to rat eye enhances sympathetic nerve activity, whereas it depresses parasympathetic nerve activity. Thus, environmental light is implicated not only in the phase-shift through the retinohypthalamic tract (RHT), but also control of autonomic nerve activities through the RHT, It is also discussed in this review how the two divisions are interconnected and how environmental light is involved in this interconnection. PMID:20431263

  20. Light-sampling behavior in photoentrainment of a rodent circadian rhythm.

    PubMed

    DeCoursey, P J

    1986-08-01

    Behavioral aspects of photoentrainment of circadian locomotor activity rhythms were recorded for a nocturnal den-dwelling rodent, the flying squirrel, Glaucomys volans. Methods included both telemetric monitoring and infrared observations of animals under constant dark (DD) or light-dark (LD) schedules in either standard wheel cages or in newly developed simulated den cages. By means of the den cages, several aspects of a circadian activity cycle could be simultaneously measured emphasizing the arousal from rest, the light-sampling behavior by which a squirrel assessed the environmental photoregimen, and the phase-shifting by which photoentrainment was achieved. Each animal in a den cage remained for 12 or more hours of its rest period almost exclusively in the darkened nest box, then at an abrupt arousal time moved to the light-sampling porthole. In darkness each animal initiated wheel activity immediately after arousal; light at arousal time, however, induced a return to the nest box for a nap and a delay phase-shift in onset of activity of approximately 40 min. On subsequent days, each animal appeared to be free-running (tau FR less than 24 h) until onset again advanced into the light period. A squirrel usually viewed only a few minutes light per day, and on free-running days occasionally saw none of the 12-h light period. The significance of these data for theories of circadian photoentrainment is discussed. PMID:3761222

  1. Habitual moderate alcohol consumption desynchronizes circadian physiologic rhythms and affects reaction-time performance.

    PubMed

    Reinberg, Alain; Touitou, Yvan; Lewy, Hadas; Mechkouri, Mohamed

    2010-10-01

    The authors studied longitudinally four healthy young adults to explore if habitual evening intake of a "moderate" amount of wine alters parameters, including period (?) of circadian rhythms. Subjects, synchronized by diurnal activity from 07.30?h?±?60?min to 23.00?h?±?90?min and nocturnal rest, were studied during a continuous 22-day span: 11 days without alcohol (control) and 11 days with a glass (200?mL) of wine nightly at supper (alcohol). The amount of alcohol ingested with dinner ranged from 0.28 to 0.42?g/kg/24?h/participant and the estimated evening blood alcohol level ranged from 0.02 to 0.10?g/L/participant. Single reaction time (SRT; yellow light signal), three-choice reaction time (CRT) (red, green, and yellow signals) of both hands, related cumulated errors (c-errors), as well as oral temperature (OT) and grip strength (GS) were measured four to seven times/24?h. Time series were analyzed individually to quantify 24-h means (M), circadian ? (power spectra), and cosinor, and correlation, ?(2), and t tests were performed. The sleep-wake ? (actography) was 24?h in every subject for both conditions. With alcohol, all subjects showed an OT circadian ? shorter than the control one. The SRT circadian M was longer (poorer performance) with wine versus control in three subjects, while CRT was longer with wine versus control in only one subject. Correlation analyses also showed the detrimental effect of alcohol on the same variables. Number of days with <2 c-errors was predominant in control and decreased with alcohol, especially for SRT. The desynchronization of the 10 different documented rhythms was greater with alcohol with reference to control in two of the four studied subjects. This work shows that habitual "moderate" wine drinking at supper reduces the performance of subjects, increases the level of c-errors/24?h, especially for SRT, suggesting a "moderate" amount of alcohol has the potential to increase accident risk, and it can also desynchronize circadian time organization. PMID:20969532

  2. Bright light therapy protects women from circadian rhythm desynchronization during chemotherapy for breast cancer.

    PubMed

    Neikrug, Ariel B; Rissling, Michelle; Trofimenko, Vera; Liu, Lianqi; Natarajan, Loki; Lawton, Susan; Parker, Barbara A; Ancoli-Israel, Sonia

    2012-01-01

    Circadian rhythms (CRs) are commonly disrupted in women undergoing chemotherapy for breast cancer (BC). Bright light improves and strengthens CRs in other populations. This randomized controlled study examined the effect of morning administration of bright light therapy on CRs in women undergoing chemotherapy for BC. It was hypothesized that women receiving bright light therapy would exhibit more robust rhythms than women exposed to dim light. Thirty-nine women newly diagnosed with BC and scheduled for chemotherapy were randomized into 2 groups: bright white light (BWL) or dim red light (DRL). Women were instructed to use the light box every morning for 30 min during their first 4 cycles of chemotherapy. Wrist actigraphy was recorded at 5 time points: prior to chemotherapy (baseline), Cycle-1 treatment week (C1TW), Cycle-1 recovery week (C1RW), Cycle-4 treatment week (C4TW), and Cycle-4 recovery week (C4RW). There was a Group × Time interaction at C4TW compared to baseline such that the DRL group showed significant deterioration in the mean of the activity rhythm (mesor) and amplitude, whereas the BWL group exhibited a significant increase in both mesor and amplitude. The DRL group also exhibited significant deterioration in overall rhythm robustness at C1TW, C4TW, and C4RW. Women in the BWL group also showed significant decreases in overall rhythm robustness at C1TW and C4TW, but returned to baseline levels at both recovery weeks. The results suggest that morning administration of bright light may protect women from experiencing CR deterioration during chemotherapy. PMID:22742438

  3. Passalurus ambiguus: new insights into copromicroscopic diagnosis and circadian rhythm of egg excretion.

    PubMed

    Rinaldi, Laura; Russo, Tamara; Schioppi, Mariangela; Pennacchio, Saverio; Cringoli, Giuseppe

    2007-08-01

    The present paper reports a study on the in vivo diagnosis and egg excretion rhythm of the pinworm Passalurus ambiguus in domesticated rabbits. Three copromicroscopic techniques were compared: the cellophane tape test, the McMaster technique, and the FLOTAC technique. Out of the 51 New Zealand White rabbit does examined, 42 (82.3%) resulted positive when examined with the FLOTAC technique, 39 (76.5%) with the cellophane tape test, and 29 (56.9%) with the McMaster technique. The agreement between the FLOTAC technique and the cellophane tape test was almost perfect (greater than 0.8); only moderate were the agreements (0.4) between the FLOTAC and the McMaster techniques and between the McMaster technique and the cellophane tape test. The results showed that the FLOTAC technique can be used for the quali-quantitative coprological diagnosis of P. ambiguus in rabbits due to its great sensitivity, as already shown for parasites of other animal species. The circadian rhythm of egg excretion by P. ambiguus was studied utilizing 42 individually caged rabbit does; fecal samples were collected from each cage every 6 h, i.e., at 6:00-12:00 hours, 12:00-18:00 hours, 18:00-24:00 hours, and 24:00-6:00 hours, and were analyzed by the FLOTAC technique. A circadian rhythm of P. ambiguus egg excretion was found, with significant lower values at 6:00-12:00 hours. In conclusion, the present study showed that the FLOTAC technique is the best copromicroscopic method for assessing P. ambiguus prevalence and intensity in rabbits and that the afternoon and evening hours are the best times for fecal sampling to perform the pinworm diagnosis. PMID:17372763

  4. Enhancement and suppression of ultradian and circadian rhythms across the female hamster reproductive cycle.

    PubMed

    Prendergast, Brian J; Beery, Annaliese K; Paul, Matthew J; Zucker, Irving

    2012-06-01

    The impact of ovarian hormones on hamster ultradian rhythms (URs) is unknown. We concurrently monitored URs and circadian rhythms (CRs) of home cage locomotor activity during the estrous cycle, pregnancy, and lactation of Syrian hamsters. URs with a mean period of 4-5 h were evident during the dark phase in more than 90% of females on days 1 and 2 of the estrous cycle but were significantly less prevalent on cycle days 3 and 4. The period of the UR did not vary as a function of estrous cycle stage, but at all stages, the UR period was longer in the dark than the light phase. The UR acrophase occurred significantly earlier on cycle day 4 than on days 1 and 2, and UR robustness and amplitude were reduced on days 3 and 4. Robustness, mesor, and amplitude of CRs were greater during cycle days 3 and 4; timing of the CR acrophase was delayed on day 4 relative to all other cycle days. Effects of the estrous cycle on URs were evident only during the dark phase. The proportion of hamsters displaying dark phase URs increased significantly during early and late gestation and decreased during lactation. Pregnancy significantly increased UR complexity, robustness, and amplitude. The emergence of URs over gestation was paralleled by decrements in the robustness and amplitude of CRs, which also were absent in a significant proportion of dams during lactation but re-emerged at weaning of litters. The changing endocrine profile of the estrous cycle, hormonal dynamics of pregnancy and lactation, and nursing demands placed on dams are each associated with alterations in the expression of ultradian and circadian locomotor rhythms. Diminution of CRs and augmentation of URs may afford greater behavioral flexibility during life stages when interactions with mates and offspring are less predictable. PMID:22653893

  5. Circadian Rhythms in Executive Function during the Transition to Adolescence: The Effect of Synchrony between Chronotype and Time of Day

    ERIC Educational Resources Information Center

    Hahn, Constanze; Cowell, Jason M.; Wiprzycka, Ursula J.; Goldstein, David; Ralph, Martin; Hasher, Lynn; Zelazo, Philip David

    2012-01-01

    To explore the influence of circadian rhythms on executive function during early adolescence, we administered a battery of executive function measures (including a Go-Nogo task, the Iowa Gambling Task, a Self-ordered Pointing task, and an Intra/Extradimensional Shift task) to Morning-preference and Evening-preference participants (N = 80) between…

  6. Dening the role of Drosophila lateral neurons in the control of circadian activity and eclosion rhythms by

    E-print Network

    Rouyer, Francois

    ) and pigment dispersing factor (pdf) genes play a major role in the control of circadian activity rhythms, that synthesize the pigment dispersing factor (PDF) neuropeptide (reviewed in Helfrich-FoÈrster et al., 1998 is detected in scattered glial cells and at least four groups of neurons (Siwicki et al., 1988; Zerr et al.,

  7. Circadian rhythms of locomotor activity and hippocampal clock genes expression are dampened in vitamin A-deficient rats.

    PubMed

    Navigatore-Fonzo, Lorena S; Delgado, Silvia M; Golini, Rebeca S; Anzulovich, Ana C

    2014-04-01

    The main external time giver is the day-night cycle; however, signals from feeding and the activity/rest cycles can entrain peripheral clocks, such as the hippocampus, in the absence of light. Knowing that vitamin A and its derivatives, the retinoids, may act as regulators of the endogenous clock activity, we hypothesized that the nutritional deficiency of vitamin A may influence the locomotor activity rhythm as well as the endogenous circadian patterns of clock genes in the rat hippocampus. Locomotor activity was recorded during the last week of the treatment period. Circadian rhythms of clock genes expression were analyzed by reverse transcription-polymerase chain reaction in hippocampus samples that were isolated every 4 hours during a 24-hour period. Reduced glutathione (GSH) levels were also determined by a kinetic assay. Regulatory regions of clock PER2, CRY1, and CRY2 genes were scanned for RXRE, RARE, and RORE sites. As expected, the locomotor activity pattern of rats shifted rightward under constant dark conditions. Clock genes expression and GSH levels displayed robust circadian oscillations in the rat hippocampus. We found RXRE and RORE sites on regulatory regions of clock genes. Vitamin A deficiency dampened rhythms of locomotor activity as well as modified endogenous rhythms of clock genes expression and GSH levels. Thus, vitamin A may have a role in endogenous clock functioning and participate in the circadian regulation of the cellular redox state in the hippocampus, a peripheral clock with relevant function in memory and learning. PMID:24774069

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

    PubMed Central

    Guerriero, Maria L.; Akman, Ozgur E.; van Ooijen, Gerben

    2014-01-01

    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-h 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 well studied. PMID:25374576

  9. Adjustment of sleep and the circadian temperature rhythm after flights across nine time zones

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.; Myhre, Grete; Graeber, R. Curtis; Lauber, John K.; Andersen, Harald T.

    1989-01-01

    The adjustment of sleep-wake patterns and the circadian temperature rhythm was monitored in nine Royal Norwegian Airforce volunteers operating P-3 aircraft during a westward training deployment across nine time zones. Subjects recorded all sleep and nap times, rated nightly sleep quality, and completed personality inventories. Rectal temperature, heart rate, and wrist activity were continuously monitored. Adjustment was slower after the return eastward flight than after the outbound westward flight. The eastward flight produced slower readjustment of sleep timing to local time and greater interindividual variability in the patterns of adjustment of sleep and temperature. One subject apparently exhibited resynchronization by partition, with the temperature rhythm undergoing the reciprocal 15-h delay. In contrast, average heart rates during sleep were significantly elevated only after westward flight. Interindividual differences in adjustment of the temperature rhythm were correlated with some of the personality measures. Larger phase delays in the overall temperature waveform (as measured on the 5th day after westward flight) were exhibited by extraverts, and less consistently by evening types.

  10. Dopamine receptor 1 neurons in the dorsal striatum regulate food anticipatory circadian activity rhythms in mice

    PubMed Central

    Gallardo, Christian M; Darvas, Martin; Oviatt, Mia; Chang, Chris H; Michalik, Mateusz; Huddy, Timothy F; Meyer, Emily E; Shuster, Scott A; Aguayo, Antonio; Hill, Elizabeth M; Kiani, Karun; Ikpeazu, Jonathan; Martinez, Johan S; Purpura, Mari; Smit, Andrea N; Patton, Danica F; Mistlberger, Ralph E; Palmiter, Richard D; Steele, Andrew D

    2014-01-01

    Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduced FAA, whereas mice lacking the dopamine D2 receptor have normal FAA. To determine where dopamine exerts its effect, we limited expression of dopamine signaling to the dorsal striatum of dopamine-deficient mice; these mice developed FAA. Within the dorsal striatum, the daily rhythm of clock gene period2 expression was markedly suppressed in D1R KO mice. Pharmacological activation of D1R at the same time daily was sufficient to establish anticipatory activity in wild-type mice. These results demonstrate that dopamine signaling to D1R-expressing neurons in the dorsal striatum plays an important role in manifestation of FAA, possibly by synchronizing circadian oscillators that modulate motivational processes and behavioral output. DOI: http://dx.doi.org/10.7554/eLife.03781.001 PMID:25217530

  11. Inter-Individual Differences in Neurobehavioural Impairment following Sleep Restriction Are Associated with Circadian Rhythm Phase

    PubMed Central

    Sletten, Tracey L.; Segal, Ahuva Y.; Flynn-Evans, Erin E.; Lockley, Steven W.; Rajaratnam, Shantha M. W.

    2015-01-01

    Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M) aged 22.5 ± 3.1 (mean ± SD) years maintained a regular 8:16 h sleep:wake routine for at least three weeks prior to laboratory admission. Sleep opportunity was restricted to 5 hours time-in-bed at home the night before admission and 3 hours time-in-bed in the laboratory, aligned by wake time. Hourly saliva samples were collected from 5.5 h before until 5 h after the pre-laboratory scheduled bedtime to assess dim light melatonin onset (DLMO) as a marker of circadian phase. Participants completed a 10-min auditory Psychomotor Vigilance Task (PVT), the Karolinska Sleepiness Scale (KSS) and had slow eye movements (SEM) measured by electrooculography two hours after waking. We observed substantial inter-individual variability in neurobehavioural performance, particularly in the number of PVT lapses. Increased PVT lapses (r = -0.468, p < 0.01), greater sleepiness (r = 0.510, p < 0.0001), and more slow eye movements (r = 0.375, p = 0.022) were significantly associated with later DLMO, consistent with participants waking at an earlier circadian phase. When the difference between DLMO and sleep onset was less than 2 hours, individuals were significantly more likely to have at least three attentional lapses the following morning. This study demonstrates that the phase of an individual’s circadian system is an important variable in predicting the degree of neurobehavioural performance impairment in the hours after waking following sleep restriction, and confirms that other factors influencing performance decrements require further investigation. PMID:26043207

  12. Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders

    PubMed Central

    Boivin, DB

    2000-01-01

    Recent evidence shows that the temporal alignment between the sleep-wake cycle and the circadian pacemaker affects self-assessment of mood in healthy subjects. Despite the differences in affective state between healthy subjects and patients with psychiatric disorders, these results have implications for analyzing diurnal variation of mood in unipolar and bipolar affective disorders and sleep disturbances in other major psychiatric conditions such as chronic schizophrenia. In a good proportion of patients with depression, mood often improves over the course of the day; an extension of waking often has an antidepressant effect. Sleep deprivation has been described as a treatment for depression for more than 30 years, and approximately 50% to 60% of patients with depression respond to this approach, especially those patients who report that their mood improves over the course of the day. The mechanisms by which sleep deprivation exerts its antidepressant effects are still controversial, but a reduction in rapid eye movement sleep (REM sleep), sleep pressure and slow-wave sleep (SWS), or a circadian phase disturbance, have been proposed. Although several studies support each of these hypotheses, none is sufficient to explain all observations reported to date. Unfortunately, the disturbed sleep-wake cycle or behavioural activities of depressed patients often explain several of the abnormalities reported in the diurnal rhythms of these patients. Thus, protocols that specifically manipulate the sleep-wake cycle to unmask the expression of the endogenous circadian pacemaker are greatly needed. In chronic schizophrenia, significant disturbances in sleep continuity, REM sleep, and SWS have been consistently reported. These disturbances are different from those observed in depression, especially with regard to REM sleep. Circadian phase abnormalities in schizophrenic patients have also been reported. Future research is expected to clarify the nature of these abnormalities. Images Fig. 1 PMID:11109296

  13. Effects of Exposure to Intermittent versus Continuous Red Light on Human Circadian Rhythms, Melatonin Suppression, and Pupillary Constriction

    PubMed Central

    Ho Mien, Ivan; Chua, Eric Chern-Pin; Lau, Pauline; Tan, Luuan-Chin; Lee, Ivan Tian-Guang; Yeo, Sing-Chen; Tan, Sara Shuhui; Gooley, Joshua J.

    2014-01-01

    Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n?=?24, 21–28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm?2 s?1), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n?=?8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P?=?0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light. PMID:24797245

  14. Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

    PubMed

    Ho Mien, Ivan; Chua, Eric Chern-Pin; Lau, Pauline; Tan, Luuan-Chin; Lee, Ivan Tian-Guang; Yeo, Sing-Chen; Tan, Sara Shuhui; Gooley, Joshua J

    2014-01-01

    Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n?=?24, 21-28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2) s(-1)), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n?=?8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P?=?0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light. PMID:24797245

  15. Repeated psychosocial stress at night affects the circadian activity rhythm of male mice.

    PubMed

    Bartlang, Manuela S; Oster, Henrik; Helfrich-Förster, Charlotte

    2015-06-01

    We have recently shown that molecular rhythms in the murine suprachiasmatic nucleus (SCN) are affected by repeated social defeat (SD) during the dark/active phase (social defeat dark [SDD]), while repeated SD during the light/inactive phase (social defeat light [SDL]) had no influence on PERIOD2::LUCIFERASE explant rhythms in the SCN. Here we assessed the effects of the same stress paradigm by in vivo biotelemetry on 2 output rhythms of the circadian clock (i.e., activity and core body temperature) in wild-type (WT) and clock-deficient Period (Per)1/2 double-mutant mice during and following repeated SDL and SDD. In general, stress had more pronounced effects on activity compared to body temperature rhythms. Throughout the SD procedure, activity and body temperature were markedly increased during the 2 h of stressor exposure at zeitgeber time (ZT) 1 to ZT3 (SDL mice) and ZT13 to ZT15 (SDD mice), which was compensated by decreased activity during the remaining dark phase (SDL and SDD mice) and light phase (SDL mice) in both genotypes. Considerable differences in the activity between SDL and SDD mice were seen in the poststress period. SDD mice exhibited a reduced first activity bout at ZT13, delayed activity onset, and, consequently, a more narrow activity bandwidth compared with single-housed control (SHC) and SDL mice. Given that this effect was absent in Per1/2 mutant SDD mice and persisted under constant darkness conditions in SDD WT mice, it suggests an involvement of the endogenous clock. Taken together, the present findings demonstrate that SDD has long-lasting consequences for the functional output of the biological clock that, at least in part, appear to depend on the clock genes Per1 and Per2. PMID:25900040

  16. A tunable artificial circadian clock in clock-defective mice

    PubMed Central

    D'Alessandro, Matthew; Beesley, Stephen; Kim, Jae Kyoung; Chen, Rongmin; Abich, Estela; Cheng, Wayne; Yi, Paul; Takahashi, Joseph S.; Lee, Choogon

    2015-01-01

    Self-sustaining oscillations are essential for diverse physiological functions such as the cell cycle, insulin secretion and circadian rhythms. Synthetic oscillators using biochemical feedback circuits have been generated in cell culture. These synthetic systems provide important insight into design principles for biological oscillators, but have limited similarity to physiological pathways. Here we report the generation of an artificial, mammalian circadian clock in vivo, capable of generating robust, tunable circadian rhythms. In mice deficient in Per1 and Per2 genes (thus lacking circadian rhythms), we artificially generate PER2 rhythms and restore circadian sleep/wake cycles with an inducible Per2 transgene. Our artificial clock is tunable as the period and phase of the rhythms can be modulated predictably. This feature, and other design principles of our work, might enhance the study and treatment of circadian dysfunction and broader aspects of physiology involving biological oscillators. PMID:26617050

  17. A tunable artificial circadian clock in clock-defective mice.

    PubMed

    D'Alessandro, Matthew; Beesley, Stephen; Kim, Jae Kyoung; Chen, Rongmin; Abich, Estela; Cheng, Wayne; Yi, Paul; Takahashi, Joseph S; Lee, Choogon

    2015-01-01

    Self-sustaining oscillations are essential for diverse physiological functions such as the cell cycle, insulin secretion and circadian rhythms. Synthetic oscillators using biochemical feedback circuits have been generated in cell culture. These synthetic systems provide important insight into design principles for biological oscillators, but have limited similarity to physiological pathways. Here we report the generation of an artificial, mammalian circadian clock in vivo, capable of generating robust, tunable circadian rhythms. In mice deficient in Per1 and Per2 genes (thus lacking circadian rhythms), we artificially generate PER2 rhythms and restore circadian sleep/wake cycles with an inducible Per2 transgene. Our artificial clock is tunable as the period and phase of the rhythms can be modulated predictably. This feature, and other design principles of our work, might enhance the study and treatment of circadian dysfunction and broader aspects of physiology involving biological oscillators. PMID:26617050

  18. Osteoarthritis-like pathologic changes in the knee joint induced by environmental disruption of circadian rhythms is potentiated by a high-fat diet

    PubMed Central

    Kc, Ranjan; Li, Xin; Forsyth, Christopher B.; Voigt, Robin M.; Summa, Keith C.; Vitaterna, Martha Hotz; Tryniszewska, Beata; Keshavarzian, Ali; Turek, Fred W.; Meng, Qing-Jun; Im, Hee-Jeong

    2015-01-01

    A variety of environmental factors contribute to progressive development of osteoarthritis (OA). Environmental factors that upset circadian rhythms have been linked to various diseases. Our recent work establishes chronic environmental circadian disruption - analogous to rotating shiftwork-associated disruption of circadian rhythms in humans - as a novel risk factor for the development of OA. Evidence suggests shift workers are prone to obesity and also show altered eating habits (i.e., increased preference for high-fat containing food). In the present study, we investigated the impact of chronic circadian rhythm disruption in combination with a high-fat diet (HFD) on progression of OA in a mouse model. Our study demonstrates that when mice with chronically circadian rhythms were fed a HFD, there was a significant proteoglycan (PG) loss and fibrillation in knee joint as well as increased activation of the expression of the catabolic mediators involved in cartilage homeostasis. Our results, for the first time, provide the evidence that environmental disruption of circadian rhythms plus HFD potentiate OA-like pathological changes in the mouse joints. Thus, our findings may open new perspectives on the interactions of chronic circadian rhythms disruption with diet in the development of OA and may have potential clinical implications. PMID:26584570

  19. Osteoarthritis-like pathologic changes in the knee joint induced by environmental disruption of circadian rhythms is potentiated by a high-fat diet.

    PubMed

    Kc, Ranjan; Li, Xin; Forsyth, Christopher B; Voigt, Robin M; Summa, Keith C; Vitaterna, Martha Hotz; Tryniszewska, Beata; Keshavarzian, Ali; Turek, Fred W; Meng, Qing-Jun; Im, Hee-Jeong

    2015-01-01

    A variety of environmental factors contribute to progressive development of osteoarthritis (OA). Environmental factors that upset circadian rhythms have been linked to various diseases. Our recent work establishes chronic environmental circadian disruption - analogous to rotating shiftwork-associated disruption of circadian rhythms in humans - as a novel risk factor for the development of OA. Evidence suggests shift workers are prone to obesity and also show altered eating habits (i.e., increased preference for high-fat containing food). In the present study, we investigated the impact of chronic circadian rhythm disruption in combination with a high-fat diet (HFD) on progression of OA in a mouse model. Our study demonstrates that when mice with chronically circadian rhythms were fed a HFD, there was a significant proteoglycan (PG) loss and fibrillation in knee joint as well as increased activation of the expression of the catabolic mediators involved in cartilage homeostasis. Our results, for the first time, provide the evidence that environmental disruption of circadian rhythms plus HFD potentiate OA-like pathological changes in the mouse joints. Thus, our findings may open new perspectives on the interactions of chronic circadian rhythms disruption with diet in the development of OA and may have potential clinical implications. PMID:26584570

  20. Regularity of daily life in relation to personality, age, gender, sleep quality and circadian rhythms

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Petrie, S. R.; Hayes, A. J.; Kupfer, D. J.

    1994-01-01

    A diary-like instrument to measure lifestyle regularity (the 'Social Rhythm Metric'-SRM) was given to 96 subjects (48 women, 48 men), 39 of whom repeated the study after at least one year, with additional objective measures of rest/activity. Lifestyle regularity as measured by the SRM related to age, morningness, subjective sleep quality and time-of-day variations in alertness, but not to gender, extroversion or neuroticism. Statistically significant test-retest correlations of about 0.4 emerged for SRM scores over the 12-30 month delay. Diary-based estimates of bedtime and waketime appeared fairly reliable. In a further study of healthy young men, 4 high SRM scorers ('regular') had a deeper nocturnal body temperature trough than 5 low SRM scorers ('irregular'), suggesting a better functioning circadian system in the 'regular' group.

  1. Hierarchy of models: From qualitative to quantitative analysis of circadian rhythms in cyanobacteria

    NASA Astrophysics Data System (ADS)

    Chaves, M.; Preto, M.

    2013-06-01

    A hierarchy of models, ranging from high to lower levels of abstraction, is proposed to construct "minimal" but predictive and explanatory models of biological systems. Three hierarchical levels will be considered: Boolean networks, piecewise affine differential (PWA) equations, and a class of continuous, ordinary, differential equations' models derived from the PWA model. This hierarchy provides different levels of approximation of the biological system and, crucially, allows the use of theoretical tools to more exactly analyze and understand the mechanisms of the system. The Kai ABC oscillator, which is at the core of the cyanobacterial circadian rhythm, is analyzed as a case study, showing how several fundamental properties—order of oscillations, synchronization when mixing oscillating samples, structural robustness, and entrainment by external cues—can be obtained from basic mechanisms.

  2. Effect of bedrest on circadian rhythms of plasma renin, aldosterone, and cortisol

    NASA Technical Reports Server (NTRS)

    Chavarri, M.; Ganguly, A.; Luetscher, J. A.; Zager, P. G.

    1977-01-01

    Previous studies of normal men after 5 d of bedrest showed that circulatory instability on head-up tilt or standing is preceded by increased plasma renin activity (PRA) at bedrest. In the present study, the circadian rhythms of PRA, aldosterone, and cortisol have been observed in five normal men on a constant diet. In ambulatory controls, PRA and aldosterone increased normally after standing. On the third morning of bedrest, PRA was higher than before, and at noon, PRA was higher than in standing controls. The nocturnal peaks of PRA resulting from episodic renin secretion during sleep were higher after bedrest. Plasma aldosterone was also increased by bedrest. The findings are compatible with the theory that intermittent beta-adrenergic nerve activity during sleep is increased after bedrest, but other factors, such as loss of body sodium and a lower plasma volume, may also be involved.

  3. Melatonin Regulates Aging and Neurodegeneration through Energy Metabolism, Epigenetics, Autophagy and Circadian Rhythm Pathways

    PubMed Central

    Jenwitheesuk, Anorut; Nopparat, Chutikorn; Mukda, Sujira; Wongchitrat, Prapimpun; Govitrapong, Piyarat

    2014-01-01

    Brain aging is linked to certain types of neurodegenerative diseases and identifying new therapeutic targets has become critical. Melatonin, a pineal hormone, associates with molecules and signaling pathways that sense and influence energy metabolism, autophagy, and circadian rhythms, including insulin-like growth factor 1 (IGF-1), Forkhead box O (FoxOs), sirtuins and mammalian target of rapamycin (mTOR) signaling pathways. This review summarizes the current understanding of how melatonin, together with molecular, cellular and systemic energy metabolisms, regulates epigenetic processes in the neurons. This information will lead to a greater understanding of molecular epigenetic aging of the brain and anti-aging mechanisms to increase lifespan under healthy conditions. PMID:25247581

  4. Melatonin regulates aging and neurodegeneration through energy metabolism, epigenetics, autophagy and circadian rhythm pathways.

    PubMed

    Jenwitheesuk, Anorut; Nopparat, Chutikorn; Mukda, Sujira; Wongchitrat, Prapimpun; Govitrapong, Piyarat

    2014-01-01

    Brain aging is linked to certain types of neurodegenerative diseases and identifying new therapeutic targets has become critical. Melatonin, a pineal hormone, associates with molecules and signaling pathways that sense and influence energy metabolism, autophagy, and circadian rhythms, including insulin-like growth factor 1 (IGF-1), Forkhead box O (FoxOs), sirtuins and mammalian target of rapamycin (mTOR) signaling pathways. This review summarizes the current understanding of how melatonin, together with molecular, cellular and systemic energy metabolisms, regulates epigenetic processes in the neurons. This information will lead to a greater understanding of molecular epigenetic aging of the brain and anti-aging mechanisms to increase lifespan under healthy conditions. PMID:25247581

  5. A Circadian Clock in Antarctic Krill: An Endogenous Timing System Governs Metabolic Output Rhythms in the Euphausid Species Euphausia superba

    PubMed Central

    Teschke, Mathias; Wendt, Sabrina; Kawaguchi, So; Kramer, Achim; Meyer, Bettina

    2011-01-01

    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. PMID:22022521

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

    PubMed

    Teschke, Mathias; Wendt, Sabrina; Kawaguchi, So; Kramer, Achim; Meyer, Bettina

    2011-01-01

    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. PMID:22022521

  7. The effects of feedback lighting on the circadian drinking rhythm in the diurnal new world primate Saimiri sciureus

    NASA Technical Reports Server (NTRS)

    Ferraro, J. S.; Sulzman, F. M.

    1988-01-01

    Feedback lighting provides illumination primarily during the subjective night (i.e., the photosensitive portion of the circadian cycle) in response to a given behavior. This technique has previously been used to test the nonparametric model of entrainment in nocturnal rodents. In three species (Rattus norvegicus, Mesocricetus auratus, and Mus musculus), the free-running period of the locomotor activity rhythm was similar whether the animals were exposed to continuous light or discrete light pulses occurring essentially only during the subjective night (i.e., feedback lighting). In the current experiments, feedback lighting was presented to squirrel monkeys so that light fell predominantly during the subjective night. Feedback lighting was linked to the drinking behavior in this diurnal primate so that when the animal drank, the lights went out. Despite the seemingly adverse predicament, the monkeys maintained regular circadian drinking rhythms. Furthermore, just as the period of the free-running activity rhythms of nocturnal rodents exposed to continuous light or feedback lighting were similar, the period of the drinking rhythms of the squirrel monkeys in continuous light and feedback lighting were comparable (25.6 +/- 0.1 and 25.9 +/- 0.1 hours, respectively), despite a substantial decrease in the total amount of light exposure associated with feedback lighting. The free-running period of monkeys exposed to continuous dark (24.5 +/- 0.1 hours) was significantly shorter than either of the two lighting conditions (P < 0.001). The results presented for the drinking rhythm were confirmed by examination of the temperature and activity rhythms. Therefore, discrete light pulses given predominately during the subjective night are capable of simulating the effects of continuous light on the free-running period of the circadian rhythms of a diurnal primate. The response of squirrel monkeys to feedback lighting thus lends further support for the model and suggests that the major entrainment mechanisms are similar in nocturnal rodents and diurnal primates.

  8. Alterations in endogenous circadian rhythm of core temperature in senescent Fischer 344 rats

    NASA Technical Reports Server (NTRS)

    McDonald, R. B.; Hoban-Higgins, T. M.; Ruhe, R. C.; Fuller, C. A.; Horwitz, B. A.

    1999-01-01

    We assessed whether alterations in endogenous circadian rhythm of core temperature (CRT) in aging rats are associated with chronological time or with a biological marker of senescence, i.e., spontaneous rapid body weight loss. CRT was measured in male Fischer 344 (F344) rats beginning at age 689 days and then continuously until death. Young rats were also monitored. The rats were housed under constant dim red light at 24-26 degrees C, and core temperature was recorded every 10 min via biotelemetry. The CRT amplitude of the body weight-stable (presenescent) old rats was significantly less than that of young rats at all analysis periods. At the onset of spontaneous rapid weight loss (senescence), all measures of endogenous CRT differed significantly from those in the presenescent period. The suprachiasmatic nucleus (a circadian pacemaker) of the senescent rats maintained its light responsiveness as determined by an increase in c-fos expression after a brief light exposure. These data demonstrate that some characteristics of the CRT are altered slowly with chronological aging, whereas others occur rapidly with the onset of senescence.

  9. The Clock gene clone and its circadian rhythms in Pelteobagrus vachelli

    NASA Astrophysics Data System (ADS)

    Qin, Chuanjie; Shao, Ting

    2015-05-01

    The Clock gene, a key molecule in circadian systems, is widely distributed in the animal kingdom. We isolated a 936-bp partial cDNA sequence of the Clock gene ( Pva-clock) from the darkbarbel catfish Pelteobagrus vachelli that exhibited high identity with Clock genes of other species of fish and animals (65%-88%). The putative domains included a basic helix-loop-helix (bHLH) domain and two period-ARNT-single-minded (PAS) domains, which were also similar to those in other species of fish and animals. Pva-Clock was primarily expressed in the brain, and was detected in all of the peripheral tissues sampled. Additionally, the pattern of Pva-Clock expression over a 24-h period exhibited a circadian rhythm in the brain, liver and intestine, with the acrophase at zeitgeber time 21:35, 23:00, and 23:23, respectively. Our results provide insight into the function of the molecular Clock of P. vachelli.

  10. Circadian rhythms are not involved in the regulation of circannual reproductive cycles in a sub-tropical bird, the spotted munia.

    PubMed

    Budki, Puja; Malik, Shalie; Rani, Sangeeta; Kumar, Vinod

    2014-07-15

    Circannual rhythms regulate seasonal reproduction in many vertebrates. The present study investigated whether circannual reproductive phenotypes (rhythms in growth of gonads and molt) were generated independently of the circadian clocks in the subtropical non-photoperiodic spotted munia (Lonchura punctulata). Birds were subjected to light:dark (LD) cycles with identical light but varying dark hours, such that the period of LD cycle (T) equaled 16 h (T16; 12 h L:4 h D), 21 h (T21; 12 h L:9 h D), 24 h (T24; 12 h L:12 h D) and 27 h (T27; 12 h L:15 h D), or to continuous light (LL, 24 h L:0 h D) at ~18°C. During the ~21 month exposure, munia underwent at least two cycles of gonadal development and molt; changes in body mass were not rhythmic. This was similar to the occurrence of annual cycles in reproduction and molt observed in wild birds. A greater asynchrony between circannual cycles of gonad development and molt indicated their independent regulation. Females showed reproductive rhythms with similar circannual periods, whilst in males, circannual periods measured between peak gonadal size were longer in T21 and T24 than in T16 or T27. This suggested a sex-dependent timing of annual reproduction in the spotted munia. Also, food availability periods may not influence the circannual timing of reproduction, as shown by the results on the rhythm in gonadal growth and regression in munia under T-photocycles and LL that provided differential light (feeding) hours. Further, a short-term experiment revealed that activity-rest patterns in munia were synchronized with T-photocycles, but were arrhythmic under LL. We conclude that circadian rhythms are not involved in the timing of the annual reproductive cycle in the spotted munia. PMID:24803462

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

    SciTech Connect

    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/sup +/ strain, five proteins of molecular weights (M/sub r/) 9000, 19,000, 22,000, 140,000, and 200,000 were labelled with (/sup 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/sup 2 +/ are proposed; clock mutations are postulated to affect Ca/sup 2 +/ transporters and the mitochondrial membrane; and phase-shifting effects are accounted for by changes in Ca/sup 2 +/ or ATP levels.

  12. Voluntary exercise enhances activity rhythms and ameliorates anxiety- and depression-like behaviors in the sand rat model of circadian rhythm-related mood changes.

    PubMed

    Tal-Krivisky, Katy; Kronfeld-Schor, Noga; Einat, Haim

    2015-11-01

    Physical exercise is a non-pharmacological treatment for affective disorders. The mechanisms of its effects are unknown although some suggest a relationship to synchronization of circadian rhythms. One way to explore mechanisms is to utilize animal models. We previously demonstrated that the diurnal fat sand rat is an advantageous model for studying the interactions between photoperiods and mood. The current study was designed to evaluate the effects of voluntary exercise on activity rhythms and anxiety and depression-like behaviors in sand rats as a step towards better understanding of the underlying mechanisms. Male sand rats were housed in short photoperiod (SP; 5h light/19h dark) or neutral light (NP; 12h light/12h dark) regimens for 3weeks and divided into subgroups with or without running wheels. Activity was monitored for 3 additional weeks and then animals were tested in the elevated plus-maze, the forced swim test and the social interaction test. Activity rhythms were enhanced by the running wheels. As hypothesized, voluntary exercise had significant effects on SP animals' anxiety- and depression-like behaviors but not on NP animals. Results are discussed in the context of interactions between physical exercise, circadian rhythms and mood. We suggest that the sand rat model can be used to explore the underlying mechanism of the effects of physical exercise for mood disorders. PMID:26253214

  13. Effects of menstrual cycle phase and oral contraceptives on alertness, cognitive performance, and circadian rhythms during sleep deprivation

    NASA Technical Reports Server (NTRS)

    Wright, K. P. Jr; Badia, P.; Czeisler, C. A. (Principal Investigator)

    1999-01-01

    The influence of menstrual cycle phase and oral contraceptive use on neurobehavioral function and circadian rhythms were studied in healthy young women (n = 25) using a modified constant routine procedure during 24 h of sleep deprivation. Alertness and performance worsened across sleep deprivation and also varied with circadian phase. Entrained circadian rhythms of melatonin and body temperature were evident in women regardless of menstrual phase or oral contraceptive use. No significant difference in melatonin levels, duration, or phase was observed between women in the luteal and follicular phases, whereas oral contraceptives appeared to increase melatonin levels. Temperature levels were higher in the luteal phase and in oral contraceptive users compared to women in the follicular phase. Alertness on the maintenance of wakefulness test and some tests of cognitive performance were poorest for women in the follicular phase especially near the circadian trough of body temperature. These observations suggest that hormonal changes associated with the menstrual cycle and the use of oral contraceptives contribute to changes in nighttime waking neurobehavioral function and temperature level whereas these factors do not appear to affect circadian phase.

  14. Maximum entropy spectral analysis for circadian rhythms: theory, history and practice.

    PubMed

    Dowse, Harold B

    2013-01-01

    There is an array of numerical techniques available to estimate the period of circadian and other biological rhythms. Criteria for choosing a method include accuracy of period measurement, resolution of signal embedded in noise or of multiple periodicities, and sensitivity to the presence of weak rhythms and robustness in the presence of stochastic noise. Maximum Entropy Spectral Analysis (MESA) has proven itself excellent in all regards. The MESA algorithm fits an autoregressive model to the data and extracts the spectrum from its coefficients. Entropy in this context refers to "ignorance" of the data and since this is formally maximized, no unwarranted assumptions are made. Computationally, the coefficients are calculated efficiently by solution of the Yule-Walker equations in an iterative algorithm. MESA is compared here to other common techniques. It is normal to remove high frequency noise from time series using digital filters before analysis. The Butterworth filter is demonstrated here and a danger inherent in multiple filtering passes is discussed. PMID:23844660

  15. Caffeine does not entrain the circadian clock but improves daytime alertness in blind patients with non-24-hour rhythms

    PubMed Central

    St. Hilaire, Melissa A.; Lockley, Steven W.

    2015-01-01

    Objective/Background Totally blind individuals are highly likely to suffer from Non-24-Hour Sleep-Wake Disorder due to a failure of light to reset the circadian pacemaker in the suprachiasmatic nuclei. In this outpatient case series, we investigated whether daily caffeine administration could entrain the circadian pacemaker in non-entrained blind patients to alleviate symptoms of non-24-hour sleep–wake disorder. Patients/Methods Three totally blind males (63.0?±?7.5 years old) were studied at home over ~4 months. Urinary 6-sulphatoxymelatonin (aMT6s) rhythms were measured for 48?h every 1–2 weeks. Participants completed daily sleep–wake logs, and rated their alertness and mood using nine-point scales every ~2–4?h while awake on urine sampling days. Caffeine capsules (150?mg per os) were self-administered daily at 10 a.m. for approximately one circadian beat cycle based on each participant's endogenous circadian period ? and compared to placebo (n?=?2) or no treatment (n?=?1) in a single-masked manner. Results Non-24-h aMT6s rhythms were confirmed in all three participants (? range?=?24.32–24.57?h). Daily administration of 150?mg caffeine did not entrain the circadian clock. Caffeine treatment significantly improved daytime alertness at adverse circadian phases (p?circadian disorder means that an entraining agent is required to treat Non-24-Hour Sleep–Wake Disorder in the blind appropriately. PMID:25891543

  16. Influence of head-down bed rest on the circadian rhythms of hormones and electrolytes involved in hydroelectrolytic regulation

    NASA Technical Reports Server (NTRS)

    Millet, C.; Custaud, M. A.; Allevard, A. M.; Zaouali-Ajina, M.; Monk, T. H.; Arnaud, S. B.; Claustrat, B.; Gharib, C.; Gauquelin-Koch, G.

    2001-01-01

    We investigated in six men the impact of a 17-day head-down bed rest (HDBR) on the circadian rhythms of the hormones and electrolytes involved in hydroelectrolytic regulation. This HDBR study was designed to mimic an actual spaceflight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of aldosterone, arginine vasopressin (AVP), cyclic guanosine monophosphate (cGMP), cortisol, electrolytes (Na+ and K+) and creatinine were determined. HDBR resulted in a significant reduction of body mass (P < 0.01) and of caloric intake [mean (SEM) 2,778 (37) kcal.24 h(-1) to 2,450 (36) kcal.24 h(-1), where 1 kcal.h(-1) = 1.163 J.s(-1); P< 0.01]. There was a significant increase in diastolic blood pressure [71.8 (0.7) mmHg vs 75.6 (0.91) mmHg], with no significant changes in either systolic blood pressure or heart rate. The nocturnal hormonal decrease of aldosterone was clearly evident only before and after HDBR, but the day/night difference did not appear during HDBR. The rhythm of K+ excretion was unchanged during HDBR, whereas for Na+ excretion, a large decrease was shown during the night as compared to the day. The circadian rhythm of cortisol persisted. These data suggest that exposure to a 17-day HDBR could induce an exaggeration of the amplitude of the Na+ rhythm and abolition of the aldosterone rhythm.

  17. Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day

    NASA Technical Reports Server (NTRS)

    Wyatt, J. K.; Ritz-De Cecco, A.; Czeisler, C. A.; Dijk, D. J.

    1999-01-01

    The interaction of homeostatic and circadian processes in the regulation of waking neurobehavioral functions and sleep was studied in six healthy young subjects. Subjects were scheduled to 15-24 repetitions of a 20-h rest/activity cycle, resulting in desynchrony between the sleep-wake cycle and the circadian rhythms of body temperature and melatonin. The circadian components of cognitive throughput, short-term memory, alertness, psychomotor vigilance, and sleep disruption were at peak levels near the temperature maximum, shortly before melatonin secretion onset. These measures exhibited their circadian nadir at or shortly after the temperature minimum, which in turn was shortly after the melatonin maximum. Neurobehavioral measures showed impairment toward the end of the 13-h 20-min scheduled wake episodes. This wake-dependent deterioration of neurobehavioral functions can be offset by the circadian drive for wakefulness, which peaks in the latter half of the habitual waking day during entrainment. The data demonstrate the exquisite sensitivity of many neurobehavioral functions to circadian phase and the accumulation of homeostatic drive for sleep.

  18. The effects on human sleep and circadian rhythms of 17 days of continuous bedrest in the absence of daylight

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Buysse, D. J.; Billy, B. D.; Kennedy, K. S.; Kupfer, D. J.

    1997-01-01

    As part of a larger bedrest study involving various life science experiments, a study was conducted on the effects of 17 days of continuous bedrest and elimination of daylight on circadian rectal temperature rhythms, mood, alertness, and sleep (objective and diary) in eight healthy middle-aged men. Sleep was timed from 2300 to 0700 hours throughout. Three 72-hour measurement blocks were compared: ambulatory prebedrest, early bedrest (days 5-7), and late bedrest (days 15-17). Temperature rhythms showed reduced amplitude and later phases resulting from the bedrest conditions. This was associated with longer nocturnal sleep onset latencies and poorer subjectively rated sleep but with no reliable changes in any of the other sleep parameters. Daily changes in posture and/or exposure to daylight appear to be important determinants of a properly entrained circadian system.

  19. Time dictates: emerging clinical analyses of the impact of circadian rhythms on diagnosis, prognosis and treatment of disease.

    PubMed

    Nagy, Andras D; Reddy, Akhilesh B

    2015-12-01

    Since the advent of modern molecular tools, researchers have extensively shown that essential cellular machineries have robust circadian (roughly 24 hours) variations in their pace. This molecular rhythmicity translates directly into time-of-day-dependent variation in physiology in most organ systems, which in turn provides the mechanistic rationale for why timing on a daily basis should matter in many aspects of human health. However, these basic science findings have been slow to move from bench to bedside because clinical studies are still lacking to demonstrate the importance of timing. Therefore, it has not been clear how physicians should incorporate knowledge of natural 24-hour rhythms into routine practice. This review is a brief summary of results from recently completed clinical studies on hypertension, myocardial infarction, diabetes mellitus, and adrenal dysfunction that highlights new evidence for the emerging importance of circadian rhythms in diagnosis, prognosis and treatment of disease. PMID:26634682

  20. The Effects of the Mars Exploration Rovers (MER) Work Schedule Regime on Locomotor Activity Circadian Rhythms, Sleep and Fatigue

    NASA Technical Reports Server (NTRS)

    DeRoshia, Charles W.; Colletti, Laura C.; Mallis, Melissa M.

    2008-01-01

    This study assessed human adaptation to a Mars sol by evaluating sleep metrics obtained by actigraphy and subjective responses in 22 participants, and circadian rhythmicity in locomotor activity in 9 participants assigned to Mars Exploration Rover (MER) operational work schedules (24.65 hour days) at the Jet Propulsion Laboratory in 2004. During MER operations, increased work shift durations and reduced sleep durations and time in bed were associated with the appearance of pronounced 12-hr (circasemidian) rhythms with reduced activity levels. Sleep duration, workload, and circadian rhythm stability have important implications for adaptability and maintenance of operational performance not only of MER operations personnel but also in space crews exposed to a Mars sol of 24.65 hours during future Mars missions.

  1. Albuminuria, renal dysfunction and circadian blood pressure rhythm in older men: a population-based longitudinal cohort study

    PubMed Central

    Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Cederholm, Tommy; Sjögren, Per; Lindholm, Bengt; Ärnlöv, Johan; Carrero, Juan Jesús

    2015-01-01

    Background Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each other's effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men. Methods This was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression). Results UAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73 m2) in its association with the changes of both night-time systolic BP (SBP) and night–day SBP ratio. After stratification, UAER strongly predicted night–day SBP ratio change only in those with concurrent kidney dysfunction. At re-examination, 221 new cases of non-dipper were identified. In multivariable logistic models, high UAER associated with increased likelihood of non-dipper progression, but more strongly so among individuals with concurrent kidney dysfunction. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER. Conclusions UAER associates with circadian BP rhythm variation and non-dipper progression in elderly men. Concurrent renal dysfunction modifies and exacerbates these associations. PMID:26413281

  2. Circadian rhythm in the pineal organ of the yellow-bellied toad, Bombina variegata (L.), under laboratory conditions.

    PubMed

    Sura, P

    1992-01-01

    A circadian morphological rhythm of the pineal organ, as judged by changes in the nuclear volume of the photoreceptor cells, was found in sexually mature male Yellow-bellied toads (Bombina variegata) maintained continuously at 26 degrees C and on a 17L/7D illumination cycle. The greatest nuclear volume occurred at the photophase (16.00 h), and the lowest at the end of the scotophase (4.00 h). PMID:1306508

  3. Health Impact of Fasting in Saudi Arabia during Ramadan: Association with Disturbed Circadian Rhythm and Metabolic and Sleeping Patterns

    PubMed Central

    Ajabnoor, Ghada M.; Bahijri, Suhad; Borai, Anwar; Abdulkhaliq, Altaf A.; Al-Aama, Jumana Y.; Chrousos, George P.

    2014-01-01

    Background Muslims go through strict Ramadan fasting from dawn till sunset for one month yearly. These practices are associated with disturbed feeding and sleep patterns. We recently demonstrated that, during Ramadan, circadian cortisol rhythm of Saudis is abolished, exposing these subjects to continuously increased cortisol levels. Hypothesis Secretory patterns of other hormones and metabolic parameters associated with cortisol, and insulin resistance, might be affected during Ramadan. Protocol Ramadan practitioners (18 males, 5 females; mean age ±SEM?=?23.16±1.2 years) were evaluated before and two weeks into Ramadan. Blood was collected for measurements of endocrine and metabolic parameters at 9 am (±1 hour) and again twelve hours later. Results In Ramadan, glucose concentration was kept within normal range, with a significant increase in the morning. Mean morning concentration of leptin was significantly higher than pre-Ramadan values (p?=?0.001), in contrast to that of adiponectin, which was significantly lower (p<0.001). These changes were associated with increased insulin resistance in morning and evening. Concentrations of hsCRP were lower during Ramadan than those during regular living conditions, however, normal circadian fluctuation was abolished (p?=?0.49). Even though means of liver enzymes, total bilirubin, total protein and albumin were all decreased during Ramadan, statistically lower means were only noted for GGT, total protein, and albumin (p?=?0.018, 0.002 and 0.001 respectively). Discussion Saudi Ramadan practitioners have altered adipokine patterns, typical of insulin resistance. The noted decreases of hsCRP, liver enzymes, total protein, and albumin, are most likely a result of fasting, while loss of circadian rhythmicity of hsCRP is probably due to loss of circadian cortisol rhythm. Conclusions Modern Ramadan practices in Saudi Arabia, which are associated with evening hypercortisolism, are also characterized by altered adipokines patterns, and an abolished hsCRP circadian rhythm, all likely to increase cardiometabolic risk. PMID:24810091

  4. Prospective cohort study of the circadian rhythm pattern in allogeneic sibling donors undergoing standard granulocyte colony-stimulating factor mobilization

    PubMed Central

    2013-01-01

    Introduction Prior in vivo murine studies suggest circadian oscillations for hematopoietic stem cell release, which are maintained following administration of granulocyte colony-stimulating factor (G-CSF) or plerixafor. Furthermore, retrospective data analysis of healthy donors who underwent G-CSF-induced mobilization demonstrated significantly increased CD34+ cell yields when collected in the afternoon compared with the morning. Methods A prospective study was conducted to directly examine the number of peripheral blood CD34+ and CD34+CD38– progenitor/stem cells at baseline and then every 6 hours for 24 hours on days 4 to 5 of G-CSF (10 ?g/kg/day in the morning) mobilization in 11 allogeneic donors. Data were analyzed using mixed-model analysis of repeated measures. Results Whereas we observed a significant increase in CD34+ cell counts toward the evening, counts were then sustained on the morning of day 5. The correlation between CD34+CD38– cell counts and the less defined CD34+ populations was weak. Conclusions Our results suggest that the pharmacodynamic activity and timing of G-CSF may alter endogenous progenitor rhythms. Donor age, medical history, and medications may also impact circadian rhythm. Further studies should examine the circadian rhythm at the peak of G-CSF mobilization and should consider potential confounders such as the time of G-CSF administration and the age of the subjects. PMID:23514984

  5. Circadian and ultradian extrasystole rhythms in healthy individuals at elevated versus lowland altitudes

    NASA Astrophysics Data System (ADS)

    Kujanik, Stefan; Mikulecky, Miroslav

    2010-09-01

    We defined chronobiologic norms for supraventricular and ventricular single extrasystoles (SV and VE, respectively) in healthy older males in lowland areas. The study was extended to higher altitudes, where hypobaric hypoxia was expected to increase extrasystole frequency, while perhaps not changing rhythmicity. In healthy men (lowland n = 37, altitude n = 22), aged 49-72 years, mean numbers of SVs and VEs were counted over a 24-h period. Cosinor regression was used to test the 24-h rhythm and its 2nd-10th harmonics. The resulting approximating function for either extrasystole type includes its point, 95% confidence interval of the mean, and 95% tolerance for single measurement estimates. Separate hourly differences (delta) between altitude and lowland ( n = 59) were also analysed. Hourly means were significantly higher in the mountains versus lowland, by +0.8 beats/h on average for SVs, and by +0.9 beats/h for VEs. A relatively rich chronogram for VEs in mountains versus lowland exists. Delta VEs clearly display a 24-h component and its 2nd, 3rd, 4th and 7th harmonics. This results in significantly higher accumulation of VEs around 8.00 a.m., 11.00 a.m. and 3.00 p.m. in the mountains. The increase in extrasystole occurrence in the mountains is probably caused by higher hypobaric hypoxia and resulting sympathetic drive. Healthy men at elevated altitudes show circadian and several ultradian rhythms of single VEs dependent on the hypoxia level. This new methodological approach—evaluating the differences between two locations using delta values—promises to provide deeper insight into the occurrence of premature beats.

  6. Effect of melatonin on circadian rhythm, locomotor activity and body temperature in the intact house sparrow, Japanese quail and owl.

    PubMed

    Murakami, N; Kawano, T; Nakahara, K; Nasu, T; Shiota, K

    2001-01-19

    We compared the effect of melatonin on circadian rhythm, body temperature, and locomotion in the intact house sparrow, Japanese quail and owl. Daily treatment with melatonin at a fixed time did not entrain the free-running rhythm of locomotor activity in the house sparrow and the disrupted rhythm in Japanese quail under constant dim light. However, melatonin clearly inhibited movement for several hours after treatment. The duration of resting after injection of melatonin was dose-dependent. Body temperature was significantly decreased after melatonin treatment, the effect being more potent during the active phase than in the resting phase. Although this effect of melatonin on body temperature was also dose-dependent, the magnitude of the decrease in body temperature after injection of melatonin was greater in the house sparrow than in the Japanese quail. On the other hand, melatonin induced a further large decrease of body temperature in a nocturnal bird, the owl, whose pineal gland is degenerate. The decrease of body temperature was larger in the active phase than in the resting phase, and melatonin did not prevent movement in spite of the decrease in body temperature. These results suggest that the effects of melatonin on circadian rhythm, locomotor activity and body temperature differ among avian species, and that these mechanisms may not be linked to each other. PMID:11166707

  7. Sleep and heart rate circadian rhythm in depression: the necessity to separate.

    PubMed

    Taillard, J; Lemoine, P; Boule, P; Drogue, M; Mouret, J

    1993-02-01

    In order to determine whether a decrease in the amplitude of heart rate circadian rhythm (HRCR) could represent a chronobiological marker of depression and to answer the question of the possible role of this alteration in the reduction of rapid eye movement sleep latency (REM latency) observed in depression, 22 major depressed patients (DSM III R, Montgomery Asberg Depression Rating Scale) and 11 healthy volunteers entered this study, which included the simultaneous recordings of sleep and heart rate (HR) during two consecutive 24-h periods. After a smoothing procedure, the HR data, obtained from a portable device providing mean HR/min, were computed with the single cosinor method for the classical circadian parameters. We also determined the cosinor fitting index (CFI = percentage to fit). When studied as a single group and compared to the control group, the depressed patients, who had difficulties in sleep initiation and whose REM latencies were within normal limits, were characterized by a dampening of the amplitude HRCR and of the day-night HR difference. This was linked to a lesser increase of HR during the day and a reduced decrease at night. No significant phase modification of HRCR was observed in this group of depressives. In a second step, the depressives were divided into a depressed arrhythmic group (DAG, CFI < 50%, 11 patients) and a depressed rhythmic group (DRG, CFI > 50%, 11 patients) who did not differ on MADRS scores. Even though the amplitude of HRCR was reduced in the DAG only, with HR higher at night and lower during the daytime than for controls, both DAG and DRG significantly differed from controls on those items related to sleep induction and maintenance. In the DAG only was there a tendency toward a reduction of total sleep time and REM sleep time while REM latency was normal. This finding suggests that sleep problems are not responsible for the differences in HRCR parameters between the two depressed groups. These differences in HR and sleep parameters between two groups of similarly depressed patients also suggest that a short REM latency does not systematically imply a disruption of all circadian clocks. PMID:8443845

  8. UNC79 and UNC80, Putative Auxiliary Subunits of the NARROW ABDOMEN Ion Channel, Are Indispensable for Robust Circadian Locomotor Rhythms in Drosophila

    PubMed Central

    Lear, Bridget C.; Darrah, Eric J.; Aldrich, Benjamin T.; Gebre, Senetibeb; Scott, Robert L.; Allada, Ravi

    2013-01-01

    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. PMID:24223770

  9. Effects of systemically applied nAChR?7 agonists and antagonists on light-induced phase shifts of hamster circadian activity rhythms.

    PubMed

    Gannon, Robert L; Garcia, David A; Millan, Mark J

    2014-06-01

    Many physiological systems in mammals are linked to the body's master circadian rhythm in the sleep/wake cycle and dysfunctions in this rhythm has been associated with neurological diseases such as major depression, Alzheimer's Disease and schizophrenia. There is some evidence that nicotinic cholinergic input to the master circadian pacemaker, the suprachiasmatic nucleus, may modulate circadian activity rhythms, but data employing in vivo preparations is sparse. Therefore we examined the ability of intraperitoneally applied nicotinic agonists and antagonists relatively selective for the ?7 nicotinic receptor to modulate light-induced phase shifts of hamster circadian wheel running rhythms. Hamsters were maintained in constant darkness and exposed to light pulses early and late in their active period, mimicking dusk and dawn respectively, which elicited phase delays and advances of their circadian wheel running rhythms. The ?7 receptor antagonists bPiDDB (0.03-3mg/kg) and methyllacaconitine (0.1-1mg/kg) inhibited both light- induced phase advances and delays of circadian wheel running rhythms by as much as 75% versus vehicle injections. In contrast, systemic injections of the ?7 agonists PHA 543613 and ABT107, both at 0.156-2.5mg/kg, had no effect on light induced phase advances or delays. Further, ?7 nicotinic receptors were identified in the hamster suprachiasmatic nucleus using an antibody that recognizes ?7 nicotinic receptors. These results clearly identify the ability of ?7 nicotinic receptor antagonists to inhibit light-entrainment of the hamster circadian pacemaker. Therefore, nicotinic compounds may be useful for the treatment of circadian dysfunction associated with neurological diseases. PMID:24388152

  10. Impact of anxiety level on circadian rhythm of blood pressure in hypertensive patients

    PubMed Central

    Özpelit, Mehmet Emre; Özpelit, Ebru; Do?an, Nazile Bilgin; Pekel, Nihat; Ozyurtlu, Ferhat; Y?lmaz, Akar; Sayg?, Serkan; Tengiz, ?stemihan; Ercan, Ertugrul

    2015-01-01

    Introduction: Considering the high prevalence rates and growing incidences of hypertension (HT) and anxiety disorders in the modern world, a full understanding of anxiety’s relationship to HT is crucial. In this study we aimed to investigate the effects of anxiety level on circadian rhythm of blood pressure (BP) in hypertensive patients. Material and method: This cross-sectional study included 160 previously diagnosed essential hypertensive patients (80 female, 80 male, mean age: 55.3±15.1 years). All participants underwent 24 h ambulatory blood pressure monitoring (ABPM) and filled State-Trait Anxiety Inventory (STAI) (trait) Questionnaire. The study population was divided into 2 groups according to their STAI scores; an anxiety group (n=97; STAI ?45) and a control group (n=63; STAI<44). Clinical characteristics, laboratory findings and ABPM measurements were compared between the groups. Results: There was no significant difference between the groups for ABPM parameters except morning blood pressure surge (MBPS). Anxiety group had a significantly higher MBPS compared to control group (14.4±17.0 vs 9.1±11.9 mmHg, P:0.03). Multivariate analysis showed that duration of HT and STAI score were the only independent predictors of MBPS. Conclusion: Patients’ anxiety level is associated with MBPS which is an independent risk factor for cardiovascular complications. Assessment and control of anxiety seems to be worthy in effective treatment of hypertension. PMID:26629141

  11. Effects of restricted fructose access on body weight and blood pressure circadian rhythms.

    PubMed

    Senador, Danielle; Shewale, Swapnil; Irigoyen, Maria Claudia; Elased, Khalid M; Morris, Mariana

    2012-01-01

    High-fructose diet is known to produce cardiovascular and metabolic pathologies. The objective was to determine whether the timing of high fructose (10% liquid solution) intake affect the metabolic and cardiovascular outcomes. Male C57BL mice with radiotelemetric probes were divided into four groups: (1) 24 h water (control); (2) 24 h fructose (F24); (3) 12 h fructose during the light phase (F12L); (4) 12 h fructose during the dark phase (F12D). All fructose groups had higher fluid intake. Body weight was increased in mice on restricted access with no difference in total caloric intake. Fasting glycemia was higher in groups with restricted access. F24 mice showed a fructose-induced blood pressure increase during the dark period. Blood pressure circadian rhythms were absent in F12L mice. Results suggest that the timing of fructose intake is an important variable in the etiology of cardiovascular and metabolic pathologies produced by high fructose consumption. PMID:22536215

  12. Interpersonal sensitivity predicts depressive symptom response to the circadian rhythm disruption of nightwork.

    PubMed

    Adeniran, R; Healy, D; Sharp, H; Williams, J M; Minors, D; Waterhouse, J M

    1996-11-01

    This paper reports the results of a study designed to explore the validity of a shiftwork model of affective disorders. Fifty-five student nurses doing nightwork for the first time were recruited to a study designed both to replicate an earlier study of the effects of nightwork on cognitive, emotional and neurovegetative measures and to assess the effects of nightwork on personality measures and the role of personality factors and nightwork induced disturbances in predicting accommodation to nightwork. As in the earlier study, concentration, interest, energy, sleep and appetite were significantly disturbed by nightwork and there was an increased perception of recent criticism from other. The findings from both studies were, therefore, aggregated to explore further possible relations between outcomes and the pre-nightwork level of affective symptoms and sensitivity to interpersonal criticism. These predicted poor response. In contrast, measures of cognitive style and symptom interpretation did not predict outcome. The findings are not inconsistent with proposals that disturbance of circadian rhythms consequent on psychosocial disruptions may play a part in the genesis of or maintenance of depression. They also support a proposal that nightwork induced changes may be a suitable human model for investigation of aspects of the affective disorders. PMID:8931167

  13. BIOLOGICAL RHYTHMS AS TEMPORAL DISSIPATIVE STRUCTURES

    E-print Network

    Goldbeter, Albert

    of cAMP B. Link with Pulsatile Hormone Secretion VI. Circadian Rhythms A. Circadian Rhythms-Term Suppression of Circadian Rhythms by a Single Light Pulse E. Stochastic Versus Deterministic Models for Circadian Rhythms VII. The Cell-Cycle Clock VIII. Newly Discovered Cellular Rhythms A. Oscillations of p53

  14. Effects of afternoon "siesta" naps on sleep, alertness, performance, and circadian rhythms in the elderly

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Buysse, D. J.; Carrier, J.; Billy, B. D.; Rose, L. R.

    2001-01-01

    STUDY OBJECTIVES: To determine the effects of a 90-minute afternoon nap regimen on nocturnal sleep, circadian rhythms, and evening alertness and performance levels in the healthy elderly. DESIGN AND SETTING: Nine healthy elderly subjects (4m, 5f, age range 74y-87y) each experienced both nap and no-nap conditions in two studies each lasting 17 days (14 at home, 3 in the laboratory). In the nap condition a 90-minute nap was enforced between 13:30 and 15:00 every day, in the no-nap condition daytime napping was prohibited, and activity encouraged in the 13:30-15:00 interval. The order of the two conditions was counterbalanced. PARTICIPANTS: N/A INTERVENTIONS: N/A MEASUREMENTS: Diary measures, pencil and paper alertness tests, and wrist actigraphy were used at home. In the 72 hour laboratory studies, these measures were augmented by polysomnographic sleep recording, continuous rectal temperature measurement, a daily evening single trial of a Multiple Sleep Latency Test (MSLT), and computerized tests of mood, activation and performance efficiency. RESULTS: By the second week in the "at home" study, an average of 58 minutes of sleep was reported per siesta nap; in the laboratory, polysomnography confirmed an average of 57 minutes of sleep per nap. When nap and no-nap conditions were compared, mixed effects on nocturnal sleep were observed. Diary measures indicated no significant difference in nocturnal sleep duration, but a significant increase (of 38 mins.) in 24-hour Total Sleep Time (TST) when nocturnal sleeps and naps were added together (p<0.025). The laboratory study revealed a decrease of 2.4% in nocturnal sleep efficiency in the nap condition (p<0.025), a reduction of nocturnal Total Sleep Time (TST) by 48 mins. in the nap condition (p<0.001) which resulted primarily from significantly earlier waketimes (p<0.005), but no reliable effects on Wake After Sleep Onset (WASO), delta sleep measures, or percent stages 1 & 2. Unlike the diary study, the laboratory study yielded no overall increase in 24-hour TST consequent upon the siesta nap regimen. The only measure of evening alertness or performance to show an improvement was sleep latency in a single-trial evening MSLT (nap: 15.6 mins., no nap: 11.5 mins., p<0.005). No significant change in circadian rhythm parameters was observed. CONCLUSIONS: Healthy seniors were able to adopt a napping regimen involving a 90-minute siesta nap each day between 13:30 and 15:00, achieving about one hour of actual sleep per nap. There were some negative consequences for nocturnal sleep in terms of reduced sleep efficiency and earlier waketimes, but also some positive consequences for objective evening performance and (in the diary study) 24-hour sleep totals. Subjective alertness measures and performance measures showed no reliable effects and circadian phase parameters appeared unchanged.

  15. l-5-hydroxytryptophan resets the circadian locomotor activity rhythm of the nocturnal Indian pygmy field mouse, Mus terricolor

    NASA Astrophysics Data System (ADS)

    Basu, Priyoneel; Singaravel, Muniyandi; Haldar, Chandana

    2012-03-01

    We report that l-5-hydroxytryptophan (5-HTP), a serotonin precursor, resets the overt circadian rhythm in the Indian pygmy field mouse, Mus terricolor, in a phase- and dose-dependent manner. We used wheel running to assess phase shifts in the free-running locomotor activity rhythm. Following entrainment to a 12:12 h light-dark cycle, 5-HTP (100 mg/kg in saline) was intraperitoneally administered in complete darkness at circadian time (CT)s 0, 3, 6, 9, 12, 15, 18, and 21, and the ensuing phase shifts in the locomotor activity rhythm were calculated. The results show that 5-HTP differentially shifts the phase of the rhythm, causing phase advances from CT 0 to CT 12 and phase delays from CT 12 to CT 21. Maximum advance phase shift was at CT 6 (1.18 ± 0.37 h) and maximum delay was at CT 18 (-2.36 ± 0.56 h). No extended dead zone is apparent. Vehicle (saline) at any CT did not evoke a significant phase shift. Investigations with different doses (10, 50, 100, and 200 mg/kg) of 5-HTP revealed that the phase resetting effect is dose-dependent. The shape of the phase-response curve (PRC) has a strong similarity to PRCs obtained using some serotonergic agents. There was no significant increase in wheel-running activity after 5-HTP injection, ruling out behavioral arousal-dependent shifts. This suggests that this phase resetting does not completely depend on feedback of the overt rhythmic behavior on the circadian clock. A mechanistic explanation of these shifts is currently lacking.

  16. Impairment of Circadian Rhythms in Peripheral Clocks by Constant Light Is Partially Reversed by Scheduled Feeding or Exercise.

    PubMed

    Hamaguchi, Yutaro; Tahara, Yu; Hitosugi, Masashi; Shibata, Shigenobu

    2015-12-01

    In mammals, circadian rhythms in peripheral organs are impaired when animals are maintained in abnormal environmental light-dark cycles such as constant light (LL). This conclusion is based on averaged data from groups of experimental animals sacrificed at each time point. To investigate the effect of LL housing on the peripheral clocks of individual mice, an in vivo imaging system was used to observe the circadian bioluminescence rhythm in peripheral tissues of the liver, kidney, and submandibular salivary gland in PER2::LUCIFERASE knock-in mice. Using this technique, we demonstrated that the majority of individual peripheral tissues still had rhythmic oscillations of their circadian clocks in LL conditions. However, LL housing caused decreased amplitudes and a broad distribution of peak phases in PER2::LUCIFERASE oscillations irrespective of the state of the animals' behavioral rhythmicity. Because both scheduled feeding and scheduled exercise are effective recovery stimuli for circadian clock deficits, we examined whether scheduled feeding or scheduled exercise could reverse this impairment. The results showed that scheduled feeding or exercise could not restore the amplitude of peripheral clocks in LL. On the other hand, the LL-induced broad phase distribution was reversed, and peak phases were entrained to a specific time point by scheduled feeding but only slightly by scheduled exercise. The present results demonstrate that LL housing impairs peripheral circadian clock oscillations by altering both amplitude and phase in individual mice. The broad distribution of clock phases was clearly reversed by scheduled feeding, suggesting the importance of scheduled feeding as an entraining stimulus for impaired peripheral clocks. PMID:26467286

  17. Suprachiasmatic regulation of circadian rhythms of gene expression in hamster peripheral organs: effects of transplanting the pacemaker.

    PubMed

    Guo, Hongnian; Guo, Hongian; Brewer, Judy McKinley; Lehman, Michael N; Bittman, Eric L

    2006-06-14

    Neurotransplantation of the suprachiasmatic nucleus (SCN) was used to assess communication between the central circadian pacemaker and peripheral oscillators in Syrian hamsters. Free-running rhythms of haPer1, haPer2, and Bmal1 expression were documented in liver, kidney, spleen, heart, skeletal muscle, and adrenal medulla after 3 d or 11 weeks of exposure to constant darkness. Ablation of the SCN of heterozygote tau mutants eliminated not only rhythms of locomotor activity but also rhythmic expression of these genes in all peripheral organs studied. The Per:Bmal ratio suggests that this effect was attributable not to asynchronous rhythmicity between SCN-lesioned individuals but to arrhythmicity within individuals. Grafts of wild-type SCN to heterozygous, SCN-lesioned tau mutant hamsters not only restored locomotor rhythms with the period of the donor but also led to recovery of rhythmic expression of haPer1, haPer2, and haBmal1 in liver and kidney. The phase of these rhythms most closely resembled that of intact wild-type hamsters. Rhythmic gene expression was also restored in skeletal muscle, but the phase was altered. Behaviorally effective SCN transplants failed to reinstate rhythms of clock gene expression in heart, spleen, or adrenal medulla. These findings confirm that peripheral organs differ in their response to SCN-dependent cues. Furthermore, the results indicate that conventional models of internal entrainment may need to be revised to explain control of the periphery by the pacemaker. PMID:16775127

  18. Functional genomics of the avian circadian system 

    E-print Network

    Bailey, Michael J

    2006-04-12

    The genetic identification of molecular mechanisms responsible for circadian rhythm generation has advanced tremendously over the past 25 years. However the molecular identities of the avian clock remain largely unexplored. The present studies seek...

  19. A circadian rhythm in heart rate variability contributes to the increased cardiac sympathovagal response to awakening in the morning.

    PubMed

    Boudreau, Philippe; Yeh, Wei Hsien; Dumont, Guy A; Boivin, Diane B

    2012-07-01

    Morning hours are associated with a heightened risk of adverse cardiovascular events. Recent evidence suggests that the sleep-wake cycle and endogenous circadian system modulate cardiac function in humans and may contribute to these epidemiological findings. The aim of the present study was to investigate the interaction between circadian and sleep-wake-dependent processes on heart rate variability (HRV). Fifteen diurnally active healthy young adults underwent a 72-h ultradian sleep-wake cycle (USW) procedure (alternating 60-min wake episodes in dim light and 60-min nap opportunities in total darkness) in time isolation. The present study revealed a significant main effect of sleep-wake-dependent and circadian processes on cardiac rhythmicity, as well as a significant interaction between these processes. Turning the lights off was associated with a rapid increase in mean RR interval and cardiac parasympathetic modulation (high-frequency [HF] power), whereas low-frequency (LF) power and sympathovagal balance (LF:HF ratio) were reduced (p???.001). A significant circadian rhythm in mean RR interval and HRV components was observed throughout the wake and nap episodes (p???.001). Sleep-to-wake transitions occurring in the morning were associated with maximal shifts towards sympathetic autonomic activation as compared to those occurring during the rest of the day. Namely, peak LF:HF ratio was observed in the morning, coincidental with peak salivary cortisol levels. These results contribute to our understanding of the observed increase in cardiovascular vulnerability after awakening in the morning. PMID:22734576

  20. Nocturnal eczema: Review of sleep and circadian rhythms in children with atopic dermatitis and future research directions.

    PubMed

    Fishbein, Anna B; Vitaterna, Olivia; Haugh, Isabel M; Bavishi, Aakash A; Zee, Phyllis C; Turek, Fred W; Sheldon, Stephen H; Silverberg, Jonathan I; Paller, Amy S

    2015-11-01

    Children with atopic dermatitis (AD) experience significant sleep disruption, and clinically, the disease is noted to worsen in a circadian manner at night. Epidemiologic findings highlight many negative consequences of AD, such as impaired linear growth, which is uniquely related to disturbed sleep. Clinical guidelines currently recommend assessing sleep in patients with AD as a crucial parameter of disease control with appropriate treatment. In this review we describe our current understanding of the roles of sleep cycles and circadian rhythms in the nighttime exacerbation of AD (nocturnal eczema). We present a schematic to explain the mechanism of nocturnal eczema. Treatment options for sleep disturbance and future directions for research are discussed in the context of AD. PMID:26549635

  1. Influence of the circadian rhythm of body temperature on the physiological response to microwaves: Day versus night exposure

    SciTech Connect

    Lotz, W.G.

    1981-10-01

    The results of this study demonstrate an influence of the circadian rhythm on the effects of microwave exposure on plasma cortisol and rectal temperature. The lower rectal temperature during night exposures was presumably due to the lower sham-condition temperature at night, since the temperature increase over sham levels was similar for either day or night exposures. The absence of a cortisol response during night exposures may be simply related to the absolute body temperature reached, although more complex circadian influences cannot be eliminated by these data. Although the results were insufficient to provide a clear understanding of the mechanisms involved, it was shown conclusively that the responses studied depended not only on the independent variables of microwave exposure selected, but also on the baseline levels of the normal physiological state that existed at the time of exposure.

  2. Circadian Rhythm of Leaves of Phaseolus angularis Plants Grown in a Controlled Carbon Dioxide and Humidity Environment 1

    PubMed Central

    Alford, D. K.; Tibbitts, T. W.

    1970-01-01

    Leaf movements of primary leaves of Phaseolus angularis Wight. were studied in an environment with controlled levels of CO2, relative humidity, temperature, light, nutrient concentrations, and water tension. Rhythmic circadian movements and irregular short period movements were evident as the leaves unfolded and persisted during development of the leaves. The mean period in rhythmic circadian movement was 27.3 hours with no significant differences in period between plants of the same or different experiments. The leaf movements of separate plants were not closely synchronized. A system is described for growing plants for extended periods while collecting data with time lapse photography. The system was developed to minimize disturbances to the plants. The occurrence of leaf movements in plants grown from the time of seeding in an environment free of any recognized fluctuation which could stimulate leaf movements supports the hypothesis that leaf movement rhythms originate spontaneously within the plant. Images PMID:16657429

  3. Effects of circadian rhythm phase alteration on physiological and psychological variables: Implications to pilot performance (including a partially annotated bibliography)

    NASA Technical Reports Server (NTRS)

    Holley, D. C.; Winger, C. M.; Deroshia, C. W.; Heinold, M. P.; Edgar, D. M.; Kinney, N. E.; Langston, S. E.; Markley, C. L.; Anthony, J. A.

    1981-01-01

    The effects of environmental synchronizers upon circadian rhythmic stability in man and the deleterious alterations in performance and which result from changes in this stability are points of interest in a review of selected literature published between 1972 and 1980. A total of 2,084 references relevant to pilot performance and circadian phase alteration are cited and arranged in the following categories: (1) human performance, with focus on the effects of sleep loss or disturbance and fatigue; (2) phase shift in which ground based light/dark alteration and transmeridian flight studies are discussed; (3) shiftwork; (4)internal desynchronization which includes the effect of evironmental factors on rhythmic stability, and of rhythm disturbances on sleep and psychopathology; (5) chronotherapy, the application of methods to ameliorate desynchronization symptomatology; and (6) biorythm theory, in which the birthdate based biorythm method for predicting aircraft accident susceptability is critically analyzed. Annotations are provided for most citations.

  4. Sleep and circadian rhythm regulate circulating complement factors and immunoregulatory properties of C5a.

    PubMed

    Reis, Edimara S; Lange, Tanja; Köhl, Gabriele; Herrmann, Anne; Tschulakow, Alexander V; Naujoks, Julius; Born, Jan; Köhl, Jörg

    2011-10-01

    The sleep-wake cycle is characterized by complex interactions among the central nervous, the endocrine and the immune systems. Continuous 24-h wakefulness prevents sleep-associated hormone regulation resulting in impaired pro-inflammatory cytokine production. Importantly, cytokines and hormones also modulate the complement system, which in turn regulates several adaptive immune responses. However, it is unknown whether sleep affects the activation and the immunoregulatory properties of the complement system. Here, we determined whether the 24-h sleep-wake cycle has an impact on: (i) the levels of circulating complement factors; and (ii) TLR4-mediated IL-12 production from human IFN-? primed monocytes in the presence or absence of C5a receptor signaling. For this purpose, we analyzed the blood and blood-derived monocytes of 13 healthy donors during a regular sleep-wake cycle in comparison to 24 h of continuous wakefulness. We found decreased plasma levels of C3 and C4 during nighttime hours that were not affected by sleep. In contrast, sleep was associated with increased complement activation as reflected by elevated C3a plasma levels during nighttime sleep. Sleep deprivation prevented such activation. At the cellular level, C5a negatively regulated TLR4-mediated IL-12p40 and p70 production from human monocytes. Importantly, this regulatory effect of C5a on IL-12p70 production was effective only during daytime hours. Thus, similar to hormones, some complement factors and immunoregulatory properties of C5a are influenced by sleep and the circadian rhythm. Our findings that continuous wakefulness has a negative impact on complement activation may provide a rationale for the immunosupportive functions of sleep. PMID:21539909

  5. Relation between circadian blood pressure rhythm and serum albumin level in non-diabetic patients with proteinuria.

    PubMed

    Ando, Daisaku; Hirawa, Nobuhito; Yasuda, Gen

    2016-02-01

    It remains unclear whether the abnormal circadian blood pressure (BP) rhythm in non-diabetic chronic kidney disease (CKD) is related to hypoalbuminemia. We evaluated relationships between circadian BP rhythm and serum albumin concentration (SAC) and also examined autonomic nervous activities. Non-diabetic CKD patients with proteinuria (n?=?197; 105 men, 92 women; aged 47.0?±?13.3 years; estimated glomerular filtration rate??30 ml/min) were divided into nephrotic syndrome (NS: n?=?46, SAC???30 g/l), hypoalbuminemia (n?=?65, 30?circadian BP rhythms were related to SAC and 24 h sympathovagal imbalance. PMID:26462818

  6. SLEEPAND CIRCADIAN NEUROBIOLOGY (SCN)

    E-print Network

    Kay, Mark A.

    STANFORD SLEEPAND CIRCADIAN NEUROBIOLOGY (SCN) LABORATORY STANFORD SLEEP DISORDERS CLINIC the enormous unmet needs of sleep disorders medicine and disorders of circadian timekeeping. The Stanford Sleep of new types of pharmaceuticals for sleep disorders medicine and circadian rhythm disorders

  7. Pilot Investigation of the Circadian Plasma Melatonin Rhythm across the Menstrual Cycle in a Small Group of Women with Premenstrual Dysphoric Disorder

    PubMed Central

    Shechter, Ari; Lespérance, Paul; Ng Ying Kin, N. M. K.; Boivin, Diane B.

    2012-01-01

    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. PMID:23284821

  8. Effects of 9-hour time zone changes on fatigue and circadian rhythms of sleep/wake and core temperature

    NASA Technical Reports Server (NTRS)

    Gander, P. H.; Myhre, G.; Graeber, R. C.; Andersen, H. T.; Lauber, J. K.

    1985-01-01

    Physiological and psychological disruptions caused by transmeridian flights may affect the ability of flight crews to meet operational demands. To study these effects, 9 Royal Norwegian Airforces P3-Orion crewmembers flew from Norway to California (-9 hr), and back (+9 hr). Rectal temperature, heart rate and wrist activity were recorded every 2 min, fatigue and mood were rated every 2 hr during the waking day, and logs were kept of sleep times and ratings. Subjects also completed 4 personality inventories. The time-zone shifts produced negative changes in mood which persisted longer after westward flights. Sleep quality (subjective and objective) and duration were slightly disrupted (more after eastward flights). The circadian rhythms of sleep/wake and temperature both completed the 9-hr delay by day 5 in California, although temperature adjusted more slowly. The size of the delay shift was significantly correlated with scores on extraversion and achievement need personality scales. Response to the 9-hr advance were more variable. One subject exhibited a 15-hr delay in his temperature rhythm, and an atypical sleep/nap pattern. On average, the sleep/wake cycle (but not the temperature rhythm), completed the 9-hr advance by the end of the study. Both rhythms adapted more slowly after the eastward flight.

  9. Effect of sleep-wake reversal and sleep deprivation on the circadian rhythm of oxygen toxicity seizure susceptibility.

    NASA Technical Reports Server (NTRS)

    Dexter, J. D.; Hof, D. G.; Mengel, C. E.

    1972-01-01

    Albino Sprague-Dawley rats were exposed in a previously O2 flushed, CO2 free chamber. The exposure began with attainment of 60 psi (gauge) and the end point was the first generalized oxygen toxicity seizure. Animals were exposed to reversal diurnal conditions since weanlings until their sleep-wake cycles had completely reversed, and then divided into four groups of 20 based on the time of day exposed. The time of exposure to oxygen at high pressure prior to seizure was now significantly longer in the group exposed from 1900 to 2000 hr and a reversal of the circadian rhythm of oxygen toxicity seizure susceptibility was noted. Animals maintained on normal diurnal conditions were deprived of sleep on the day of exposure for the 12 hours prior to exposure at 1900 hr, while controls were allowed to sleep. There was no significant differences in the time prior to seizure between the deprived animals and the controls with an n = 40. Thus the inherent threshold in susceptibility to high-pressure oxygen seizures seems not to be a function of sleep itself, but of some biochemical/physiologic event which manifests a circadian rhythm.

  10. Abnormal circadian rhythm and cortisol excretion in autistic children: a clinical study

    PubMed Central

    Lakshmi Priya, Malarveni Damodaran; Geetha, Arumugam; Suganya, Vijayashankar; Sujatha, Sridharan

    2013-01-01

    Aim To determine the circadian rhythm alteration of cortisol excretion and the level of corticosteroids in children with different grades of autism severity. Methods The study included 45 children with different grades of autism severity (low [LFA], medium [MFA], and high functioning autism [HFA]), 15 in each group, and 45 age/sex-matched children with typical development. The urinary levels of free cortisol (at three phases of 24-hour cycle), corticosteroids, vanilylmandelic acid, and 5-hydroxyindole acetic acid were determined. Results Alteration in the pattern of cortisol excretion (Phases I, II, and III) was observed in children with LFA (Phase I: 43.8?±?4.43 vs 74.30±8.62, P?=?0.000; Phase II: 21.1±2.87 vs 62±7.68, P?

  11. Relationship of endogenous circadian melatonin and temperature rhythms to self-reported preference for morning or evening activity in young and older people

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

    BACKGROUND: Morningness-eveningness refers to interindividual differences in preferred timing of behavior (i.e., bed and wake times). Older people have earlier wake times and rate themselves as more morning-like than young adults. It has been reported that the phase of circadian rhythms is earlier in morning-types than in evening types, and that older people have earlier phases than young adults. These changes in phase have been considered to be the chronobiological basis of differences in preferred bed and wake times and age-related changes therein. Whether such differences in phase are associated with changes in the phase relationship between endogenous circadian rhythms and the sleep-wake cycle has not been investigated previously. METHODS: We investigated the association between circadian phase, the phase relationship between the sleep-wake cycle and circadian rhythms, and morningness-eveningness, and their interaction with aging. In this circadian rhythm study, 68 young and 40 older subjects participated. RESULTS: Among the young subjects, the phase of the melatonin and core temperature rhythms occurred earlier in morning than in evening types and the interval between circadian phase and usual wake time was longer in morning types. Thus, while evening types woke at a later clock hour than morning types, morning types actually woke at a later circadian phase. Comparing young and older morning types we found that older morning types had an earlier circadian phase and a shorter phase-wake time interval. The shorter phase-waketime interval in older "morning types" is opposite to the change associated with morningness in young people, and is more similar to young evening types. CONCLUSIONS: These findings demonstrate an association between circadian phase, the relationship between the sleep-wake cycle and circadian phase, and morningness-eveningness in young adults. Furthermore, they demonstrate that age-related changes in phase angle cannot be attributed fully to an age-related shift toward morningness. These findings have important implications for understanding individual preferences in sleep-wake timing and age-related changes in the timing of sleep.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  13. Circadian Clocks in the Immune System.

    PubMed

    Labrecque, Nathalie; Cermakian, Nicolas

    2015-08-01

    The immune system is a complex set of physiological mechanisms whose general aim is to defend the organism against non-self-bodies, such as pathogens (bacteria, viruses, parasites), as well as cancer cells. Circadian rhythms are endogenous 24-h variations found in virtually all physiological processes. These circadian rhythms are generated by circadian clocks, located in most cell types, including cells of the immune system. This review presents an overview of the clocks in the immune system and of the circadian regulation of the function of immune cells. Most immune cells express circadian clock genes and present a wide array of genes expressed with a 24-h rhythm. This has profound impacts on cellular functions, including a daily rhythm in the synthesis and release of cytokines, chemokines and cytolytic factors, the daily gating of the response occurring through pattern recognition receptors, circadian rhythms of cellular functions such as phagocytosis, migration to inflamed or infected tissue, cytolytic activity, and proliferative response to antigens. Consequently, alterations of circadian rhythms (e.g., clock gene mutation in mice or environmental disruption similar to shift work) lead to disturbed immune responses. We discuss the implications of these data for human health and the areas that future research should aim to address. PMID:25900041

  14. Explaining the sawtooth: latitudinal periodicity in a circadian gene correlates with shifts in generation number.

    PubMed

    Levy, R C; Kozak, G M; Wadsworth, C B; Coates, B S; Dopman, E B

    2015-01-01

    Many temperate insects take advantage of longer growing seasons at lower latitudes by increasing their generation number or voltinism. In some insects, development time abruptly decreases when additional generations are fit into the season. Consequently, latitudinal 'sawtooth' clines associated with shifts in voltinism are seen for phenotypes correlated with development time, like body size. However, latitudinal variation in voltinism has not been linked to genetic variation at specific loci. Here, we show a pattern in allele frequency among voltinism ecotypes of the European corn borer moth (Ostrinia nubilalis) that is reminiscent of a sawtooth cline. We characterized 145 autosomal and sex-linked SNPs and found that period, a circadian gene that is genetically linked to a major QTL determining variation in post-diapause development time, shows cyclical variation between voltinism ecotypes. Allele frequencies at an unlinked circadian clock gene cryptochrome1 were correlated with period. These results suggest that selection on development time to 'fit' complete life cycles into a latitudinally varying growing season produces oscillations in alleles associated with voltinism, primarily through changes at loci underlying the duration of transitions between diapause and other life history phases. Correlations among clock loci suggest possible coupling between the circadian clock and the circannual rhythms for synchronizing seasonal life history. We anticipate that latitudinal oscillations in allele frequency will represent signatures of adaptation to seasonal environments in other insects and may be critical to understanding the ecological and evolutionary consequences of variable environments, including response to global climate change. PMID:25430782

  15. Leptin-sensitive neurons in the arcuate nucleus integrate activity and temperature circadian rhythms and anticipatory responses to food restriction

    PubMed Central

    Li, Ai-Jun; Dinh, Thu T.; Jansen, Heiko T.; Ritter, Sue

    2013-01-01

    Previously, we investigated the role of neuropeptide Y and leptin-sensitive networks in the mediobasal hypothalamus in sleep and feeding and found profound homeostatic and circadian deficits with an intact suprachiasmatic nucleus. We propose that the arcuate nuclei (Arc) are required for the integration of homeostatic circadian systems, including temperature and activity. We tested this hypothesis using saporin toxin conjugated to leptin (Lep-SAP) injected into Arc in rats. Lep-SAP rats became obese and hyperphagic and progressed through a dynamic phase to a static phase of growth. Circadian rhythms were examined over 49 days during the static phase. Rats were maintained on a 12:12-h light-dark (LD) schedule for 13 days and, thereafter, maintained in continuous dark (DD). After the first 13 days of DD, food was restricted to 4 h/day for 10 days. We found that the activity of Lep-SAP rats was arrhythmic in DD, but that food anticipatory activity was, nevertheless, entrainable to the restricted feeding schedule, and the entrained rhythm persisted during the subsequent 3-day fast in DD. Thus, for activity, the circuitry for the light-entrainable oscillator, but not for the food-entrainable oscillator, was disabled by the Arc lesion. In contrast, temperature remained rhythmic in DD in the Lep-SAP rats and did not entrain to restricted feeding. We conclude that the leptin-sensitive network that includes the Arc is required for entrainment of activity by photic cues and entrainment of temperature by food, but is not required for entrainment of activity by food or temperature by photic cues. PMID:23986359

  16. Differential maturation of circadian rhythms in clock gene proteins in the suprachiasmatic nucleus and the pars tuberalis during mouse ontogeny

    PubMed Central

    Ansari, Nariman; Agathagelidis, Manuel; Lee, Choogon; Korf, Horst-Werner; von Gall, Charlotte

    2009-01-01

    Circadian rhythms of many body functions in mammals are controlled by a master pacemaker residing in the hypothalamic suprachiasmatic nucleus (SCN) that synchronises peripheral oscillators. The SCN and peripheral oscillators share several components of the molecular clockwork and comprise transcriptional activators (BMAL1 and CLOCK/NPAS2) and inhibitors (mPER1/2 and mCRY1/2). Here we compared the ontogenetic maturation of the clockwork in the SCN and pars tuberalis (PT). The PT is a peripheral oscillator that strongly depends on rhythmic melatonin signals. Immunoreactions for clock gene proteins were determined in the SCN and PT at four different timepoints during four differential stages of mouse ontogeny: foetal (embryonic day 18), newborn (2-day-old), infantile (10-day-old), and adult. In the foetal SCN levels of immunoreactions of all clock proteins were significantly lower as compared to adult levels except for BMAL1. In the newborn SCN the clock protein immunoreactions had not yet reached adult levels, but the infantile SCN showed similar levels of immunreactions as the adult. In contrast, immunoreactions for all clock gene proteins in the foetal PT were as intense as in newborn, infantile, and adult and showed the same phase. As the foetal pineal gland is not yet capable of rhythmic melatonin production, the rhythms in clock gene proteins in the foetal PT are presumably dependent on the maternal melatonin signal. Thus, our data provide the first evidence that maternal melatonin is important for establishing and maintaining circadian rhythms in a foetal peripheral oscillator. PMID:19222558

  17. Research on sleep, circadian rhythms and aging - Applications to manned spaceflight

    NASA Technical Reports Server (NTRS)

    Czeisler, Charles A.; Chiasera, August J.; Duffy, Jeanne F.

    1991-01-01

    Disorders of sleep and circadian rhythmicity are characteristic of both advancing age and manned spaceflight. Sleep fragmentation, reduced nocturnal sleep tendency and sleep efficiency, reduced daytime alertness, and increased daytime napping are common to both of these conditions. Recent research on the pathophysiology and treatment of disrupted sleep in older people has led to a better understanding of how the human circadian pacemaker regulates the timing of the daily sleep-wake cycle and how it responds to the periodic changes in the light-dark cycle to which we are ordinarily exposed. These findings have led to new treatments for some of the sleep disorders common to older individuals, using carefully timed exposure to bright light and darkness to manipulate the phase and/or amplitude of the circadian timing system. These insights and treatment approaches have direct applications in the design of countermeasures allowing astronauts to overcome some of the challenges which manned spaceflight poses for the human circadian timing system. We have conducted an operational feasibility study on the use of scheduled exposure to bright light and darkness prior to launch in order to facilitate adaptation of the circadian system of a NASA Space Shuttle crew to the altered sleep-wake schedule required for their mission. The results of this study illustrate how an understanding of the properties of the human circadian timing system and the consequences of circadian disruption can be applied to manned spaceflight.

  18. Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC2-signaling deficient mice

    PubMed Central

    Hughes, Alun T.L.; Croft, Cara. L.; Samuels, Rayna E.; Myung, Jihwan; Takumi, Toru; Piggins, Hugh D.

    2015-01-01

    Individual neurons in the suprachiasmatic nuclei (SCN) contain an intracellular molecular clock and use intercellular signaling to synchronize their timekeeping activities so that the SCN can coordinate brain physiology and behavior. The neuropeptide vasoactive intestinal polypeptide (VIP) and its VPAC2 receptor form a key component of intercellular signaling systems in the SCN and critically control cellular coupling. Targeted mutations in either the intracellular clock or intercellular neuropeptide signaling mechanisms, such as VIP-VPAC2 signaling, can lead to desynchronization of SCN neuronal clocks and loss of behavioral rhythms. An important goal in chronobiology is to develop interventions to correct deficiencies in circadian timekeeping. Here we show that extended exposure to constant light promotes synchrony among SCN clock cells and the expression of ~24?h rhythms in behavior in mice in which intercellular signaling is disrupted through loss of VIP-VPAC2 signaling. This study highlights the importance of SCN synchrony for the expression of rhythms in behavior and reveals how non-invasive manipulations in the external environment can be used to overcome neurochemical communication deficits in this important brain system. PMID:26370467

  19. Circadian activity rhythms in high-alcohol-preferring and low-alcohol-preferring mice.

    PubMed

    Hofstetter, John R; Grahame, Nicholas J; Mayeda, Aimee R

    2003-05-01

    The circadian periods of high-alcohol-preferring (HAP) and low-alcohol-preferring (LAP) selected lines of mice were compared. The mice were ethanol-naive. Circadian periods were calculated from records of running-wheel activity in constant dark. The number of daily wheel revolutions and body weights of the two lines of mice were also compared. The HAP line had a shorter period of wheel running than that of the LAP lines. The HAP mice also had a tendency to run more on wheels than did LAP mice. These findings support the suggestion that genes affecting ethanol consumption in mice have pleiotropic effects on circadian period. PMID:12878278

  20. Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons

    E-print Network

    Huettner, James E.

    receptor, VPAC2, are required for cellular synchrony and maintaining daily oscillations across the SCN (8. The rate of PERIOD2 protein accumulation on the previous cycle reliably predicted the spontane- ous onset). The protein products of these genes return to the nucleus after a delay of many hours to repress their own

  1. Roles of eating, rumination, and arterial pressure in determination of the circadian rhythm of renal blood flow in sheep.

    PubMed

    Tebot, I; Bonnet, J-M; Junot, S; Ayoub, J-Y; Paquet, C; Cirio, A

    2009-02-01

    To assess the roles of feeding behavior (eating and rumination) and systemic arterial pressure (SAP) on determination of the circadian rhythm of renal blood flow (RBF), 20 sheep fitted with ultrasonic flow-metering probes around both renal arteries and a submandibular balloon to monitor jaw movements (6 of them with a telemetry measurement system into the carotid artery for SAP recording), were successively assigned to 6 feeding patterns: once daily in the morning (0900 to 1100 h), afternoon (1700 to 1900 h), or evening (1900 to 2100 h); twice daily at 0900 to 1100 h and 1700 to 1900 h; ad libitum (food renewed each 2 h); and fasting (40 h). All protocols were carried out in autumn-winter, and the fasting pattern was repeated in spring-summer to evaluate the effect of the daylight length on RBF. In the once-daily feeding patterns, a rapid increase in RBF (P < 0.05 vs. 1-h prefeeding mean values) subsequent to the onset of meals was observed, followed by a progressive increase (P < 0.05), reaching a maximum 4 to 6 h after the beginning of eating, and a subsequent gradual decline until the next meal [differences vs. prefeeding values were no longer significant after 11 h (morning pattern), 13 h (afternoon pattern), and 15 h (evening pattern) from the beginning of eating]. In the twice-daily feeding pattern, each meal was also followed by an increase in RBF (P < 0.05 vs. prefeeding values), reaching a maximum 3 to 5 h after the onset of meals, and a posterior decline [differences vs. prefeeding values were no longer significant after 8 h (morning meal) and 5 h (afternoon meal) from the beginning of eating]. In the ad libitum feeding, no apparent rhythm in RBF was found. During fasting, a progressive reduction of RBF was observed from 2 h after the beginning of fasting (P < 0.05 vs. the mean value of the first fasting hour), with a slight rebound (P < 0.05) lasting several hours from approximately 0700 h in autumn-winter and approximately 0500 h in spring-summer. No change in the RBF profile was observed in association with rumination. Except during meals, no correlation was found between RBF and SAP. A detailed description of RBF and SAP recordings is presented. In conclusion, results showed a circadian rhythm of RBF determined by eating behavior, but not by rumination, that was independent of blood pressure and that seemed superimposed on a primary lighting-cycle-dependent RBF rhythm. PMID:18849386

  2. CAVIN-3 regulates circadian period length and PER:CRY protein abundance and interactions

    E-print Network

    Halazonetis, Thanos

    CAVIN-3 regulates circadian period length and PER:CRY protein abundance and interactions Kim complexes is essential for the generation of circadian rhythms. We have identified CAVIN-3 as a new, cytoplasmic PER2-interacting protein influencing circadian clock properties. Thus, CAVIN-3 loss- and gain

  3. Differential effects of chronic lead intoxication on circadian rhythm of ambulatory activity and on regional brain norepinephrine levels in rats

    SciTech Connect

    Shafiq-ur-Rehman; Khushnood-ur-Rehman; Kabir-ud-Din; Chandra, O.

    1986-01-01

    Changes in biochemical mechanisms and amine concentrations in the brain have been manifested in the form of varying disorders and abnormalities in behavior, including motor-activity, which has been proved with a number of psychoactive drugs. It has been reported that increased level of cerebral norepinephrine (NE) has been shown to be associated with motor hyper-activity, and in lead exposed rats. No study is available which could account for the pattern of changes in spontaneous ambulatory responses in an open field situation together with the steady state regional levels of NE in the brain of chronically lead exposed rats. Therefore, it seemed to be worthwhile to study the circadian rhythm of ambulatory activity and its association with NE levels in various brain regions of rats exposed to lead.

  4. SRC-2 is an essential coactivator for orchestrating metabolism and circadian rhythm.

    PubMed

    Stashi, Erin; Lanz, Rainer B; Mao, Jianqiang; Michailidis, George; Zhu, Bokai; Kettner, Nicole M; Putluri, Nagireddy; Reineke, Erin L; Reineke, Lucas C; Dasgupta, Subhamoy; Dean, Adam; Stevenson, Connor R; Sivasubramanian, Natarajan; Sreekumar, Arun; Demayo, Francesco; York, Brian; Fu, Loning; O'Malley, Bert W

    2014-02-27

    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:CLOCK transcriptional networks is largely unexplored. Here, we show diurnal hepatic steroid receptor coactivator 2 (SRC-2) recruitment to the genome that extensively overlaps with the BMAL1 cistrome during the light phase, targeting genes that enrich for circadian and metabolic processes. Notably, SRC-2 ablation impairs wheel-running behavior, alters circadian gene expression in several peripheral tissues, alters the rhythmicity of the hepatic metabolome, and deregulates the synchronization of cell-autonomous metabolites. We identify SRC-2 as a potent coregulator of BMAL1:CLOCK and find that SRC-2 targets itself with BMAL1:CLOCK in a feedforward loop. Collectively, our data suggest that SRC-2 is a transcriptional coactivator of the BMAL1:CLOCK oscillators and establish SRC-2 as a critical positive regulator of the mammalian circadian clock. PMID:24529706

  5. [Influence of sleep habit and nocturnal lifestyle on circadian rhythm of blood pressure among workers in Okinawa].

    PubMed

    Sugawara, Mayo; Higashiuesato, Yasushi; Yamane, Nobuhisa

    2012-11-01

    We estimated the influence of sleep habit and nocturnal lifestyle on circadian rhythm of blood pressure by use of ambulatory blood pressure monitoring (ABPM) and self-estimating questionnaire formats. A total of 30 workers aged 21 to 58 years old voluntarily participated. None had any chronic diseases or regular medication. The average subject daily worked for 8 hours, waked-up at 6:00, went-to-bed at 23:45, and had 6.25-hour sleep (median). The subjects were divided into 3 groups according to % dipping of sleep blood pressure; 10 to 20% dipping as a dipper, <10% as a non-dipper, and > or = 20% as an extreme-dipper. This characterization resulted in 15 dippers (50%), 8 non-dippers(27%) and 7 extreme-dippers (23%). Of the parameters estimated, (1) sleeping hours of non-dippers were significantly shorter than those of dippers (p=0.02), (2) nighttime blood pressure of extreme-dippers were significantly lower than dippers (p=0.04), (3) the lowest blood pressure in nighttime of non-dippers were significantly higher when compared with the remaining 2 groups, (4) morning surges of blood pressure of non-dippers were the significantly smallest, whereas those of extreme-dippers were the greatest, and (5)refreshing scores of OSA sleep inventory MA version of non-dippers were significantly poorer when compared to extreme-dippers. This study could indicate the significant influence of nocturnal lifestyle with short sleep on circadian rhythm of blood pressure, and the extended prospective-study might be promising for a precise conclusion. PMID:23383574

  6. Circadian rhythms in blood pressure regulation and optimization of hypertension treatment with ACE inhibitor and ARB medications.

    PubMed

    Hermida, Ramón C; Ayala, Diana E; Fernández, José R; Portaluppi, Francesco; Fabbian, Fabio; Smolensky, Michael H

    2011-04-01

    Specific features of the 24 h-blood pressure (BP) pattern are linked to the progressive injury of target tissues and risk of cardiac and cerebrovascular events. Studies have consistently shown an association between blunted asleep BP decline and increased incidence of fatal and nonfatal cardiovascular events. Thus, there is growing interest in how to achieve better BP control during nighttime sleep in addition to during daytime activity, according to the particular requirements of each hypertension patient. One approach takes into consideration the endogenous circadian rhythm-determinants of the 24-h BP pattern, especially, the prominent day-night variation of the renin-angiotensin-aldosterone system, which activates during nighttime sleep. A series of clinical studies have demonstrated a different effect of the angiotensin-converting enzyme (ACE) inhibitors benazepril, captopril, enalapril, lisinopril, perindopril, quinapril, ramipril, spirapril, and trandolapril when routinely ingested in the morning vs. the evening. In most cases, the evening schedule exerts a more marked effect on the asleep than awake BP means. Similarly, a once-daily evening, in comparison to morning, ingestion schedule of the angiotensin receptor blockers (ARBs) irbesartan, olmesartan, telmisartan, and valsartan exerts greater therapeutic effect on asleep BP, plus significant increase in the sleep-time relative BP decline, with normalization of the circadian BP profile toward a more dipping pattern, independent of drug terminal half-life. Chronotherapy, the timing of treatment to body rhythms, is a cost-effective means of both individualizing and optimizing the treatment of hypertension through normalization of the 24-h BP level and profile, and it may constitute an effective option to reduce cardiovascular risk. PMID:20930708

  7. BRN 3.1 Knockouts Affect the Vestibular, Autonomic, and Circadian Rhythm Responses to 2G Exposure

    NASA Technical Reports Server (NTRS)

    Murakami, D. M.; Erkman, L.; Rosenfeld, M. G.; Fuller, C. A.

    1999-01-01

    Our previous studies have demonstrated that 2G exposure via centrifugation significantly attenuated the daily mean and circadian rhythm amplitude of rat body temperature (Tb), heart rate, and activity (Act). In addition, 2G exposure activates neural responses in several vestibular, autonomic, and circadian nuclei. Although we have characterized the effect of 2G on an animal's physiological, neuronal, and behavioral responses, it will be important to understand the underlying neural and physiological mechanisms that mediate those responses. For example, the vestibular responses, proprioceptive feedback, or fluid shifts may be the critical factors that mediate the responses to 2G. As a first step to understand the relative importance of these different response pathways to altered gravitational fields, this study examined the contribution of the vestibular system by utilizing an animal model from molecular biology. Brain 3.1 (Bm 3.1) is a POU domain homeobox gene involved in the normal development of the vestibular and auditory system. Brn 3.1 deletion results in a loss of hair cells in the otoliths, semicircular canals, and cochlea. As a result mice with a Brn 3.1 deletion do not have a functioning vestibular or auditory system. The BRN 3.1 knockout mouse could be a very useful animal model for isolating the role of the vestibular system in mediating the physiological responses to 2G exposure. Therefore, this study compared the effect of 2G exposure via centrifugation between Brn 3.1 knockout (KO) versus Wildtype (W) mice.

  8. The frequency of hippocampal theta rhythm is modulated on a circadian period and is entrained by food availability

    PubMed Central

    Munn, Robert G. K.; Tyree, Susan M.; McNaughton, Neil; Bilkey, David K.

    2015-01-01

    The hippocampal formation plays a critical role in the generation of episodic memory. While the encoding of the spatial and contextual components of memory have been extensively studied, how the hippocampus encodes temporal information, especially at long time intervals, is less well understood. The activity of place cells in hippocampus has previously been shown to be modulated at a circadian time-scale, entrained by a behavioral stimulus, but not entrained by light. The experimental procedures used in the previous study of this phenomenon, however, necessarily conflated two alternative entraining stimuli, the exposure to the recording environment and the availability of food, making it impossible to distinguish between these possibilities. Here we demonstrate that the frequency of theta-band hippocampal EEG varies with a circadian period in freely moving animals and that this periodicity mirrors changes in the firing rate of hippocampal neurons. Theta activity serves, therefore, as a proxy of circadian-modulated hippocampal neuronal activity. We then demonstrate that the frequency of hippocampal theta driven by stimulation of the reticular formation also varies with a circadian period. Because this effect can be observed without having to feed the animal to encourage movement we were able to identify what stimulus entrains the circadian oscillation. We show that with reticular-activated recordings started at various times of the day the frequency of theta varies quasi-sinusoidally with a 25 h period and phase-aligned when referenced to the animal’s regular feeding time, but not the recording start time. Furthermore, we show that theta frequency consistently varied with a circadian period when the data obtained from repeated recordings started at various times of the day were referenced to the start of food availability in the recording chamber. This pattern did not occur when data were referenced to the start of the recording session or to the actual time of day when this was not also related to feeding time. This double dissociation demonstrates that hippocampal theta is modulated with a circadian timescale, and that this modulation is strongly entrained by food. One interpretation of this finding is that the hippocampus is responsive to a food entrainable oscillator (FEO) that might modulate foraging behavior over circadian periods. PMID:25814943

  9. Explaining the sawtooth: latitudinal periodicity in a circadian gene correlates with shifts in generation number

    E-print Network

    Dopman, Erik B.

    , Genetics Laboratory, Iowa State University, Ames, IA, USA Keywords: circadian rhythms; developmental timing p e a n S o c i e t y F o r E v o l u t i o n a r y B i o l o g y . J . E v o l . B i o l . 2 8 ( 2Explaining the sawtooth: latitudinal periodicity in a circadian gene correlates with shifts

  10. Modulation of copper deficiency responses by diurnal and circadian rhythms in Arabidopsis thaliana.

    PubMed

    Perea-García, Ana; Andrés-Bordería, Amparo; Mayo de Andrés, Sonia; Sanz, Amparo; Davis, Amanda M; Davis, Seth J; Huijser, Peter; Peñarrubia, Lola

    2016-01-01

    Copper homeostasis under deficiency is regulated by the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE7 (SPL7) transcription factor. The daily oscillating expression of two SPL7-dependent copper deficiency markers, COPPER TRANSPORTER (COPT2) and IRON SUPEROXIDE DISMUTASE (FSD1), has been followed by quantitative PCR and in promoter:LUCIFERASE transgenic plants. Both genes showed circadian and diurnal regulation. Under copper deficiency, their expression decreased drastically in continuous darkness. Accordingly, total copper content was slightly reduced in etiolated seedlings under copper deficiency. The expression of SPL7 and its targets COPT2 and FSD1 was differently regulated in various light signalling mutants. On the other hand, increased copper levels reduced the amplitude of nuclear circadian clock components, such as GIGANTEA (GI). The alteration of copper homeostasis in the COPT1 overexpression line and spl7 mutants also modified the amplitude of a classical clock output, namely the circadian oscillation of cotyledon movements. In the spl7 mutant, the period of the oscillation remained constant. These results suggest a feedback of copper transport on the circadian clock and the integration of rhythmic copper homeostasis into the central oscillator of plants. PMID:26516126

  11. Modulation of copper deficiency responses by diurnal and circadian rhythms in Arabidopsis thaliana

    PubMed Central

    Perea-García, Ana; Andrés-Bordería, Amparo; Mayo de Andrés, Sonia; Sanz, Amparo; Davis, Amanda M.; Davis, Seth J.; Huijser, Peter; Peñarrubia, Lola

    2016-01-01

    Copper homeostasis under deficiency is regulated by the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE7 (SPL7) transcription factor. The daily oscillating expression of two SPL7-dependent copper deficiency markers, COPPER TRANSPORTER (COPT2) and IRON SUPEROXIDE DISMUTASE (FSD1), has been followed by quantitative PCR and in promoter:LUCIFERASE transgenic plants. Both genes showed circadian and diurnal regulation. Under copper deficiency, their expression decreased drastically in continuous darkness. Accordingly, total copper content was slightly reduced in etiolated seedlings under copper deficiency. The expression of SPL7 and its targets COPT2 and FSD1 was differently regulated in various light signalling mutants. On the other hand, increased copper levels reduced the amplitude of nuclear circadian clock components, such as GIGANTEA (GI). The alteration of copper homeostasis in the COPT1 overexpression line and spl7 mutants also modified the amplitude of a classical clock output, namely the circadian oscillation of cotyledon movements. In the spl7 mutant, the period of the oscillation remained constant. These results suggest a feedback of copper transport on the circadian clock and the integration of rhythmic copper homeostasis into the central oscillator of plants. PMID:26516126

  12. Free Access to a Running-Wheel Advances the Phase of Behavioral and Physiological Circadian Rhythms and Peripheral Molecular Clocks in Mice

    PubMed Central

    Yasumoto, Yuki; Nakao, Reiko; Oishi, Katsutaka

    2015-01-01

    Behavioral and physiological circadian rhythms are controlled by endogenous oscillators in animals. Voluntary wheel-running in rodents is thought to be an appropriate model of aerobic exercise in humans. We evaluated the effects of chronic voluntary exercise on the circadian system by analyzing temporal profiles of feeding, core body temperature, plasma hormone concentrations and peripheral expression of clock and clock-controlled genes in mice housed under sedentary (SED) conditions or given free access to a running-wheel (RW) for four weeks. Voluntary wheel-running activity advanced the circadian phases of increases in body temperature, food intake and corticosterone secretion in the mice. The circadian expression of clock and clock-controlled genes was tissue- and gene-specifically affected in the RW mice. The temporal expression of E-box-dependent circadian clock genes such as Per1, Per2, Nr1d1 and Dbp were slightly, but significantly phase-advanced in the liver and white adipose tissue, but not in brown adipose tissue and skeletal muscle. Peak levels of Per1, Per2 and Nr1d1 expression were significantly increased in the skeletal muscle of RW mice. The circadian phase and levels of hepatic mRNA expression of the clock-controlled genes that are involved in cholesterol and fatty acid metabolism significantly differed between SED and RW mice. These findings indicated that endogenous clock-governed voluntary wheel-running activity provides feedback to the central circadian clock that systemically governs behavioral and physiological rhythms. PMID:25615603

  13. Two mechanisms of rephasal of circadian rhythms in response to a 180 deg phase shift /simulated 12-hr time zone change/

    NASA Technical Reports Server (NTRS)

    Deroshia, C. W.; Winget, C. M.; Bond, G. H.

    1976-01-01

    A model developed by Wever (1966) is considered. The model describes the behavior of circadian rhythms in response to photoperiod phase shifts simulating time zone changes, as a function of endogenous periodicity, light intensity, and direction of phase shift. A description is given of an investigation conducted to test the model upon the deep body temperature rhythm in unrestrained subhuman primates. An evaluation is conducted regarding the applicability of the model in predicting the type and duration of desynchronization induced by simulated time zone changes as a function of endogenous periodicity.

  14. Metabolic rhythms of the cyanobacterium Cyanothece sp. ATCC 51142 correlate with modeled dynamics of circadian clock.

    PubMed

    Cervený, Jan; Nedbal, Ladislav

    2009-08-01

    These experiments aim to reveal the dynamic features that occur during the metabolism of the unicellular, nitrogen fixing cyanobacterium Cyanothece sp. when exposed to diverse circadian forcing patterns (LD 16:8, LD 12:12, LD 8:16, LD 6:6). The chlorophyll concentration grew rapidly from subjective morning when first illuminated to around noon, then remained stable from later in the afternoon and throughout the night. The optical density measured at 735 nm was stable during the morning chlorophyll accumulation, then increased in the early afternoon toward a peak, followed at dusk by a rapid decline toward the late night steady state. The authors propose that these dynamics largely reflect accumulation and subsequent consumption of glycogen granules. This hypothesis is consistent with the sharp peak of respiration that coincides with the putative hydrocarbon catabolism. In the long-day regimen (LD 16:8), these events may mark the transition from the aerobic photosynthetic metabolism to microaerobic nitrogen metabolism that occurs at dusk, and thus cannot be triggered by the darkness that comes later. Rather, control is likely to originate in the circadian clock signaling an approaching night. To explore the dynamics of the link between respiration and circadian oscillations, the authors extrapolated an earlier model of the KaiABC oscillator from Synechococcus elongatus to Cyanothece sp. The measured peak of respiratory activity at dusk correlated strongly in its timing and time width with the modeled peak in accumulation of the KaiB(4) complex, which marks the late afternoon phase of the circadian clock. The authors propose a hypothesis that high levels of KaiB(4) (or of its Cyanothece sp. analog) trigger the glycogen catabolism that is reflected in the experiments in the respiratory peak. The degree of the correlation between the modeled KaiB(4) dynamics and the dynamics of experimentally measured peaks of respiratory activity was further tested during the half-circadian regimen (LD 6:6). The model predicted an irregular pattern of the KaiABC oscillator, quite unlike mechanical or electrical clock pacemakers that are strongly damped when driven at double their endogenous frequency. This highly unusual dynamic pattern was confirmed experimentally, supporting strongly the validity of the circadian model and of the proposed direct link to respiration. PMID:19625731

  15. Control mechanisms of circadian rhythms in body composition: Implications for manned spaceflight

    NASA Technical Reports Server (NTRS)

    Moore-Ede, M. C.

    1976-01-01

    The mechanisms underlying the internal synchronization of the circadian variations in electrolyte content in body compartments were investigated, and the significance of these oscillations for manned spaceflight were examined. The experiments were performed with a chair-acclimatized squirrel monkey system, in which the animal sits in a chair, restrained only around the waist. The following information was given: (1) experimental methodology description, (2) summary of results obtained during the first contract year, and (3) discussion of the research performed during the second contract year. This included the following topics: physiological mechanisms promoting normal circadian internal synchronization, factors precipitating internal desynchronization, pathophysiological consequences of internal desynchronization of particular relevance to spaceflight, and validation of a chair-acclimatized system.

  16. Adaptive and pathological inhibition of neuroplasticity associated with circadian rhythms and sleep.

    PubMed

    Heller, H Craig; Ruby, Norman F; Rolls, Asya; Makam, Megha; Colas, Damien

    2014-06-01

    The circadian system organizes sleep and wake through imposing a daily cycle of sleep propensity on the organism. Sleep has been shown to play an important role in learning and memory. Apart from the daily cycle of sleep propensity, however, direct effects of the circadian system on learning and memory also have been well documented. Many mechanistic components of the memory consolidation process ranging from the molecular to the systems level have been identified and studied. The question that remains is how do these various processes and components work together to produce cycles of increased and decreased learning abilities, and why should there be times of day when neural plasticity appears to be restricted? Insights into this complex problem can be gained through investigations of the learning disabilities caused by circadian disruption in Siberian hamsters and by aneuploidy in Down's syndrome mice. A simple working hypothesis that has been explored in this work is that the observed learning disabilities are due to an altered excitation/inhibition balance in the CNS. Excessive inhibition is the suspected cause of deficits in memory consolidation. In this article we present the evidence that excessive inhibition in these cases of learning disability involves GABAergic neurotransmission, that treatment with GABA receptor inhibitors can reverse the learning disability, and that the efficacy of the treatment is time sensitive coincident with the major daily sleep phase, and that it depends on sleep. The evidence we present leads us to hypothesize that a function of the circadian system is to reduce neuroplasticity during the daily sleep phase when processes of memory consolidation are taking place. PMID:24886189

  17. http://jbr.sagepub.com Journal of Biological Rhythms

    E-print Network

    Rouyer, Francois

    Publications Circadian rhythms have been described in most liv- ing organisms and are generated by endogenous clocks that are synchronized to day-night cycles. Circadian oscillators are based on transcriptional feed the transcription of the vrille (vri) and Par domain protein 1 (pdp1) genes, whose products appear to regulate

  18. Requirement of Mammalian Timeless for Circadian

    E-print Network

    Gillette, Martha U.

    a circadian rhythm in neuronal firing rate with a peak near circadian time (CT) 7 over two cycles (22) In control slices, the SCN maintained a circadian rhythm in neuronal firing rate with a peak near circadianRequirement of Mammalian Timeless for Circadian Rhythmicity Jessica W. Barnes,1 * Shelley A

  19. The importance of circadian rhythms on drug response in hypertension and coronary heart disease--from mice and man.

    PubMed

    Lemmer, Björn

    2006-09-01

    The cardiovascular system is highly organised in time; blood pressure (BP), heart rate (HR), peripheral resistance, pressure and the release/activity of vasodilating hormones all display pronounced circadian variations. Pathophysiological events within the cardiovascular system are also not random, as shown for instance by sudden cardiac death (SCD), stroke, ventricular arrhythmias (VA), arterial embolism, and symptoms of coronary heart disease (CHD) such as myocardial infarction (MI) and ischemia, angina attacks (AA) in stable angina (stA) or variant angina (varA) or silent ischemia. In hypertensive patients various anti-hypertensive drugs were investigated in crossover studies (morning vs. evening dosing); however consistent data were only obtained for angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers. Whereas in dippers ACE inhibitors had a super-dipping effect when dosed at night, no consistent difference in BP lowering effect on the 24-hr BP profile was found with calcium channel blockers after morning and evening dosing. In non-dippers the calcium channel blockers isradipine and amlodipine consistently transformed non-dippers into dippers, after evening dosing. Diuretics are also able to normalize a non-dipping behaviour. Moreover, a circadian phase-dependency in pharmacokinetics has been demonstrated for various cardiovascular active drugs such as beta-blockers, calcium channel blockers, oral nitrates and ACE inhibitors, modified by the pharmaceutical formulation. There is evidence that in hypertensive dippers anti-hypertensive drugs should be given in the early morning, whereas in non-dippers it may be necessary to add an evening dose or even to use a single evening dose in order to not only reduce high BP but also to normalize a disturbed non-dipping 24 hr BP profile. In CHD, calcium channel blockers-mainly short acting and non-retarded preparations-seem to be less effective than beta-adrenoceptor antagonists in reducing ischemic events during the night and early morning. However, the role of formulation and/or subclasses of the calcium channel blockers remains to be elucidated. In order to get more insight into the circadian regulation of the cardiovascular system animal models of primary and secondary hypertension have been studied in various strains of normotensive and hypertensive rats and mice. At least in rodents there is ample evidence that the 24-hr rhythms in BP and HR are under the control of biological clock(s) as they persist under constant darkness (i.e. in free-run conditions) with a period deviating from 24 hr; these rhythms are abolished by lesioning of the "master clock" located in the suprachiasmatic nuclei (SCN). In conclusion, chronobiological and chronopharmacological studies are important experimental and clinical approaches to get a better insight into the physiological and pathophysiological regulation of the cardiovascular system including their rhythmic organisation. Circadian time-dependent clinical studies also have implications for drug therapy in hypertension and CHD. PMID:16480770

  20. Orchestrating time: arrangements of the brain circadian clock

    E-print Network

    Silver, Rae

    in regulating the overall activity of the circadian clock: some cells within the SCN rhythmically express `clock time: how to synchronize 20 000 clocks Biological processes exhibit daily rhythms that enable organisms generated by the 20 000 neurons [1] that constitute the master circadian pacemaker located in the SCN

  1. Integration of human sleep-wake regulation and circadian rhythmicity

    NASA Technical Reports Server (NTRS)

    Dijk, Derk-Jan; Lockley, Steven W.

    2002-01-01

    The human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. The sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. It is also timed at a specific phase relative to internal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of the circadian pacemaker to light. Variations in these internal and external phase relationships, such as those that occur in blindness, aging, morning and evening, and advanced and delayed sleep-phase syndrome, lead to sleep disruptions and complaints. Changes in ocular circadian photoreception, interindividual variation in the near-24-h intrinsic period of the circadian pacemaker, and sleep homeostasis can contribute to variations in external and internal phase. Recent findings on the physiological and molecular-genetic correlates of circadian sleep disorders suggest that the timing of the sleep-wake cycle and circadian rhythms is closely integrated but is, in part, regulated differentially.

  2. Serotonin antagonists do not attenuate activity-induced phase shifts of circadian rhythms in the Syrian hamster.

    PubMed

    Antle, M C; Marchant, E G; Niel, L; Mistlberger, R E

    1998-11-30

    A variety of observations from several rodent species suggest that a serotonin (5-HT) input to the suprachiasmatic nucleus (SCN) circadian pacemaker may play a role in resetting or entrainment of circadian rhythms by non-photic stimuli such as scheduled wheel running. If 5-HT activity within the SCN is necessary for activity-induced phase shifting, then it should be possible to block or attenuate these phase shifts by reducing 5-HT release or by blocking post-synaptic 5-HT receptors. Animals received one of four serotonergic drugs and were then locked in a novel wheel for 3 h during the mid-rest phase, when novelty-induced activity produces maximal phase advance shifts. Drugs tested at several doses were metergoline (5-HT1/2 antagonist; i.p.), (+)-WAY100135 (5-HT1A postsynaptic antagonist, which may also reduce 5-HT release by an agonist effect at 5-HT1A raphe autoreceptors; i.p.), NAN-190 (5-HT1A postsynaptic antagonist, which also reduces 5-HT release via an agonist effect at 5-HT1A raphe autoreceptors; i.p.) and ritanserin (5-HT2/7 antagonist; i.p. and i.c.v.). Mean and maximal phase shifts to running in novel wheels were not significantly affected by any drug at any dose. These results do not support a hypothesis that 5-HT release or activity at 5HT1, 2 and 7 receptors in the SCN is necessary for the production of activity-induced phase shifts in hamsters. PMID:9824687

  3. Pineal melatonin is a circadian time-giver for leptin rhythm in Syrian hamsters.

    PubMed

    Chakir, Ibtissam; Dumont, Stéphanie; Pévet, Paul; Ouarour, Ali; Challet, Etienne; Vuillez, Patrick

    2015-01-01

    Nocturnal secretion of melatonin from the pineal gland may affect central and peripheral timing, in addition to its well-known involvement in the control of seasonal physiology. The Syrian hamster is a photoperiodic species, which displays gonadal atrophy and increased adiposity when adapted to short (winter-like) photoperiods. Here we investigated whether pineal melatonin secreted at night can impact daily rhythmicity of metabolic hormones and glucose in that seasonal species. For that purpose, daily variations of plasma leptin, cortisol, insulin and glucose were analyzed in pinealectomized hamsters, as compared to sham-operated controls kept under very long (16 h light/08 h dark) or short photoperiods (08 h light/16 h dark). Daily rhythms of leptin under both long and short photoperiods were blunted by pinealectomy. Furthermore, the phase of cortisol rhythm under a short photoperiod was advanced by 5.6 h after pinealectomy. Neither plasma insulin, nor blood glucose displays robust daily rhythmicity, even in sham-operated hamsters. Pinealectomy, however, totally reversed the decreased levels of insulin under short days and the photoperiodic variations in mean levels of blood glucose (i.e., reduction and increase in long and short days, respectively). Together, these findings in Syrian hamsters show that circulating melatonin at night drives the daily rhythmicity of plasma leptin, participates in the phase control of cortisol rhythm and modulates glucose homeostasis according to photoperiod-dependent metabolic state. PMID:26074760

  4. Pineal melatonin is a circadian time-giver for leptin rhythm in Syrian hamsters

    PubMed Central

    Chakir, Ibtissam; Dumont, Stéphanie; Pévet, Paul; Ouarour, Ali; Challet, Etienne; Vuillez, Patrick

    2015-01-01

    Nocturnal secretion of melatonin from the pineal gland may affect central and peripheral timing, in addition to its well-known involvement in the control of seasonal physiology. The Syrian hamster is a photoperiodic species, which displays gonadal atrophy and increased adiposity when adapted to short (winter-like) photoperiods. Here we investigated whether pineal melatonin secreted at night can impact daily rhythmicity of metabolic hormones and glucose in that seasonal species. For that purpose, daily variations of plasma leptin, cortisol, insulin and glucose were analyzed in pinealectomized hamsters, as compared to sham-operated controls kept under very long (16 h light/08 h dark) or short photoperiods (08 h light/16 h dark). Daily rhythms of leptin under both long and short photoperiods were blunted by pinealectomy. Furthermore, the phase of cortisol rhythm under a short photoperiod was advanced by 5.6 h after pinealectomy. Neither plasma insulin, nor blood glucose displays robust daily rhythmicity, even in sham-operated hamsters. Pinealectomy, however, totally reversed the decreased levels of insulin under short days and the photoperiodic variations in mean levels of blood glucose (i.e., reduction and increase in long and short days, respectively). Together, these findings in Syrian hamsters show that circulating melatonin at night drives the daily rhythmicity of plasma leptin, participates in the phase control of cortisol rhythm and modulates glucose homeostasis according to photoperiod-dependent metabolic state. PMID:26074760

  5. Circadian adaptations to meal timing: neuroendocrine mechanisms

    PubMed Central

    Patton, Danica F.; Mistlberger, Ralph E.

    2013-01-01

    Circadian rhythms of behavior and physiology are generated by central and peripheral circadian oscillators entrained by periodic environmental or physiological stimuli. A master circadian pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) is directly entrained by daily light-dark (LD) cycles, and coordinates the timing of other oscillators by direct and indirect neural, hormonal and behavioral outputs. The daily rhythm of food intake provides stimuli that entrain most peripheral and central oscillators, some of which can drive a daily rhythm of food anticipatory activity if food is restricted to one daily mealtime. The location of food-entrainable oscillators (FEOs) that drive food anticipatory rhythms, and the food-related stimuli that entrain these oscillators, remain to be clarified. Here, we critically examine the role of peripheral metabolic hormones as potential internal entrainment stimuli or outputs for FEOs controlling food anticipatory rhythms in rats and mice. Hormones for which data are available include corticosterone, ghrelin, leptin, insulin, glucagon, and glucagon-like peptide 1. All of these hormones exhibit daily rhythms of synthesis and secretion that are synchronized by meal timing. There is some evidence that ghrelin and leptin modulate the expression of food anticipatory rhythms, but none of the hormones examined so far are necessary for entrainment. Ghrelin and leptin likely modulate food-entrained rhythms by actions in hypothalamic circuits utilizing melanocortin and orexin signaling, although again food-entrained behavioral rhythms can persist in lesion and gene knockout models in which these systems are disabled. Actions of these hormones on circadian oscillators in central reward circuits remain to be evaluated. Food-entrained activity rhythms are likely mediated by a distributed system of circadian oscillators sensitive to multiple feeding related inputs. Metabolic hormones appear to play a modulatory role within this system. PMID:24133410

  6. Winter Depression: Integrating mood, circadian rhythms, and the sleep/wake and light/dark cycles into a bio-psycho-social-environmental model

    PubMed Central

    Emens, Jonathan S.; Songer, Jeannie B.; Sims, Neelam; Laurie, Amber L.; Fiala, Steven C.; Buti, Allie L.

    2009-01-01

    Synopsis The phase shift hypothesis (PSH) states that most patients with SAD become depressed in the winter because of a delay in circadian rhythms with respect to the sleep/wake cycle: According to the PSH, these patients should preferentially respond to the antidepressant effects of bright light exposure when it is scheduled in the morning so as to provide a corrective phase advance and restore optimum alignment between the circadian rhythms tightly coupled to the endogenous circadian pacemaker and those rhythms that are related to the sleep/wake cycle. Recent support for the PSH has come from studies in which symptom severity was shown to correlate with the degree of circadian misalignment: it appears that a subgroup of patients are phase advanced, not phase delayed; however, the phase-delayed type is predominant in SAD and perhaps in other disorders as well, such as non-seasonal unipolar depression. It is expected that during the next few years the PSH will be tested in these and other conditions, particularly since healthy subjects appear to have more severe symptoms of sub-clinical dysphoria correlating with phase-delayed circadian misalignment; critically important will be the undertaking of treatment trials to investigate the therapeutic efficacy of morning bright light or afternoon/evening low-dose melatonin in these disorders in which symptoms are more severe as the dim light melatonin onset (DLMO) is delayed with respect to the sleep/wake cycle (non-restorative sleep should also be evaluated, as well as bipolar disorder). The possibility that some individuals (and disorders) will be of the phase-advanced type should be considered, taking into account that the correct timing of phase-resetting agents for them will be bright light scheduled in the evening and/or low-dose melatonin taken in the morning. While sleep researchers and clinicians are accustomed to phase-typing patients with circadian-rhythm sleep disorders according to the timing of sleep, phase typing based on the DLMO with respect to the sleep/wake cycle may lead to quite different recommendations for the optimal scheduling of phase-resetting agents, particularly for the above disorders and conditions. PMID:20160896

  7. Positive allosteric modulators at GABAB receptors exert intrinsic actions and enhance the influence of baclofen on light-induced phase shifts of hamster circadian activity rhythms.

    PubMed

    Gannon, Robert L; Millan, Mark J

    2011-10-01

    Light-induced phase shifts of hamster circadian activity rhythms are modulated by GABA(B) receptors. Recently, positive allosteric modulators (PAM)s at GABA(B) receptors were described, but it is not known whether they affect light-induced entrainment of circadian rhythms. Therefore, we studied the effects of two GABA(B) PAMs, GS39783 and RacBHFF, upon light-induced phase advances and delays of hamster circadian wheel-running activity rhythms. Wheel running activity was recorded for Syrian hamsters maintained in constant darkness. Drugs administered intraperitoneally were evaluated for their ability to modulate a light-induced shift of the circadian activity rhythm. Baclofen (3.75-15 mg/kg) dose-dependently inhibited both light-induced phase advances and delays of hamster wheel running rhythms, and its actions were blocked by the selective GABA(B) antagonist, SCH50911 (5mg/kg). Neither GS39783 (3-30 mg/kg) nor RacBHFF (0.63-10mg/kg) affected phase advances when injected alone, but both GS39783 (3mg/kg) and RacBHFF (10mg/kg) augmented the inhibitory effect of baclofen (5mg/kg). At doses above 3mg/kg, GS39783 and RacBHFF significantly inhibited phase delays alone, consistent with the notion of "agonist-allosteric" properties. GS39783 (0.5mg/kg), but not RacBHFF (10mg/kg), augmented the inhibitory action of baclofen on phase delays. These data are consistent with the possibility that GS39783 and RacBHFF act as PAMs at GABA(B) receptors inhibiting light-induced phase advances, yet that they also posses "allosteric agonist" actions at the (presumably separate) population of GABA(B) receptors modulating light-induced phase delays. GABA(B) receptors clearly warrant further investigation as agents for modulation of circadian dysfunction associated with CNS disorders such as depression. PMID:21756929

  8. Recent advances in the molecular mechanisms determining tissue sensitivity to glucocorticoids: novel mutations, circadian rhythm and ligand-induced repression of the human glucocorticoid receptor

    PubMed Central

    2014-01-01

    Glucocorticoids are pleiotropic hormones, which are involved in almost every cellular, molecular and physiologic network of the organism, and regulate a broad spectrum of physiologic functions essential for life. The cellular response to glucocorticoids displays profound variability both in magnitude and in specificity of action. Tissue sensitivity to glucocorticoids differs among individuals, within tissues of the same individual and within the same cell. The actions of glucocorticoids are mediated by the glucocorticoid receptor, a ubiquitously expressed intracellular, ligand-dependent transcription factor. Multiple mechanisms, such as pre-receptor ligand metabolism, receptor isoform expression, and receptor-, tissue-, and cell type-specific factors, exist to generate diversity as well as specificity in the response to glucocorticoids. Alterations in the molecular mechanisms of glucocorticoid receptor action impair glucocorticoid signal transduction and alter tissue sensitivity to glucocorticoids. This review summarizes the recent advances in our understanding of the molecular mechanisms determining tissue sensitivity to glucocorticoids with particular emphasis on novel mutations and new information on the circadian rhythm and ligand-induced repression of the glucocorticoid receptor. PMID:25155432

  9. The genetics of circadian rhythms in Neurospora crassa : do multiple oscillators exist? 

    E-print Network

    Kortum, Karen

    2013-02-22

    again. " Ftmgal Crenetics arul Biology 29; 1-8, 2000. Brzezinski, A. "Melatonin in humans. " N Fngld Med 336: 186-195, 1997. Chang, B. and H Nakashima "Isolation of temperature-sensitive rhythm mutant in Neurvspora crassa" J. Plant Res. 110: 449... stream_source_info 2001 Fellows Thesis K68.pdf.txt stream_content_type text/plain stream_size 42229 Content-Encoding ISO-8859-1 stream_name 2001 Fellows Thesis K68.pdf.txt Content-Type text/plain; charset=ISO-8859-1...

  10. Plant-pathogen interaction, circadian rhythm, and hormone-related gene expression provide indicators of phytoplasma infection in Paulownia fortunei.

    PubMed

    Fan, Guoqiang; Dong, Yanpeng; Deng, Minjie; Zhao, Zhenli; Niu, Suyan; Xu, Enkai

    2014-01-01

    Phytoplasmas are mycoplasma-like pathogens of witches' broom disease, and are responsible for serious yield losses of Paulownia trees worldwide. The molecular mechanisms of disease development in Paulownia are of considerable interest, but still poorly understood. Here, we have applied transcriptome sequencing technology and a de novo assembly approach to analyze gene expression profiles in Paulownia fortunei infected by phytoplasmas. Our previous researches suggested that methyl methane sulfonated (MMS) could reverse the effects of the infection. In this study, leaf samples from healthy, infected, and both infected and methyl methane sulfonate treated plants were analyzed. The results showed that the gene expression profile of P. fortunei underwent dramatic changes after Paulownia witches' broom (PaWB) phytoplasma infection. Genes that encoded key enzymes in plant-pathogen interaction processes were significantly up-regulated in the PaWB-infected Paulownia. Genes involved in circadian rhythm and hormone-related genes were also altered in Paulownia after PaWB infection. However, after the PaWB-infected plants were treated with MMS, the expression profiles of these genes returned to the levels in the healthy controls. The data will help identify potential PaWB disease-resistance genes that could be targeted to inhibit the growth and reproduction of the pathogen and to increase plant resistance. PMID:25514414

  11. Circadian rhythm mediates the relationship between physical activity and quality of life in younger and older cancer survivors.

    PubMed

    Su, Ching-Ching; Su, Pei-Yuan; Wang, Shu-Yi; Lin, Chia-Chin

    2015-12-01

    Increasing evidence suggests that physical activity (PA) improves the quality of life (QoL) of cancer survivors. However, the biological mechanisms underlying the relationship between PA and QoL are unclear. The purpose of this study was to determine whether the relationship between PA and QoL differs in younger and older cancer survivors and whether circadian rhythm (CR) mediates this relationship. We also explored the effect of the CR on QoL. The participants were 235 cancer survivors, comprising 143 younger and 92 older patients. Data were collected using the Taiwanese versions of the Physical Activity Scale for the Elderly and Short Form-36. The robustness and stability of the CR were measured using an actigraph. Mediation was tested using multiple mediation analyses. The CR mediated the relationship between PA and the physical domain of QoL in younger and older cancer survivors (23% and 59% mediating effects, respectively). The CR partially mediated the effect of PA on the mental dimension of QoL in older cancer survivors (36% mediating effect), but not in younger cancer survivors. Cancer survivors with a more robust CR had a significantly higher QoL, particularly in the physical functioning domain (d?=?0.43, p?

  12. Plant-Pathogen Interaction, Circadian Rhythm, and Hormone-Related Gene Expression Provide Indicators of Phytoplasma Infection in Paulownia fortunei

    PubMed Central

    Fan, Guoqiang; Dong, Yanpeng; Deng, Minjie; Zhao, Zhenli; Niu, Suyan; Xu, Enkai

    2014-01-01

    Phytoplasmas are mycoplasma-like pathogens of witches’ broom disease, and are responsible for serious yield losses of Paulownia trees worldwide. The molecular mechanisms of disease development in Paulownia are of considerable interest, but still poorly understood. Here, we have applied transcriptome sequencing technology and a de novo assembly approach to analyze gene expression profiles in Paulownia fortunei infected by phytoplasmas. Our previous researches suggested that methyl methane sulfonated (MMS) could reverse the effects of the infection. In this study, leaf samples from healthy, infected, and both infected and methyl methane sulfonate treated plants were analyzed. The results showed that the gene expression profile of P. fortunei underwent dramatic changes after Paulownia witches’ broom (PaWB) phytoplasma infection. Genes that encoded key enzymes in plant-pathogen interaction processes were significantly up-regulated in the PaWB-infected Paulownia. Genes involved in circadian rhythm and hormone-related genes were also altered in Paulownia after PaWB infection. However, after the PaWB-infected plants were treated with MMS, the expression profiles of these genes returned to the levels in the healthy controls. The data will help identify potential PaWB disease-resistance genes that could be targeted to inhibit the growth and reproduction of the pathogen and to increase plant resistance. PMID:25514414

  13. Host preferences and circadian rhythm of Culicoides (Diptera: Ceratopogonidae), vectors of African horse sickness and bluetongue viruses in Senegal.

    PubMed

    Fall, Moussa; Fall, Assane G; Seck, Momar T; Bouyer, Jérémy; Diarra, Maryam; Lancelot, Renaud; Gimonneau, Geoffrey; Garros, Claire; Bakhoum, Mame T; Faye, Ousmane; Baldet, Thierry; Balenghien, Thomas

    2015-09-01

    African horse sickness- and bluetongue virus are orbiviruses transmitted by Culicoides biting midges (Diptera: Ceratopogonidae) to horses and to ruminants, respectively. Since the last epizootic outbreak of African horse sickness in 2007 in Senegal, extensive investigations have been undertaken to improve our knowledge on Culicoides species involved locally in the transmission of the virus. The purpose of this study was to compare and quantify the host preferences of potential vectors of these orbiviruses on horse and sheep and to study their circadian rhythm. We found that Culicoides oxystoma and species of the sub-genus Avaritia (Culicoides imicola, Culicoides bolitinos and Culicoides pseudopallidipennis) had a preference for horse when compared to sheep (the predicted ratio between horse and sheep was 80 for C. oxystoma and 26 for C. imicola), and were mostly crepuscular: C. oxystoma had continuous activity throughout the diel with peaks in numbers collected after sunrise and sunset, while C. imicola was mostly nocturnal with peak after sunset. Unexpectedly, species of the subgenus Lasiohelea was also collected during this study. This diurnal biting species was a nuisance pest for both animal species used as bait. PMID:26099680

  14. Exposure to T-cycles of 22 and 23 h during lactation modifies the later dissociation of motor activity and temperature circadian rhythms in rats.

    PubMed

    Anglès-Pujolràs, Montserrat; Díez-Noguera, Antoni; Cambras, Trinitat

    2007-01-01

    Early environmental conditions may affect the development and manifestation of circadian rhythms. This study sought to determine whether the maintenance of rats under different T-cycles during lactation influences the subsequent degree of dissociation of the circadian rhythms of motor activity and core body temperature. Two groups of 22 day-old Wistar rats were kept after weaning under T-cycles of 22 h (T22) or 23 h (T23) for 70 days. Subsequently, they were kept in constant darkness (DD). Half of the animals in each group were born and reared under these experimental conditions, while the other half were reared until weaning under 24 h LD cycles (T24). Rats transferred from T24 to T22 or T23 showed two circadian components in motor activity and temperature, one entrained by light and the other free-running. In T22, there was also desynchronization between temperature and motor activity. Rats submitted to T23 from birth showed higher stability of the 23 h component than rats transferred from T24 to T23 after weaning. However, in comparison to rats born under T24 and subsequently changed to T22, animals submitted to T22 from birth showed shorter values of the period of the non-light-dependent component during T22, more aftereffects when transferred to DD, and a lack of desynchronization between motor activity and temperature. The results suggest that T-cycles in the early environment may modify overt rhythms by altering the internal coupling of the circadian pacemaker. PMID:18075798

  15. Spotlight on fish: light pollution affects circadian rhythms of European perch but does not cause stress.

    PubMed

    Brüning, Anika; Hölker, Franz; Franke, Steffen; Preuer, Torsten; Kloas, Werner

    2015-04-01

    Flora and fauna evolved under natural day and night cycles. However, natural light is now enhanced by artificial light at night, particularly in urban areas. This alteration of natural light environments during the night is hypothesised to alter biological rhythms in fish, by effecting night-time production of the hormone melatonin. Artificial light at night is also expected to increase the stress level of fish, resulting in higher cortisol production. In laboratory experiments, European perch (Perca fluviatilis) were exposed to four different light intensities during the night, 0 lx (control), 1 lx (potential light level in urban waters), 10 lx (typical street lighting at night) and 100 lx. Melatonin and cortisol concentrations were measured from water samples every 3h during a 24 hour period. This study revealed that the nocturnal increase in melatonin production was inhibited even at the lowest light level of 1 lx. However, cortisol levels did not differ between control and treatment illumination levels. We conclude that artificial light at night at very low intensities may disturb biological rhythms in fish since nocturnal light levels around 1 lx are already found in urban waters. However, enhanced stress induction could not be demonstrated. PMID:25577738

  16. Development of Insect Habitat System for Studying Long Duration Circadian Rhythm Changes on Mir Space Station

    NASA Technical Reports Server (NTRS)

    Savage, P. D.; Hayward, E. F.; Dalton, Bonnie P. (Technical Monitor)

    1997-01-01

    A habitat for housing up to 32 black body beetles (Trigonoscelis gigas) has been developed at Ames Research Center for conducting studies to evaluate the effects of long duration spaceflight upon insect circadian timing systems. This habitat, identified as the Beetle Kit Assembly, provides an automatically controlled lighting system and activity and temperature recording devices, as well as individual beetle enclosures. Each of the 32 enclosures allows for ad lib movement of the beetle, as well as providing a simple food source and allowing ventilation of the beetle volume via an externally operated hand pump. The Beetle Kit Assemblies will be launched on STS-84 (Shuttle-Mir Mission-06) in May, 1997 and will be transferred to the Priroda module of the Russian Mir space station. he beetles will remain on Mir for approximately 125 days, and will be returned to earth on STS-86 in September, 1997.

  17. Circadian rhythm disruption by a novel running wheel: roles of exercise and arousal in blockade of the luteinizing hormone surge.

    PubMed

    Duncan, Marilyn J; Franklin, Kathleen M; Peng, Xiaoli; Yun, Christopher; Legan, Sandra J

    2014-05-28

    Exposure of proestrous Syrian hamsters to a new room, cage, and novel running wheel blocks the luteinizing hormone (LH) surge until the next day in ~75% of hamsters [1]. The studies described here tested the hypotheses that 1) exercise and/or 2) orexinergic neurotransmission mediate novel wheel blockade of the LH surge and circadian phase advances. Female hamsters were exposed to a 14L:10D photoperiod and activity rhythms were monitored with infra-red detectors. In Expt. 1, to test the effect of exercise, hamsters received jugular cannulae and on the next day, proestrus (Day 1), shortly before zeitgeber time 5 (ZT 5, 7h before lights-off) the hamsters were transported to the laboratory. After obtaining a blood sample at ZT 5, the hamsters were transferred to a new cage with a novel wheel that was either freely rotating (unlocked), or locked until ZT 9, and exposed to constant darkness (DD). Blood samples were collected hourly for 2days from ZT 5-11 under red light for determination of plasma LH levels by radioimmunoassay. Running rhythms were monitored continuously for the next 10-14days. The locked wheels were as effective as unlocked wheels in blocking LH surges (no Day 1 LH surge in 6/9 versus 8/8 hamsters, P>0.05) and phase advances in the activity rhythms did not differ between the groups (P=0.28), suggesting that intense exercise is not essential for novel wheel blockade and phase advance of the proestrous LH surge. Expt. 2 tested whether orexin neurotransmission is essential for these effects. Hamsters were treated the same as those in Expt. 1 except that they were injected (i.p.) at ZT 4.5 and 5 with either the orexin 1 receptor antagonist SB334867 (15mg/kg per injection) or vehicle (25% DMSO in 2-hydroxypropyl-beta-cyclodextrin (HCD)). SB-334867 inhibited novel wheel blockade of the LH surge (surges blocked in 2/6 SB334867-injected animals versus 16/18 vehicle-injected animals, P<0.02) and also inhibited wheel running and circadian phase shifts, indicating that activation of orexin 1 receptors is necessary for these effects. Expt. 3 tested the hypothesis that novel wheel exposure activates orexin neurons. Proestrous hamsters were transferred at ZT 5 to a nearby room within the animal facility and were exposed to a new cage with a locked or unlocked novel wheel or left in their home cages. At ZT 8, the hamsters were anesthetized, blood was withdrawn, they were perfused with fixative and brains were removed for immunohistochemical localization of Fos, GnRH, and orexin. Exposure to a wheel, whether locked or unlocked, suppressed circulating LH concentrations at ZT 8, decreased the proportion of Fos-activated GnRH neurons, and increased Fos-immunoreactive orexin cells. Unlocked wheels had greater effects than locked wheels on all three endpoints. Thus in a familiar environment, exercise potentiated the effect of the novel wheel on Fos expression because a locked wheel was not a sufficient stimulus to block the LH surge. In conclusion, these studies indicate that novel wheel exposure activates orexin neurons and that blockade of orexin 1 receptors prevents novel wheel blockade of the LH surge. These findings are consistent with a role for both exercise and arousal in mediating novel wheel blockade of the LH surge. PMID:24727338

  18. Circadian control of tissue homeostasis and adult stem cells.

    PubMed

    Janich, Peggy; Meng, Qing-Jun; Benitah, Salvador Aznar

    2014-12-01

    The circadian timekeeping mechanism adapts physiology to the 24-hour light/dark cycle. However, how the outputs of the circadian clock in different peripheral tissues communicate and synchronize each other is still not fully understood. The circadian clock has been implicated in the regulation of numerous processes, including metabolism, the cell cycle, cell differentiation, immune responses, redox homeostasis, and tissue repair. Accordingly, perturbation of the machinery that generates circadian rhythms is associated with metabolic disorders, premature ageing, and various diseases including cancer. Importantly, it is now possible to target circadian rhythms through systemic or local delivery of time cues or compounds. Here, we summarize recent findings in peripheral tissues that link the circadian clock machinery to tissue-specific functions and diseases. PMID:25016176

  19. The timing of the human circadian clock is accurately represented by the core body temperature rhythm following phase shifts to a three-cycle light stimulus near the critical zone

    NASA Technical Reports Server (NTRS)

    Jewett, M. E.; Duffy, J. F.; Czeisler, C. A.

    2000-01-01

    A double-stimulus experiment was conducted to evaluate the phase of the underlying circadian clock following light-induced phase shifts of the human circadian system. Circadian phase was assayed by constant routine from the rhythm in core body temperature before and after a three-cycle bright-light stimulus applied near the estimated minimum of the core body temperature rhythm. An identical, consecutive three-cycle light stimulus was then applied, and phase was reassessed. Phase shifts to these consecutive stimuli were no different from those obtained in a previous study following light stimuli applied under steady-state conditions over a range of circadian phases similar to those at which the consecutive stimuli were applied. These data suggest that circadian phase shifts of the core body temperature rhythm in response to a three-cycle stimulus occur within 24 h following the end of the 3-day light stimulus and that this poststimulus temperature rhythm accurately reflects the timing of the underlying circadian clock.

  20. Circadian rhythm in adenosine A1 receptor of mouse cerebral cortex

    SciTech Connect

    Florio, C.; Rosati, A.M.; Traversa, U.; Vertua, R. )

    1991-01-01

    In order to investigate diurnal variation in adenosine A1 receptors binding parameters, Bmax and Kd values of specifically bound N6-cyclohexyl-({sup 3}H)adenosine were determined in the cerebral cortex of mice that had been housed under controlled light-dark cycles for 4 weeks. Significant differences were found for Bmax values measured at 3-hr intervals across a 24-h period, with low Bmax values during the light period and high Bmax values during the dark period. The amplitude between 03.00 and 18.00 hr was 33%. No substantial rhythm was found in the Kd values. It is suggested that the changes in the density of A1 receptors could reflect a physiologically-relevant mechanism by which adenosine exerts its modulatory role in the central nervous system.

  1. Mechanisms of action of light on circadian rhythms in the monkey

    NASA Technical Reports Server (NTRS)

    Winget, C. M.; Rosenblatt, L. S.; DeRoshia, C. W.; Hetherington, N. W.

    1970-01-01

    Light is considered by many investigators to be the primary Zeitgeber for most physiologic rhythms. In order to study the effects on biorhythms of changing photoperiods and to provide information on the nature of the wave forms and the mechanisms of entrainment, unrestrained male monkeys (Cebus albifrons, Macaca nemestrina) were maintained in a sound-proofed environmental chamber. The Cebus was initially maintained on a 12L:12D schedule; it was subjected to a 180 degrees phase shift for 14 days, then returned to the original photoperiod. In two experiments (24 days; 27 days each) the same monkey was again maintained on a 12L:12D schedule which was gradually altered to a constant light environment. Deep body temperature (DBT) data were obtained with miniature radiotransmitters. Locomotor activity (LMA) was measured by strain gauges. Under the 12L:12D regimens the Macaca DBT cycles were uniform as to phase and wave form for over 60 weeks. These wave forms were analyzed by the use of periodogram and correlogram analyses and by fitting to the Volterra Integro-Differential Equation. Phase angle relationships between Zeitgeber and physiologic parameters were characterized. After the photoperiod phase shift the DBT cycle rephased in about 9 days. During the rephasing process the wave form changed. The shapes of the wave forms of DBT and activity were maintained with increasing light until an 18L:6D photoperiod was reached. The rhythms were entrained to the onset of darkness rather than lights on. Major and minor periods of LMA were detected. Hysteresis diagrams showed that DBT led the onset of major LA by 6 hr and the end of major activity by 2 hr.

  2. Mechanisms of action of light on circadian rhythms in the monkey.

    PubMed

    Winget, C M; Rosenblatt, L S; DeRoshia, C W; Hetherington, N W

    1970-01-01

    Light is considered by many investigators to be the primary Zeitgeber for most physiologic rhythms. In order to study the effects on biorhythms of changing photoperiods and to provide information on the nature of the wave forms and the mechanisms of entrainment, unrestrained male monkeys (Cebus albifrons, Macaca nemestrina) were maintained in a sound-proofed environmental chamber. The Cebus was initially maintained on a 12L:12D schedule; it was subjected to a 180 degrees phase shift for 14 days, then returned to the original photoperiod. In two experiments (24 days; 27 days each) the same monkey was again maintained on a 12L:12D schedule which was gradually altered to a constant light environment. Deep body temperature (DBT) data were obtained with miniature radiotransmitters. Locomotor activity (LMA) was measured by strain gauges. Under the 12L:12D regimens the Macaca DBT cycles were uniform as to phase and wave form for over 60 weeks. These wave forms were analyzed by the use of periodogram and correlogram analyses and by fitting to the Volterra Integro-Differential Equation. Phase angle relationships between Zeitgeber and physiologic parameters were characterized. After the photoperiod phase shift the DBT cycle rephased in about 9 days. During the rephasing process the wave form changed. The shapes of the wave forms of DBT and activity were maintained with increasing light until an 18L:6D photoperiod was reached. The rhythms were entrained to the onset of darkness rather than lights on. Major and minor periods of LMA were detected. Hysteresis diagrams showed that DBT led the onset of major LA by 6 hr and the end of major activity by 2 hr. PMID:11826886

  3. Circadian rhythms in Synechococcus elongatus PCC 7942: insights into the regulatory mechanisms of the cyanobacterial clock system 

    E-print Network

    Mackey, Shannon Rose

    2009-06-02

    was examined by studying the circadian regulation of the psbA gene family. Overall, these data provide insight into the complex molecular events that occur to create a circadian timing circuit in S. elongatus....

  4. Molecular Mechanisms of Circadian Regulation During Spaceflight

    NASA Technical Reports Server (NTRS)

    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 ipRGC and melanopsin expression, which may be a contributing cause of circadian disruption during spaceflight.

  5. Circadian rhythm of water balance and aldosterone excretion in the whitebellied sunbird Nectarinia talatala.

    PubMed

    Fleming, P A; Gray, D A; Nicolson, S W

    2004-05-01

    Nectarivorous whitebellied sunbirds, Nectarinia talatala, demonstrate distinct circadian patterns in osmoregulatory parameters. We recorded intake of a 1 mol/l sucrose solution which enabled calculation of total water gain, and collected cloacal fluid for measurements of volume, osmolality and aldosterone concentration. These variables were assessed hourly over 12 h of photophase, and averaged over the 12-h scotophase period. Overnight, when sunbirds were in negative water balance, aldosterone concentrations and outputs were significantly higher than diurnal levels, reflecting a shut-down of cloacal fluid production. Early morning was marked by a high rate of osmotic excretion, disproportionate to water gain or cloacal fluid output, followed by steady intake and cloacal fluid output during the morning and early afternoon. Reduced water flux (decreased feeding and cloacal fluid output) during mid-afternoon was accompanied by a paradoxical decline in osmotic excretion, whilst a significant increase in the discrepancy between water intake and output was recorded as the birds effectively stored water before the scotophase. These patterns of intake and excretion may be informative in explaining drinking and foraging behaviour in the field. PMID:14997332

  6. Role of cardiomyocyte circadian clock in myocardial metabolic adaptation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marked circadian rhythmicities in cardiovascular physiology and pathophysiology exist. The cardiomyocyte circadian clock has recently been linked to circadian rhythms in myocardial gene expression, metabolism, and contractile function. For instance, the cardiomyocyte circadian clock is essential f...

  7. The Q175 Mouse Model of Huntington’s Disease Shows Gene Dosage- and Age-Related Decline in Circadian Rhythms of Activity and Sleep

    PubMed Central

    Loh, Dawn H.; Kudo, Takashi; Truong, Danny; Wu, Yingfei; Colwell, Christopher S.

    2013-01-01

    Sleep and circadian disruptions are commonly reported by patients with neurodegenerative diseases, suggesting these may be an endophenotype of the disorders. Several mouse models of Huntington’s disease (HD) that recapitulate the disease progression and motor dysfunction of HD also exhibit sleep and circadian rhythm disruption. Of these, the strongest effects are observed in the transgenic models with multiple copies of mutant huntingtin gene. For developing treatments of the human disease, knock-in (KI) models offer advantages of genetic precision of the insertion and control of mutation copy number. Therefore, we assayed locomotor activity and immobility-defined sleep in a new model of HD with an expansion of the KI repeats (Q175). We found evidence for gene dose- and age-dependent circadian disruption in the behavior of the Q175 line. We did not see evidence for loss of cells or disruption of the molecular oscillator in the master pacemaker, the suprachiasmatic nucleus (SCN). The combination of the precise genetic targeting in the Q175 model and the observed sleep and circadian disruptions make it tractable to study the interaction of the underlying pathology of HD and the mechanisms by which the disruptions occur. PMID:23936129

  8. Modafinil [2-[(diphenylmethyl)sulfinyl]acetamide] and circadian rhythms in syrian hamsters: assessment of the chronobiotic potential of a novel alerting compound.

    PubMed

    Webb, Ian C; Pollock, Michael S; Mistlberger, Ralph E

    2006-05-01

    In Syrian hamsters, behavioral procedures for inducing arousal (e.g., running in a novel wheel or gentle handling) can shift circadian rhythms when applied during the usual sleep period ("subjective day") and can attenuate phase shifts to light during the active period ("subjective night"). This raises the possibility that drugs that affect behavioral state may have "chronobiotic" potential. We characterized the effects of modafinil (2-[(diphenylmethyl)sulfinyl]acetamide), an atypical alerting compound, on circadian rhythms in male Syrian hamsters. Electroencephalogram recordings and video observations confirmed that modafinil dose dependently increases wakefulness at the expense of slow-wave and paradoxical sleep with no increase in locomotor activity per unit of time awake. Despite inducing arousal, modafinil at these doses (150 or 300 mg/kg), administered in the subjective day or early or late in the subjective night, did not perturb circadian phase. Modafinil (300 mg/kg) also had no effect on phase shifts to light exposure either early or late in the night and did not alter the size of phase shifts induced by running in a novel wheel for 3 h during the mid-day. Modafinil (300 mg/kg) did, however, decrease by approximately 50% the amount of novel wheel-stimulated running, moving leftward the dose-response relation between wheel revolutions and shift magnitude. These results indicate that, in Syrian hamsters, modafinil alone has no significant chronobiotic efficacy. Nevertheless, this agent may increase the sensitivity of the circadian pacemaker to nonphotic stimuli and may thus have some potential as a tool for promoting clock resetting in combination with behavioral strategies. PMID:16461586

  9. Circadian rhythms, Wnt/beta-catenin pathway and PPAR alpha/gamma profiles in diseases with primary or secondary cardiac dysfunction

    PubMed Central

    Lecarpentier, Yves; Claes, Victor; Duthoit, Guillaume; Hébert, Jean-Louis

    2014-01-01

    Circadian clock mechanisms are far-from-equilibrium dissipative structures. Peroxisome proliferator-activated receptors (PPAR alpha, beta/delta, and gamma) play a key role in metabolic regulatory processes, particularly in heart muscle. Links between circadian rhythms (CRs) and PPARs have been established. Mammalian CRs involve at least two critical transcription factors, CLOCK and BMAL1 (Gekakis et al., 1998; Hogenesch et al., 1998). PPAR gamma plays a major role in both glucose and lipid metabolisms and presents circadian properties which coordinate the interplay between metabolism and CRs. PPAR gamma is a major component of the vascular clock. Vascular PPAR gamma is a peripheral regulator of cardiovascular rhythms controlling circadian variations in blood pressure and heart rate through BMAL1. We focused our review on diseases with abnormalities of CRs and with primary or secondary cardiac dysfunction. Moreover, these diseases presented changes in the Wnt/beta-catenin pathway and PPARs, according to two opposed profiles. Profile 1 was defined as follows: inactivation of the Wnt/beta-catenin pathway with increased expression of PPAR gamma. Profile 2 was defined as follows: activation of the Wnt/beta-catenin pathway with decreased expression of PPAR gamma. A typical profile 1 disease is arrhythmogenic right ventricular cardiomyopathy, a genetic cardiac disease which presents mutations of the desmosomal proteins and is mainly characterized by fatty acid accumulation in adult cardiomyocytes mainly in the right ventricle. The link between PPAR gamma dysfunction and desmosomal genetic mutations occurs via inactivation of the Wnt/beta-catenin pathway presenting oscillatory properties. A typical profile 2 disease is type 2 diabetes, with activation of the Wnt/beta-catenin pathway and decreased expression of PPAR gamma. CRs abnormalities are present in numerous pathologies such as cardiovascular diseases, sympathetic/parasympathetic dysfunction, hypertension, diabetes, neurodegenerative diseases, cancer which are often closely inter-related. PMID:25414671

  10. Systems Biology of the Mammalian Circadian Clock

    E-print Network

    Spang, Rainer

    Molecular Chronobiology #12;The circadian oscillator Circadian rhythm Oster et al., 2002 Feedback loops rhythms disrupted -TrCP1-Mediated Degradation of PERIOD2 Is Essential for Circadian Dynamics Reischl et alSystems Biology of the Mammalian Circadian Clock Hanspeter Herzel Institute for Theoretical Biology

  11. Brain-Specific Rescue of Clock Reveals System-Driven Transcriptional Rhythms in Peripheral Tissue

    PubMed Central

    Hughes, Michael E.; Hong, Hee-Kyung; Chong, Jason L.; Indacochea, Alejandra A.; Lee, Samuel S.; Han, Michael; Takahashi, Joseph S.; Hogenesch, John B.

    2012-01-01

    The circadian regulatory network is organized in a hierarchical fashion, with a central oscillator in the suprachiasmatic nuclei (SCN) orchestrating circadian oscillations in peripheral tissues. The nature of the relationship between central and peripheral oscillators, however, is poorly understood. We used the tetOFF expression system to specifically restore Clock function in the brains of Clock?19 mice, which have compromised circadian clocks. Rescued mice showed normal locomotor rhythms in constant darkness, with activity period lengths approximating wildtype controls. We used microarray analysis to assess whether brain-specific rescue of circadian rhythmicity was sufficient to restore circadian transcriptional output in the liver. Compared to Clock mutants, Clock-rescue mice showed significantly larger numbers of cycling transcripts with appropriate phase and period lengths, including many components of the core circadian oscillator. This indicates that the SCN oscillator overcomes local circadian defects and signals directly to the molecular clock. Interestingly, the vast majority of core clock genes in liver were responsive to Clock expression in the SCN, suggesting that core clock genes in peripheral tissues are intrinsically sensitive to SCN cues. Nevertheless, most circadian output in the liver was absent or severely low-amplitude in Clock-rescue animals, demonstrating that the majority of peripheral transcriptional rhythms depend on a fully functional local circadian oscillator. We identified several new system-driven rhythmic genes in the liver, including Alas1 and Mfsd2. Finally, we show that 12-hour transcriptional rhythms (i.e., circadian “harmonics") are disrupted by Clock loss-of-function. Brain-specific rescue of Clock converted 12-hour rhythms into 24-hour rhythms, suggesting that signaling via the central circadian oscillator is required to generate one of the two daily peaks of expression. Based on these data, we conclude that 12-hour rhythms are driven by interactions between central and peripheral circadian oscillators. PMID:22844252

  12. Use of Novel Light Sources and Melatonin Delivery Systems in the Maintenance of Temporal Organization of Physiological and Behavioral Circadian Rhythms

    NASA Technical Reports Server (NTRS)

    Winget, C. M.; Singh, M. S.; Syrkin, N. C.; Holley, D. C.

    1998-01-01

    The synchronization of physiological and behavioral rhythms are controlled by an endogenous biological clock. It is generally accepted that environmental lighting is the strongest entrainer of this clock. The pineal gland is an important physiological transducer of environmental lighting via systemic melatonin secretion. We have used a novel light source using light emitting diode (LED) technology to entrain circadian rhythms in rats, and propose a novel percutaneous exogenous melatonin delivery system to entrain rat rhythms. We used 5 groups of Sprague-Dawley rats (175-350 g; N = 8/group) and showed normal entrainment of gross locomotor activity, feeding, and drinking circadian rhythms at light intensities varying from 80 lux to 0.1 lux (22.4 to 0.03 sq cm). To improve the delivery of melatonin across the skin stratum corneum it was formulated in a suitable vehicle in a transdermal drug delivery system. Various saturated and unsaturated fatty acids were used E, akin penetration enhancers. Our best vehicle formulation was achieved with a combination-of ethano1:water (60:40) along with 5% oleic acid as the enhancer. This formulation mixture was studied using Franz diffusion cell (0.636 sq cm diffusional area) and 1 cu cm dorsal skin isolated from Sprague Dawley rats. Our results showed that oleic acid in combination with the water ethanol mixture improved the flux of melatonin by more than 18 fold. The lag time for melatonin permeation was 2-3 hrs and the peak concentrations were achieved in 8-10 hrs. Our approaches in the future will involve the use of our transdermal melatonin delivery system and under the influence of LED light and microgravity.

  13. Circadian rhythm of serum 25 (OH) vitamin D, calcium and phosphorus levels in the treatment and management of type-2 diabetic patients.

    PubMed

    Masood, Tariq; Kushwaha, Rajeev S; Singh, Ranjana; Sailwal, Shivani; Pandey, Himanshu; Varma, Amit; Singh, Raj K; Cornelissen, Germaine

    2015-02-01

    The circadian time structure of serum 25 (OH) vitamin D (25-OHD), calcium (Ca) and phosphorus (P) may prove to be helpful in prevention, efficacy and management of diabetes mellitus. Ten newly diagnosed patients with type-2 diabetes mellitus (6 men and 4 women), 30-65 years of age, and 10 age-matched clinically healthy volunteers (7 men and 3 women) were synchronized for one week with diurnal activity from about 06:00 to about 22:00 and nocturnal rest. Breakfast was served around 08:00, lunch around 13:30 and dinner around 20:00. Drugs/nutraceuticals known to affect the vitamin D-calcium metabolism and status were not taken. Blood samples were collected at 6-h intervals for 24 h under standardized, 24-h synchronized conditions. Serum 25-OHD, Ca, P, Ca-P product and Ca-P ratio were determined. A marked circadian variation was demonstrated for 25-OHD in healthy volunteers (p = 0.030) and of borderline statistical significance in the diabetic patients (p = 0.083) by population-mean cosinor analysis. Similarly, healthy volunteers showed borderline significance for serum Ca, P and Ca-P ratio. The circadian acrophase of Ca occurred later in the patients as compared to healthy controls. Mapping the circadian rhythm (an important component of the broader time structure or chronome, which includes a.o., trends with age and extra-circadian components) of vitamin D and calcium is needed for exploring their role as markers in the treatment and management of diabetic patients. PMID:25788054

  14. Carbon Monoxide and Nitric Oxide: Interacting Messengers in Muscarinic Signaling to the Brain's Circadian Clock

    E-print Network

    Gillette, Martha U.

    NO produc- tion generates cGMP tone that primes the clock for cholinergic signaling, whereas HO/CO transmit obscure how ACh modifies the biological clock that synchronizes sleep/wake cycles with circadian rhythms in the range of physiological functions. Cholinergic regulation of the circadian clock origi- nates

  15. Activation of MT2 melatonin receptors in rat suprachiasmatic nucleus phase advances the circadian clock

    E-print Network

    Gillette, Martha U.

    , only at night. Thus the SCN clock generates the circadian rhythm of melatonin, ensuringActivation of MT2 melatonin receptors in rat suprachiasmatic nucleus phase advances the circadian clock AMANDA E. HUNT,1 WALID M. AL-GHOUL,2 MARTHA U. GILLETTE,1,3 AND MARGARITA L. DUBOCOVICH2 1

  16. Journal of Theoretical Biology 230 (2004) 541562 Modeling the mammalian circadian clock: Sensitivity analysis and

    E-print Network

    Goldbeter, Albert

    2004-01-01

    Journal of Theoretical Biology 230 (2004) 541­562 Modeling the mammalian circadian clock Plaine, C.P. 231, B-1050 Brussels, Belgium Received 24 April 2004; accepted 27 April 2004 Available correspond to circadian rhythms autonomously generated by suprachiasmatic nuclei and by some peripheral

  17. 1062 NATURE MEDICINE VOLUME 5 NUMBER 9 SEPTEMBER 1999 Biological circadian clocks oscillate with an approximately

    E-print Network

    Marc, Robert E.

    . These kindreds represent a well-characterized familial circadian rhythm variant in humans and provide a unique advantage by anticipating the transitions between day and night. The circadian rhythms of sleep, melatonin the existence of familial human circadian rhythm variants3,4 but none of the human circadian rhythm disorders

  18. The Roles of the Dimeric and Tetrameric Structures of the Clock Protein KaiB in the Generation of Circadian Oscillations in Cyanobacteria*

    PubMed Central

    Murakami, Reiko; Mutoh, Risa; Iwase, Ryo; Furukawa, Yukio; Imada, Katsumi; Onai, Kiyoshi; Morishita, Megumi; Yasui, So; Ishii, Kentaro; Valencia Swain, Jonathan Orville; Uzumaki, Tatsuya; Namba, Keiichi; Ishiura, Masahiro

    2012-01-01

    The molecular machinery of the cyanobacterial circadian clock consists of three proteins, KaiA, KaiB, and KaiC. The three Kai proteins interact with each other and generate circadian oscillations in vitro in the presence of ATP (an in vitro KaiABC clock system). KaiB consists of four subunits organized as a dimer of dimers, and its overall shape is that of an elongated hexagonal plate with a positively charged cleft flanked by two negatively charged ridges. We found that a mutant KaiB with a C-terminal deletion (KaiB1–94), which lacks the negatively charged ridges, was a dimer. Despite its dimeric structure, KaiB1–94 interacted with KaiC and generated normal circadian oscillations in the in vitro KaiABC clock system. KaiB1–94 also generated circadian oscillations in cyanobacterial cells, but they were weak, indicating that the C-terminal region and tetrameric structure of KaiB are necessary for the generation of normal gene expression rhythms in vivo. KaiB1–94 showed the highest affinity for KaiC among the KaiC-binding proteins we examined and inhibited KaiC from forming a complex with SasA, which is involved in the main output pathway from the KaiABC clock oscillator in transcription regulation. This defect explains the mechanism underlying the lack of normal gene expression rhythms in cells expressing KaiB1–94. PMID:22722936

  19. Circadian Disruption in Psychiatric Disorders.

    PubMed

    Jones, Stephanie G; Benca, Ruth M

    2015-12-01

    Evidence suggests that abnormalities in circadian rhythms might prove causally or pathophysiologically significant in psychiatric illness. The circadian regulation of hormonal and behavioral timekeeping processes is often altered in patients with major depression, bipolar disorder, and schizophrenia, and a susceptibility to rhythm instability may contribute to the functional impairment. For some patients, interventions that stabilize or resynchronize circadian rhythms prove therapeutically effective. Circadian disruption in the clinical profiles of most psychiatric illnesses and the treatment efficacy of chronobiological interventions suggest that attention to circadian phenotypes in a range of psychiatric disorders may help to uncover shared pathophysiologic mechanisms. PMID:26568124

  20. The effects of circadian phase, time awake, and imposed sleep restriction on performing complex visual tasks

    E-print Network

    Pomplun, Marc

    experiments. Keywords: circadian rhythm, neurobehavioral performance, biological rhythm, visual attentionThe effects of circadian phase, time awake, and imposed sleep restriction on performing complex time of day (circadian phase). Previous studies have shown that both factors influence accuracy rather

  1. Circadian Activity Rhythms and Voluntary Ethanol Intake in Male and Female Ethanol-Preferring Rats: Effects of Long-Term Ethanol Access

    PubMed Central

    Rosenwasser, Alan M.; McCulley, Walter D.; Fecteau, Matthew

    2014-01-01

    Chronic alcohol (ethanol) intake alters fundamental properties of the circadian clock. While previous studies have reported significant alterations in free-running circadian period during chronic ethanol access, these effects are typically subtle and appear to require high levels of intake. In the present study we examined the effects of long-term voluntary ethanol intake on ethanol consumption and free-running circadian period in male and female, selectively bred ethanol-preferring P and HAD2 rats. In light of previous reports that intermittent access can result in escalated ethanol intake, an initial 2-week water-only baseline was followed by either continuous or intermittent ethanol access (i.e., alternating 15-day epochs of ethanol access and ethanol deprivation) in separate groups of rats. Thus, animals were exposed to either 135 days of continuous ethanol access or to five 15-day access periods alternating with four 15-day periods of ethanol deprivation. Animals were maintained individually in running-wheel cages under continuous darkness throughout the experiment to allow monitoring of free-running activity and drinking rhythms, and 10% (v/v) ethanol and plain water were available continuously via separate drinking tubes during ethanol access. While there were no initial sex differences in ethanol drinking, ethanol preference increased progressively in male P and HAD2 rats under both continuous and intermittent-access conditions, and eventually exceeded that seen in females. Free-running period shortened during the initial ethanol-access epoch in all groups, but the persistence of this effect showed complex dependence on sex, breeding line, and ethanol-access schedule. Finally, while females of both breeding lines displayed higher levels of locomotor activity than males, there was little evidence for modulation of activity level by ethanol access. These results are consistent with previous findings that chronic ethanol intake alters free-running circadian period, and show further that the development of chronobiological tolerance to ethanol may vary by sex and genotype. PMID:25281289

  2. Telemetry provides new insights into entrainment of activity wheel circadian rhythms and the role of body temperature in the development of ulcers in the activity-stress paradigm.

    PubMed

    Murphy, Helen M; Wideman, Cyrilla H; Aquila, Louise A; Nadzam, George R

    2002-01-01

    Two methods of monitoring the circadian rhythm of activity in rodents: (1) an activity wheel cage, which detects the number of wheel revolutions, and (2) an internal radio transmitter, which records gross motor activity (GMA) of the animal, were compared in both normal circadian cycles and during the development of activity-stress ulcers. Rats were implanted with a biotelemetry transmitter that detected GMA and body temperature (BT) and placed in activity wheel cages. A 12 hour/12 hour light/dark cycle was maintained throughout the experiment. Subjects were subdivided into two groups: (1) unlimited access to activity wheel (AW) cages and (2) locked activity wheel (LW) cages. Following an ad-libitum habituation period, animals were allowed food access for 1 hour/day during the light. In the habituation period, the animals showed higher GMA and BT during the dark phase when housed in AW cages than in LW cages. Both GMA and number of wheel revolutions increased dramatically after the onset of food restriction for the AW animals. There was a deleterious drop in BT in AW animals as the food-restricted period continued and a significant correlation existed between severity of ulcerations and BT. The findings of this experiment demonstrate that the activity wheel imposes an alternation of the circadian cycle, which, in turn, influences rhythmicity through reentrainment. Additionally, in the activity-stress paradigm, a significant drop in BT correlates with severity of ulcerations. A disrupted circadian cycle, involving hypothermia, is proposed as the mechanism underlying the demise of animals in the activity-stress paradigm. PMID:12435213

  3. Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics

    NASA Technical Reports Server (NTRS)

    Dijk, D. J.; Duffy, J. F.

    1999-01-01

    The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed.

  4. Double Dissociation between Emotion Generation and Emotion Regulation 1 DOUBLE DISSOCIATION: CIRCADIAN OFF-PEAK TIMES

    E-print Network

    Double Dissociation between Emotion Generation and Emotion Regulation 1 DOUBLE DISSOCIATION: CIRCADIAN OFF-PEAK TIMES INCREASE EMOTIONAL REACTIVITY; AGING IMPAIRS EMOTION REGULATION VIA REAPPRAISAL Running Head: Double Dissociation between

  5. Dissociation of ultradian and circadian phenotypes in female and male Siberian hamsters.

    PubMed

    Prendergast, Brian J; Cisse, Yasmine M; Cable, Erin J; Zucker, Irving

    2012-08-01

    Three experiments addressed whether pronounced alterations in the circadian system yielded concomitant changes in ultradian timing. Female Siberian hamsters were housed in a 16L:8D photoperiod after being subjected to a disruptive phase-shifting protocol that produced 3 distinct permanent circadian phenotypes: some hamsters entrained their circadian rhythms (CRs) with predominantly nocturnal locomotor activity (ENTR), others displayed free-running CRs (FR), and a third cohort was circadian arrhythmic (ARR). The period of the ultradian locomotor rhythm (UR) did not differ among the 3 circadian phenotypes; neuroendocrine generation of URs remains viable in the absence of coherent circadian organization and appears to be mediated by substrates functionally and anatomically distinct from those that generate CRs. Pronounced light-dark differences in several UR characteristics in ENTR hamsters were completely absent in circadian arrhythmic hamsters. The disruptive phase-shifting protocol may compromise direct visual input to ultradian oscillators but more likely indirectly affects URs by interrupting visual afference to the circadian system. Additional experiments documented that deuterium oxide and constant light, each of which substantially lengthened the period of free-running CRs, failed to change the period of concurrently monitored URs. The resistance of URs to deuteration contrasts with the slowing of virtually all other biological timing processes, including CRs. Considered together, the present results point to the existence of separable control mechanisms for generation of circadian and ultradian rhythms. PMID:22855573

  6. Circadian Rhythm Sleep Disorders

    MedlinePLUS

    ... begin approximately one to two days after air travel across at least two time zones. Exposure to light at inappropriate times may ... and other people who have little exposure to time cues such as light, activity and ... lag can affect anyone who travels by air, but symptoms may be more severe ...

  7. The circadian clock controls the expression pattern of the circadian input photoreceptor, phytochrome B

    E-print Network

    Millar, Andrew J.

    and physiological responses are regulated by light throughout the entire life cycle of higher plants. To sense responses, including most light responses, also are mod- ulated by circadian rhythms that are generated are synchronized and entrained by environmental time cues, of which light is among the most important. Light

  8. Suprachiasmatic nuclei and Circadian rhythms. The role of suprachiasmatic nuclei on rhythmic activity of neurons in the lateral hypothalamic area, ventromedian nuclei and pineal gland

    NASA Technical Reports Server (NTRS)

    Nishino, H.

    1977-01-01

    Unit activity of lateral hypothalamic area (LHA) and Ventromedian nuclei (VMN) was recorded in urethane anesthetized male rats. A 5 to 10 sec. a 3-5 min and a circadian rhythmicity were observed. In about 15% of all neurons, spontaneous activity of LHA and VMN showed reciprocal relationships. Subthreshold stimuli applied at a slow rate in the septum and the suprachiasmatic nuclei (SCN) suppressed the rhythms without changing firing rates. On the other hand, stimulation of the optic nerve at a rate of 5 to 10/sec increased firing rates in 1/3 of neurons of SCN. Iontophoretically applied acetylcholine increased 80% of tested neurons of SCN, whereas norepinephrine, dopamine and 5 HT inhibited 64, 60 and 75% of SCN neurons respectively. These inhibitions were much stronger in neurons, the activity of which was increased by optic nerve stimulation. Stimulation of the SCN inhibited the tonic activity in cervical sympathetic nerves.

  9. Interplay between cellular redox oscillations and circadian clocks.

    PubMed

    Rey, G; Reddy, A B

    2015-09-01

    The circadian clock is a cellular timekeeping mechanism that helps organisms from bacteria to humans to organize their behaviour and physiology around the solar cycle. Current models for circadian timekeeping incorporate transcriptional/translational feedback loop mechanisms in the predominant model systems. However, recent evidence suggests that non-transcriptional oscillations such as metabolic and redox cycles may play a fundamental role in circadian timekeeping. Peroxiredoxins, an antioxidant protein family, undergo rhythmic oxidation on the circadian time scale in a variety of species, including bacteria, insects and mammals, but also in red blood cells, a naturally occurring, non-transcriptional system. The profound interconnectivity between circadian and redox pathways strongly suggests that a conserved timekeeping mechanism based on redox cycles could be integral to generating circadian rhythms. PMID:26332969

  10. Interplay between circadian rhythm, time of the day and osmotic stress constraints in the regulation of the expression of a Solanum Double B-box gene

    PubMed Central

    Kie?bowicz-Matuk, Agnieszka; Rey, Pascal; Rorat, Tadeusz

    2014-01-01

    Background and Aims Double B-box zinc finger (DBB) proteins are recently identified plant transcription regulators that participate in the response to sodium chloride-induced stress in arabidopsis plants. Little is known regarding their subcellular localization and expression patterns, particularly in relation to other osmotic constraints and the day/night cycle. This study investigated natural variations in the amount of a Solanum DBB protein, SsBBX24, during plant development, and also under various environmental constraints leading to cell dehydration in relation to the circadian clock and the time of day. Methods SsBBX24 transcript and protein abundance in various organs of phytotron-grown Solanum tuberosum and S. sogarandinum plants were investigated at different time points of the day and under various osmotic constraints. The intracellular location of SsBBX24 was determined by western blot analysis of subcellular fractions. Key Results Western blot analysis of SsBBX24 protein revealed that it was located in the nucleus at the beginning of the light period and in the cytosol at the end, suggesting movement (‘trafficking’) during the light phase. SsBBX24 gene expression exhibited circadian cycling under control conditions, with the highest and lowest abundances of both transcript and protein occurring 8 and 18 h after dawn, respectively. Exposing Solanum plants to low temperature, salinity and polyethylene glycol (PEG), but not to drought, disturbed the circadian regulation of SsBBX24 gene expression at the protein level. SsBBX24 transcript and protein accumulated in Solanum plants in response to salt and PEG treatments, but not in response to low temperature or water deficit. Most interestingly, the time of the day modulated the magnitude of SsBBX24 expression in response to high salt concentration. Conclusions The interplay between circadian rhythm and osmotic constraints in the regulation of the expression of a Solanum DBB transcriptional regulator is demonstrated. It is proposed that stress-dependent, post-transcriptional mechanisms alter the regulation by the circadian clock of the amount of SsBBX24. PMID:24562097

  11. The EMBO Journal vol.15 no.7 pp.1625-1631, 1996 A novel circadianly expressed Drosophila

    E-print Network

    Krasnow, Mark A.

    circadian rhythms of locomotion and eclosion. per mRNA is expressed with a circadian rhythm whose mRNA is expressed in fly heads with a circadian rhythm nearly identical to that of the per gene oscillate in abundancewith a circadian rhythm. ThephaseofDreg-5 protein oscillation, however, is different

  12. The effect of blue-blocking intraocular lenses on circadian biological rhythm: protocol for a randomised controlled trial (CLOCK-IOL colour study)

    PubMed Central

    Nishi, Tomo; Saeki, Keigo; Obayashi, Kenji; Miyata, Kimie; Tone, Nobuhiro; Tsujinaka, Hiroki; Yamashita, Mariko; Masuda, Naonori; Mizusawa, Yutarou; Okamoto, Masahiro; Hasegawa, Taiji; Maruoka, Shinji; Ueda, Tetsuo; Kojima, Masashi; Matsuura, Toyoaki; Kurumatani, Norio; Ogata, Nahoko

    2015-01-01

    Introduction Blue light information plays an important role in synchronising internal biological rhythm within the external environment. Circadian misalignment is associated with the increased risk of sleep disturbance, obesity, diabetes mellitus, depression, ischaemic heart disease, stroke and cancer. Meanwhile, blue light causes photochemical damage to the retina, and may be associated with age-related macular degeneration (AMD). At present, clear intraocular lenses (IOLs) and blue-blocking IOLs are both widely used for cataract surgery; there is currently a lack of randomised controlled trials to determine whether clear or blue-blocking IOLs should be used. Methods and analysis This randomised controlled trial will recruit 1000 cataract patients and randomly allocate them to receive clear IOLs or blue-blocking IOLs in a ratio of 1:1. The primary outcomes are mortality and the incidence of cardiovascular disease, cancer and AMD. Secondary outcomes are fasting plasma glucose, triglycerides, cholesterol, glycated haemoglobin, sleep quality, daytime sleepiness depressive symptoms, light sensitivity, the circadian rhythm of physical activity, wrist skin temperature and urinary melatonin metabolite. Primary outcomes will be followed until 20?years after surgery, and secondary outcomes will be assessed at baseline and 1?year after surgery. Ethics and dissemination Ethical approval has been obtained from the Institutional Review Board of Nara Medical University (No. 13-032). The findings of this study will be communicated to healthcare professionals, participants and the public through peer-reviewed publications, scientific conferences and the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) home page. Trial registration number UMIN000014680. PMID:25968007

  13. d-amino acid oxidase knockout (Dao(-/-) ) mice show enhanced short-term memory performance and heightened anxiety, but no sleep or circadian rhythm disruption.

    PubMed

    Pritchett, David; Hasan, Sibah; Tam, Shu K E; Engle, Sandra J; Brandon, Nicholas J; Sharp, Trevor; Foster, Russell G; Harrison, Paul J; Bannerman, David M; Peirson, Stuart N

    2015-05-01

    d-amino acid oxidase (DAO, DAAO) is an enzyme that degrades d-serine, the primary endogenous co-agonist of the synaptic N-methyl-d-aspartate receptor. Convergent evidence implicates DAO in the pathophysiology and potential treatment of schizophrenia. To better understand the functional role of DAO, we characterized the behaviour of the first genetically engineered Dao knockout (Dao(-/-) ) mouse. Our primary objective was to assess both spatial and non-spatial short-term memory performance. Relative to wildtype (Dao(+/+) ) littermate controls, Dao(-/-) mice demonstrated enhanced spatial recognition memory performance, improved odour recognition memory performance, and enhanced spontaneous alternation in the T-maze. In addition, Dao(-/-) mice displayed increased anxiety-like behaviour in five tests of approach/avoidance conflict: the open field test, elevated plus maze, successive alleys, light/dark box and novelty-suppressed feeding. Despite evidence of a reciprocal relationship between anxiety and sleep and circadian function in rodents, we found no evidence of sleep or circadian rhythm disruption in Dao(-/-) mice. Overall, our observations are consistent with, and extend, findings in the natural mutant ddY/Dao(-) line. These data add to a growing body of preclinical evidence linking the inhibition, inactivation or deletion of DAO with enhanced cognitive performance. Our results have implications for the development of DAO inhibitors as therapeutic agents. PMID:25816902

  14. Consequences of Circadian Disruption on Neurologic Health.

    PubMed

    Videnovic, Aleksandar; Zee, Phyllis C

    2015-12-01

    Circadian rhythms have a major role in physiology and behavior. Circadian disruption has negative consequences for physiologic homeostasis at molecular, cellular, organ-system, and whole-organism levels. The onset of many cerebrovascular insults shows circadian temporal trends. Impaired sleep-wake cycle, the most robust output rhythms of the circadian system, is significantly affected by neurodegenerative disorders, may precede them by decades, and may also affect their progression. Emerging evidence suggests that circadian disruption may be a risk factor for these neurologic disorders. This article discusses the implications of circadian rhythms in brain disorders, with an emphasis on cerebrovascular and neurodegenerative disorders. PMID:26568123

  15. http://jbr.sagepub.com Journal of Biological Rhythms

    E-print Network

    Bradshaw, William E.

    Biol Rhythms William E. Bradshaw and Christina M. Holzapfel What Season Is It Anyway? Circadian, highly predictable rhythms of the biosphere. The internal circadian clock enables organisms to track that circadian rhythms formed the basis (Grundlage) for photoperiodic response to day length. Historical inertia

  16. Photosynthetic entrainment of the Arabidopsis thaliana circadian clock

    E-print Network

    Haydon, Michael J.; Mielczarek, Olga; Robertson, Fiona C.; Hubbard, Katherine E.; Webb, Alex A. R.

    2013-10-23

    of the circadian clock in plants. Here we show that these rhythmic, endogenous sugar signals can entrain circadian rhythms in Arabidopsis thaliana by regulating the gene expression of circadian clock components early in the photoperiod, thus defining a ‘metabolic...

  17. Biophotonics: Circadian photonics

    NASA Astrophysics Data System (ADS)

    Rea, Mark S.

    2011-05-01

    A growing body of medical evidence suggests that disrupting the body's biological clock can have adverse effects on health. Researchers are now creating the photonic tools to monitor, predict and influence the circadian rhythm.

  18. Stochastic Models for Circadian Oscillations: Emergence of a

    E-print Network

    Goldbeter, Albert

    Stochastic Models for Circadian Oscillations: Emergence of a Biological Rhythm DIDIER GONZE, JOSE. Deterministic models based on such genetic regulatory processes account for the occurrence of circadian rhythms Periodicals, Inc. Int J Quantum Chem 98: 228­238, 2004 Key words: circadian rhythms; stochastic simulations

  19. FORUM REVIEW ARTICLE Brain Circadian Oscillators and Redox Regulation

    E-print Network

    Gillette, Martha U.

    in light and energy. Mammalian circadian rhythms are orchestrated by the hypothalamic suprachiasmatic an autonomous circadian rhythm. Redox state is relatively reduced in daytime, when neuronal activity is high energy metabolism, neuronal activity, and circadian rhythms is critical to developing therapeutic

  20. http://www.springer.com/0-387-23641-4 Basic Mechanisms of Circadian

    E-print Network

    Gillette, Martha U.

    http://www.springer.com/0-387-23641-4 2006, #12;Basic Mechanisms of Circadian Rhythms that these circadian rhythms are simply a reflection of the external day-night cycle. However, when all exogenous tim slightly from 24 hours, making it circadian, or `about a day.' Unperturbed, this circadian rhythm persists