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Sample records for human circadian system

  1. Plasticity of the intrinsic period of the human circadian timing system.

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    Frank A J L Scheer

    2007-08-01

    Full Text Available Human expeditions to Mars will require adaptation to the 24.65-h Martian solar day-night cycle (sol, which is outside the range of entrainment of the human circadian pacemaker under lighting intensities to which astronauts are typically exposed. Failure to entrain the circadian time-keeping system to the desired rest-activity cycle disturbs sleep and impairs cognitive function. Furthermore, differences between the intrinsic circadian period and Earth's 24-h light-dark cycle underlie human circadian rhythm sleep disorders, such as advanced sleep phase disorder and non-24-hour sleep-wake disorders. Therefore, first, we tested whether exposure to a model-based lighting regimen would entrain the human circadian pacemaker at a normal phase angle to the 24.65-h Martian sol and to the 23.5-h day length often required of astronauts during short duration space exploration. Second, we tested here whether such prior entrainment to non-24-h light-dark cycles would lead to subsequent modification of the intrinsic period of the human circadian timing system. Here we show that exposure to moderately bright light ( approximately 450 lux; approximately 1.2 W/m(2 for the second or first half of the scheduled wake episode is effective for entraining individuals to the 24.65-h Martian sol and a 23.5-h day length, respectively. Estimations of the circadian periods of plasma melatonin, plasma cortisol, and core body temperature rhythms collected under forced desynchrony protocols revealed that the intrinsic circadian period of the human circadian pacemaker was significantly longer following entrainment to the Martian sol as compared to following entrainment to the 23.5-h day. The latter finding of after-effects of entrainment reveals for the first time plasticity of the period of the human circadian timing system. Both findings have important implications for the treatment of circadian rhythm sleep disorders and human space exploration.

  2. The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors.

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    Frank A J L Scheer

    Full Text Available Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (~9 AM, potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1 platelet function and (2 platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise.We studied 12 healthy adults (6 female who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p ≤ 0.01. These circadian peaks occurred at a circadian phase corresponding to 8-9 AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8 PM. The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors.These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans--independent of the sleep/wake cycle, other behavioral influences and the environment. The 9 AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous

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

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

    2016-02-26

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

  4. Neurobiology of circadian systems.

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    Schulz, Pierre; Steimer, Thierry

    2009-01-01

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

  5. Numerical study of entrainment of the human circadian system and recovery by light treatment.

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    Kim, Soon Ho; Goh, Segun; Han, Kyungreem; Kim, Jong Won; Choi, MooYoung

    2018-05-09

    While the effects of light as a zeitgeber are well known, the way the effects are modulated by features of the sleep-wake system still remains to be studied in detail. A mathematical model for disturbance and recovery of the human circadian system is presented. The model combines a circadian oscillator and a sleep-wake switch that includes the effects of orexin. By means of simulations, we characterize the period-locking zone of the model, where a stable 24-hour circadian rhythm exists, and the occurrence of circadian disruption due to both insufficient light and imbalance in orexin. We also investigate how daily bright light treatments of short duration can recover the normal circadian rhythm. It is found that the system exhibits continuous phase advance/delay at lower/higher orexin levels. Bright light treatment simulations disclose two optimal time windows, corresponding to morning and evening light treatments. Among the two, the morning light treatment is found effective in a wider range of parameter values, with shorter recovery time. This approach offers a systematic way to determine the conditions under which circadian disruption occurs, and to evaluate the effects of light treatment. In particular, it could potentially offer a way to optimize light treatments for patients with circadian disruption, e.g., sleep and mood disorders, in clinical settings.

  6. Response of the human circadian system to millisecond flashes of light.

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    Jamie M Zeitzer

    Full Text Available Ocular light sensitivity is the primary mechanism by which the central circadian clock, located in the suprachiasmatic nucleus (SCN, remains synchronized with the external geophysical day. This process is dependent on both the intensity and timing of the light exposure. Little is known about the impact of the duration of light exposure on the synchronization process in humans. In vitro and behavioral data, however, indicate the circadian clock in rodents can respond to sequences of millisecond light flashes. In a cross-over design, we tested the capacity of humans (n = 7 to respond to a sequence of 60 2-msec pulses of moderately bright light (473 lux given over an hour during the night. Compared to a control dark exposure, after which there was a 3.5±7.3 min circadian phase delay, the millisecond light flashes delayed the circadian clock by 45±13 min (p<0.01. These light flashes also concomitantly increased subjective and objective alertness while suppressing delta and sigma activity (p<0.05 in the electroencephalogram (EEG. Our data indicate that phase shifting of the human circadian clock and immediate alerting effects can be observed in response to brief flashes of light. These data are consistent with the hypothesis that the circadian system can temporally integrate extraordinarily brief light exposures.

  7. Circadian Rhythms, Sleep Deprivation, and Human Performance

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

    2014-01-01

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

  8. A train of blue light pulses delivered through closed eyelids suppresses melatonin and phase shifts the human circadian system

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    Figueiro MG

    2013-10-01

    Full Text Available Mariana G Figueiro, Andrew Bierman, Mark S ReaLighting Research Center, Rensselaer Polytechnic Institute, Troy, NY, USAAbstract: A model of circadian phototransduction was published in 2005 to predict the spectral sensitivity of the human circadian system to narrow-band and polychromatic light sources by combining responses to light from the spectral-opponent “blue” versus “yellow” cone bipolar pathway with direct responses to light by the intrinsically photosensitive retinal ganglion cells. In the model, depolarizing “blue” responses, but not hyperpolarizing “yellow” responses, from the “blue” versus “yellow” pathway are combined with the intrinsically photosensitive retinal ganglion cell responses. Intrinsically photosensitive retinal ganglion cell neurons are known to be much slower to respond to light than the cone pathway, so an implication of the model is that periodic flashes of “blue” light, but not “yellow” light, would be effective for stimulating the circadian system. A within-subjects study was designed to test the implications of the model regarding retinal exposures to brief flashes of light. The study was also aimed at broadening the foundation for clinical treatment of circadian sleep disorders by delivering flashing light through closed eyelids while people were asleep. In addition to a dark control night, the eyelids of 16 subjects were exposed to three light-stimulus conditions in the phase delay portion of the phase response curve while they were asleep: (1 2-second flashes of 111 W/m2 of blue (λmax ≈ 480 nm light once every minute for 1 hour, (2 131 W/m2 of green (λmax ≈ 527 nm light, continuously on for 1 hour, and (3 2-second flashes of the same green light once every minute for 1 hour. Inferential statistics showed that the blue flash light-stimulus condition significantly delayed circadian phase and significantly suppressed nocturnal melatonin. The results of this study further our

  9. Day-night contrast as source of health for the human circadian system.

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    Martinez-Nicolas, Antonio; Madrid, Juan Antonio; Rol, Maria Angeles

    2014-04-01

    Modern societies are characterized by a 24/7 lifestyle (LS) with no environmental differences between day and night, resulting in weak zeitgebers (weak day light, absence of darkness during night, constant environmental temperature, sedentary LS and frequent snacking), and as a consequence, in an impaired circadian system (CS) through a process known as chronodisruption. Both weak zeitgebers and CS impairment are related to human pathologies (certain cancers, metabolic syndrome and affective and cognitive disorders), but little is known about how to chronoenhance the CS. The aim of this work is to propose practical strategies for chronoenhancement, based on accentuating the day/night contrast. For this, 131 young subjects were recruited, and their wrist temperature (WT), activity, body position, light exposure, environmental temperature and sleep were recorded under free-living conditions for 1 week. Subjects with high contrast (HC) and low contrast (LC) for each variable were selected to analyze the HC effect in activity, body position, environmental temperature, light exposure and sleep would have on WT. We found that HC showed better rhythms than LC for every variable except sleep. Subjects with HC and LC for WT also demonstrated differences in LS, where HC subjects had a slightly advanced night phase onset and a general increase in day/night contrast. In addition, theoretical high day/night contrast calculated using mathematical models suggests an improvement by means of LS contrast. Finally, some individuals classified as belonging to the HC group in terms of WT when they are exposed to the LS characteristic of the LC group, while others exhibit WT arrhythmicity despite their good LS habits, revealing two different WT components: an exogenous component modified by LS and another endogenous component that is refractory to it. Therefore, intensifying day/night contrast in subject's LS has proven to be a feasible measure to chronoenhance the CS.

  10. Physiological effects of light on the human circadian pacemaker

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

    2000-01-01

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

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

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    Wilking, Melissa; Ndiaye, Mary; Mukhtar, Hasan

    2013-01-01

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

  12. Hierarchical organization of the circadian timing system

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    Steensel, Mariska van

    2006-01-01

    In order to cope with and to predict 24-hour rhythms in the environment, most, if not all, organisms have a circadian timing system. The most important mammalian circadian pacemaker is located in the suprachiasmatic nucleus at the base of the hypothalamus in the brain. Over the years, it has become

  13. Light and the human circadian clock.

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

    2013-01-01

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

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

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    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...

  15. Circadian light

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    Bierman Andrew

    2010-02-01

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

  16. Circadian systems biology: When time matters

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    Luise Fuhr

    2015-01-01

    In this manuscript we review the combination of experimental methodologies, bioinformatics and theoretical models that have been essential to explore this remarkable timing-system. Such an integrative and interdisciplinary approach may provide new strategies with regard to chronotherapeutic treatment and new insights concerning the restoration of the circadian timing in clock-associated diseases.

  17. Measuring Relative Coupling Strength in Circadian Systems.

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

    2018-02-01

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

  18. Combination of light and melatonin time cues for phase advancing the human circadian clock.

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    Burke, Tina M; Markwald, Rachel R; Chinoy, Evan D; Snider, Jesse A; Bessman, Sara C; Jung, Christopher M; Wright, Kenneth P

    2013-11-01

    Photic and non-photic stimuli have been shown to shift the phase of the human circadian clock. We examined how photic and non-photic time cues may be combined by the human circadian system by assessing the phase advancing effects of one evening dose of exogenous melatonin, alone and in combination with one session of morning bright light exposure. Randomized placebo-controlled double-blind circadian protocol. The effects of four conditions, dim light (∼1.9 lux, ∼0.6 Watts/m(2))-placebo, dim light-melatonin (5 mg), bright light (∼3000 lux, ∼7 Watts/m(2))-placebo, and bright light-melatonin on circadian phase was assessed by the change in the salivary dim light melatonin onset (DLMO) prior to and following treatment under constant routine conditions. Melatonin or placebo was administered 5.75 h prior to habitual bedtime and 3 h of bright light exposure started 1 h prior to habitual wake time. Sleep and chronobiology laboratory environment free of time cues. Thirty-six healthy participants (18 females) aged 22 ± 4 y (mean ± SD). Morning bright light combined with early evening exogenous melatonin induced a greater phase advance of the DLMO than either treatment alone. Bright light alone and melatonin alone induced similar phase advances. Information from light and melatonin appear to be combined by the human circadian clock. The ability to combine circadian time cues has important implications for understanding fundamental physiological principles of the human circadian timing system. Knowledge of such principles is important for designing effective countermeasures for phase-shifting the human circadian clock to adapt to jet lag, shift work, and for designing effective treatments for circadian sleep-wakefulness disorders.

  19. Evidence for widespread dysregulation of circadian clock progression in human cancer

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    Jarrod Shilts

    2018-01-01

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

  20. System identification of the Arabidopsis plant circadian system

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

    2015-02-01

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

  1. Light and the human circadian clock

    NARCIS (Netherlands)

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

    2013-01-01

    The circadian clock can only reliably fulfil its function if it is stably entrained. Most clocks use the light-dark cycle as environmental signal (zeitgeber) for this active synchronisation. How we think about clock function and entrainment has been strongly influenced by the early concepts of the

  2. Aging and Circadian Rhythms

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

    2015-01-01

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

  3. The cholinergic system, circadian rhythmicity, and time memory

    NARCIS (Netherlands)

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

    2011-01-01

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

  4. New methods to assess circadian clocks in humans

    Czech Academy of Sciences Publication Activity Database

    Nováková, Marta; Sumová, Alena

    2014-01-01

    Roč. 52, č. 5 (2014), s. 404-412 ISSN 0019-5189 R&D Projects: GA MZd(CZ) NT11474 Grant - others:Univerzita Karlova(CZ) 22810 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : circadian * clock gene * melatonin * human Subject RIV: ED - Physiology Impact factor: 0.835, year: 2014

  5. Chronotherapeutic drug delivery systems: an approach to circadian rhythms diseases.

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    Sunil, S A; Srikanth, M V; Rao, N Sreenivasa; Uhumwangho, M U; Latha, K; Murthy, K V Ramana

    2011-11-01

    The purpose of writing this review on chronotherapeutic drug delivery systems (ChrDDs) is to review the literatures with special focus on ChrDDs and the various dosage forms, techniques that are used to target the circadian rhythms (CR) of various diseases. Many functions of the human body vary considerably in a day. ChrDDs refers to a treatment method in which in vivo drug availability is timed to match circadian rhythms of disease in order to optimize therapeutic outcomes and minimize side effects. Several techniques have been developed but not many dosage forms for all the diseases are available in the market. ChrDDs are gaining importance in the field of pharmaceutical technology as these systems reduce dosing frequency, toxicity and deliver the drug that matches the CR of that particular disease when the symptoms are maximum to worse. Finally, the ultimate benefit goes to the patient due the compliance and convenience of the dosage form. Some diseases that follow circadian rhythms include cardiovascular diseases, asthma, arthritis, ulcers, diabetes etc. ChrDDs in the market were also discussed and the current technologies used to formulate were also stated. These technologies include Contin® , Chronotopic®, Pulsincaps®, Ceform®, Timerx®, Oros®, Codas®, Diffucaps®, Egalet®, Tablet in capsule device, Core-in-cup tablet technology. A coated drug-core tablet matrix, A bi-layered tablet, Multiparticulate-based chronotherapeutic drug delivery systems, Chronoset and Controlled release microchips.

  6. Circadian Rhythm Management System, Phase I

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    National Aeronautics and Space Administration — The value of measuring sleep-wake cycles is significantly enhanced by measuring other physiological signals that depend on circadian rhythms (such as heart rate and...

  7. Uncovering the mystery of opposite circadian rhythms between mouse and human leukocytes in humanized mice.

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    Zhao, Yue; Liu, Min; Chan, Xue Ying; Tan, Sue Yee; Subramaniam, Sharrada; Fan, Yong; Loh, Eva; Chang, Kenneth Tou En; Tan, Thiam Chye; Chen, Qingfeng

    2017-11-02

    Many immune parameters show circadian rhythms during the 24-hour day in mammals. The most striking circadian oscillation is the number of circulating immune cells that display an opposite rhythm between humans and mice. The physiological roles and mechanisms of circadian variations in mouse leukocytes are well studied, whereas for humans they remain unclear because of the lack of a proper model. In this study, we found that consistent with their natural host species, mouse and human circulating leukocytes exhibited opposite circadian oscillations in humanized mice. This cyclic pattern of trafficking correlated well with the diurnal expression levels of C-X-C chemokine receptor 4, which were controlled by the intracellular hypoxia-inducible factor 1α/aryl hydrocarbon receptor nuclear translocator-like heterodimer. Furthermore, we also discovered that p38 mitogen-activated protein kinases/mitogen-activated 2 had opposite effects between mice and humans in generating intracellular reactive oxygen species, which subsequently regulated HIF-1α expression. In conclusion, we propose humanized mice as a robust model for human circadian studies and reveal insights on a novel molecular clock network in the human circadian rhythm. © 2017 by The American Society of Hematology.

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

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

    2018-06-20

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

  9. Circadian rhythm in melatonin release as a mechanism to reinforce the temporal organization of the circadian system in crayfish.

    Science.gov (United States)

    Mendoza-Vargas, Leonor; Báez-Saldaña, Armida; Alvarado, Ramón; Fuentes-Pardo, Beatriz; Flores-Soto, Edgar; Solís-Chagoyán, Héctor

    2017-06-01

    Melatonin (MEL) is a conserved molecule with respect to its synthesis pathway and functions. In crayfish, MEL content in eyestalks (Ey) increases at night under the photoperiod, and this indoleamine synchronizes the circadian rhythm of electroretinogram amplitude, which is expressed by retinas and controlled by the cerebroid ganglion (CG). The aim of this study was to determine whether MEL content in eyestalks and CG or circulating MEL in hemolymph (He) follows a circadian rhythm under a free-running condition; in addition, it was tested whether MEL might directly influence the spontaneous electrical activity of the CG. Crayfish were maintained under constant darkness and temperature, a condition suitable for studying the intrinsic properties of circadian systems. MEL was quantified in samples obtained from He, Ey, and CG by means of an enzyme-linked immunosorbent assay, and the effect of exogenous MEL on CG spontaneous activity was evaluated by electrophysiological recording. Variation of MEL content in He, Ey, and CG followed a circadian rhythm that peaked at the same circadian time (CT). In addition, a single dose of MEL injected into the crayfish at different CTs reduced the level of spontaneous electrical activity in the CG. Results suggest that the circadian increase in MEL content directly affects the CG, reducing its spontaneous electrical activity, and that MEL might act as a periodical signal to reinforce the organization of the circadian system in crayfish.

  10. Circadian system from conception till adulthood

    Czech Academy of Sciences Publication Activity Database

    Sumová, Alena; Sládek, Martin; Polidarová, Lenka; Nováková, Marta; Houdek, Pavel

    2012-01-01

    Roč. 199, č. 2012 (2012), s. 83-103 ISSN 0079-6123 R&D Projects: GA ČR(CZ) GA305/09/0321; GA ČR(CZ) GAP303/11/0668; GA MŠk(CZ) LC554; GA MZd(CZ) NT11474; GA ČR(CZ) GAP303/12/1108 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : ontogenesis * suprachiasmatic nucleus * peripheral circadian clocks * clock gene Subject RIV: ED - Physiology Impact factor: 4.191, year: 2012

  11. Identification of human circadian genes based on time course gene expression profiles by using a deep learning method.

    Science.gov (United States)

    Cui, Peng; Zhong, Tingyan; Wang, Zhuo; Wang, Tao; Zhao, Hongyu; Liu, Chenglin; Lu, Hui

    2018-06-01

    Circadian genes express periodically in an approximate 24-h period and the identification and study of these genes can provide deep understanding of the circadian control which plays significant roles in human health. Although many circadian gene identification algorithms have been developed, large numbers of false positives and low coverage are still major problems in this field. In this study we constructed a novel computational framework for circadian gene identification using deep neural networks (DNN) - a deep learning algorithm which can represent the raw form of data patterns without imposing assumptions on the expression distribution. Firstly, we transformed time-course gene expression data into categorical-state data to denote the changing trend of gene expression. Two distinct expression patterns emerged after clustering of the state data for circadian genes from our manually created learning dataset. DNN was then applied to discriminate the aperiodic genes and the two subtypes of periodic genes. In order to assess the performance of DNN, four commonly used machine learning methods including k-nearest neighbors, logistic regression, naïve Bayes, and support vector machines were used for comparison. The results show that the DNN model achieves the best balanced precision and recall. Next, we conducted large scale circadian gene detection using the trained DNN model for the remaining transcription profiles. Comparing with JTK_CYCLE and a study performed by Möller-Levet et al. (doi: https://doi.org/10.1073/pnas.1217154110), we identified 1132 novel periodic genes. Through the functional analysis of these novel circadian genes, we found that the GTPase superfamily exhibits distinct circadian expression patterns and may provide a molecular switch of circadian control of the functioning of the immune system in human blood. Our study provides novel insights into both the circadian gene identification field and the study of complex circadian-driven biological

  12. Experience-independent development of the hamster circadian visual system.

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    August Kampf-Lassin

    2011-04-01

    Full Text Available Experience-dependent functional plasticity is a hallmark of the primary visual system, but it is not known if analogous mechanisms govern development of the circadian visual system. Here we investigated molecular, anatomical, and behavioral consequences of complete monocular light deprivation during extended intervals of postnatal development in Syrian hamsters. Hamsters were raised in constant darkness and opaque contact lenses were applied shortly after eye opening and prior to the introduction of a light-dark cycle. In adulthood, previously-occluded eyes were challenged with visual stimuli. Whereas image-formation and motion-detection were markedly impaired by monocular occlusion, neither entrainment to a light-dark cycle, nor phase-resetting responses to shifts in the light-dark cycle were affected by prior monocular deprivation. Cholera toxin-b subunit fluorescent tract-tracing revealed that in monocularly-deprived hamsters the density of fibers projecting from the retina to the suprachiasmatic nucleus (SCN was comparable regardless of whether such fibers originated from occluded or exposed eyes. In addition, long-term monocular deprivation did not attenuate light-induced c-Fos expression in the SCN. Thus, in contrast to the thalamocortical projections of the primary visual system, retinohypothalamic projections terminating in the SCN develop into normal adult patterns and mediate circadian responses to light largely independent of light experience during development. The data identify a categorical difference in the requirement for light input during postnatal development between circadian and non-circadian visual systems.

  13. Human circadian phase estimation from signals collected in ambulatory conditions using an autoregressive model

    NARCIS (Netherlands)

    Gil, Enrique A; Aubert, Xavier L; Møst, Els I S; Beersma, Domien G M

    Phase estimation of the human circadian rhythm is a topic that has been explored using various modeling approaches. The current models range from physiological to mathematical, all attempting to estimate the circadian phase from different physiological or behavioral signals. Here, we have focused on

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

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    Tung T Nguyen

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

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

    Science.gov (United States)

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

    2018-05-22

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

  16. Circadian System and Melatonin Hormone: Risk Factors for Complications during Pregnancy

    Directory of Open Access Journals (Sweden)

    F. J. Valenzuela

    2015-01-01

    Full Text Available Pregnancy is a complex and well-regulated temporal event in which several steps are finely orchestrated including implantation, decidualization, placentation, and partum and any temporary alteration has serious effects on fetal and maternal health. Interestingly, alterations of circadian rhythms (i.e., shiftwork have been correlated with increased risk of preterm delivery, intrauterine growth restriction, and preeclampsia. In the last few years evidence is accumulating that the placenta may have a functional circadian system and express the clock genes Bmal1, Per1-2, and Clock. On the other hand, there is evidence that the human placenta synthesizes melatonin, hormone involved in the regulation of the circadian system in other tissues. Moreover, is unknown the role of this local production of melatonin and whether this production have a circadian pattern. Available information indicates that melatonin induces in placenta the expression of antioxidant enzymes catalase and superoxide dismutase, prevents the injury produced by oxidative stress, and inhibits the expression of vascular endothelial growth factor (VEGF a gene that in other tissues is controlled by clock genes. In this review we aim to analyze available information regarding clock genes and clock genes controlled genes such as VEGF and the possible role of melatonin synthesis in the placenta.

  17. Relationships between the circadian system and Alzheimer's disease-like symptoms in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dani M Long

    Full Text Available Circadian clocks coordinate physiological, neurological, and behavioral functions into circa 24 hour rhythms, and the molecular mechanisms underlying circadian clock oscillations are conserved from Drosophila to humans. Clock oscillations and clock-controlled rhythms are known to dampen during aging; additionally, genetic or environmental clock disruption leads to accelerated aging and increased susceptibility to age-related pathologies. Neurodegenerative diseases, such as Alzheimer's disease (AD, are associated with a decay of circadian rhythms, but it is not clear whether circadian disruption accelerates neuronal and motor decline associated with these diseases. To address this question, we utilized transgenic Drosophila expressing various Amyloid-β (Aβ peptides, which are prone to form aggregates characteristic of AD pathology in humans. We compared development of AD-like symptoms in adult flies expressing Aβ peptides in the wild type background and in flies with clocks disrupted via a null mutation in the clock gene period (per01. No significant differences were observed in longevity, climbing ability and brain neurodegeneration levels between control and clock-deficient flies, suggesting that loss of clock function does not exacerbate pathogenicity caused by human-derived Aβ peptides in flies. However, AD-like pathologies affected the circadian system in aging flies. We report that rest/activity rhythms were impaired in an age-dependent manner. Flies expressing the highly pathogenic arctic Aβ peptide showed a dramatic degradation of these rhythms in tune with their reduced longevity and impaired climbing ability. At the same time, the central pacemaker remained intact in these flies providing evidence that expression of Aβ peptides causes rhythm degradation downstream from the central clock mechanism.

  18. Circadian rhythms, metabolism, and chrononutrition in rodents and humans

    Science.gov (United States)

    Chrononutrition is an emerging discipline that builds on the intimate relation between endogenous circadian (24-h) rhythms and metabolism. Circadian regulation of metabolic function can be observed from the level of intracellular biochemistry to whole-organism physiology and even postprandial respon...

  19. Entrainment of the circadian clock in humans: mechanism and implications for sleep disorders.

    Directory of Open Access Journals (Sweden)

    David Metcalfe

    2007-01-01

    Full Text Available Humans exhibit behaviour and physiology controlled by a circadian clock. The circadian period is genetically determined and administered by a series of interlocked autoregulatory feedback loops largely in the suprachiasmatic nuclei of the hypothalamus. The phase of the clock is, however, synchronised by a number of external environmental cues such as light. A failure or change in any one of the requisite clock components may result in the onset of a long-term sleep disorder. This review discusses the mechanism regulating circadian physiology in humans and explores how disturbances of this mechanism may result in sleep pathologies.

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

    Science.gov (United States)

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

    2015-01-01

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

  1. Evolution of circadian rhythms: from bacteria to human.

    Science.gov (United States)

    Bhadra, Utpal; Thakkar, Nirav; Das, Paromita; Pal Bhadra, Manika

    2017-07-01

    The human body persists in its rhythm as per its initial time zone, and transition always occur according to solar movements around the earth over 24 h. While traveling across different latitudes and longitudes, at the pace exceeding the earth's movement, the changes in the external cues exceed the level of toleration of the body's biological clock. This poses an alteration in our physiological activities of sleep-wake pattern, mental alertness, organ movement, and eating habits, causing them to temporarily lose the track of time. This is further re-synchronized with the physiological cues of the destination over time. The mechanism of resetting of the clocks with varying time zones and cues occur in organisms from bacteria to humans. It is the result of the evolution of different pathways and molecular mechanisms over the time. There has been evolution of numerous comprehensive mechanisms using various research tools to get a deeper insight into the rapid turnover of molecular mechanisms in various species. This review reports insights into the evolution of the circadian mechanism and its evolutionary shift which is vital and plays a major role in assisting different organisms to adapt in different zones and controls their internal biological clocks with changing external cues. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-02-01

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

  3. The Effects of Spaceflight on the Rat Circadian Timing System

    Science.gov (United States)

    Fuller, Charles A.; Murakami, Dean M.; Hoban-Higgins, Tana M.; Fuller, Patrick M.; Robinson, Edward L.; Tang, I.-Hsiung

    2003-01-01

    Two fundamental environmental influences that have shaped the evolution of life on Earth are gravity and the cyclic changes occurring over the 24-hour day. Light levels, temperature, and humidity fluctuate over the course of a day, and organisms have adapted to cope with these variations. The primary adaptation has been the evolution of a biological timing system. Previous studies have suggested that this system, named the circadian (circa - about; dies - a day) timing system (CTS), may be sensitive to changes in gravity. The NASA Neurolab spaceflight provided a unique opportunity to evaluate the effects of microgravity on the mammalian CTS. Our experiment tested the hypotheses that microgravity would affect the period, phasing, and light sensitivity of the CTS. Twenty-four Fisher 344 rats were exposed to 16 days of microgravity on the Neurolab STS-90 mission, and 24 Fisher 344 rats were also studied on Earth as one-G controls. Rats were equipped with biotelemetry transmitters to record body temperature (T(sub b)) and heart rate (HR) continuously while the rats moved freely. In each group, 18 rats were exposed to a 24-hour light-dark (LD 12:12) cycle, and six rats were exposed to constant dim red-light (LL). The ability of light to induce a neuronal activity marker (c-fos) in the circadian pacemaker of the brain, the suprachiasmatic nucleus (SCN), was examined in rats studied on flight days two (FD2) and 14 (FD14), and postflight days two (R+1) and 14 (R+13). The flight rats in LD remained synchronized with the LD cycle. However, their T(sub b), rhythm was markedly phase-delayed relative to the LD cycle. The LD flight rats also had a decreased T(sub b) and a change in the waveform of the T(sub b) rhythm compared to controls. Rats in LL exhibited free-running rhythms of T(sub b), and HR; however, the periods were longer in microgravity. Circadian period returned to preflight values after landing. The internal phase angle between rhythms was different in flight than

  4. Preliminary evidence for a change in spectral sensitivity of the circadian system at night

    Directory of Open Access Journals (Sweden)

    Parsons Robert H

    2005-12-01

    Full Text Available Abstract Background It is well established that the absolute sensitivity of the suprachiasmatic nucleus to photic stimulation received through the retino-hypothalamic tract changes throughout the 24-hour day. It is also believed that a combination of classical photoreceptors (rods and cones and melanopsin-containing retinal ganglion cells participate in circadian phototransduction, with a spectral sensitivity peaking between 440 and 500 nm. It is still unknown, however, whether the spectral sensitivity of the circadian system also changes throughout the solar day. Reported here is a new study that was designed to determine whether the spectral sensitivity of the circadian retinal phototransduction mechanism, measured through melatonin suppression and iris constriction, varies at night. Methods Human adult males were exposed to a high-pressure mercury lamp [450 lux (170 μW/cm2 at the cornea] and an array of blue light emitting diodes [18 lux (29 μW/cm2 at the cornea] during two nighttime experimental sessions. Both melatonin suppression and iris constriction were measured during and after a one-hour light exposure just after midnight and just before dawn. Results An increase in the percentage of melatonin suppression and an increase in pupil constriction for the mercury source relative to the blue light source at night were found, suggesting a temporal change in the contribution of photoreceptor mechanisms leading to melatonin suppression and, possibly, iris constriction by light in humans. Conclusion The preliminary data presented here suggest a change in the spectral sensitivity of circadian phototransduction mechanisms at two different times of the night. These findings are hypothesized to be the result of a change in the sensitivity of the melanopsin-expressing retinal ganglion cells to light during the night.

  5. Circadian timekeeping : from basic clock function to implications for health

    NARCIS (Netherlands)

    Lucassen, Eliane Alinda

    2016-01-01

    In modern society, circadian rhythms and sleep are often disturbed, which may negatively affect health. This thesis examines these associations and focuses on the basic functioning of sleep and the circadian system in mice and in humans. Circadian rhythms are orchestrated by ~20,000 neurons in the

  6. The clock is ticking. Ageing of the circadian system: From physiology to cell cycle.

    Science.gov (United States)

    Terzibasi-Tozzini, Eva; Martinez-Nicolas, Antonio; Lucas-Sánchez, Alejandro

    2017-10-01

    The circadian system is the responsible to organise the internal temporal order in relation to the environment of every process of the organisms producing the circadian rhythms. These rhythms have a fixed phase relationship among them and with the environment in order to optimise the available energy and resources. From a cellular level, circadian rhythms are controlled by genetic positive and negative auto-regulated transcriptional and translational feedback loops, which generate 24h rhythms in mRNA and protein levels of the clock components. It has been described about 10% of the genome is controlled by clock genes, with special relevance, due to its implications, to the cell cycle. Ageing is a deleterious process which affects all the organisms' structures including circadian system. The circadian system's ageing may produce a disorganisation among the circadian rhythms, arrhythmicity and, even, disconnection from the environment, resulting in a detrimental situation to the organism. In addition, some environmental conditions can produce circadian disruption, also called chronodisruption, which may produce many pathologies including accelerated ageing. Finally, some strategies to prevent, palliate or counteract chronodisruption effects have been proposed to enhance the circadian system, also called chronoenhancement. This review tries to gather recent advances in the chronobiology of the ageing process, including cell cycle, neurogenesis process and physiology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Circadian rhythms and reproduction.

    Science.gov (United States)

    Boden, Michael J; Kennaway, David J

    2006-09-01

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

  8. Circadian rhythm and its role in malignancy

    Directory of Open Access Journals (Sweden)

    Mahmood Saqib

    2010-03-01

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

  9. Recent Advances in Circadian Rhythms in Cardiovascular System

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    Lihong eChen

    2015-04-01

    Full Text Available Growing evidence shows that intrinsic circadian clocks are tightly related to cardiovascular functions. The diurnal changes in blood pressure and heart rate are well known circadian rhythms. Endothelial function, platelet aggregation and thrombus formation exhibit circadian changes as well. The onset of many cardiovascular diseases (CVDs or events, such as myocardial infarction, stroke, arrhythmia, and sudden cardiac death, also exhibits temporal trends. Furthermore, there is strong evidence from animal models and epidemiological studies showing that disruption of circadian rhythms is a significant risk factor for many CVDs, and the intervention of CVDs may have a time dependent effect. In this mini review, we summarized recent advances in our understanding of the relationship between circadian rhythm and cardiovascular physiology and diseases including blood pressure regulation and myocardial infarction.

  10. l-Serine Enhances Light-Induced Circadian Phase Resetting in Mice and Humans.

    Science.gov (United States)

    Yasuo, Shinobu; Iwamoto, Ayaka; Lee, Sang-Il; Ochiai, Shotaro; Hitachi, Rina; Shibata, Satomi; Uotsu, Nobuo; Tarumizu, Chie; Matsuoka, Sayuri; Furuse, Mitsuhiro; Higuchi, Shigekazu

    2017-12-01

    Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood. Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans. Methods: Male CBA/N mice were orally administered 1 of 20 l-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before l-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of l-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase. Results: l-Serine administration enhanced light-induced phase shifts in mice (1.86-fold; P light-dark cycle by 6 h, l-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, l-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-l-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances. © 2017 American Society for Nutrition.

  11. The physiological period length of the human circadian clock in vivo is directly proportional to period in human fibroblasts.

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    Lucia Pagani

    Full Text Available BACKGROUND: Diurnal behavior in humans is governed by the period length of a circadian clock in the suprachiasmatic nuclei of the brain hypothalamus. Nevertheless, the cell-intrinsic mechanism of this clock is present in most cells of the body. We have shown previously that for individuals of extreme chronotype ("larks" and "owls", clock properties measured in human fibroblasts correlated with extreme diurnal behavior. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have measured circadian period in human primary fibroblasts taken from normal individuals and, for the first time, compared it directly with physiological period measured in vivo in the same subjects. Human physiological period length was estimated via the secretion pattern of the hormone melatonin in two different groups of sighted subjects and one group of totally blind subjects, each using different methods. Fibroblast period length was measured via cyclical expression of a lentivirally delivered circadian reporter. Within each group, a positive linear correlation was observed between circadian period length in physiology and in fibroblast gene expression. Interestingly, although blind individuals showed on average the same fibroblast clock properties as sighted ones, their physiological periods were significantly longer. CONCLUSIONS/SIGNIFICANCE: We conclude that the period of human circadian behaviour is mostly driven by cellular clock properties in normal individuals and can be approximated by measurement in peripheral cells such as fibroblasts. Based upon differences among sighted and blind subjects, we also speculate that period can be modified by prolonged unusual conditions such as the total light deprivation of blindness.

  12. Software tools for data modelling and processing of human body temperature circadian dynamics.

    Science.gov (United States)

    Petrova, Elena S; Afanasova, Anastasia I

    2015-01-01

    This paper is presenting a software development for simulating and processing thermometry data. The motivation of this research is the miniaturization of actuators attached to human body which allow frequent temperature measurements and improve the medical diagnosis procedures related to circadian dynamics.

  13. The Progression of Circadian Phase during Light Exposure in Animals and Humans

    NARCIS (Netherlands)

    Beersma, Domien G. M.; Comas, Marian; Hut, Roelof A.; Gordijn, Marijke C. M.; Rueger, Melanie; Daan, Serge

    Studies in humans and mice revealed that circadian phase shifting effects of light are larger at the beginning of a light exposure interval than during subsequent exposure. Little is known about the dynamics of this response reduction phenomenon. Here the authors propose a method to obtain

  14. Acute and phase-shifting effects of ocular and extraocular light in human circadian physiology

    NARCIS (Netherlands)

    Rüger, Melanie; Gordijn, Marijke C.M.; Beersma, Domien G.M.; de Vries, Bonnie; Daan, Serge

    2003-01-01

    Light can influence physiology and performance of humans in two distinct ways. It can acutely change the level of physiological and behavioral parameters, and it can induce a phase shift in the circadian oscillators underlying variations in these levels. Until recently, both effects were thought to

  15. Interdependence of nutrient metabolism and the circadian clock system: Importance for metabolic health

    Science.gov (United States)

    Ribas-Latre, Aleix; Eckel-Mahan, Kristin

    2016-01-01

    Background While additional research is needed, a number of large epidemiological studies show an association between circadian disruption and metabolic disorders. Specifically, obesity, insulin resistance, cardiovascular disease, and other signs of metabolic syndrome all have been linked to circadian disruption in humans. Studies in other species support this association and generally reveal that feeding that is not in phase with the external light/dark cycle, as often occurs with night or rotating shift workers, is disadvantageous in terms of energy balance. As food is a strong driver of circadian rhythms in the periphery, understanding how nutrient metabolism drives clocks across the body is important for dissecting out why circadian misalignment may produce such metabolic effects. A number of circadian clock proteins as well as their accessory proteins (such as nuclear receptors) are highly sensitive to nutrient metabolism. Macronutrients and micronutrients can function as zeitgebers for the clock in a tissue-specific way and can thus impair synchrony between clocks across the body, or potentially restore synchrony in the case of circadian misalignment. Circadian nuclear receptors are particularly sensitive to nutrient metabolism and can alter tissue-specific rhythms in response to changes in the diet. Finally, SNPs in human clock genes appear to be correlated with diet-specific responses and along with chronotype eventually may provide valuable information from a clinical perspective on how to use diet and nutrition to treat metabolic disorders. Scope of review This article presents a background of the circadian clock components and their interrelated metabolic and transcriptional feedback loops, followed by a review of some recent studies in humans and rodents that address the effects of nutrient metabolism on the circadian clock and vice versa. We focus on studies in which results suggest that nutrients provide an opportunity to restore or, alternatively

  16. Circadian phase assessment by ambulatory monitoring in humans: correlation with dim light melatonin onset.

    Science.gov (United States)

    Bonmati-Carrion, M A; Middleton, B; Revell, V; Skene, D J; Rol, M A; Madrid, J A

    2014-02-01

    The increased prevalence of circadian disruptions due to abnormal coupling between internal and external time makes the detection of circadian phase in humans by ambulatory recordings a compelling need. Here, we propose an accurate practical procedure to estimate circadian phase with the least possible burden for the subject, that is, without the restraints of a constant routine protocol or laboratory techniques such as melatonin quantification, both of which are standard procedures. In this validation study, subjects (N = 13) wore ambulatory monitoring devices, kept daily sleep diaries and went about their daily routine for 10 days. The devices measured skin temperature at wrist level (WT), motor activity and body position on the arm, and light exposure by means of a sensor placed on the chest. Dim light melatonin onset (DLMO) was used to compare and evaluate the accuracy of the ambulatory variables in assessing circadian phase. An evening increase in WT: WTOnset (WTOn) and "WT increase onset" (WTiO) was found to anticipate the evening increase in melatonin, while decreases in motor activity (Activity Offset or AcOff), body position (Position Offset (POff)), integrative TAP (a combination of WT, activity and body position) (TAPOffset or TAPOff) and an increase in declared sleep propensity were phase delayed with respect to DLMO. The phase markers obtained from subjective sleep (R = 0.811), WT (R = 0.756) and the composite variable TAP (R = 0.720) were highly and significantly correlated with DLMO. The findings strongly support a new method to calculate circadian phase based on WT (WTiO) that accurately predicts and shows a temporal association with DLMO. WTiO is especially recommended due to its simplicity and applicability to clinical use under conditions where knowing endogenous circadian phase is important, such as in cancer chronotherapy and light therapy.

  17. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression

    Science.gov (United States)

    Zeitzer, J. M.; Dijk, D. J.; Kronauer, R.; Brown, E.; Czeisler, C.

    2000-01-01

    Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.

  18. The state of immune system circadian rhythms in rats at exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Kuz'menko, O.V.; Nyikyiforova, N.A.; Yivanenko, M.O.

    2010-01-01

    Circadian rhythms of the immune system parameters restoration in rats with different response to stress, exposed to single total irradiation at dose of 6 Gy at various time of the day was investigated.

  19. The effects of gender on circadian rhythm of human physiological indexes in high temperature environment

    Science.gov (United States)

    Zheng, G. Z.; Li, K.; Bu, W. T.; Lu, Y. Z.; Wang, Y. J.

    2018-03-01

    In the context of frequent high temperature weather in recent years, peoples’ physical health is seriously threatened by the indoor high temperature. The physiological activities of human body show a certain changes of circadian rhythm. In this paper, the circadian rhythms of the physiological indexes in indoor high temperature environment were quantified and compared between the male subjects and female subjects. Ten subjects (five males and five females) were selected. The temperature conditions were set at 28°C, 32°C, 36°C and 38°C, respectively. The blood pressure, heart rate, rectal temperature, eardrum temperature, forehead temperature and mean skin temperature were measured for 24 hours continuously. The medians, amplitudes and acrophases of the circadian rhythms were obtained by the cosinor analysis method. Then the effects of gender on the circadian rhythm of the human body in high temperature environment were analyzed. The results indicate that, compared with the female subjects, the male medians of the systolic pressure and diastolic pressure were higher, and the male medians of heart rate and rectal temperature were lower, however, no significant differences were found between eardrum temperature, forehead temperature and mean skin temperature. This study can provide scientific basis for the health protection of the indoor relevant personnel.

  20. Nighttime dim light exposure alters the responses of the circadian system.

    Science.gov (United States)

    Shuboni, D; Yan, L

    2010-11-10

    The daily light dark cycle is the most salient entraining factor for the circadian system. However, in modern society, darkness at night is vanishing as light pollution steadily increases. The impact of brighter nights on wild life ecology and human physiology is just now being recognized. In the present study, we tested the possible detrimental effects of dim light exposure on the regulation of circadian rhythms, using CD1 mice housed in light/dim light (LdimL, 300 lux:20 lux) or light/dark (LD, 300 lux:1 lux) conditions. We first examined the expression of clock genes in the suprachiasmatic nucleus (SCN), the locus of the principal brain clock, in the animals of the LD and LdimL groups. Under the entrained condition, there was no difference in PER1 peak expression between the two groups, but at the trough of the PER 1 rhythm, there was an increase in PER1 in the LdimL group, indicating a decrease in the amplitude of the PER1 rhythm. After a brief light exposure (30 min, 300 lux) at night, the light-induced expression of mPer1 and mPer2 genes was attenuated in the SCN of LdimL group. Next, we examined the behavioral rhythms by monitoring wheel-running activity to determine whether the altered responses in the SCN of LdimL group have behavioral consequence. Compared to the LD controls, the LdimL group showed increased daytime activity. After being released into constant darkness, the LdimL group displayed shorter free-running periods. Furthermore, following the light exposure, the phase shifting responses were smaller in the LdimL group. The results indicate that nighttime dim light exposure can cause functional changes of the circadian system, and suggest that altered circadian function could be one of the mechanisms underlying the adverse effects of light pollution on wild life ecology and human physiology. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Endogenous Circadian Regulation of Pro-inflammatory Cytokines and Chemokines in the Presence of Bacterial Lipopolysaccharide in Humans

    Science.gov (United States)

    Rahman, Shadab A.; Castanon-Cervantes, Oscar; Scheer, Frank A.J.L.; Shea, Steven A.; Czeisler, Charles A.; Davidson, Alec J.; Lockley, Steven W.

    2015-01-01

    Various aspects of immune response exhibit 24-hour variations suggesting that infection susceptibility and treatment efficacy may vary by time of day. Whether these 24-hour variations are endogenous or evoked by changes in environmental or behavioral conditions is not known. We assessed the endogenous circadian control and environmental and behavioral influences on ex-vivo lipopolysaccharide stimulation of whole blood in thirteen healthy participants under 48 hours of baseline conditions with standard sleep-wake schedules and 40–50 hours of constant environmental and behavioral (constant routine; CR) conditions. Significant 24-hour rhythms were observed under baseline conditions in Monocyte Chemotactic Protein, Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin 8 but not Tumor Necrosis Factor alpha whereas significant 24-hour rhythms were observed in all four immune factors under CR conditions. The rhythm amplitudes, expressed as a percentage of mean, were comparable between immune factors and across conditions. In contrast, the acrophase time (time of the fitted peak) was different between immune factors, and included daytime and nighttime peaks and changes across behavioral conditions. These results suggest that the endogenous circadian system underpins the temporal organization of immune responses in humans with additional effects of external environmental and behavioral cycles. These findings have implications for understanding the adverse effects of recurrent circadian disruption and sleep curtailment on immune function. PMID:25452149

  2. Influence of Electric, Magnetic, and Electromagnetic Fields on the Circadian System: Current Stage of Knowledge

    Science.gov (United States)

    Żak, Arkadiusz

    2014-01-01

    One of the side effects of each electrical device work is the electromagnetic field generated near its workplace. All organisms, including humans, are exposed daily to the influence of different types of this field, characterized by various physical parameters. Therefore, it is important to accurately determine the effects of an electromagnetic field on the physiological and pathological processes occurring in cells, tissues, and organs. Numerous epidemiological and experimental data suggest that the extremely low frequency magnetic field generated by electrical transmission lines and electrically powered devices and the high frequencies electromagnetic radiation emitted by electronic devices have a potentially negative impact on the circadian system. On the other hand, several studies have found no influence of these fields on chronobiological parameters. According to the current state of knowledge, some previously proposed hypotheses, including one concerning the key role of melatonin secretion disruption in pathogenesis of electromagnetic field induced diseases, need to be revised. This paper reviews the data on the effect of electric, magnetic, and electromagnetic fields on melatonin and cortisol rhythms—two major markers of the circadian system as well as on sleep. It also provides the basic information about the nature, classification, parameters, and sources of these fields. PMID:25136557

  3. Human seasonal and circadian studies in Antarctica (Halley, 75°S).

    Science.gov (United States)

    Arendt, Josephine; Middleton, Benita

    2018-03-01

    Living for extended periods in Antarctica exposes base personnel to extremes of daylength (photoperiod) and temperature. At the British Antarctic Survey base of Halley, 75°S, the sun does not rise for 110 d in the winter and does not set for 100 d in summer. Photoperiod is the major time cue governing the timing of seasonal events such as reproduction in many species. The neuroendocrine signal providing photoperiodic information to body physiology is the duration of melatonin secretion which reflects the length of the night: longer in the short days of winter and shorter in summer. Light of sufficient intensity and spectral composition serves to suppress production of melatonin and to set the circadian timing and the duration of the rhythm. In humans early observations suggested that bright (>2000 lux) white light was needed to suppress melatonin completely. Shortly thereafter winter depression (Seasonal Affective Disorder or SAD) was described, and its successful treatment by an artificial summer photoperiod of bright white light, sufficient to shorten melatonin production. At Halley dim artificial light intensity during winter was measured, until 2003, at a maximum of approximately 500 lux in winter. Thus a strong seasonal and circadian time cue was absent. It seemed likely that winter depression would be common in the extended period of winter darkness and could be treated with an artificial summer photoperiod. These observations, and predictions, inspired a long series of studies regarding human seasonal and circadian status, and the effects of light treatment, in a small overwintering, isolated community, living in the same conditions for many months at Halley. We found little evidence of SAD, or change in duration of melatonin production with season. However the timing of the melatonin rhythm itself, and/or that of its metabolite 6-sulphatoxymelatonin (aMT6s), was used as a primary marker of seasonal, circadian and treatment changes. A substantial phase

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

    Science.gov (United States)

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

    2018-05-13

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

  5. Development of a Low-cost, Comprehensive Recording System for Circadian Rhythm Behavior.

    Science.gov (United States)

    Kwon, Jea; Park, Min Gu; Lee, Seung Eun; Lee, C Justin

    2018-02-01

    Circadian rhythm is defined as a 24-hour biological oscillation, which persists even without any external cues but also can be re-entrained by various environmental cues. One of the widely accepted circadian rhythm behavioral experiment is measuring the wheel-running activity (WRA) of rodents. However, the price for commercially available WRA recording system is not easily affordable for researchers due to high-cost implementation of sensors for wheel rotation. Here, we developed a cost-effective and comprehensive system for circadian rhythm recording by measuring the house-keeping activities (HKA). We have monitored animal's HKA as electrical signal by simply connecting animal housing cage with a standard analog/digital converter: input to the metal lid and ground to the metal grid floor. We show that acquired electrical signals are combined activities of eating, drinking and natural locomotor behaviors which are well-known indicators of circadian rhythm. Post-processing of measured electrical signals enabled us to draw actogram, which verifies HKA to be reliable circadian rhythm indicator. To provide easy access of HKA recording system for researchers, we have developed user-friendly MATLAB-based software, Circa Analysis. This software provides functions for easy extraction of scalable "touch activity" from raw data files by automating seven steps of post-processing and drawing actograms with highly intuitive user-interface and various options. With our cost-effective HKA circadian rhythm recording system, we have estimated the cost of our system to be less than $150 per channel. We anticipate our system will benefit many researchers who would like to study circadian rhythm.

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

    Science.gov (United States)

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

    2015-11-01

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

  7. Proteomics of the photoneuroendocrine circadian system of the brain

    DEFF Research Database (Denmark)

    Møller, Morten; Lund-Andersen, Casper; Rovsing, Louise

    2010-01-01

    controls circadian activity of the brain and peripheral tissues. The endogenous oscillator of the SCN is each day entrained to the length of the daily photoperiod by light that reach the retina, and specialized photoreceptors transmit impulses to the SCN via the optic nerves. Mass screening for day...

  8. Circadian variation of EEG power spectra in NREM and REM sleep in humans: dissociation from body temperature

    Science.gov (United States)

    Dijk, D. J.

    1999-01-01

    In humans, EEG power spectra in REM and NREM sleep, as well as characteristics of sleep spindles such as their duration, amplitude, frequency and incidence, vary with circadian phase. Recently it has been hypothesized that circadian variations in EEG spectra in humans are caused by variations in brain or body temperature and may not represent phenomena relevant to sleep regulatory processes. To test this directly, a further analysis of EEG power spectra - collected in a forced desynchrony protocol in which sleep episodes were scheduled to a 28-h period while the rhythms of body temperature and plasma melatonin were oscillating at their near 24-h period - was carried out. EEG power spectra were computed for NREM and REM sleep occurring between 90-120 and 270-300 degrees of the circadian melatonin rhythm, i.e. just after the clearance of melatonin from plasma in the 'morning' and just after the 'evening' increase in melatonin secretion. Average body temperatures during scheduled sleep at these two circadian phases were identical (36.72 degrees C). Despite identical body temperatures, the power spectra in NREM sleep were very different at these two circadian phases. EEG activity in the low frequency spindle range was significantly and markedly enhanced after the evening increase in plasma melatonin as compared to the morning phase. For REM sleep, significant differences in power spectra during these two circadian phases, in particular in the alpha range, were also observed. The results confirm that EEG power spectra in NREM and REM sleep vary with circadian phase, suggesting that the direct contribution of temperature to the circadian variation in EEG power spectra is absent or only minor, and are at variance with the hypothesis that circadian variations in EEG power spectra are caused by variations in temperature.

  9. Redox regulation and pro-oxidant reactions in the physiology of circadian systems.

    Science.gov (United States)

    Méndez, Isabel; Vázquez-Martínez, Olivia; Hernández-Muñoz, Rolando; Valente-Godínez, Héctor; Díaz-Muñoz, Mauricio

    2016-05-01

    Rhythms of approximately 24 h are pervasive in most organisms and are known as circadian. There is a molecular circadian clock in each cell sustained by a feedback system of interconnected "clock" genes and transcription factors. In mammals, the timing system is formed by a central pacemaker, the suprachiasmatic nucleus, in coordination with a collection of peripheral oscillators. Recently, an extensive interconnection has been recognized between the molecular circadian clock and the set of biochemical pathways that underlie the bioenergetics of the cell. A principle regulator of metabolic networks is the flow of electrons between electron donors and acceptors. The concomitant reduction and oxidation (redox) reactions directly influence the balance between anabolic and catabolic processes. This review summarizes and discusses recent findings concerning the mutual and dynamic interactions between the molecular circadian clock, redox reactions, and redox signaling. The scope includes the regulatory role played by redox coenzymes (NAD(P)+/NAD(P)H, GSH/GSSG), reactive oxygen species (superoxide anion, hydrogen peroxide), antioxidants (melatonin), and physiological events that modulate the redox state (feeding condition, circadian rhythms) in determining the timing capacity of the molecular circadian clock. In addition, we discuss a purely metabolic circadian clock, which is based on the redox enzymes known as peroxiredoxins and is present in mammalian red blood cells and in other biological systems. Both the timing system and the metabolic network are key to a better understanding of widespread pathological conditions such as the metabolic syndrome, obesity, and diabetes. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

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

    Science.gov (United States)

    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.

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

    OpenAIRE

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

    2010-01-01

    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 ...

  12. [Effect of Earth magnetic field on circadian rhythm of total antioxidant capacity of human saliva in the North].

    Science.gov (United States)

    Borisenkov, M F

    2007-01-01

    In the inhabitants of the North during increase of geomagnetic activity and during magnetic calm the decrease of amplitude of circadian rhythm of total antioxidant capacity of saliva is observed. The most favorable conditions to display the circadian rhythm are observed at Kp from 0,5 up to 2. The long residing in the North is connected to influence of irregularly varying geomagnetic activity causing disturbance of function of circadian and antioxidant systems that, probably, is one of the reasons of acceleration of process of aging at northerner and of higher risk of occurrence in them the age associated diseases.

  13. Peripheral circadian misalignment: contributor to systemic insulin resistance and potential intervention to improve bariatric surgical outcomes

    Science.gov (United States)

    Kunze, Kyle N.; Hanlon, Erin C.; Prachand, Vivek N.

    2016-01-01

    Thirteen percent of the world's population suffers from obesity and 39% from being overweight, which correlates with an increase in numerous secondary metabolic complications, such as Type 2 diabetes mellitus. Bariatric surgery is the most effective treatment for severe obesity and results in significant weight loss and the amelioration of obesity-related comorbidities through changes in enteroendocrine activity, caloric intake, and alterations in gut microbiota composition. The circadian system has recently been found to be a critical regulatory component in the control of metabolism and, thus, may potentially play an important role in inappropriate weight gain. Indeed, some behaviors and lifestyle factors associated with an increased risk of obesity are also risk factors for misalignment in the circadian clock system and for the metabolic syndrome. It is thus possible that alterations in peripheral circadian clocks in metabolically relevant tissues are a contributor to the current obesity epidemic. As such, it is plausible that postsurgical alterations in central circadian alignment, as well as peripheral gene expression in metabolic tissues may represent another mechanism for the beneficial effects of bariatric surgery. Bariatric surgery may represent an opportunity to identify changes in the circadian expression of clock genes that have been altered by environmental factors, allowing for a better understanding of the mechanism of action of surgery. These studies could also reveal an overlooked target for behavioral intervention to improve metabolic outcomes following bariatric surgery. PMID:27465735

  14. An evolutionary fitness enhancement conferred by the circadian system in cyanobacteria

    International Nuclear Information System (INIS)

    Ma, Peijun; Woelfle, Mark A.; Johnson, Carl Hirschie

    2013-01-01

    Circadian clocks are found in a wide variety of organisms from cyanobacteria to mammals. Many believe that the circadian clock system evolved as an adaption to the daily cycles in light and temperature driven by the rotation of the earth. Studies on the cyanobacterium, Synechococcus elongatus PCC 7942, have confirmed that the circadian clock in resonance with environmental cycles confers an adaptive advantage to cyanobacterial strains with different clock properties when grown in competition under light–dark cycles. The results thus far suggest that in a cyclic environment, the cyanobacterial strains whose free running periods are closest to the environmental period are the most fit and the strains lacking a functional circadian clock are at a competitive disadvantage relative to strains with a functional clock. In contrast, the circadian system provides little or no advantage to cyanobacteria grown in competition in constant light. To explain the potential mechanism of this clock-mediated enhancement in fitness in cyanobacteria, several models have been proposed; these include the limiting resource model, the diffusible inhibitor model and the cell-to-cell communication model. None of these models have been excluded by the currently available experimental data and the mechanistic basis of clock-mediated fitness enhancement remains elusive

  15. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    and clocks driving such rhythms have been studied for a long time now, our ... passage of time using near 24 h oscillation as a reference process, and (iii) Output .... Bünning's work on circadian rhythms across model systems ranging from ..... E Bünning, The Physiological Clock, Revised 3rd Edition, The English. Universities ...

  16. The Circadian Timing System: Making Sense of day/night gene expression

    Directory of Open Access Journals (Sweden)

    HANS G RICHTER

    2004-01-01

    Full Text Available The circadian time-keeping system ensures predictive adaptation of individuals to the reproducible 24-h day/night alternations of our planet by generating the 24-h (circadian rhythms found in hormone release and cardiovascular, biophysical and behavioral functions, and others. In mammals, the master clock resides in the suprachiasmatic nucleus (SCN of the hypothalamus. The molecular events determining the functional oscillation of the SCN neurons with a period of 24-h involve recurrent expression of several clock proteins that interact in complex transcription/translation feedback loops. In mammals, a glutamatergic monosynaptic pathway originating from the retina regulates the clock gene expression pattern in the SCN neurons, synchronizing them to the light:dark cycle. The emerging concept is that neural/humoral output signals from the SCN impinge upon peripheral clocks located in other areas of the brain, heart, lung, gastrointestinal tract, liver, kidney, fibroblasts, and most of the cell phenotypes, resulting in overt circadian rhythms in integrated physiological functions. Here we review the impact of day/night alternation on integrated physiology; the molecular mechanisms and input/output signaling pathways involved in SCN circadian function; the current concept of peripheral clocks; and the potential role of melatonin as a circadian neuroendocrine transducer

  17. Disruption of Circadian Rhythms by Light During Day and Night.

    Science.gov (United States)

    Figueiro, Mariana G

    2017-06-01

    This study aims to discuss possible reasons why research to date has not forged direct links between light at night, acute melatonin suppression or circadian disruption, and risks for disease. Data suggest that irregular light-dark patterns or light exposures at the wrong circadian time can lead to circadian disruption and disease risks. However, there remains an urgent need to: (1) specify light stimulus in terms of circadian rather than visual response; (2) when translating research from animals to humans, consider species-specific spectral and absolute sensitivities to light; (3) relate the characteristics of photometric measurement of light at night to the operational characteristics of the circadian system; and (4) examine how humans may be experiencing too little daytime light, not just too much light at night. To understand the health effects of light-induced circadian disruption, we need to measure and control light stimulus during the day and at night.

  18. Circadian rhythm of blood pressure and the renin-angiotensin system in the kidney.

    Science.gov (United States)

    Ohashi, Naro; Isobe, Shinsuke; Ishigaki, Sayaka; Yasuda, Hideo

    2017-05-01

    Activation of the intrarenal renin-angiotensin system (RAS) has a critical role in the pathophysiology of the circadian rhythm of blood pressure (BP) and renal injury, independent of circulating RAS. Although it is clear that the circulating RAS has a circadian rhythm, reports of a circadian rhythm in tissue-specific RAS are limited. Clinical studies evaluating intrarenal RAS activity by urinary angiotensinogen (AGT) levels have indicated that urinary AGT levels were equally low during both the daytime and nighttime in individuals without chronic kidney disease (CKD) and that urinary AGT levels were higher during the daytime than at nighttime in patients with CKD. Moreover, urinary AGT levels of the night-to-day (N/D) ratio of urinary AGT were positively correlated with the levels of N/D of urinary protein, albumin excretion and BP. In addition, animal studies have demonstrated that the expression of intrarenal RAS components, such as AGT, angiotensin II (AngII) and AngII type 1 receptor proteins, increased and peaked at the same time as BP and urinary protein excretion during the resting phase, and the amplitude of the oscillations of these proteins was augmented in a chronic progressive nephritis animal compared with a control. Thus, the circadian rhythm of intrarenal RAS activation may lead to renal damage and hypertension, which both are associated with diurnal variations in BP. It is possible that augmented glomerular permeability increases AGT excretion levels into the tubular lumen and that circadian fluctuation of glomerular permeability influences the circadian rhythm of the intrarenal RAS.

  19. Circadian activity rhythms during the last days of Nothobranchius rachovii's life: a descriptive model of circadian system breakdown.

    Science.gov (United States)

    Lucas-Sánchez, Alejandro; Martínez-Nicolás, Antonio; Madrid, Juan Antonio; Almaida-Pagán, Pedro Francisco; Mendiola, Pilar; de Costa, Jorge

    2015-04-01

    Several studies have been performed to identify age-related changes in the circadian system (CS) but the impairment of the CS and its chronodisruption at the end of an organism life have not been studied in depth. Aging commonly affects the input pathways into the biological clock or restraints their processing, therefore simplifying the system output, the overt rhythms. The purpose of this work was to do a complete characterization of changes that occurs in the CS in the last stage of a vertebrate organism life and to develop tools able to detect in which moment of the last days of life is the animal, using an overt rhythm, the rest-activity rhythm (RAR). For that, a fish species proposed as model for aging studies, Nothobranchius rachovii, has been used. A progressive and sequential CS breakdown has been described for the last 22 d of life of N. rachovii (∼7% of total life), suffering a general RAR impairment mainly reflected by changes in phase regularity, complexity, amplitude and the ability to stay synchronized to the LD cycle. Also, an equation of days remaining of life, based on the RAR description, has been calculated and proposed as a tool to identify close-to-death individuals which could be subjected to an adequate restoring treatment to enhance the CS function and improve their well-being.

  20. Functional analysis of Casein Kinase 1 in a minimal circadian system.

    Directory of Open Access Journals (Sweden)

    Gerben van Ooijen

    Full Text Available The Earth's rotation has driven the evolution of cellular circadian clocks to facilitate anticipation of the solar cycle. Some evidence for timekeeping mechanism conserved from early unicellular life through to modern organisms was recently identified, but the components of this oscillator are currently unknown. Although very few clock components appear to be shared across higher species, Casein Kinase 1 (CK1 is known to affect timekeeping across metazoans and fungi, but has not previously been implicated in the circadian clock in the plant kingdom. We now show that modulation of CK1 function lengthens circadian rhythms in Ostreococcustauri, a unicellular marine algal species at the base of the green lineage, separated from humans by ~1.5 billion years of evolution. CK1 contributes to timekeeping in a phase-dependent manner, indicating clock-mediated gating of CK1 activity. Label-free proteomic analyses upon overexpression as well as inhibition revealed CK1-responsive phosphorylation events on a set of target proteins, including highly conserved potentially clock-relevant cellular regulator proteins. These results have major implications for our understanding of cellular timekeeping and can inform future studies in any circadian organism.

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

    Science.gov (United States)

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

    1988-01-01

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

  2. Circadian and ultradian components of hunger in human non-homeostatic meal-to-meal eating.

    Science.gov (United States)

    Wuorinen, Elizabeth C; Borer, Katarina T

    2013-10-02

    A unifying physiological explanation of the urge to initiate eating is still not available as human hunger in meal-to-meal eating may not be under homeostatic control. We hypothesized that a central circadian and a gastrointestinal ultradian timing mechanism coordinate non-deprivation meal-to-meal eating. We examined hunger as a function of time of day, inter-meal (IM) energy expenditure (EE), and concentrations of proposed hunger-controlling hormones ghrelin, leptin, and insulin. In two crossover studies, 10 postmenopausal women, BMI 23-26 kg/m(2) engaged in exercise (EX) and sedentary (SED) trials. Weight maintenance meals were provided at 6h intervals with an ad libitum meal at 13 h in study 1 and 21 h snack in study 2. EE during IM intervals was measured by indirect calorimetry and included EX EE of 801 kcal in study 1, and 766-1,051 kcal in study 2. Hunger was assessed with a visual analog scale and blood was collected for hormonal determination. Hunger displayed a circadian variation with acrophase at 13 and 19 h and was unrelated to preceding EE. Hunger was suppressed by EX between 10 and 16 h and bore no relationship to either EE during preceding IM intervals or changes in leptin, insulin, and ghrelin; however leptin reflected IM energy changes and ghrelin and insulin, prandial events. During non-deprivation meal-to-meal eating, hunger appears to be under non-homeostatic central circadian control as it is unrelated to EE preceding meals or concentrations of proposed appetite-controlling hormones. Gastrointestinal meal processing appears to intermittently suppress this control and entrain an ultradian hunger pattern. © 2013 Elsevier Inc. All rights reserved.

  3. Circadian Macronutrients Variations over the First 7 Weeks of Human Milk Feeding of Preterm Infants.

    Science.gov (United States)

    Moran-Lev, Hadar; Mimouni, Francis B; Ovental, Amit; Mangel, Laurence; Mandel, Dror; Lubetzky, Ronit

    2015-09-01

    Little is known about circadian variations of macronutrients content of expressed preterm human milk (HM). This study evaluated diurnal variations of macronutrients and energy content of preterm HM over the first 7 weeks of lactation and tested the hypothesis that values obtained during a morning sample are predictive of those obtained from an evening sample. Expressed HM was obtained from 32 mothers of preterm infants (26-33 weeks in gestational age), who routinely expressed all their milk every 3 hours from the beginning of the second to the seventh week after delivery. One aliquot was obtained from the first morning expression and the second from the evening expression. Energy and macronutrients contents were measured using an HM analyzer. Mean fat and energy contents of all samples obtained during the whole period were significantly higher in evening samples (p < 0.0001). There were no significant differences between morning and evening carbohydrates and protein contents. Concentrations of protein, carbohydrates, and fat from morning samples were predictive of evening concentrations to different extents (R(2) = 0.720, R(2) = 0.663, and R(2) = 0.20, respectively; p < 0.02). The predictability of evening values by morning values was not influenced by the week of lactation at sampling or by individual patients. In repeated-measures analysis of variance performed on 11 patients who completed the whole 7-week period, over time, there was a significant decrease in fat, energy, and protein contents, whereas carbohydrates content remained unchanged. Day-night differences remained significant only for fat content. Circadian variations in fat and energy concentrations of HM are consistent over the first 7 weeks of lactation. There are no consistent circadian variations in HM protein and carbohydrates. Over a given day, there are little variations in protein and carbohydrates content, but fat concentrations are more variable, and evening values are less well predicted by

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Ivan Ho Mien

    Full Text Available 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.

  6. A longitudinal assessment of sleep timing, circadian phase, and phase angle of entrainment across human adolescence.

    Directory of Open Access Journals (Sweden)

    Stephanie J Crowley

    Full Text Available The aim of this descriptive analysis was to examine sleep timing, circadian phase, and phase angle of entrainment across adolescence in a longitudinal study design. Ninety-four adolescents participated; 38 (21 boys were 9-10 years ("younger cohort" and 56 (30 boys were 15-16 years ("older cohort" at the baseline assessment. Participants completed a baseline and then follow-up assessments approximately every six months for 2.5 years. At each assessment, participants wore a wrist actigraph for at least one week at home to measure self-selected sleep timing before salivary dim light melatonin onset (DLMO phase - a marker of the circadian timing system - was measured in the laboratory. Weekday and weekend sleep onset and offset and weekend-weekday differences were derived from actigraphy. Phase angles were the time durations from DLMO to weekday sleep onset and offset times. Each cohort showed later sleep onset (weekend and weekday, later weekend sleep offset, and later DLMO with age. Weekday sleep offset shifted earlier with age in the younger cohort and later in the older cohort after age 17. Weekend-weekday sleep offset differences increased with age in the younger cohort and decreased in the older cohort after age 17. DLMO to sleep offset phase angle narrowed with age in the younger cohort and became broader in the older cohort. The older cohort had a wider sleep onset phase angle compared to the younger cohort; however, an age-related phase angle increase was seen in the younger cohort only. Individual differences were seen in these developmental trajectories. This descriptive study indicated that circadian phase and self-selected sleep delayed across adolescence, though school-day sleep offset advanced until no longer in high school, whereupon offset was later. Phase angle changes are described as an interaction of developmental changes in sleep regulation interacting with psychosocial factors (e.g., bedtime autonomy.

  7. Short wavelength light filtering by the natural human lens and IOLs -- implications for entrainment of circadian rhythm

    DEFF Research Database (Denmark)

    Brøndsted, Adam Elias; Lundeman, Jesper Holm; Kessel, Line

    2013-01-01

    Photoentrainment of circadian rhythm begins with the stimulation of melanopsin containing retinal ganglion cells that respond directly to blue light. With age, the human lens becomes a strong colour filter attenuating transmission of short wavelengths. The purpose of the study was to examine the ...

  8. IgE-dependent activation of human mast cells and fMLP-mediated activation of human eosinophils is controlled by the circadian clock.

    Science.gov (United States)

    Baumann, Anja; Feilhauer, Katharina; Bischoff, Stephan C; Froy, Oren; Lorentz, Axel

    2015-03-01

    Symptoms of allergic attacks frequently exhibit diurnal variations. Accordingly, we could recently demonstrate that mast cells and eosinophils - known as major effector cells of allergic diseases - showed an intact circadian clock. Here, we analyzed the role of the circadian clock in the functionality of mast cells and eosinophils. Human intestinal mast cells (hiMC) were isolated from intestinal mucosa; human eosinophils were isolated from peripheral blood. HiMC and eosinophils were synchronized by dexamethasone before stimulation every 4h around the circadian cycle by FcɛRI crosslinking or fMLP, respectively. Signaling molecule activation was examined using Western blot, mRNA expression by real-time RT-PCR, and mediator release by multiplex analysis. CXCL8 and CCL2 were expressed and released in a circadian manner by both hiMC and eosinophils in response to activation. Moreover, phosphorylation of ERK1/2, known to be involved in activation of hiMC and eosinophils, showed circadian rhythms in both cell types. Interestingly, all clock genes hPer1, hPer2, hCry1, hBmal1, and hClock were expressed in a similar circadian pattern in activated and unstimulated cells indicating that the local clock controls hiMC and eosinophils and subsequently allergic reactions but not vice versa. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. A dual-color luciferase assay system reveals circadian resetting of cultured fibroblasts by co-cultured adrenal glands.

    Directory of Open Access Journals (Sweden)

    Takako Noguchi

    Full Text Available In mammals, circadian rhythms of various organs and tissues are synchronized by pacemaker neurons in the suprachiasmatic nucleus (SCN of the hypothalamus. Glucocorticoids released from the adrenal glands can synchronize circadian rhythms in other tissues. Many hormones show circadian rhythms in their plasma concentrations; however, whether organs outside the SCN can serve as master synchronizers to entrain circadian rhythms in target tissues is not well understood. To further delineate the function of the adrenal glands and the interactions of circadian rhythms in putative master synchronizing organs and their target tissues, here we report a simple co-culture system using a dual-color luciferase assay to monitor circadian rhythms separately in various explanted tissues and fibroblasts. In this system, circadian rhythms of organs and target cells were simultaneously tracked by the green-emitting beetle luciferase from Pyrearinus termitilluminans (ELuc and the red-emitting beetle luciferase from Phrixothrix hirtus (SLR, respectively. We obtained tissues from the adrenal glands, thyroid glands, and lungs of transgenic mice that expressed ELuc under control of the promoter from a canonical clock gene, mBmal1. The tissues were co-cultured with Rat-1 fibroblasts as representative target cells expressing SLR under control of the mBmal1 promoter. Amplitudes of the circadian rhythms of Rat-1 fibroblasts were potentiated when the fibroblasts were co-cultured with adrenal gland tissue, but not when co-cultured with thyroid gland or lung tissue. The phases of Rat-1 fibroblasts were reset by application of adrenal gland tissue, whereas the phases of adrenal gland tissue were not influenced by Rat-1 fibroblasts. Furthermore, the effect of the adrenal gland tissue on the fibroblasts was blocked by application of a glucocorticoid receptor (GR antagonist. These results demonstrate that glucocorticoids are strong circadian synchronizers for fibroblasts and that

  10. Individual recognition of social rank and social memory performance depends on a functional circadian system.

    Science.gov (United States)

    Müller, L; Weinert, D

    2016-11-01

    In a natural environment, social abilities of an animal are important for its survival. Particularly, it must recognize its own social rank and the social rank of a conspecific and have a good social memory. While the role of the circadian system for object and spatial recognition and memory is well known, the impact of the social rank and circadian disruptions on social recognition and memory were not investigated so far. In the present study, individual recognition of social rank and social memory performance of Djungarian hamsters revealing different circadian phenotypes were investigated. Wild type (WT) animals show a clear and well-synchronized daily activity rhythm, whereas in arrhythmic (AR) hamsters, the suprachiasmatic nuclei (SCN) do not generate a circadian signal. The aim of the study was to investigate putative consequences of these deteriorations in the circadian system for animalś cognitive abilities. Hamsters were bred and kept under standardized housing conditions with food and water ad libitum and a 14l/10 D lighting regimen. Experimental animals were assigned to different groups (WT and AR) according to their activity pattern obtained by means of infrared motion sensors. Before the experiments, the animals were given to develop a dominant-subordinate relationship in a dyadic encounter. Experiment 1 dealt with individual recognition of social rank. Subordinate and dominant hamsters were tested in an open arena for their behavioral responses towards a familiar (known from the agonistic encounters) or an unfamiliar hamster (from another agonistic encounter) which had the same or an opposite social rank. The investigation time depended on the social rank of the WT subject hamster and its familiarity with the stimulus animal. Both subordinate and dominant WT hamsters preferred an unfamiliar subordinate stimulus animal. In contrast, neither subordinate nor dominant AR hamsters preferred any of the stimulus animals. Thus, disruptions in circadian

  11. Circadian changes in urinary Na + /K + ratio in humans: is there a ...

    African Journals Online (AJOL)

    Background: There are indications that the renal excretion of Na+ and K+ is affected by the body's circadian rhythm. Aldosterone is known to be the major determinant of urinary Na+/K+ ratio. However, recent reports suggest that the circadian rhythm of K+ excretion does not depend on endogenous aldosterone.

  12. Ambulatory assessment of human circadian phase and related sleep disorders from heart rate variability and other non-invasive physiological measurements

    NARCIS (Netherlands)

    Gil Ponce, Enrique

    2017-01-01

    The circadian system plays a key role in our well-being and its effects can be seen in many aspects of our lives. Our master circadian clock, located deep in our brain, influences various physiological processes such as heart rate, body temperature, energy metabolism, hormones, and sleep, to name a

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

    Science.gov (United States)

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

    2016-05-10

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

    Many physiological processes fluctuate throughout the day/night and daily fluctuations are observed in brain and peripheral levels of several hormones, neuropeptides and transmitters. In turn, mediators under the "control" of the "master biological clock" reciprocally influence its function. Dysregulation in the rhythmicity of hormone release as well as hormone receptor sensitivity and availability in different tissues, is a common risk-factor for multiple clinical conditions, including psychiatric and metabolic disorders. At the same time circadian rhythms remain in a strong, reciprocal interaction with the hypothalamic-pituitary-adrenal (HPA) axis. Recent findings point to a role of circadian disturbances and excessive stress in the development of obesity and related food consumption and metabolism abnormalities, which constitute a major health problem worldwide. Appetite, food intake and energy balance are under the influence of several brain neuropeptides, including the orexigenic agouti-related peptide, neuropeptide Y, orexin, melanin-concentrating hormone and relaxin-3. Importantly, orexigenic neuropeptide neurons remain under the control of the circadian timing system and are highly sensitive to various stressors, therefore the potential neuronal mechanisms through which disturbances in the daily rhythmicity and stress-related mediator levels contribute to food intake abnormalities rely on reciprocal interactions between these elements.

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

    Directory of Open Access Journals (Sweden)

    Mathias Teschke

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

  17. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Uduak S. Udoh

    2015-10-01

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

  18. Toward a complex system understanding of bipolar disorder: A chaotic model of abnormal circadian activity rhythms in euthymic bipolar disorder.

    Science.gov (United States)

    Hadaeghi, Fatemeh; Hashemi Golpayegani, Mohammad Reza; Jafari, Sajad; Murray, Greg

    2016-08-01

    In the absence of a comprehensive neural model to explain the underlying mechanisms of disturbed circadian function in bipolar disorder, mathematical modeling is a helpful tool. Here, circadian activity as a response to exogenous daily cycles is proposed to be the product of interactions between neuronal networks in cortical (cognitive processing) and subcortical (pacemaker) areas of the brain. To investigate the dynamical aspects of the link between disturbed circadian activity rhythms and abnormalities of neurotransmitter functioning in frontal areas of the brain, we developed a novel mathematical model of a chaotic system which represents fluctuations in circadian activity in bipolar disorder as changes in the model's parameters. A novel map-based chaotic system was developed to capture disturbances in circadian activity across the two extreme mood states of bipolar disorder. The model uses chaos theory to characterize interplay between neurotransmitter functions and rhythm generation; it aims to illuminate key activity phenomenology in bipolar disorder, including prolonged sleep intervals, decreased total activity and attenuated amplitude of the diurnal activity rhythm. To test our new cortical-circadian mathematical model of bipolar disorder, we utilized previously collected locomotor activity data recorded from normal subjects and bipolar patients by wrist-worn actigraphs. All control parameters in the proposed model have an important role in replicating the different aspects of circadian activity rhythm generation in the brain. The model can successfully replicate deviations in sleep/wake time intervals corresponding to manic and depressive episodes of bipolar disorder, in which one of the excitatory or inhibitory pathways is abnormally dominant. Although neuroimaging research has strongly implicated a reciprocal interaction between cortical and subcortical regions as pathogenic in bipolar disorder, this is the first model to mathematically represent this

  19. Evidences of Polymorphism Associated with Circadian System and Risk of Pathologies: A Review of the Literature

    Directory of Open Access Journals (Sweden)

    F. J. Valenzuela

    2016-01-01

    Full Text Available The circadian system is a supraphysiological system that modulates different biological functions such as metabolism, sleep-wake, cellular proliferation, and body temperature. Different chronodisruptors have been identified, such as shift work, feeding time, long days, and stress. The environmental changes and our modern lifestyle can alter the circadian system and increase the risk of developing pathologies such as cancer, preeclampsia, diabetes, and mood disorder. This system is organized by transcriptional/tranductional feedback loops of clock genes Clock, Bmal1, Per1–3, and Cry1-2. How molecular components of the clock are able to influence the development of diseases and their risk relation with genetic components of polymorphism of clock genes is unknown. This research describes different genetic variations in the population and how these are associated with risk of cancer, metabolic diseases such as diabetes, obesity, and dyslipidemias, and also mood disorders such as depression, bipolar disease, excessive alcohol intake, and infertility. Finally, these findings will need to be implemented and evaluated at the level of genetic interaction and how the environment factors trigger the expression of these pathologies will be examined.

  20. Short-Wavelength Countermeasures for Circadian Desynchrony

    National Research Council Canada - National Science Library

    Heller, H. C; Smith, Mark

    2008-01-01

    .... Exposure of humans to bright light for an hour or more at the right phase of the circadian cycle produces significant phase shifts of circadian rhythms speeding recovery from jet-lag, and optimizing...

  1. Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures.

    Science.gov (United States)

    Potter, Gregory D M; Skene, Debra J; Arendt, Josephine; Cade, Janet E; Grant, Peter J; Hardie, Laura J

    2016-12-01

    Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important.

  2. Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures

    Science.gov (United States)

    Skene, Debra J.; Arendt, Josephine; Cade, Janet E.; Grant, Peter J.; Hardie, Laura J.

    2016-01-01

    Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important. PMID:27763782

  3. Interaction between circadian rhythms and stress

    Directory of Open Access Journals (Sweden)

    C.E. Koch

    2017-02-01

    Full Text Available Life on earth has adapted to the day-night cycle by evolution of internal, so-called circadian clocks that adjust behavior and physiology to the recurring changes in environmental conditions. In mammals, a master pacemaker located in the suprachiasmatic nucleus (SCN of the hypothalamus receives environmental light information and synchronizes peripheral tissues and central non-SCN clocks to geophysical time. Regulatory systems such as the hypothalamus-pituitary-adrenal (HPA axis and the autonomic nervous system (ANS, both being important for the regulation of stress responses, receive strong circadian input. In this review, we summarize the interaction of circadian and stress systems and the resulting physiological and pathophysiological consequences. Finally, we critically discuss the relevance of rodent stress studies for humans, addressing complications of translational approaches and offering strategies to optimize animal studies from a chronobiological perspective.

  4. Neural Mechanisms of Circadian Regulation of Natural and Drug Reward

    Directory of Open Access Journals (Sweden)

    Lauren M. DePoy

    2017-01-01

    Full Text Available Circadian rhythms are endogenously generated near 24-hour variations of physiological and behavioral functions. In humans, disruptions to the circadian system are associated with negative health outcomes, including metabolic, immune, and psychiatric diseases, such as addiction. Animal models suggest bidirectional relationships between the circadian system and drugs of abuse, whereby desynchrony, misalignment, or disruption may promote vulnerability to drug use and the transition to addiction, while exposure to drugs of abuse may entrain, disrupt, or perturb the circadian timing system. Recent evidence suggests natural (i.e., food and drug rewards may influence overlapping neural circuitry, and the circadian system may modulate the physiological and behavioral responses to these stimuli. Environmental disruptions, such as shifting schedules or shorter/longer days, influence food and drug intake, and certain mutations of circadian genes that control cellular rhythms are associated with altered behavioral reward. We highlight the more recent findings associating circadian rhythms to reward function, linking environmental and genetic evidence to natural and drug reward and related neural circuitry.

  5. Effect of age, gender and exercise on salivary dehydroepiandrosterone circadian rhythm profile in human volunteers.

    Science.gov (United States)

    Al-Turk, Walid; Al-Dujaili, Emad A S

    2016-02-01

    There has been a lot of effort by scientists to elucidate the multi functions of the naturally occurring hormone, dehydroepiandrosterone (DHEA). However, to plan research experiments optimally, it is important first to characterize the diurnal rhythm in healthy individuals. The aim of this research was to investigate the daily circadian rhythms of DHEA among the 2 genders, and the effect of age and exercise on salivary DHEA circadian rhythms. Volunteers (20-39 and 40-60 years) were recruited for 2 studies investigating the salivary DHEA circadian rhythm. The first study looked at the effect of gender and age on DHEA levels on 2 non-consecutive days, and the second study explored the effect of exercise on DHEA circadian rhythm in males. DHEA levels were estimated by a sensitive and specific ELISA method. The results showed a clear daily circadian rhythm in salivary DHEA in all participants groups, however the profile was flatter in the older female group. There was a significant difference between age and gender groups particularly at 8.00 h. In young males DHEA reduced from 541.1 ± 101.3 (mean ± sd) at 8.00 h to 198.9 ± 90.7 pg/mL at 18.00 h; pcircadian rhythm in salivary DHEA in all participants was observed, but the profile was flatter in the older groups. Copyright © 2016. Published by Elsevier Inc.

  6. Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock

    OpenAIRE

    David M. Virshup; Rajesh Narasimamurthy

    2017-01-01

    An approximately 24-h biological timekeeping mechanism called the circadian clock is present in virtually all light-sensitive organisms from cyanobacteria to humans. The clock system regulates our sleep–wake cycle, feeding–fasting, hormonal secretion, body temperature, and many other physiological functions. Signals from the master circadian oscillator entrain peripheral clocks using a variety of neural and hormonal signals. Even centrally controlled internal temperature fluctuations can entr...

  7. Genetic polymorphisms in the serotonergic system are associated with circadian manifestations of bruxism.

    Science.gov (United States)

    Oporto, G H; Bornhardt, T; Iturriaga, V; Salazar, L A

    2016-11-01

    Bruxism (BRX) is a condition of great interest for researchers and clinicians in dental and medical areas. BRX has two circadian manifestations; it can occur during sleep (sleep bruxism, SB) or during wakefulness (awake bruxism, WB). However, it can be suffered together. Recent investigations suggest that central nervous system neurotransmitters and their genes could be involved in the genesis of BRX. Serotonin is responsible for the circadian rhythm, maintaining arousal, regulating stress response, muscle tone and breathing. Thus, serotonin could be associated with BRX pathogenesis. The aim of this work was to evaluate the frequency of genetic polymorphisms in the genes HTR1A (rs6295), HTR2A (rs1923884, rs4941573, rs6313, rs2770304), HTR2C (rs17260565) and SLC6A4 (rs63749047) in subjects undergoing BRX treatment. Patients included were classified according to their diagnosis in awake bruxism (61 patients), sleep bruxism (26 patients) and both (43 patients). The control group included 59 healthy patients with no signs of BRX. Data showed significant differences in allelic frequencies for the HTR2A rs2770304 polymorphism, where the C allele was associated with increased risk of SB (odds ratio = 2·13, 95% confidence interval: 1·08-4·21, P = 0·03). Our results suggest that polymorphisms in serotonergic pathways are involved in sleep bruxism. Further research is needed to clarify and increase the current understanding of BRX physiopathology. © 2016 John Wiley & Sons Ltd.

  8. Extraocular light via the ear canal does not acutely affect human circadian physiology, alertness and psychomotor vigilance performance.

    Science.gov (United States)

    Bromundt, Vivien; Frey, Sylvia; Odermatt, Jonas; Cajochen, Christian

    2014-04-01

    We aimed at testing potential effects of extraocular bright light via the ear canals on human evening melatonin levels, sleepiness and psychomotor vigilance performance. Twenty healthy young men and women (10/10) kept a regular sleep-wake cycle during the 2-week study. The volunteers reported to the laboratory on three evenings, 2 h 15 min before usual bedtime, on average at 21:45 h. They were exposed to three different light conditions, each lasting for 12 min: extraocular bright light via the ear canal, ocular bright light as an active control condition and a control condition (extraocular light therapy device with completely blacked out LEDs). The timing of exposure was on average from 22:48 to 23:00 h. During the 2-h protocol, saliva samples were collected in 15-min intervals for melatonin assays along with subjective sleepiness ratings, and the volunteers performed a 10-min visual psychomotor vigilance task (PVT) prior to and after each light condition. The evening melatonin rise was significantly attenuated after the 12-min ocular bright light exposure while no significant changes were observed after the extraocular bright light and sham light condition. Subjective sleepiness decreased immediately over a short period only after ocular light exposure. No significant differences were observed for mean reaction times and the number of lapses for the PVT between the three light conditions. We conclude that extraocular transcranial light exposure in the late evening does not suppress melatonin, reduce subjective sleepiness or improve performance, and therefore, does not acutely influence the human circadian timing system.

  9. Circadian dysregulation in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Aleksandar Videnovic

    2017-01-01

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

  10. 76 FR 16646 - Circadian, Inc., Clean Energy Combustion, Inc. (n/k/a Clean Energy Combustion Systems, Inc...

    Science.gov (United States)

    2011-03-24

    ... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] Circadian, Inc., Clean Energy Combustion, Inc. (n/k/a Clean Energy Combustion Systems, Inc.), Collectible Concepts Group, Inc., Communitronics of... is a lack of current and accurate information concerning the securities of Clean Energy Combustion...

  11. Circadian system functionality, hippocampal oxidative stress, and spatial memory in the APPswe/PS1dE9 transgenic model of Alzheimer disease: effects of melatonin or ramelteon.

    Science.gov (United States)

    Baño Otalora, Beatriz; Popovic, Natalija; Gambini, Juan; Popovic, Miroljub; Viña, José; Bonet-Costa, Vicent; Reiter, Russel J; Camello, Pedro Javier; Rol, Maria Ángeles; Madrid, Juan Antonio

    2012-08-01

    Alzheimer disease (AD) is a neurodegenerative disorder that primarily causes β-amyloid accumulation in the brain, resulting in cognitive and behavioral deficits. AD patients, however, also suffer from severe circadian rhythm disruptions, and the underlying causes are still not fully known. Patients with AD show reduced systemic melatonin levels. This may contribute to their symptoms, since melatonin is an effective chronobiotic and antioxidant with neuroprotective properties. Here, the authors critically assessed the effects of long-term melatonin treatment on circadian system function, hippocampal oxidative stress, and spatial memory performance in the APPswe/PS1 double transgenic (Tg) mouse model of AD. To test if melatonin MT1/MT2 receptor activation, alone, was involved, the authors chronically treated some mice with the selective MT1/MT2 receptor agonist ramelteon. The results indicate that many of the circadian and behavioral parameters measured, including oxidative stress markers, were not significantly affected in these AD mice. During the day, though, Tg controls (Tg-CON) showed significantly higher mean activity and body temperature (BT) than wild-type (WT) mice. Overall, BT rhythm amplitude was significantly lower in Tg than in WT mice. Although melatonin treatment had no effect, ramelteon significantly reduced the amplitude of the BT rhythm in Tg mice. Towards the end of the experiment, Tg mice treated with ramelteon (Tg-RAM) showed significantly higher circadian rhythm fragmentation than Tg-CON and reduced circadian BT rhythm strength. The free-running period (τ) for the BT and locomotor activity (LA) rhythms of Tg-CON was RAM compared with Tg-CON animals. These results suggest that not all aspects of the circadian system are affected in the APPswe/PS1 mice. Therefore, care should be taken when extending the results obtained in Tg mice to develop new therapies in humans. This study also revealed the complexity in the therapeutic actions of melatonin

  12. The Circadian System : A Regulatory Feedback Network of Periphery and Brain

    NARCIS (Netherlands)

    Buijs, Frederik N; León-Mercado, Luis; Guzmán-Ruiz, Mara; Guerrero-Vargas, Natali N; Romo-Nava, Francisco; Buijs, Ruud M

    Circadian rhythms are generated by the autonomous circadian clock, the suprachiasmatic nucleus (SCN), and clock genes that are present in all tissues. The SCN times these peripheral clocks, as well as behavioral and physiological processes. Recent studies show that frequent violations of conditions

  13. A personalised and adaptive intelligent system to adjust circadian lighting for elderly housing

    DEFF Research Database (Denmark)

    Flyvholm, Anton; Sen, Sumit; Xylakis, Emmanouil

    2016-01-01

    With the rapid population ageing in Europe and in Denmark, there is an increasing interest in technologies and designs that can support the elderly citizens in sustaining well-being and health along with preventing functional decline [1]. To date, the designs of lighting systems in elderly housing...... detection, actigraphy, etc.) and c) anthropological (mood and behaviour). This way, the effect of circadian lighting on well-being, can be also documented, before this new technology can be recommended for implementation in elderly housing. A test installation is planned at “Sundhedshuset” in Albertslund...... places, nursing homes, domestic applications, and smart cities. Accelerate SSL - Innovation for Europe. SSL-Erate. Available from: http://lightingforpeople.eu/2016/wp-content/uploads/2016/03/SSLerate-3.2-3.4-v4.pdf. [3] Mobily PR, Skemp Kelley LS. (1991). Iatrogenesis in the elderly. Factors...

  14. Developmental programming by androgen affects the circadian timing system in female mice.

    Science.gov (United States)

    Mereness, Amanda L; Murphy, Zachary C; Sellix, Michael T

    2015-04-01

    Circadian clocks play essential roles in the timing of events in the mammalian hypothalamo-pituitary-ovarian (HPO) axis. The molecular oscillator driving these rhythms has been localized to tissues of the HPO axis. It has been suggested that synchrony among these oscillators is a feature of normal reproductive function. The impact of fertility disorders on clock function and the role of the clock in the etiology of endocrine pathology remain unknown. Polycystic ovarian syndrome (PCOS) is a particularly devastating fertility disorder, affecting 5%-10% of women at childbearing age with features including a polycystic ovary, anovulation, and elevated serum androgen. Approximately 40% of these women have metabolic syndrome, marked by hyperinsulinemia, dyslipidemia, and insulin resistance. It has been suggested that developmental exposure to excess androgen contributes to the etiology of fertility disorders, including PCOS. To better define the role of the timing system in these disorders, we determined the effects of androgen-dependent developmental programming on clock gene expression in tissues of the metabolic and HPO axes. Female PERIOD2::luciferase (PER2::LUC) mice were exposed to androgen (dihydrotestosterone [DHT]) in utero (Days 16-18 of gestation) or for 9-10 wk (DHT pellet) beginning at weaning (pubertal androgen excess [PAE]). As expected, both groups of androgen-treated mice had disrupted estrous cycles. Analysis of PER2::LUC expression in tissue explants revealed that excess androgen produced circadian misalignment via tissue-dependent effects on phase distribution. In vitro treatment with DHT differentially affected the period of PER2::LUC expression in tissue explants and granulosa cells, indicating that androgen has direct and tissue-specific effects on clock gene expression that may account for the effects of developmental programming on the timing system. © 2015 by the Society for the Study of Reproduction, Inc.

  15. A novel algorithm for detecting human circadian rhythms using a thoracic temperature sensor

    Directory of Open Access Journals (Sweden)

    Aly Chkeir

    2017-07-01

    Full Text Available Circadian rhythms undergo high perturbations due to cancer progression and worsening of metabolic diseases. This paper proposes an original method for detecting such perturbations using a novel thoracic temperature sensor. Such an infrared sensor records the skin temperature every five minutes, although some data might be missing. In this pilot study, five control subjects were evaluated over four days of recordings. In order to overcome the problem of missing data, first four different interpolation methods were compared. Using interpolation helps covering the gaps and extending the recordings frequency, subsequently prolonging sensor battery life. Afterwards, a Cosinor model was proposed to characterize circadian rhythms, and extract relevant parameters, with their confidence limits. A divergence study is then performed to detect changes in these parameters. The results are promising, supporting the enlargement of the sample size and warranting further assessment in cancer patients.

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

    Directory of Open Access Journals (Sweden)

    Julie S Pendergast

    2010-01-01

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

  17. Circadian disorganization alters intestinal microbiota.

    Directory of Open Access Journals (Sweden)

    Robin M Voigt

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

  18. Lack of circadian variation in the activity of the autonomic nervous system after major abdominal operations

    DEFF Research Database (Denmark)

    Gögenur, Ismail; Rosenberg-Adamsen, Susan; Lie, Claus

    2002-01-01

    OBJECTIVE: Most sudden postoperative deaths occur during the night and we conjectured that this was associated with circadian variations in the autonomic nervous tone, reflected in heart rate variability. DESIGN: Prospective clinical study. SETTINGS: University hospital, Denmark. SUBJECTS: 44...... OUTCOME MEASURES: Heart rate and heart rate variability. RESULTS: Circadian variation calculated from the SDNN (p = 0.43) the pNN50 (p = 0.11), the RMSSD (p = 0.47), and mean NN:SDNN ratio (p = 0.13) was absent postoperatively. Circadian variation in the heart rate was present but was set on a higher...... level compared with reference values. CONCLUSION: After major abdominal operations there was a lack of circadian variation in the autonomic nervous tone....

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

    Science.gov (United States)

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

    2018-02-01

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

  20. Circadian Rhythms in Cyanobacteria

    Science.gov (United States)

    Golden, Susan S.

    2015-01-01

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

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

    Science.gov (United States)

    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).

  2. Circadian Rhythms

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 11. Circadian Rhythms ... M Vaze1 Vijay Kumar Sharma1. Chronobiology Laboratory Evolutionary and Organismal Biology Unit, Jawaharlal Nehru Centre for Advanced Scientific Research Jakkur, PO Box 6436, Bangalore 560 064, India.

  3. Circadian Rhythms

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 2. Circadian Rhythms: Why do ... Nikhil Vijay Kumar Sharma1. Chronobiology Laboratory Evolutionary and Organismal Biology Unit Jawaharlal Nehru Centre for Advanced Scientific Research Jakkur, PO Box 6436, Bangalore 560 064, India.

  4. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    Early studies on circadian rhythms focussed on unravelling the fundamental .... careful analysis revealed that deaths of most arrhythmic indi- viduals were due to .... is no more a sci-fi movie script and is achievable through a technique called ...

  5. Circadian Clock Dysfunction and Psychiatric Disease: Could Fruit Flies have a Say?

    Science.gov (United States)

    Zordan, Mauro Agostino; Sandrelli, Federica

    2015-01-01

    There is evidence of a link between the circadian system and psychiatric diseases. Studies in humans and mammals suggest that environmental and/or genetic disruption of the circadian system leads to an increased liability to psychiatric disease. Disruption of clock genes and/or the clock network might be related to the etiology of these pathologies; also, some genes, known for their circadian clock functions, might be associated to mental illnesses through clock-independent pleiotropy. Here, we examine the features which we believe make Drosophila melanogaster a model apt to study the role of the circadian clock in psychiatric disease. Despite differences in the organization of the clock system, the molecular architecture of the Drosophila and mammalian circadian oscillators are comparable and many components are evolutionarily related. In addition, Drosophila has a rather complex nervous system, which shares much at the cell and neurobiological level with humans, i.e., a tripartite brain, the main neurotransmitter systems, and behavioral traits: circadian behavior, learning and memory, motivation, addiction, social behavior. There is evidence that the Drosophila brain shares some homologies with the vertebrate cerebellum, basal ganglia, and hypothalamus-pituitary-adrenal axis, the dysfunctions of which have been tied to mental illness. We discuss Drosophila in comparison to mammals with reference to the: organization of the brain and neurotransmitter systems; architecture of the circadian clock; clock-controlled behaviors. We sum up current knowledge on behavioral endophenotypes, which are amenable to modeling in flies, such as defects involving sleep, cognition, or social interactions, and discuss the relationship of the circadian system to these traits. Finally, we consider if Drosophila could be a valuable asset to understand the relationship between circadian clock malfunction and psychiatric disease.

  6. Circadian clock dysfunction and psychiatric disease: could fruit flies have a say?

    Directory of Open Access Journals (Sweden)

    Mauro Agostino Zordan

    2015-04-01

    Full Text Available There is evidence of a link between the circadian system and psychiatric diseases. Studies in humans and mammals suggest that environmental and/or genetic disruption of the circadian system lead to an increased liability to psychiatric disease. Disruption of clock genes and/or the clock network might be related to the etiology of these pathologies; also, some genes, known for their circadian clock functions, might be associated to mental illnesses through clock-independent pleiotropy. Here we examine the features which we believe make Drosophila melanogaster a model apt to study the role of the circadian clock in psychiatric disease. Despite differences in the organization of the clock system, the molecular architecture of the Drosophila and mammalian circadian oscillators are comparable and many components are evolutionarily related. In addition, Drosophila has a rather complex nervous system, which shares much at the cell and neurobiological level with humans, i.e. a tripartite brain, the main neurotransmitter systems, and behavioral traits: circadian behavior, learning and memory, motivation, addiction, social behavior. There is evidence that the Drosophila brain shares some homologies with the vertebrate cerebellum, basal ganglia and hypothalamus-pituitary-adrenal axis, the dysfunctions of which have been tied to mental illness. We discuss Drosophila in comparison to mammals with reference to the: organization of the brain and neurotransmitter systems; architecture of the circadian clock; clock-controlled behaviors. We sum up current knowledge on behavioral endophenotypes which are amenable to modeling in flies, such as defects involving sleep, cognition, or social interactions and discuss the relationship of the circadian system to these traits. Finally, we consider if Drosophila could be a valuable asset to understand the relationship between circadian clock malfunction and psychiatric disease.

  7. N-acetyltransferase (nat) is a critical conjunct of photoperiodism between the circadian system and endocrine axis in Antheraea pernyi.

    Science.gov (United States)

    Mohamed, Ahmed A M; Wang, Qiushi; Bembenek, Jadwiga; Ichihara, Naoyuki; Hiragaki, Susumu; Suzuki, Takeshi; Takeda, Makio

    2014-01-01

    Since its discovery in 1923, the biology of photoperiodism remains a mystery in many ways. We sought the link connecting the circadian system to an endocrine switch, using Antheraea pernyi. PER-, CLK- and CYC-ir were co-expressed in two pairs of dorsolateral neurons of the protocerebrum, suggesting that these are the circadian neurons that also express melatonin-, NAT- and HIOMT-ir. The results suggest that a melatonin pathway is present in the circadian neurons. Melatonin receptor (MT2 or MEL-1B-R)-ir in PTTH-ir neurons juxtaposing clock neurons suggests that melatonin gates PTTH release. RIA showed a melatonin rhythm with a peak four hours after lights off in adult brain both under LD16:8 (LD) and LD12:12 (SD), and both the peak and the baseline levels were higher under LD than SD, suggesting a photoperiodic influence. When pupae in diapause were exposed to 10 cycles of LD, or stored at 4 °C for 4 months under constant darkness, an increase of NAT activity was observed when PTTH released ecdysone. DNA sequence upstream of nat contained E-boxes to which CYC/CLK could bind, and nat transcription was turned off by clk or cyc dsRNA. dsRNA(NAT) caused dysfunction of photoperiodism. dsRNA(PER) upregulated nat transcription as anticipated, based on findings in the Drosophila melanogaster circadian system. Transcription of nat, cyc and clk peaked at ZT12. RIA showed that dsRNA(NAT) decreased melatonin while dsRNA(PER) increased melatonin. Thus nat, a clock controlled gene, is the critical link between the circadian clock and endocrine switch. MT-binding may release PTTH, resulting in termination of diapause. This study thus examined all of the basic functional units from the clock: a photoperiodic counter as an accumulator of mRNA(NAT), to endocrine switch for photoperiodism in A. pernyi showing this system is self-complete without additional device especially for photoperiodism.

  8. Is the food-entrainable circadian oscillator in the digestive system?

    Science.gov (United States)

    Davidson, A. J.; Poole, A. S.; Yamazaki, S.; Menaker, M.

    2003-01-01

    Food-anticipatory activity (FAA) is the increase in locomotion and core body temperature that precedes a daily scheduled meal. It is driven by a circadian oscillator but is independent of the suprachiasmatic nuclei. Recent results that reveal meal-entrained clock gene expression in rat and mouse peripheral organs raise the intriguing possibility that the digestive system is the site of the feeding-entrained oscillator (FEO) that underlies FAA. We tested this possibility by comparing FAA and Per1 rhythmicity in the digestive system of the Per1-luciferase transgenic rat. First, rats were entrained to daytime restricted feeding (RF, 10 days), then fed ad libitum (AL, 10 days), then food deprived (FD, 2 days). As expected FAA was evident during RF and disappeared during subsequent AL feeding, but returned at the correct phase during deprivation. The phase of Per1 in liver, stomach and colon shifted from a nocturnal to a diurnal peak during RF, but shifted back to nocturnal phase during the subsequent AL and remained nocturnal during food deprivation periods. Second, rats were entrained to two daily meals at zeitgeber time (ZT) 0400 and ZT 1600. FAA to both meals emerged after about 10days of dual RF. However, all tissues studied (all five liver lobes, esophagus, antral stomach, body of stomach, colon) showed entrainment consistent with only the night-time meal. These two results are inconsistent with the hypothesis that FAA arises as an output of rhythms in the gastrointestinal (GI) system. The results also highlight an interesting diversity among peripheral oscillators in their ability to entrain to meals and the direction of the phase shift after RF ends.

  9. Circadian rhythms and obesity in mammals.

    Science.gov (United States)

    Froy, Oren

    2012-01-01

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

  10. Development of a Configurable Growth Chamber with a Computer Vision System to Study Circadian Rhythm in Plants

    Directory of Open Access Journals (Sweden)

    Marcos Egea-Cortines

    2012-11-01

    Full Text Available Plant development is the result of an endogenous morphogenetic program that integrates environmental signals. The so-called circadian clock is a set of genes that integrates environmental inputs into an internal pacing system that gates growth and other outputs. Study of circadian growth responses requires high sampling rates to detect changes in growth and avoid aliasing. We have developed a flexible configurable growth chamber comprising a computer vision system that allows sampling rates ranging between one image per 30 s to hours/days. The vision system has a controlled illumination system, which allows the user to set up different configurations. The illumination system used emits a combination of wavelengths ensuring the optimal growth of species under analysis. In order to obtain high contrast of captured images, the capture system is composed of two CCD cameras, for day and night periods. Depending on the sample type, a flexible image processing software calculates different parameters based on geometric calculations. As a proof of concept we tested the system in three different plant tissues, growth of petunia- and snapdragon (Antirrhinum majus flowers and of cladodes from the cactus Opuntia ficus-indica. We found that petunia flowers grow at a steady pace and display a strong growth increase in the early morning, whereas Opuntia cladode growth turned out not to follow a circadian growth pattern under the growth conditions imposed. Furthermore we were able to identify a decoupling of increase in area and length indicating that two independent growth processes are responsible for the final size and shape of the cladode.

  11. CIRCADIAN REGULATION METABOLIC SIGNALING MECHANISMS OF HUMAN BREAST CANCER GROWTH BY THE NOCTURNAL MELATONIN SIGNAL AND THE CONSEQUENCES OF ITS DISRUPTION BY LIGHT AT NIGHT

    Science.gov (United States)

    Blask, David E.; Hill, Steven M.; Dauchy, Robert T.; Xiang, Shulin; Yuan, Lin; Duplessis, Tamika; Mao, Lulu; Dauchy, Erin; Sauer, Leonard A.

    2011-01-01

    This review article discusses recent work on the melatonin-mediated circadian regulation and integration of molecular, dietary and metabolic signaling mechanisms involved in human breast cancer growth and the consequences of circadian disruption by exposure to light-at-night (LAN). The antiproliferative effects of the circadian melatonin signal are mediated through a major mechanism involving the activation of MT1 melatonin receptors expressed in human breast cancer cell lines and xenografts. In estrogen receptor (ERα+) human breast cancer cells, melatonin suppresses both ERα mRNA expression and estrogen-induced transcriptional activity of the ERα via MT1-induced activation of Gαi2 signaling and reduction of cAMP levels. Melatonin also regulates the transactivation of additional members of the steroid hormone/nuclear receptor super-family, enzymes involved in estrogen metabolism, expression/activation of telomerase and the expression of core clock and clock-related genes. The anti-invasive/anti-metastatic actions of melatonin involve the blockade of p38 phosphorylation and the expression of matrix metalloproteinases. Melatonin also inhibits the growth of human breast cancer xenografts via another critical pathway involving MT1-mediated suppression of cAMP leading to blockade of linoleic acid (LA) uptake and its metabolism to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Down-regulation of 13-HODE reduces the activation of growth factor pathways supporting cell proliferation and survival. Experimental evidence in rats and humans indicating that LAN-induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism and signaling provides the strongest mechanistic support, thus far, for population and ecological studies demonstrating elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LAN. PMID:21605163

  12. Generation of activity-rest patterns by dual circadian pacemaker systems : a model

    NARCIS (Netherlands)

    Beersma, Domien G.M.; Daan, Serge

    1992-01-01

    Activity-rest patterns displayed by an animal under various circumstances are suggested to result from the combined influences of two virtually identical circadian pacemaker components. Increased output of each component proportionally increases the probability of activity of the animal. Such a dual

  13. Circadian Rhythms in Fear Conditioning: An Overview of Behavioral, Brain System, and Molecular Interactions

    Directory of Open Access Journals (Sweden)

    Anne Albrecht

    2017-01-01

    Full Text Available The formation of fear memories is a powerful and highly evolutionary conserved mechanism that serves the behavioral adaptation to environmental threats. Accordingly, classical fear conditioning paradigms have been employed to investigate fundamental molecular processes of memory formation. Evidence suggests that a circadian regulation mechanism allows for a timestamping of such fear memories and controlling memory salience during both their acquisition and their modification after retrieval. These mechanisms include an expression of molecular clocks in neurons of the amygdala, hippocampus, and medial prefrontal cortex and their tight interaction with the intracellular signaling pathways that mediate neural plasticity and information storage. The cellular activities are coordinated across different brain regions and neural circuits through the release of glucocorticoids and neuromodulators such as acetylcholine, which integrate circadian and memory-related activation. Disturbance of this interplay by circadian phase shifts or traumatic experience appears to be an important factor in the development of stress-related psychopathology, considering these circadian components are of critical importance for optimizing therapeutic approaches to these disorders.

  14. Moderate Changes in the Circadian System of Alzheimer's Disease Patients Detected in Their Home Environment

    Czech Academy of Sciences Publication Activity Database

    Weissová, Kamila; Bartoš, A.; Sládek, Martin; Nováková, Marta; Sumová, Alena

    2016-01-01

    Roč. 11, č. 1 (2016), e0146200 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : circadian * melatonin * clock gene * Alzheimer's disease Subject RIV: FH - Neurology Impact factor: 2.806, year: 2016

  15. The circadian system of patients with bipolar disorder differs in episodes of mania and depression

    Czech Academy of Sciences Publication Activity Database

    Nováková, Marta; Praško, J.; Látalová, K.; Sládek, Martin; Sumová, Alena

    2015-01-01

    Roč. 17, č. 3 (2015), s. 303-314 ISSN 1398-5647 R&D Projects: GA MZd(CZ) NT11474 Institutional support: RVO:67985823 Keywords : bipolar disorder * circadian * clock gene * melatonin * Nr1d1 * Per1 Subject RIV: FH - Neurology Impact factor: 4.882, year: 2015

  16. Disturbance and strategies for reactivation of the circadian rhythm system in aging and Alzheimer's disease

    NARCIS (Netherlands)

    Wu, Y.-H.; Swaab, D.F.

    2007-01-01

    Circadian rhythm disturbances, such as sleep disorders, are frequently seen in aging and are even more pronounced in Alzheimer's disease (AD). Alterations in the biological clock, the suprachiasmatic nucleus (SCN), and the pineal gland during aging and AD are considered to be the biological basis

  17. Circadian clocks, epigenetics, and cancer

    KAUST Repository

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

    2015-01-01

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

  18. Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock.

    Science.gov (United States)

    Narasimamurthy, Rajesh; Virshup, David M

    2017-01-01

    An approximately 24-h biological timekeeping mechanism called the circadian clock is present in virtually all light-sensitive organisms from cyanobacteria to humans. The clock system regulates our sleep-wake cycle, feeding-fasting, hormonal secretion, body temperature, and many other physiological functions. Signals from the master circadian oscillator entrain peripheral clocks using a variety of neural and hormonal signals. Even centrally controlled internal temperature fluctuations can entrain the peripheral circadian clocks. But, unlike other chemical reactions, the output of the clock system remains nearly constant with fluctuations in ambient temperature, a phenomenon known as temperature compensation. In this brief review, we focus on recent advances in our understanding of the posttranslational modifications, especially a phosphoswitch mechanism controlling the stability of PER2 and its implications for the regulation of temperature compensation.

  19. Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock

    Directory of Open Access Journals (Sweden)

    David M. Virshup

    2017-04-01

    Full Text Available An approximately 24-h biological timekeeping mechanism called the circadian clock is present in virtually all light-sensitive organisms from cyanobacteria to humans. The clock system regulates our sleep–wake cycle, feeding–fasting, hormonal secretion, body temperature, and many other physiological functions. Signals from the master circadian oscillator entrain peripheral clocks using a variety of neural and hormonal signals. Even centrally controlled internal temperature fluctuations can entrain the peripheral circadian clocks. But, unlike other chemical reactions, the output of the clock system remains nearly constant with fluctuations in ambient temperature, a phenomenon known as temperature compensation. In this brief review, we focus on recent advances in our understanding of the posttranslational modifications, especially a phosphoswitch mechanism controlling the stability of PER2 and its implications for the regulation of temperature compensation.

  20. Regulation of reproduction by the circadian rhythms.

    Science.gov (United States)

    Zhang, Wen-Xiang; Chen, Si-Yu; Liu, Chang

    2016-12-25

    Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. Circadian rhythm is controlled by the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and the peripheral clocks in various tissues. More importantly, the central clock can integrate photic/nonphotic signals to generate rhythmic outputs, and then drive the slave oscillators in peripheral tissues through neuroendocrine and behavioral signals. Human reproductive activities, as some other physiological functions, are controlled by the biological clocks. Accumulating lines of epidemiological and genetic evidence indicate that disruption of circadian clock can be directly involved in multiple pathological processes, including infertility. In this review, we mainly discuss the presence of a circadian clock in reproductive tissues and its roles in follicles development, ovulation, spermatogenesis, fertilization and embryo implantation, etc. As the increased shift work and assisted reproductive technologies possibly disrupt circadian rhythmicity to impact reproduction, the importance of circadian rhythms should be highlighted in the regulation of reproductive process.

  1. Neurohormones as putative circadian clock output signals in the central nervous system of two cricket species

    Czech Academy of Sciences Publication Activity Database

    Sehadová, H.; Shao, Q. M.; Sehnal, František; Takeda, M.

    2007-01-01

    Roč. 328, č. 1 (2007), s. 239-255 ISSN 0302-766X Grant - others:Japan Society for the Promotion of Science(JP) 99L01205; Japan Society for the Promotion of Science(JP) ID No. P04197 Institutional research plan: CEZ:AV0Z50070508 Keywords : circadian rhythm * corazonin * CCAP Subject RIV: ED - Physiology Impact factor: 2.613, year: 2007

  2. Circadian System and Melatonin Hormone: Risk Factors for Complications during Pregnancy

    OpenAIRE

    Valenzuela, F. J.; Vera, J.; Venegas, C.; Pino, F.; Lagunas, C.

    2015-01-01

    Pregnancy is a complex and well-regulated temporal event in which several steps are finely orchestrated including implantation, decidualization, placentation, and partum and any temporary alteration has serious effects on fetal and maternal health. Interestingly, alterations of circadian rhythms (i.e., shiftwork) have been correlated with increased risk of preterm delivery, intrauterine growth restriction, and preeclampsia. In the last few years evidence is accumulating that the placenta may ...

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

    Directory of Open Access Journals (Sweden)

    Patrick Vancura

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

  4. Circadian Rhythm Sleep-Wake Disorders.

    Science.gov (United States)

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

    2015-12-01

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

  5. In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells.

    Science.gov (United States)

    Fang, Mingzhu; Kang, Hwan-Goo; Park, Youngil; Estrella, Brian; Zarbl, Helmut

    2017-09-28

    The circadian rhythm is a fundamental physiological process present in all organisms that regulates biological processes ranging from gene expression to sleep behavior. In vertebrates, circadian rhythm is controlled by a molecular oscillator that functions in both the suprachiasmatic nucleus (SCN; central pacemaker) and individual cells comprising most peripheral tissues. More importantly, disruption of circadian rhythm by exposure to light-at-night, environmental stressors and/or toxicants is associated with increased risk of chronic diseases and aging. The ability to identify agents that can disrupt central and/or peripheral biological clocks, and agents that can prevent or mitigate the effects of circadian disruption, has significant implications for prevention of chronic diseases. Although rodent models can be used to identify exposures and agents that induce or prevent/mitigate circadian disruption, these experiments require large numbers of animals. In vivo studies also require significant resources and infrastructure, and require researchers to work all night. Thus, there is an urgent need for a cell-type appropriate in vitro system to screen for environmental circadian disruptors and enhancers in cell types from different organs and disease states. We constructed a vector that drives transcription of the destabilized luciferase in eukaryotic cells under the control of the human PERIOD 2 gene promoter. This circadian reporter construct was stably transfected into human mammary epithelial cells, and circadian responsive reporter cells were selected to develop the in vitro bioluminescence assay. Here, we present a detailed protocol to establish and validate the assay. We further provide details for proof of concept experiments demonstrating the ability of our in vitro assay to recapitulate the in vivo effects of various chemicals on the cellular biological clock. The results indicate that the assay can be adapted to a variety of cell types to screen for both

  6. Circadian Plasticity in the Brain of Insects and Rodents

    Directory of Open Access Journals (Sweden)

    Wojciech Krzeptowski

    2018-05-01

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

  7. Circadian analysis of large human populations: inferences from the power grid.

    Science.gov (United States)

    Stowie, Adam C; Amicarelli, Mario J; Crosier, Caitlin J; Mymko, Ryan; Glass, J David

    2015-03-01

    Few, if any studies have focused on the daily rhythmic nature of modern industrialized populations. The present study utilized real-time load data from the U.S. Pacific Northwest electrical power grid as a reflection of human operative household activity. This approach involved actigraphic analyses of continuously streaming internet data (provided in 5 min bins) from a human subject pool of approximately 43 million primarily residential users. Rhythm analyses reveal striking seasonal and intra-week differences in human activity patterns, largely devoid of manufacturing and automated load interference. Length of the diurnal activity period (alpha) is longer during the spring than the summer (16.64 h versus 15.98 h, respectively; p job-related or other weekday morning arousal cues, substantiating a preference or need to sleep longer on weekends. Finally, a shift in onset time can be seen during the transition to Day Light Saving Time, but not the transition back to Standard Time. The use of grid power load as a means for human actimetry assessment thus offers new insights into the collective diurnal activity patterns of large human populations.

  8. The relationship between circadian disruption and the development of metabolic syndrome and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Karatsoreos IN

    2014-12-01

    Full Text Available Ilia N Karatsoreos Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA Abstract: Circadian (daily rhythms are pervasive in nature, and expressed in nearly every behavioral and physiological process. In mammals, circadian rhythms are regulated by the master brain clock in the suprachiasmatic nucleus of the hypothalamus that coordinates the activity of “peripheral” oscillators throughout the brain and body. While much progress has been made in understanding the basic functioning of the circadian clock at the level of genes, molecules, and cells, our understanding of how these clocks interact with complex systems is still in its infancy. Much recent work has focused on the role of circadian clocks in the etiology of disorders as diverse as cancer, diabetes, and obesity. Given the rapid rise in obesity, and the economic costs involved in treating its associated cardiometabolic disorders such as heart disease and diabetes mellitus, understanding the development of obesity and metabolic dysregulation is crucial. Significant epidemiological data indicate a role for circadian rhythms in metabolic disorders. Shift workers have a higher incidence of obesity and diabetes, and laboratory studies in humans show misaligning sleep and the circadian clock leads to hyperinsulinemia. In animal models, body-wide “clock gene” knockout mice are prone to obesity. Further, disrupting the circadian clock by manipulating the light–dark cycle can result in metabolic dysregulation and development of obesity. At the molecular level, elegant studies have shown that targeted disruption of the genetic circadian clock in the pancreas leads to diabetes, highlighting the fact that the circadian clock is directly coupled to metabolism at the cellular level. Keywords: glucose, metabolism, sleep, rhythms, obesity

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

    Science.gov (United States)

    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.

  10. Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.

    Science.gov (United States)

    Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

    2018-05-01

    Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic-pituitary-adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases.

  11. Hypothalamic neurosecretory and circadian vasopressinergic neuronal systems in the blind cone-rod homeobox knock out mouse (Crx(-/-) ) and the 129sv wild type mouse

    DEFF Research Database (Denmark)

    Rovsing, Louise; Rath, Martin Fredensborg; Møller, Morten

    2013-01-01

    circadian AVP-rhythm. We have in this study of the brown 129sv mouse and the visual blind cone-rod homeobox gene knock out mouse (Crx(-/-) ) with degeneration of the retinal rods and cones, but a preserved non-image forming optic system, studied the temporal Avp-expression in both the neurosecretory...

  12. Links between circadian rhythms and psychiatric disease

    Directory of Open Access Journals (Sweden)

    Ilia N Karatsoreos

    2014-05-01

    Full Text Available Determining the cause of psychiatric disorders is a goal of modern neuroscience, and will hopefully lead to the discovery of treatments to either prevent or alleviate the suffering caused by these diseases. One roadblock to attaining this goal is the realization that neuropsychiatric diseases are rarely due to a single gene polymorphism, environmental exposure, or developmental insult. Rather, it is a complex interaction between these various influences that likely leads to the development of clinically relevant syndromes. Our lab is exploring the links between environmental exposures and neurobehavioral function by investigating how disruption of the circadian (daily clock alters the structure and function of neural circuits, with the hypothesis that disrupting this crucial homeostatic system can directly contribute to altered vulnerability of the organism to other factors that interact to produce psychiatric illness. This review explores some historical and more recent findings that link disrupted circadian clocks to neuropsychiatric disorders, particularly depression, mania, and schizophrenia. We take a comparative approach by exploring the effects observed in human populations, as well as some experimental models used in the laboratory to unravel mechanistic and causal relationships between disruption of the circadian clock and behavioral abnormalities. This is a rich area of research that we predict will contribute greatly to our understanding of how genes, environment, and development interact to modulate an individual’s vulnerability to psychiatric disorders.

  13. The Drosophila melanogaster circadian pacemaker circuit

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Keywords. circadian rhythm; neuronal network; ion channel; behaviour; neurotransmitter; electrophysiology; Drosophila. Abstract. As an experimental model system, the fruit fly Drosophila melanogaster has been seminal in shaping our understanding of the circadian clockwork. The wealth of genetic tools ...

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

    NARCIS (Netherlands)

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

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

  15. Cell-permeable Circadian Clock Proteins

    National Research Council Canada - National Science Library

    Johnson, Carl

    2002-01-01

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

  16. Dysglycemia induces abnormal circadian blood pressure variability

    Directory of Open Access Journals (Sweden)

    Kumarasamy Sivarajan

    2011-11-01

    Full Text Available Abstract Background Prediabetes (PreDM in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV. Hypothesis Systemic inflammation and glycemia influence circadian blood pressure variability. Methods Dahl salt-sensitive (S rats (n = 19 after weaning were fed either an American (AD or a standard (SD diet. The AD (high-glycemic-index, high-fat simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG, adipokines (leptin and adiponectin, and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1 and tumor necrosis factor-α (TNF-α] were measured. Rats were surgically implanted with C40 transmitters and blood pressure (BP-both systolic; SBP and diastolic; DBP and heart rate (HR were recorded by telemetry every 5 minutes during both sleep (day and active (night periods. Pulse pressure (PP was calculated (PP = SBP-DBP. Results [mean(SEM]: The AD fed group displayed significant increase in body weight (after 90 days; p Conclusion These data validate our stated hypothesis that systemic inflammation and glycemia influence circadian blood pressure variability. This study, for the first time, demonstrates a cause and effect relationship between caloric excess, enhanced systemic inflammation, dysglycemia, loss of blood pressure control and abnormal CBPV. Our results provide the fundamental basis for examining the relationship between dysglycemia and perturbation of the underlying mechanisms (adipose tissue dysfunction induced local and systemic inflammation, insulin resistance and alteration of adipose tissue precursors for the renin-aldosterone-angiotensin system which generate abnormal CBPV.

  17. Molecular Mechanisms of Circadian Regulation During Spaceflight

    Science.gov (United States)

    Zanello, S. B.; Boyle, R.

    2012-01-01

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

  18. Coordination of the maize transcriptome by a conserved circadian clock

    Directory of Open Access Journals (Sweden)

    Harmon Frank G

    2010-06-01

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

  19. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright-light duration?

    Science.gov (United States)

    Crowley, Stephanie J; Eastman, Charmane I

    2015-02-01

    Efficient treatments to phase-advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early-morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright-light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. Fifty adults (27 males) aged 25.9 ± 5.1 years participated. Sleep/dark was advanced 1 h/day for three treatment days. Participants took 0.5 mg of melatonin 5 h before the baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright-light (~5000 lux) patterns upon waking each morning: four 30-min exposures separated by 30 min of room light (2-h group), four 15-min exposures separated by 45 min of room light (1-h group), and one 30-min exposure (0.5-h group). Dim-light melatonin onsets (DLMOs) before and after treatment determined the phase advance. Compared to the 2-h group (phase shift = 2.4 ± 0.8 h), smaller phase-advance shifts were seen in the 1-h (1.7 ± 0.7 h) and 0.5-h (1.8 ± 0.8 h) groups. The 2-h pattern produced the largest phase advance; however, the single 30-min bright-light exposure was as effective as 1 h of bright light spread over 3.25 h, and it produced 75% of the phase shift observed with 2 h of bright light. A 30-min morning bright-light exposure with afternoon melatonin is an efficient treatment to phase-advance human circadian rhythms. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright light duration?

    Science.gov (United States)

    Crowley, Stephanie J.; Eastman, Charmane I.

    2015-01-01

    OBJECTIVE Efficient treatments to phase advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. METHODS Fifty adults (27 males) aged 25.9±5.1 years participated. Sleep/dark was advanced 1 hour/day for 3 treatment days. Participants took 0.5 mg melatonin 5 hours before baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright light (~5000 lux) patterns upon waking each morning: four 30-minute exposures separated by 30 minutes of room light (2 h group); four 15-minute exposures separated by 45 minutes of room light (1 h group), and one 30-minute exposure (0.5 h group). Dim light melatonin onsets (DLMOs) before and after treatment determined the phase advance. RESULTS Compared to the 2 h group (phase shift=2.4±0.8 h), smaller phase advance shifts were seen in the 1 h (1.7±0.7 h) and 0.5 h (1.8±0.8 h) groups. The 2-hour pattern produced the largest phase advance; however, the single 30-minute bright light exposure was as effective as 1 hour of bright light spread over 3.25 h, and produced 75% of the phase shift observed with 2 hours of bright light. CONCLUSIONS A 30-minute morning bright light exposure with afternoon melatonin is an efficient treatment to phase advance human circadian rhythms. PMID:25620199

  1. The role of the endocrine system in feeding-induced tissue-specific circadian entrainment.

    Science.gov (United States)

    Sato, Miho; Murakami, Mariko; Node, Koichi; Matsumura, Ritsuko; Akashi, Makoto

    2014-07-24

    The circadian clock is entrained to environmental cycles by external cue-mediated phase adjustment. Although the light input pathway has been well defined, the mechanism of feeding-induced phase resetting remains unclear. The tissue-specific sensitivity of peripheral entrainment to feeding suggests the involvement of multiple pathways, including humoral and neuronal signals. Previous in vitro studies with cultured cells indicate that endocrine factors may function as entrainment cues for peripheral clocks. However, blood-borne factors that are well characterized in actual feeding-induced resetting have yet to be identified. Here, we report that insulin may be involved in feeding-induced tissue-type-dependent entrainment in vivo. In ex vivo culture experiments, insulin-induced phase shift in peripheral clocks was dependent on tissue type, which was consistent with tissue-specific insulin sensitivity, and peripheral entrainment in insulin-sensitive tissues involved PI3K- and MAPK-mediated signaling pathways. These results suggest that insulin may be an immediate early factor in feeding-mediated tissue-specific entrainment. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-01-01

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

  3. Application of an ex vivo cellular model of circadian variation for bipolar disorder research: a proof of concept study.

    Science.gov (United States)

    Bamne, Mikhil N; Ponder, Christine A; Wood, Joel A; Mansour, Hader; Frank, Ellen; Kupfer, David J; Young, Michael W; Nimgaonkar, Vishwajit L

    2013-09-01

    Disruption of circadian function has been observed in several human disorders, including bipolar disorder (BD). Research into these disorders can be facilitated by human cellular models that evaluate external factors (zeitgebers) that impact circadian pacemaker activity. Incorporating a firefly luciferase reporter system into human fibroblasts provides a facile, bioluminescent readout that estimates circadian phase, while leaving the cells intact. We evaluated whether this system can be adapted to clinical BD research and whether it can incorporate zeitgeber challenge paradigms. Fibroblasts from patients with bipolar I disorder (BD-I) (n = 13) and controls (n = 12) were infected ex vivo with a lentiviral reporter incorporating the promoter sequences for Bmal1, a circadian gene to drive expression of the firefly luciferase gene. Following synchronization, the bioluminescence was used to estimate period length. Phase response curves (PRCs) were also generated following forskolin challenge and the phase response patterns were characterized. Period length and PRCs could be estimated reliably from the constructs. There were no significant case-control differences in period length, with a nonsignificant trend for differences in PRCs following the phase-setting experiments. An ex vivo cellular fibroblast-based model can be used to investigate circadian function in BD-I. It can be generated from specific individuals and this could usefully complement ongoing circadian clinical research. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Biochemical Frequency Control by Synchronisation of Coupled Repressilators: An In Silico Study of Modules for Circadian Clock Systems

    Science.gov (United States)

    Hinze, Thomas; Schumann, Mathias; Bodenstein, Christian; Heiland, Ines; Schuster, Stefan

    2011-01-01

    Exploration of chronobiological systems emerges as a growing research field within bioinformatics focusing on various applications in medicine, agriculture, and material sciences. From a systems biological perspective, the question arises whether biological control systems for regulation of oscillatory signals and their technical counterparts utilise similar mechanisms. If so, modelling approaches and parameterisation adopted from building blocks can help to identify general components for frequency control in circadian clocks along with gaining insight into mechanisms of clock synchronisation to external stimuli like the daily rhythm of sunlight and darkness. Phase-locked loops could be an interesting candidate in this context. Both, biology and engineering, can benefit from a unified view resulting from systems modularisation. In a first experimental study, we analyse a model of coupled repressilators. We demonstrate its ability to synchronise clock signals in a monofrequential manner. Several oscillators initially deviate in phase difference and frequency with respect to explicit reaction and diffusion rates. Accordingly, the duration of the synchronisation process depends on dedicated reaction and diffusion parameters whose settings still lack to be sufficiently captured analytically. PMID:22046179

  5. Circadian Rhythms in Diet-Induced Obesity.

    Science.gov (United States)

    Engin, Atilla

    2017-01-01

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

  6. Paternal irradiation perturbs the expression of circadian genes in offspring

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  7. Paternal irradiation perturbs the expression of circadian genes in offspring

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-15

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

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

    OpenAIRE

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

    2013-01-01

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

  9. Involvement of cortisol and sirtuin1 during the response to stress of hypothalamic circadian system and food intake-related peptides in rainbow trout, Oncorhynchus mykiss.

    Science.gov (United States)

    Naderi, Fatemeh; Hernández-Pérez, Juan; Chivite, Mauro; Soengas, José L; Míguez, Jesús M; López-Patiño, Marcos A

    2018-05-08

    Stress is conditioning animal welfare by negatively affecting a wide range of physiological and behavioral functions. This may be applied to circadian physiology and food intake. Cortisol, the stress-related hormone, may mediate such effect of stress, but other indirect mediators might be considered, such as sirtuin1. Then, either the independent modulatory effect or the existence of any interaction between mediators may be responsible. The circadian system is the main modulator of several integrative mechanisms at both central and peripheral levels that are rhythmically presented, thus influencing different processes such as food intake. In this way, food intake is controlled by the circadian system, as demonstrated by the persistence of such rhythms of food intake in the absence of environmental external cues. Our study aimed to evaluate the daily profile of hypothalamic mRNA abundance of circadian clock genes (clock1a, bmal1, per1 and rev-erbβ-like), and food intake regulators (crf, pomc-a1, cart, and npy) in rainbow trout (Oncorhynchus mykiss), the impact of stress on such rhythms, and the involvement of cortisol and sirtuin1 as mediators. Four cohorts of trout were subjected to 1) normal stocking density (control group), 2) high stocking density for 72 hours (stress group), 3) normal stocking density and implanted with mifepristone, a glucocorticoid receptors antagonist, and 4) mifepristone administered and stressed for 72 hours. Fish from each group were sampled every 4-h along the 24-h LD cycle, and cortisol, glucose and lactate plasma levels were evaluated. Hypothalamic mRNA abundance of clock genes, food intake regulators, glucocorticoid receptors and sirtuin1 were qPCR assayed. Our results reveal the impact of stress on most of the genes assayed, but different mechanisms appear to be involved. The rhythm of clock genes displayed decreased amplitude and averaged levels in stressed trout, with no changes of the acrophase being observed. This effect was

  10. Circadian Rhythm Disruption Promotes Lung Tumorigenesis.

    Science.gov (United States)

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

    2016-08-09

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

  11. Use of Circadian Lighting System to improve night shift alertness and performance of NRC Headquarters Operations Officers

    Energy Technology Data Exchange (ETDEWEB)

    Baker, T.L.; Morisseau, D.; Murphy, N.M. [ShiftWork Systems, Cambridge, MA (United States)] [and others

    1995-04-01

    The Nuclear Regulatory Commission`s (NRC) Headquarters Operations Officers (HOOs) receive and respond to events reported in the nuclear industry on a 24-hour basis. The HOOs have reported reduced alertness on the night shift, leading to a potential deterioration in their on-shift cognitive performance during the early morning hours. For some HOOs, maladaptation to the night shift was also reported to be the principal cause of: (a) reduced alertness during the commute to and from work, (b) poor sleep quality, and (c) personal lifestyle problems. ShiftWork Systems, Inc. (SWS) designed and installed a Circadian Lighting System (CLS) at both the Bethesda and Rockville HOO stations with the goal of facilitating the HOOs physiological adjustment to their night shift schedules. The data indicate the following findings: less subjective fatigue on night shifts; improved night shift alertness and mental performance; higher HOO confidence in their ability to assess event reports; longer, deeper and more restorative day sleep after night duty shifts; swifter adaptation to night work; and a safer commute, particularly for those with extensive drives.

  12. Use of Circadian Lighting System to improve night shift alertness and performance of NRC Headquarters Operations Officers

    International Nuclear Information System (INIS)

    Baker, T.L.; Morisseau, D.; Murphy, N.M.

    1995-01-01

    The Nuclear Regulatory Commission's (NRC) Headquarters Operations Officers (HOOs) receive and respond to events reported in the nuclear industry on a 24-hour basis. The HOOs have reported reduced alertness on the night shift, leading to a potential deterioration in their on-shift cognitive performance during the early morning hours. For some HOOs, maladaptation to the night shift was also reported to be the principal cause of: (a) reduced alertness during the commute to and from work, (b) poor sleep quality, and (c) personal lifestyle problems. ShiftWork Systems, Inc. (SWS) designed and installed a Circadian Lighting System (CLS) at both the Bethesda and Rockville HOO stations with the goal of facilitating the HOOs physiological adjustment to their night shift schedules. The data indicate the following findings: less subjective fatigue on night shifts; improved night shift alertness and mental performance; higher HOO confidence in their ability to assess event reports; longer, deeper and more restorative day sleep after night duty shifts; swifter adaptation to night work; and a safer commute, particularly for those with extensive drives

  13. [Circadian markers and genes in bipolar disorder].

    Science.gov (United States)

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

    2015-09-01

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

  14. Radioimmunological analysis of circadian rhythms of cortisol and melatonin in saliva

    International Nuclear Information System (INIS)

    Demel, A.W.

    1990-12-01

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

  15. Radioimmunological analysis of circadian rhythms of cortisol and melatonin in saliva

    International Nuclear Information System (INIS)

    Demel, A.W.

    1990-12-01

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

  16. Circadian Metabolomics in Time and Space

    Directory of Open Access Journals (Sweden)

    Kenneth A. Dyar

    2017-07-01

    Full Text Available Circadian rhythms are widely known to govern human health and disease, but specific pathogenic mechanisms linking circadian disruption to metabolic diseases are just beginning to come to light. This is thanks in part to the development and application of various “omics”-based tools in biology and medicine. Current high-throughput technologies allow for the simultaneous monitoring of multiple dynamic cellular events over time, ranging from gene expression to metabolite abundance and sub-cellular localization. These fundamental temporal and spatial perspectives have allowed for a more comprehensive understanding of how various dynamic cellular events and biochemical processes are related in health and disease. With advances in technology, metabolomics has become a more routine “omics” approach for studying metabolism, and “circadian metabolomics” (i.e., studying the 24-h metabolome has recently been undertaken by several groups. To date, circadian metabolomes have been reported for human serum, saliva, breath, and urine, as well as tissues from several species under specific disease or mutagenesis conditions. Importantly, these studies have consistently revealed that 24-h rhythms are prevalent in almost every tissue and metabolic pathway. Furthermore, these circadian rhythms in tissue metabolism are ultimately linked to and directed by internal 24-h biological clocks. In this review, we will attempt to put these data-rich circadian metabolomics experiments into perspective to find out what they can tell us about metabolic health and disease, and what additional biomarker potential they may reveal.

  17. The Regulation of Mammalian Circadian Physiology by Light

    National Research Council Canada - National Science Library

    Foster, Russel

    1997-01-01

    .... Our work studies on retinally degenerate mammals have shown that visual blindness need not mean circadian blindness, and that two functionally distinct systems for processing light information must...

  18. Circadian rhythms of women with fibromyalgia

    Science.gov (United States)

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

    2001-01-01

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

  19. The effects of hydrogen peroxide on the circadian rhythms of Microcystis aeruginosa.

    Directory of Open Access Journals (Sweden)

    Haifeng Qian

    Full Text Available 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 (H(2O(2 on the expression of clock genes and some circadian genes in M. aeruginosa during the light/dark (LD cycle. RESULTS: The results revealed that H(2O(2 changes the expression patterns of clock genes (kaiA, kaiB, kaiC and sasA and significantly decreases the transcript levels of kaiB, kaiC and sasA. H(2O(2 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 H(2O(2 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.

  20. Implications of Circadian Rhythm in Dopamine and Mood Regulation.

    Science.gov (United States)

    Kim, Jeongah; Jang, Sangwon; Choe, Han Kyoung; Chung, Sooyoung; Son, Gi Hoon; Kim, Kyungjin

    2017-07-31

    Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-erbα induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

  1. Mathematical Models of the Circadian Sleep-Wake Cycle.

    Science.gov (United States)

    1984-05-01

    circadian geber , 97,98 system precision, 4 Form factor Damped oscillators, mutual excitation of, and relationship to ratio of deviations, 37 self-sustainment...rhythms, 5-6 Forced internal desynebronization, by Zeit- incorporation of, into models of circadian geber , 97,98 system precision, 4 Form factor Damped...equation, for modeling of circadian geber phase, and modification by fre- rhythms, 19 quency coefficient, 54,55,56 Oscillatory range, effects of

  2. Circadian Rhythms and Obesity in Mammals

    OpenAIRE

    Froy, Oren

    2012-01-01

    Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating the circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabol...

  3. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    nature of the system underlying such rhythms and inspired one of the ... behaviours and physiological processes were discovered in a wide range of animals. ... is thought to coordinate internal physiology, and thereby confer benefits to living ...

  4. Circadian Rhythm Sleep Disorders

    Directory of Open Access Journals (Sweden)

    Erhan Akinci

    2016-06-01

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

  5. Circadian rhythm disruption was observed in hand, foot, and mouth disease patients.

    Science.gov (United States)

    Zhu, Yu; Jiang, Zhou; Xiao, Guoguang; Cheng, Suting; Wen, Yang; Wan, Chaomin

    2015-03-01

    Hand, foot, and mouth disease (HFMD) with central nerve system complications may rapidly progress to fulminated cardiorespiratory failure, with higher mortality and worse prognosis. It has been reported that circadian rhythms of heart rate (HR) and respiratory rate are useful in predicting prognosis of severe cardiovascular and neurological diseases. The present study aims to investigate the characteristics of the circadian rhythms of HR, respiratory rate, and temperature in HFMD patients with neurological complications. Hospitalized HFMD patients including 33 common cases (common group), 61 severe cases (severe group), and 9 critical cases (critical group) were contrasted retrospectively. Their HR, respiratory rate, and temperatures were measured every 4 hours during the first 48-hour in the hospital. Data were analyzed with the least-squares fit of a 24-hour cosine function by the single cosinor and population-mean cosinor method. Results of population-mean cosinor analysis demonstrated that the circadian rhythm of HR, respiratory rate, and temperature was present in the common and severe group, but absent in the critical group. The midline-estimating statistic of rhythm (MESOR) (P = 0.016) and acrophase (P circadian characteristics of HR among 3 groups. Compared with the common group, the MESOR of temperature and respiratory rate was significantly higher, and acrophase of temperature and respiratory rate was 2 hours ahead in the severe group, critical HFMD patients lost their population-circadian rhythm of temperature, HR, and respiratory rate. The high values of temperature and respiratory rate for the common group were concentrated between 3 and 9 PM, whereas those for the severe group were more dispersive. And the high values for the critical group were equally distributed in 24 hours of the day. Circadian rhythm of patients' temperature in the common group was the same as the normal rhythm of human body temperature. Circadian rhythm of patients

  6. Distribution of circadian clock-related proteins in the cephalic nervous system of the silkworm, Bombyx mori

    Czech Academy of Sciences Publication Activity Database

    Sehadová, Hana; Markova, E. P.; Sehnal, František; Takeda, M.

    2004-01-01

    Roč. 19, č. 6 (2004), s. 466-482 ISSN 0748-7304 Grant - others:JSPS(JP) 99L01205 Institutional research plan: CEZ:AV0Z5007907 Keywords : circadian rhythm * PER * CYC Subject RIV: ED - Physiology Impact factor: 2.979, year: 2004

  7. Evolution of circadian organization in vertebrates

    Directory of Open Access Journals (Sweden)

    M. Menaker

    1997-03-01

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

  8. Why and how do we model circadian rhythms?

    NARCIS (Netherlands)

    Beersma, DGM

    In our attempts to understand the circadian system, we unavoidably rely on abstractions. Instead of describing the behavior of the circadian system in all its complexity, we try to derive basic features from which we form a global concept on how the system works. Such a basic concept is a model of

  9. Circadian Rhythm Control: Neurophysiological Investigations

    Science.gov (United States)

    Glotzbach, S. F.

    1985-01-01

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

  10. Epigenetic control and the circadian clock: linking metabolism to neuronal responses.

    Science.gov (United States)

    Orozco-Solis, R; Sassone-Corsi, P

    2014-04-04

    Experimental and epidemiological evidence reveal the profound influence that industrialized modern society has imposed on human social habits and physiology during the past 50 years. This drastic change in life-style is thought to be one of the main causes of modern diseases including obesity, type 2 diabetes, mental illness such as depression, sleep disorders, and certain types of cancer. These disorders have been associated to disruption of the circadian clock, an intrinsic time-keeper molecular system present in virtually all cells and tissues. The circadian clock is a key element in homeostatic regulation by controlling a large array of genes implicated in cellular metabolism. Importantly, intimate links between epigenetic regulation and the circadian clock exist and are likely to prominently contribute to the plasticity of the response to the environment. In this review, we summarize some experimental and epidemiological evidence showing how environmental factors such as stress, drugs of abuse and changes in circadian habits, interact through different brain areas to modulate the endogenous clock. Furthermore we point out the pivotal role of the deacetylase silent mating-type information regulation 2 homolog 1 (SIRT1) as a molecular effector of the environment in shaping the circadian epigenetic landscape. Published by Elsevier Ltd.

  11. Physiological links of circadian clock and biological clock of aging.

    Science.gov (United States)

    Liu, Fang; Chang, Hung-Chun

    2017-07-01

    Circadian rhythms orchestrate biochemical and physiological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold self-sustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photoperiod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles. With aging, circadian desynchrony occurs at the expense of peripheral metabolic pathologies and central neurodegenerative disorders with sleep symptoms, and genetic ablation of circadian genes in model organisms resembled the aging-related features. Notably, a number of studies have linked longevity nutrient sensing pathways in modulating circadian clocks. Therapeutic strategies that bridge the nutrient sensing pathways and circadian clock might be rational designs to defy aging.

  12. Circadian organization in hemimetabolous insects.

    Science.gov (United States)

    Tomioka, Kenji; Abdelsalam, Salaheldin

    2004-12-01

    The circadian system of hemimetabolous insects is reviewed in respect to the locus of the circadian clock and multioscillatory organization. Because of relatively easy access to the nervous system, the neuronal organization of the clock system in hemimetabolous insects has been studied, yielding identification of the compound eye as the major photoreceptor for entrainment and the optic lobe for the circadian clock locus. The clock site within the optic lobe is inconsistent among reported species; in cockroaches the lobula was previously thought to be a most likely clock locus but accessory medulla is recently stressed to be a clock center, while more distal part of the optic lobe including the lamina and the outer medulla area for the cricket. Identification of the clock cells needs further critical studies. Although each optic lobe clock seems functionally identical, in respect to photic entrainment and generation of the rhythm, the bilaterally paired clocks form a functional unit. They interact to produce a stable time structure within individual insects by exchanging photic and temporal information through neural pathways, in which serotonin and pigment-dispersing factor (PDF) are involved as chemical messengers. The mutual interaction also plays an important role in seasonal adaptation of the rhythm.

  13. The circadian rhythm of core body temperature (Part I: The use of modern telemetry systems to monitor core body temperature variability

    Directory of Open Access Journals (Sweden)

    Słomko Joanna

    2016-06-01

    Full Text Available The best known daily rhythms in humans include: the sleep-wake rhythm, the circadian core body temperature variability, daily fluctuations in arterial blood pressure and heartbeat frequency, and daily changes in hormone secretion: e.g. melatonin, cortisol, growth hormone, prolactin. The core body temperature in humans has a characteristic sinusoidal course, with the maximum value occurring between 3:00-5:00 pm and the minimum between 3:00-5:00 am. Analysis of literature indicates that the obtained results concerning core body temperature are to a large extent influenced by the type of method applied in the measurement. Depending on test protocols, we may apply various methodologies to measuring core body temperature. One of the newest methods of measuring internal and external body temperature consists in the utilisation of remote temperature sensors transmitting the obtained value via a radio signal. The advantages of this method includes the ability to perform: continuous core temperature measurement, observe dynamic changes in core body temperature occurring in circadian rhythm and the repeatability and credibility of the obtained results, which is presented in numerous scientific reports.

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

    Directory of Open Access Journals (Sweden)

    Taishi Yoshii

    2009-04-01

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

  15. Absence of an increase in the duration of the circadian melatonin secretory episode in totally blind human subjects

    Science.gov (United States)

    Klerman, E. B.; Zeitzer, J. M.; Duffy, J. F.; Khalsa, S. B.; Czeisler, C. A.

    2001-01-01

    The daily rhythm of melatonin influences multiple physiological measures, including sleep tendency, circadian rhythms, and reproductive function in seasonally breeding mammals. The biological signal for photoperiodic changes in seasonally breeding mammals is a change in the duration of melatonin secretion, which in a natural environment reflects the different durations of daylight across the year, with longer nights leading to a longer duration of melatonin secretion. These seasonal changes in the duration of melatonin secretion do not simply reflect the known acute suppression of melatonin secretion by ocular light exposure, but also represent long-term changes in the endogenous nocturnal melatonin episode that persist in constant conditions. As the eyes of totally blind individuals do not transmit ocular light information, we hypothesized that the duration of the melatonin secretory episode in blind subjects would be longer than those in sighted individuals, who are exposed to light for all their waking hours in an urban environment. We assessed the melatonin secretory profile during constant posture, dim light conditions in 17 blind and 157 sighted adults, all of whom were healthy and using no prescription or nonprescription medications. The duration of melatonin secretion was not significantly different between blind and sighted individuals. Healthy blind individuals after years without ocular light exposure do not have a longer duration of melatonin secretion than healthy sighted individuals.

  16. Human factors information system

    International Nuclear Information System (INIS)

    Goodman, P.C.; DiPalo, C.A.

    1991-01-01

    Nuclear power plant safety is dependent upon human performance related to plant operations. To provide improvements in human performance, data collection and assessment play key roles. This paper reports on the Human factors Information System (HFIS) which is designed to meet the needs of the human factors specialists of the United States Nuclear Regulatory Commission. These specialists identify personnel errors and provide guidance designed to prevent such errors. HFIS is a simple and modular system designed for use on a personal computer. It is designed to contain four separate modules that provide information indicative of program or function effectiveness as well as safety-related human performance based on programmatic and performance data. These modules include the Human Factors Status module; the Regulatory Programs module; the Licensee Event Report module; and the Operator Requalification Performance module. Information form these modules can either be used separately or can be combined due to the integrated nature of the system. HFIS has the capability, therefore, to provide insights into those areas of human factors that can reduce the probability of events caused by personnel error at nuclear power plants and promote the health and safety of the public. This information system concept can be applied to other industries as well as the nuclear industry

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

    Directory of Open Access Journals (Sweden)

    Rabinovich Gabriel A

    2010-04-01

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

  18. The sleep and circadian modulation of neural reward pathways: a protocol for a pair of systematic reviews.

    Science.gov (United States)

    Byrne, Jamie E M; Murray, Greg

    2017-12-02

    Animal research suggests that neural reward activation may be systematically modulated by sleep and circadian function. Whether humans also exhibit sleep and circadian modulation of neural reward pathways is unclear. This area is in need of further research, as it has implications for the involvement of sleep and circadian function in reward-related disorders. The aim of this paper is to describe the protocol for a pair of systematic literature reviews to synthesise existing literature related to (1) sleep and (2) circadian modulation of neural reward pathways in healthy human populations. A systematic review of relevant online databases (Scopus, PubMed, Web of Science, ProQuest, PsycINFO and EBSCOhost) will be conducted. Reference lists, relevant reviews and supplementary data will be searched for additional articles. Articles will be included if (a) they contain a sleep- or circadian-related predictor variable with a neural reward outcome variable, (b) use a functional magnetic resonance imaging protocol and (c) use human samples. Articles will be excluded if study participants had disorders known to affect the reward system. The articles will be screened by two independent authors. Two authors will complete the data extraction form, with two authors independently completing the quality assessment tool for the selected articles, with a consensus reached with a third author if needed. Narrative synthesis methods will be used to analyse the data. The findings from this pair of systematic literature reviews will assist in the identification of the pathways involved in the sleep and circadian function modulation of neural reward in healthy individuals, with implications for disorders characterised by dysregulation in sleep, circadian rhythms and reward function. PROSPERO CRD42017064994.

  19. Human Systems Design Criteria

    DEFF Research Database (Denmark)

    Rasmussen, Jens

    1982-01-01

    This paper deals with the problem of designing more humanised computer systems. This problem can be formally described as the need for defining human design criteria, which — if used in the design process - will secure that the systems designed get the relevant qualities. That is not only...... the necessary functional qualities but also the needed human qualities. The author's main argument is, that the design process should be a dialectical synthesis of the two points of view: Man as a System Component, and System as Man's Environment. Based on a man's presentation of the state of the art a set...... of design criteria is suggested and their relevance discussed. The point is to focus on the operator rather than on the computer. The crucial question is not to program the computer to work on its own conditions, but to “program” the operator to function on human conditions....

  20. Identification of circadian clock modulators from existing drugs.

    Science.gov (United States)

    Tamai, T Katherine; Nakane, Yusuke; Ota, Wataru; Kobayashi, Akane; Ishiguro, Masateru; Kadofusa, Naoya; Ikegami, Keisuke; Yagita, Kazuhiro; Shigeyoshi, Yasufumi; Sudo, Masaki; Nishiwaki-Ohkawa, Taeko; Sato, Ayato; Yoshimura, Takashi

    2018-04-17

    Chronic circadian disruption due to shift work or frequent travel across time zones leads to jet-lag and an increased risk of diabetes, cardiovascular disease, and cancer. The development of new pharmaceuticals to treat circadian disorders, however, is costly and hugely time-consuming. We therefore performed a high-throughput chemical screen of existing drugs for circadian clock modulators in human U2OS cells, with the aim of repurposing known bioactive compounds. Approximately 5% of the drugs screened altered circadian period, including the period-shortening compound dehydroepiandrosterone (DHEA; also known as prasterone). DHEA is one of the most abundant circulating steroid hormones in humans and is available as a dietary supplement in the USA Dietary administration of DHEA to mice shortened free-running circadian period and accelerated re-entrainment to advanced light-dark (LD) cycles, thereby reducing jet-lag. Our drug screen also revealed the involvement of tyrosine kinases, ABL1 and ABL2, and the BCR serine/threonine kinase in regulating circadian period. Thus, drug repurposing is a useful approach to identify new circadian clock modulators and potential therapies for circadian disorders. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  1. Human Performance Evaluation System

    International Nuclear Information System (INIS)

    Hardwick, R.J. Jr.

    1985-01-01

    Operating nuclear power plants requires high standards of performance, extensive training and responsive management. Despite our best efforts inappropriate human actions do occur, but they can be managed. An extensive review of License Event Reports (LERs) was conducted which indicated continual inadequacy in human performance and in evaluation of root causes. Of some 31,000 LERs, about 5,000 or 16% were directly attributable to inappropriate actions. A recent analysis of 87 Significant Event Reports (issued by INPO in 1983) identified inappropriate actions as being the most frequent root cause (44% of the total). A more recent analysis of SERs issued in 1983 and 1984 indicate that 52% of the root causes were attributed to human performance. The Human Performance Evaluation System (HPES) is a comprehensive, coordinated utility/industry system for evaluating and reporting human performance situtations. HPES is a result of the realization that current reporting system provide limited treatment of human performance and rarely provide adequate information about root causes of inappropriate actions by individuals. The HPES was implemented to identify and eliminate root causes of inappropriate actions

  2. Age-related changes in the transmission properties of the human lens and their relevance to circadian entrainment

    DEFF Research Database (Denmark)

    Kessel, Line; Lundeman, Jesper Holm; Herbst, Kristina

    2010-01-01

    To characterize age-related changes in the transmission of light through noncataractous human lenses.......To characterize age-related changes in the transmission of light through noncataractous human lenses....

  3. Vitamin concentrations in human milk vary with time within feed, circadian rhythm, and single-dose supplementation

    Science.gov (United States)

    Importance: Human milk is the subject of many nutrition studies but methods for representative sample collection are not established. Our recently improved, validated methods for analyzing micronutrients in human milk now enable systematic study of factors affecting their concentration. Objective...

  4. Advanced Solid State Lighting for Human Evaluation

    Data.gov (United States)

    National Aeronautics and Space Administration — Lighting intensity and color have a significant impact on human circadian rhythms.  Advanced solid state lighting was developed for the Advanced Exploration System...

  5. Circadian variation in sports performance.

    Science.gov (United States)

    Atkinson, G; Reilly, T

    1996-04-01

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

  6. Regulation of circadian blood pressure: from mice to astronauts.

    Science.gov (United States)

    Agarwal, Rajiv

    2010-01-01

    Circadian variation is commonly seen in healthy people; aberration in these biological rhythms is an early sign of disease. Impaired circadian variation of blood pressure (BP) has been shown to be associated with greater target organ damage and with an elevated risk of cardiovascular events independent of the BP load. The purpose of this review is to examine the physiology of circadian BP variation and propose a tripartite model that explains the regulation of circadian BP. The time-keeper in mammals resides centrally in the suprachiasmatic nucleus. Apart from this central clock, molecular clocks exist in most peripheral tissues including vascular tissue and the kidney. These molecular clocks regulate sodium balance, sympathetic function and vascular tone. A physiological model is proposed that integrates our understanding of molecular clocks in mice with the circadian BP variation among humans. The master regulator in this proposed model is the sleep-activity cycle. The equivalents of peripheral clocks are endothelial and adrenergic functions. Thus, in the proposed model, the variation in circadian BP is dependent upon three major factors: physical activity, autonomic function, and sodium sensitivity. The integrated consideration of physical activity, autonomic function, and sodium sensitivity appears to explain the physiology of circadian BP variation and the pathophysiology of disrupted BP rhythms in various conditions and disease states. Our understanding of molecular clocks in mice may help to explain the provenance of blunted circadian BP variation even among astronauts.

  7. The circadian response of intrinsically photosensitive retinal ganglion cells.

    Directory of Open Access Journals (Sweden)

    Andrew J Zele

    Full Text Available Intrinsically photosensitive retinal ganglion cells (ipRGC signal environmental light level to the central circadian clock and contribute to the pupil light reflex. It is unknown if ipRGC activity is subject to extrinsic (central or intrinsic (retinal network-mediated circadian modulation during light entrainment and phase shifting. Eleven younger persons (18-30 years with no ophthalmological, medical or sleep disorders participated. The activity of the inner (ipRGC and outer retina (cone photoreceptors was assessed hourly using the pupil light reflex during a 24 h period of constant environmental illumination (10 lux. Exogenous circadian cues of activity, sleep, posture, caffeine, ambient temperature, caloric intake and ambient illumination were controlled. Dim-light melatonin onset (DLMO was determined from salivary melatonin assay at hourly intervals, and participant melatonin onset values were set to 14 h to adjust clock time to circadian time. Here we demonstrate in humans that the ipRGC controlled post-illumination pupil response has a circadian rhythm independent of external light cues. This circadian variation precedes melatonin onset and the minimum ipRGC driven pupil response occurs post melatonin onset. Outer retinal photoreceptor contributions to the inner retinal ipRGC driven post-illumination pupil response also show circadian variation whereas direct outer retinal cone inputs to the pupil light reflex do not, indicating that intrinsically photosensitive (melanopsin retinal ganglion cells mediate this circadian variation.

  8. The importance of hormonal circadian rhythms in daily feeding patterns: An illustration with simulated pigs.

    Science.gov (United States)

    Boumans, Iris J M M; de Boer, Imke J M; Hofstede, Gert Jan; la Fleur, Susanne E; Bokkers, Eddie A M

    2017-07-01

    The interaction between hormonal circadian rhythms and feeding behaviour is not well understood. This study aimed to deepen our understanding of mechanisms underlying circadian feeding behaviour in animals, using pigs, Sus scrofa, as a case study. Pigs show an alternans feeding pattern, that is, a small peak of feed intake at the beginning of the day and a larger peak at the end of the day. We simulated the feeding behaviour of pigs over a 24h period. The simulation model contained mechanisms that regulate feeding behaviour of animals, including: processing of feed in the gastrointestinal tract, fluctuation in energy balance, circadian rhythms of melatonin and cortisol and motivational decision-making. From the interactions between these various processes, feeding patterns (e.g. feed intake, meal frequency, feeding rate) emerge. These feeding patterns, as well as patterns for the underlying mechanisms (e.g. energy expenditure), fitted empirical data well, indicating that our model contains relevant mechanisms. The circadian rhythms of cortisol and melatonin explained the alternans pattern of feeding in pigs. Additionally, the timing and amplitude of cortisol peaks affected the diurnal and nocturnal peaks in feed intake. Furthermore, our results suggest that circadian rhythms of other hormones, such as leptin and ghrelin, are less important in circadian regulation of feeding behaviour than previously thought. These results are relevant to animal species with a metabolic and endocrine system similar to that of pigs, such as humans. Moreover, the modelling approach to understand feeding behaviour can be applied to other animal species. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    1994-04-01

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

  10. Circadian physiology of metabolism.

    Science.gov (United States)

    Panda, Satchidananda

    2016-11-25

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

  11. Immunity's fourth dimension: approaching the circadian-immune connection.

    Science.gov (United States)

    Arjona, Alvaro; Silver, Adam C; Walker, Wendy E; Fikrig, Erol

    2012-12-01

    The circadian system ensures the generation and maintenance of self-sustained ~24-h rhythms in physiology that are linked to internal and environmental changes. In mammals, daily variations in light intensity and other cues are integrated by a hypothalamic master clock that conveys circadian information to peripheral molecular clocks that orchestrate physiology. Multiple immune parameters also vary throughout the day and disruption of circadian homeostasis is associated with immune-related disease. Here, we discuss the molecular links between the circadian and immune systems and examine their outputs and disease implications. Understanding the mechanisms that underlie circadian-immune crosstalk may prove valuable for devising novel prophylactic and therapeutic interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. How does healthy aging impact on the circadian clock?

    Science.gov (United States)

    Popa-Wagner, Aurel; Buga, Ana-Maria; Dumitrascu, Dinu Iuliu; Uzoni, Adriana; Thome, Johannes; Coogan, Andrew N

    2017-02-01

    Circadian rhythms are recurring patterns in a host of physiological and other parameters that recur with periods of near 24 h. These rhythms reflect the temporal organization of an organism's homeostatic control systems and as such are key processes in ensuring optimal physiological performance. Dysfunction of circadian processes is linked with adverse health conditions. In this review we highlight the evidence that normal, healthy aging is associated with changes in the circadian system; we examine the molecular mechanisms through which such changes may arise, discuss whether more robust circadian function is a predictor of longevity and highlight the role of circadian rhythms in age-related diseases. Overall, the literature shows that aging is associated with marked changes in circadian processes, both at the behavioral and molecular levels, and the molecular mechanisms through which such changes arise remain to be elucidated, but may involve inflammatory process, redox homeostasis and epigenetic modifications. Understanding the nature of age-related circadian dysfunction will allow for the design of chronotherapeutic intervention strategies to attenuate circadian dysfunction and thus improve health and quality of life.

  13. Human Systems Roadmap Review

    Science.gov (United States)

    2016-02-09

    Impact of Human Systems Community of Interest D O T M L P F $450M COI Budget Has Broad Impact in Several DOTMLPF Areas Decision Making Selection...and fit to a military career. • 26 personality dimensions such as optimism, excitement seeking, and non- delinquency • Applicant chooses from...Adaptive Collaborative Control Technologies ( IMPACT ) architecture designed • IMPACT “DoD Virtual Lab” established (Year 1) • 1 operator x 6 vehicles

  14. Diurnal oscillations of soybean circadian clock and drought responsive genes.

    Directory of Open Access Journals (Sweden)

    Juliana Marcolino-Gomes

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

  15. Molecular cogs of the insect circadian clock.

    Science.gov (United States)

    Shirasu, Naoto; Shimohigashi, Yasuyuki; Tominaga, Yoshiya; Shimohigashi, Miki

    2003-08-01

    During the last five years, enormous progress has been made in understanding the molecular basis of circadian systems, mainly by molecular genetic studies using the mouse and fly. Extensive evidence has revealed that the core clock machinery involves "clock genes" and "clock proteins" functioning as molecular cogs. These participate in transcriptional/translational feedback loops and many homologous clock-components in the fruit fly Drosophila are also expressed in mammalian clock tissues with circadian rhythms. Thus, the mechanisms of the central clock seem to be conserved across animal kingdom. However, some recent studies imply that the present widely accepted molecular models of circadian clocks may not always be supported by the experimental evidence.

  16. Circadian Rhythm Sleep-Wake Disorders in Older Adults.

    Science.gov (United States)

    Kim, Jee Hyun; Duffy, Jeanne F

    2018-03-01

    The timing, duration, and consolidation of sleep result from the interaction of the circadian timing system with a sleep-wake homeostatic process. When aligned and functioning optimally, this allows wakefulness throughout the day and a long consolidated sleep episode at night. Mismatch between the desired timing of sleep and the ability to fall and remain asleep is a hallmark of the circadian rhythm sleep-wake disorders. This article discusses changes in circadian regulation of sleep with aging; how age influences the prevalence, diagnosis, and treatment of circadian rhythm sleep-wake disorders; and how neurologic diseases in older patients affect circadian rhythms and sleep. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Circadian Control of the Estrogenic Circuits Regulating GnRH Secretion and the Preovulatory Luteinizing Hormone Surge

    Directory of Open Access Journals (Sweden)

    Lance J Kriegsfeld

    2012-05-01

    Full Text Available Female reproduction requires the precise temporal organization of interacting, estradiol-sensitive neural circuits that converge to optimally drive hypothalamo-pituitary-gonadal (HPG axis functioning. In mammals, the master circadian pacemaker in the suprachaismatic nucleus (SCN of the anterior hypothalamus coordinates reproductively-relevant neuroendocrine events necessary to maximize reproductive success. Likewise, in species where periods of fertility are brief, circadian oversight of reproductive function ensures that estradiol-dependent increases in sexual motivation coincide with ovulation. Across species, including humans, disruptions to circadian timing (e.g., through rotating shift work, night shift work, poor sleep hygiene lead to pronounced deficits in ovulation and fecundity. Despite the well-established roles for the circadian system in female reproductive functioning, the specific neural circuits and neurochemical mediators underlying these interactions are not fully understood. Most work to date has focused on the direct and indirect communication from the SCN to the GnRH system in control of the preovulatory LH surge. However, the same clock genes underlying circadian rhythms at the cellular level in SCN cells are also common to target cell populations of the SCN, including the GnRH neuronal network. Exploring the means by which the master clock synergizes with subordinate clocks in GnRH cells and its upstream modulatory systems represents an exciting opportunity to further understand the role of endogenous timing systems in female reproduction. Herein we provide an overview of the state of knowledge regarding interactions between the circadian timing system and estradiol-sensitive neural circuits driving GnRH secretion and the preovulatory LH surge.

  18. Biological Clocks & Circadian Rhythms

    Science.gov (United States)

    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…

  19. Circadian rhythms regulate amelogenesis.

    Science.gov (United States)

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

    2013-07-01

    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 the 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 (24 h) intervals both at RNA and protein levels. This study also reveals that the two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory stage ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation stage 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 stages of amelogenesis might be under circadian control. Changes in clock gene expression patterns might result in significant alterations of enamel apposition and mineralization. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Circadian rhythmicity of the urinary excretion of mercury, potassium and catecholamines in unconventional shift-work systems.

    Science.gov (United States)

    Vokac, Z; Gundersen, N; Magnus, P; Jebens, E; Bakka, T

    1980-09-01

    The round the clock urinary excretion rates of mercury were assessed for two series of unconventional patterns of activity and sleep in subjects who were not exposed to occupational, medical, or other obvious sources of mercury. In the first series the urine was collected in 3-h periods from six subjects during the first and last 2 d of a four-week, continuous 6-h shift (car ferry, watches either 0800--1400 and 2000--0200 or 1400--2000 and 0200--0800). In the second series the urine was collected in 4-h periods from five subjects working an 8-h experimental rotation shift compressed into 5 d (work two mornings--8-h interval--work two nights--8-h interval--work two afternoons). The mean daily excretion rate of the 11 subjects (48 investigation days, 334 urine samples) was 14.5 pmol of mercury/min (range 5.5--24.4 pmol of mercury/min). The mercury excretion oscillated regularly during 24 h by +/- 20--25% of the individual's daily mean excretion rates. The peak excretion rates were found at 0652 in the first and 0642 in the second series (cosinor treatment). Due to the circadian rhythm the mean 24-h excretion rates were best represented (correlation coefficient 0.92) by analyses of urine produced around noon (spot samples, collection periods 1100--1400 and 1000-1400, respectively). The circadian oscillations of mercury excretion were not influenced by the widely different and varying activity-sleep patterns of the two series. The rhythmicity of potassium excretion (peaks at around 1400) was more irregular. The stable oscillations of mercury excretion contrasted most with the excretion of adrenaline and noradrenaline, which, without losing the basic 24-h rhythmicity, closely followed the unconventional patterns of activity and sleep.

  1. Circadian Metabolism in the Light of Evolution

    DEFF Research Database (Denmark)

    Gerhart-Hines, Zachary; Lazar, Mitchell A.

    2015-01-01

    was originally set. A bombardment of artificial lighting, heating, and cooling systems that maintain const. ambient temp.; sedentary lifestyle; and the availability of inexpensive, high-calorie foods has threatened even the most powerful and ancient circadian programming mechanisms. Such environmental changes...

  2. Insights into the role of the habenular circadian clock in addiction

    Directory of Open Access Journals (Sweden)

    Nora L Salaberry

    2016-01-01

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

  3. Manipulating the Circadian and Sleep Cycles to Protect Against Metabolic Disease

    OpenAIRE

    Nohara, Kazunari; Yoo, Seung-Hee; Chen, Zheng (Jake)

    2015-01-01

    Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that reg...

  4. Circadian Regulation of Glutamate Transporters

    Directory of Open Access Journals (Sweden)

    Donají Chi-Castañeda

    2018-06-01

    Full Text Available L-glutamate is the major excitatory amino acid in the mammalian central nervous system (CNS. This neurotransmitter is essential for higher brain functions such as learning, cognition and memory. A tight regulation of extra-synaptic glutamate levels is needed to prevent a neurotoxic insult. Glutamate removal from the synaptic cleft is carried out by a family of sodium-dependent high-affinity transporters, collectively known as excitatory amino acid transporters. Dysfunction of glutamate transporters is generally involved in acute neuronal injury and neurodegenerative diseases, so characterizing and understanding the mechanisms that lead to the development of these disorders is an important goal in the design of novel treatments for the neurodegenerative diseases. Increasing evidence indicates glutamate transporters are controlled by the circadian system in direct and indirect manners, so in this contribution we focus on the mechanisms of circadian regulation (transcriptional, translational, post-translational and post-transcriptional regulation of glutamate transport in neuronal and glial cells, and their consequence in brain function.

  5. Circadian rhythm in idiopathic normal pressure hydrocephalus.

    Science.gov (United States)

    Eleftheriou, Andreas; Ulander, Martin; Lundin, Fredrik

    2018-01-01

    The pathogenesis of idiopathic normal pressure hydrocephalus (iNPH) takes place in structures close to the cerebral ventricular system. Suprachiasmatic nucleus (SCN), situated close to the third ventricle, is involved in circadian rhythm. Diurnal disturbances are well-known in demented patients. The cognitive decline in iNPH is potentially reversible after a shunt operation. Diurnal rhythm has never been studied in iNPH. We hypothesize that there is a disturbance of circadian rhythm in iNPH-patients and the aim was to study any changes of the diurnal rhythm (mesor and circadian period) as well as any changes of the diurnal amplitude and acrophase of the activity in iNPH-patients before and after a shunt operation. Twenty consecutive iNPH-patients fulfilling the criteria of the American iNPH-guidelines, 9 males and 11 females, mean age 73 (49-81) years were included. The patients underwent a pre-operative clinical work-up including 10m walk time (w10mt) steps (w10ms), TUG-time (TUGt) and steps (TUGs) and for cognitive function an MMSE score was measured. In order to receive circadian rhythm data actigraphic recordings were performed using the SenseWear 2 (BodyMedia Inc Pittsburgh, PA, USA) actigraph. Cosinor analyses of accelerometry data were performed in "R" using non-linear regression with Levenburg- Marquardt estimation. Pre- and post-operative data regarding mesor, amplitude and circadian period were compared using Wilcoxon-Mann-Whitney test for paired data. Twenty patients were evaluated before and three month post-operatively. Motor function (w10mt, w10ms, TUGt, TUGs) was significantly improved while MMSE was not significantly changed. Actigraphic measurements (mesor, amplitude and circadian period) showed no significant changes after shunt operation. This is the first systematic study of circadian rhythm in iNPH-patients. We found no significant changes in circadian rhythm after shunt surgery. The conceptual idea of diurnal rhythm changes in hydrocephalus is

  6. Bright to Dim Oscillatory Response of the Neurospora Circadian Oscillator

    OpenAIRE

    Gooch, Van D.; Johnson, Alicia E.; Larrondo, Luis F.; Loros, Jennifer J.; Dunlap, Jay C.

    2014-01-01

    The fungus Neurospora crassa constitutes an important model system extensively used in chronobiology. Several studies have addressed how environmental cues, such as light, can reset or synchronize a circadian system. By means of an optimized firefly luciferase reporter gene and a controllable lighting system, we show that Neurospora can display molecular circadian rhythms in dim light when cultures receive bright light prior to entering dim light conditions. We refer to this behavior as the “...

  7. Radioimmunological analysis of circadian rhythms of cortisol and melatonin in saliva

    International Nuclear Information System (INIS)

    Demel, A.W.

    1990-12-01

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

  8. Cellular Clocks : Coupled Circadian Dispatch and Cell Division Cycles

    NARCIS (Netherlands)

    Merrow, Martha; Roenneberg, Till

    2004-01-01

    Gating of cell division by the circadian clock is well known, yet its mechanism is little understood. Genetically tractable model systems have led to new hypotheses and questions concerning the coupling of these two cellular cycles.

  9. Circadian rhythm and sleep influences on digestive physiology and disorders

    OpenAIRE

    Vaughn, Bradley; Rotolo,Sean; Roth,Heidi

    2014-01-01

    Bradley V Vaughn, Sean Rotolo, Heidi L Roth Division of Sleep Medicine, Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC, USA Abstract: Circadian rhythms and sleep influence a variety of physiological functions, including the digestive system. The digestive system also has intrinsic rhythms that interact dynamically with circadian rhythms. New advances in understanding the interaction of these rhythms and sleep provide the prospect of evaluating their...

  10. Circadian adaptations to meal timing: Neuroendocrine mechanisms

    Directory of Open Access Journals (Sweden)

    Danica F Patton

    2013-10-01

    Full Text Available 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 is directly entrained by daily light-dark 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

  11. Photoperiodic plasticity in circadian clock neurons in insects

    Directory of Open Access Journals (Sweden)

    Sakiko eShiga

    2013-08-01

    Full Text Available Since Bünning’s observation of circadian rhythms and photoperiodism in the runner bean Phaseolus multiflorus in 1936, many studies have shown that photoperiodism is based on the circadian clock system. In insects, involvement of circadian clock genes or neurons has been recently shown in the photoperiodic control of developmental arrests, diapause. Based on molecular and neuronal studies in Drosophila melanogaster, photoperiodic changes have been reported for expression patterns of the circadian clock genes, subcellular distribution of clock proteins, fiber distribution, or the number of plausible clock neurons in different species. Photoperiod sets peaks of per or tim mRNA abundance at lights-off in Sarcophaga crassipalpis, Chymomyza costata and Protophormia terraenovae. Abundance of per and Clock mRNA changes by photoperiod in Pyrrhocoris apterus. Subcellular Per distribution in circadian clock neurons changes with photoperiod in P. terraenovae. Although photoperiodism is not known in Leucophaea maderae, under longer day length, more stomata and longer commissural fibers of circadian clock neurons have been found. These plastic changes in the circadian clock neurons could be an important constituent for photoperiodic clock mechanisms to integrate repetitive photoperiodic information and produce different outputs based on day length.

  12. The Development of the circadian heart rate rhytm (CDR) in Asian infants

    OpenAIRE

    Stanislaus Sandarupa, Drs., M.A., Ph.D.

    2011-01-01

    Although the human fetus can follow the maternal circadian thythm, the enterained expression of the circadian clock, based in the suprachiasmatic nucleus (SCN) of the hypothalamus awaits postnatal maturation of the retinal hypothalamic tract, and melatonin neurotransmission. Objective: To test the hypothesis that term-born Asian Infants, at reduced risk to die of Sudden Infant Death Syndrome (SIDS) exhibit a circadian heat rate thythm (CHR) at a later age than non-Asian term infants.

  13. Temperature compensation and entrainment in circadian rhythms

    International Nuclear Information System (INIS)

    Bodenstein, C; Heiland, I; Schuster, S

    2012-01-01

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

  14. Circadian rhythms in cognitive performance: implications for neuropsychological assessment

    Directory of Open Access Journals (Sweden)

    Valdez P

    2012-12-01

    Full Text Available Pablo Valdez, Candelaria Ramírez, Aída GarcíaLaboratory of Psychophysiology, School of Psychology, University of Nuevo León, Monterrey, Nuevo León, MéxicoAbstract: Circadian variations have been found in human performance, including the efficiency to execute many tasks, such as sensory, motor, reaction time, time estimation, memory, verbal, arithmetic calculations, and simulated driving tasks. Performance increases during the day and decreases during the night. Circadian rhythms have been found in three basic neuropsychological processes (attention, working memory, and executive functions, which may explain oscillations in the performance of many tasks. The time course of circadian rhythms in cognitive performance may be modified significantly in patients with brain disorders, due to chronotype, age, alterations of the circadian rhythm, sleep deprivation, type of disorder, and medication. This review analyzes the recent results on circadian rhythms in cognitive performance, as well as the implications of these rhythms for the neuropsychological assessment of patients with brain disorders such as traumatic head injury, stroke, dementia, developmental disorders, and psychiatric disorders.Keywords: human circadian rhythms, cognitive performance, neuropsychological assessment, attention, working memory, executive functions

  15. Circadian polymorphisms associated with affective disorders

    Directory of Open Access Journals (Sweden)

    Shekhtman Tatyana

    2009-01-01

    Full Text Available Abstract Background Clinical symptoms of affective disorders, their response to light treatment, and sensitivity to other circadian interventions indicate that the circadian system has a role in mood disorders. Possibly the mechanisms involve circadian seasonal and photoperiodic mechanisms. Since genetic susceptibilities contribute a strong component to affective disorders, we explored whether circadian gene polymorphisms were associated with affective disorders in four complementary studies. Methods Four groups of subjects were recruited from several sources: 1 bipolar proband-parent trios or sib-pair-parent nuclear families, 2 unrelated bipolar participants who had completed the BALM morningness-eveningness questionnaire, 3 sib pairs from the GenRed Project having at least one sib with early-onset recurrent unipolar depression, and 4 a sleep clinic patient group who frequently suffered from depression. Working mainly with the SNPlex assay system, from 2 to 198 polymorphisms in genes related to circadian function were genotyped in the participant groups. Associations with affective disorders were examined with TDT statistics for within-family comparisons. Quantitative trait associations were examined within the unrelated samples. Results In NR1D1, rs2314339 was associated with bipolar disorder (P = 0.0005. Among the unrelated bipolar participants, 3 SNPs in PER3 and CSNK1E were associated with the BALM score. A PPARGC1B coding SNP, rs7732671, was associated with affective disorder with nominal significance in bipolar family groups and independently in unipolar sib pairs. In TEF, rs738499 was associated with unipolar depression; in a replication study, rs738499 was also associated with the QIDS-SR depression scale in the sleep clinic patient sample. Conclusion Along with anti-manic effects of lithium and the antidepressant effects of bright light, these findings suggest that perturbations of the circadian gene network at several levels may

  16. Metabolic effects of bariatric surgery in mouse models of circadian disruption.

    Science.gov (United States)

    Arble, D M; Sandoval, D A; Turek, F W; Woods, S C; Seeley, R J

    2015-08-01

    Mounting evidence supports a link between circadian disruption and metabolic disease. Humans with circadian disruption (for example, night-shift workers) have an increased risk of obesity and cardiometabolic diseases compared with the non-disrupted population. However, it is unclear whether the obesity and obesity-related disorders associated with circadian disruption respond to therapeutic treatments as well as individuals with other types of obesity. Here, we test the effectiveness of the commonly used bariatric surgical procedure, Vertical Sleeve Gastrectomy (VSG), in mouse models of genetic and environmental circadian disruption. VSG led to a reduction in body weight and fat mass in both Clock(Δ19) mutant and constant-light mouse models (Pdisruption. Interestingly, the decrease in body weight occurred without altering diurnal feeding or activity patterns (P>0.05). Within circadian-disrupted models, VSG also led to improved glucose tolerance and lipid handling (Pdisruption, and that the potent effects of bariatric surgery are orthogonal to circadian biology. However, as the effects of bariatric surgery are independent of circadian disruption, VSG cannot be considered a cure for circadian disruption. These data have important implications for circadian-disrupted obese patients. Moreover, these results reveal new information about the metabolic pathways governing the effects of bariatric surgery as well as of circadian disruption.

  17. Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease.

    Science.gov (United States)

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

    2014-04-01

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

  18. Human-Systems Integration Processes

    Data.gov (United States)

    National Aeronautics and Space Administration — The goal of this project is to baseline a Human-Systems Integration Processes (HSIP) document as a companion to the NASA-STD-3001 and Human Integration Design...

  19. A Circadian Clock Gene, Cry, Affects Heart Morphogenesis and Function in Drosophila as Revealed by Optical Coherence Microscopy.

    Directory of Open Access Journals (Sweden)

    Aneesh Alex

    Full Text Available Circadian rhythms are endogenous, entrainable oscillations of physical, mental and behavioural processes in response to local environmental cues such as daylight, which are present in the living beings, including humans. Circadian rhythms have been related to cardiovascular function and pathology. However, the role that circadian clock genes play in heart development and function in a whole animal in vivo are poorly understood. The Drosophila cryptochrome (dCry is a circadian clock gene that encodes a major component of the circadian clock negative feedback loop. Compared to the embryonic stage, the relative expression levels of dCry showed a significant increase (>100-fold in Drosophila during the pupa and adult stages. In this study, we utilized an ultrahigh resolution optical coherence microscopy (OCM system to perform non-invasive and longitudinal analysis of functional and morphological changes in the Drosophila heart throughout its post-embryonic lifecycle for the first time. The Drosophila heart exhibited major morphological and functional alterations during its development. Notably, heart rate (HR and cardiac activity period (CAP of Drosophila showed significant variations during the pupa stage, when heart remodeling took place. From the M-mode (2D + time OCM images, cardiac structural and functional parameters of Drosophila at different developmental stages were quantitatively determined. In order to study the functional role of dCry on Drosophila heart development, we silenced dCry by RNAi in the Drosophila heart and mesoderm, and quantitatively measured heart morphology and function in those flies throughout its development. Silencing of dCry resulted in slower HR, reduced CAP, smaller heart chamber size, pupal lethality and disrupted posterior segmentation that was related to increased expression of a posterior compartment protein, wingless. Collectively, our studies provided novel evidence that the circadian clock gene, dCry, plays

  20. A Circadian Clock Gene, Cry, Affects Heart Morphogenesis and Function in Drosophila as Revealed by Optical Coherence Microscopy

    Science.gov (United States)

    Zeng, Xianxu; Tate, Rebecca E.; McKee, Mary L.; Capen, Diane E.; Zhang, Zhan; Tanzi, Rudolph E.; Zhou, Chao

    2015-01-01

    Circadian rhythms are endogenous, entrainable oscillations of physical, mental and behavioural processes in response to local environmental cues such as daylight, which are present in the living beings, including humans. Circadian rhythms have been related to cardiovascular function and pathology. However, the role that circadian clock genes play in heart development and function in a whole animal in vivo are poorly understood. The Drosophila cryptochrome (dCry) is a circadian clock gene that encodes a major component of the circadian clock negative feedback loop. Compared to the embryonic stage, the relative expression levels of dCry showed a significant increase (>100-fold) in Drosophila during the pupa and adult stages. In this study, we utilized an ultrahigh resolution optical coherence microscopy (OCM) system to perform non-invasive and longitudinal analysis of functional and morphological changes in the Drosophila heart throughout its post-embryonic lifecycle for the first time. The Drosophila heart exhibited major morphological and functional alterations during its development. Notably, heart rate (HR) and cardiac activity period (CAP) of Drosophila showed significant variations during the pupa stage, when heart remodeling took place. From the M-mode (2D + time) OCM images, cardiac structural and functional parameters of Drosophila at different developmental stages were quantitatively determined. In order to study the functional role of dCry on Drosophila heart development, we silenced dCry by RNAi in the Drosophila heart and mesoderm, and quantitatively measured heart morphology and function in those flies throughout its development. Silencing of dCry resulted in slower HR, reduced CAP, smaller heart chamber size, pupal lethality and disrupted posterior segmentation that was related to increased expression of a posterior compartment protein, wingless. Collectively, our studies provided novel evidence that the circadian clock gene, dCry, plays an essential

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

    Science.gov (United States)

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

    2017-01-01

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

  2. Phase delaying the human circadian clock with a single light pulse and moderate delay of the sleep/dark episode: no influence of iris color.

    Science.gov (United States)

    Canton, Jillian L; Smith, Mark R; Choi, Ho-Sun; Eastman, Charmane I

    2009-07-17

    Light exposure in the late evening and nighttime and a delay of the sleep/dark episode can phase delay the circadian clock. This study assessed the size of the phase delay produced by a single light pulse combined with a moderate delay of the sleep/dark episode for one day. Because iris color or race has been reported to influence light-induced melatonin suppression, and we have recently reported racial differences in free-running circadian period and circadian phase shifting in response to light pulses, we also tested for differences in the magnitude of the phase delay in subjects with blue and brown irises. Subjects (blue-eyed n = 7; brown eyed n = 6) maintained a regular sleep schedule for 1 week before coming to the laboratory for a baseline phase assessment, during which saliva was collected every 30 minutes to determine the time of the dim light melatonin onset (DLMO). Immediately following the baseline phase assessment, which ended 2 hours after baseline bedtime, subjects received a 2-hour bright light pulse (~4,000 lux). An 8-hour sleep episode followed the light pulse (i.e. was delayed 4 hours from baseline). A final phase assessment was conducted the subsequent night to determine the phase shift of the DLMO from the baseline to final phase assessment.Phase delays of the DLMO were compared in subjects with blue and brown irises. Iris color was also quantified from photographs using the three dimensions of red-green-blue color axes, as well as a lightness scale. These variables were correlated with phase shift of the DLMO, with the hypothesis that subjects with lighter irises would have larger phase delays. The average phase delay of the DLMO was -1.3 +/- 0.6 h, with a maximum delay of ~2 hours, and was similar for subjects with blue and brown irises. There were no significant correlations between any of the iris color variables and the magnitude of the phase delay. A single 2-hour bright light pulse combined with a moderate delay of the sleep/dark episode

  3. Phase delaying the human circadian clock with a single light pulse and moderate delay of the sleep/dark episode: no influence of iris color

    Directory of Open Access Journals (Sweden)

    Choi Ho-Sun

    2009-07-01

    Full Text Available Abstract Background Light exposure in the late evening and nighttime and a delay of the sleep/dark episode can phase delay the circadian clock. This study assessed the size of the phase delay produced by a single light pulse combined with a moderate delay of the sleep/dark episode for one day. Because iris color or race has been reported to influence light-induced melatonin suppression, and we have recently reported racial differences in free-running circadian period and circadian phase shifting in response to light pulses, we also tested for differences in the magnitude of the phase delay in subjects with blue and brown irises. Methods Subjects (blue-eyed n = 7; brown eyed n = 6 maintained a regular sleep schedule for 1 week before coming to the laboratory for a baseline phase assessment, during which saliva was collected every 30 minutes to determine the time of the dim light melatonin onset (DLMO. Immediately following the baseline phase assessment, which ended 2 hours after baseline bedtime, subjects received a 2-hour bright light pulse (~4,000 lux. An 8-hour sleep episode followed the light pulse (i.e. was delayed 4 hours from baseline. A final phase assessment was conducted the subsequent night to determine the phase shift of the DLMO from the baseline to final phase assessment. Phase delays of the DLMO were compared in subjects with blue and brown irises. Iris color was also quantified from photographs using the three dimensions of red-green-blue color axes, as well as a lightness scale. These variables were correlated with phase shift of the DLMO, with the hypothesis that subjects with lighter irises would have larger phase delays. Results The average phase delay of the DLMO was -1.3 ± 0.6 h, with a maximum delay of ~2 hours, and was similar for subjects with blue and brown irises. There were no significant correlations between any of the iris color variables and the magnitude of the phase delay. Conclusion A single 2-hour bright light

  4. Circadian Rhythms in Human Memory.

    Science.gov (United States)

    Folkard, Simon; Monk, Timothy H.

    1980-01-01

    Two experiments are described that examined the influence of time-of-day of presentation on immediate and delayed retention and its potential effects on retrieval from long-term memory. Time of presentation was found to influence both immediate and delayed (28 day) retention, but not retrieval from long-term memory. (Author/SJL)

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

    Science.gov (United States)

    Stevens, Richard G

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

  6. Circadian Pacemaker – Temperature Compensation

    NARCIS (Netherlands)

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

    2009-01-01

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

  7. The effects of chronic marijuana use on circadian entrainment.

    Science.gov (United States)

    Whitehurst, Lauren N; Fogler, Kethera; Hall, Kate; Hartmann, Matthew; Dyche, Jeff

    2015-05-01

    Animal literature suggests a connection between marijuana use and altered circadian rhythms. However, the effect has not yet been demonstrated in humans. The present study examined the effect of chronic marijuana use on human circadian function. Participants consisted of current users who reported smoking marijuana daily for at least a year and non-marijuana user controls. Participants took a neurocognitive assessment, wore actigraphs and maintained sleep diaries for three weeks. While no significant cognitive changes were found between groups, data revealed that chronic marijuana use may act as an additional zeitgeber and lead to increased entrainment in human users.

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

    Science.gov (United States)

    Wang, Haifang; Du, Jiulin; Yan, Jun

    2013-01-01

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

  9. The effect of lens aging and cataract surgery on circadian rhythm.

    Science.gov (United States)

    Yan, Shen-Shen; Wang, Wei

    2016-01-01

    Many organisms have evolved an approximately 24-hour circadian rhythm that allows them to achieve internal physiological homeostasis with external environment. Suprachiasmatic nucleus (SCN) is the central pacemaker of circadian rhythm, and its activity is entrained to the external light-dark cycle. The SCN controls circadian rhythm through regulating the synthesis of melatonin by pineal gland via a multisynaptic pathway. Light, especially short-wavelength blue light, is the most potent environmental time cue in circadian photoentrainment. Recently, the discovery of a novel type of retinal photoreceptors, intrinsically photosensitive retinal ganglion cells, sheds light on the mechanism of circadian photoentrainment and raises concerns about the effect of ocular diseases on circadian system. With age, light transmittance is significantly decreased due to the aging of crystalline lens, thus possibly resulting in progressive loss of circadian photoreception. In the current review, we summarize the circadian physiology, highlight the important role of light in circadian rhythm regulation, discuss about the correlation between age-related cataract and sleep disorders, and compare the effect of blue light- filtering intraocular lenses (IOLs) and ultraviolet only filtering IOLs on circadian rhythm.

  10. Metabolic Compensation and Circadian Resilience in Prokaryotic Cyanobacteria

    Science.gov (United States)

    Johnson, Carl Hirschie; Egli, Martin

    2014-01-01

    For a biological oscillator to function as a circadian pacemaker that confers a fitness advantage, its timing functions must be stable in response to environmental and metabolic fluctuations. One such stability enhancer, temperature compensation, has long been a defining characteristic of these timekeepers. However, an accurate biological timekeeper must also resist changes in metabolism, and this review suggests that temperature compensation is actually a subset of a larger phenomenon, namely metabolic compensation, which maintains the frequency of circadian oscillators in response to a host of factors that impinge on metabolism and would otherwise destabilize these clocks. The circadian system of prokaryotic cyanobacteria is an illustrative model because it is composed of transcriptional and nontranscriptional oscillators that are coupled to promote resilience. Moreover, the cyanobacterial circadian program regulates gene activity and metabolic pathways, and it can be manipulated to improve the expression of bioproducts that have practical value. PMID:24905782

  11. Speed control: cogs and gears that drive the circadian clock.

    Science.gov (United States)

    Zheng, Xiangzhong; Sehgal, Amita

    2012-09-01

    In most organisms, an intrinsic circadian (~24-h) timekeeping system drives rhythms of physiology and behavior. Within cells that contain a circadian clock, specific transcriptional activators and repressors reciprocally regulate each other to generate a basic molecular oscillator. A mismatch of the period generated by this oscillator with the external environment creates circadian disruption, which can have adverse effects on neural function. Although several clock genes have been extensively characterized, a fundamental question remains: how do these genes work together to generate a ~24-h period? Period-altering mutations in clock genes can affect any of multiple regulated steps in the molecular oscillator. In this review, we examine the regulatory mechanisms that contribute to setting the pace of the circadian oscillator. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Imaging of serotonin transporters with [123I]FP-CIT SPECT in the human hypothalamus

    NARCIS (Netherlands)

    Borgers, A.J.; Alkemade, A.; Van de Giessen, E.M.; Drent, M.L.; Booij, J.; Bisschop, P.H.; Fliers, E.

    2013-01-01

    Background: Serotonergic neurons in the rodent hypothalamus are implicated in key neuroendocrine and metabolic functions, including circadian rhythmicity. However, the assessment of the serotonergic system in the human hypothalamus in vivo is difficult as delineation of the hypothalamus is

  13. Sex and ancestry determine the free-running circadian period.

    Science.gov (United States)

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

    2017-10-01

    The endogenous, free-running circadian period (τ) determines the phase relationship that an organism assumes when entrained to the 24-h day. We found a shorter circadian period in African Americans compared to non-Hispanic European Americans (24.07 versus 24.33 h). We speculate that a short circadian period, closer to 24 h, was advantageous to humans living around the equator, but when humans migrated North out of Africa, where the photoperiod changes with seasons, natural selection favoured people with longer circadian periods. Recently, in evolutionary terms, immigrants came from Europe and Africa to America ('the New World'). The Europeans were descendents of people who had lived in Europe for thousands of years with changing photoperiods (and presumably longer periods), whereas Africans had ancestors who had always lived around the equator (with shorter periods). It may have been advantageous to have a longer circadian period while living in Europe early in the evolution of humans. In our modern world, however, it is better to have a shorter period, because it helps make our circadian rhythms earlier, which is adaptive in our early-bird-dominated society. European American women had a shorter circadian period than men (24.24 versus 24.41), but there was no sex difference in African Americans (24.07 for both men and women). We speculate that selection pressures in Europe made men develop a slightly longer period than women to help them track dawn which could be useful for hunters, but less important for women as gatherers. © 2017 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

  14. Circadian rhythm and sleep influences on digestive physiology and disorders

    Directory of Open Access Journals (Sweden)

    Vaughn BV

    2014-09-01

    Full Text Available Bradley V Vaughn, Sean Rotolo, Heidi L Roth Division of Sleep Medicine, Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC, USA Abstract: Circadian rhythms and sleep influence a variety of physiological functions, including the digestive system. The digestive system also has intrinsic rhythms that interact dynamically with circadian rhythms. New advances in understanding the interaction of these rhythms and sleep provide the prospect of evaluating their role in normal physiology and the link of their disruption to pathological conditions. Recent work has demonstrated that sleep and circadian factors influence appetite, nutrient absorption, and metabolism. Disruption of sleep and circadian rhythms may increase vulnerability to digestive disorders, including reflux, ulcers, inflammatory bowel issues, irritable bowel disease, and gastrointestinal cancer. As our knowledge of the link between circadian timing and gastrointestinal physiology grows, so do our opportunities to provide promising diagnostic and therapeutic approaches for gastrointestinal disorders. Keywords: digestion, digestive diseases, gastrointestinal reflux, sleep, circadian rhythm 

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

    Science.gov (United States)

    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.

  16. Gremlin-2 is a BMP antagonist that is regulated by the circadian clock

    DEFF Research Database (Denmark)

    Yeung, Ching-Yan Chloé; Gossan, Nicole; Lu, Yinhui

    2014-01-01

    knowledge of tendon gene regulation is essential for a complete understanding of FCT biology. Here we show autonomous circadian rhythms in mouse tendon and primary human tenocytes, controlled by an intrinsic molecular circadian clock. Time-series microarrays identified the first circadian transcriptome...... of murine tendon, revealing that 4.6% of the transcripts (745 genes) are expressed in a circadian manner. One of these genes was Grem2, which oscillated in antiphase to BMP signaling. Moreover, recombinant human Gremlin-2 blocked BMP2-induced phosphorylation of Smad1/5 and osteogenic differentiation...... of human tenocytes in vitro. We observed dampened Grem2 expression, deregulated BMP signaling, and spontaneously calcifying tendons in young CLOCKΔ19 arrhythmic mice and aged wild-type mice. Thus, disruption of circadian control, through mutations or aging, of Grem2/BMP signaling becomes a new focus...

  17. Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture

    OpenAIRE

    Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

    2017-01-01

    Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Droso...

  18. Circadian rhythm in ''1''5O-labeled water uptake manner of a soybean plant by PETIS (Positron Emitting Tracer Imaging System)

    International Nuclear Information System (INIS)

    Nakanishi, Tomoko M.; Yokota, Harumi; Tanoi, Keitaro; Furukawa, Jun; Ikeue, Natsuko; Ookuni, Yoko; Uchida, Hiroshi; Tsuji, Atsunori

    2001-01-01

    We present a circadian rhythm of water uptake manner in a soybean plant through realtime imaging of water, labeled with 15 O. Nitrogen gas was irradiated with deuterons accelerated by a cyclotron at Hamamatsu Photonics Co. to produce 15 O-labeled water. Then the 15 O-labeled water was supplied to a soybean plant from the root and the realtime water uptake amount was measured for 20 min by Positron Emitting Tracer Imaging System (PETIS). All the targeting positions for the measurements were stems, two points at an internode between root and the first leaves, between the first leaves and the first trifoliates and between the first trifoliates and the second trifoliates. The water uptake amount was gradually increased and showed its maximum at around 13:00, especially at the basal part of the stem. Then the water uptake activity was gradually decreased until 17:00. The water amount taken up by a plant at 13:00 was about 40% higher than that at 17:00. (author)

  19. Circadian rhythm in ''1''5O-labeled water uptake manner of a soybean plant by PETIS (Positron Emitting Tracer Imaging System)

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Tomoko M.; Yokota, Harumi; Tanoi, Keitaro; Furukawa, Jun; Ikeue, Natsuko; Ookuni, Yoko [Tokyo Univ. (Japan). Graduate School of Agricultural and Life Sciences; Uchida, Hiroshi; Tsuji, Atsunori

    2001-05-01

    We present a circadian rhythm of water uptake manner in a soybean plant through realtime imaging of water, labeled with {sup 15}O. Nitrogen gas was irradiated with deuterons accelerated by a cyclotron at Hamamatsu Photonics Co. to produce {sup 15}O-labeled water. Then the {sup 15}O-labeled water was supplied to a soybean plant from the root and the realtime water uptake amount was measured for 20 min by Positron Emitting Tracer Imaging System (PETIS). All the targeting positions for the measurements were stems, two points at an internode between root and the first leaves, between the first leaves and the first trifoliates and between the first trifoliates and the second trifoliates. The water uptake amount was gradually increased and showed its maximum at around 13:00, especially at the basal part of the stem. Then the water uptake activity was gradually decreased until 17:00. The water amount taken up by a plant at 13:00 was about 40% higher than that at 17:00. (author)

  20. Nocturia: The circadian voiding disorder

    Directory of Open Access Journals (Sweden)

    Jin Wook Kim

    2016-05-01

    Full Text Available Nocturia is a prevalent condition of waking to void during the night. The concept of nocturia has evolved from being a symptomatic aspect of disease associated with the prostate or bladder to a form of lower urinary tract disorder. However, recent advances in circadian biology and sleep science suggest that it might be important to consider nocturia as a form of circadian dysfunction. In the current review, nocturia is reexamined with an introduction to sleep disorders and recent findings in circadian biology in an attempt to highlight the importance of rediscovering nocturia as a problem of chronobiology.

  1. Manipulating the circadian and sleep cycles to protect against metabolic disease

    Directory of Open Access Journals (Sweden)

    Kazunari eNohara

    2015-03-01

    Full Text Available Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that regulates internal rhythms such as the sleep/wake cycle and also responses to external stimuli including light and food. Initially thought to be mainly involved in the timing of sleep, the clock and/or clock genes may also play a role in sleep architecture and homeostasis. Importantly, an extensive body of evidence has firmly established a master regulatory role of the clock in energy balance. Together, a close relationship between well-timed circadian/sleep cycles and metabolic health is emerging. Exploiting this functional connection, an important holistic strategy toward curbing the epidemic of metabolic disorders (e.g. obesity involves corrective measures on the circadian clock and sleep. In addition to behavioral and environmental interventions including meal timing and light control, pharmacological agents targeting sleep and circadian clocks promise convenient and effective applications. Recent studies, for example, have reported small molecules targeting specific clock components and displaying robust beneficial effects on sleep and metabolism. Furthermore, a group of clock-amplitude enhancing small molecules (CEMs identified via high-throughput chemical screens are of particular interest for future in vivo studies of their metabolic and sleep efficacies. Elucidating the functional relationship between clock, sleep and metabolism will also have far-reaching implications for various chronic human diseases and aging.

  2. Manipulating the circadian and sleep cycles to protect against metabolic disease.

    Science.gov (United States)

    Nohara, Kazunari; Yoo, Seung-Hee; Chen, Zheng Jake

    2015-01-01

    Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that regulates internal rhythms such as the sleep/wake cycle and also responses to external stimuli including light and food. Initially thought to be mainly involved in the timing of sleep, the clock, and/or clock genes may also play a role in sleep architecture and homeostasis. Importantly, an extensive body of evidence has firmly established a master regulatory role of the clock in energy balance. Together, a close relationship between well-timed circadian/sleep cycles and metabolic health is emerging. Exploiting this functional connection, an important holistic strategy toward curbing the epidemic of metabolic disorders (e.g., obesity) involves corrective measures on the circadian clock and sleep. In addition to behavioral and environmental interventions including meal timing and light control, pharmacological agents targeting sleep and circadian clocks promise convenient and effective applications. Recent studies, for example, have reported small molecules targeting specific clock components and displaying robust beneficial effects on sleep and metabolism. Furthermore, a group of clock-amplitude-enhancing small molecules (CEMs) identified via high-throughput chemical screens are of particular interest for future in vivo studies of their metabolic and sleep efficacies. Elucidating the functional relationship between clock, sleep, and metabolism will also have far-reaching implications for various chronic human diseases and aging.

  3. Genetic Disruption of the Core Circadian Clock Impairs Hippocampus-Dependent Memory

    Science.gov (United States)

    Wardlaw, Sarah M.; Phan, Trongha X.; Saraf, Amit; Chen, Xuanmao; Storm, Daniel R.

    2014-01-01

    Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1[superscript -/-] mice, which are arrhythmic…

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

    Science.gov (United States)

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

    2014-11-11

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

  5. Postoperative circadian disturbances

    DEFF Research Database (Denmark)

    Gögenur, Ismail

    2010-01-01

    ) in urine the first night after both minor and major surgery. This delay after major surgery was correlated to the duration of surgery. The amplitude in the melatonin rhythm was unchanged the first night but increased in the second night after major surgery. The amplitude in AMT6s was reduced the first...... night after minimally invasive surgery. The core body temperature rhythm was disturbed after both major and minor surgery. There was a change in the sleep wake cycle with a significantly increased duration of REM-sleep in the day and evening time after major surgery compared with preoperatively....... There was also a shift in the autonomic nervous balance after major surgery with a significantly increased number of myocardial ischaemic episodes during the nighttime period. The circadian activity rhythm was also disturbed after both minor and major surgery. The daytime AMT6s excretion in urine after major...

  6. Modeling of Embedded Human Systems

    Science.gov (United States)

    2013-07-01

    ISAT study [7] for DARPA in 20051 concretized the notion of an embedded human, who is a necessary component of the system. The proposed work integrates...Technology, IEEE Transactions on, vol. 16, no. 2, pp. 229–244, March 2008. [7] C. J. Tomlin and S. S. Sastry, “Embedded humans,” tech. rep., DARPA ISAT

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

    Directory of Open Access Journals (Sweden)

    James E C Jepson

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

  8. Homeostasis in Primates in the Hyperdynamic Environment. [circadian timekeeping and effects of lower body positive pressure on sleep

    Science.gov (United States)

    Fuller, C. A.

    1985-01-01

    The influence of chronic centrifugation upon the homestatic regulation of the circadian timekeeping system was examined. The interactions of body temperature regulation and the behavioral state of arousal were studied by evaluating the influence of cephalic fluid shifts induced by lower body positive air pressure (LBPP), upon these systems. The small diurnal squirrel monkey (Saimiri sciureus) was used as the non-human primate model. Results show that the circadian timekeeping system of these primates is functional in the hyperdynamic environment, however, some of its components appear to be regulated at different homeostatic levels. The LBPP resulted in an approximate 0.7 C decrease in DBT (p 0.01). However, although on video some animals appeared drowsy during LBPP, sleep recording revealed no significant changes in state of arousal. Thus, the physiological mechanisms underlying this lowering of body temperature can be independent of the arousal state.

  9. Increased Sensitivity of the Circadian System to Temporal Changes in the Feeding Regime of Spontaneously Hypertensive Rats - A Potential Role for Bmal2 in the Liver

    Czech Academy of Sciences Publication Activity Database

    Polidarová, Lenka; Sládek, Martin; Nováková, Marta; Parkanová, Daniela; Sumová, Alena

    2013-01-01

    Roč. 8, č. 9 (2013), e75690 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP303/11/0668 Institutional support: RVO:67985823 Keywords : circadian * clock gene * metabolism * liver * feeding regime * Bmal2 * spontaneously hypertensive rat Subject RIV: ED - Physiology Impact factor: 3.534, year: 2013

  10. Human resources in innovation systems

    DEFF Research Database (Denmark)

    Nielsen, René Nesgaard

    2007-01-01

    Human resources in innovation systems: With focus on introduction of highly educated labour in small Danish firms This thesis has two purposes: (1) a ‘general' purpose to enhance our knowledge on the relationship between innovation, technological and organisational change, and human resources......, including knowledge and skills embodied in human resources, and (2) a more ‘specific' purpose to enhance our knowledge on introduction of highly educated labour, innovation, and upgrading changes in small Danish firms. Chapter 1 establishes the relevance of this research interest, and it also states...... stemming from human resources - such as insight, understanding, creativity, and action - are inherently important to all innovation processes. The chapter also suggests a tentative conceptual and analytical framework for studying human resources and their development within a system of innovation approach...

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

    Science.gov (United States)

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

    2017-04-21

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

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

    Directory of Open Access Journals (Sweden)

    Oliver eRawashdeh

    2012-03-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer's disease?

    Science.gov (United States)

    Kent, Brianne A

    2014-01-01

    Alzheimer's disease (AD) is a global epidemic. Unfortunately, we are still without effective treatments or a cure for this disease, which is having devastating consequences for patients, their families, and societies around the world. Until effective treatments are developed, promoting overall health may hold potential for delaying the onset or preventing neurodegenerative diseases such as AD. In particular, chronobiological concepts may provide a useful framework for identifying the earliest signs of age-related disease as well as inexpensive and noninvasive methods for promoting health. It is well reported that AD is associated with disrupted circadian functioning to a greater extent than normal aging. However, it is unclear if the central circadian clock (i.e., the suprachiasmatic nucleus) is dysfunctioning, or whether the synchrony between the central and peripheral clocks that control behavior and metabolic processes are becoming uncoupled. Desynchrony of rhythms can negatively affect health, increasing morbidity and mortality in both animal models and humans. If the uncoupling of rhythms is contributing to AD progression or exacerbating symptoms, then it may be possible to draw from the food-entrainment literature to identify mechanisms for re-synchronizing rhythms to improve overall health and reduce the severity of symptoms. The following review will briefly summarize the circadian system, its potential role in AD, and propose using a feeding-related neuropeptide, such as ghrelin, to synchronize uncoupled rhythms. Synchronizing rhythms may be an inexpensive way to promote healthy aging and delay the onset of neurodegenerative disease such as AD.

  15. Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators

    Science.gov (United States)

    Saini, Camille; Morf, Jörg; Stratmann, Markus; Gos, Pascal; Schibler, Ueli

    2012-01-01

    The circadian pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus maintains phase coherence in peripheral cells through metabolic, neuronal, and humoral signaling pathways. Here, we investigated the role of daily body temperature fluctuations as possible systemic cues in the resetting of peripheral oscillators. Using precise temperature devices in conjunction with real-time monitoring of the bioluminescence produced by circadian luciferase reporter genes, we showed that simulated body temperature cycles of mice and even humans, with daily temperature differences of only 3°C and 1°C, respectively, could gradually synchronize circadian gene expression in cultured fibroblasts. The time required for establishing the new steady-state phase depended on the reporter gene, but after a few days, the expression of each gene oscillated with a precise phase relative to that of the temperature cycles. Smooth temperature oscillations with a very small amplitude could synchronize fibroblast clocks over a wide temperature range, and such temperature rhythms were also capable of entraining gene expression cycles to periods significantly longer or shorter than 24 h. As revealed by genetic loss-of-function experiments, heat-shock factor 1 (HSF1), but not HSF2, was required for the efficient synchronization of fibroblast oscillators to simulated body temperature cycles. PMID:22379191

  16. Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators.

    Science.gov (United States)

    Saini, Camille; Morf, Jörg; Stratmann, Markus; Gos, Pascal; Schibler, Ueli

    2012-03-15

    The circadian pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus maintains phase coherence in peripheral cells through metabolic, neuronal, and humoral signaling pathways. Here, we investigated the role of daily body temperature fluctuations as possible systemic cues in the resetting of peripheral oscillators. Using precise temperature devices in conjunction with real-time monitoring of the bioluminescence produced by circadian luciferase reporter genes, we showed that simulated body temperature cycles of mice and even humans, with daily temperature differences of only 3°C and 1°C, respectively, could gradually synchronize circadian gene expression in cultured fibroblasts. The time required for establishing the new steady-state phase depended on the reporter gene, but after a few days, the expression of each gene oscillated with a precise phase relative to that of the temperature cycles. Smooth temperature oscillations with a very small amplitude could synchronize fibroblast clocks over a wide temperature range, and such temperature rhythms were also capable of entraining gene expression cycles to periods significantly longer or shorter than 24 h. As revealed by genetic loss-of-function experiments, heat-shock factor 1 (HSF1), but not HSF2, was required for the efficient synchronization of fibroblast oscillators to simulated body temperature cycles.

  17. Circadian rhythm asynchrony in man during hypokinesis.

    Science.gov (United States)

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

    1972-01-01

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

  18. Circadian control of the sleep-wake cycle

    NARCIS (Netherlands)

    Beersma, Domien G. M.; Gordijn, Marijke C. M.

    2007-01-01

    It is beyond doubt that the timing of sleep is under control of the circadian pacemaker. Humans are a diurnal species; they sleep mostly at night, and they do so at approximately 24-h intervals. If they do not adhere to this general pattern, for instance when working night shifts or when travelling

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

    Science.gov (United States)

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

    2015-06-01

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

  20. Circadian rhythms and memory: not so simple as cogs and gears.

    Science.gov (United States)

    Eckel-Mahan, Kristin L; Storm, Daniel R

    2009-06-01

    The influence of circadian rhythms on memory has long been studied; however, the molecular prerequisites for their interaction remain elusive. The hippocampus, which is a region of the brain important for long-term memory formation and temporary maintenance, shows circadian rhythmicity in pathways central to the memory-consolidation process. As neuronal plasticity is the translation of numerous inputs, illuminating the direct molecular links between circadian rhythms and memory consolidation remains a daunting task. However, the elucidation of how clock genes contribute to synaptic plasticity could provide such a link. Furthermore, the idea that memory training could actually function as a zeitgeber for hippocampal neurons is worth consideration, based on our knowledge of the entrainment of the circadian clock system. The integration of many inputs in the hippocampus affects memory consolidation at both the cellular and the systems level, leaving the molecular connections between circadian rhythmicity and memory relatively obscure but ripe for investigation.

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

    Directory of Open Access Journals (Sweden)

    Roberto Salgado-Delgado

    2011-01-01

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

  2. Opioid system and human emotions.

    Science.gov (United States)

    Nummenmaa, Lauri; Tuominen, Lauri

    2017-04-10

    Emotions are states of vigilant readiness that guide human and animal behaviour during survival-salient situations. Categorical models of emotions posit neurally and physiologically distinct basic human emotions (anger, fear, disgust, happiness, sadness and surprise) that govern different survival functions. Opioid receptors are expressed abundantly in the mammalian emotion circuit, and the opioid system modulates a variety of functions related to arousal and motivation. Yet, its specific contribution to different basic emotions has remained poorly understood. Here, we review how the endogenous opioid system and particularly the μ receptor contribute to emotional processing in humans. Activation of the endogenous opioid system is consistently associated with both pleasant and unpleasant emotions. In general, exogenous opioid agonists facilitate approach-oriented emotions (anger, pleasure) and inhibit avoidance-oriented emotions (fear, sadness). Opioids also modulate social bonding and affiliative behaviour, and prolonged opioid abuse may render both social bonding and emotion recognition circuits dysfunctional. However, there is no clear evidence that the opioid system is able to affect the emotions associated with surprise and disgust. Taken together, the opioid systems contribute to a wide array of positive and negative emotions through their general ability to modulate the approach versus avoidance motivation associated with specific emotions. Because of the protective effects of opioid system-mediated prosociality and positive mood, the opioid system may constitute an important factor contributing to psychological and psychosomatic resilience. © 2017 The British Pharmacological Society.

  3. [11C]Doxepin binding to histamine H1 receptors in living human brain in association with attentive waking and circadian rhythm

    Directory of Open Access Journals (Sweden)

    Kazuhiko eYanai

    2012-06-01

    Full Text Available Molecular imaging in neuroscience is a new research field that enables visualization of the impact of molecular events on brain structure and function in humans. While magnetic resonance-based imaging techniques can provide complex information at the level of system, positron emission tomography (PET enables determination of the distribution and density of receptor and enzyme in the human brain. Previous studies using [11C]raclopride revealed that the release of neuronal dopamine was increased in human brain by psychostimulants or reward stimuli. Following on from these previous studies, we examined whether the levels of neuronal release of histamine might change [11C]doxepin binding to the H1 receptors under the influence of physiological stimuli. The purpose of the present study was to evaluate the test-retest reliability of quantitative measurement of [11C]doxepin binding between morning and afternoon and between resting and attentive waking conditions in healthy human subjects. There was a trend for a decrease in [11C]doxepin binding during attentive calculation tasks compared with that in resting conditions, but the difference (approximately 10% was not significant. In contrast, the binding potential of [11C]doxepin in the anterior cingulate gyrus was significantly higher in the morning than that in the afternoon (approximately 19%, suggesting that higher histamine release in the morning would decrease the [11C]doxepin binding in the afternoon. This study suggests that non-invasive measurement of neuronal histamine release is feasible in humans by PET ligand-activation study, although the development of a tracer with better signal-to-noise properties is needed.

  4. Familial circadian rhythm disorder in the diurnal primate, Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Irina V Zhdanova

    Full Text Available In view of the inverse temporal relationship of central clock activity to physiological or behavioral outputs in diurnal and nocturnal species, understanding the mechanisms and physiological consequences of circadian disorders in humans would benefit from studies in a diurnal animal model, phylogenetically close to humans. Here we report the discovery of the first intrinsic circadian disorder in a family of diurnal non-human primates, the rhesus monkey. The disorder is characterized by a combination of delayed sleep phase, relative to light-dark cycle, mutual desynchrony of intrinsic rhythms of activity, food intake and cognitive performance, enhanced nighttime feeding or, in the extreme case, intrinsic asynchrony. The phenotype is associated with normal length of intrinsic circadian period and requires an intact central clock, as demonstrated by an SCN lesion. Entrainment to different photoperiods or melatonin administration does not eliminate internal desynchrony, though melatonin can temporarily reinstate intrinsic activity rhythms in the animal with intrinsic asynchrony. Entrainment to restricted feeding is highly effective in animals with intrinsic or SCN lesion-induced asynchrony. The large isolated family of rhesus macaques harboring the disorder provides a powerful new tool for translational research of regulatory circuits underlying circadian disorders and their effective treatment.

  5. Natural selection against a circadian clock gene mutation in mice.

    Science.gov (United States)

    Spoelstra, Kamiel; Wikelski, Martin; Daan, Serge; Loudon, Andrew S I; Hau, Michaela

    2016-01-19

    Circadian rhythms with an endogenous period close to or equal to the natural light-dark cycle are considered evolutionarily adaptive ("circadian resonance hypothesis"). Despite remarkable insight into the molecular mechanisms driving circadian cycles, this hypothesis has not been tested under natural conditions for any eukaryotic organism. We tested this hypothesis in mice bearing a short-period mutation in the enzyme casein kinase 1ε (tau mutation), which accelerates free-running circadian cycles. We compared daily activity (feeding) rhythms, survivorship, and reproduction in six replicate populations in outdoor experimental enclosures, established with wild-type, heterozygous, and homozygous mice in a Mendelian ratio. In the release cohort, survival was reduced in the homozygote mutant mice, revealing strong selection against short-period genotypes. Over the course of 14 mo, the relative frequency of the tau allele dropped from initial parity to 20%. Adult survival and recruitment of juveniles into the population contributed approximately equally to the selection for wild-type alleles. The expression of activity during daytime varied throughout the experiment and was significantly increased by the tau mutation. The strong selection against the short-period tau allele observed here contrasts with earlier studies showing absence of selection against a Period 2 (Per2) mutation, which disrupts internal clock function, but does not change period length. These findings are consistent with, and predicted by the theory that resonance of the circadian system plays an important role in individual fitness.

  6. Calculating activation energies for temperature compensation in circadian rhythms

    International Nuclear Information System (INIS)

    Bodenstein, C; Heiland, I; Schuster, S

    2011-01-01

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

  7. Photoperiodic regulation of the hamster testis: dependence on circadian rhythms

    International Nuclear Information System (INIS)

    Eskes, G.A.; Zucker, I.

    1978-01-01

    The testes of hamsters exposed to short days (10 hr of light per day) regress within 13 weeks. Administration of 7.5 percent deuterium oxide to hamsters lengthens the period of free running circadian activity rhythms by 2.2 percent and prevents testicular regression during short-day exposure. This is consistent with predictions derived from an external coincidence model for photoperiodic time measurement: Deuterium oxide changes phase relationships between the light-dark cycle and the circadian system, the hamster's daily photosensitive phase is stimulated with light during short days, and the testes remain large. Conservation of the period of circadian rhythms within narrow limits has adaptive significance for hamster photoperiodism and for the occurrence and phasing of the annual reproductive cycle

  8. Molecular Cogs: Interplay between Circadian Clock and Cell Cycle.

    Science.gov (United States)

    Gaucher, Jonathan; Montellier, Emilie; Sassone-Corsi, Paolo

    2018-05-01

    The cell cycle and the circadian clock operate as biological oscillators whose timed functions are tightly regulated. Accumulating evidence illustrates the presence of molecular links between these two oscillators. This mutual interplay utilizes various coupling mechanisms, such as the use of common regulators. The connection between these two cyclic systems has unique interest in the context of aberrant cell proliferation since both of these oscillators are frequently misregulated in cancer cells. Further studies will provide deeper understanding of the detailed molecular connections between the cell cycle and the circadian clock and may also serve as a basis for the design of innovative therapeutic strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Human-system Interfaces for Automatic Systems

    Energy Technology Data Exchange (ETDEWEB)

    OHara, J.M.; Higgins,J. (BNL); Fleger, S.; Barnes V. (NRC)

    2010-11-07

    Automation is ubiquitous in modern complex systems, and commercial nuclear- power plants are no exception. Automation is applied to a wide range of functions including monitoring and detection, situation assessment, response planning, and response implementation. Automation has become a 'team player' supporting personnel in nearly all aspects of system operation. In light of its increasing use and importance in new- and future-plants, guidance is needed to conduct safety reviews of the operator's interface with automation. The objective of this research was to develop such guidance. We first characterized the important HFE aspects of automation, including six dimensions: levels, functions, processes, modes, flexibility, and reliability. Next, we reviewed literature on the effects of all of these aspects of automation on human performance, and on the design of human-system interfaces (HSIs). Then, we used this technical basis established from the literature to identify general principles for human-automation interaction and to develop review guidelines. The guidelines consist of the following seven topics: automation displays, interaction and control, automation modes, automation levels, adaptive automation, error tolerance and failure management, and HSI integration. In addition, our study identified several topics for additional research.

  10. Circadian rhythms in mitochondrial respiration

    NARCIS (Netherlands)

    de Goede, Paul; Wefers, Jakob; Brombacher, Eline Constance; Schrauwen, P; Kalsbeek, A.

    2018-01-01

    Many physiological processes are regulated with a 24h periodicity to anticipate the environmental changes of day to nighttime and vice versa. These 24h regulations, commonly termed circadian rhythms, amongst others control the sleep-wake cycle, locomotor activity and preparation for food

  11. Circadian Clocks: Unexpected Biochemical Cogs.

    Science.gov (United States)

    Mori, Tetsuya; Mchaourab, Hassane; Johnson, Carl Hirschie

    2015-10-05

    A circadian oscillation can be reconstituted in vitro from three proteins that cycles with a period of ∼ 24 h. Two recent studies provide surprising biochemical answers to why this remarkable oscillator has such a long time constant and how it can switch effortlessly between alternating enzymatic modes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Circadian Clocks: Unexpected Biochemical Cogs

    OpenAIRE

    Mori, Tetsuya; Mchaourab, Hassane; Johnson, Carl Hirschie

    2015-01-01

    A circadian oscillation can be reconstituted in vitro from three proteins that cycles with a period of ~24 h. Two recent studies provide surprising biochemical answers to why this remarkable oscillator has such a long time constant and how it can switch effortlessly between alternating enzymatic modes.

  13. Ischemic stroke destabilizes circadian rhythms

    Directory of Open Access Journals (Sweden)

    Borjigin Jimo

    2008-10-01

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

  14. Circadian rhythms in the hypothalamo-pituitary-adrenal (HPA) axis

    NARCIS (Netherlands)

    Kalsbeek, A.; van der Spek, R.; Lei, J.; Endert, E.; Buijs, R. M.; Fliers, E.

    2012-01-01

    The pronounced daily variation in the release of adrenal hormones has been at the heart of the deciphering and understanding of the circadian timing system. Indeed, the first demonstration of an endocrine day/night rhythm was provided by Pincus (1943), by showing a daily pattern of 17-keto-steroid

  15. Circadian rhythm in salivary melatonin in narcoleptic patiens

    Czech Academy of Sciences Publication Activity Database

    Blažejová, K.; Illnerová, Helena; Hájek, Ivan; Nevšímalová, S.

    2008-01-01

    Roč. 437, č. 2 (2008), s. 162-164 ISSN 0304-3940 R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : narcolepsy * circadian system * melatonin Subject RIV: FH - Neurology Impact factor: 2.200, year: 2008

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

    Science.gov (United States)

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

    1998-01-01

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

  17. PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP.

    Science.gov (United States)

    Yeom, Miji; Lee, HansongI; Shin, Seoungwoo; Park, Deokhoon; Jung, Eunsun

    2018-03-23

    Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE) increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.

  18. PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP

    Directory of Open Access Journals (Sweden)

    Miji Yeom

    2018-03-01

    Full Text Available Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1 and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.

  19. Valproic acid disrupts the oscillatory expression of core circadian rhythm transcription factors.

    Science.gov (United States)

    Griggs, Chanel A; Malm, Scott W; Jaime-Frias, Rosa; Smith, Catharine L

    2018-01-15

    Valproic acid (VPA) is a well-established therapeutic used in treatment of seizure and mood disorders as well as migraines and a known hepatotoxicant. About 50% of VPA users experience metabolic disruptions, including weight gain, hyperlipidemia, and hyperinsulinemia, among others. Several of these metabolic abnormalities are similar to the effects of circadian rhythm disruption. In the current study, we examine the effect of VPA exposure on the expression of core circadian transcription factors that drive the circadian clock via a transcription-translation feedback loop. In cells with an unsynchronized clock, VPA simultaneously upregulated the expression of genes encoding core circadian transcription factors that regulate the positive and negative limbs of the feedback loop. Using low dose glucocorticoid, we synchronized cultured fibroblast cells to a circadian oscillatory pattern. Whether VPA was added at the time of synchronization or 12h later at CT12, we found that VPA disrupted the oscillatory expression of multiple genes encoding essential transcription factors that regulate circadian rhythm. Therefore, we conclude that VPA has a potent effect on the circadian rhythm transcription-translation feedback loop that may be linked to negative VPA side effects in humans. Furthermore, our study suggests potential chronopharmacology implications of VPA usage. Copyright © 2017. Published by Elsevier Inc.

  20. Combining annual daylight simulation with photobiology data to assess the relative circadian efficacy of interior spaces

    Energy Technology Data Exchange (ETDEWEB)

    Pechacek, C.S.; Andersen, M. [Massachusetts Inst. of Technology, Cambridge, MA (United States). Dept. of Architecture, Building Technology; Lockley, S.W. [Harvard Medical School, Boston, MA (United States). Div. of Sleep Medicine, Brigham and Women' s Hospital

    2008-07-01

    This paper addressed the issue of hospital design and the role of daylight in patient health care. It presented a new approach for integrating empirical data and findings in photobiology into the performance assessment of a space, thus combining both visual and health-related criteria. Previous studies have reported significant health care outcomes in daylit environments, although the mechanism and photoreceptor systems controlling these effects remain unknown. This study focused on furthering the previous studies beyond windows to describing the characteristics of daylight that may promote human health by providing daylighting for the appropriate synchronization of circadian rhythms, and then make specific daylighting recommendations, grounded in biological findings. In particular, this study investigated the use of daylight autonomy (DA) to simulate the probabilistic and temporal potential of daylight for human health needs. Results of photobiology research were used to define threshold values for lighting, which were then used as goals for simulations. These goals included spectrum, intensity and timing of light at the human eye. The study investigated the variability of key architectural decisions in hospital room design to determine their influence on achieving the goals. The simulations showed how choices in building orientation, window size, user-window position and interior finishes affect the circadian efficacy of a space. Design decisions can improve or degrade the health potential for the space considered. While the findings in this research were specific to hospitals, the results can be applied to other building types such as office buildings and residences. 33 refs., 7 figs.

  1. A Human Body Analysis System

    Directory of Open Access Journals (Sweden)

    Girondel Vincent

    2006-01-01

    Full Text Available This paper describes a system for human body analysis (segmentation, tracking, face/hands localisation, posture recognition from a single view that is fast and completely automatic. The system first extracts low-level data and uses part of the data for high-level interpretation. It can detect and track several persons even if they merge or are completely occluded by another person from the camera's point of view. For the high-level interpretation step, static posture recognition is performed using a belief theory-based classifier. The belief theory is considered here as a new approach for performing posture recognition and classification using imprecise and/or conflicting data. Four different static postures are considered: standing, sitting, squatting, and lying. The aim of this paper is to give a global view and an evaluation of the performances of the entire system and to describe in detail each of its processing steps, whereas our previous publications focused on a single part of the system. The efficiency and the limits of the system have been highlighted on a database of more than fifty video sequences where a dozen different individuals appear. This system allows real-time processing and aims at monitoring elderly people in video surveillance applications or at the mixing of real and virtual worlds in ambient intelligence systems.

  2. Multicellular models of intercellular synchronization in circadian neural networks

    International Nuclear Information System (INIS)

    Henson, Michael A.

    2013-01-01

    The circadian clock generates 24 h rhythms that drive physiological and behavioral processes in a diverse range of organisms including microbes, plants, insects, and mammals. Recent experimental advances have produced improved understanding of the molecular mechanisms involved in circadian rhythm generation at the single cell level. However, the intercellular mechanisms that allow large populations of coupled pacemaker cells to synchronize and coordinate their rhythms remain poorly understood. The purpose of this article is to review recent progress in dynamic modeling of the circadian clock with a focus on multicellular models required to describe cell population synchronization. Mammalian systems are emphasized to illustrate the highly heterogeneous structure and rich dynamical behavior of multicellular circadian systems. Available multicellular models are characterized with respect to their single cell descriptions, intercellular coupling mechanisms, and network topologies. Examples drawn from our own research are used to demonstrate the advantages associated with integrating detailed single cell models within realistic multicellular networks for prediction of mammalian system dynamics. Mathematical modeling is shown to represent a powerful tool for understanding the intracellular and intercellular mechanisms utilized to robustly synchronize large populations of highly heterogeneous and sparsely coupled single cell oscillators. The article concludes with some possible directions for future research

  3. The Importance of the Circadian Clock in Regulating Plant Metabolism

    Directory of Open Access Journals (Sweden)

    Jin A Kim

    2017-12-01

    Full Text Available Carbohydrates are the primary energy source for plant development. Plants synthesize sucrose in source organs and transport them to sink organs during plant growth. This metabolism is sensitive to environmental changes in light quantity, quality, and photoperiod. In the daytime, the synthesis of sucrose and starch accumulates, and starch is degraded at nighttime. The circadian clock genes provide plants with information on the daily environmental changes and directly control many developmental processes, which are related to the path of primary metabolites throughout the life cycle. The circadian clock mechanism and processes of metabolism controlled by the circadian rhythm were studied in the model plant Arabidopsis and in the crops potato and rice. However, the translation of molecular mechanisms obtained from studies of model plants to crop plants is still difficult. Crop plants have specific organs such as edible seed and tuber that increase the size or accumulate valuable metabolites by harvestable metabolic components. Human consumers are interested in the regulation and promotion of these agriculturally significant crops. Circadian clock manipulation may suggest various strategies for the increased productivity of food crops through using environmental signal or overcoming environmental stress.

  4. Drosophila spaghetti and doubletime link the circadian clock and light to caspases, apoptosis and tauopathy.

    Directory of Open Access Journals (Sweden)

    John C Means

    2015-05-01

    Full Text Available While circadian dysfunction and neurodegeneration are correlated, the mechanism for this is not understood. It is not known if age-dependent circadian dysfunction leads to neurodegeneration or vice-versa, and the proteins that mediate the effect remain unidentified. Here, we show that the knock-down of a regulator (spag of the circadian kinase Dbt in circadian cells lowers Dbt levels abnormally, lengthens circadian rhythms and causes expression of activated initiator caspase (Dronc in the optic lobes during the middle of the day or after light pulses at night. Likewise, reduced Dbt activity lengthens circadian period and causes expression of activated Dronc, and a loss-of-function mutation in Clk also leads to expression of activated Dronc in a light-dependent manner. Genetic epistasis experiments place Dbt downstream of Spag in the pathway, and Spag-dependent reductions of Dbt are shown to require the proteasome. Importantly, activated Dronc expression due to reduced Spag or Dbt activity occurs in cells that do not express the spag RNAi or dominant negative Dbt and requires PDF neuropeptide signaling from the same neurons that support behavioral rhythms. Furthermore, reduction of Dbt or Spag activity leads to Dronc-dependent Drosophila Tau cleavage and enhanced neurodegeneration produced by human Tau in a fly eye model for tauopathy. Aging flies with lowered Dbt or Spag function show markers of cell death as well as behavioral deficits and shortened lifespans, and even old wild type flies exhibit Dbt modification and activated caspase at particular times of day. These results suggest that Dbt suppresses expression of activated Dronc to prevent Tau cleavage, and that the circadian clock defects confer sensitivity to expression of activated Dronc in response to prolonged light. They establish a link between the circadian clock factors, light, cell death pathways and Tau toxicity, potentially via dysregulation of circadian neuronal remodeling in

  5. Relationship between circadian rhythm amplitude and stability with sleep quality and sleepiness among shift nurses and health care workers.

    Science.gov (United States)

    Jafari Roodbandi, Akram; Choobineh, Alireza; Daneshvar, Somayeh

    2015-01-01

    Sleep is affected by the circadian cycle and its features. Amplitude and stability of circadian rhythm are important parameters of the circadian cycle. This study aims to examine the relationship between amplitude and stability of circadian rhythm with sleep quality and sleepiness. In this cross-sectional research, 315 shift nurses and health care workers from educational hospitals of Kerman University of Medical Sciences (KUMS), Iran, were selected using a random sampling method. The Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Circadian Type Inventory (CTI) were used to collect the required data. In this study, 83.2% suffered from poor sleep and one-half had moderate and excessive sleepiness. The results showed that flexibility in circadian rhythm stability, job stress and sleepiness are among the factors affecting quality sleep in shift workers. Those whose circadian rhythm amplitude was languid suffered more from sleepiness and those whose circadian stability was flexible had a better sleep. Variables including circadian rhythm stability (flexible/rigid) and amplitude (languid/vigorous) can act as predictive indices in order to employ people in a shift work system so that sleepiness and a drop in quality of sleep are prevented.

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

    Science.gov (United States)

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

    2006-09-01

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

  7. Modelling and Analysis of the Feeding Regimen Induced Entrainment of Hepatocyte Circadian Oscillators Using Petri Nets

    Science.gov (United States)

    Tareen, Samar Hayat Khan; Ahmad, Jamil

    2015-01-01

    Circadian rhythms are certain periodic behaviours exhibited by living organism at different levels, including cellular and system-wide scales. Recent studies have found that the circadian rhythms of several peripheral organs in mammals, such as the liver, are able to entrain their clocks to received signals independent of other system level clocks, in particular when responding to signals generated during feeding. These studies have found SIRT1, PARP1, and HSF1 proteins to be the major influencers of the core CLOCKBMAL1:PER-CRY circadian clock. These entities, along with abstracted feeding induced signals were modelled collectively in this study using Petri Nets. The properties of the model show that the circadian system itself is strongly robust, and is able to continually evolve. The modelled feeding regimens suggest that the usual 3 meals/day and 2 meals/day feeding regimens are beneficial with any more or less meals/day negatively affecting the system. PMID:25789928

  8. Modelling and analysis of the feeding regimen induced entrainment of hepatocyte circadian oscillators using petri nets.

    Directory of Open Access Journals (Sweden)

    Samar Hayat Khan Tareen

    Full Text Available Circadian rhythms are certain periodic behaviours exhibited by living organism at different levels, including cellular and system-wide scales. Recent studies have found that the circadian rhythms of several peripheral organs in mammals, such as the liver, are able to entrain their clocks to received signals independent of other system level clocks, in particular when responding to signals generated during feeding. These studies have found SIRT1, PARP1, and HSF1 proteins to be the major influencers of the core CLOCKBMAL1:PER-CRY circadian clock. These entities, along with abstracted feeding induced signals were modelled collectively in this study using Petri Nets. The properties of the model show that the circadian system itself is strongly robust, and is able to continually evolve. The modelled feeding regimens suggest that the usual 3 meals/day and 2 meals/day feeding regimens are beneficial with any more or less meals/day negatively affecting the system.

  9. Activity/inactivity circadian rhythm shows high similarities between young obesity-induced rats and old rats.

    Science.gov (United States)

    Bravo Santos, R; Delgado, J; Cubero, J; Franco, L; Ruiz-Moyano, S; Mesa, M; Rodríguez, A B; Uguz, C; Barriga, C

    2016-03-01

    The objective of the present study was to compare differences between elderly rats and young obesity-induced rats in their activity/inactivity circadian rhythm. The investigation was motivated by the differences reported previously for the circadian rhythms of both obese and elderly humans (and other animals), and those of healthy, young or mature individuals. Three groups of rats were formed: a young control group which was fed a standard chow for rodents; a young obesity-induced group which was fed a high-fat diet for four months; and an elderly control group with rats aged 2.5 years that was fed a standard chow for rodents. Activity/inactivity data were registered through actimetry using infrared actimeter systems in each cage to detect activity. Data were logged on a computer and chronobiological analysis were performed. The results showed diurnal activity (sleep time), nocturnal activity (awake time), amplitude, acrophase, and interdaily stability to be similar between the young obesity-induced group and the elderly control group, but different in the young control group. We have concluded that obesity leads to a chronodisruption status in the body similar to the circadian rhythm degradation observed in the elderly.

  10. Evolutionary history of the PER3 variable number of tandem repeats (VNTR): idiosyncratic aspect of primate molecular circadian clock.

    Science.gov (United States)

    Sabino, Flávia Cal; Ribeiro, Amanda Oliveira; Tufik, Sérgio; Torres, Laila Brito; Oliveira, José Américo; Mello, Luiz Eugênio Araújo Moraes; Cavalcante, Jeferson Souza; Pedrazzoli, Mario

    2014-01-01

    The PER3 gene is one of the clock genes, which function in the core mammalian molecular circadian system. A variable number of tandem repeats (VNTR) locus in the 18th exon of this gene has been strongly associated to circadian rhythm phenotypes and sleep organization in humans, but it has not been identified in other mammals except primates. To better understand the evolution and the placement of the PER3 VNTR in a phylogenetical context, the present study enlarges the investigation about the presence and the structure of this variable region in a large sample of primate species and other mammals. The analysis of the results has revealed that the PER3 VNTR occurs exclusively in simiiforme primates and that the number of copies of the primitive unit ranges from 2 to 11 across different primate species. Two transposable elements surrounding the 18th exon of PER3 were found in primates with published genome sequences, including the tarsiiforme Tarsius syrichta, which lacks the VNTR. These results suggest that this VNTR may have evolved in a common ancestor of the simiiforme branch and that the evolutionary copy number differentiation of this VNTR may be associated with primate simiiformes sleep and circadian phenotype patterns.

  11. Evolutionary history of the PER3 variable number of tandem repeats (VNTR: idiosyncratic aspect of primate molecular circadian clock.

    Directory of Open Access Journals (Sweden)

    Flávia Cal Sabino

    Full Text Available The PER3 gene is one of the clock genes, which function in the core mammalian molecular circadian system. A variable number of tandem repeats (VNTR locus in the 18th exon of this gene has been strongly associated to circadian rhythm phenotypes and sleep organization in humans, but it has not been identified in other mammals except primates. To better understand the evolution and the placement of the PER3 VNTR in a phylogenetical context, the present study enlarges the investigation about the presence and the structure of this variable region in a large sample of primate species and other mammals. The analysis of the results has revealed that the PER3 VNTR occurs exclusively in simiiforme primates and that the number of copies of the primitive unit ranges from 2 to 11 across different primate species. Two transposable elements surrounding the 18th exon of PER3 were found in primates with published genome sequences, including the tarsiiforme Tarsius syrichta, which lacks the VNTR. These results suggest that this VNTR may have evolved in a common ancestor of the simiiforme branch and that the evolutionary copy number differentiation of this VNTR may be associated with primate simiiformes sleep and circadian phenotype patterns.

  12. Genetic disruption of the core circadian clock impairs hippocampus-dependent memory

    OpenAIRE

    2014-01-01

    Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1−/− mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippoca...

  13. Minimal tool set for a prokaryotic circadian clock.

    Science.gov (United States)

    Schmelling, Nicolas M; Lehmann, Robert; Chaudhury, Paushali; Beck, Christian; Albers, Sonja-Verena; Axmann, Ilka M; Wiegard, Anika

    2017-07-21

    Circadian clocks are found in organisms of almost all domains including photosynthetic Cyanobacteria, whereby large diversity exists within the protein components involved. In the model cyanobacterium Synechococcus elongatus PCC 7942 circadian rhythms are driven by a unique KaiABC protein clock, which is embedded in a network of input and output factors. Homologous proteins to the KaiABC clock have been observed in Bacteria and Archaea, where evidence for circadian behavior in these domains is accumulating. However, interaction and function of non-cyanobacterial Kai-proteins as well as homologous input and output components remain mainly unclear. Using a universal BLAST analyses, we identified putative KaiC-based timing systems in organisms outside as well as variations within Cyanobacteria. A systematic analyses of publicly available microarray data elucidated interesting variations in circadian gene expression between different cyanobacterial strains, which might be correlated to the diversity of genome encoded clock components. Based on statistical analyses of co-occurrences of the clock components homologous to Synechococcus elongatus PCC 7942, we propose putative networks of reduced and fully functional clock systems. Further, we studied KaiC sequence conservation to determine functionally important regions of diverged KaiC homologs. Biochemical characterization of exemplary cyanobacterial KaiC proteins as well as homologs from two thermophilic Archaea demonstrated that kinase activity is always present. However, a KaiA-mediated phosphorylation is only detectable in KaiC1 orthologs. Our analysis of 11,264 genomes clearly demonstrates that components of the Synechococcus elongatus PCC 7942 circadian clock are present in Bacteria and Archaea. However, all components are less abundant in other organisms than Cyanobacteria and KaiA, Pex, LdpA, and CdpA are only present in the latter. Thus, only reduced KaiBC-based or even simpler, solely KaiC-based timing systems

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

    Science.gov (United States)

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

    2013-11-01

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

  15. Human tissue in systems medicine.

    Science.gov (United States)

    Caie, Peter D; Schuur, Klaas; Oniscu, Anca; Mullen, Peter; Reynolds, Paul A; Harrison, David J

    2013-12-01

    Histopathology, the examination of an architecturally artefactual, two-dimensional and static image remains a potent tool allowing diagnosis and empirical expectation of prognosis. Considerable optimism exists that the advent of molecular genetic testing and other biomarker strategies will improve or even replace this ancient technology. A number of biomarkers already add considerable value for prediction of whether a treatment will work. In this short review we argue that a systems medicine approach to pathology will not seek to replace traditional pathology, but rather augment it. Systems approaches need to incorporate quantitative morphological, protein, mRNA and DNA data. A significant challenge for clinical implementation of systems pathology is how to optimize information available from tissue, which is frequently sub-optimal in quality and amount, and yet generate useful predictive models that work. The transition of histopathology to systems pathophysiology and the use of multiscale data sets usher in a new era in diagnosis, prognosis and prediction based on the analysis of human tissue. © 2013 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.

  16. Tunability of the circadian action of tetrachromatic solid-state light sources

    International Nuclear Information System (INIS)

    Žukauskas, A.; Vaicekauskas, R.

    2015-01-01

    An approach to the optimization of the spectral power distribution of solid-state light sources with the tunable non-image forming photobiological effect on the human circadian rhythm is proposed. For tetrachromatic clusters of model narrow-band (direct-emission) light-emitting diodes (LEDs), the limiting tunability of the circadian action factor (CAF), which is the ratio of the circadian efficacy to luminous efficacy of radiation, was established as a function of constraining color fidelity and luminous efficacy of radiation. For constant correlated color temperatures (CCTs), the CAF of the LED clusters can be tuned above and below that of the corresponding blackbody radiators, whereas for variable CCT, the clusters can have circadian tunability covering that of a temperature-tunable blackbody radiator

  17. Tunability of the circadian action of tetrachromatic solid-state light sources

    Energy Technology Data Exchange (ETDEWEB)

    Žukauskas, A., E-mail: arturas.zukauskas@ff.vu.lt [Institute of Applied Research, Vilnius University, Saulėtekio al. 9-III, LT-10222 Vilnius (Lithuania); Vaicekauskas, R. [Department of Computer Science, Vilnius University, Didlaukio g. 47, Vilnius LT-08303 (Lithuania)

    2015-01-26

    An approach to the optimization of the spectral power distribution of solid-state light sources with the tunable non-image forming photobiological effect on the human circadian rhythm is proposed. For tetrachromatic clusters of model narrow-band (direct-emission) light-emitting diodes (LEDs), the limiting tunability of the circadian action factor (CAF), which is the ratio of the circadian efficacy to luminous efficacy of radiation, was established as a function of constraining color fidelity and luminous efficacy of radiation. For constant correlated color temperatures (CCTs), the CAF of the LED clusters can be tuned above and below that of the corresponding blackbody radiators, whereas for variable CCT, the clusters can have circadian tunability covering that of a temperature-tunable blackbody radiator.

  18. Are circadian rhythms new pathways to understand Autism Spectrum Disorder?

    Science.gov (United States)

    Geoffray, M-M; Nicolas, A; Speranza, M; Georgieff, N

    2016-11-01

    Autism Spectrum Disorder (ASD) is a frequent neurodevelopmental disorder. ASD is probably the result of intricate interactions between genes and environment altering progressively the development of brain structures and functions. Circadian rhythms are a complex intrinsic timing system composed of almost as many clocks as there are body cells. They regulate a variety of physiological and behavioral processes such as the sleep-wake rhythm. ASD is often associated with sleep disorders and low levels of melatonin. This first point raises the hypothesis that circadian rhythms could have an implication in ASD etiology. Moreover, circadian rhythms are generated by auto-regulatory genetic feedback loops, driven by transcription factors CLOCK and BMAL1, who drive transcription daily patterns of a wide number of clock-controlled genes (CCGs) in different cellular contexts across tissues. Among these, are some CCGs coding for synapses molecules associated to ASD susceptibility. Furthermore, evidence emerges about circadian rhythms control of time brain development processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Circadian remodeling of neuronal circuits involved in rhythmic behavior.

    Directory of Open Access Journals (Sweden)

    María Paz Fernández

    2008-03-01

    Full Text Available Clock output pathways are central to convey timing information from the circadian clock to a diversity of physiological systems, ranging from cell-autonomous processes to behavior. While the molecular mechanisms that generate and sustain rhythmicity at the cellular level are well understood, it is unclear how this information is further structured to control specific behavioral outputs. Rhythmic release of pigment dispersing factor (PDF has been proposed to propagate the time of day information from core pacemaker cells to downstream targets underlying rhythmic locomotor activity. Indeed, such circadian changes in PDF intensity represent the only known mechanism through which the PDF circuit could communicate with its output. Here we describe a novel circadian phenomenon involving extensive remodeling in the axonal terminals of the PDF circuit, which display higher complexity during the day and significantly lower complexity at nighttime, both under daily cycles and constant conditions. In support to its circadian nature, cycling is lost in bona fide clockless mutants. We propose this clock-controlled structural plasticity as a candidate mechanism contributing to the transmission of the information downstream of pacemaker cells.

  20. Circadian clock genes Per1 and Per2 regulate the response of metabolism-associated transcripts to sleep disruption.

    Directory of Open Access Journals (Sweden)

    Jana Husse

    Full Text Available Human and animal studies demonstrate that short sleep or poor sleep quality, e.g. in night shift workers, promote the development of obesity and diabetes. Effects of sleep disruption on glucose homeostasis and liver physiology are well documented. However, changes in adipokine levels after sleep disruption suggest that adipocytes might be another important peripheral target of sleep. Circadian clocks regulate metabolic homeostasis and clock disruption can result in obesity and the metabolic syndrome. The finding that sleep and clock disruption have very similar metabolic effects prompted us to ask whether the circadian clock machinery may mediate the metabolic consequences of sleep disruption. To test this we analyzed energy homeostasis and adipocyte transcriptome regulation in a mouse model of shift work, in which we prevented mice from sleeping during the first six hours of their normal inactive phase for five consecutive days (timed sleep restriction--TSR. We compared the effects of TSR between wild-type and Per1/2 double mutant mice with the prediction that the absence of a circadian clock in Per1/2 mutants would result in a blunted metabolic response to TSR. In wild-types, TSR induces significant transcriptional reprogramming of white adipose tissue, suggestive of increased lipogenesis, together with increased secretion of the adipokine leptin and increased food intake, hallmarks of obesity and associated leptin resistance. Some of these changes persist for at least one week after the end of TSR, indicating that even short episodes of sleep disruption can induce prolonged physiological impairments. In contrast, Per1/2 deficient mice show blunted effects of TSR on food intake, leptin levels and adipose transcription. We conclude that the absence of a functional clock in Per1/2 double mutants protects these mice from TSR-induced metabolic reprogramming, suggesting a role of the circadian timing system in regulating the physiological effects

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

    Directory of Open Access Journals (Sweden)

    Marco Proietto

    2015-07-01

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

  2. The Circadian Clock Gene BMAL1 Coordinates Intestinal RegenerationSummary

    Directory of Open Access Journals (Sweden)

    Kyle Stokes

    2017-07-01

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

  3. Individual differences in circadian locomotor parameters correlate with anxiety- and depression-like behavior.

    Directory of Open Access Journals (Sweden)

    Jeffrey Anyan

    Full Text Available Disrupted circadian rhythms are a core feature of mood and anxiety disorders. Circadian rhythms are coordinated by a light-entrainable master clock located in the suprachiasmatic nucleus. Animal models of mood and anxiety disorders often exhibit blunted rhythms in locomotor activity and clock gene expression. Interestingly, the changes in circadian rhythms correlate with mood-related behaviours. Although animal models of depression and anxiety exhibit aberrant circadian rhythms in physiology and behavior, it is possible that the methodology being used to induce the behavioral phenotype (e.g., brain lesions, chronic stress, global gene deletion affect behavior independently of circadian system. This study investigates the relationship between individual differences in circadian locomotor parameters and mood-related behaviors in healthy rats. The circadian phenotype of male Lewis rats was characterized by analyzing wheel running behavior under standard 12h:12h LD conditions, constant dark, constant light, and rate of re-entrainment to a phase advance. Rats were then tested on a battery of behavioral tests: activity box, restricted feeding, elevated plus maze, forced swim test, and fear conditioning. Under 12h:12h LD conditions, percent of daily activity in the light phase and variability in activity onset were associated with longer latency to immobility in the forced swim test. Variability in onset also correlated positively with anxiety-like behavior in the elevated plus maze. Rate of re-entrainment correlated positively with measures of anxiety in the activity box and elevated plus maze. Lastly, we found that free running period under constant dark was associated with anxiety-like behaviors in the activity box and elevated plus maze. Our results provide a previously uncharacterized relationship between circadian locomotor parameters and mood-related behaviors in healthy rats and provide a basis for future examination into circadian clock

  4. Drosophila: An Emergent Model for Delineating Interactions between the Circadian Clock and Drugs of Abuse

    Directory of Open Access Journals (Sweden)

    Aliza K. De Nobrega

    2017-01-01

    Full Text Available Endogenous circadian oscillators orchestrate rhythms at the cellular, physiological, and behavioral levels across species to coordinate activity, for example, sleep/wake cycles, metabolism, and learning and memory, with predictable environmental cycles. The 21st century has seen a dramatic rise in the incidence of circadian and sleep disorders with globalization, technological advances, and the use of personal electronics. The circadian clock modulates alcohol- and drug-induced behaviors with circadian misalignment contributing to increased substance use and abuse. Invertebrate models, such as Drosophila melanogaster, have proven invaluable for the identification of genetic and molecular mechanisms underlying highly conserved processes including the circadian clock, drug tolerance, and reward systems. In this review, we highlight the contributions of Drosophila as a model system for understanding the bidirectional interactions between the circadian system and the drugs of abuse, alcohol and cocaine, and illustrate the highly conserved nature of these interactions between Drosophila and mammalian systems. Research in Drosophila provides mechanistic insights into the corresponding behaviors in higher organisms and can be used as a guide for targeted inquiries in mammals.

  5. Development of a circadian light source

    Science.gov (United States)

    Nicol, David B.; Ferguson, Ian T.

    2002-11-01

    Solid state lighting presents a new paradigm for lighting - controllability. Certain characteristics of the lighting environment can be manipulated, because of the possibility of using multiple LEDs of different emission wavelengths as the illumination source. This will provide a new, versatile, general illumination source due to the ability to vary the spectral power distribution. New effects beyond the visual may be achieved that are not possible with conventional light sources. Illumination has long been the primary function of lighting but as the lighting industry has matured the psychological aspects of lighting have been considered by designers; for example, choosing a particular lighting distribution or color variation in retail applications. The next step in the evolution of light is to consider the physiological effects of lighting that cause biological changes in a person within the environment. This work presents the development of a source that may have important bearing on this area of lighting. A circadian light source has been developed to provide an illumination source that works by modulating its correlated color temperature to mimic the changes in natural daylight through the day. In addition, this source can cause or control physiological effects for a person illuminated by it. The importance of this is seen in the human circadian rhythm's peak response corresponding to blue light at ~460 nm which corresponds to the primary spectral difference in increasing color temperature. The device works by adding blue light to a broadband source or mixing polychromatic light to mimic the variation of color temperature observed for the Planckian Locus on the CIE diagram. This device can have several applications including: a tool for researchers in this area, a general illumination lighting technology, and a light therapy device.

  6. Development of cortisol circadian rhythm in infancy.

    NARCIS (Netherlands)

    Weerth, C. de; Zijl, R.H.

    2003-01-01

    BACKGROUND AND AIMS: Cortisol is the final product of the hypothalamus-pituitary-adrenal (HPA) axis. It is secreted in a pulsatile fashion that displays a circadian rhythm. Infants are born without a circadian rhythm in cortisol and they acquire it during their first year of life. Studies do not

  7. Human Factors Interface with Systems Engineering for NASA Human Spaceflights

    Science.gov (United States)

    Wong, Douglas T.

    2009-01-01

    This paper summarizes the past and present successes of the Habitability and Human Factors Branch (HHFB) at NASA Johnson Space Center s Space Life Sciences Directorate (SLSD) in including the Human-As-A-System (HAAS) model in many NASA programs and what steps to be taken to integrate the Human-Centered Design Philosophy (HCDP) into NASA s Systems Engineering (SE) process. The HAAS model stresses systems are ultimately designed for the humans; the humans should therefore be considered as a system within the systems. Therefore, the model places strong emphasis on human factors engineering. Since 1987, the HHFB has been engaging with many major NASA programs with much success. The HHFB helped create the NASA Standard 3000 (a human factors engineering practice guide) and the Human Systems Integration Requirements document. These efforts resulted in the HAAS model being included in many NASA programs. As an example, the HAAS model has been successfully introduced into the programmatic and systems engineering structures of the International Space Station Program (ISSP). Success in the ISSP caused other NASA programs to recognize the importance of the HAAS concept. Also due to this success, the HHFB helped update NASA s Systems Engineering Handbook in December 2007 to include HAAS as a recommended practice. Nonetheless, the HAAS model has yet to become an integral part of the NASA SE process. Besides continuing in integrating HAAS into current and future NASA programs, the HHFB will investigate incorporating the Human-Centered Design Philosophy (HCDP) into the NASA SE Handbook. The HCDP goes further than the HAAS model by emphasizing a holistic and iterative human-centered systems design concept.

  8. Circadian rhythms, time-restricted feeding, and healthy aging.

    Science.gov (United States)

    Manoogian, Emily N C; Panda, Satchidananda

    2017-10-01

    Circadian rhythms optimize physiology and health by temporally coordinating cellular function, tissue function, and behavior. These endogenous rhythms dampen with age and thus compromise temporal coordination. Feeding-fasting patterns are an external cue that profoundly influence the robustness of daily biological rhythms. Erratic eating patterns can disrupt the temporal coordination of metabolism and physiology leading to chronic diseases that are also characteristic of aging. However, sustaining a robust feeding-fasting cycle, even without altering nutrition quality or quantity, can prevent or reverse these chronic diseases in experimental models. In humans, epidemiological studies have shown erratic eating patterns increase the risk of disease, whereas sustained feeding-fasting cycles, or prolonged overnight fasting, is correlated with protection from breast cancer. Therefore, optimizing the timing of external cues with defined eating patterns can sustain a robust circadian clock, which may prevent disease and improve prognosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Cancer Clocks Out for Lunch: Disruption of Circadian Rhythm and Metabolic Oscillation in Cancer.

    Science.gov (United States)

    Altman, Brian J

    2016-01-01

    Circadian rhythms are 24-h oscillations present in most eukaryotes and many prokaryotes that synchronize activity to the day-night cycle. They are an essential feature of organismal and cell physiology that coordinate many of the metabolic, biosynthetic, and signal transduction pathways studied in biology. The molecular mechanism of circadian rhythm is controlled both by signal transduction and gene transcription as well as by metabolic feedback. The role of circadian rhythm in cancer cell development and survival is still not well understood, but as will be discussed in this Review, accumulated research suggests that circadian rhythm may be altered or disrupted in many human cancers downstream of common oncogenic alterations. Thus, a complete understanding of the genetic and metabolic alterations in cancer must take potential circadian rhythm perturbations into account, as this disruption itself will influence how gene expression and metabolism are altered in the cancer cell compared to its non-transformed neighbor. It will be important to better understand these circadian changes in both normal and cancer cell physiology to potentially design treatment modalities to exploit this insight.

  10. The Impact of Sleep and Circadian Disturbance on Hormones and Metabolism

    Directory of Open Access Journals (Sweden)

    Tae Won Kim

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Astha Malik

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

  12. The Influence of Circadian Variation on Aetiological Markers of Ankle Injury.

    Science.gov (United States)

    Brogden, Chris; Marrin, Kelly; Page, Richard; Greig, Matt

    2018-03-15

    Clinical and functional assessments are performed regularly in sporting environments to screen for performance deficits and injury risk. Circadian rhythms have been demonstrated to affect human performance, however the influence of time of day on a battery of multiple ankle injury risk factors has yet to be established within athletic populations. To investigate the influence of circadian variation on a battery of tests, used to screen for ankle aetiological risk factors. Randomised crossover design. University laboratory. Thirty-three semi-professional soccer players (age 24.9 ± 4.4 years; height 1.77 ± 0.17 m; body mass 75.47 ± 7.98 kg) completed three randomized experimental trials (07:00 h, 12:00 h, 19:00 h) Main Outcome Measures: Trials involved the completion of a standardized test battery comprising Biodex Stability System (BSS), Star Excursion Balance Test (SEBT), isokinetic inversion: eversion ratio, joint position sense, and a drop landing inversion cutting manoeuvre. Repeated measures analysis of variance revealed significantly (P < 0.05) lower values for all BSS indicia; Overall Stability Index (1.10 ± 0.31 a.u), Anterior-Posterior (0.76 ± 0.21 a.u) and Medio-Lateral (0.68 ± 0.23) at 12:00 h when compared to 07:00 h. (1.30 ± 0.45 a.u; 0.96 ± 0.26 a.u; 0.82 ± 0.40 a.u) respectively. However, no significant (P ≥ 0.05) main effects for time of day were reported for any other test. Circadian influence on ankle aetiological risk factors was task dependent, with measures of proprioception, strength and SEBT displaying no circadian variation, indicating no association between time of day and markers of injury risk. However, the BSS displayed improved performance at midday, indicating postural stability tasks requiring unanticipated movements to display a time of day effect and potential increased injury risk. Consequently, time of testing for this task should be standardized to ensure correct interpretations of assessments and/or interventions.

  13. Effect of circadian phase on memory acquisition and recall: operant conditioning vs. classical conditioning.

    Science.gov (United States)

    Garren, Madeleine V; Sexauer, Stephen B; Page, Terry L

    2013-01-01

    There have been several studies on the role of circadian clocks in the regulation of associative learning and memory processes in both vertebrate and invertebrate species. The results have been quite variable and at present it is unclear to what extent the variability observed reflects species differences or differences in methodology. Previous results have shown that following differential classical conditioning in the cockroach, Rhyparobia maderae, in an olfactory discrimination task, formation of the short-term and long-term memory is under strict circadian control. In contrast, there appeared to be no circadian regulation of the ability to recall established memories. In the present study, we show that following operant conditioning of the same species in a very similar olfactory discrimination task, there is no impact of the circadian system on either short-term or long-term memory formation. On the other hand, ability to recall established memories is strongly tied to the circadian phase of training. On the basis of these data and those previously reported for phylogenetically diverse species, it is suggested that there may be fundamental differences in the way the circadian system regulates learning and memory in classical and operant conditioning.

  14. Effect of circadian phase on memory acquisition and recall: operant conditioning vs. classical conditioning.

    Directory of Open Access Journals (Sweden)

    Madeleine V Garren

    Full Text Available There have been several studies on the role of circadian clocks in the regulation of associative learning and memory processes in both vertebrate and invertebrate species. The results have been quite variable and at present it is unclear to what extent the variability observed reflects species differences or differences in methodology. Previous results have shown that following differential classical conditioning in the cockroach, Rhyparobia maderae, in an olfactory discrimination task, formation of the short-term and long-term memory is under strict circadian control. In contrast, there appeared to be no circadian regulation of the ability to recall established memories. In the present study, we show that following operant conditioning of the same species in a very similar olfactory discrimination task, there is no impact of the circadian system on either short-term or long-term memory formation. On the other hand, ability to recall established memories is strongly tied to the circadian phase of training. On the basis of these data and those previously reported for phylogenetically diverse species, it is suggested that there may be fundamental differences in the way the circadian system regulates learning and memory in classical and operant conditioning.

  15. Circadian Misalignment Increases C-Reactive Protein and Blood Pressure in Chronic Shift Workers.

    Science.gov (United States)

    Morris, Christopher J; Purvis, Taylor E; Mistretta, Joseph; Hu, Kun; Scheer, Frank A J L

    2017-04-01

    Shift work is a risk factor for inflammation, hypertension, and cardiovascular disease. This increased risk cannot be fully explained by classical risk factors. Shift workers' behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in shift workers, independent of differences in work stress, food quality, and other factors that are likely to differ between night and day shifts. Thus, our objectives were to determine the independent effect of circadian misalignment on 24-h high-sensitivity C-reactive protein (hs-CRP; a marker of systemic inflammation) and blood pressure levels-cardiovascular disease risk factors-in chronic shift workers. Chronic shift workers undertook two 3-day laboratory protocols that simulated night work, comprising 12-hour inverted behavioral and environmental cycles (circadian misalignment) or simulated day work (circadian alignment), using a randomized, crossover design. Circadian misalignment increased 24-h hs-CRP by 11% ( p shift workers. This may help explain the increased inflammation, hypertension, and cardiovascular disease risk in shift workers.

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

    Science.gov (United States)

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

    2017-05-01

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

  17. Human Adaptive Mechatronics and Human-System Modelling

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    2013-03-01

    Full Text Available Several topics in projects for mechatronics studies, which are 'Human Adaptive Mechatronics (HAM' and 'Human-System Modelling (HSM', are presented in this paper. The main research theme of the HAM project is a design strategy for a new intelligent mechatronics system, which enhances operators' skills during machine operation. Skill analyses and control system design have been addressed. In the HSM project, human modelling based on hierarchical classification of skills was studied, including the following five types of skills: social, planning, cognitive, motion and sensory-motor skills. This paper includes digests of these research topics and the outcomes concerning each type of skill. Relationships with other research activities, knowledge and information that will be helpful for readers who are trying to study assistive human-mechatronics systems are also mentioned.

  18. Human responses to bright light of different durations.

    Science.gov (United States)

    Chang, Anne-Marie; Santhi, Nayantara; St Hilaire, Melissa; Gronfier, Claude; Bradstreet, Dayna S; Duffy, Jeanne F; Lockley, Steven W; Kronauer, Richard E; Czeisler, Charles A

    2012-07-01

    Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying bright light. Thirty-nine young healthy participants (16 female; 22.18±3.62 years) completed a 9-day inpatient study. Following three baseline days, participants underwent an initial circadian phase assessment procedure in dim light (light pulse (∼10,000 lux) of 0.2 h, 1.0 h, 2.5 h or 4.0 h duration during a 4.5 h controlled-posture episode centred in a 16 h wake episode. After another 8 h sleep episode, participants completed a second circadian phase assessment. Phase shifts were calculated from the difference in the clock time of the dim light melatonin onset (DLMO) between the initial and final phase assessments. Exposure to varying durations of bright light reset the circadian pacemaker in a dose-dependent, non-linear manner. Per minute of exposure, the 0.2 h duration was over 5 times more effective at phase delaying the circadian pacemaker (1.07±0.36 h) as compared with the 4.0 h duration (2.65±0.24 h). Acute melatonin suppression and subjective sleepiness also had a dose-dependent response to light exposure duration. These results provide strong evidence for a non-linear resetting response of the human circadian pacemaker to light duration.

  19. CIRCADIAN RHYTHMS FROM MULTIPLE OSCILLATORS: LESSONS FROM DIVERSE ORGANISMS

    OpenAIRE

    Bell-Pedersen, Deborah; Cassone, Vincent M.; Earnest, David J.; Golden, Susan S.; Hardin, Paul E.; Thomas, Terry L.; Zoran, Mark J.

    2005-01-01

    The organization of biological activities into daily cycles is universal in organisms as diverse as cyanobacteria, fungi, algae, plants, flies, birds and man. Comparisons of circadian clocks in unicellular and multicellular organisms using molecular genetics and genomics have provided new insights into the mechanisms and complexity of clock systems. Whereas unicellular organisms require stand-alone clocks that can generate 24-hour rhythms for diverse processes, organisms with differentiated t...

  20. Shiftwork-Mediated Disruptions of Circadian Rhythms and Sleep Homeostasis Cause Serious Health Problems

    Directory of Open Access Journals (Sweden)

    Suliman Khan

    2018-01-01

    Full Text Available Shiftwork became common during the last few decades with the growing demands of human life. Despite the social inactivity and irregularity in habits, working in continuous irregular shifts causes serious health issues including sleep disorders, psychiatric disorders, cancer, and metabolic disorders. These health problems arise due to the disruption in circadian clock system, which is associated with alterations in genetic expressions. Alteration in clock controlling genes further affects genes linked with disorders including major depression disorder, bipolar disorder, phase delay and phase advance sleep syndromes, breast cancer, and colon cancer. A diverse research work is needed focusing on broad spectrum changes caused by jet lag in brain and neuronal system. This review is an attempt to motivate the researchers to conduct advanced studies in this area to identify the risk factors and mechanisms. Its goal is extended to make the shift workers aware about the risks associated with shiftwork.

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Guo-Xiang Ruan

    2008-10-01

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

  3. Bright to dim oscillatory response of the Neurospora circadian oscillator.

    Science.gov (United States)

    Gooch, Van D; Johnson, Alicia E; Larrondo, Luis F; Loros, Jennifer J; Dunlap, Jay C

    2014-02-01

    The fungus Neurospora crassa constitutes an important model system extensively used in chronobiology. Several studies have addressed how environmental cues, such as light, can reset or synchronize a circadian system. By means of an optimized firefly luciferase reporter gene and a controllable lighting system, we show that Neurospora can display molecular circadian rhythms in dim light when cultures receive bright light prior to entering dim light conditions. We refer to this behavior as the "bright to dim oscillatory response" (BDOR). The bright light treatment can be applied up to 76 h prior to dim exposure, and it can be as short as 15 min in duration. We have characterized this response in respect to the duration of the light pulse, the time of the light pulse before dim, the intensity of dim light, and the oscillation dynamics in dim light. Although the molecular mechanism that drives the BDOR remains obscure, these findings suggest that a long-term memory of bright light exists as part of the circadian molecular components. It is important to consider the ecological significance of such dim light responses in respect to how organisms naturally maintain their timing mechanism in moonlight.

  4. Toward a detailed computational model for the mammalian circadian clock

    Science.gov (United States)

    Leloup, Jean-Christophe; Goldbeter, Albert

    2003-06-01

    We present a computational model for the mammalian circadian clock based on the intertwined positive and negative regulatory loops involving the Per, Cry, Bmal1, Clock, and Rev-Erb genes. In agreement with experimental observations, the model can give rise to sustained circadian oscillations in continuous darkness, characterized by an antiphase relationship between Per/Cry/Rev-Erb and Bmal1 mRNAs. Sustained oscillations correspond to the rhythms autonomously generated by suprachiasmatic nuclei. For other parameter values, damped oscillations can also be obtained in the model. These oscillations, which transform into sustained oscillations when coupled to a periodic signal, correspond to rhythms produced by peripheral tissues. When incorporating the light-induced expression of the Per gene, the model accounts for entrainment of the oscillations by light-dark cycles. Simulations show that the phase of the oscillations can then vary by several hours with relatively minor changes in parameter values. Such a lability of the phase could account for physiological disorders related to circadian rhythms in humans, such as advanced or delayed sleep phase syndrome, whereas the lack of entrainment by light-dark cycles can be related to the non-24h sleep-wake syndrome. The model uncovers the possible existence of multiple sources of oscillatory behavior. Thus, in conditions where the indirect negative autoregulation of Per and Cry expression is inoperative, the model indicates the possibility that sustained oscillations might still arise from the negative autoregulation of Bmal1 expression.

  5. The Metronome of Symbiosis: Interactions Between Microbes and the Host Circadian Clock.

    Science.gov (United States)

    Heath-Heckman, Elizabeth A C

    2016-11-01

    The entrainment of circadian rhythms, physiological cycles with a period of about 24 h, is regulated by a variety of mechanisms, including nonvisual photoreception. While circadian rhythms have been shown to be integral to many processes in multicellular organisms, including immune regulation, the effect of circadian rhythms on symbiosis, or host-microbe interactions, has only recently begun to be studied. This review summarizes recent work in the interactions of both pathogenic and mutualistic associations with host and symbiont circadian rhythms, focusing specifically on three mutualistic systems in which this phenomenon has been best studied. One important theme taken from these studies is the fact that mutualisms are profoundly affected by the circadian rhythms of the host, but that the microbial symbionts in these associations can, in turn, manipulate host rhythms. The interplay between circadian rhythms and symbiosis is a promising new field with effects that should be kept in mind when designing future studies across biology. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Lingling Ma

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

  8. Mini Screening of Kinase Inhibitors Affecting Period-length of Mammalian Cellular Circadian Clock

    International Nuclear Information System (INIS)

    Yagita, Kazuhiro; Yamanaka, Iori; Koinuma, Satoshi; Shigeyoshi, Yasufumi; Uchiyama, Yasuo

    2009-01-01

    In mammalian circadian rhythms, the transcriptional-translational feedback loop (TTFL) consisting of a set of clock genes is believed to elicit the circadian clock oscillation. The TTFL model explains that the accumulation and degradation of mPER and mCRY proteins control the period-length (tau) of the circadian clock. Although recent studies revealed that the Casein Kinase Iεδ (CKIεδ) regurates the phosphorylation of mPER proteins and the circadian period-length, other kinases are also likely to contribute the phosphorylation of mPER. Here, we performed small scale screening using 84 chemical compounds known as kinase inhibitors to identify candidates possibly affecting the circadian period-length in mammalian cells. Screening by this high-throughput real-time bioluminescence monitoring system revealed that the several chemical compounds apparently lengthened the cellular circadian clock oscillation. These compounds are known as inhibitors against kinases such as Casein Kinase II (CKII), PI3-kinase (PI3K) and c-Jun N-terminal Kinase (JNK) in addition to CKIεδ. Although these kinase inhibitors may have some non-specific effects on other factors, our mini screening identified new candidates contributing to period-length control in mammalian cells

  9. The Human-Robot Interaction Operating System

    Science.gov (United States)

    Fong, Terrence; Kunz, Clayton; Hiatt, Laura M.; Bugajska, Magda

    2006-01-01

    In order for humans and robots to work effectively together, they need to be able to converse about abilities, goals and achievements. Thus, we are developing an interaction infrastructure called the "Human-Robot Interaction Operating System" (HRI/OS). The HRI/OS provides a structured software framework for building human-robot teams, supports a variety of user interfaces, enables humans and robots to engage in task-oriented dialogue, and facilitates integration of robots through an extensible API.

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

    Science.gov (United States)

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

    2012-01-01

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

  11. Circadian control of kisspeptin and a gated GnRH response mediate the preovulatory luteinizing hormone surge

    DEFF Research Database (Denmark)

    Williams, Wilbur P; Jarjisian, Stephan G; Mikkelsen, Jens D

    2011-01-01

    In spontaneously ovulating rodents, the preovulatory LH surge is initiated on the day of proestrus by a timed, stimulatory signal originating from the circadian clock in the suprachiasmatic nucleus (SCN). The present studies explored whether kisspeptin is part of the essential neural circuit...... linking the SCN to the GnRH system to stimulate ovulation in Syrian hamsters (Mesocricetus auratus). Kisspeptin neurons exhibit an estrogen-dependent, daily pattern of cellular activity consistent with a role in the circadian control of the LH surge. The SCN targets kisspeptin neurons via vasopressinergic...... of ovulatory control with interactions among the circadian system, kisspeptin signaling, and a GnRH gating mechanism of control....

  12. Stupid Tutoring Systems, Intelligent Humans

    Science.gov (United States)

    Baker, Ryan S.

    2016-01-01

    The initial vision for intelligent tutoring systems involved powerful, multi-faceted systems that would leverage rich models of students and pedagogies to create complex learning interactions. But the intelligent tutoring systems used at scale today are much simpler. In this article, I present hypotheses on the factors underlying this development,…

  13. Circadian Rhythms, Sleep, and Disorders of Aging.

    Science.gov (United States)

    Mattis, Joanna; Sehgal, Amita

    2016-04-01

    Sleep-wake cycles are known to be disrupted in people with neurodegenerative disorders. These findings are now supported by data from animal models for some of these disorders, raising the question of whether the disrupted sleep/circadian regulation contributes to the loss of neural function. As circadian rhythms and sleep consolidation also break down with normal aging, changes in these may be part of what makes aging a risk factor for disorders like Alzheimer's disease (AD). Mechanisms underlying the connection between circadian/sleep dysregulation and neurodegeneration remain unclear, but several recent studies provide interesting possibilities. While mechanistic analysis is under way, it is worth considering treatment of circadian/sleep disruption as a means to alleviate symptoms of neurodegenerative disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Mathematical Modeling of Circadian/Performance Countermeasures

    Data.gov (United States)

    National Aeronautics and Space Administration — We developed and refined our current mathematical model of circadian rhythms to incorporate melatonin as a marker rhythm. We used an existing physiologically based...

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

    Science.gov (United States)

    Harrison, Elizabeth M; Gorman, Michael R

    2015-12-01

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

  16. Disruption of the circadian period of body temperature by the anesthetic propofol.

    Science.gov (United States)

    Touitou, Yvan; Mauvieux, Benoit; Reinberg, Alain; Dispersyn, Garance

    2016-01-01

    The circadian time structure of an organism can be desynchronized in a large number of instances, including the intake of specific drugs. We have previously found that propofol, which is a general anesthetic, induces a desynchronization of the circadian time structure in rats, with a 60-80 min significant phase advance of body temperature circadian rhythm. We thus deemed it worthwhile to examine whether this phase shift of body temperature was related to a modification of the circadian period Tau. Propofol was administered at three different Zeitgeber Times (ZTs): ZT6 (middle of the rest period), ZT10 (2 h prior to the beginning of activity period), ZT16 (4 h after the beginning of the activity period), with ZT0 being the beginning of the rest period (light onset) and ZT12 being the beginning of the activity period (light offset). Control rats (n = 20) were injected at the same ZTs with 10% intralipid, which is a control lipidic solution. Whereas no modification of the circadian period of body temperature was observed in the control rats, propofol administration resulted in a significant shortening of the period by 96 and 180 min at ZT6 and ZT10, respectively. By contrast, the period was significantly lengthened by 90 min at ZT16. We also found differences in the time it took for the rats to readjust their body temperature to the original 24-h rhythm. At ZT16, the speed of readjustment was more rapid than at the two other ZTs that we investigated. This study hence shows (i) the disruptive effects of the anesthetic propofol on the body temperature circadian rhythm, and it points out that (ii) the period Tau for body temperature responds to this anesthetic drug according to a Tau-response curve. By sustaining postoperative sleep-wake disorders, the disruptive effects of propofol on circadian time structure might have important implications for the use of this drug in humans.

  17. Feedbacks in human-landscape systems

    Science.gov (United States)

    Chin, Anne

    2015-04-01

    As human interactions with Earth systems intensify in the "Anthropocene", understanding the complex relationships among human activity, landscape change, and societal responses to those changes is increasingly important. Interdisciplinary research centered on the theme of "feedbacks" in human-landscape systems serves as a promising focus for unraveling these interactions. Deciphering interacting human-landscape feedbacks extends our traditional approach of considering humans as unidirectional drivers of change. Enormous challenges exist, however, in quantifying impact-feedback loops in landscapes with significant human alterations. This paper illustrates an example of human-landscape interactions following a wildfire in Colorado (USA) that elicited feedback responses. After the 2012 Waldo Canyon Fire, concerns for heightened flood potential and debris flows associated with post-fire hydrologic changes prompted local landowners to construct tall fences at the base of a burned watershed. These actions changed the sediment transport regime and promoted further landscape change and human responses in a positive feedback cycle. The interactions ultimately increase flood and sediment hazards, rather than dampening the effects of fire. A simple agent-based model, capable of integrating social and hydro-geomorphological data, demonstrates how such interacting impacts and feedbacks could be simulated. Challenges for fully capturing human-landscape feedback interactions include the identification of diffuse and subtle feedbacks at a range of scales, the availability of data linking impact with response, the identification of multiple thresholds that trigger feedback mechanisms, and the varied metrics and data needed to represent both the physical and human systems. By collaborating with social scientists with expertise in the human causes of landscape change, as well as the human responses to those changes, geoscientists could more fully recognize and anticipate the coupled

  18. NASA Human System Risk Assessment Process

    Science.gov (United States)

    Francisco, D.; Romero, E.

    2016-01-01

    NASA utilizes an evidence based system to perform risk assessments for the human system for spaceflight missions. The center of this process is the multi-disciplinary Human System Risk Board (HSRB). The HSRB is chartered from the Chief Health and Medical Officer (OCHMO) at NASA Headquarters. The HSRB reviews all human system risks via an established comprehensive risk and configuration management plan based on a project management approach. The HSRB facilitates the integration of human research (terrestrial and spaceflight), medical operations, occupational surveillance, systems engineering and many other disciplines in a comprehensive review of human system risks. The HSRB considers all factors that influence human risk. These factors include pre-mission considerations such as screening criteria, training, age, sex, and physiological condition. In mission factors such as available countermeasures, mission duration and location and post mission factors such as time to return to baseline (reconditioning), post mission health screening, and available treatments. All of the factors influence the total risk assessment for each human risk. The HSRB performed a comprehensive review of all potential inflight medical conditions and events and over the course of several reviews consolidated the number of human system risks to 30, where the greatest emphasis is placed for investing program dollars for risk mitigation. The HSRB considers all available evidence from human research and, medical operations and occupational surveillance in assessing the risks for appropriate mitigation and future work. All applicable DRMs (low earth orbit for 6 and 12 months, deep space for 30 days and 1 year, a lunar mission for 1 year, and a planetary mission for 3 years) are considered as human system risks are modified by the hazards associated with space flight such as microgravity, exposure to radiation, distance from the earth, isolation and a closed environment. Each risk has a summary

  19. Linking Core Promoter Classes to Circadian Transcription.

    Directory of Open Access Journals (Sweden)

    Pål O Westermark

    2016-08-01

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

  20. Circadian clocks are resounding in peripheral tissues.

    Directory of Open Access Journals (Sweden)

    Andrey A Ptitsyn

    2006-03-01

    Full Text Available Circadian rhythms are prevalent in most organisms. Even the smallest disturbances in the orchestration of circadian gene expression patterns among different tissues can result in functional asynchrony, at the organism level, and may to contribute to a wide range of physiologic disorders. It has been reported that as many as 5%-10% of transcribed genes in peripheral tissues follow a circadian expression pattern. We have conducted a comprehensive study of circadian gene expression on a large dataset representing three different peripheral tissues. The data have been produced in a large-scale microarray experiment covering replicate daily cycles in murine white and brown adipose tissues as well as in liver. We have applied three alternative algorithmic approaches to identify circadian oscillation in time series expression profiles. Analyses of our own data indicate that the expression of at least 7% to 21% of active genes in mouse liver, and in white and brown adipose tissues follow a daily oscillatory pattern. Indeed, analysis of data from other laboratories suggests that the percentage of genes with an oscillatory pattern may approach 50% in the liver. For the rest of the genes, oscillation appears to be obscured by stochastic noise. Our phase classification and computer simulation studies based on multiple datasets indicate no detectable boundary between oscillating and non-oscillating fractions of genes. We conclude that greater attention should be given to the potential influence of circadian mechanisms on any biological pathway related to metabolism and obesity.

  1. What time is it? Deep learning approaches for circadian rhythms.

    Science.gov (United States)

    Agostinelli, Forest; Ceglia, Nicholas; Shahbaba, Babak; Sassone-Corsi, Paolo; Baldi, Pierre

    2016-06-15

    Circadian rhythms date back to the origins of life, are found in virtually every species and every cell, and play fundamental roles in functions ranging from metabolism to cognition. Modern high-throughput technologies allow the measurement of concentrations of transcripts, metabolites and other species along the circadian cycle creating novel computational challenges and opportunities, including the problems of inferring whether a given species oscillate in circadian fashion or not, and inferring the time at which a set of measurements was taken. We first curate several large synthetic and biological time series datasets containing labels for both periodic and aperiodic signals. We then use deep learning methods to develop and train BIO_CYCLE, a system to robustly estimate which signals are periodic in high-throughput circadian experiments, producing estimates of amplitudes, periods, phases, as well as several statistical significance measures. Using the curated data, BIO_CYCLE is compared to other approaches and shown to achieve state-of-the-art performance across multiple metrics. We then use deep learning methods to develop and train BIO_CLOCK to robustly estimate the time at which a particular single-time-point transcriptomic experiment was carried. In most cases, BIO_CLOCK can reliably predict time, within approximately 1 h, using the expression levels of only a small number of core clock genes. BIO_CLOCK is shown to work reasonably well across tissue types, and often with only small degradation across conditions. BIO_CLOCK is used to annotate most mouse experiments found in the GEO database with an inferred time stamp. All data and software are publicly available on the CircadiOmics web portal: circadiomics.igb.uci.edu/ fagostin@uci.edu or pfbaldi@uci.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

    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.

  4. Circadian rhythms, food timing and obesity.

    Science.gov (United States)

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

    2016-11-01

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

  5. Light exposure at night disrupts host/cancer circadian regulatory dynamics: impact on the Warburg effect, lipid signaling and tumor growth prevention.

    Directory of Open Access Journals (Sweden)

    David E Blask

    Full Text Available The central circadian clock within the suprachiasmatic nucleus (SCN plays an important role in temporally organizing and coordinating many of the processes governing cancer cell proliferation and tumor growth in synchrony with the daily light/dark cycle which may contribute to endogenous cancer prevention. Bioenergetic substrates and molecular intermediates required for building tumor biomass each day are derived from both aerobic glycolysis (Warburg effect and lipid metabolism. Using tissue-isolated human breast cancer xenografts grown in nude rats, we determined that circulating systemic factors in the host and the Warburg effect, linoleic acid uptake/metabolism and growth signaling activities in the tumor are dynamically regulated, coordinated and integrated within circadian time structure over a 24-hour light/dark cycle by SCN-driven nocturnal pineal production of the anticancer hormone melatonin. Dim light at night (LAN-induced melatonin suppression disrupts this circadian-regulated host/cancer balance among several important cancer preventative signaling mechanisms, leading to hyperglycemia and hyperinsulinemia in the host and runaway aerobic glycolysis, lipid signaling and proliferative activity in the tumor.

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

    NARCIS (Netherlands)

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

    2001-01-01

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

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

    Science.gov (United States)

    Preußner, Marco; Heyd, Florian

    2016-06-01

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

  8. Effects of (± 3,4-Methylenedioxymethamphetamine (MDMA on Sleep and Circadian Rhythms

    Directory of Open Access Journals (Sweden)

    Una D. McCann

    2007-01-01

    Full Text Available Abuse of stimulant drugs invariably leads to a disruption in sleep-wake patterns by virtue of the arousing and sleep-preventing effects of these drugs. Certain stimulants, such as 3,4-methylenedioxymethamphetamine (MDMA, may also have the potential to produce persistent alterations in circadian regulation and sleep because they can be neurotoxic toward brain monoaminergic neurons involved in normal sleep regulation. In particular, MDMA has been found to damage brain serotonin (5-HT neurons in a variety of animal species, including nonhuman primates, with growing evidence that humans are also susceptible to MDMA-induced brain 5-HT neurotoxicity. 5-HT is an important modulator of sleep and circadian rhythms and, therefore, individuals who sustain MDMA-induced 5-HT neurotoxicity may be at risk for developing chronic abnormalities in sleep and circadian patterns. In turn, such abnormalities could play a significant role in other alterations reported in abstinent in MDMA users (e.g., memory disturbance. This paper will review preclinical and clinical studies that have explored the effects of prior MDMA exposure on sleep, circadian activity, and the circadian pacemaker, and will highlight current gaps in knowledge and suggest areas for future research.

  9. Dim Light Melatonin Onset and Affect in Adolescents With an Evening Circadian Preference.

    Science.gov (United States)

    Dolsen, Michael R; Harvey, Allison G

    2018-01-01

    A shift toward an evening circadian preference and the onset of mood problems often occur during adolescence. Although these changes are linked to poorer outcomes, few studies have considered how positive and negative affect are related to the circadian rhythm during adolescence. This study examined the relationship between evening and morning affect ratings and dim light melatonin onset (DLMO), a measure of endogenous circadian rhythm. Age and sex were tested as moderators. This study is based on a subset of 163 (94 female, age = 14.7) adolescents with an evening circadian preference from a National Institute of Child Health and Human Development-funded study. Participants provided saliva for melatonin analysis and rated evening and morning affect. Higher evening negative affect was related to a later DLMO. Evening positive affect was not significantly related to DLMO timing. Age but not sex was a significant moderator such that higher negative and lower positive affect were related to a later DLMO for 10- to 13-year-olds, whereas higher positive affect was related to a later DLMO for 17- to 18-year-olds. DLMO was not significantly related to morning affect ratings. There is evidence that higher negative and lower positive affect may be related to the shift toward an evening circadian preference observed in adolescents, particularly for younger adolescents. Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  10. Analysis of circadian properties and healthy levels of blue light from smartphones at night

    Science.gov (United States)

    Oh, Ji Hye; Yoo, Heeyeon; Park, Hoo Keun; Do, Young Rag

    2015-06-01

    This study proposes representative figures of merit for circadian and vision performance for healthy and efficient use of smartphone displays. The recently developed figures of merit for circadian luminous efficacy of radiation (CER) and circadian illuminance (CIL) related to human health and circadian rhythm were measured to compare three kinds of commercial smartphone displays. The CIL values for social network service (SNS) messenger screens from all three displays were higher than 41.3 biolux (blx) in a dark room at night, and the highest CIL value reached 50.9 blx. These CIL values corresponded to melatonin suppression values (MSVs) of 7.3% and 11.4%, respectively. Moreover, smartphone use in a bright room at night had much higher CIL and MSV values (58.7 ~ 105.2 blx and 15.4 ~ 36.1%, respectively). This study also analyzed the nonvisual and visual optical properties of the three smartphone displays while varying the distance between the screen and eye and controlling the brightness setting. Finally, a method to possibly attenuate the unhealthy effects of smartphone displays was proposed and investigated by decreasing the emitting wavelength of blue LEDs in a smartphone LCD backlight and subsequently reducing the circadian effect of the display.

  11. Hypercholesterolemia Causes Circadian Dysfunction: A Potential Risk Factor for Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Makoto Akashi

    2017-06-01

    Full Text Available Hypercholesterolemia is a well-known risk factor for a wide range of diseases in developed countries. Here, we report that mice lacking functional LDLR (low density lipoprotein receptor, an animal model of human familial hypercholesterolemia, show circadian abnormalities. In free running behavioral experiments in constant darkness, these mice showed a prolonged active phase and distinctly bimodal rhythms. Even when the circadian rhythms were entrained by light and dark cycles, these mice showed a significant attenuation of behavioral onset intensity at the start of the dark period. Further, we hypothesized that the combination of hypercholesterolemia and circadian abnormalities may affect cardiovascular disease progression. To examine this possibility, we generated LDLR-deficient mice with impaired circadian rhythms by simultaneously introducing a mutation into Period2, a core clock gene, and found that these mice showed a significant enlargement of artery plaque area with an increase in inflammatory cytokine IL-6 levels. These results suggest that circadian dysfunction may be associated with the development or progression of cardiovascular diseases.

  12. Circadian rhythms in effects of hypnotics and sleep inducers.

    Science.gov (United States)

    Reinberg, A

    1986-01-01

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

  13. ON THE ROLE OF PERIOD-2 IN THE CIRCADIAN AND HOMEOSTATIC REGULATION OF SLEEP

    OpenAIRE

    La Spada, F.

    2013-01-01

    Humans spend one third of their life sleeping, then we could raise the basic question: Why do we sleep? Despite the fact that we still don't fully understand its function, we made much progress in understanding at different levels how sleep is regulated. One model suggests that sleep is regulated by two processes: a homeostatic process that tracks the need for sleep and by a circadian rhythm that determines the preferred time-of-day sleep occurs. At the molecular level circadian rhythms ar...

  14. Control system oriented human interface

    International Nuclear Information System (INIS)

    Barale, P.; Jacobson, V.; Kilgore, R.; Rondeau, D.

    1976-11-01

    The on-line control system interface for magnet beam steering and focusing in the Bevalac is described. An Aydin model 5205B display generator was chosen. This display generator will allow the computer to completely rewrite a monitor screen in less than 50 ms and is also capable of controlling a color monitor

  15. Human engineering in mobile radwaste systems

    International Nuclear Information System (INIS)

    Jones, D.; McMahon, J.; Motl, G.

    1988-01-01

    To a large degree, mobile radwaste systems are replacing installed plant systems at US nuclear plants due to regulatory obsolescence, high capital and maintenance costs, and increased radiation exposure. Well over half the power plants in the United States now use some sort of mobile system similar to those offered by LN Technologies Corporation. Human engineering is reflected in mobile radwaste system design due to concerns about safety, efficiency, and cost. The radwaste services business is so competitive that vendors must reflect human engineering in several areas of equipment design in order to compete. The paper discusses radiation exposure control, contamination control, compact components, maintainability, operation, and transportability

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

    Science.gov (United States)

    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

  17. The mammalian circadian clock and its entrainment by stress and exercise.

    Science.gov (United States)

    Tahara, Yu; Aoyama, Shinya; Shibata, Shigenobu

    2017-01-01

    The mammalian circadian clock regulates day-night fluctuations in various physiological processes. The circadian clock consists of the central clock in the suprachiasmatic nucleus of the hypothalamus and peripheral clocks in peripheral tissues. External environmental cues, including light/dark cycles, food intake, stress, and exercise, provide important information for adjusting clock phases. This review focuses on stress and exercise as potent entrainment signals for both central and peripheral clocks, especially in regard to the timing of stimuli, types of stressors/exercises, and differences in the responses of rodents and humans. We suggest that the common signaling pathways of clock entrainment by stress and exercise involve sympathetic nervous activation and glucocorticoid release. Furthermore, we demonstrate that physiological responses to stress and exercise depend on time of day. Therefore, using exercise to maintain the circadian clock at an appropriate phase and amplitude might be effective for preventing obesity, diabetes, and cardiovascular disease.

  18. A case for human systems neuroscience.

    Science.gov (United States)

    Gardner, J L

    2015-06-18

    Can the human brain itself serve as a model for a systems neuroscience approach to understanding the human brain? After all, how the brain is able to create the richness and complexity of human behavior is still largely mysterious. What better choice to study that complexity than to study it in humans? However, measurements of brain activity typically need to be made non-invasively which puts severe constraints on what can be learned about the internal workings of the brain. Our approach has been to use a combination of psychophysics in which we can use human behavioral flexibility to make quantitative measurements of behavior and link those through computational models to measurements of cortical activity through magnetic resonance imaging. In particular, we have tested various computational hypotheses about what neural mechanisms could account for behavioral enhancement with spatial attention (Pestilli et al., 2011). Resting both on quantitative measurements and considerations of what is known through animal models, we concluded that weighting of sensory signals by the magnitude of their response is a neural mechanism for efficient selection of sensory signals and consequent improvements in behavioral performance with attention. While animal models have many technical advantages over studying the brain in humans, we believe that human systems neuroscience should endeavor to validate, replicate and extend basic knowledge learned from animal model systems and thus form a bridge to understanding how the brain creates the complex and rich cognitive capacities of humans. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Circadian and dark-pulse activation of orexin/hypocretin neurons

    Directory of Open Access Journals (Sweden)

    Marston Oliver J

    2008-12-01

    Full Text Available Temporal control of brain and behavioral states emerges as a consequence of the interaction between circadian and homeostatic neural circuits. This interaction permits the daily rhythm of sleep and wake, regulated in parallel by circadian cues originating from the suprachiasmatic nuclei (SCN and arousal-promoting signals arising from the orexin-containing neurons in the tuberal hypothalamus (TH. Intriguingly, the SCN circadian clock can be reset by arousal-promoting stimuli while activation of orexin/hypocretin neurons is believed to be under circadian control, suggesting the existence of a reciprocal relationship. Unfortunately, since orexin neurons are themselves activated by locomotor promoting cues, it is unclear how these two systems interact to regulate behavioral rhythms. Here mice were placed in conditions of constant light, which suppressed locomotor activity, but also revealed a highly pronounced circadian pattern in orexin neuronal activation. Significantly, activation of orexin neurons in the medial and lateral TH occurred prior to the onset of sustained wheel-running activity. Moreover, exposure to a 6 h dark pulse during the subjective day, a stimulus that promotes arousal and phase advances behavioral rhythms, activated neurons in the medial and lateral TH including those containing orexin. Concurrently, this stimulus suppressed SCN activity while activating cells in the median raphe. In contrast, dark pulse exposure during the subjective night did not reset SCN-controlled behavioral rhythms and caused a transient suppression of neuronal activation in the TH. Collectively these results demonstrate, for the first time, pronounced circadian control of orexin neuron activation and implicate recruitment of orexin cells in dark pulse resetting of the SCN circadian clock.

  20. The bipolarity of light and dark: A review on Bipolar Disorder and circadian cycles.

    Science.gov (United States)

    Abreu, T; Bragança, M

    2015-10-01

    Bipolar Disorder is characterized by episodes running the full mood spectrum, from mania to depression. Between mood episodes, residual symptoms remain, as sleep alterations, circadian cycle disturbances, emotional deregulation, cognitive impairment and increased risk for comorbidities. The present review intends to reflect about the most recent and relevant information concerning the biunivocal relation between bipolar disorder and circadian cycles. It was conducted a literature search on PubMed database using the search terms "bipolar", "circadian", "melatonin", "cortisol", "body temperature", "Clock gene", "Bmal1 gene", "Per gene", "Cry gene", "GSK3β", "chronotype", "light therapy", "dark therapy", "sleep deprivation", "lithum" and "agomelatine". Search results were manually reviewed, and pertinent studies were selected for inclusion as appropriate. Several studies support the relationship between bipolar disorder and circadian cycles, discussing alterations in melatonin, body temperature and cortisol rhythms; disruption of sleep/wake cycle; variations of clock genes; and chronotype. Some therapeutics for bipolar disorder directed to the circadian cycles disturbances are also discussed, including lithium carbonate, agomelatine, light therapy, dark therapy, sleep deprivation and interpersonal and social rhythm therapy. This review provides a summary of an extensive research for the relevant literature on this theme, not a patient-wise meta-analysis. In the future, it is essential to achieve a better understanding of the relation between bipolar disorder and the circadian system. It is required to establish new treatment protocols, combining psychotherapy, therapies targeting the circadian rhythms and the latest drugs, in order to reduce the risk of relapse and improve affective behaviour. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Plasma FGF21 displays a circadian rhythm during a 72-h fast in healthy female volunteers

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Beck-Nielsen, Henning; Højlund, Kurt

    2011-01-01

    Fibroblast growth factor (FGF21) is a potent regulator of glucose and lipid metabolism. In rodents, the hepatic expression of FGF21 is controlled by fasting and a circadian regulation, but the physiological role and regulation of FGF21 in humans is not well established. Therefore, the objective...

  2. Electroencephalogram Power Density and Slow Wave Sleep as a Function of Prior Waking and Circadian Phase

    NARCIS (Netherlands)

    Dijk, Derk-Jan; Brunner, Daniel P.; Beersma, Domien G.M.; Borbély, Alexander A.

    1990-01-01

    Human sleep electroencephalograms, recorded in four experiments, were subjected to spectral analysis. Waking prior to sleep varied from 12 to 36 h and sleep was initiated at different circadian phases. Power density of delta and theta frequencies in rapid-eye-movement (REM) sleep and non-REM (NREM)

  3. Adrenal clocks and the role of adrenal hormones in the regulation of circadian physiology.

    Science.gov (United States)

    Leliavski, Alexei; Dumbell, Rebecca; Ott, Volker; Oster, Henrik

    2015-02-01

    The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) and subordinate clocks that disseminate time information to various central and peripheral tissues. While the function of the SCN in circadian rhythm regulation has been extensively studied, we still have limited understanding of how peripheral tissue clock function contributes to the regulation of physiological processes. The adrenal gland plays a special role in this context as adrenal hormones show strong circadian secretion rhythms affecting downstream physiological processes. At the same time, they have been shown to affect clock gene expression in various other tissues, thus mediating systemic entrainment to external zeitgebers and promoting internal circadian alignment. In this review, we discuss the function of circadian clocks in the adrenal gland, how they are reset by the SCN and may further relay time-of-day information to other tissues. Focusing on glucocorticoids, we conclude by outlining the impact of adrenal rhythm disruption on neuropsychiatric, metabolic, immune, and malignant disorders. © 2014 The Author(s).

  4. Circadian Rhythm of Pyrocystis fusiformis

    Science.gov (United States)

    Weishaar, B.

    2016-12-01

    For the Academy of Science St. Louis Science Fair, I tested how different photoperiods affect the morphology of Pyrocystis fusiformis with respect to the placement and formation of the chloroplasts. I set up four different rooms to observe the effect the different times in the photoperiod on location of chloroplasts in the cell. At 3:00pm, one room has been in the dark for 12 hours, one for 6 hours, one had been in the light phase for 12 hours and the fourth in the light phase for 6 hours. P fusiformis samples were obtained from each room, observed, photographed at X100 power, and categorized as being a 1, 2, 3, or 4 depending on the position of the chloroplasts. The samples in the different rooms were observed once a week for two weeks, then the samples were rotated to see if P. fusiformis would synchronize the same to the new photoperiod. It was observed that the cells changed morphological stages in the circadian cycle, the chloroplasts moved further away from the nucleus when exposed to light and moved closer to the nucleus when experiencing no light.

  5. Does circadian disruption play a role in the metabolic-hormonal link to delayed lactogenesis II?

    Directory of Open Access Journals (Sweden)

    Manjie eFu

    2015-02-01

    Full Text Available Breastfeeding improves maternal and child health. The American Academy of Pediatrics recommends exclusive breastfeeding for six months, with continued breastfeeding for at least one year. However, in the US, only 18.8% of infants are exclusively breastfed until six months of age. For mothers who initiate breastfeeding, the early postpartum period sets the stage for sustained breastfeeding. Mothers who experience breastfeeding problems in the early postpartum period are more likely to discontinue breastfeeding within two weeks. A major risk factor for shorter breastfeeding duration is delayed lactogenesis II (i.e. onset of milk coming in more than 72 h postpartum. Recent studies report a metabolic-hormonal link to delayed lactogenesis II. This is not surprising because around the time of birth the mother’s entire metabolism changes to direct nutrients to mammary glands. Circadian and metabolic systems are closely linked, and our rodent studies suggest circadian clocks coordinate hormonal and metabolic changes to support lactation. Molecular and environmental disruption of the circadian system decreases a dam’s ability to initiate lactation and negatively impacts milk production. Circadian and metabolic systems evolved to be functional and adaptive when lifestyles and environmental exposures were quite different from modern times. We now have artificial lights, longer work days, and increases in shift work. Disruption in the circadian system due to shift work, jet lag, sleep disorders and other modern life style choices are associated with metabolic disorders, obesity, and impaired reproduction. We hypothesize delayed lactogenesis II is related to disruption of the mother’s circadian system. Here we review literature that supports this hypothesis, and describe interventions that may help to increase breastfeeding success.

  6. Shift work and cancer risk: potential mechanistic roles of circadian disruption, light at night, and sleep deprivation.

    Science.gov (United States)

    Haus, Erhard L; Smolensky, Michael H

    2013-08-01

    Shift work that includes a nighttime rotation has become an unavoidable attribute of today's 24-h society. The related disruption of the human circadian time organization leads in the short-term to an array of jet-lag-like symptoms, and in the long-run it may contribute to weight gain/obesity, metabolic syndrome/type II diabetes, and cardiovascular disease. Epidemiologic studies also suggest increased cancer risk, especially for breast cancer, in night and rotating female shift workers. If confirmed in more controlled and detailed studies, the carcinogenic effect of night and shift work will constitute additional serious medical, economic, and social problems for a substantial proportion of the working population. Here, we examine the possible multiple and interconnected cancer-promoting mechanisms as a consequence of shift work, i.e., repeated disruption of the circadian system, pineal hormone melatonin suppression by exposure to light at night, sleep-deprivation-caused impairment of the immune system, plus metabolic changes favoring obesity and generation of proinflammatory reactive oxygen species. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Human Systems Integration (HSI) Practitioner's Guide

    Science.gov (United States)

    Zumbado, Jennifer Rochlis

    2015-01-01

    The NASA/SP-2015-3709, Human Systems Integration (HSI) Practitioner's Guide, also known as the "HSIPG," provides a tool for implementing HSI activities within the NASA systems engineering framework. The HSIPG is written to aid the HSI practitioner engaged in a program or project (P/P), and serves as a knowledge base to allow the practitioner to step into an HSI lead or team member role for NASA missions. Additionally, this HSIPG is written to address the role of HSI in the P/P management and systems engineering communities and aid their understanding of the value added by incorporating good HSI practices into their programs and projects. Through helping to build a community of knowledgeable HSI practitioners, this document also hopes to build advocacy across the Agency for establishing strong, consistent HSI policies and practices. Human Systems Integration (HSI) has been successfully adopted (and adapted) by several federal agencies-most notably the U.S. Department of Defense (DoD) and the Nuclear Regulatory Commission (NRC)-as a methodology for reducing system life cycle costs (LCCs). These cost savings manifest themselves due to reductions in required numbers of personnel, the practice of human-centered design, decreased reliance on specialized skills for operations, shortened training time, efficient logistics and maintenance, and fewer safety-related risks and mishaps due to unintended human/system interactions. The HSI process for NASA establishes how cost savings and mission success can be realized through systems engineering. Every program or project has unique attributes. This HSIPG is not intended to provide one-size-fits-all recommendations for HSI implementation. Rather, HSI processes should be tailored to the size, scope, and goals of individual situations. The instructions and processes identified here are best used as a starting point for implementing human-centered system concepts and designs across programs and projects of varying types, including

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

    Science.gov (United States)

    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...

  9. Human System Risk Management for Space Flight

    Science.gov (United States)

    Davis, Jeffrey

    2015-01-01

    This brief abstract reviews the development of the current day approach to human system risk management for space flight and the development of the critical components of this process over the past few years. The human system risk management process now provides a comprehensive assessment of each human system risk by design reference mission (DRM) and is evaluated not only for mission success but also for long-term health impacts for the astronauts. The discipline of bioastronautics is the study of the biological and medical effects of space flight on humans. In 1997, the Space Life Sciences Directorate (SLSD) initiated the Bioastronautics Roadmap (Roadmap) as the "Critical Path Roadmap", and in 1998 participation in the roadmap was expanded to include the National Space Biomedical Research Institute (NSBRI) and the external community. A total of 55 risks and 250 questions were identified and prioritized and in 2000, the Roadmap was base-lined and put under configuration control. The Roadmap took into account several major advisory committee reviews including the Institute of Medicine (IOM) "Safe Passage: Astronaut care for Exploration Missions", 2001. Subsequently, three collaborating organizations at NASA HQ (Chief Health and Medical Officer, Office of Space Flight and Office of Biological & Physical Research), published the Bioastronautics Strategy in 2003, that identified the human as a "critical subsystem of space flight" and noted that "tolerance limits and safe operating bands must be established" to enable human space flight. These offices also requested a review by the IOM of the Roadmap and that review was published in October 2005 as "A Risk Reduction Strategy for Human Exploration of Space: A Review of NASA's Bioastronautics Roadmap", that noted several strengths and weaknesses of the Roadmap and made several recommendations. In parallel with the development of the Roadmap, the Office of the Chief Health and Medical Officer (OCHMO) began a process in

  10. Dissection of the couplings between cellular messengers and the circadian clock

    International Nuclear Information System (INIS)

    Tong Jian; Edmunds, L.N.

    1995-12-01

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

  11. [Circadian blood pressure variation under several pathophysiological conditions including secondary hypertension].

    Science.gov (United States)

    Imai, Yutaka; Hosaka, Miki; Satoh, Michihiro

    2014-08-01

    Abnormality of circadian blood pressure (BP) variation, i.e. non-dipper, riser, nocturnal hypertension etc, is brought by several pathophysiological conditions especially by secondary hypertension. These pathophysiological conditions are classified into several categories, i.e. disturbance of autonomic nervous system, metabolic disorder, endocrine disorder, disorder of Na and water excretion (e.g. sodium sensitivity), severe target organ damage and ischemia, cardiovascular complications and drug induced hypertension. Each pathophysiological condition which brings disturbance of circadian BP variation is included in several categories, e.g. diabetes mellitus is included in metabolic disorder, autonomic imbalance, sodium sensitivity and endocrine disorder. However, it seems that unified principle of the genesis of disturbance of circadian BP variation in many pathophysiological conditions is autonomic imbalance. Thus, it is concluded that disturbance of circadian BP variation is not purposive biological behavior but the result of autonomic imbalance which looks as if compensatory reaction such as exaggerated Na-water excretion during night in patient with Na-water retention who reveals disturbed circadian BP variation.

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

    Science.gov (United States)

    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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Sleep and circadian disruption and incident breast cancer risk: An evidence-based and theoretical review.

    Science.gov (United States)

    Samuelsson, Laura B; Bovbjerg, Dana H; Roecklein, Kathryn A; Hall, Martica H

    2018-01-01

    Opportunities for restorative sleep and optimal sleep-wake schedules are becoming luxuries in industrialized cultures, yet accumulating research has revealed multiple adverse health effects of disruptions in sleep and circadian rhythms, including increased risk of breast cancer. The literature on breast cancer risk has focused largely on adverse effects of night shift work and exposure to light at night (LAN), without considering potential effects of associated sleep disruptions. As it stands, studies on breast cancer risk have not considered the impact of both sleep and circadian disruption, and the possible interaction of the two through bidirectional pathways, on breast cancer risk in the population at large. We review and synthesize this literature, including: 1) studies of circadian disruption and incident breast cancer; 2) evidence for bidirectional interactions between sleep and circadian systems; 3) studies of sleep and incident breast cancer; and 4) potential mechanistic pathways by which interrelated sleep and circadian disruption may contribute to the etiology of breast cancer. Copyright © 2017. Published by Elsevier Ltd.

  14. Circadian Dysfunction in Response to in Vivo Treatment with the Mitochondrial Toxin 3-Nitropropionic Acid

    Directory of Open Access Journals (Sweden)

    Takashi Kudo

    2013-12-01

    Full Text Available Sleep disorders are common in neurodegenerative diseases including Huntington's disease (HD and develop early in the disease process. Mitochondrial alterations are believed to play a critical role in the pathophysiology of neurodegenerative diseases. In the present study, we evaluated the circadian system of mice after inhibiting mitochondrial complex II of the respiratory chain with the toxin 3-nitropropionic acid (3-NP. We found that a subset of mice treated with low doses of 3-NP exhibited severe circadian deficit in behavior. The temporal patterning of sleep behavior is also disrupted in some mice with evidence of difficulty in the initiation of sleep behavior. Using the open field test during the normal sleep phase, we found that the 3-NP-treated mice were hyperactive. The molecular clockwork responsible for the generation of circadian rhythms as measured by PER2::LUCIFERASE was disrupted in a subset of mice. Within the SCN, the 3-NP treatment resulted in a reduction in daytime firing rate in the subset of mice which had a behavioral deficit. Anatomically, we confirmed that all of the treated mice showed evidence for cell loss within the striatum but we did not see evidence for gross SCN pathology. Together, the data demonstrates that chronic treatment with low doses of the mitochondrial toxin 3-NP produced circadian deficits in a subset of treated mice. This work does raise the possibility that the neural damage produced by mitochondrial dysfunction can contribute to the sleep/circadian dysfunction seen so commonly in neurodegenerative diseases.

  15. Group & Intergroup Relations in Living Human Systems.

    Science.gov (United States)

    1980-06-01

    organizational diagnosis , the group is itself a living human system. A group may be underbounded, overbounded, or optimally bounded. The state of group...very im- portant to understand and to use in order to conduct organizational diagnosis " using group methods. 2 -43 (Alderfer, 1977b). The group...Boundary Relations and Organizational Diagnosis . In H. Meltzer and F.W. Wickert (eds.) Humanizing Organizational Behavior. Springfield, Illinois: Thomas

  16. CORRELATION BETWEEN HUMAN NEEDS SYSTEM - PERSONALITY - HUMAN MOTIVATION

    Directory of Open Access Journals (Sweden)

    Mirela MINICA

    2015-07-01

    Full Text Available The article highlights the main attributes of an economic approach of needs and preferences, with detailed focus on the correlation between meta-needs and personality, by correlating the principle of hierarchy established by Maslow with the balance theory. Adopting an integrated system of human capital motivation, which takes into account the complex aspects involved in the knowledge society, represents a managerial requirement for any organisation.

  17. Intact interval timing in circadian CLOCK mutants.

    Science.gov (United States)

    Cordes, Sara; Gallistel, C R

    2008-08-28

    While progress has been made in determining the molecular basis for the circadian clock, the mechanism by which mammalian brains time intervals measured in seconds to minutes remains a mystery. An obvious question is whether the interval-timing mechanism shares molecular machinery with the circadian timing mechanism. In the current study, we trained circadian CLOCK +/- and -/- mutant male mice in a peak-interval procedure with 10 and 20-s criteria. The mutant mice were more active than their wild-type littermates, but there were no reliable deficits in the accuracy or precision of their timing as compared with wild-type littermates. This suggests that expression of the CLOCK protein is not necessary for normal interval timing.

  18. A chemical biology approach reveals period shortening of the mammalian circadian clock by specific inhibition of GSK-3beta.

    Science.gov (United States)

    Hirota, Tsuyoshi; Lewis, Warren G; Liu, Andrew C; Lee, Jae Wook; Schultz, Peter G; Kay, Steve A

    2008-12-30

    The circadian clock controls daily oscillations of gene expression at the cellular level. We report the development of a high-throughput circadian functional assay system that consists of luminescent reporter cells, screening automation, and a data analysis pipeline. We applied this system to further dissect the molecular mechanisms underlying the mammalian circadian clock using a chemical biology approach. We analyzed the effect of 1,280 pharmacologically active compounds with diverse structures on the circadian period length that is indicative of the core clock mechanism. Our screening paradigm identified many compounds previously known to change the circadian period or phase, demonstrating the validity of the assay system. Furthermore, we found that small molecule inhibitors of glycogen synthase kinase 3 (GSK-3) consistently caused a strong short period phenotype in contrast to the well-known period lengthening by lithium, another presumed GSK-3 inhibitor. siRNA-mediated knockdown of GSK-3beta also caused a short period, confirming the phenotype obtained with the small molecule inhibitors. These results clarify the role of GSK-3beta in the period regulation of the mammalian clockworks and highlight the effectiveness of chemical biology in exploring unidentified mechanisms of the circadian clock.

  19. The regulations and role of circadian clock and melatonin in uterine receptivity and pregnancy-An immunological perspective.

    Science.gov (United States)

    Man, Gene Chi Wai; Zhang, Tao; Chen, Xiaoyan; Wang, Jianzhang; Wu, Fangrong; Liu, Yingyu; Wang, Chi Chiu; Cheong, Ying; Li, Tin Chiu

    2017-08-01

    During normal pregnancy, the mechanism by which the fetus escapes immunological rejection by the maternal womb remains elusive. Given the biological complexities, the immunological mechanism is unlikely to be simply an allograft response in acceptance or rejection of the early pregnancy. Circadian clock responsible for the mammalian circadian rhythm is an endogenously generated rhythm associated with almost all physiological processes including reproduction. There is now growing evidence to suggest that the circadian clocks are intricately linked to the immune system and pregnancy. When perturbed, the role of immune cells can be affected on maintaining the enriched vascular system needed for placentation. This alteration can be triggered by the irregular production of maternal and placental melatonin. Hence, the role of circadian rhythm modulators such as melatonin offers intriguing opportunities for therapy. In this review, we evaluate the complex interaction between the circadian clock and melatonin within the immune system and their roles in the circadian regulation and maintenance of normal pregnancy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Age-related changes in sleep and circadian rhythms: impact on cognitive performance and underlying neuroanatomical networks

    Directory of Open Access Journals (Sweden)

    Christina eSchmidt

    2012-07-01

    Full Text Available Circadian and homeostatic sleep-wake regulatory processes interact in a fine tuned manner to modulate human cognitive performance. Dampening of the circadian alertness signal and attenuated deterioration of psychomotor vigilance in response to elevated sleep pressure with aging change this interaction pattern. As evidenced by neuroimaging studies, both homeostatic sleep pressure and circadian sleep-wake promotion impact on cognition-related cortical and arousal-promoting subcortical brain regions including the thalamus, the anterior hypothalamus and the brainstem locus coeruleus (LC. However, how age- related changes in circadian and homeostatic processes impact on the cerebral activity subtending waking performance remains largely unexplored. Post-mortem studies point to neuronal degeneration in the SCN and age-related modifications to aging in the arousal-promoting LC. Alongside, cortical frontal brain areas are particularly susceptible both to aging and misalignment between circadian and homeostatic processes. In this perspective, we summarise and discuss here the potential neuroanatomical networks underlying age-related changes in circadian and homeostatic modulation of waking performance, ranging from basic arousal to higher order cognitive behaviours.

  1. The biological clock modulates the human cortisol response in a multiplicative fashion

    NARCIS (Netherlands)

    van de Werken, Maan; Booij, Sanne H.; van der Zwan, J Esi; Simons, Mirre J. P.; Gordijn, Marijke C. M.; Beersma, Domien G. M.

    Human cortisol levels follow a clear circadian rhythm. We investigated the contribution of alternation of sleep and wakefulness and the circadian clock, using forced desynchrony. Cortisol levels were best described by a multiplication of a circadian and a wake-time component. The human cortisol

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

    Directory of Open Access Journals (Sweden)

    Goldstein-Kral Lauren

    2011-01-01

    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.

  3. A computational model clarifies the roles of positive and negative feedback loops in the Drosophila circadian clock

    International Nuclear Information System (INIS)

    Wang Junwei; Zhou Tianshou

    2010-01-01

    Previous studies showed that a single negative feedback structure should be sufficient for robust circadian oscillations. It is thus pertinent to ask why current cellular clock models almost universally have interlocked negative feedback loop (NFL) and positive feedback loop (PFL). Here, we propose a molecular model that reflects the essential features of the Drosophila circadian clock to clarify the different roles of negative and positive feedback loops. In agreement with experimental observations, the model can simulate circadian oscillations in constant darkness, entrainment by light-dark cycles, as well as phenotypes of per 01 and clk Jrk mutants. Moreover, sustained oscillations persist when the PFL is removed, implying the crucial role of NFL for rhythm generation. Through parameter sensitivity analysis, it is revealed that incorporation of PFL increases the robustness of the system to regulatory processes in PFL itself. Such reduced models can aid understanding of the design principles of circadian clocks in Drosophila and other organisms with complex transcriptional feedback structures.

  4. Human performance modeling for system of systems analytics.

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Kevin R.; Lawton, Craig R.; Basilico, Justin Derrick; Longsine, Dennis E. (INTERA, Inc., Austin, TX); Forsythe, James Chris; Gauthier, John Henry; Le, Hai D.

    2008-10-01

    A Laboratory-Directed Research and Development project was initiated in 2005 to investigate Human Performance Modeling in a System of Systems analytic environment. SAND2006-6569 and SAND2006-7911 document interim results from this effort; this report documents the final results. The problem is difficult because of the number of humans involved in a System of Systems environment and the generally poorly defined nature of the tasks that each human must perform. A two-pronged strategy was followed: one prong was to develop human models using a probability-based method similar to that first developed for relatively well-understood probability based performance modeling; another prong was to investigate more state-of-art human cognition models. The probability-based modeling resulted in a comprehensive addition of human-modeling capability to the existing SoSAT computer program. The cognitive modeling resulted in an increased understanding of what is necessary to incorporate cognition-based models to a System of Systems analytic environment.

  5. Ribosomal S6 Kinase Cooperates with Casein Kinase 2 to Modulate the Drosophila Circadian Molecular Oscillator

    Science.gov (United States)

    Akten, Bikem; Tangredi, Michelle M.; Jauch, Eike; Roberts, Mary A.; Ng, Fanny; Raabe, Thomas; Jackson, F. Rob

    2009-01-01

    There is a universal requirement for post-translational regulatory mechanisms in circadian clock systems. Previous work in Drosophila has identified several kinases, phosphatases and an E3 ligase that are critical for determining the nuclear translocation and/or stability of clock proteins. The present study evaluated the function of p90 ribosomal S6 kinase (RSK) in the Drosophila circadian system. In mammals, RSK1 is a light- and clock-regulated kinase known to be activated by the MAPK pathway, but there is no direct evidence that it functions as a component of the circadian system. Here, we show that Drosophila S6KII RNA displays rhythms in abundance, indicative of circadian control. Importantly, an S6KII null mutant exhibits a short-period circadian phenotype that can be rescued by expression of the wild-type gene in clock neurons, indicating a role for S6KII in the molecular oscillator. Peak PER clock protein expression is elevated in the mutant, indicative of enhanced stability, whereas per mRNA level is decreased, consistent with enhanced feedback repression. Gene reporter assays show that decreased S6KII is associated with increased PER repression. Surprisingly, we demonstrate a physical interaction between S6KII and the Casein Kinase 2 regulatory subunit (CK2β), suggesting a functional relationship between the two kinases. In support of such a relationship, there are genetic interactions between S6KII and CK2 mutations, in vivo, which indicate that CK2 activity is required for S6KII action. We propose that the two kinases cooperate within clock neurons to fine-tune circadian period, improving the precision of the clock mechanism. PMID:19144847

  6. The circadian variation of premature atrial contractions

    DEFF Research Database (Denmark)

    Larsen, Bjørn Strøier; Kumarathurai, Preman; Nielsen, Olav W

    2016-01-01

    AIMS: The aim of the study was to assess a possible circadian variation of premature atrial contractions (PACs) in a community-based population and to determine if the daily variation could be used to assess a more vulnerable period of PACs in predicting later incidence of atrial fibrillation (AF...... variation in heart rate. After adjusting for relevant risk factors, the risk of AF was equal in all time intervals throughout the day. CONCLUSION: Premature atrial contractions showed a circadian variation in subjects with frequent PACs. No specific time interval of the day was more predictive of AF than...

  7. Circadian clock components in the rat neocortex

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  8. Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage.

    Science.gov (United States)

    Dodd, Antony N; Salathia, Neeraj; Hall, Anthony; Kévei, Eva; Tóth, Réka; Nagy, Ferenc; Hibberd, Julian M; Millar, Andrew J; Webb, Alex A R

    2005-07-22

    Circadian clocks are believed to confer an advantage to plants, but the nature of that advantage has been unknown. We show that a substantial photosynthetic advantage is conferred by correct matching of the circadian clock period with that of the external light-dark cycle. In wild type and in long- and short-circadian period mutants of Arabidopsis thaliana, plants with a clock period matched to the environment contain more chlorophyll, fix more carbon, grow faster, and survive better than plants with circadian periods differing from their environment. This explains why plants gain advantage from circadian control.

  9. Protein phosphorylation systems in postmortem human brain

    International Nuclear Information System (INIS)

    Walaas, S.I.; Perdahl-Wallace, E.; Winblad, B.; Greengard, P.

    1989-01-01

    Protein phosphorylation systems regulated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), or calcium in conjunction with calmodulin or phospholipid/diacylglycerol, have been studied by phosphorylation in vitro of particulate and soluble fractions from human postmortem brain samples. One-dimensional or two-dimensional gel electrophoretic protein separations were used for analysis. Protein phosphorylation catalyzed by cyclic AMP-dependent protein kinase was found to be highly active in both particulate and soluble preparations throughout the human CNS, with groups of both widely distributed and region-specific substrates being observed in different brain nuclei. Dopamine-innervated parts of the basal ganglia and cerebral cortex contained the phosphoproteins previously observed in rodent basal ganglia. In contrast, calcium/phospholipid-dependent and calcium/calmodulin-dependent protein phosphorylation systems were less prominent in human postmortem brain than in rodent brain, and only a few widely distributed substrates for these protein kinases were found. Protein staining indicated that postmortem proteolysis, particularly of high-molecular-mass proteins, was prominent in deeply located, subcortical regions in the human brain. Our results indicate that it is feasible to use human postmortem brain samples, when obtained under carefully controlled conditions, for qualitative studies on brain protein phosphorylation. Such studies should be of value in studies on human neurological and/or psychiatric disorders

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

    Directory of Open Access Journals (Sweden)

    William D Hendricks

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

  11. Virginia power's human performance evaluation system (HPES)

    International Nuclear Information System (INIS)

    Patterson, W.E.

    1991-01-01

    This paper reports on the Human Performance Evaluation System (HPES) which was initially developed by the Institute of Nuclear Power Operations (INPO) using the Aviation Safety Reporting System (ASRS) as a guide. After a pilot program involving three utilities ended in 1983, the present day program was instituted. A methodology was developed, for specific application to nuclear power plant employees, to aid trained coordinators/evaluators in determining those factors that exert a negative influence on human behavior in the nuclear power plant environment. HPES is for anyone and everyone on site, from contractors to plant staff to plant management. No one is excluded from participation. Virginia Power's HPES program goal is to identify and correct the root causes of human performance problems. Evaluations are performed on reported real or perceived conditions that may have an adverse influence on members of the nuclear team. A report is provided to management identifying root cause and contributing factors along with recommended corrective actions

  12. Validation of human factor engineering integrated system

    International Nuclear Information System (INIS)

    Fang Zhou

    2013-01-01

    Apart from hundreds of thousands of human-machine interface resources, the control room of a nuclear power plant is a complex system integrated with many factors such as procedures, operators, environment, organization and management. In the design stage, these factors are considered by different organizations separately. However, whether above factors could corporate with each other well in operation and whether they have good human factors engineering (HFE) design to avoid human error, should be answered in validation of the HFE integrated system before delivery of the plant. This paper addresses the research and implementation of the ISV technology based on case study. After introduction of the background, process and methodology of ISV, the results of the test are discussed. At last, lessons learned from this research are summarized. (authors)

  13. How to Bootstrap a Human Communication System

    Science.gov (United States)

    Fay, Nicolas; Arbib, Michael; Garrod, Simon

    2013-01-01

    How might a human communication system be bootstrapped in the absence of conventional language? We argue that motivated signs play an important role (i.e., signs that are linked to meaning by structural resemblance or by natural association). An experimental study is then reported in which participants try to communicate a range of pre-specified…

  14. The Human Resources Management System: Part 1.

    Science.gov (United States)

    Ceriello, Vincent R.

    1982-01-01

    Presents a systematic and disciplined approach to planning for the development and implementation of an information system which will collect, store, maintain, and report human resources data. Discusses guidelines, priorities, training requirements, security, auditing, interface with payroll, and personnel reporting. (CT)

  15. Cooperative mobility systems: The human factor challenges.

    NARCIS (Netherlands)

    Martens, Marieke; Kroon, Elisabeth

    2014-01-01

    This paper presents a vision on cooperative mobility systems from a human factors perspective. To create a common ground for future developments, it’s important to define the common research themes and knowledge gaps. This article presents what steps need to be taken in order to come to proper

  16. Visuals and Visualisation of Human Body Systems

    Science.gov (United States)

    Mathai, Sindhu; Ramadas, Jayashree

    2009-01-01

    This paper explores the role of diagrams and text in middle school students' understanding and visualisation of human body systems. We develop a common framework based on structure and function to assess students' responses across diagram and verbal modes. Visualisation is defined in terms of understanding transformations on structure and relating…

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

    Science.gov (United States)

    Mieda, Michihiro; Okamoto, Hitoshi; Sakurai, Takeshi

    2016-09-26

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

  18. Sensorimotor learning configures the human mirror system.

    Science.gov (United States)

    Catmur, Caroline; Walsh, Vincent; Heyes, Cecilia

    2007-09-04

    Cells in the "mirror system" fire not only when an individual performs an action but also when one observes the same action performed by another agent [1-4]. The mirror system, found in premotor and parietal cortices of human and monkey brains, is thought to provide the foundation for social understanding and to enable the development of theory of mind and language [5-9]. However, it is unclear how mirror neurons acquire their mirror properties -- how they derive the information necessary to match observed with executed actions [10]. We address this by showing that it is possible to manipulate the selectivity of the human mirror system, and thereby make it operate as a countermirror system, by giving participants training to perform one action while observing another. Before this training, participants showed event-related muscle-specific responses to transcranial magnetic stimulation over motor cortex during observation of little- and index-finger movements [11-13]. After training, this normal mirror effect was reversed. These results indicate that the mirror properties of the mirror system are neither wholly innate [14] nor fixed once acquired; instead they develop through sensorimotor learning [15, 16]. Our findings indicate that the human mirror system is, to some extent, both a product and a process of social interaction.

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

    Directory of Open Access Journals (Sweden)

    Zhao NB

    2013-01-01

    Full Text Available Ningbo Zhao,* Hong Tang,* Kai Yang, Dan Chen Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China*These authors contributed equally to this workBackground: 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

  20. Circadian rhythms in handwriting kinematics and legibility

    NARCIS (Netherlands)

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

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

  1. EFFECTS OF CIRCADIAN RHYTHM ON BALANCE PERFORMANCE

    Directory of Open Access Journals (Sweden)

    Karagul Osman

    2017-09-01

    Full Text Available Introduction. The aim of the study was to examine the effect of circadian rhythm on dynamic balance performance and to determine the role of physical activity level, body temperature, chronotype, and gender in this possible effect. Material and

  2. Circadian behaviour in neuroglobin deficient mice

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  3. Circadian rhythms in handwriting kinematics and legibility.

    Science.gov (United States)

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

    2011-08-01

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

  4. Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

    Directory of Open Access Journals (Sweden)

    Maria Angeles Bonmati-Carrion

    2014-12-01

    Full Text Available 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.

  5. Analysis of precision in chemical oscillators: implications for circadian clocks

    International Nuclear Information System (INIS)

    D'Eysmond, Thomas; De Simone, Alessandro; Naef, Felix

    2013-01-01

    Biochemical reaction networks often exhibit spontaneous self-sustained oscillations. An example is the circadian oscillator that lies at the heart of daily rhythms in behavior and physiology in most organisms including humans. While the period of these oscillators evolved so that it resonates with the 24 h daily environmental cycles, the precision of the oscillator (quantified via the Q factor) is another relevant property of these cell-autonomous oscillators. Since this quantity can be measured in individual cells, it is of interest to better understand how this property behaves across mathematical models of these oscillators. Current theoretical schemes for computing the Q factors show limitations for both high-dimensional models and in the vicinity of Hopf bifurcations. Here, we derive low-noise approximations that lead to numerically stable schemes also in high-dimensional models. In addition, we generalize normal form reductions that are appropriate near Hopf bifurcations. Applying our approximations to two models of circadian clocks, we show that while the low-noise regime is faithfully recapitulated, increasing the level of noise leads to species-dependent precision. We emphasize that subcomponents of the oscillator gradually decouple from the core oscillator as noise increases, which allows us to identify the subnetworks responsible for robust rhythms. (paper)

  6. Using the principles of circadian physiology enhances shift schedule design

    International Nuclear Information System (INIS)

    Connolly, J.J.; Moore-Ede, M.C.

    1987-01-01

    Nuclear power plants must operate 24 h, 7 days a week. For the most part, shift schedules currently in use at nuclear power plants have been designed to meet operational needs without considering the biological clocks of the human operators. The development of schedules that also take circadian principles into account is a positive step that can be taken to improve plant safety by optimizing operator alertness. These schedules reduce the probability of human errors especially during backshifts. In addition, training programs that teach round-the-clock workers how to deal with the problems of shiftwork can help to optimize performance and alertness. These programs teach shiftworkers the underlying causes of the sleep problems associated with shiftwork and also provide coping strategies for improving sleep and dealing with the transition between shifts. When these training programs are coupled with an improved schedule, the problems associated with working round-the-clock can be significantly reduced

  7. Extended sequence diagram for human system interaction

    International Nuclear Information System (INIS)

    Hwang, Jong Rok; Choi, Sun Woo; Ko, Hee Ran; Kim, Jong Hyun

    2012-01-01

    Unified Modeling Language (UML) is a modeling language in the field of object oriented software engineering. The sequence diagram is a kind of interaction diagram that shows how processes operate with one another and in what order. It is a construct of a message sequence chart. It depicts the objects and classes involved in the scenario and the sequence of messages exchanged between the objects needed to carry out the functionality of the scenario. This paper proposes the Extended Sequence Diagram (ESD), which is capable of depicting human system interaction for nuclear power plants, as well as cognitive process of operators analysis. In the conventional sequence diagram, there is a limit to only identify the activities of human and systems interactions. The ESD is extended to describe operators' cognitive process in more detail. The ESD is expected to be used as a task analysis method for describing human system interaction. The ESD can also present key steps causing abnormal operations or failures and diverse human errors based on cognitive condition

  8. Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture.

    Science.gov (United States)

    Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

    2017-01-01

    Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC)-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER) protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF), which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the intact circadian

  9. Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture

    Directory of Open Access Journals (Sweden)

    Virginie Sabado

    2017-10-01

    Full Text Available Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF, which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the

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

    Directory of Open Access Journals (Sweden)

    Nicole Purrier

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

  11. Parkinsonian syndromes presenting with circadian rhythm sleep disorder- advanced sleep-phase type.

    Science.gov (United States)

    Shukla, Garima; Kaul, Bhavna; Gupta, Anupama; Goyal, Vinay; Behari, Madhuri

    2015-01-01

    Circadian rhythm sleep disorder-advanced sleep-phase type is a relatively uncommon disorder, mostly seen among the elderly population. Impaired circadian rhythms have been reported in neurodegenerative conditions; however, there are no reports of any circadian rhythm sleep disorder among patients with Parkinsonian syndromes. We report two patients who presented with this circadian rhythm disorder, and were then diagnosed with a Parkinsonian syndrome. The cases. A 65-year-old retired man presented with history of abrupt change in sleep schedules, sleeping around 6.30-7 p.m. and waking up around 3-4 a.m. for the last 2 months. On detailed examination, the patient was observed to have symmetrical bradykinesia and cogwheel rigidity of limbs. A diagnosis of multiple system atrophy was made, supported by MRI findings and evidence of autonomic dysfunction. Symptoms of change in sleep-wake cycles resolved over the next 1 year, while the patient was treated with dopaminergic therapy. A 47-year-old man, who was being evaluated for presurgical investigation for refractory temporal lobe epilepsy, presented with complaints suggestive of dysarthria, bradykinesia of limbs and frequent falls for 5 months. Simultaneously, he began to sleep around 7 p.m. and wake up at about 2-3 a.m. Examination revealed severe axial rigidity, restricted vertical gaze and bradykinesia of limbs. A diagnosis of progressive supranuclear palsy was made. This is the first report of Parkinson's plus syndromes presenting with a circadian rhythm sleep disorder-advanced sleep-phase type. More prospective assessment for circadian sleep disorders may introduce useful insights into similar associations. Copyright 2015, NMJI.

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

    Science.gov (United States)

    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.

  13. Circadian modulation of GABA function in the rat suprachiasmatic nucleus: excitatory effects during the night phase.

    NARCIS (Netherlands)

    De Jeu, M.T.G.; Pennartz, C.M.A.

    2002-01-01

    Gramicidin-perforated patch-clamp recordings were made from slices of the suprachiasmatic nucleus (SCN) of adult rats to characterize the role of gamma-amino butyric acid (GABA) in the circadian timing system. During the day, activation of GABA(A) receptors hyperpolarized the membrane of SCN

  14. Long-term fitness training improves the circadian rest-activity rhythm in healthy elderly males

    NARCIS (Netherlands)

    van Someren, E. J.; Lijzenga, C.; Mirmiran, M.; Swaab, D. F.

    1997-01-01

    In old age, the circadian timing system loses optimal functioning. This process is even accelerated in Alzheimer's disease. Because pharmacological treatment of day-night rhythm disturbances usually is not very effective and may have considerable side effects, nonpharmacological treatments deserve

  15. Aggressive and sexual social stimuli do not phase shift the circadian temperature rhythm in rats

    NARCIS (Netherlands)

    Meerlo, P; Daan, S

    1998-01-01

    The objective of the present study was to determine whether the rat circadian system is sensitive to social stimuli. Male rats were subjected to a sociosexual interaction with an estrous female or to an aggressive interaction with a dominant male conspecific. The interactions lasted for Ih and took

  16. Transcutaneous electrical nerve stimulation (TENS) improves circadian rhythm disturbances in Alzheimer disease

    NARCIS (Netherlands)

    van Someren, E. J.; Scherder, E. J.; Swaab, D. F.

    1998-01-01

    In patients with Alzheimer disease (AD), an irregular day-night rhythm with behavioral restlessness during the night makes a strong demand on caregivers and is among the most important reasons for institutionalization. A dysfunctioning circadian timing system is supposed to underlie the disturbance

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  18. Circadian and age-related modulation of thermoception and temperature regulation: mechanisms and functional implications.

    NARCIS (Netherlands)

    van Someren, E.J.W.; Raymann, RJEM; Scherder, E.J.A.; Daanen, H.A.M.; Swaab, D.F.

    2002-01-01

    At older ages, the circadian rhythm of body temperature shows a decreased amplitude, an advanced phase, and decreased stability. The present review evaluates to what extent these changes may result from age-related deficiencies at several levels of the thermoregulatory system, including

  19. Circadian and age-related modulation of thermoreception and temperature regulation: mechanisms and functional implications

    NARCIS (Netherlands)

    van Someren, Eus J. W.; Raymann, Roy J. E. M.; Scherder, Erik J. A.; Daanen, Hein A. M.; Swaab, Dick F.

    2002-01-01

    At older ages, the circadian rhythm of body temperature shows a decreased amplitude, an advanced phase, and decreased stability. The present review evaluates to what extent these changes may result from age-related deficiencies at several levels of the thermoregulatory system, including

  20. Putative pacemakers in the eyestalk and brain of the crayfish Procambarus clarkii show circadian oscillations in levels of mRNA for crustacean hyperglycemic hormone.

    Directory of Open Access Journals (Sweden)

    Janikua Nelson-Mora

    Full Text Available Crustacean hyperglycemic hormone (CHH synthesizing cells in the optic lobe, one of the pacemakers of the circadian system, have been shown to be present in crayfish. However, the presence of CHH in the central brain, another putative pacemaker of the multi-oscillatory circadian system, of this decapod and its circadian transcription in the optic lobe and brain have yet to be explored. Therefore, using qualitative and quantitative PCR, we isolated and cloned a CHH mRNA fragment from two putative pacemakers of the multi-oscillatory circadian system of Procambarus clarkii, the optic lobe and the central brain. This CHH transcript synchronized to daily light-dark cycles and oscillated under dark, constant conditions demonstrating statistically significant daily and circadian rhythms in both structures. Furthermore, to investigate the presence of the peptide in the central brain of this decapod, we used immunohistochemical methods. Confocal microscopy revealed the presence of CHH-IR in fibers and cells of the protocerebral and tritocerebal clusters and neuropiles, particularly in some neurons located in clusters 6, 14, 15 and 17. The presence of CHH positive neurons in structures of P. clarkii where clock proteins have been reported suggests a relationship between the circadian clockwork and CHH. This work provides new insights into the circadian regulation of CHH, a pleiotropic hormone that regulates many physiological processes such as glucose metabolism and osmoregulatory responses to stress.

  1. Osteoarthritis-like pathologic changes in the knee joint induced by environmental disruption of circadian rhythms is potentiated by a high-fat diet.

    Science.gov (United States)

    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

    2015-11-20

    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.

  2. Strengths and limitations of period estimation methods for circadian data.

    Directory of Open Access Journals (Sweden)

    Tomasz Zielinski

    Full Text Available A key step in the analysis of circadian data is to make an accurate estimate of the underlying period. There are many different techniques and algorithms for determining period, all with different assumptions and with differing levels of complexity. Choosing which algorithm, which implementation and which measures of accuracy to use can offer many pitfalls, especially for the non-expert. We have developed the BioDare system, an online service allowing data-sharing (including public dissemination, data-processing and analysis. Circadian experiments are the main focus of BioDare hence performing period analysis is a major feature of the system. Six methods have been incorporated into BioDare: Enright and Lomb-Scargle periodograms, FFT-NLLS, mFourfit, MESA and Spectrum Resampling. Here we review those six techniques, explain the principles behind each algorithm and evaluate their performance. In order to quantify the methods' accuracy, we examine the algorithms against artificial mathematical test signals and model-generated mRNA data. Our re-implementation of each method in Java allows meaningful comparisons of the computational complexity and computing time associated with each algorithm. Finally, we provide guidelines on which algorithms are most appropriate for which data types, and recommendations on experimental design to extract optimal data for analysis.

  3. Calcium Channel Genes Associated with Bipolar Disorder Modulate Lithium's Amplification of Circadian Rhythms

    Science.gov (United States)

    McCarthy, Michael J.; LeRoux, Melissa; Wei, Heather; Beesley, Stephen; Kelsoe, John R.; Welsh, David K.

    2015-01-01

    Bipolar disorder (BD) is associated with mood episodes and low amplitude circadian rhythms. Previously, we demonstrated that fibroblasts grown from BD patients show weaker amplification of circadian rhythms by lithium compared to control cells. Since calcium signals impact upon the circadian clock, and L-type calcium channels (LTCC) have emerged as genetic risk factors for BD, we examined whether loss of function in LTCCs accounts for the attenuated response to lithium in BD cells. We used fluorescent dyes to measure Ca2+ changes in BD and control fibroblasts after lithium treatment, and bioluminescent reporters to measure Per2∷luc rhythms in fibroblasts from BD patients, human controls, and mice while pharmacologically or genetically manipulating calcium channels. Longitudinal expression of LTCC genes (CACNA1C, CACNA1D and CACNB3) was then measured over 12-24 hr in BD and control cells. Our results indicate that independently of LTCCs, lithium stimulated intracellular Ca2+ less effectively in BD vs. control fibroblasts. In longitudinal studies, pharmacological inhibition of LTCCs or knockdown of CACNA1A, CACNA1C, CACNA1D and CACNB3 altered circadian rhythm amplitude. Diltiazem and knockdown of CACNA1C or CACNA1D eliminated lithium's ability to amplify rhythms. Knockdown of CACNA1A or CACNB3 altered baseline rhythms, but did not affect rhythm amplification by lithium. In human fibroblasts, CACNA1C genotype predicted the amplitude response to lithium, and the expression profiles of CACNA1C, CACNA1D and CACNB3 were altered in BD vs. controls. We conclude that in cells from BD patients, calcium signaling is abnormal, and that LTCCs underlie the failure of lithium to amplify circadian rhythms. PMID:26476274

  4. Circadian gene expression in peripheral blood leukocytes of rotating night shift nurses.

    Science.gov (United States)

    Reszka, Edyta; Peplonska, Beata; Wieczorek, Edyta; Sobala, Wojciech; Bukowska, Agnieszka; Gromadzinska, Jolanta; Lie, Jenny-Anne; Kjuus, Helge; Wasowicz, Wojciech

    2013-03-01

    It has been hypothesized that the underlying mechanism of elevated breast cancer risk among long-term, night-working women involves circadian genes expression alteration caused by exposure to light at night and/or irregular work hours. The aim of the present study was to determine the effect of rotating night shift work on expression of selected core circadian genes. The cross-sectional study was conducted on 184 matched nurses and midwives, who currently work either day or rotating night shifts, to determine the effect of irregular work at night on circadian gene expression in peripheral blood leukocytes. Transcript levels of BMAL1, CLOCK, CRY1, CRY2, PER1, PER2, and PER3 were determined by means of quantitative real-time polymerase chain reaction (PCR). After adjusting for hour of blood collection, there were no statistically significant changes of investigated circadian genes among nurses and midwives currently working rotating night shifts compared to nurses working day shifts. The highest expression of PER1 messenger ribonucleic acid (mRNA) was observed for women currently working shifts who had worked >15 years in rotating night shift work. PER1 gene expression was associated with the lifetime duration of rotating night shift work among women currently working night shifts (P=0.04). PER1 and PER3 transcript levels in blood leukocytes were significantly down-regulated in the later versus early hours of the morning between 06.00-10.00 hours (β-coefficient -0.226, P=0.001 and β-coefficient -0.181, Pnight shift work does not affect circadian gene expression in human circulating leukocytes. In analysis of the peripheral clock in human studies, the hour of blood collection should be precisely specified.

  5. Human performance modeling for system of systems analytics :soldier fatigue.

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, Craig R.; Campbell, James E.; Miller, Dwight Peter

    2005-10-01

    The military has identified Human Performance Modeling (HPM) as a significant requirement and challenge of future systems modeling and analysis initiatives as can be seen in the Department of Defense's (DoD) Defense Modeling and Simulation Office's (DMSO) Master Plan (DoD 5000.59-P 1995). To this goal, the military is currently spending millions of dollars on programs devoted to HPM in various military contexts. Examples include the Human Performance Modeling Integration (HPMI) program within the Air Force Research Laboratory, which focuses on integrating HPMs with constructive models of systems (e.g. cockpit simulations) and the Navy's Human Performance Center (HPC) established in September 2003. Nearly all of these initiatives focus on the interface between humans and a single system. This is insufficient in the era of highly complex network centric SoS. This report presents research and development in the area of HPM in a system-of-systems (SoS). Specifically, this report addresses modeling soldier fatigue and the potential impacts soldier fatigue can have on SoS performance.

  6. Circadian expression profiles of chromatin remodeling factor genes in Arabidopsis.

    Science.gov (United States)

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

    2015-01-01

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

  7. Role of human factors in system safety

    International Nuclear Information System (INIS)

    Brooks, D. M.; Robert, C.; Graham, T.

    2008-01-01

    What happens when technology goes wrong? Three Mile Island, Chernobyl, space shuttles Challenger and Columbia, numerous airplane crashes, and other notable and newsworthy as well as many more incidents that are not reported on the news, have all been attributed to human error. Millions of dollars in fines are levied against industry under the General Duty clause for ergonomic violations, all avoidable. These incidents and situations indicate a lack of consideration for the humans in the system during the design phase. As a consequence, all of these organizations had to retrofit, had to redesign and had to pay countless dollars for medical costs, Worker's Compensation, OSHA fines and in some instances had irrecoverable damage to their public image. Human Factors, otherwise known as Engineering Psychology or Ergonomics, found its origins in loss, loss of life, loss of confidence, loss of technology, loss of property. Without loss, there would be no need for human factors. No one really 'attends' to discomfort...nor are errors attended to that have little consequence. Often it is ultimately the compilation and cumulative effects of these smaller and often ignored occurrences that lead to the bigger and more tragic incidents that make the evening news. When an incident or accident occurs, they are frequently attributed to accomplished, credible, experienced people. In reality however, the crisis was inevitable when a series of events happen such that a human is caught in the whirlwind of accident sequence. The world as known is becoming smaller and more complex. Highly technical societies have been hard at work for several centuries rebuilding the world out of cold steel that is very far removed from ancient instincts and traditions and is becoming more remote to human users. The growth of technology is more than exponential, and is virtually beyond comprehension for many people. Humans, feeling comfortable with the familiar, fulfill their propensity to implement new

  8. Chronic ethanol intake alters circadian phase shifting and free-running period in mice.

    Science.gov (United States)

    Seggio, Joseph A; Fixaris, Michael C; Reed, Jeffrey D; Logan, Ryan W; Rosenwasser, Alan M

    2009-08-01

    Chronic alcohol intake is associated with widespread disruptions in sleep and circadian rhythms in both human alcoholics and in experimental animals. Recent studies have demonstrated that chronic and acute ethanol treatments alter fundamental properties of the circadian pacemaker--including free-running period and responsiveness to photic and nonphotic phase-shifting stimuli--in rats and hamsters. In the present work, the authors extend these observations to the C57BL/6J mouse, an inbred strain characterized by very high levels of voluntary ethanol intake and by reliable and stable free-running circadian activity rhythms. Mice were housed individually in running-wheel cages under conditions of either voluntary or forced ethanol intake, whereas controls were maintained on plain water. Forced ethanol intake significantly attenuated photic phase delays (but not phase advances) and shortened free-running period in constant darkness, but voluntary ethanol intake failed to affect either of these parameters. Thus, high levels of chronic ethanol intake, beyond those normally achieved under voluntary drinking conditions, are required to alter fundamental circadian pacemaker properties in C57BL/6J mice. These observations may be related to the relative ethanol insensitivity displayed by this strain in several other phenotypic domains, including ethanol-induced sedation, ataxia, and withdrawal. Additional experiments will investigate chronobiological sensitivity to ethanol in a range of inbred strains showing diverse ethanol-related phenotypes.

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

    Science.gov (United States)

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

    2014-01-01

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

  10. First human systemic infection caused by Spiroplasma.

    Science.gov (United States)

    Aquilino, Ana; Masiá, Mar; López, Pilar; Galiana, Antonio J; Tovar, Juan; Andrés, María; Gutiérrez, Félix

    2015-02-01

    Spiroplasma species are organisms that normally colonize plants and insects. We describe the first case of human systemic infection caused by Spiroplasma bacteria in a patient with hypogammaglobulinemia undergoing treatment with biological disease-modifying antirheumatic agents. Spiroplasma turonicum was identified through molecular methods in several blood cultures. The infection was successfully treated with doxycycline plus levofloxacin. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Human-Systems Integration (HSI) Methodology Development for NASA

    Data.gov (United States)

    National Aeronautics and Space Administration — Human-Systems Integration (HSI) refers to design activities associated with ensuring that manpower, personnel, training, human factors engineering, safety, health...

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

    Directory of Open Access Journals (Sweden)

    Hirokazu Yamada

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

  13. Signals from the brainstem sleep/wake centers regulate behavioral timing via the circadian clock.

    Directory of Open Access Journals (Sweden)

    Sabra M Abbott

    Full Text Available Sleep-wake cycling is controlled by the complex interplay between two brain systems, one which controls vigilance state, regulating the transition between sleep and wake, and the other circadian, which communicates time-of-day. Together, they align sleep appropriately with energetic need and the day-night cycle. Neural circuits connect brain stem sites that regulate vigilance state with the suprachiasmatic nucleus (SCN, the master circadian clock, but the function of these connections has been unknown. Coupling discrete stimulation of pontine nuclei controlling vigilance state with analytical chemical measurements of intra-SCN microdialysates in mouse, we found significant neurotransmitter release at the SCN and, concomitantly, resetting of behavioral circadian rhythms. Depending upon stimulus conditions and time-of-day, SCN acetylcholine and/or glutamate levels were augmented and generated shifts of behavioral rhythms. These results establish modes of neurochemical communication from brain regions controlling vigilance state to the central circadian clock, with behavioral consequences. They suggest a basis for dynamic integration across brain systems that regulate vigilance states, and a potential vulnerability to altered communication in sleep disorders.

  14. Signals from the brainstem sleep/wake centers regulate behavioral timing via the circadian clock.

    Science.gov (United States)

    Abbott, Sabra M; Arnold, Jennifer M; Chang, Qing; Miao, Hai; Ota, Nobutoshi; Cecala, Christine; Gold, Paul E; Sweedler, Jonathan V; Gillette, Martha U

    2013-01-01

    Sleep-wake cycling is controlled by the complex interplay between two brain systems, one which controls vigilance state, regulating the transition between sleep and wake, and the other circadian, which communicates time-of-day. Together, they align sleep appropriately with energetic need and the day-night cycle. Neural circuits connect brain stem sites that regulate vigilance state with the suprachiasmatic nucleus (SCN), the master circadian clock, but the function of these connections has been unknown. Coupling discrete stimulation of pontine nuclei controlling vigilance state with analytical chemical measurements of intra-SCN microdialysates in mouse, we found significant neurotransmitter release at the SCN and, concomitantly, resetting of behavioral circadian rhythms. Depending upon stimulus conditions and time-of-day, SCN acetylcholine and/or glutamate levels were augmented and generated shifts of behavioral rhythms. These results establish modes of neurochemical communication from brain regions controlling vigilance state to the central circadian clock, with behavioral consequences. They suggest a basis for dynamic integration across brain systems that regulate vigilance states, and a potential vulnerability to altered communication in sleep disorders.

  15. Integrating spaceflight human system risk research

    Science.gov (United States)

    Mindock, Jennifer; Lumpkins, Sarah; Anton, Wilma; Havenhill, Maria; Shelhamer, Mark; Canga, Michael

    2017-10-01

    NASA is working to increase the likelihood of exploration mission success and to maintain crew health, both during exploration missions and long term after return to Earth. To manage the risks in achieving these goals, a system modelled after a Continuous Risk Management framework is in place. ;Human System Risks; (Risks) have been identified, and 32 are currently being actively addressed by NASA's Human Research Program (HRP). Research plans for each of HRP's Risks have been developed and are being executed. Inter-disciplinary ties between the research efforts supporting each Risk have been identified; however, efforts to identify and benefit from these connections have been mostly ad hoc. There is growing recognition that solutions developed to address the full set of Risks covering medical, physiological, behavioural, vehicle, and organizational aspects of exploration missions must be integrated across Risks and disciplines. This paper discusses how a framework of factors influencing human health and performance in space is being applied as the backbone for bringing together sometimes disparate information relevant to the individual Risks. The resulting interrelated information enables identification and visualization of connections between Risks and research efforts in a systematic and standardized manner. This paper also discusses the applications of the visualizations and insights into research planning, solicitation, and decision-making processes.

  16. Lateralization of the human mirror neuron system.

    Science.gov (United States)

    Aziz-Zadeh, Lisa; Koski, Lisa; Zaidel, Eran; Mazziotta, John; Iacoboni, Marco

    2006-03-15

    A cortical network consisting of the inferior frontal, rostral inferior parietal, and posterior superior temporal cortices has been implicated in representing actions in the primate brain and is critical to imitation in humans. This neural circuitry may be an evolutionary precursor of neural systems associated with language. However, language is predominantly lateralized to the left hemisphere, whereas the degree of lateralization of the imitation circuitry in humans is unclear. We conducted a functional magnetic resonance imaging study of imitation of finger movements with lateralized stimuli and responses. During imitation, activity in the inferior frontal and rostral inferior parietal cortex, although fairly bilateral, was stronger in the hemisphere ipsilateral to the visual stimulus and response hand. This ipsilateral pattern is at variance with the typical contralateral activity of primary visual and motor areas. Reliably increased signal in the right superior temporal sulcus (STS) was observed for both left-sided and right-sided imitation tasks, although subthreshold activity was also observed in the left STS. Overall, the data indicate that visual and motor components of the human mirror system are not left-lateralized. The left hemisphere superiority for language, then, must be have been favored by other types of language precursors, perhaps auditory or multimodal action representations.

  17. The interactive evolution of human communication systems.

    Science.gov (United States)

    Fay, Nicolas; Garrod, Simon; Roberts, Leo; Swoboda, Nik

    2010-04-01

    This paper compares two explanations of the process by which human communication systems evolve: iterated learning and social collaboration. It then reports an experiment testing the social collaboration account. Participants engaged in a graphical communication task either as a member of a community, where they interacted with seven different partners drawn from the same pool, or as a member of an isolated pair, where they interacted with the same partner across the same number of games. Participants' horizontal, pair-wise interactions led "bottom up" to the creation of an effective and efficient shared sign system in the community condition. Furthermore, the community-evolved sign systems were as effective and efficient as the local sign systems developed by isolated pairs. Finally, and as predicted by a social collaboration account, and not by an iterated learning account, interaction was critical to the creation of shared sign systems, with different isolated pairs establishing different local sign systems and different communities establishing different global sign systems. Copyright © 2010 Cognitive Science Society, Inc.

  18. Sleep, circadian rhythms, and athletic performance.

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Circadian clock, cell cycle and cancer

    Directory of Open Access Journals (Sweden)

    Cansu Özbayer

    2011-12-01

    Full Text Available There are a few rhythms of our daily lives that we are under the influence. One of them is characterized by predictable changes over a 24-hour timescale called circadian clock. This cellular clock is coordinated by the suprachiasmatic nucleus in the anterior hypothalamus. The clock consist of an autoregulatory transcription-translation feedback loop compose of four genes/proteins; BMAL1, Clock, Cyrptochrome, and Period. BMAL 1 and Clock are transcriptional factors and Period and Cyrptochrome are their targets. Period and Cyrptochrome dimerize in the cytoplasm to enter the nucleus where they inhibit Clock/BMAL activity.It has been demonstrate that circadian clock plays an important role cellular proliferation, DNA damage and repair mechanisms, checkpoints, apoptosis and cancer.

  20. Circadian oscillators in the mouse brain

    DEFF Research Database (Denmark)

    Rath, Martin F; Rovsing, Louise; Møller, Morten

    2014-01-01

    with conditional cell-specific clock gene deletions. This prompted us to analyze the molecular clockwork of the mouse neocortex and cerebellum in detail. Here, by use of in situ hybridization and quantitative RT-PCR, we show that clock genes are expressed in all six layers of the neocortex and the Purkinje...... and granular cell layers of the cerebellar cortex of the mouse brain. Among these, Per1, Per2, Cry1, Arntl, and Nr1d1 exhibit circadian rhythms suggesting that local running circadian oscillators reside within neurons of the mouse neocortex and cerebellar cortex. The temporal expression profiles of clock genes...... are similar in the neocortex and cerebellum, but they are delayed by 5 h as compared to the SCN, suggestively reflecting a master-slave relationship between the SCN and extra-hypothalamic oscillators. Furthermore, ARNTL protein products are detectable in neurons of the mouse neocortex and cerebellum...

  1. Human-centered design of the human-system interfaces of medical equipment: thyroid uptake system

    International Nuclear Information System (INIS)

    Monteiro, Jonathan K.R.; Farias, Marcos S.; Santos, Isaac J.A. Luquetti; Monteiro, Beany G.

    2013-01-01

    Technology plays an important role in modern medical centers, making healthcare increasingly complex, relying on complex technical equipment. This technical complexity is particularly noticeable in the nuclear medicine. Poorly design human-system interfaces can increase the risks for human error. The human-centered approach emphasizes the development of the equipment with a deep understanding of the users activities, current work practices, needs and abilities of the users. An important concept of human-centered design is that the ease-of-use of the equipment can be ensured only if users are actively incorporated in all phases of the life cycle of design process. Representative groups of users are exposed to the equipment at various stages in development, in a variety of testing, evaluation and interviewing situations. The users feedback obtained is then used to refine the design, with the result serving as input to the next interaction of design process. The limits of the approach are that the users cannot address any particular future needs without prior experience or knowledge about the equipment operation. The aim of this paper is to present a methodological framework that contributes to the design of the human-system interfaces, through an approach related to the users and their activities. A case study is described in which the methodological framework is being applied in development of new human-system interfaces of the thyroid uptake system. (author)

  2. Composition and functional property of photosynthetic pigments under circadian rhythm in the cyanobacterium Spirulina platensis.

    Science.gov (United States)

    Kumar, Deepak; Kannaujiya, Vinod K; Richa; Pathak, Jainendra; Sundaram, Shanthy; Sinha, Rajeshwar P

    2018-05-01

    Circadian rhythm is an important endogenous biological signal for sustainable growth and development of cyanobacteria in natural ecosystems. Circadian effects of photosynthetically active radiation (PAR), ultraviolet-A (UV-A) and ultraviolet-B (UV-B) radiations on pigment composition have been studied in the cyanobacterium Spirulina platensis under light (L)/dark (D) oscillation with a combination of 4/20, 8/16, 12/12, 16/8, 20/4 and 24/24 h time duration. Circadian exposure of PAR + UV-A (PA) and PAR + UV-A + UV-B (PAB) showed more than twofold decline in Chl a, total protein and phycocyanin (PC) in light phase and significant recovery was achieved in dark phase. The fluorescence emission wavelength of PC was shifted towards lower wavelengths in the light phase of PAB in comparison to P and PA whereas the same wavelength was retrieved in the dark phase. The production of free radicals was accelerated twofold in the light phase (24 h L) whereas the same was retrieved to the level of control during the dark phase. Oxidatively induced damage was alleviated by antioxidative enzymes such as catalase (CAT), peroxidase (POD), superoxide dismutase (SOD) and ascorbate peroxidase (APX) in the light phase (0-24-h L) whereas the dark phase showed significant inhibition of the same enzymes. Similar characteristic inhibition of free radicals and recovery of PC was observed inside cellular filament after circadian rhythm of 24/24 h (L/D). Circadian exposure of P, PA and PAB significantly altered the synthesis and recovery of pigments that could be crucial for optimization and sustainable production of photosynthetic products for human welfare.

  3. Circadian and Metabolic Effects of Light: Implications in Weight Homeostasis and Health

    Directory of Open Access Journals (Sweden)

    Santiago A. Plano

    2017-10-01

    Full Text Available Daily interactions between the hypothalamic circadian clock at the suprachiasmatic nucleus (SCN and peripheral circadian oscillators regulate physiology and metabolism to set temporal variations in homeostatic regulation. Phase coherence of these circadian oscillators is achieved by the entrainment of the SCN to the environmental 24-h light:dark (LD cycle, coupled through downstream neural, neuroendocrine, and autonomic outputs. The SCN coordinate activity and feeding rhythms, thus setting the timing of food intake, energy expenditure, thermogenesis, and active and basal metabolism. In this work, we will discuss evidences exploring the impact of different photic entrainment conditions on energy metabolism. The steady-state interaction between the LD cycle and the SCN is essential for health and wellbeing, as its chronic misalignment disrupts the circadian organization at different levels. For instance, in nocturnal rodents, non-24 h protocols (i.e., LD cycles of different durations, or chronic jet-lag simulations might generate forced desynchronization of oscillators from the behavioral to the metabolic level. Even seemingly subtle photic manipulations, as the exposure to a “dim light” scotophase, might lead to similar alterations. The daily amount of light integrated by the clock (i.e., the photophase duration strongly regulates energy metabolism in photoperiodic species. Removing LD cycles under either constant light or darkness, which are routine protocols in chronobiology, can also affect metabolism, and the same happens with disrupted LD cycles (like shiftwork of jetlag and artificial light at night in humans. A profound knowledge of the photic and metabolic inputs to the clock, as well as its endocrine and autonomic outputs to peripheral oscillators driving energy metabolism, will help us to understand and alleviate circadian health alterations including cardiometabolic diseases, diabetes, and obesity.

  4. Circadian Phase Preference in Pediatric Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Kerri L. Kim

    2014-03-01

    Full Text Available Pediatric bipolar disorder (BD rates have notably increased over the past three decades. Given the significant morbidity and mortality associated with BD, efforts are needed to identify factors useful in earlier detection to help address this serious public health concern. Sleep is particularly important to consider given the sequelae of disrupted sleep on normative functioning and that sleep is included in diagnostic criteria for both Major Depressive and Manic Episodes. Here, we examine one component of sleep—i.e., circadian phase preference with the behavioral construct of morningness/eveningness (M/E. In comparing 30 BD and 45 typically developing control (TDC participants, ages 7–17 years, on the Morningness-Eveningness Scale for Children (MESC, no between-group differences emerged. Similar results were found when comparing three groups (BD−ADHD; BD+ADHD; TDC. Consistent with data available on circadian phase preference in adults with BD, however, we found that BD adolescents, ages 13 years and older, endorsed significantly greater eveningness compared to their TDC peers. While the current findings are limited by reliance on subjective report and the high-rate of comorbid ADHD among the BD group, this finding that BD teens demonstrate an exaggerated shift towards eveningness than would be developmentally expected is important. Future studies should compare the circadian rhythms across the lifespan for individuals diagnosed with BD, as well as identify the point at which BD youth part ways with their healthy peers in terms of phase preference. In addition, given our BD sample was overall euthymic, it may be that M/E is more state vs. trait specific in latency age youth. Further work would benefit from assessing circadian functioning using a combination of rating forms and laboratory-based measures. Improved understanding of sleep in BD may identify behavioral targets for inclusion in prevention and intervention protocols.

  5. The circadian clock, reward and memory

    Directory of Open Access Journals (Sweden)

    Urs eAlbrecht

    2011-11-01

    Full Text Available During our daily activities, we experience variations in our cognitive performance, which is often accompanied by cravings for small rewards, such as consuming coffee or chocolate. This indicates that the time of day, cognitive performance and reward may be related to one another. This review will summarize data that describes the influence of the circadian clock on addiction and mood-related behavior and put the data into perspective in relation to memory processes.

  6. Clinical Trial of Exercise on Circadian Clock Resetting

    National Research Council Canada - National Science Library

    Czeisler, Charles

    2001-01-01

    ...: test the hypothesis that multiple nightly bouts of exercise will induce significant delays in the endogenous circadian rhythms of core body temperature, plasma melatonin, reaction time, alertness...

  7. NONO couples the circadian clock to the cell cycle.

    Science.gov (United States)

    Kowalska, Elzbieta; Ripperger, Juergen A; Hoegger, Dominik C; Bruegger, Pascal; Buch, Thorsten; Birchler, Thomas; Mueller, Anke; Albrecht, Urs; Contaldo, Claudio; Brown, Steven A

    2013-01-29

    Mammalian circadian clocks restrict cell proliferation to defined time windows, but the mechanism and consequences of this interrelationship are not fully understood. Previously we identified the multifunctional nuclear protein NONO as a partner of circadian PERIOD (PER) proteins. Here we show that it also conveys circadian gating to the cell cycle, a connection surprisingly important for wound healing in mice. Specifically, although fibroblasts from NONO-deficient mice showed approximately normal circadian cycles, they displayed elevated cell doubling and lower cellular senescence. At a molecular level, NONO bound to the p16-Ink4A cell cycle checkpoint gene and potentiated its circadian activation in a PER protein-dependent fashion. Loss of either NONO or PER abolished this activation and circadian expression of p16-Ink4A and eliminated circadian cell cycle gating. In vivo, lack of NONO resulted in defective wound repair. Because wound healing defects were also seen in multiple circadian clock-deficient mouse lines, our results therefore suggest that coupling of the cell cycle to the circadian clock via NONO may be useful to segregate in temporal fashion cell proliferation from tissue organization.

  8. Time-of-day effects in implicit racial in-group preferences are likely selection effects, not circadian rhythms

    Directory of Open Access Journals (Sweden)

    Timothy P. Schofield

    2016-04-01

    Full Text Available Time-of-day effects in human psychological functioning have been known of since the 1800s. However, outside of research specifically focused on the quantification of circadian rhythms, their study has largely been neglected. Moves toward online data collection now mean that psychological investigations take place around the clock, which affords researchers the ability to easily study time-of-day effects. Recent analyses have shown, for instance, that implicit attitudes have time-of-day effects. The plausibility that these effects indicate circadian rhythms rather than selection effects is considered in the current study. There was little evidence that the time-of-day effects in implicit attitudes shifted appropriately with factors known to influence the time of circadian rhythms. Moreover, even variables that cannot logically show circadian rhythms demonstrated stronger time-of-day effects than did implicit attitudes. Taken together, these results suggest that time-of-day effects in implicit attitudes are more likely to represent processes of selection rather than circadian rhythms, but do not rule out the latter possibility.

  9. Time-of-day effects in implicit racial in-group preferences are likely selection effects, not circadian rhythms.

    Science.gov (United States)

    Schofield, Timothy P

    2016-01-01

    Time-of-day effects in human psychological functioning have been known of since the 1800s. However, outside of research specifically focused on the quantification of circadian rhythms, their study has largely been neglected. Moves toward online data collection now mean that psychological investigations take place around the clock, which affords researchers the ability to easily study time-of-day effects. Recent analyses have shown, for instance, that implicit attitudes have time-of-day effects. The plausibility that these effects indicate circadian rhythms rather than selection effects is considered in the current study. There was little evidence that the time-of-day effects in implicit attitudes shifted appropriately with factors known to influence the time of circadian rhythms. Moreover, even variables that cannot logically show circadian rhythms demonstrated stronger time-of-day effects than did implicit attitudes. Taken together, these results suggest that time-of-day effects in implicit attitudes are more likely to represent processes of selection rather than circadian rhythms, but do not rule out the latter possibility.

  10. Factors influencing circadian rhythms in acetaminophen lethality.

    Science.gov (United States)

    Schnell, R C; Bozigian, H P; Davies, M H; Merrick, B A; Park, K S; McMillan, D A

    1984-01-01

    Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00-18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00-06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice.

  11. Circadian behaviour in neuroglobin deficient mice.

    Directory of Open Access Journals (Sweden)

    Christian A Hundahl

    Full Text Available Neuroglobin (Ngb, a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN. The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1 and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night.

  12. How to bootstrap a human communication system.

    Science.gov (United States)

    Fay, Nicolas; Arbib, Michael; Garrod, Simon

    2013-01-01

    How might a human communication system be bootstrapped in the absence of conventional language? We argue that motivated signs play an important role (i.e., signs that are linked to meaning by structural resemblance or by natural association). An experimental study is then reported in which participants try to communicate a range of pre-specified items to a partner using repeated non-linguistic vocalization, repeated gesture, or repeated non-linguistic vocalization plus gesture (but without using their existing language system). Gesture proved more effective (measured by communication success) and more efficient (measured by the time taken to communicate) than non-linguistic vocalization across a range of item categories (emotion, object, and action). Combining gesture and vocalization did not improve performance beyond gesture alone. We experimentally demonstrate that gesture is a more effective means of bootstrapping a human communication system. We argue that gesture outperforms non-linguistic vocalization because it lends itself more naturally to the production of motivated signs. © 2013 Cognitive Science Society, Inc.

  13. Robustness of circadian clocks to daylight fluctuations: hints from the picoeucaryote Ostreococcus tauri.

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    Quentin Thommen

    Full Text Available The development of systemic approaches in biology has put emphasis on identifying genetic modules whose behavior can be modeled accurately so as to gain insight into their structure and function. However, most gene circuits in a cell are under control of external signals and thus, quantitative agreement between experimental data and a mathematical model is difficult. Circadian biology has been one notable exception: quantitative models of the internal clock that orchestrates biological processes over the 24-hour diurnal cycle have been constructed for a few organisms, from cyanobacteria to plants and mammals. In most cases, a complex architecture with interlocked feedback loops has been evidenced. Here we present the first modeling results for the circadian clock of the green unicellular alga Ostreococcus tauri. Two plant-like clock genes have been shown to play a central role in the Ostreococcus clock. We find that their expression time profiles can be accurately reproduced by a minimal model of a two-gene transcriptional feedback loop. Remarkably, best adjustment of data recorded under light/dark alternation is obtained when assuming that the oscillator is not coupled to the diurnal cycle. This suggests that coupling to light is confined to specific time intervals and has no dynamical effect when the oscillator is entrained by the diurnal cycle. This intriguing property may reflect a strategy to minimize the impact of fluctuations in daylight intensity on the core circadian oscillator, a type of perturbation that has been rarely considered when assessing the robustness of circadian clocks.

  14. Circadian clocks, rhythmic synaptic plasticity and the sleep-wake cycle in zebrafish.

    Science.gov (United States)

    Elbaz, Idan; Foulkes, Nicholas S; Gothilf, Yoav; Appelbaum, Lior

    2013-01-01

    The circadian clock and homeostatic processes are fundamental mechanisms that regulate sleep. Surprisingly, despite decades of research, we still do not know why we sleep. Intriguing hypotheses suggest that sleep regulates synaptic plasticity and consequently has a beneficial role in learning and memory. However, direct evidence is still limited and the molecular regulatory mechanisms remain unclear. The zebrafish provides a powerful vertebrate model system that enables simple genetic manipulation, imaging of neuronal circuits and synapses in living animals, and the monitoring of behavioral performance during day and night. Thus, the zebrafish has become an attractive model to study circadian and homeostatic processes that regulate sleep. Zebrafish clock- and sleep-related genes have been cloned, neuronal circuits that exhibit circadian rhythms of activity and synaptic plasticity have been studied, and rhythmic behavioral outputs have been characterized. Integration of this data could lead to a better understanding of sleep regulation. Here, we review the progress of circadian clock and sleep studies in zebrafish with special emphasis on the genetic and neuroendocrine mechanisms that regulate rhythms of melatonin secretion, structural synaptic plasticity, locomotor activity and sleep.

  15. Circadian clocks, rhythmic synaptic plasticity and the sleep-wake cycle in zebrafish

    Directory of Open Access Journals (Sweden)

    Idan eElbaz

    2013-02-01

    Full Text Available The circadian clock and homeostatic processes are fundamental mechanisms that regulate sleep. Surprisingly, despite decades of research, we still do not know why we sleep. Intriguing hypotheses suggest that sleep regulates synaptic plasticity and consequently has a beneficial role in learning and memory. However, direct evidence is still limited and the molecular regulatory mechanisms remain unclear. The zebrafish provides a powerful vertebrate model system that enables simple genetic manipulation, imaging of neuronal circuits and synapses in living animals, and the monitoring of behavioral performance during day and night. Thus, the zebrafish has become an attractive model to study circadian and homeostatic processes that regulate sleep. Zebrafish clock- and sleep-related genes have been cloned, neuronal circuits that exhibit circadian rhythms of activity and synaptic plasticity have been studied, and rhythmic behavioral outputs have been characterized. Integration of this data could lead to a better understanding of sleep regulation. Here, we review the progress of circadian clock and sleep studies in zebrafish with special emphasis on the genetic and neuroendocrine mechanisms that regulate rhythms of melatonin secretion, structural synaptic plasticity, locomotor activity and sleep.

  16. Relationship between alertness, performance, and body temperature in humans

    Science.gov (United States)

    Wright, Kenneth P Jr; Hull, Joseph T.; Czeisler, Charles A.

    2002-01-01

    Body temperature has been reported to influence human performance. Performance is reported to be better when body temperature is high/near its circadian peak and worse when body temperature is low/near its circadian minimum. We assessed whether this relationship between performance and body temperature reflects the regulation of both the internal biological timekeeping system and/or the influence of body temperature on performance independent of circadian phase. Fourteen subjects participated in a forced desynchrony protocol allowing assessment of the relationship between body temperature and performance while controlling for circadian phase and hours awake. Most neurobehavioral measures varied as a function of internal biological time and duration of wakefulness. A number of performance measures were better when body temperature was elevated, including working memory, subjective alertness, visual attention, and the slowest 10% of reaction times. These findings demonstrate that an increased body temperature, associated with and independent of internal biological time, is correlated with improved performance and alertness. These results support the hypothesis that body temperature modulates neurobehavioral function in humans.

  17. Independence of circadian entrainment state and responses to melatonin in male Siberian hamsters

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    Gorman Michael R

    2003-10-01

    Full Text Available Abstract Background Seasonal fluctuations in physiology and behavior depend on the duration of nocturnal melatonin secretion programmed by the circadian system. A melatonin signal of a given duration, however, can elicit different responses depending on whether an animal was previously exposed to longer or shorter photoperiod signals (i.e., its photoperiodic history. This report examined in male Siberian hamsters which of two aspects of photoperiod history – prior melatonin exposure or entrainment state of the circadian system – is critical for generating contingent responses to a common photoperiodic signal. Results In Experiment #1, daily melatonin infusions of 5 or 10 h duration stimulated or inhibited gonadal growth, respectively, but had no effect on entrainment of the locomotor activity rhythm to long or short daylengths, thereby demonstrating that melatonin history and entrainment status could be experimentally dissociated. These manipulations were repeated in Experiment #2, and animals were subsequently exposed to a 12 week regimen of naturalistic melatonin signals shown in previous experiments to reveal photoperiodic history effects. Gonadal responses differed as a function of prior melatonin exposure but were unaffected by the circadian entrainment state. Experiment #3 demonstrated that a new photoperiodic history could be imparted during four weeks of exposure to long photoperiods. This effect, moreover, was blocked in animals treated concurrently with constant release melatonin capsules that obscured the endogenous melatonin signal: Following removal of the implants, the gonadal response depended not on the immediately antecedent circadian entrainment state, but on the more remote photoperiodic conditions prior to the melatonin implant. Conclusions The interpretation of photoperiodic signals as a function of prior conditions depends specifically on the history of melatonin exposure. The photoperiodic regulation of circadian

  18. Circadian time structure of circulating plasma lipid peroxides, antioxidant enzymes and other small molecules in peptic ulcers.

    Science.gov (United States)

    Singh, Ranjana; Singh, Rajesh Kumar; Masood, Tariq; Tripathi, Anil Kumar; Mahdi, Abbas Ali; Singh, Raj Kumar; Schwartzkopff, Othild; Cornelissen, Germaine

    2015-12-07

    The circadian rhythm, as part of a broad time structure (chronome) of lipid peroxides and antioxidant defense mechanisms may relate to prevention, efficacy and management of preventive and curative chronotherapy. Fifty newly diagnosed patients with peptic ulcers, 30-45 years of age, and 60 age-matched clinically healthy volunteers were synchronized for one week with diurnal activity from about 06:00 to about 22:00 and nocturnal rest. Breakfast was served around 08:30, lunch around 13:30 and dinner around 20:30. Drugs known to affect the free-radical systems were not taken. Blood samples were collected at 6-hour intervals for 24h under standardized, presumably 24-hour synchronized conditions. Plasma lipid peroxides, in the form of malondialdehyde (MDA), blood superoxide dismutase (SOD), glutathione peroxide (GPx), glutathione reductase (GR), catalase (CAT) activities, and serum total protein, albumin, ascorbic acid, total serum cholesterol, and HDL-cholesterol concentrations were determined. By population-mean cosinor analysis, a marked circadian variation was demonstrated for all variables in healthy subjects and in ulcer patients (pascorbic acid, and HDL-C. They also had smaller circadian amplitude of SOD, CAT, GPx, GR, ascorbic acid, T-C, and HDL-C, but larger circadian amplitude of MDA and albumin. As compared to healthy subjects, the circadian acrophase of ulcer patients occurred later for MDA and GR and earlier for GPx. Mapping circadian rhythms, important chronome components that include trends with age and extra-circadian components characterizing antioxidants and pro-oxidants, is needed for exploring their putative role as markers in the treatment and management of peptic ulcers. Copyright © 2015. Published by Elsevier B.V.

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

    Science.gov (United States)

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

    2015-02-11

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

  20. Guidance for Human-system Interfaces to Automatic Systems

    Energy Technology Data Exchange (ETDEWEB)

    O' Hara, J.M.; Higgins, J.; Stephen Fleger; Valerie Barnes

    2010-09-27

    Automation is ubiquitous in modern complex systems, and commercial nuclear- power plants are no exception. Automation is applied to a wide range of functions, including monitoring and detection, situation assessment, response planning, and response implementation. Automation has become a 'team player' supporting personnel in nearly all aspects of system operation. In light of its increasing use and importance in new- and future-plants, guidance is needed to conduct safety reviews of the operator's interface with automation. The objective of this research was to develop such guidance. We first characterized the important HFE aspects of automation, including six dimensions: Levels, functions, processes, modes, flexibility, and reliability. Next, we reviewed literature on the effects of all of these aspects of automation on human performance, and on the design of human-system interfaces (HSIs). Then, we used this technical basis established from the literature to identify general principles for human-automation interaction and to develop review guidelines. The guidelines consist of the following seven topics: Automation displays, interaction and control, automation modes, automation levels, adaptive automation, error tolerance and failure management, and HSI integration.

  1. Complementary approaches to understanding the plant circadian clock

    Directory of Open Access Journals (Sweden)

    Ozgur E. Akman

    2010-02-01

    Full Text Available Circadian clocks are oscillatory genetic networks that help organisms adapt to the 24-hour day/night cycle. The clock of the green alga Ostreococcus tauri is the simplest plant clock discovered so far. Its many advantages as an experimental system facilitate the testing of computational predictions. We present a model of the Ostreococcus clock in the stochastic process algebra Bio-PEPA and exploit its mapping to different analysis techniques, such as ordinary differential equations, stochastic simulation algorithms and model-checking. The small number of molecules reported for this system tests the limits of the continuous approximation underlying differential equations. We investigate the difference between continuous-deterministic and discrete-stochastic approaches. Stochastic simulation and model-checking allow us to formulate new hypotheses on the system behaviour, such as the presence of self-sustained oscillations in single cells under constant light conditions. We investigate how to model the timing of dawn and dusk in the context of model-checking, which we use to compute how the probability distributions of key biochemical species change over time. These show that the relative variation in expression level is smallest at the time of peak expression, making peak time an optimal experimental phase marker. Building on these analyses, we use approaches from evolutionary systems biology to investigate how changes in the rate of mRNA degradation impacts the phase of a key protein likely to affect fitness. We explore how robust this circadian clock is towards such potential mutational changes in its underlying biochemistry. Our work shows that multiple approaches lead to a more complete understanding of the clock.

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

    Science.gov (United States)

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

    2017-08-09

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

  3. Investigation of human system interface design in nuclear power plant

    International Nuclear Information System (INIS)

    Feng Yan; Zhang Yunbo; Wang Zhongqiu

    2012-01-01

    The paper introduces the importance of HFE in designing nuclear power plant, and introduces briefly the content and scope of HFE, discusses human system interface design of new built nuclear power plants. This paper also describes human system interface design of foreign nuclear power plant, and describes in detail human system interface design of domestic nuclear power plant. (authors)

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Adolf M. Sandbichler

    2018-04-01

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

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

    Directory of Open Access Journals (Sweden)

    A.M.O. Leal

    1997-12-01

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

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

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    Naoto Hayasaka

    Full Text Available Regulators of G protein signaling (RGS are a multi-functional protein family, which functions