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Sample records for feeding uncouples circadian

  1. The importance of hormonal circadian rhythms in daily feeding patterns

    NARCIS (Netherlands)

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

    2017-01-01

    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,

  2. Feeding period restriction alters the expression of peripheral circadian rhythm genes without changing body weight in mice.

    Directory of Open Access Journals (Sweden)

    Hagoon Jang

    Full Text Available Accumulating evidence suggests that the circadian clock is closely associated with metabolic regulation. However, whether an impaired circadian clock is a direct cause of metabolic dysregulation such as body weight gain is not clearly understood. In this study, we demonstrate that body weight gain in mice is not significantly changed by restricting feeding period to daytime or nighttime. The expression of peripheral circadian clock genes was altered by feeding period restriction, while the expression of light-regulated hypothalamic circadian clock genes was unaffected by either a normal chow diet (NCD or a high-fat diet (HFD. In the liver, the expression pattern of circadian clock genes, including Bmal1, Clock, and Per2, was changed by different feeding period restrictions. Moreover, the expression of lipogenic genes, gluconeogenic genes, and fatty acid oxidation-related genes in the liver was also altered by feeding period restriction. Given that feeding period restriction does not affect body weight gain with a NCD or HFD, it is likely that the amount of food consumed might be a crucial factor in determining body weight. Collectively, these data suggest that feeding period restriction modulates the expression of peripheral circadian clock genes, which is uncoupled from light-sensitive hypothalamic circadian clock genes.

  3. 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.

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

    NARCIS (Netherlands)

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

    2017-01-01

    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

  5. 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.

  6. 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

  7. 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.

  8. Circadian cycles in growth and feeding rates of heterotrophic protist plankton

    DEFF Research Database (Denmark)

    Jakobsen, Hans Henrik; Strom, S.L.

    2004-01-01

    Growth and feeding rates of four species of planktonic marine heterotrophic protists showed pronounced diel cycles. In most cases, rates were higher during the day and lower at night. However, for the ciliate Strobilidium sp., growth was highest at night. In another ciliate species, Balanion...... comatum, no day-night difference in growth and feeding rates was found. Maintenance of day-night rate differences during 24-h exposures to continuous darkness demonstrated that most of these protists had circadian cycles. The heterotrophic dinoflagellate Oxyrrhis marina exhibited a clear irradiance...... to culturing in a day: night light cycle in O. marina and found that resetting the circadian cycle in this dinoflagellate temporarily arrested growth and feeding. We suggest that protists use a time-integrated light threshold rather than an instantaneous irradiance to maintain the circadian cell cycle...

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

    Science.gov (United States)

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

    2007-04-18

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

  10. Circadian control of insulin secretion is independent of the temporal distribution of feeding

    NARCIS (Netherlands)

    Kalsbeek, Andries; Strubbe, JH

    1998-01-01

    To investigate whether there is a circadian regulation of insulin secretion, rats were adapted to a feeding regimen of six meals equally distributed over 24 h. Under these conditions basal glucose and insulin levels increased during the light phase and decreased during the dark phase. Maximal blood

  11. Temporal organization of feeding in Syrian hamsters with a genetically altered circadian period

    NARCIS (Netherlands)

    Oklejewicz, M; Overkamp, GJF; Stirland, JA; Daan, S

    2001-01-01

    The variation in spontaneous meal patterning was studied in three genotypes (tau +/+, tau +/- and tau -/-) of the Syrian hamster with an altered circadian period. Feeding activity was monitored continuously in 13 individuals from each genotype in constant dim light conditions. All three genotypes

  12. Fasting, circadian rhythms, and time restricted feeding in healthy lifespan

    OpenAIRE

    Longo, Valter D.; Panda, Satchidananda

    2016-01-01

    Feeding in most animals is confined to a defined period, leaving short periods of fasting that coincide with sleep. Fasting enables organisms to enter alternative metabolic phases, which rely less on glucose and more on ketone body-like carbon sources. Both intermittent and periodic fasting result in benefits ranging from prevention to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in which feeding time is restricted to certain hours of the day, allows the daily...

  13. Fasting, circadian rhythms, and time restricted feeding in healthy lifespan

    Science.gov (United States)

    Longo, Valter D.; Panda, Satchidananda

    2016-01-01

    Summary Feeding in most animals is confined to a defined period, leaving short periods of fasting that coincide with sleep. Fasting enables organisms to enter alternative metabolic phases, which rely less on glucose and more on ketone body-like carbon sources. Both intermittent and periodic fasting result in benefits ranging from prevention to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in which feeding time is restricted to certain hours of the day, allows the daily fasting period to last >12 h, thus imparting pleiotropic benefits in multiple organisms. Understanding the mechanistic link between nutrients and the fasting benefits is leading to the identification of fasting mimicking diets (FMDs) that achieve changes similar to those caused by fasting. Given the pleiotropic and sustained benefits of TRF and FMD, both basic science and translational research are warranted to develop fasting-associated interventions into effective and inexpensive treatments with the potential to improve healthspan. PMID:27304506

  14. 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

  15. 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.

  16. Uncoupling Marriages.

    Science.gov (United States)

    Kane, Barbara

    1979-01-01

    In counseling groups, uncoupling partners learn to say their good-byes and accept the death of the marriage. They complete their unfinished business with each other. An organizational strategy is necessary. Skill in helping partners uncouple is a vital function of a marriage counselor, who must be proficient in group counseling. (Author)

  17. Metabolic response to feeding in Tupinambis merianae: circadian rhythm and a possible respiratory constraint.

    Science.gov (United States)

    Klein, Wilfried; Perry, Steven F; Abe, Augusto S; Andrade, Denis V

    2006-01-01

    The diurnal tegu lizard Tupinambis merianae exhibits a marked circadian variation in metabolism that is characterized by the significant increase in metabolism during part of the day. These increases in metabolic rate, found in the fasting animal, are absent during the first 2 d after meal ingestion but reappear subsequently, and the daily increase in metabolic rate is added to the increase in metabolic rate caused by digestion. During the first 2 d after feeding, priority is given to digestion, while on the third and following days, the metabolic demands are clearly added to each other. This response seems to be a regulated response of the animal, which becomes less active after food ingestion, rather than an inability of the respiratory system to support simultaneous demands at the beginning of digestion. The body cavity of Tupinambis is divided into two compartments by a posthepatic septum (PHS). Animals that had their PHS surgically removed showed no significant alteration in the postprandial metabolic response compared to tegus with intact PHS. The maximal metabolic increment during digestion, the relative cost of meal digestion, and the duration of the process were virtually unaffected by the removal of the PHS.

  18. Effects of short-term feed deprivation and melatonin implants on circadian patterns of leptin in the horse.

    Science.gov (United States)

    Buff, P R; Morrison, C D; Ganjam, V K; Keisler, D H

    2005-05-01

    Leptin is a protein hormone produced by adipose tissue that influences hypothalamic mechanisms regulating appetite and energy balance. In species tested thus far, including horses, concentrations of leptin increase as animal fat mass increases. The variables and mechanisms that influence the secretion of leptin are not well known, nor is it known in equine species how the secretion of leptin is influenced by acute alterations in energy balance, circadian patterns, and/or reproductive competence. Our objectives were to determine in horses: 1) whether plasma concentrations of leptin are secreted in a circadian and/or a pulsatile pattern; 2) whether a 48-h period of feed restriction would alter plasma concentrations of leptin, growth hormone, or insulin; and 3) whether ovariectomy and/or a melatonin implant would affect leptin. In Exp. 1, mares exposed to ambient photoperiod of visible light (11 h, 33 min to 11 h, 38 min), received treatments consisting of a 48-h feed restriction (RES) or 48 h of alfalfa hay fed ad libitum (FED). Mares were maintained in a dry lot before sampling and were tethered to a rail during sampling. Analyses revealed that leptin was not secreted in a pulsatile manner, and that mean leptin concentrations were greater (P < 0.001) in FED vs. RES mares (17.20 +/- 0.41 vs. 7.29 +/- 0.41 ng/mL). Plasma growth hormone was pulsatile, and mean concentrations were greater in RES than FED mares (2.15 +/- 0.31 vs. 1.08 +/- 0.31 ng/mL; P = 0.05). Circadian patterns of leptin secretion were observed, but only in FED mares (15.39 +/- 0.58 ng/mL for morning vs. 19.00 +/- 0.58 ng/mL for evening; P < 0.001). In Exp. 2, mares that were ovariectomized or intact received either a s.c. melatonin implant or a sham implant. Thereafter, blood was sampled at weekly intervals at 1000 and 1700. Concentrations of leptin in samples collected at 1700 were greater (P < 0.001) than in those collected at 1000 (28.24 +/- 1.7 vs. 22.07 +/- 1.7 ng/mL). Neither ovariectomy nor

  19. Timed feeding of mice modulates light-entrained circadian rhythms of reticulated platelet abundance and plasma thrombopoietin and affects gene expression in megakaryocytes.

    Science.gov (United States)

    Hartley, Paul S; Sheward, John; Scholefield, Emma; French, Karen; Horn, Jacqueline M; Holmes, Megan C; Harmar, Anthony J

    2009-07-01

    Circadian (c. 24 h) rhythms of physiology are entrained to either the environmental light-dark cycle or the timing of food intake. In the current work the hypothesis that rhythms of platelet turnover in mammals are circadian and entrained by food intake was explored in mice. Mice were entrained to 12 h light-dark cycles and given either ad libitum (AL) or restricted access (RF) to food during the light phase. Blood and megakaryocytes were then collected from mice every 4 h for 24 h. It was found that total and reticulated platelet numbers, plasma thrombopoietin (TPO) concentration and the mean size of mature megakaryocytes were circadian but not entrained by food intake. In contrast, a circadian rhythm in the expression of Arnt1 in megakaryocytes was entrained by food. Although not circadian, the expression in megakaryocytes of Nfe2, Gata1, Itga2b and Tubb1 expression was downregulated by RF, whereas Ccnd1 was not significantly affected by the feeding protocol. It is concluded that circadian rhythms of total platelet number, reticulated platelet number and plasma TPO concentration are entrained by the light-dark cycle rather than the timing of food intake. These findings imply that circadian clock gene expression regulates platelet turnover in mammals.

  20. Reduced neurophysin immunoreactivity in rat suprachiasmatic nucleus parallels dissociation of circadian feeding rhythm in constant light

    NARCIS (Netherlands)

    Steinhorst, B; Mai, JK; Rietveld, WJ

    Several distinct neuronal populations can be outlined in the suprachiasmatic nucleus (SCN) by employing immunohistochemistry. Understanding their interaction may serve as the key to the proc esses involved in the generation of circadian rhythms by the SCN. 15 adult rats were exposed to constant dim

  1. 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

  2. A circadian clock in the olfactory bulb anticipates feeding during food anticipatory activity.

    Science.gov (United States)

    Nolasco, Nahum; Juárez, Claudia; Morgado, Elvira; Meza, Enrique; Caba, Mario

    2012-01-01

    Rabbit pups ingest food, in this case milk, once a day with circadian periodicity and are a natural model of food anticipatory activity. During nursing, several sensory systems receive information about properties of the food, one of them being the olfactory system, which has received little attention in relation to synchronization by food. In addition, the olfactory bulb has a circadian pacemaker that exhibits rhythms independently of the suprachiasmatic nucleus, but the biological functions of these rhythms are largely unknown. In the present contribution, we hypothesized that circadian suckling of milk synchronizes rhythms in the olfactory bulb. To this aim we explored by immunohistochemistry, rhythms of FOS and PER1 proteins, as indicators of activation and reporter of oscillations, respectively, through a complete 24-h cycle in periglomerular, mitral and granular cell layers of both the main and the accessory olfactory bulb. Subjects were 7-day-old rabbit pups scheduled to nurse during the night (02:00 h) or day (10:00 h), and also fasted subjects, to explore the possible persistence of oscillations. In the three layers of the main olfactory bulb, FOS was high at time of nursing, then further increased 1.5 h afterward, and then decreased to increase again in advance of the next nursing bout. This pattern persisted, without the postprandial increase, in fasted subjects with a shift in subjects nursed at 02:00. PER1 was increased 2-8 h after nursing and this increase persisted in most cell layers, with a shift, in fasted subjects. In the accessory olfactory bulb we only observed a consistent pattern of FOS expression in the mitral cell layer of nursed subjects, similar to that of the main olfactory bulb. We conclude that the main olfactory bulb is synchronized during milk ingestion, but during fasting its oscillations perhaps are modulated by the suprachiasmatic nucleus, as proposed for rodents.

  3. A circadian clock in the olfactory bulb anticipates feeding during food anticipatory activity.

    Directory of Open Access Journals (Sweden)

    Nahum Nolasco

    Full Text Available Rabbit pups ingest food, in this case milk, once a day with circadian periodicity and are a natural model of food anticipatory activity. During nursing, several sensory systems receive information about properties of the food, one of them being the olfactory system, which has received little attention in relation to synchronization by food. In addition, the olfactory bulb has a circadian pacemaker that exhibits rhythms independently of the suprachiasmatic nucleus, but the biological functions of these rhythms are largely unknown. In the present contribution, we hypothesized that circadian suckling of milk synchronizes rhythms in the olfactory bulb. To this aim we explored by immunohistochemistry, rhythms of FOS and PER1 proteins, as indicators of activation and reporter of oscillations, respectively, through a complete 24-h cycle in periglomerular, mitral and granular cell layers of both the main and the accessory olfactory bulb. Subjects were 7-day-old rabbit pups scheduled to nurse during the night (02:00 h or day (10:00 h, and also fasted subjects, to explore the possible persistence of oscillations. In the three layers of the main olfactory bulb, FOS was high at time of nursing, then further increased 1.5 h afterward, and then decreased to increase again in advance of the next nursing bout. This pattern persisted, without the postprandial increase, in fasted subjects with a shift in subjects nursed at 02:00. PER1 was increased 2-8 h after nursing and this increase persisted in most cell layers, with a shift, in fasted subjects. In the accessory olfactory bulb we only observed a consistent pattern of FOS expression in the mitral cell layer of nursed subjects, similar to that of the main olfactory bulb. We conclude that the main olfactory bulb is synchronized during milk ingestion, but during fasting its oscillations perhaps are modulated by the suprachiasmatic nucleus, as proposed for rodents.

  4. 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

  5. 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.

  6. The Effect Of Reversed Light-Dark Cycle And Restricted Feeding Regime On The Circadian Rhythm Of Cortisol And Serotonin In Male Rats

    International Nuclear Information System (INIS)

    Abdel-Rahman, M.; El-Masry, H.; El-Hennamy, R.E.; Abdel-Kader, S.

    2013-01-01

    Biological clock plays an important role in the regulation of different physiological processes and behaviour. The present study aimed to investigate the effect of the reversed light-dark cycle and restricted feeding regime for one and two weeks on the circadian rhythm of cortisol and serotonin in male rats. Serum cortisol and brain serotonin levels were delayed after exposing rats to a reversed light-dark cycle for one week which may be due to the action of the gene Per2 that delay the phase of the clock. On the other hand, their levels highly elevated and peaked at the same time after two weeks which may be due to continuous stressful events. The serum cortisol reached its highest level at the meal time after one week of restricted feeding while after two weeks, its level was higher at several time intervals, which may be due to the need of the body to energy. The peak of the brain serotonin rhythm was delayed during the day after one week while after two weeks, it exhibited the same pattern of the circadian rhythm of control group. From the present results and previous studies, it could be concluded that the reversed light-dark cycle and restricted feeding regime are able to shift the phase of the circadian rhythm of the studied physiological parameters which led to many mental and physiological disorders

  7. Impact of Time-Restricted Feeding and Dawn-to-Sunset Fasting on Circadian Rhythm, Obesity, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Ayse L. Mindikoglu

    2017-01-01

    Full Text Available Obesity now affects millions of people and places them at risk of developing metabolic syndrome, nonalcoholic fatty liver disease (NAFLD, and even hepatocellular carcinoma. This rapidly emerging epidemic has led to a search for cost-effective methods to prevent the metabolic syndrome and NAFLD as well as the progression of NAFLD to cirrhosis and hepatocellular carcinoma. In murine models, time-restricted feeding resets the hepatic circadian clock and enhances transcription of key metabolic regulators of glucose and lipid homeostasis. Studies of the effect of dawn-to-sunset Ramadan fasting, which is akin to time-restricted feeding model, have also identified significant improvement in body mass index, serum lipid profiles, and oxidative stress parameters. Based on the findings of studies conducted on human subjects, dawn-to-sunset fasting has the potential to be a cost-effective intervention for obesity, metabolic syndrome, and NAFLD.

  8. Impact of Time-Restricted Feeding and Dawn-to-Sunset Fasting on Circadian Rhythm, Obesity, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Gagan, Sood K.

    2017-01-01

    Obesity now affects millions of people and places them at risk of developing metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), and even hepatocellular carcinoma. This rapidly emerging epidemic has led to a search for cost-effective methods to prevent the metabolic syndrome and NAFLD as well as the progression of NAFLD to cirrhosis and hepatocellular carcinoma. In murine models, time-restricted feeding resets the hepatic circadian clock and enhances transcription of key metabolic regulators of glucose and lipid homeostasis. Studies of the effect of dawn-to-sunset Ramadan fasting, which is akin to time-restricted feeding model, have also identified significant improvement in body mass index, serum lipid profiles, and oxidative stress parameters. Based on the findings of studies conducted on human subjects, dawn-to-sunset fasting has the potential to be a cost-effective intervention for obesity, metabolic syndrome, and NAFLD. PMID:29348746

  9. The mitochondrial uncoupling proteins

    OpenAIRE

    Ledesma, Amalia; de Lacoba, Mario García; Rial, Eduardo

    2002-01-01

    The uncoupling proteins (UCPs) are transporters, present in the mitochondrial inner membrane, that mediate a regulated discharge of the proton gradient that is generated by the respiratory chain. This energy-dissipatory mechanism can serve functions such as thermogenesis, maintenance of the redox balance, or reduction in the production of reactive oxygen species. Some UCP homologs may not act as true uncouplers, however, and their activity has yet to be defined. The UCPs are integral membrane...

  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. 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.

  12. Circadian light

    Directory of Open Access Journals (Sweden)

    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.

  13. Phase Control of Ultradian Feeding Rhythms in the Common Vole (Microtus arvalis) : The Roles of Light and the Circadian System

    NARCIS (Netherlands)

    Gerkema, Menno P.; Daan, Serge; Wilbrink, Marieke; Hop, Martina W.; van der Leest, Floris

    1993-01-01

    In their ultradian (2- to 3-hr) feeding rhythm, common voles show intraindividual synchrony from day to day, as well as interindividual synchrony between members of the population, even at remote distances. This study addresses the question of how resetting of the ultradian rhythm, a prerequisite

  14. 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.

  15. 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.

  16. 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 ...

  17. 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 ...

  18. 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...

  19. Restricted daytime feeding attenuates reentrainment of the circadian melatonin rhythm after an 8-h phase advance of the light-dark cycle

    NARCIS (Netherlands)

    Kalsbeek, A.; Barassin, S.; van Heerikhuize, J. J.; van der Vliet, J.; Buijs, R. M.

    2000-01-01

    It is well established that in the absence of photic cues, the circadian rhythms of rodents can be readily phase-shifted and entrained by various nonphotic stimuli that induce increased levels of locomotor activity (i.e., benzodiazepines, a new running wheel, and limited food access). In the

  20. Diverse development and higher sensitivity of the circadian clocks to changes in maternal-feeding regime in a rat model of cardio-metabolic disease

    Czech Academy of Sciences Publication Activity Database

    Olejníková, Lucie; Polidarová, Lenka; Paušlyová, Lucia; Sládek, Martin; Sumová, Alena

    2015-01-01

    Roč. 32, č. 4 (2015), s. 531-547 ISSN 0742-0528 R&D Projects: GA ČR(CZ) GAP303/12/1108 Grant - others:Program interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111202 Institutional support: RVO:67985823 Keywords : circadian clock * clock gene * colon * liver * SHR * supraciasmatic nucleus Subject RIV: ED - Physiology Impact factor: 3.540, year: 2015

  1. Diet and Circadian Rhythm of the Feeding Activity of Tamoatá Hoplosternum Littorale (Hancock, 1828 (Siluriformes, Callichthydae Captured In Vacacaí River, Rio Grande do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Éverton Luís Zardo

    2013-12-01

    Full Text Available This paper aims at contributing to biological and ecological knowledge about Hoplosternum littorale by studying its diet in the Vacacaí River, RS. With this aim, samples were taken in all seasons in four points selected along the Vacacaí River, using gill nets with meshes 1.5, 2.0, 2.5, 3.0, 4.0; 5.0, 6.0 and 8.0 cm between adjacent knots. The nets remained in the water for 24 hours, being revised every six hours. The fish which was caught was fixed in 10% formalin and later preserved in 70% alcohol. The specimens were weighed, measured and had the digestive tract removed for diet analysis. The items found in stomach contents were separated into six categories: Insects, Mollusks, Detritus/Silt, Vegetables, Scales and Nematodes, each category being analyzed by frequency of occurrence and volumetric method, being combined to obtain the Feeding Index" (IAi. The stomach repletion index (SRI and Repletion Index (RI were also estimated to assess the feeding activity according to the circadian rhythm. The most important items in the diet of this species according to IAi were insects, sediment and plant. H. littorale showed greater feeding activity in early morning, coinciding with greater capture also in reviewing this time, suggesting a nocturnal activity.

  2. Synchronizing noisy nonidentical oscillators by transient uncoupling

    Energy Technology Data Exchange (ETDEWEB)

    Tandon, Aditya, E-mail: adityat@iitk.ac.in; Mannattil, Manu, E-mail: mmanu@iitk.ac.in [Department of Physics, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016 (India); Schröder, Malte, E-mail: malte@nld.ds.mpg.de [Network Dynamics, Max Planck Institute for Dynamics and Self-Organization (MPIDS), 37077 Göttingen (Germany); Timme, Marc, E-mail: timme@nld.ds.mpg.de [Network Dynamics, Max Planck Institute for Dynamics and Self-Organization (MPIDS), 37077 Göttingen (Germany); Department of Physics, Technical University of Darmstadt, 64289 Darmstadt (Germany); Chakraborty, Sagar, E-mail: sagarc@iitk.ac.in [Department of Physics, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016 (India); Mechanics and Applied Mathematics Group, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016 (India)

    2016-09-15

    Synchronization is the process of achieving identical dynamics among coupled identical units. If the units are different from each other, their dynamics cannot become identical; yet, after transients, there may emerge a functional relationship between them—a phenomenon termed “generalized synchronization.” Here, we show that the concept of transient uncoupling, recently introduced for synchronizing identical units, also supports generalized synchronization among nonidentical chaotic units. Generalized synchronization can be achieved by transient uncoupling even when it is impossible by regular coupling. We furthermore demonstrate that transient uncoupling stabilizes synchronization in the presence of common noise. Transient uncoupling works best if the units stay uncoupled whenever the driven orbit visits regions that are locally diverging in its phase space. Thus, to select a favorable uncoupling region, we propose an intuitive method that measures the local divergence at the phase points of the driven unit's trajectory by linearizing the flow and subsequently suppresses the divergence by uncoupling.

  3. Mitochondrial uncouplers with an extraordinary dynamic range.

    Science.gov (United States)

    Lou, Phing-How; Hansen, Birgit S; Olsen, Preben H; Tullin, Søren; Murphy, Michael P; Brand, Martin D

    2007-10-01

    We have discovered that some weak uncouplers (typified by butylated hydroxytoluene) have a dynamic range of more than 10(6) in vitro: the concentration giving measurable uncoupling is less than one millionth of the concentration causing full uncoupling. They achieve this through a high-affinity interaction with the mitochondrial adenine nucleotide translocase that causes significant but limited uncoupling at extremely low uncoupler concentrations, together with more conventional uncoupling at much higher concentrations. Uncoupling at the translocase is not by a conventional weak acid/anion cycling mechanism since it is also caused by substituted triphenylphosphonium molecules, which are not anionic and cannot protonate. Covalent attachment of the uncoupler to a mitochondrially targeted hydrophobic cation sensitizes it to membrane potential, giving a small additional effect. The wide dynamic range of these uncouplers in isolated mitochondria and intact cells reveals a novel allosteric activation of proton transport through the adenine nucleotide translocase and provides a promising starting point for designing safer uncouplers for obesity therapy.

  4. Polymorphisms and haplotypes in the bovine neuropeptide Y, growth hormone receptor, ghrelin, insulin-like growth factor 2, and uncoupling proteins 2 and 3 genes and their associations with measures of growth, performance, feed efficiency, and carcass merit in beef cattle.

    Science.gov (United States)

    Sherman, E L; Nkrumah, J D; Murdoch, B M; Li, C; Wang, Z; Fu, A; Moore, S S

    2008-01-01

    Genes that regulate metabolism and energy partitioning have the potential to influence economically important traits in farm animals, as do polymorphisms within these genes. In the current study, SNP in the bovine neuropeptide Y (NPY), growth hormone receptor (GHR), ghrelin (GHRL), uncoupling proteins 2 and 3 (UCP2 and UCP3), IGF2, corticotrophin-releasing hormone (CRH), cocaine and amphetamine regulated transcript (CART), melanocortin-4 receptor (MC4R), proopiomelanocortin (POMC), and GH genes were evaluated for associations with growth, feed efficiency, and carcass merit in beef steers. In total, 24 SNP were evaluated for associations with these traits and haplotypes were constructed within each gene when 2 or more SNP showed significant associations. An A/G SNP located in intron 4 of the GHR gene had the largest effects on BW of the animals (dominance effect P GHRL gene tended to show effects on residual feed intake, FCR, and partial efficiency of growth (P < 0.10). The IGF2 SNP most strongly affected LM area (P < 0.01), back fat, ADG, and FCR (P < 0.05). The SNP in the CART, MC4R, POMC, GH, and CRH genes did not show associations at P < 0.05 with any of the traits. Although most of the SNP that showed associations do not cause amino acid changes, these SNP could be linked to other yet to be detected causative mutations or nearby QTL. It will be very important to verify these results in other cattle populations.

  5. Circadian and ultradian rhythms in the feeding behaviour and nutrient intakes of oil refinery operators with shift-work every 3--4 days.

    Science.gov (United States)

    Reinberg, A; Migraine, C; Apfelbaum, M; Brigant, L; Ghata, J; Vieux, N; Laporte, A; Nicolai

    1979-03-01

    Seven healthy adult men, five shift-workers and two non-shift-workers (from 21 to 36 years; mean = 26.4) volunteered to record what and when they ate, both at work and at home, every day, during eight consecutive weeks (Oct. - Dec. 1974). 1) All the subjects maintained the timing of main-meal (lunch and supper) during all shifts. 2) The major intake of protein and lipid was concentrated on the two main meals during all shifts. 3) Only the pattern of carbohydrate intake was modified by the shift-work: e.g. night-shift is associated with nibbling behaviour. 4) However, shift-work and in particular the occurence of nibbling behaviour did not result in change either in the mean 24 h caloric intake, or in the percentage of protein calories. 5) The comparison between the constancy of the timing of major meals and the shift of the timing of circadian rhythm acrophases of the 5 shift-workers leads to conclude that meal timing had a poor synchronizing effect, if any.

  6. Aging and Circadian Rhythms

    Science.gov (United States)

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

    2015-01-01

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

  7. Lactating performance, water and feed consumption of rabbit does reared under a Mediterranean summer circadian cycle of temperature v. comfort temperature conditions.

    Science.gov (United States)

    Bakr, M H; Tusell, L; Rafel, O; Terré, M; Sánchez, J P; Piles, M

    2015-07-01

    The general aim of this research was to study the effect of high ambient temperature on the performance of does during lactation, specifically the following factors: average daily feed (ADFI) and water (ADWI) intakes, daily milk yield (DMY); milk composition: dry matter (DM), CP and gross energy (GE); doe BW (DW); individual kit weaning weight (IWW) and litter survival rate during lactation (SR). The study was undertaken comparing the performance of two groups of contemporary does reared under the same management, feeding regime and environmental conditions, except the environmental temperature and humidity. A total of 80 females were randomly allocated, at 60 days of age, into two identical and continuous rooms. In one room, the temperature was maintained permanently within the thermo-neutral zone (between 18°C to 22°C); thus, environmental conditions in this room were considered as comfort conditions. In the second room, the environmental temperature pattern simulated the daily temperature cycles that were characteristic of the summer in Mediterranean countries (24°C at 0800 h, increasing up to 29°C until 1100 h; maintenance at 29°C to 31°C for 4 h and decreasing to about 24°C to 26°C around 1700 h until 0800 h of the following day), which were considered as thermal stress conditions. Females followed a semi-intensive reproductive rhythm, first artificial insemination at 4.5 months of age, with subsequent 42-day reproductive cycles. Traits were recorded from a total of 138 lactations. Does were controlled up to the 5th lactation. Data were analyzed using linear and linear mixed models. High ambient temperature led to a lower ADFI (-9.4%), DW (-6.2%) and IWW (-8%), but it did not affect ADWI. No significant difference was found either for DMY, milk composition (DM, CP and GE) and SR during the lactation period. Heat stress was moderate, and does were able to adapt to it behaviorally by decreasing feed intake (to reduce heat production), but also live

  8. 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

  9. Quantitative analysis of circadian single cell oscillations in response to temperature.

    Science.gov (United States)

    Abraham, Ute; Schlichting, Julia Katharina; Kramer, Achim; Herzel, Hanspeter

    2018-01-01

    Body temperature rhythms synchronize circadian oscillations in different tissues, depending on the degree of cellular coupling: the responsiveness to temperature is higher when single circadian oscillators are uncoupled. So far, the role of coupling in temperature responsiveness has only been studied in organotypic tissue slices of the central circadian pacemaker, because it has been assumed that peripheral target organs behave like uncoupled multicellular oscillators. Since recent studies indicate that some peripheral tissues may exhibit cellular coupling as well, we asked whether peripheral network dynamics also influence temperature responsiveness. Using a novel technique for long-term, high-resolution bioluminescence imaging of primary cultured cells, exposed to repeated temperature cycles, we were able to quantitatively measure period, phase, and amplitude of central (suprachiasmatic nuclei neuron dispersals) and peripheral (mouse ear fibroblasts) single cell oscillations in response to temperature. Employing temperature cycles of different lengths, and different cell densities, we found that some circadian characteristics appear cell-autonomous, e.g. period responses, while others seem to depend on the quality/degree of cellular communication, e.g. phase relationships, robustness of the oscillation, and amplitude. Overall, our findings indicate a strong dependence on the cell's ability for intercellular communication, which is not only true for neuronal pacemakers, but, importantly, also for cells in peripheral tissues. Hence, they stress the importance of comparative studies that evaluate the degree of coupling in a given tissue, before it may be used effectively as a target for meaningful circadian manipulation.

  10. DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition.

    Science.gov (United States)

    Liu, Xiao; Dang, Yunkun; Matsu-Ura, Toru; He, Yubo; He, Qun; Hong, Christian I; Liu, Yi

    2017-07-20

    Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here, we show that DNA replication is required for circadian clock function in Neurospora. Genetic and pharmacological inhibition of DNA replication abolished both overt and molecular rhythmicities by repressing frequency (frq) gene transcription. DNA replication is essential for the rhythmic changes of nucleosome composition at the frq promoter. The FACT complex, known to be involved in histone disassembly/reassembly, is required for clock function and is recruited to the frq promoter in a replication-dependent manner to promote replacement of histone H2A.Z by H2A. Finally, deletion of H2A.Z uncoupled the dependence of the circadian clock on DNA replication. Together, these results establish circadian clock and cell cycle as interdependent coupled oscillators and identify DNA replication as a critical process in the circadian mechanism. Published by Elsevier Inc.

  11. Small heterodimer partner (NROB2) coordinates nutrient signaling and the circadian clock in mice

    Science.gov (United States)

    Circadian rhythm regulates multiple metabolic processes and in turn is readily entrained by feeding-fasting cycles. However, the molecular mechanisms by which the peripheral clock senses nutrition availability remain largely unknown. Bile acids are under circadian control and also increase postprand...

  12. Role of Uncoupling Proteins in Cancer

    International Nuclear Information System (INIS)

    Valle, Adamo; Oliver, Jordi; Roca, Pilar

    2010-01-01

    Uncoupling proteins (UCPs) are a family of inner mitochondrial membrane proteins whose function is to allow the re-entry of protons to the mitochondrial matrix, by dissipating the proton gradient and, subsequently, decreasing membrane potential and production of reactive oxygen species (ROS). Due to their pivotal role in the intersection between energy efficiency and oxidative stress, UCPs are being investigated for a potential role in cancer. In this review we compile the latest evidence showing a link between uncoupling and the carcinogenic process, paying special attention to their involvement in cancer initiation, progression and drug chemoresistance

  13. Role of Uncoupling Proteins in Cancer

    Directory of Open Access Journals (Sweden)

    Adamo Valle

    2010-04-01

    Full Text Available Uncoupling proteins (UCPs are a family of inner mitochondrial membrane proteins whose function is to allow the re-entry of protons to the mitochondrial matrix, by dissipating the proton gradient and, subsequently, decreasing membrane potential and production of reactive oxygen species (ROS. Due to their pivotal role in the intersection between energy efficiency and oxidative stress, UCPs are being investigated for a potential role in cancer. In this review we compile the latest evidence showing a link between uncoupling and the carcinogenic process, paying special attention to their involvement in cancer initiation, progression and drug chemoresistance.

  14. Neurobiology of circadian systems.

    Science.gov (United States)

    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

  15. Mitochondrial uncoupling proteins and energy metabolism

    Directory of Open Access Journals (Sweden)

    Rosa Anna Busiello

    2015-02-01

    Full Text Available Understanding the metabolic factors that contribute to energy metabolism (EM is critical for the development of new treatments for obesity and related diseases. Mitochondrial oxidative phosphorylation is not perfectly coupled to ATP synthesis, and the process of proton-leak plays a crucial role. Proton-leak accounts for a significant part of the resting metabolic rate and therefore enhancement of this process represents a potential target for obesity treatment. Since their discovery, uncoupling proteins have stimulated great interest due to their involvement in mitochondrial-inducible proton-leak. Despite the widely accepted uncoupling/thermogenic effect of uncoupling protein one (UCP1, which was the first in this family to be discovered, the reactions catalyzed by its homologue UCP3 and the physiological role remain under debate.This review provides an overview of the role played by UCP1 and UCP3 in mitochondrial uncoupling/functionality as well as EM and suggests that they are a potential therapeutic target for treating obesity and its related diseases such as type II diabetes mellitus.

  16. 30 CFR 56.14215 - Coupling or uncoupling cars.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at minimum...

  17. Certain aspects of uncoupling due to mitochondrial uncoupling proteins in vitro and in vivo

    Czech Academy of Sciences Publication Activity Database

    Dlasková, Andrea; Špaček, Tomáš; Škobisová, Eva; Šantorová, Jitka; Ježek, Petr

    2006-01-01

    Roč. 1757, č. 5-6 (2006), s. 467-473 ISSN 0005-2728 R&D Projects: GA MŠk(CZ) 1P05ME794; GA ČR(CZ) GA521/02/0183; GA AV ČR(CZ) IAA5011106 Institutional research plan: CEZ:AV0Z50110509 Keywords : fatty acid-induced uncoupling * uncoupling protein-1 * carnitine cycle Subject RIV: CE - Biochemistry Impact factor: 4.237, year: 2006

  18. Rhythms of mammalian body temperature can sustain peripheral circadian clocks.

    Science.gov (United States)

    Brown, Steven A; Zumbrunn, Gottlieb; Fleury-Olela, Fabienne; Preitner, Nicolas; Schibler, Ueli

    2002-09-17

    Low-amplitude temperature oscillations can entrain the phase of circadian rhythms in several unicellular and multicellular organisms, including Neurospora and Drosophila. Because mammalian body temperature is subject to circadian variations of 1 degrees C-4 degrees C, we wished to determine whether these temperature cycles could serve as a Zeitgeber for circadian gene expression in peripheral cell types. In RAT1 fibroblasts cultured in vitro, circadian gene expression could be established by a square wave temperature rhythm with a (Delta)T of 4 degrees C (12 hr 37 degrees C/12 hr 33 degrees C). To examine whether natural body temperature rhythms can also affect circadian gene expression, we first measured core body temperature cycles in the peritoneal cavities of mice by radiotelemetry. We then reproduced these rhythms with high precision in the liquid medium of cultured fibroblasts for several days by means of a homemade computer-driven incubator. While these "in vivo" temperature rhythms were incapable of establishing circadian gene expression de novo, they could maintain previously induced rhythms for multiple days; by contrast, the rhythms of control cells kept at constant temperature rapidly dampened. Moreover, circadian oscillations of environmental temperature could reentrain circadian clocks in the livers of mice, probably via the changes they imposed upon both body temperature and feeding behavior. Interestingly, these changes in ambient temperature did not affect the phase of the central circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. We postulate that both endogenous and environmental temperature cycles can participate in the synchronization of peripheral clocks in mammals.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. Development of the circadian clockwork in the kidney

    DEFF Research Database (Denmark)

    Mészáros, Krisztina; Pruess, Linda; Szabó, Attila J.

    2014-01-01

    was modified postpartum. Clock, Rev-erbα, Per2, αENaC, SGK1, NHE3, and AVPR2 showed circadian expression at the end of intrauterine development. By 1 week, all genes oscillated with a distinct acrophase shift toward the time of peak feeding activity. Daily 4-hour withdrawal of mothers induced a 12-hour phase...

  4. 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…

  5. 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.

  6. 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.

  7. A procedure for noise uncoupling in laser interferometry

    CERN Document Server

    Barone, F; Rosa, R D; Eleuteri, A; Milano, L; Qipiani, K

    2002-01-01

    A numerical procedure for noise recognition and uncoupling is described. The procedure is applied to a Michelson interferometer and is effective in seismic and acoustic noise uncoupling from the output signal of the interferometer. Due to the low data flow coming from the instrumentation this uncoupling can be performed in real time and it is useful as a data quality procedure for interferometer data output.

  8. Optimal parameters uncoupling vibration modes of oscillators

    Science.gov (United States)

    Le, K. C.; Pieper, A.

    2017-07-01

    This paper proposes a novel optimization concept for an oscillator with two degrees of freedom. By using specially defined motion ratios, we control the action of springs to each degree of freedom of the oscillator. We aim at showing that, if the potential action of the springs in one period of vibration, used as the payoff function for the conservative oscillator, is maximized among all admissible parameters and motions satisfying Lagrange's equations, then the optimal motion ratios uncouple vibration modes. A similar result holds true for the dissipative oscillator having dampers. The application to optimal design of vehicle suspension is discussed.

  9. Mitochondrial uncoupling proteins and phylogenesis - UCP4 as the ancestral uncoupling protein

    Czech Academy of Sciences Publication Activity Database

    Hanák, Petr; Ježek, Petr

    2001-01-01

    Roč. 495, č. 3 (2001), s. 137-141 ISSN 0014-5793 R&D Projects: GA ČR GA301/98/0568; GA AV ČR IAA5011106 Institutional research plan: CEZ:AV0Z5011922 Keywords : phylogenesis of mitochondrial uncoupling protein * specific sequence motif Subject RIV: CE - Biochemistry Impact factor: 3.644, year: 2001

  10. 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.

  11. 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.

  12. Metabolism as an Integral Cog in the Mammalian Circadian Clockwork

    Science.gov (United States)

    Gamble, Karen L.; Young, Martin E.

    2013-01-01

    Circadian rhythms are an integral part of life. These rhythms are apparent in virtually all biological processes studies to date, ranging from the individual cell (e.g., DNA synthesis) to the whole organism (e.g., behaviors such as physical activity). Oscillations in metabolism have been characterized extensively in various organisms, including mammals. These metabolic rhythms often parallel behaviors such as sleep/wake and fasting/feeding cycles that occur on a daily basis. What has become increasingly clear over the past several decades is that many metabolic oscillations are driven by cell autonomous circadian clocks, which orchestrate metabolic processes in a temporally appropriate manner. During the process of identifying the mechanisms by which clocks influence metabolism, molecular-based studies have revealed that metabolism should be considered an integral circadian clock component. The implications of such an interrelationship include the establishment of a vicious cycle during cardiometabolic disease states, wherein metabolism-induced perturbations in the circadian clock exacerbate metabolic dysfunction. The purpose of this review is therefore to highlight recent insights gained regarding links between cell autonomous circadian clocks and metabolism, and the implications of clock dysfunction in the pathogenesis of cardiometabolic diseases. PMID:23594144

  13. 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.

  14. Circadian rhythms and food anticipatory behavior in Wfs1-deficient mice

    DEFF Research Database (Denmark)

    Luuk, Hendrik; Fahrenkrug, Jan; Hannibal, Jens

    2012-01-01

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

  15. Emergence of noise-induced oscillations in the central circadian pacemaker.

    Directory of Open Access Journals (Sweden)

    Caroline H Ko

    2010-10-01

    Full Text Available Bmal1 is an essential transcriptional activator within the mammalian circadian clock. We report here that the suprachiasmatic nucleus (SCN of Bmal1-null mutant mice, unexpectedly, generates stochastic oscillations with periods that overlap the circadian range. Dissociated SCN neurons expressed fluctuating levels of PER2 detected by bioluminescence imaging but could not generate circadian oscillations intrinsically. Inhibition of intercellular communication or cyclic-AMP signaling in SCN slices, which provide a positive feed-forward signal to drive the intracellular negative feedback loop, abolished the stochastic oscillations. Propagation of this feed-forward signal between SCN neurons then promotes quasi-circadian oscillations that arise as an emergent property of the SCN network. Experimental analysis and mathematical modeling argue that both intercellular coupling and molecular noise are required for the stochastic rhythms, providing a novel biological example of noise-induced oscillations. The emergence of stochastic circadian oscillations from the SCN network in the absence of cell-autonomous circadian oscillatory function highlights a previously unrecognized level of circadian organization.

  16. 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.

  17. 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

  18. 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.

  19. Uncoupling proteins of invertebrates: A review.

    Science.gov (United States)

    Slocinska, Malgorzata; Barylski, Jakub; Jarmuszkiewicz, Wieslawa

    2016-09-01

    Uncoupling proteins (UCPs) mediate inducible proton conductance in the mitochondrial inner membrane. Herein, we summarize our knowledge regarding UCPs in invertebrates. Since 2001, the presence of UCPs has been demonstrated in nematodes, mollusks, amphioxi, and insects. We discuss the following important issues concerning invertebrate UCPs: their evolutionary relationships, molecular and functional properties, and physiological impact. Evolutionary analysis indicates that the branch of vertebrate and invertebrate UCP4-5 diverged early in the evolutionary process prior to the divergence of the animal groups. Several proposed physiological roles of invertebrate UCPs are energy control, metabolic balance, and preventive action against oxidative stress. © 2016 IUBMB Life, 68(9):691-699, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  20. Mitochondrial uncoupling proteins in unicellular eukaryotes.

    Science.gov (United States)

    Jarmuszkiewicz, Wieslawa; Woyda-Ploszczyca, Andrzej; Antos-Krzeminska, Nina; Sluse, Francis E

    2010-01-01

    Uncoupling proteins (UCPs) are members of the mitochondrial anion carrier protein family that are present in the mitochondrial inner membrane and mediate free fatty acid (FFA)-activated, purine nucleotide (PN)-inhibited proton conductance. Since 1999, the presence of UCPs has been demonstrated in some non-photosynthesising unicellular eukaryotes, including amoeboid and parasite protists, as well as in non-fermentative yeast and filamentous fungi. In the mitochondria of these organisms, UCP activity is revealed upon FFA-induced, PN-inhibited stimulation of resting respiration and a decrease in membrane potential, which are accompanied by a decrease in membranous ubiquinone (Q) reduction level. UCPs in unicellular eukaryotes are able to divert energy from oxidative phosphorylation and thus compete for a proton electrochemical gradient with ATP synthase. Our recent work indicates that membranous Q is a metabolic sensor that might utilise its redox state to release the PN inhibition of UCP-mediated mitochondrial uncoupling under conditions of phosphorylation and resting respiration. The action of reduced Q (QH2) could allow higher or complete activation of UCP. As this regulatory feature was demonstrated for microorganism UCPs (A. castellanii UCP), plant and mammalian UCP1 analogues, and UCP1 in brown adipose tissue, the process could involve all UCPs. Here, we discuss the functional connection and physiological role of UCP and alternative oxidase, two main energy-dissipating systems in the plant-type mitochondrial respiratory chain of unicellular eukaryotes, including the control of cellular energy balance as well as preventive action against the production of reactive oxygen species. Copyright © 2009 Elsevier B.V. All rights reserved.

  1. 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.

  2. 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.

  3. 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...

  4. 30 CFR 57.14215 - Coupling or uncoupling cars.

    Science.gov (United States)

    2010-07-01

    ... NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Machinery... uncoupling shall not be attempted from the inside of curves unless the railroad and cars are designed to...

  5. Conduction slowing by the gap junctional uncoupler carbenoxolone

    NARCIS (Netherlands)

    de Groot, [No Value; Veenstra, T; Verkerk, AO; Wilders, R; Smits, JPP; Wilms-Schopman, FJG; Wiegerinck, RF; Bourier, J; Belterman, CNW; Coronel, R; Verheijck, EE

    2003-01-01

    Background: Cellular electrical coupling is essential for normal propagation of the cardiac action potential, whereas reduced electrical coupling is associated with arrhythrmas. Known cellular uncoupling agents have severe side effects on membrane ionic currents. We investigated the effect of

  6. 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.

  7. Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

    Science.gov (United States)

    Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

    2015-04-01

    The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  8. 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.

  9. 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.

  10. Uncoupled thermoelasticity solutions applied on beam dumps

    Directory of Open Access Journals (Sweden)

    A. Ouzia

    2016-06-01

    Full Text Available In particle accelerators the process of beam absorption is vital. At CERN particle beams are accelerated at energies of the order of TeV. In the event of a system failure or following collisions, the beam needs to be safely absorbed by dedicated protecting blocks. The thermal shock caused by the rapid energy deposition within the absorbing block causes thermal stresses that may rise above critical levels. The present paper provides a convenient expression of such stresses under hypotheses described hereafter. The temperature field caused by the beam energy deposition is assumed to be Gaussian. Such a field models a non-diffusive heat deposition. These effects are described as thermoelastic as long as the stresses remain below the proportional limit and can be analytically modeled by the coupled equations of thermoelasticity. The analytical solution to the uncoupled thermoelastic problem in an infinite domain is presented herein and matched with a finite unit radius sphere. The assumption of zero diffusion as well as the validity of the match with a finite geometry is quantified such that the obtained solutions can be rigorously applied to real problems. Furthermore, truncated series solutions, which are not novel, are used for comparison purposes. All quantities are nondimensional and the problem reduces to a dependence of five dimensionless parameters. The equations of elasticity are presented in the potential formulation where the shear potential is assumed to be nil due to the source being a gradient and the absence of boundaries. Nevertheless equivalent three-dimensional stresses are computed using the compressive potential and optimized using standard analytical optimization methods. An alternative algorithm for finding the critical points of the three-dimensional stress function is presented. Finally, a case study concerning the proton synchrotron booster dump is presented where the aforementioned analytical solutions are used and the

  11. 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

  12. 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.

  13. 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...

  14. A brief history of circadian time: The emergence of redox oscillations as a novel component of biological rhythms

    OpenAIRE

    Wulund, Lisa; Reddy, Akhilesh B.

    2015-01-01

    Circadian rhythms are present in all living organisms. They organise processes such as gene transcription, mitosis, feeding, and rest at different times of day and night. These rhythms are orchestrated by a network of core ‘clock genes’ that are organised into transcription–translation feedback loops (TTFLs), producing oscillations with a period of approximately 24 h. The modern understanding of circadian timekeeping has revolved around the TTFL paradigm. Recently, however, this has been chal...

  15. Triclosan is a Mitochondrial Uncoupler in Live Zebrafish

    Science.gov (United States)

    Shim, Juyoung; Weatherly, Lisa M.; Luc, Richard H.; Dorman, Maxwell T.; Neilson, Andy; Ng, Ryan; Kim, Carol H.; Millard, Paul J.; Gosse, Julie A.

    2016-01-01

    Triclosan (TCS) is a synthetic antimicrobial agent used in many consumer goods at millimolar concentrations. As a result of exposure, TCS has been detected widely in humans. We have recently discovered that TCS is a proton ionophore mitochondrial uncoupler in multiple types of living cells. Here we present novel data indicating that TCS is also a mitochondrial uncoupler in a living organism: 24 hour post fertilization zebrafish embryos. These experiments were conducted using a Seahorse Bioscience XFe 96 Extracellular Flux Analyzer modified for bidirectional temperature control, using the XF96 spheroid plate to position and measure one zebrafish embryo per well. Using this method, following acute exposure to TCS, basal oxygen consumption rate (OCR) increases, without a decrease in survival or heartbeat rate. TCS also decreases ATP-linked respiration and spare respiratory capacity and increases proton leak: all indicators of mitochondrial uncoupling. Our data indicate, that TCS is a mitochondrial uncoupler in vivo, which should be taken into consideration when assessing the toxicity and/or pharmaceutical uses of TCS. This is the first example of usage of a Seahorse Extracellular Flux Analyzer to measure bioenergetic flux of a single zebrafish embryo per well in a 96 well assay format. The method developed in this study provides a high-throughput tool to identify previously-unknown mitochondrial uncouplers in a living organism. PMID:27111768

  16. Uncoupled and coupled analysis of a large HDR pipe

    International Nuclear Information System (INIS)

    Muller, W.C.

    1987-01-01

    The main differences are in the structural response. There is no clear tendency that a coupled calculation will result in lower amplitudes of the structural response, but it can be seen from the results that there is a typical difference between coupled and uncoupled analysis which increases with time. This increase is mainly due to the fact that in a coupled analysis the speed of sound of the fluid and the eigenmodes of the piping system structure are lower than in the uncoupled analysis. Coupled and uncoupled piping transient analyses show similar results for the fluiddynamic data. The differences are less than 10% and as long as the fluid is in the two phase domain they can almost be neglected

  17. Molecular cloning of amphioxus uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Kun [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Sun, Guoxun [Department of Hematology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001 (China); Lv, Zhiyuan; Wang, Chen [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Jiang, Xueyuan, E-mail: xueyuanjiang@yahoo.com.cn [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Li, Donghai, E-mail: lidonghai@gmail.com [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Zhang, Chenyu, E-mail: cyzhang@nju.edu.cn [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China)

    2010-10-01

    Research highlights: {yields} Invertebrates, for example amphioxus, do express uncoupling proteins. {yields} Both the sequence and the uncoupling activity of amphioxus UCP resemble UCP2. {yields} UCP1 is the only UCP that can form dimer on yeast mitochondria. -- Abstract: The present study describes the molecular cloning of a novel cDNA fragment from amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is highly homologous to human uncoupling proteins (UCP), this protein is therefore named amphioxus UCP. This amphioxus UCP shares more homology with and is phylogenetically more related to mammalian UCP2 as compared with UCP1. To further assess the functional similarity of amphioxus UCP to mammalian UCP1 and -2, the amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak, using pYES2 empty vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold, and the uncoupling activity was strongly inhibited by GDP, while UCP2 and amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7-fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus UCP was very similar to UCP2, but much different from UCP1. In conclusion, the amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles mammalian UCP2, but not UCP1.

  18. Molecular cloning of amphioxus uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system

    International Nuclear Information System (INIS)

    Chen, Kun; Sun, Guoxun; Lv, Zhiyuan; Wang, Chen; Jiang, Xueyuan; Li, Donghai; Zhang, Chenyu

    2010-01-01

    Research highlights: → Invertebrates, for example amphioxus, do express uncoupling proteins. → Both the sequence and the uncoupling activity of amphioxus UCP resemble UCP2. → UCP1 is the only UCP that can form dimer on yeast mitochondria. -- Abstract: The present study describes the molecular cloning of a novel cDNA fragment from amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is highly homologous to human uncoupling proteins (UCP), this protein is therefore named amphioxus UCP. This amphioxus UCP shares more homology with and is phylogenetically more related to mammalian UCP2 as compared with UCP1. To further assess the functional similarity of amphioxus UCP to mammalian UCP1 and -2, the amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak, using pYES2 empty vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold, and the uncoupling activity was strongly inhibited by GDP, while UCP2 and amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7-fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus UCP was very similar to UCP2, but much different from UCP1. In conclusion, the amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles mammalian UCP2, but not UCP1.

  19. 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.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Zhifeng Huang

    2017-08-01

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

  2. 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

  3. 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.

  4. 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.

  5. 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

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

    Science.gov (United States)

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

    2016-04-01

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

  7. Fetal alcohol exposure disrupts metabolic signaling in hypothalamic proopiomelanocortin neurons via a circadian mechanism in male mice.

    Science.gov (United States)

    Agapito, Maria A; Zhang, Changqing; Murugan, Sengottuvelan; Sarkar, Dipak K

    2014-07-01

    Early-life ethanol feeding (ELAF) alters the metabolic function of proopiomelanocortin (POMC)-producing neurons and the circadian expression of clock regulatory genes in the hypothalamus. We investigated whether the circadian mechanisms control the action of ELAF on metabolic signaling genes in POMC neurons. Gene expression measurements of Pomc and a selected group of metabolic signaling genes, Stat3, Sirt1, Pgc1-α, and Asb4 in laser-captured microdissected POMC neurons in the hypothalamus of POMC-enhanced green fluorescent protein mice showed circadian oscillations under light/dark and constant darkness conditions. Ethanol programmed these neurons such that the adult expression of Pomc, Stat3, Sirt, and Asb4 gene transcripts became arrhythmic. In addition, ELAF dampened the circadian peak of gene expression of Bmal1, Per1, and Per2 in POMC neurons. We crossed Per2 mutant mice with transgenic POMC-enhanced green fluorescent protein mice to determine the role of circadian mechanism in ELAF-altered metabolic signaling in POMC neurons. We found that ELAF failed to alter arrhythmic expression of most circadian genes, with the exception of the Bmal1 gene and metabolic signaling regulating genes in Per2 mutant mice. Comparison of the ELAF effects on the circadian blood glucose in wild-type and Per2 mutant mice revealed that ELAF dampened the circadian peak of glucose, whereas the Per2 mutation shifted the circadian cycle and prevented the ELAF dampening of the glucose peak. These data suggest the possibility that the Per2 gene mutation may regulate the ethanol actions on Pomc and the metabolic signaling genes in POMC neurons in the hypothalamus by blocking circadian mechanisms.

  8. Circadian changes in thyroid hormones of piau, Leporinus obtusidens Valenciennes, 1847 (Osteichthyes, Anostomidae after feeding = Variações circadianas dos hormônios tireoidianos de piau, Leporinus obtusidens Valenciennes, 1847 (Osteichthyes, Anostomidae após alimentação

    Directory of Open Access Journals (Sweden)

    Walter Dias Junior

    2009-10-01

    Full Text Available To evaluate circadian changes in thyroid hormones of piau, Leporinusobtusidens Valenciennes, 1847, (Osteichthyes, Anostomidae after feeding were determined the plasma levels of thyroid hormones (TH of 128 fishes, same age, immature, both sexes, distributed into four classes of weight. They were kept in 16 aquaria (100 L, with artificial aeration and 2 L min.-1 water flow, from March to August, 1996, in Aquaculture Station of the Universidade Federal de Lavras (UFLA. Daily, feed was supplied at 5% body weight. For blood samples, the fishes were anesthetized with benzocaine 10%, and plasmatic levels of TH were determined at 1, 4, 7, 10, 13, 16 and 22h after food supply during 4 consecutive days in June and in August, period of lowest temperature. The classes of weight 63, 75, 82and 91 g were considered homogeneous, showing that plasmatic concentrations of T3 and T4 were body weight independent for this fish species. The daily cycle of plasma TH were correlated with feed intake, reaching the highest levels 7 h after feeding supply (T3 = 1.75 ± 0.07 ng mL-1 and T4 = 14.9 ± 1.59 ng mL-1. It was also possible to verify that the daily intake is directly correlated with water temperature which is affected by day-light cycle.Para avaliar as variações circadianas dos hormônios tireoidianos do piau, Leporinus obtusidens Valenciennes, 1847, (Osteichthyes, Anostomidae após alimentação, foram determinados os níveis plasmáticos dos hormônios tireoidianos (HT T3 e T4 de 128 peixes, de mesma idade, imaturos, ambos os sexos, distribuídos em quatro classes de peso e mantidos em 16 aquários (100 L, com aeração artificial e fluxo constante de água de 2 L min.-1, de março a agosto de 1996, na Estação de Aquicultura da Universidade Federal de Lavras (UFLA. Diariamente, a ração foi fornecida a 5% do peso corporal. Nas pesagens e amostragens de sangue, os animais foram anestesiados com benzocaína a 10% e os níveis plasmáticos dos HT foram

  9. 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

  10. Class IIa histone deacetylases are conserved regulators of circadian function.

    Science.gov (United States)

    Fogg, Paul C M; O'Neill, John S; Dobrzycki, Tomasz; Calvert, Shaun; Lord, Emma C; McIntosh, Rebecca L L; Elliott, Christopher J H; Sweeney, Sean T; Hastings, Michael H; Chawla, Sangeeta

    2014-12-05

    Class IIa histone deacetylases (HDACs) regulate the activity of many transcription factors to influence liver gluconeogenesis and the development of specialized cells, including muscle, neurons, and lymphocytes. Here, we describe a conserved role for class IIa HDACs in sustaining robust circadian behavioral rhythms in Drosophila and cellular rhythms in mammalian cells. In mouse fibroblasts, overexpression of HDAC5 severely disrupts transcriptional rhythms of core clock genes. HDAC5 overexpression decreases BMAL1 acetylation on Lys-537 and pharmacological inhibition of class IIa HDACs increases BMAL1 acetylation. Furthermore, we observe cyclical nucleocytoplasmic shuttling of HDAC5 in mouse fibroblasts that is characteristically circadian. Mutation of the Drosophila homolog HDAC4 impairs locomotor activity rhythms of flies and decreases period mRNA levels. RNAi-mediated knockdown of HDAC4 in Drosophila clock cells also dampens circadian function. Given that the localization of class IIa HDACs is signal-regulated and influenced by Ca(2+) and cAMP signals, our findings offer a mechanism by which extracellular stimuli that generate these signals can feed into the molecular clock machinery. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Uncoupler resistance in E. coli Tuv and Cuv is due to the exclusion of uncoupler by the outer membrane

    DEFF Research Database (Denmark)

    Haworth, Robert S.; Jensen, Peter Ruhdal; Michelsen, Ole

    1990-01-01

    The uncoupler resistant bacterial strains E. coli Tuv and Cuv share the high deoxycholate sensitivity of the parent strain, Doc S. However, both Tuv and Cuv show greater resistance than Doc S to other detergents. Measurement of the periplasmic volume indicates that the outer membrane of Doc S is ...

  12. Uncoupling in Secondary Transport Proteins. A Mechanistic Explanation for Mutants of lac Permease with an Uncoupled Phenotype

    NARCIS (Netherlands)

    Lolkema, J.S.; Poolman, B.

    1995-01-01

    The kinetic behavior of a H+-substrate symporter has been studied in which in addition to the unloaded (E) and fully loaded states (E.S.H) of the carrier also one of the binary complexes (E.S or E.H) may reorient its binding sites. This results in two types of uncoupled mutants, the ES leak and the

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Aisling K Brady

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

  15. 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.

  16. 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.

  17. 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.

  18. Digital signal processing reveals circadian baseline oscillation in majority of mammalian genes.

    Directory of Open Access Journals (Sweden)

    Andrey A Ptitsyn

    2007-06-01

    Full Text Available In mammals, circadian periodicity has been described for gene expression in the hypothalamus and multiple peripheral tissues. It is accepted that 10%-15% of all genes oscillate in a daily rhythm, regulated by an intrinsic molecular clock. Statistical analyses of periodicity are limited by the small size of datasets and high levels of stochastic noise. Here, we propose a new approach applying digital signal processing algorithms separately to each group of genes oscillating in the same phase. Combined with the statistical tests for periodicity, this method identifies circadian baseline oscillation in almost 100% of all expressed genes. Consequently, circadian oscillation in gene expression should be evaluated in any study related to biological pathways. Changes in gene expression caused by mutations or regulation of environmental factors (such as photic stimuli or feeding should be considered in the context of changes in the amplitude and phase of genetic oscillations.

  19. 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.

  20. 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

  1. 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

  2. Arsenate uncoupling of oxidative phosphorylation in isolated plant mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Wickes, W A; Wiskich, J T

    1976-01-01

    The uncoupling by arsenate of beetroot and cauliflower bud mitochondria showed the following characteristics: arsenate stimulation of respiration above the rate found with phosphate; inhibition of arsenate-stimulated respiration by phosphate; enhancement of arsenate-stimulated respiration by ADP; only partial prevention of this ADP-enhanced respiration by atractyloside; inhibition by oligomycin of the arsenate-stimulated respiration back to the phosphate rate; and the absence of any stimulatory effect of ADP in the presence of oligomycin. These results are qualitatively analogous to those reported for arsenate uncoupling in rat liver mitochondria. Arsenate stimulated malate oxidation, presumably by stimulating malate entry, in both beetroot and cauliflower bud mitochondria; however, high rates of oxidation, and presumably entry, were only sustained with arsenate in beetroot mitochondria. NADH was oxidized rapidly in cauliflower bud mitochondria in the presence of arsenate, showing that arsenate did not inhibit electron transfer processes.

  3. Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression

    DEFF Research Database (Denmark)

    Dhamrait, Sukhbir S.; Maubaret, Cecilia; Pedersen-bjergaard, Ulrik

    2016-01-01

    Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin–angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial...... amongst UCP3-55C (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P 

  4. Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression

    DEFF Research Database (Denmark)

    Dhamrait, Sukhbir S.; Maubaret, Cecilia; Pedersen-Bjergaard, Ulrik

    2016-01-01

    Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial...... amongst UCP3-55C (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P 

  5. Possible physiological roles of mitochondrial uncoupling proteins-UCPn

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr

    2002-01-01

    Roč. 34, č. 10 (2002), s. 1190-1206 ISSN 1357-2725 R&D Projects: GA AV ČR IAA5011106; GA ČR GA301/02/1215; GA MŠk ME 389 Institutional research plan: CEZ:AV0Z5011922 Keywords : uncoupling proteins * diabetes * obesity Subject RIV: ED - Physiology Impact factor: 3.044, year: 2002

  6. eNOS-uncoupling in age-related erectile dysfunction

    OpenAIRE

    Johnson, JM; Bivalacqua, TJ; Lagoda, GA; Burnett, AL; Musicki, B

    2011-01-01

    Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ...

  7. Intrinsic uncoupling of mitochondrial proton pumps. 2. Modeling studies.

    Science.gov (United States)

    Pietrobon, D; Zoratti, M; Azzone, G F; Caplan, S R

    1986-02-25

    The thermodynamic and kinetic properties associated with intrinsic uncoupling in a six-state model of a redox proton pump have been studied by computing the flow-force relations for different degrees of coupling. Analysis of these relations shows the regulatory influence of the thermodynamic forces on the extent and relative contributions of redox slip and proton slip. Inhibition has been introduced into the model in two different ways, corresponding to possible modes of action of experimental inhibitors. Experiments relating the rate of electron transfer to delta microH at static head upon progressive inhibition of the pumps have been simulated considering (1) the limiting case that the nonzero rate of electron transfer at static head is only due to intrinsic uncoupling (no leaks) and (2) the experimentally observed case that about 30% of the nonzero rate of electron transfer at static head is due to a constant proton leakage conductance in parallel with the pumps, the rest being due to intrinsic uncoupling. The same simulations have been performed for experiments in which the rate of electron transfer is varied by varying the substrate concentration rather than by using an inhibitor. The corresponding experimental results obtained by measuring delta microH and the rate of electron transfer at different succinate concentrations in rat liver mitochondria are presented. Comparison between simulated behavior and experimental results leads to the general conclusion that the typical relationship between rate of electron transfer and delta microH found in mitochondria at static head could certainly be a manifestation of some degree of intrinsic uncoupling in the redox proton pumps.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Mitochondrial Complex I superoxide production is attenuated by uncoupling

    Czech Academy of Sciences Publication Activity Database

    Dlasková, Andrea; Hlavatá, Lydie; Ježek, Jan; Ježek, Petr

    2008-01-01

    Roč. 40, č. 10 (2008), s. 2098-2109 ISSN 1357-2725 R&D Projects: GA ČR GP303/05/P100; GA AV ČR IAA500110701; GA MŠk(CZ) 1P05ME794 Institutional research plan: CEZ:AV0Z50110509 Keywords : mitochondrial H2O2 production * mitochondrial Complex I proton pumping * uncoupling Subject RIV: CE - Biochemistry Impact factor: 4.178, year: 2008

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

    Science.gov (United States)

    Chagoya de Sánchez, V

    1995-03-01

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

  10. Use the Protonmotive Force: Mitochondrial Uncoupling and Reactive Oxygen Species.

    Science.gov (United States)

    Berry, Brandon J; Trewin, Adam J; Amitrano, Andrea M; Kim, Minsoo; Wojtovich, Andrew P

    2018-04-04

    Mitochondrial respiration results in an electrochemical proton gradient, or protonmotive force (pmf), across the mitochondrial inner membrane. The pmf is a form of potential energy consisting of charge (∆ψ m ) and chemical (∆pH) components, that together drive ATP production. In a process called uncoupling, proton leak into the mitochondrial matrix independent of ATP production dissipates the pmf and energy is lost as heat. Other events can directly dissipate the pmf independent of ATP production as well, such as chemical exposure or mechanisms involving regulated mitochondrial membrane electrolyte transport. Uncoupling has defined roles in metabolic plasticity and can be linked through signal transduction to physiologic events. In the latter case, the pmf impacts mitochondrial reactive oxygen species (ROS) production. Although capable of molecular damage, ROS also have signaling properties that depend on the timing, location, and quantity of their production. In this review, we provide a general overview of mitochondrial ROS production, mechanisms of uncoupling, and how these work in tandem to affect physiology and pathologies, including obesity, cardiovascular disease, and immunity. Overall, we highlight that isolated bioenergetic models-mitochondria and cells-only partially recapitulate the complex link between the pmf and ROS signaling that occurs in vivo. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Uncoupling of Vascular Nitric Oxide Synthase Caused by Intermittent Hypoxia

    Directory of Open Access Journals (Sweden)

    Mohammad Badran

    2016-01-01

    Full Text Available Objective. Obstructive sleep apnea (OSA, characterized by chronic intermittent hypoxia (CIH, is often present in diabetic (DB patients. Both conditions are associated with endothelial dysfunction and cardiovascular disease. We hypothesized that diabetic endothelial dysfunction is further compromised by CIH. Methods. Adult male diabetic (BKS.Cg-Dock7m +/+ Leprdb/J (db/db mice (10 weeks old and their heterozygote littermates were subjected to CIH or intermittent air (IA for 8 weeks. Mice were separated into 4 groups: IA (intermittent air nondiabetic, IH (intermittent hypoxia nondiabetic, IADB (intermittent air diabetic, and IHDB (intermittent hypoxia diabetic groups. Endothelium-dependent and endothelium-independent relaxation and modulation by basal nitric oxide (NO were analyzed using wire myograph. Plasma 8-isoprostane, interleukin-6 (IL-6, and asymmetric dimethylarginine (ADMA were measured using ELISA. Uncoupling of eNOS was measured using dihydroethidium (DHE staining. Results. Endothelium-dependent vasodilation and basal NO production were significantly impaired in the IH and IADB group compared to IA group but was more pronounced in IHDB group. Levels of 8-isoprostane, IL-6, ADMA, and eNOS uncoupling were ≈2-fold higher in IH and IADB groups and were further increased in the IHDB group. Conclusion. Endothelial dysfunction is more pronounced in diabetic mice subjected to CIH compared to diabetic or CIH mice alone. Oxidative stress, ADMA, and eNOS uncoupling were exacerbated by CIH in diabetic mice.

  12. 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 ...

  13. Hierarchical organization of the circadian timing system

    NARCIS (Netherlands)

    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

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Naoto Hayasaka

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

  16. [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

  17. 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.

  18. Robustness from flexibility in the fungal circadian clock

    Directory of Open Access Journals (Sweden)

    Akman Ozgur E

    2010-06-01

    Full Text Available Abstract Background Robustness is a central property of living systems, enabling function to be maintained against environmental perturbations. A key challenge is to identify the structures in biological circuits that confer system-level properties such as robustness. Circadian clocks allow organisms to adapt to the predictable changes of the 24-hour day/night cycle by generating endogenous rhythms that can be entrained to the external cycle. In all organisms, the clock circuits typically comprise multiple interlocked feedback loops controlling the rhythmic expression of key genes. Previously, we showed that such architectures increase the flexibility of the clock's rhythmic behaviour. We now test the relationship between flexibility and robustness, using a mathematical model of the circuit controlling conidiation in the fungus Neurospora crassa. Results The circuit modelled in this work consists of a central negative feedback loop, in which the frequency (frq gene inhibits its transcriptional activator white collar-1 (wc-1, interlocked with a positive feedback loop in which FRQ protein upregulates WC-1 production. Importantly, our model reproduces the observed entrainment of this circuit under light/dark cycles with varying photoperiod and cycle duration. Our simulations show that whilst the level of frq mRNA is driven directly by the light input, the falling phase of FRQ protein, a molecular correlate of conidiation, maintains a constant phase that is uncoupled from the times of dawn and dusk. The model predicts the behaviour of mutants that uncouple WC-1 production from FRQ's positive feedback, and shows that the positive loop enhances the buffering of conidiation phase against seasonal photoperiod changes. This property is quantified using Kitano's measure for the overall robustness of a regulated system output. Further analysis demonstrates that this functional robustness is a consequence of the greater evolutionary flexibility conferred on

  19. 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.

  20. Circadian Rhythms, Sleep Deprivation, and Human Performance

    Science.gov (United States)

    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

  1. 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.

  2. Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fas(Ipr) mice.

    Science.gov (United States)

    Lechner, O; Dietrich, H; Oliveira dos Santos, A; Wiegers, G J; Schwarz, S; Harbutz, M; Herold, M; Wick, G

    2000-06-01

    The immune system interacts with the hypothalamo-pituitary-adrenal axis via so-called glucocorticoid increasing factors, which are produced by the immune system during immune reactions, causing an elevation of systemic glucocorticoid levels that contribute to preservation of the immune reactions specificities. Previous results from our laboratory had already shown an altered immuno-neuroendocrine dialogue via the hypothalamo-pituitary-adrenal axis in autoimmune disease-prone chicken and mouse strains. In the present study, we further investigated the altered glucocorticoid response via the hypothalamo-pituitary-adrenal axis in murine lupus. We established the circadian rhythms of corticosterone, dehydroepiandrosterone-sulfate, adrenocorticotropic hormone and melatonin, as well as the time response curves after injection of interleukin-1 of the first three parameters in normal SWISS and lupus-prone MRL/MP-fas(Ipr) mice. The results show that lupus-prone MRL/ MP-fas(Ipr) mice do not react appropriately to changes of the light/dark cycle, circadian melatonin rhythms seem to uncouple from the light/dark cycle, and plasma corticosterone levels are elevated during the resting phase. Diurnal changes of dehydroepiandrosterone-sulfate and adrenocorticotropic hormone were normal compared to healthy controls. These data indicate that MRL/ MP-fas(Ipr) mice not only show an altered glucocorticoid response mediated via the hypothalamo pituitary adrenal axis to IL-1, but are also affected by disturbances of corticosterone and melatonin circadian rhythms. Our findings may have implications for intrathymic T cell development and the emergence of autoimmune disease.

  3. Recruitment of mitochondrial uncoupling protein UCP2 after lipopolysaccharide induction

    Czech Academy of Sciences Publication Activity Database

    Růžička, Michal; Škobisová, Eva; Dlasková, Andrea; Šantorová, Jitka; Smolková, Katarína; Špaček, Tomáš; Žáčková, Markéta; Modrianský, M.; Ježek, Petr

    2005-01-01

    Roč. 37, č. 4 (2005), s. 809-821 ISSN 1357-2725 R&D Projects: GA ČR(CZ) GA301/02/1215; GA ČR(CZ) GP301/01/P084; GA AV ČR(CZ) IAA5011106 Grant - others:NIH(US) TW01487 Institutional research plan: CEZ:AV0Z5011922 Keywords : lipopolysaccharide * oxidative stress in liver * mitochondrial uncoupling protein UCP2 Subject RIV: CE - Biochemistry Impact factor: 3.871, year: 2005

  4. Scheduled meals and scheduled palatable snacks synchronize circadian rhythms: consequences for ingestive behavior.

    Science.gov (United States)

    Escobar, Carolina; Salgado, Roberto; Rodriguez, Katia; Blancas Vázquez, Aurea Susana; Angeles-Castellanos, Manuel; Buijs, Ruud M

    2011-09-26

    Food is a potent time signal for the circadian system and has shown to entrain and override temporal signals transmitted by the biological clock, the suprachiasmatic nucleus, which adjusts mainly to the daily light/dark (LD) alternation. Organisms mostly ingest food in their active period and this permits a correct coordination between the LD and the food elicited time signals with the circadian system. Under conditions when feeding opportunities are shifted to the usual resting/sleep phase, the potent entraining force of food, shifts circadian fluctuations in several tissues, organs, and brain structures toward meal time, resulting a desynchrony within the body and between the organism and the external LD cycle. The daily scheduled access to a palatable snack exerts similar changes specifically to brain areas involved in motivation and reward responses. This review describes the phenomenology of food entrainment and entrainment by a palatable snack. It suggests how scheduled feeding can lead to food addiction and how shifted feeding schedules toward the sleep phase can result in altered ingestive behavior, obesity and disturbed metabolic responses. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. 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.

  6. 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...

  7. Circadian Rhythm Management System, Phase I

    Data.gov (United States)

    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...

  8. 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...

  9. 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...

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. Modelling of the protonophoric uncoupling by phenoxyacetic acid of the plasma membrane of Penicillium chrysogenum

    DEFF Research Database (Denmark)

    Henriksen, Claus Maxel; Nielsen, Jens Bredal; Villadsen, John

    1998-01-01

    negligible influence on the growth energetics due to protonophoric uncoupling of membrane potentials by passive diffusive uptake. On the other hand, when the extracellular pH is lowered to 5.00, a severe maintenance-related uncoupling effect of phenoxyacetic acid is calculated. These findings were confirmed...

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

    Directory of Open Access Journals (Sweden)

    Erika Navarrete

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

  16. 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

  17. Diurnal activity patterns of farm mink (Mustela vison) subjected to different feeding routines

    DEFF Research Database (Denmark)

    Hansen, Steffen W; Møller, Steen H

    2008-01-01

    synchronize their daily activity rhythm to the expected time of feeding. In addition, a high feeding motivation appears to be a precondition for circadian anticipatory activity in mink whereas anticipatory activity of mink fed ad libitum or close to ad libitum may be provoked by stimuli from the actual...

  18. Potential roles for uncoupling proteins in HIV lipodystrophy.

    Science.gov (United States)

    Nolan, David; Pace, Craig

    2004-07-01

    The 'HIV lipodystrophy syndrome' consists of several distinct components, including lipoatrophy (pathological subcutaneous fat loss), lipohypertrophy (abdominal/visceral adiposity), and metabolic complications including insulin resistance and dyslipidemia. Lipoatrophy appears to represent an adipose tissue-specific form of mitochondrial toxicity associated strongly with stavudine NRTI therapy, whilst the 'metabolic syndrome' phenotype is associated with HIV protease inhibitor therapy. In this context, the role of uncoupling proteins (UCPs) in modulating resting energy expenditure in response to elevated fatty acid flux associated with the 'metabolic syndrome' is supported by clinical data as well as findings of elevated adipose tissue UCP expression. The role of UCPs in this syndrome therefore exemplifies the multifactorial nature of these antiretroviral therapy complications.

  19. Astrocyte uncoupling as a cause of human temporal lobe epilepsy.

    Science.gov (United States)

    Bedner, Peter; Dupper, Alexander; Hüttmann, Kerstin; Müller, Julia; Herde, Michel K; Dublin, Pavel; Deshpande, Tushar; Schramm, Johannes; Häussler, Ute; Haas, Carola A; Henneberger, Christian; Theis, Martin; Steinhäuser, Christian

    2015-05-01

    Glial cells are now recognized as active communication partners in the central nervous system, and this new perspective has rekindled the question of their role in pathology. In the present study we analysed functional properties of astrocytes in hippocampal specimens from patients with mesial temporal lobe epilepsy without (n = 44) and with sclerosis (n = 75) combining patch clamp recording, K(+) concentration analysis, electroencephalography/video-monitoring, and fate mapping analysis. We found that the hippocampus of patients with mesial temporal lobe epilepsy with sclerosis is completely devoid of bona fide astrocytes and gap junction coupling, whereas coupled astrocytes were abundantly present in non-sclerotic specimens. To decide whether these glial changes represent cause or effect of mesial temporal lobe epilepsy with sclerosis, we developed a mouse model that reproduced key features of human mesial temporal lobe epilepsy with sclerosis. In this model, uncoupling impaired K(+) buffering and temporally preceded apoptotic neuronal death and the generation of spontaneous seizures. Uncoupling was induced through intraperitoneal injection of lipopolysaccharide, prevented in Toll-like receptor4 knockout mice and reproduced in situ through acute cytokine or lipopolysaccharide incubation. Fate mapping confirmed that in the course of mesial temporal lobe epilepsy with sclerosis, astrocytes acquire an atypical functional phenotype and lose coupling. These data suggest that astrocyte dysfunction might be a prime cause of mesial temporal lobe epilepsy with sclerosis and identify novel targets for anti-epileptogenic therapeutic intervention. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. 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.

  1. Feeding Tubes

    Science.gov (United States)

    ... feeding therapies have been exhausted. Please review product brand and method of placement carefully with your physician ... Total Parenteral Nutrition. Resources: Oley Foundation Feeding Tube Awareness Foundation Children’s Medical Nutrition Alliance APFED’s Educational Webinar ...

  2. 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.

  3. 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...

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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...

  10. 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

  11. 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....

  12. 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.

  13. Kinetics of oxygen uncoupling of a copper based oxygen carrier

    International Nuclear Information System (INIS)

    Hu, Wenting; Donat, Felix; Scott, S.A.; Dennis, J.S.

    2016-01-01

    Highlights: • The kinetics of a Cu-based oxygen carrier was determined using a TGA. • A diffusion model was applied to remove mass transfer effects from rate parameters. • Thermodynamics are separated from kinetics, usually difficult for the CLOU reaction. • The rate parameters correctly described the behaviour in a fluidised bed. • The rate parameters can be used to predict performance of large CLOU systems. - Abstract: Here, an oxygen carrier consisting of 60 wt% CuO supported on a mixture of Al_2O_3 and CaO (23 wt% and 17 wt% respectively) was synthesised by wet-mixing powdered CuO, Al(OH)_3 and Ca(OH)_2, followed by calcination at 1000 °C. Its suitability for chemical looping with oxygen uncoupling (CLOU) was investigated. After 25 repeated redox cycles in either a thermogravimetric analyser (TGA) or a laboratory-scale fluidised bed, (with 5 vol% H_2 in N_2 as the fuel, and air as the oxidant) no significant change in either the oxygen uncoupling capacity or the overall oxygen availability of the carrier was found. In the TGA, it was found that the rate of oxygen release from the material was controlled by intrinsic chemical kinetics and external transfer of mass from the surface of the particles to the bulk gas. By modelling the various resistances, values of the rate constant for the decomposition were obtained. The activation energy of the reaction was found to be 59.7 kJ/mol (with a standard error of 5.6 kJ/mol) and the corresponding pre-exponential factor was 632 m"3/mol/s. The local rate of conversion within a particle was assumed to occur either (i) by homogeneous chemical reaction, or (ii) in uniform, non-porous grains, each reacting as a kinetically-controlled shrinking core. Upon cross validation against a batch fluidised bed experiment, the homogeneous reaction model was found to be more plausible. By accurately accounting for the various artefacts (e.g. mass transfer resistances) present in both TGA and fluidised bed experiments, it was

  14. 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.

  15. Expression of uncoupling protein 1 in bovine muscle cells.

    Science.gov (United States)

    Abd Eldaim, M A; Hashimoto, O; Ohtsuki, H; Yamada, T; Murakami, M; Onda, K; Sato, R; Kanamori, Y; Qiao, Y; Tomonaga, S; Matsui, T; Funaba, M

    2016-12-01

    Uncoupling protein 1 (Ucp1) is predominantly expressed in brown/beige adipocytes in mammals. Although myogenic cells have been suggested to commit to a brown adipocyte lineage through the induction of Prdm16 expression, Prdm16 is also expressed in skeletal muscle. Thus, we examined expression of Ucp1 in bovine myogenic cells. Considering that Ucp1 is a principle molecule that induces energy expenditure in brown/beige adipocytes, expression of Ucp1 is not preferable in beef cattle because of potential decrease in energy (fattening) efficiency. The RT-PCR analyses revealed the expression of Ucp1 in the skeletal muscle of cattle; expression levels were markedly lower than those in the brown fat of calves. Immunohistochemical analyses showed that Ucp1 surrounded muscle fibers, but not adipocytes residing in skeletal muscle. Myosatellite cells cultured in myogenic medium showed an increase in the expression levels of myogenic regulatory factors ( levels were greater in cells after myogenic culture for 12 d than in those after myogenic culture for 6 d ( bovine skeletal muscle, which suggests the necessity for further studies on Ucp1-mediated energy expenditure in bovine skeletal muscle.

  16. Stochastic calculus for uncoupled continuous-time random walks.

    Science.gov (United States)

    Germano, Guido; Politi, Mauro; Scalas, Enrico; Schilling, René L

    2009-06-01

    The continuous-time random walk (CTRW) is a pure-jump stochastic process with several applications not only in physics but also in insurance, finance, and economics. A definition is given for a class of stochastic integrals driven by a CTRW, which includes the Itō and Stratonovich cases. An uncoupled CTRW with zero-mean jumps is a martingale. It is proved that, as a consequence of the martingale transform theorem, if the CTRW is a martingale, the Itō integral is a martingale too. It is shown how the definition of the stochastic integrals can be used to easily compute them by Monte Carlo simulation. The relations between a CTRW, its quadratic variation, its Stratonovich integral, and its Itō integral are highlighted by numerical calculations when the jumps in space of the CTRW have a symmetric Lévy alpha -stable distribution and its waiting times have a one-parameter Mittag-Leffler distribution. Remarkably, these distributions have fat tails and an unbounded quadratic variation. In the diffusive limit of vanishing scale parameters, the probability density of this kind of CTRW satisfies the space-time fractional diffusion equation (FDE) or more in general the fractional Fokker-Planck equation, which generalizes the standard diffusion equation, solved by the probability density of the Wiener process, and thus provides a phenomenologic model of anomalous diffusion. We also provide an analytic expression for the quadratic variation of the stochastic process described by the FDE and check it by Monte Carlo.

  17. A SNP uncoupling Mina expression from the TGFβ signaling pathway.

    Science.gov (United States)

    Lian, Shang L; Mihi, Belgacem; Koyanagi, Madoka; Nakayama, Toshinori; Bix, Mark

    2018-03-01

    Mina is a JmjC family 2-oxoglutarate oxygenase with pleiotropic roles in cell proliferation, cancer, T cell differentiation, pulmonary inflammation, and intestinal parasite expulsion. Although Mina expression varies according to cell-type, developmental stage and activation state, its transcriptional regulation is poorly understood. Across inbred mouse strains, Mina protein level exhibits a bimodal distribution, correlating with inheritance of a biallelic haplotype block comprising 21 promoter/intron 1-region SNPs. We previously showed that heritable differences in Mina protein level are transcriptionally regulated. Accordingly, we decided to test the hypothesis that at least one of the promoter/intron 1-region SNPs perturbs a Mina cis-regulatory element (CRE). Here, we have comprehensively scanned for CREs across a Mina locus-spanning 26-kilobase genomic interval. We discovered 8 potential CREs and functionally validated 4 of these, the strongest of which (E2), residing in intron 1, contained a SNP whose BALB/c-but not C57Bl/6 allele-abolished both Smad3 binding and transforming growth factor beta (TGFβ) responsiveness. Our results demonstrate the TGFβ signaling pathway plays a critical role in regulating Mina expression and SNP rs4191790 controls heritable variation in Mina expression level, raising important questions regarding the evolution of an allele that uncouples Mina expression from the TGFβ signaling pathway. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

  18. Use of source term uncoupled in radionuclide migration equations

    International Nuclear Information System (INIS)

    Silveira, Claudia Siqueira da; Lima, Zelmo Rodrigues de; Alvim, Antonio Carlos Marques

    2008-01-01

    Final repositories of high-level radioactive waste have been considered in deep, low permeability and stable geological formations. A common problem found is the migration modeling of radionuclides in a fractured rock. In this work, the physical system adopted consists of the rock matrix containing a single planar fracture situated in water saturated porous rock. The partial differential equations that describe the radionuclide transport were discretized using finite differences techniques, of which the following methods were adopted: Explicit Euler, Implicit Euler and Crank-Nicholson. For each one of these methods, the advective term was discretized with the following numerical schemes: backward differences, centered differences and forward differences. We make a comparison to determine which temporal and space discretization has the best result in relation to a reference solution. The obtained results show that the Explicit Euler Method with forward discretization in the advective term has a good accuracy. Next, with the objective of improving the answer of the Implicit Euler and Crank-Nicholson Methods it was accomplished a source term uncouplement, the diffusive flux. The obtained results were considered satisfactory by comparison with previous studies. (author)

  19. Circadian systems biology: When time matters

    Directory of Open Access Journals (Sweden)

    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.

  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. Measuring Relative Coupling Strength in Circadian Systems.

    Science.gov (United States)

    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.

  2. 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

  3. 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...

  4. 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)

  5. 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.

  6. 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

  7. 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...

  8. Degradation of brown adipocyte purine nucleotides regulates uncoupling protein 1 activity

    Directory of Open Access Journals (Sweden)

    Tobias Fromme

    2018-02-01

    Full Text Available Objective: Non-shivering thermogenesis in mammalian brown adipose tissue depends on thermogenic uncoupling protein 1. Its activity is triggered by free fatty acids while purine nucleotides mediate inhibition. During activation, it is thought that free fatty acids overcome purine-mediated inhibition. We measured the cellular concentration and the release of purine nucleotide metabolites to uncover a possible role of purine nucleotide degradation in uncoupling protein 1 activation. Methods: With mass spectrometry, purine nucleotide metabolites were quantified in cellular homogenates and supernatants of cultured primary brown adipocytes. We also determined oxygen consumption in response to a β-adrenergic agonist. Results: Upon adrenergic activation, brown adipocytes decreased the intracellular concentration of inhibitory nucleotides (ATP, ADP, GTP and GDP and released the respective degradation products. At the same time, an increase in cellular calcium occurred. None of these phenomena occurred in white adipocytes or myotubes. The brown adipocyte expression of enzymes implicated in purine metabolic remodeling is altered upon cold exposure. Pharmacological and genetic interference of purine metabolism altered uncoupling protein 1 mediated uncoupled respiration. Conclusion: Adrenergic stimulation of brown adipocytes lowers the intracellular concentration of purine nucleotides, thereby contributing to uncoupling protein 1 activation. Keywords: Purine nucleotides, Uncoupling protein 1, Brown adipose tissue, Non-shivering thermogenesis, HILIC-MS/MS, Guanosine monophosphate reductase

  9. 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

  10. Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus

    Directory of Open Access Journals (Sweden)

    Jinmi Koo

    2015-09-01

    Full Text Available BackgroundIn mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN. Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions.MethodsWe examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2 gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC knock-in mice using a real-time bioluminescence measurement system.ResultsAdministration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms.ConclusionThese findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

  11. Light and the human circadian clock.

    Science.gov (United States)

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

    2013-01-01

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

  12. Relative metabolic stability, but disrupted circadian cortisol secretion during the fasting month of Ramadan.

    Directory of Open Access Journals (Sweden)

    Suhad Bahijri

    Full Text Available BACKGROUND: Chronic feeding and sleep schedule disturbances are stressors that exert damaging effects on the organism. Practicing Muslims in Saudi Arabia go through strict Ramadan fasting from dawn till sunset for one month yearly. Modern era Ramadan practices in Saudi Arabia are associated with disturbed feeding and sleep patterns, namely abstaining from food and water and increasing daytime sleep, and staying awake and receiving food and water till dawn. HYPOTHESIS: Strict Ramadan practices in Saudi Arabia may influence metabolism, sleep and circadian cortisol secretion. PROTOCOL: Young, male Ramadan practitioners were evaluated before and two weeks into the Ramadan. Blood samples were collected at 9.00 am and 9.00 pm for measurements of metabolic parameters and cortisol. Saliva was collected serially during the day for cortisol determinations. RESULTS: Ramadan practitioners had relative metabolic stability or changes expected by the pattern of feeding. However, the cortisol circadian rhythm was abolished and circulating insulin levels and HOMA index were increased during this period. DISCUSSION: The flattening of the cortisol rhythm is typical of conditions associated with chronic stress or endogenous hypercortisolism and associated with insulin resistance. CONCLUSIONS: Modern Ramadan practices in Saudi Arabia are associated with evening hypercortisolism and increased insulin resistance. These changes might contribute to the high prevalence of chronic stress-related conditions, such as central obesity, hypertension, metabolic syndrome and diabetes mellitus type 2, and their cardiovascular sequelae observed in the Kingdom.

  13. 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.

  14. 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.

  15. Alkylsulfonates as probes of uncoupling protein transport mechanism. Ion pair transport demonstrates that direct H(+) translocation by UCP1 is not necessary for uncoupling

    Czech Academy of Sciences Publication Activity Database

    Jabůrek, M.; Vařecha, M.; Ježek, Petr; Garlid, K. D.

    2001-01-01

    Roč. 276, č. 34 (2001), s. 31897-31905 ISSN 0021-9258 R&D Projects: GA AV ČR IAA5011106 Grant - others:NIH(US) DK56273 Institutional research plan: CEZ:AV0Z5011922 Keywords : mitochondrial uncoupling proteins * alkylsulfonates * ion pair transport Subject RIV: CE - Biochemistry Impact factor: 7.258, year: 2001

  16. Ca2+-induced uncoupling of Aplysia bag cell neurons.

    Science.gov (United States)

    Dargaei, Zahra; Standage, Dominic; Groten, Christopher J; Blohm, Gunnar; Magoski, Neil S

    2015-02-01

    Electrical transmission is a dynamically regulated form of communication and key to synchronizing neuronal activity. The bag cell neurons of Aplysia are a group of electrically coupled neuroendocrine cells that initiate ovulation by secreting egg-laying hormone during a prolonged period of synchronous firing called the afterdischarge. Accompanying the afterdischarge is an increase in intracellular Ca2+ and the activation of protein kinase C (PKC). We used whole cell recording from paired cultured bag cell neurons to demonstrate that electrical coupling is regulated by both Ca2+ and PKC. Elevating Ca2+ with a train of voltage steps, mimicking the onset of the afterdischarge, decreased junctional current for up to 30 min. Inhibition was most effective when Ca2+ entry occurred in both neurons. Depletion of Ca2+ from the mitochondria, but not the endoplasmic reticulum, also attenuated the electrical synapse. Buffering Ca2+ with high intracellular EGTA or inhibiting calmodulin kinase prevented uncoupling. Furthermore, activating PKC produced a small but clear decrease in junctional current, while triggering both Ca2+ influx and PKC inhibited the electrical synapse to a greater extent than Ca2+ alone. Finally, the amplitude and time course of the postsynaptic electrotonic response were attenuated after Ca2+ influx. A mathematical model of electrically connected neurons showed that excessive coupling reduced recruitment of the cells to fire, whereas less coupling led to spiking of essentially all neurons. Thus a decrease in electrical synapses could promote the afterdischarge by ensuring prompt recovery of electrotonic potentials or making the neurons more responsive to current spreading through the network. Copyright © 2015 the American Physiological Society.

  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. 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.

  19. Titanium biomaterials with complex surfaces induced aberrant peripheral circadian rhythms in bone marrow mesenchymal stromal cells.

    Science.gov (United States)

    Hassan, Nathaniel; McCarville, Kirstin; Morinaga, Kenzo; Mengatto, Cristiane M; Langfelder, Peter; Hokugo, Akishige; Tahara, Yu; Colwell, Christopher S; Nishimura, Ichiro

    2017-01-01

    Circadian rhythms maintain a high level of homeostasis through internal feed-forward and -backward regulation by core molecules. In this study, we report the highly unusual peripheral circadian rhythm of bone marrow mesenchymal stromal cells (BMSCs) induced by titanium-based biomaterials with complex surface modifications (Ti biomaterial) commonly used for dental and orthopedic implants. When cultured on Ti biomaterials, human BMSCs suppressed circadian PER1 expression patterns, while NPAS2 was uniquely upregulated. The Ti biomaterials, which reduced Per1 expression and upregulated Npas2, were further examined with BMSCs harvested from Per1::luc transgenic rats. Next, we addressed the regulatory relationship between Per1 and Npas2 using BMSCs from Npas2 knockout mice. The Npas2 knockout mutation did not rescue the Ti biomaterial-induced Per1 suppression and did not affect Per2, Per3, Bmal1 and Clock expression, suggesting that the Ti biomaterial-induced Npas2 overexpression was likely an independent phenomenon. Previously, vitamin D deficiency was reported to interfere with Ti biomaterial osseointegration. The present study demonstrated that vitamin D supplementation significantly increased Per1::luc expression in BMSCs, though the presence of Ti biomaterials only moderately affected the suppressed Per1::luc expression. Available in vivo microarray data from femurs exposed to Ti biomaterials in vitamin D-deficient rats were evaluated by weighted gene co-expression network analysis. A large co-expression network containing Npas2, Bmal1, and Vdr was observed to form with the Ti biomaterials, which was disintegrated by vitamin D deficiency. Thus, the aberrant BMSC peripheral circadian rhythm may be essential for the integration of Ti biomaterials into bone.

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

    Directory of Open Access Journals (Sweden)

    Gwendal Le Martelot

    2009-09-01

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

  1. 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.

  2. 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.

  3. 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...

  4. 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

  5. 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.

  6. 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.

  7. The mechanism of uncoupling by picrate in Escherichia coli K-12 membrane systems.

    Science.gov (United States)

    Michels, M; Bakker, E P

    1981-06-01

    The mechanism of action of the uncoupler picrate on intact cells and everted membrane vesicles of Escherichia coli K-12 was investigated. Like in mitochondria [Hanstein, W. G. and Hatefi, Y. (1974) Proc. Natl Acad. Sci. USA, 71, 288-292], it was observed that picrate uncoupled energy-linked functions only in everted, but not in intact membrane systems. In the vesicles picrate also decreased the magnitude of the transmembrane proton-motive force at concentrations similar to those at which it caused uncoupling. Experiments with 14C-labelled picrate showed that this compound bound both to deenergized intact cells and everted vesicles. However, upon energization of the membrane, picrate was extruded from the intact cell and taken up to a larger extent by the vesicles. These energy-dependent changes in picrate uptake correlated with the magnitude of the transmembrane electrical potential, delta psi. It is therefore proposed that picrate is a permeant uncoupler, that delta psi is the driving force for picrate movement across biological membranes, and that the uncoupling activity of picrate in everted membrane systems is due to its protonophoric action.

  8. 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...

  9. 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...

  10. 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.

  11. "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.

  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. 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.

  14. Does Circadian Variation of Mothers Affect Macronutrients of Breast Milk?

    Science.gov (United States)

    Çetinkaya, Aslihan Köse; Dizdar, Evrim Alyamaç; Yarcı, Erbu; Sari, Fatma Nur; Oguz, Serife Suna; Uras, Nurdan; Canpolat, Fuat Emre

    2017-06-01

    Objective  To determine the within-day variation of fat, protein, and carbohydrate content of breast milk. Methods  The study was conducted at Zekai Tahir Burak Maternity Teaching Hospital between April 2013 and January 2014. We obtained milk samples from lactating mothers of hospitalized infants through hand expression after breast-feeding or pumping three times a day. A mid-infrared human milk analyzer was used for measuring the macronutrient contents of breast milk samples. Results  Lactating mothers of 52 infants (30 preterm, 22 term) were recruited to the study. No significant difference was found in protein, fat, and carbohydrate content of milk samples throughout the day. We compared within-day variation of macronutrients of transitional and mature milk, milk samples from the mothers of preterm and term infants, and samples collected by either hand expression or pumping. We did not find a significant difference between the groups. Conclusion  Absence of circadian variations in lipid, carbohydrate, and protein content of breast milk in our study may be related to ethnic differences, maternal nutritional status, different milk content measurement technique, and population characteristics. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. 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.

  16. Timing of host feeding drives rhythms in parasite replication

    KAUST Repository

    Prior, Kimberley F.

    2018-02-26

    Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment. Recent work shows that daily (circadian) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hosts. Because parasite rhythms matter for their fitness, understanding how they are regulated could lead to innovative ways to reduce the severity and spread of diseases. Here, we examine how host circadian rhythms influence rhythms in the asexual replication of malaria parasites. Asexual replication is responsible for the severity of malaria and fuels transmission of the disease, yet, how parasite rhythms are driven remains a mystery. We perturbed feeding rhythms of hosts by 12 hours (i.e. diurnal feeding in nocturnal mice) to desynchronise the host’s peripheral oscillators from the central, light-entrained oscillator in the brain and their rhythmic outputs. We demonstrate that the rhythms of rodent malaria parasites in day-fed hosts become inverted relative to the rhythms of parasites in night-fed hosts. Our results reveal that the host’s peripheral rhythms (associated with the timing of feeding and metabolism), but not rhythms driven by the central, light-entrained circadian oscillator in the brain, determine the timing (phase) of parasite rhythms. Further investigation reveals that parasite rhythms correlate closely with blood glucose rhythms. In addition, we show that parasite rhythms resynchronise to the altered host feeding rhythms when food availability is shifted, which is not mediated through rhythms in the host immune system. Our observations suggest that parasites actively control their developmental rhythms. Finally, counter to expectation, the severity of disease symptoms expressed by hosts was not affected by desynchronisation of their central and peripheral rhythms. Our study at the intersection of disease ecology and chronobiology opens up a new

  17. Timing of host feeding drives rhythms in parasite replication

    KAUST Repository

    Prior, Kimberley F

    2017-12-07

    Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment. Recent work shows that daily (circadian) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hosts. Because parasite rhythms matter for their fitness, understanding how they are regulated could lead to innovative ways to reduce the severity and spread of diseases. Here, we examine how host circadian rhythms influence rhythms in the asexual replication of malaria parasites. Asexual replication is responsible for the severity of malaria and fuels transmission of the disease, yet, how parasite rhythms are driven remains a mystery. We perturbed feeding rhythms of hosts by 12 hours (i.e. diurnal feeding in nocturnal mice) to desynchronise the host\\'s peripheral oscillators from the central, light-entrained oscillator in the brain and their rhythmic outputs. We demonstrate that the rhythms of rodent malaria parasites in day-fed hosts become inverted relative to the rhythms of parasites in night-fed hosts. Our results reveal that the host\\'s peripheral rhythms (associated with the timing of feeding and metabolism), but not rhythms driven by the central, light-entrained circadian oscillator in the brain, determine the timing (phase) of parasite rhythms. Further investigation reveals that parasite rhythms correlate closely with blood glucose rhythms. In addition, we show that parasite rhythms resynchronise to the altered host feeding rhythms when food availability is shifted, which is not mediated through rhythms in the host immune system. Our observations suggest that parasites actively control their developmental rhythms. Finally, counter to expectation, the severity of disease symptoms expressed by hosts was not affected by desynchronisation of their central and peripheral rhythms. Our study at the intersection of disease ecology and chronobiology opens up a new

  18. Concentration of rat brown adipose tissue uncoupling protein may not be correlated with 3H-GDP binding

    International Nuclear Information System (INIS)

    Henningfield, M.F.; Swick, A.G.; Swick, R.W.

    1986-01-01

    Rats fed diets low in protein or exposed to cold show an increase in brown adipose tissue (BAT) mitochondrial 3 H-GDP binding. To investigate this phenomenon further, the uncoupling protein associated with BAT function was measured immunochemically on nitrocellulose blots. Quantitation of uncoupling protein was achieved by densitometer scanning with a BioRad densitometer. Peaks were integrated with Chromatochart software and an Apple IIe computer. A standard curve of purified uncoupling protein (50 to 500 ng) was used to calculate uncoupling protein concentration. There is a 1.5-fold increase in uncoupling protein per mg of protein in BAT mitochondria from rats exposed to cold for 15 days. There was no decrease in uncoupling protein from rats exposed to the cold followed by 24 h at 27 0 C although 3 H-GDP binding had decreased by half. Rats fed diets containing either 5 or 15% lactalbumin for 3 weeks did not show differences in uncoupling protein concentration although 3 H-GDP binding was 1.5-fold greater in BAT mitochondria from the low protein group. These results indicate that GDP binding does not necessarily reflect the concentration of uncoupling protein in BAT mitochondria

  19. 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.

  20. The Circadian Clock-controlled Transcriptome of Developing Soybean Seeds

    Directory of Open Access Journals (Sweden)

    Karen A. Hudson

    2010-07-01

    Full Text Available A number of metabolic and physiological processes in plants are controlled by the circadian clock, which enables a plant to anticipate daily changes in the environment. Relatively little is known about circadian rhythms in developing seeds, which may be important for determining the extent and timing of nutrient storage in grain. Microarray expression profiling was used to identify genes expressed in developing soybean ( seeds that are controlled by the circadian clock. Genes with predicted functions in protein synthesis, fatty acid metabolism, and photosynthesis totaling 1.8% of the mRNAs detected in seed were found to be expressed in a circadian rhythm. Known circadian and light-controlled promoter elements were identified as over-represented in the promoters of clock-controlled seed genes, with the over-represented elements varying according to the phase of circadian expression. A subset of circadian-regulated genes were found to be expressed in different phases in developing seeds with respect to leaves from the same plants, many of which have roles in photosynthesis and carbon metabolism. These results help to characterize the genes and processes in seeds that may be regulated by the circadian clock, and provide some insight into organ-specific phasing of clock controlled gene expression.

  1. Circadian Modulation of Short-Term Memory in "Drosophila"

    Science.gov (United States)

    Lyons, Lisa C.; Roman, Gregg

    2009-01-01

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

  2. 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.

  3. 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.

  4. 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

  5. Development and entrainment of the colonic circadian clock during ontogenesis

    Czech Academy of Sciences Publication Activity Database

    Polidarová, Lenka; Olejníková, Lucie; Paušlyová, Lucia; Sládek, Martin; Soták, Matúš; Pácha, Jiří; Sumová, Alena

    2014-01-01

    Roč. 306, č. 4 (2014), G346-G356 ISSN 0193-1857 R&D Projects: GA ČR(CZ) GAP303/12/1108 Institutional support: RVO:67985823 Keywords : circadian clock * clock gene * ontogenesis * circadian entrainment Subject RIV: ED - Physiology Impact factor: 3.798, year: 2014

  6. 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.

  7. Physiological effects of light on the human circadian pacemaker

    Science.gov (United States)

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

    2000-01-01

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

  8. Discrepancy between circadian rhythms of inulin and creatinine clearance

    NARCIS (Netherlands)

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

    1992-01-01

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

  9. 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...

  10. A Circadian Rhythm Regulating Hyphal Melanization in Cercospora Kikuchii

    Science.gov (United States)

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

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

    Science.gov (United States)

    Watts, Barbara L.

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

  12. Heritable circadian period length in a wild bird population

    NARCIS (Netherlands)

    Helm, B.; Visser, M.E.

    2010-01-01

    Timing is essential, but circadian clocks, which play a crucial role in timekeeping, are almost unaddressed in evolutionary ecology. A key property of circadian clocks is their free-running period length (τ), i.e. the time taken for a full cycle under constant conditions. Under laboratory

  13. 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.

  14. Associations between circadian and stress response cortisol in children

    NARCIS (Netherlands)

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

    2017-01-01

    Hypothalamic-pituitary-adrenal (HPA) axis functioning is characterized by the baseline production of cortisol following a circadian rhythm, as well as by the superimposed production of cortisol in response to a stressor. However, it is relatively unknown whether the basal cortisol circadian rhythm

  15. Circadian variation of urinary albumin excretion in pregnancy

    NARCIS (Netherlands)

    Douma, C. E.; van der Post, J. A.; van Acker, B. A.; Boer, K.; Koopman, M. G.

    1995-01-01

    OBJECTIVE: The hypothesis was tested that circadian variations in urinary albumin excretion of pregnant women in the third trimester of normal pregnancy are different from nonpregnant individuals. DESIGN: Circadian variability in urinary albumin excretion was studied both in pregnant women and in

  16. 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

  17. 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.

  18. Impact of Sleep and Circadian Disruption on Energy Balance and Diabetes: A Summary of Workshop Discussions

    Science.gov (United States)

    Arble, Deanna M.; Bass, Joseph; Behn, Cecilia Diniz; Butler, Matthew P.; Challet, Etienne; Czeisler, Charles; Depner, Christopher M.; Elmquist, Joel; Franken, Paul; Grandner, Michael A.; Hanlon, Erin C.; Keene, Alex C.; Joyner, Michael J.; Karatsoreos, Ilia; Kern, Philip A.; Klein, Samuel; Morris, Christopher J.; Pack, Allan I.; Panda, Satchidananda; Ptacek, Louis J.; Punjabi, Naresh M.; Sassone-Corsi, Paolo; Scheer, Frank A.; Saxena, Richa; Seaquest, Elizabeth R.; Thimgan, Matthew S.; Van Cauter, Eve; Wright, Kenneth P.

    2015-01-01

    A workshop was held at the National Institute for Diabetes and Digestive and Kidney Diseases with a focus on the impact of sleep and circadian disruption on energy balance and diabetes. The workshop identified a number of key principles for research in this area and a number of specific opportunities. Studies in this area would be facilitated by active collaboration between investigators in sleep/circadian research and investigators in metabolism/diabetes. There is a need to translate the elegant findings from basic research into improving the metabolic health of the American public. There is also a need for investigators studying the impact of sleep/circadian disruption in humans to move beyond measurements of insulin and glucose and conduct more in-depth phenotyping. There is also a need for the assessments of sleep and circadian rhythms as well as assessments for sleep-disordered breathing to be incorporated into all ongoing cohort studies related to diabetes risk. Studies in humans need to complement the elegant short-term laboratory-based human studies of simulated short sleep and shift work etc. with studies in subjects in the general population with these disorders. It is conceivable that chronic adaptations occur, and if so, the mechanisms by which they occur needs to be identified and understood. Particular areas of opportunity that are ready for translation are studies to address whether CPAP treatment of patients with pre-diabetes and obstructive sleep apnea (OSA) prevents or delays the onset of diabetes and whether temporal restricted feeding has the same impact on obesity rates in humans as it does in mice. Citation: Arble DM, Bass J, Behn CD, Butler MP, Challet E, Czeisler C, Depner CM, Elmquist J, Franken P, Grandner MA, Hanlon EC, Keene AC, Joyner MJ, Karatsoreos I, Kern PA, Klein S, Morris CJ, Pack AI, Panda S, Ptacek LJ, Punjabi NM, Sassone-Corsi P, Scheer FA, Saxena R, Seaquest ER, Thimgan MS, Van Cauter E, Wright KP. Impact of sleep and

  19. 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.

  20. Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging.

    Science.gov (United States)

    Sato, Shogo; Solanas, Guiomar; Peixoto, Francisca Oliveira; Bee, Leonardo; Symeonidi, Aikaterini; Schmidt, Mark S; Brenner, Charles; Masri, Selma; Benitah, Salvador Aznar; Sassone-Corsi, Paolo

    2017-08-10

    The process of aging and circadian rhythms are intimately intertwined, but how peripheral clocks involved in metabolic homeostasis contribute to aging remains unknown. Importantly, caloric restriction (CR) extends lifespan in several organisms and rewires circadian metabolism. Using young versus old mice, fed ad libitum or under CR, we reveal reprogramming of the circadian transcriptome in the liver. These age-dependent changes occur in a highly tissue-specific manner, as demonstrated by comparing circadian gene expression in the liver versus epidermal and skeletal muscle stem cells. Moreover, de novo oscillating genes under CR show an enrichment in SIRT1 targets in the liver. This is accompanied by distinct circadian hepatic signatures in NAD + -related metabolites and cyclic global protein acetylation. Strikingly, this oscillation in acetylation is absent in old mice while CR robustly rescues global protein acetylation. Our findings indicate that the clock operates at the crossroad between protein acetylation, liver metabolism, and aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. CIRCADIAN CLOCK-ASSOCIATED 1 Inhibits Leaf Senescence in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Yi Song

    2018-03-01

    Full Text Available Leaf senescence is an integral part of plant development, and the timing and progressing rate of senescence could substantially affect the yield and quality of crops. It has been known that a circadian rhythm synchronized with external environmental cues is critical for the optimal coordination of various physiological and metabolic processes. However, the reciprocal interactions between the circadian clock and leaf senescence in plants remain unknown. Here, through measuring the physiological and molecular senescence related markers of several circadian components mutants, we found that CIRCADIAN CLOCK-ASSOCIATED 1 inhibits leaf senescence. Further molecular and genetic studies revealed that CCA1 directly activates GLK2 and suppresses ORE1 expression to counteract leaf senescence. As plants age, the expression and periodic amplitude of CCA1 declines and thus weakens the inhibition of senescence. Our findings reveal an age-dependent circadian clock component of the process of leaf senescence.

  2. Recent Advances in Circadian Rhythms in Cardiovascular System

    Directory of Open Access Journals (Sweden)

    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.

  3. Modelling of intercellular synchronization in the Drosophila circadian clock

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  4. 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.

  5. Rhythmic Degradation Explains and Unifies Circadian Transcriptome and Proteome Data

    Directory of Open Access Journals (Sweden)

    Sarah Lück

    2014-10-01

    Full Text Available The rich mammalian cellular circadian output affects thousands of genes in many cell types and has been the subject of genome-wide transcriptome and proteome studies. The results have been enigmatic because transcript peak abundances do not always follow the peaks of gene-expression activity in time. We posited that circadian degradation of mRNAs and proteins plays a pivotal role in setting their peak times. To establish guiding principles, we derived a theoretical framework that fully describes the amplitudes and phases of biomolecules with circadian half-lives. We were able to explain the circadian transcriptome and proteome studies with the same unifying theory, including cases in which transcripts or proteins appeared before the onset of increased production rates. Furthermore, we estimate that 30% of the circadian transcripts in mouse liver and Drosophila heads are affected by rhythmic posttranscriptional regulation.

  6. Circadian Effects on Simple Components of Complex Task Performance

    Science.gov (United States)

    Clegg, Benjamin A.; Wickens, Christopher D.; Vieane, Alex Z.; Gutzwiller, Robert S.; Sebok, Angelia L.

    2015-01-01

    The goal of this study was to advance understanding and prediction of the impact of circadian rhythm on aspects of complex task performance during unexpected automation failures, and subsequent fault management. Participants trained on two tasks: a process control simulation, featuring automated support; and a multi-tasking platform. Participants then completed one task in a very early morning (circadian night) session, and the other during a late afternoon (circadian day) session. Small effects of time of day were seen on simple components of task performance, but impacts on more demanding components, such as those that occur following an automation failure, were muted relative to previous studies where circadian rhythm was compounded with sleep deprivation and fatigue. Circadian low participants engaged in compensatory strategies, rather than passively monitoring the automation. The findings and implications are discussed in the context of a model that includes the effects of sleep and fatigue factors.

  7. Circadian Rhythms in Floral Scent Emission.

    Science.gov (United States)

    Fenske, Myles P; Imaizumi, Takato

    2016-01-01

    To successfully recruit pollinators, plants often release attractive floral scents at specific times of day to coincide with pollinator foraging. This timing of scent emission is thought to be evolutionarily beneficial to maximize resource efficiency while attracting only useful pollinators. Temporal regulation of scent emission is tied to the activity of the specific metabolic pathways responsible for scent production. Although floral volatile profiling in various plants indicated a contribution by the circadian clock, the mechanisms by which the circadian clock regulates timing of floral scent emission remained elusive. Recent studies using two species in the Solanaceae family provided initial insight into molecular clock regulation of scent emission timing. In Petunia hybrida, the floral volatile benzenoid/phenylpropanoid (FVBP) pathway is the major metabolic pathway that produces floral volatiles. Three MYB-type transcription factors, ODORANT 1 (ODO1), EMISSION OF BENZENOIDS I (EOBI), and EOBII, all of which show diurnal rhythms in mRNA expression, act as positive regulators for several enzyme genes in the FVBP pathway. Recently, in P. hybrida and Nicotiana attenuata, homologs of the Arabidopsis clock gene LATE ELONGATED HYPOCOTYL (LHY) have been shown to have a similar role in the circadian clock in these plants, and to also determine the timing of scent emission. In addition, in P. hybrida, PhLHY directly represses ODO1 and several enzyme genes in the FVBP pathway during the morning as an important negative regulator of scent emission. These findings facilitate our understanding of the relationship between a molecular timekeeper and the timing of scent emission, which may influence reproductive success.

  8. 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.

  9. Circadian rhythms in floral scent emission

    Directory of Open Access Journals (Sweden)

    Myles eFenske

    2016-04-01

    Full Text Available To successfully recruit pollinators, plants often release attractive floral scents at specific times of day to coincide with pollinator foraging. This timing of scent emission is thought to be evolutionarily beneficial to maximize resource efficiency while attracting only useful pollinators. Temporal regulation of scent emission is tied to the activity of the specific metabolic pathways responsible for scent production. Although floral volatile profiling in various plants indicated a contribution by the circadian clock, the mechanisms by which the circadian clock regulates timing of floral scent emission remained elusive. Recent studies using two species in the Solanaceae family provided initial insight into molecular clock regulation of scent emission timing. In Petunia hybrida, the benzenoid/phenylpropanoid (FVBP pathway is the major metabolic pathway that produces floral volatiles. Three MYB-type transcription factors, ODORANT1 (ODO1, EMISSION OF BENZENOIDS I (EOBI, and EOBII, all of which show diurnal rhythms in mRNA expression, act as positive regulators for several enzyme genes in the FVBP pathway. Recently, in P. hybrida and Nicotiana attenuata, homologs of the Arabidopsis clock gene LATE ELONGATED HYPOCOTYL (LHY have been shown to have a similar role in the circadian clock in these plants, and to also determine the timing of scent emission. In addition, in P. hybrida, PhLHY directly represses ODO1 and several enzyme genes in the FVBP pathway during the morning as an important negative regulator of scent emission. These findings facilitate our understanding of the relationship between a molecular timekeeper and the timing of scent emission, which may influence reproductive success.

  10. Persistence of a circadian rhythmicity for thyroid hormones in plasma and thyroid of hibernating male Rana ridibunda.

    Science.gov (United States)

    Kühn, E R; Delmotte, N M; Darras, V M

    1983-06-01

    The presence and circadian rhythmicity of thyroid hormones was studied in plasma and the thyroid gland of male Rana ridibunda before and during hibernation. Hibernating January frogs do have a lower T3 and T4 content of their thyroid gland whereas plasma levels of T3 are maintained and of T4 increased compared to fed September or October frogs. It seems likely that the increased photoperiod in January will be responsible for this increased T4 secretion, since controlled laboratory experiments performed in December did not reveal any influence of low temperature on circulating T3 or T4 levels. Also feeding does not influence circulating levels and thyroid content of thyroid hormones in frogs kept at room temperature during the month of January. A circadian rhythmicity of T3 and T4 in the thyroid gland is present in fed October frogs and in non fed December frogs acclimated at 5 degrees C for 12 days with an acrophase for T3 at approximately 1500 h and for T4 at around 1900 h, whereas in plasma only T3 does have circadian variations (acrophase about midnight) but not T4. When December frogs are acclimated to room temperature for 12 days, frogs are active again, but do not eat and have a lower body weight than frogs hibernating at 5 degrees C. Their T3 content of the thyroid gland has disappeared, but T4 thyroid content and plasma levels of T3 and T4 are maintained. As in hibernating frogs, no circadian variations in T4 plasma concentrations are present whereas the circadian thyroid T4 rhythm disappears. At the same time a dampening in rhythmicity for plasma T3 as judged by the significantly lower amplitude occurs. It is concluded that the persistence of circulating levels of thyroid hormones and of a circadian cyclicity for T3 in plasma in non feeding hibernating frogs may reflect the special metabolic state e.g. availability of food reserves in these animals.

  11. 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

  12. 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.

  13. Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Han Wern; Lim, Hwee Ying [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260 (Singapore); Wong, Kim Ping, E-mail: bchsitkp@nus.edu.sg [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260 (Singapore)

    2009-11-06

    Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F{sub 0}F{sub 1}-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 {mu}M, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F{sub 0}F{sub 1}-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.

  14. Renal transplantation induces mitochondrial uncoupling, increased kidney oxygen consumption, and decreased kidney oxygen tension

    NARCIS (Netherlands)

    Papazova, Diana A.; Friederich-Persson, Malou; Joles, Jaap A.; Verhaar, Marianne C.

    2015-01-01

    Hypoxia is an acknowledged pathway to renal injury and ischemia-reperfusion (I/R) and is known to reduce renal oxygen tension (PO2). We hypothesized that renal I/R increases oxidative damage and induces mitochondrial uncoupling, resulting in increased oxygen consumption and hence kidney

  15. A novel amino acid and metabolomics signature in mice overexpressing muscle uncoupling protein 3

    Science.gov (United States)

    Uncoupling protein 3 (UCP3) is highly expressed in skeletal muscle and is known to lower mitochondrial reactive oxygen species and promote fatty acid oxidation; however, the global impact of UCP3 activity on skeletal muscle and whole body metabolism has not been extensively studied. We utilized unt...

  16. Uncoupling Protein 3 Content Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes

    NARCIS (Netherlands)

    Keizer; E.E. Blaak; P. Schrauwen; G. Schaart; dr. Lars B. Borghouts; Saris; M.K.C. Hesselink

    2001-01-01

    Recently, a role for uncoupling protein-3 (UCP3) in carbohydrate metabolism and in type 2 diabetes has been suggested. Mice overexpressing UCP3 in skeletal muscle showed reduced fasting plasma glucose levels, improved glucose tolerance after an oral glucose load, and reduced fasting plasma insulin

  17. Arterial Ventricular Uncoupling with Age and Disease and Recoupling with Exercise

    Science.gov (United States)

    Chantler, Paul D

    2017-01-01

    The deterioration in arterial and cardiac function with aging impairs arterial ventricular coupling, an important determinant of cardiovascular performance. However, exercise training improves arterial ventricular coupling especially during exercise during the age and disease process. This review examines the concept of arterial-ventricular coupling, and how age, and disease uncouples but exercise training recouples the heart and arterial system. PMID:28072585

  18. Zinc Potentiates an Uncoupled Anion Conductance Associated with the Dopamine Transporter

    DEFF Research Database (Denmark)

    Meinild, Anne-Kristine; Sitte, Harald H; Gether, Ulrik

    2004-01-01

    but by a marked increase in the charge/DA flux coupling ratio as assessed from concomitant measurements of [(3)H]DA uptake and currents in voltage-clamped oocytes. These data suggest that Zn(2+) facilitates an uncoupled ion conductance mediated by DAT. Whereas this required substrate in the wild type (WT), we...

  19. Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action

    International Nuclear Information System (INIS)

    Lim, Han Wern; Lim, Hwee Ying; Wong, Kim Ping

    2009-01-01

    Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F 0 F 1 -ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 μM, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F 0 F 1 -ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.

  20. Superoxide activates mitochondrial uncoupling protein 2 from the matrix side. Studies using targeted antioxidants.

    Science.gov (United States)

    Echtay, Karim S; Murphy, Michael P; Smith, Robin A J; Talbot, Darren A; Brand, Martin D

    2002-12-06

    Superoxide activates nucleotide-sensitive mitochondrial proton transport through the uncoupling proteins UCP1, UCP2, and UCP3 (Echtay, K. S., et al. (2002) Nature 415, 1482-1486). Two possible mechanisms were proposed: direct activation of the UCP proton transport mechanism by superoxide or its products and a cycle of hydroperoxyl radical entry coupled to UCP-catalyzed superoxide anion export. Here we provide evidence for the first mechanism and show that superoxide activates UCP2 in rat kidney mitochondria from the matrix side of the mitochondrial inner membrane: (i) Exogenous superoxide inhibited matrix aconitase, showing that external superoxide entered the matrix. (ii) Superoxide-induced uncoupling was abolished by low concentrations of the mitochondrially targeted antioxidants 10-(6'-ubiquinonyl)decyltriphenylphosphonium (mitoQ) or 2-[2-(triphenylphosphonio)ethyl]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol bromide (mitoVit E), which are ubiquinone (Q) or tocopherol derivatives targeted to the matrix by covalent attachment to triphenylphosphonium cation. However, superoxide-induced uncoupling was not affected by similar concentrations of the nontargeted antioxidants Q(o), Q(1), decylubiquinone, vitamin E, or 6-hydroxy-2,5,7,8-tetramethylchroman 2-carboxylic acid (TROLOX) or of the mitochondrially targeted but redox-inactive analogs decyltriphenylphosphonium or 4-chlorobutyltriphenylphosphonium. Thus matrix superoxide appears to be necessary for activation of UCP2 by exogenous superoxide. (iii) When the reduced to oxidized ratio of mitoQ accumulated by mitochondria was increased by inhibiting cytochrome oxidase, it induced nucleotide-sensitive uncoupling that was not inhibited by external superoxide dismutase. Under these conditions quinols are known to produce superoxide, and because mitoQ is localized within the mitochondrial matrix this suggests that production of superoxide in the matrix was sufficient to activate UCP2. Furthermore, the superoxide

  1. Chronic mitochondrial uncoupling treatment prevents acute cold-induced oxidative stress in birds.

    Science.gov (United States)

    Stier, Antoine; Massemin, Sylvie; Criscuolo, François

    2014-12-01

    Endotherms have evolved two major types of thermogenesis that allow them to actively produce heat in response to cold exposure, either through muscular activity (i.e. shivering thermogenesis) or through futile electro-chemical cycles (i.e. non-shivering thermogenesis). Amongst the latter, mitochondrial uncoupling is of key importance because it is suggested to drive heat production at a low cost in terms of oxidative stress. While this has been experimentally shown in mammals, the oxidative stress consequences of cold exposure and mitochondrial uncoupling are clearly less understood in the other class of endotherms, the birds. We compared metabolic and oxidative stress responses of zebra finches chronically treated with or without a chemical mitochondrial uncoupler (2,4-dinitrophenol: DNP), undergoing an acute (24 h) and a chronic (4 weeks) cold exposure (12 °C). We predicted that control birds should present at least a transient elevation of oxidative stress levels in response to cold exposure. This oxidative stress cost should be more pronounced in control birds than in DNP-treated birds, due to their lower basal uncoupling state. Despite similar increase in metabolism, control birds presented elevated levels of DNA oxidative damage in response to acute (but not chronic) cold exposure, while DNP-treated birds did not. Plasma antioxidant capacity decreased overall in response to chronic cold exposure. These results show that acute cold exposure increases oxidative stress in birds. However, uncoupling mitochondrial functioning appears as a putative compensatory mechanism preventing cold-induced oxidative stress. This result confirms previous observations in mice and underlines non-shivering thermogenesis as a putative key mechanism for endotherms in mounting a response to cold at a low oxidative cost.

  2. Sleep, circadian rhythm and body weight: parallel developments.

    Science.gov (United States)

    Westerterp-Plantenga, Margriet S

    2016-11-01

    Circadian alignment is crucial for body-weight management, and for metabolic health. In this context, circadian alignment consists of alignment of sleep, meal patterns and physical activity. During puberty a significant reduction in sleep duration occurs, and pubertal status is inversely associated with sleep duration. A consistent inverse association between habitual sleep duration and body-weight development occurs, independent of possible confounders. Research on misalignment reveals that circadian misalignment affects sleep-architecture and subsequently disturbs glucose-insulin metabolism, substrate oxidation, leptin- and ghrelin concentrations, appetite, food reward, hypothalamic-pituitary-adrenal-axis activity and gut-peptide concentrations enhancing positive energy balance and metabolic disturbance. Not only aligning meals and sleep in a circadian way is crucial, also regular physical activity during the day strongly promotes the stability and amplitude of circadian rhythm, and thus may serve as an instrument to restore poor circadian rhythms. Endogenicity may play a role in interaction of these environmental variables with a genetic predisposition. In conclusion, notwithstanding the separate favourable effects of sufficient daily physical activity, regular meal patterns, sufficient sleep duration and quality sleep on energy balance, the overall effect of the amplitude and stability of the circadian rhythm, perhaps including genetic predisposition, may integrate the separate effects in an additive way.

  3. A circadian rhythm regulating hyphal melanization in Cercospora kikuchii.

    Science.gov (United States)

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

    2010-01-01

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

  4. Associations between circadian and stress response cortisol in children.

    Science.gov (United States)

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

    2017-01-01

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

  5. Circadian modulation of short-term memory in Drosophila.

    Science.gov (United States)

    Lyons, Lisa C; Roman, Gregg

    2009-01-01

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

  6. Photoperiodic plasticity in circadian clock neurons in insects

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    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.

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

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

    2015-07-23

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

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

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    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.

  9. A New Perspective for Parkinson's Disease: Circadian Rhythm.

    Science.gov (United States)

    Li, Siyue; Wang, Yali; Wang, Fen; Hu, Li-Fang; Liu, Chun-Feng

    2017-02-01

    Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson's disease (PD) exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative consequences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.

  10. 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

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

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    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.

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

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    Ji-Ae Yoon

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

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

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    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

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

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    A.M.O. Leal

    1997-12-01

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

  15. Circadian Clocks for All Meal-Times: Anticipation of 2 Daily Meals in Rats

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    Mistlberger, Ralph E.; Kent, Brianne A.; Chan, Sofina; Patton, Danica F.; Weinberg, Alexander; Parfyonov, Maksim

    2012-01-01

    Anticipation of a daily meal in rats has been conceptualized as a rest-activity rhythm driven by a food-entrained circadian oscillator separate from the pacemaker generating light-dark (LD) entrained rhythms. Rats can also anticipate two daily mealtimes, but whether this involves independently entrained oscillators, one ‘continuously consulted’ clock, cue-dependent non-circadian interval timing or a combination of processes, is unclear. Rats received two daily meals, beginning 3-h (meal 1) and 13-h (meal 2) after lights-on (LD 14∶10). Anticipatory wheel running began 68±8 min prior to meal 1 and 101±9 min prior to meal 2 but neither the duration nor the variability of anticipation bout lengths exhibited the scalar property, a hallmark of interval timing. Meal omission tests in LD and constant dark (DD) did not alter the timing of either bout of anticipation, and anticipation of meal 2 was not altered by a 3-h advance of meal 1. Food anticipatory running in this 2-meal protocol thus does not exhibit properties of interval timing despite the availability of external time cues in LD. Across all days, the two bouts of anticipation were uncorrelated, a result more consistent with two independently entrained oscillators than a single consulted clock. Similar results were obtained for meals scheduled 3-h and 10-h after lights-on, and for a food-bin measure of anticipation. Most rats that showed weak or no anticipation to one or both meals exhibited elevated activity at mealtime during 1 or 2 day food deprivation tests in DD, suggesting covert operation of circadian timing in the absence of anticipatory behavior. A control experiment confirmed that daytime feeding did not shift LD-entrained rhythms, ruling out displaced nocturnal activity as an explanation for daytime activity. The results favor a multiple oscillator basis for 2-meal anticipatory rhythms and provide no evidence for involvement of cue-dependent interval timing. PMID:22355393

  16. A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus

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    Guilding Clare

    2009-08-01

    Full Text Available Abstract Background In mammals, the synchronized activity of cell autonomous clocks in the suprachiasmatic nuclei (SCN enables this structure to function as the master circadian clock, coordinating daily rhythms in physiology and behavior. However, the dominance of this clock has been challenged by the observations that metabolic duress can over-ride SCN controlled rhythms, and that clock genes are expressed in many brain areas, including those implicated in the regulation of appetite and feeding. The recent development of mice in which clock gene/protein activity is reported by bioluminescent constructs (luciferase or luc now enables us to track molecular oscillations in numerous tissues ex vivo. Consequently we determined both clock activities and responsiveness to metabolic perturbations of cells and tissues within the mediobasal hypothalamus (MBH, a site pivotal for optimal internal homeostatic regulation. Results Here we demonstrate endogenous circadian rhythms of PER2::LUC expression in discrete subdivisions of the arcuate (Arc and dorsomedial nuclei (DMH. Rhythms resolved to single cells did not maintain long-term synchrony with one-another, leading to a damping of oscillations at both cell and tissue levels. Complementary electrophysiology recordings revealed rhythms in neuronal activity in the Arc and DMH. Further, PER2::LUC rhythms were detected in the ependymal layer of the third ventricle and in the median eminence/pars tuberalis (ME/PT. A high-fat diet had no effect on the molecular oscillations in the MBH, whereas food deprivation resulted in an altered phase in the ME/PT. Conclusion Our results provide the first single cell resolution of endogenous circadian rhythms in clock gene expression in any intact tissue outside the SCN, reveal the cellular basis for tissue level damping in extra-SCN oscillators and demonstrate that an oscillator in the ME/PT is responsive to changes in metabolism.

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

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

    2017-06-01

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

  18. Evaluation of circadian phenotypes utilizing fibroblasts from patients with circadian rhythm sleep disorders.

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    Hida, A; Ohsawa, Y; Kitamura, S; Nakazaki, K; Ayabe, N; Motomura, Y; Matsui, K; Kobayashi, M; Usui, A; Inoue, Y; Kusanagi, H; Kamei, Y; Mishima, K

    2017-04-25

    We evaluated the circadian phenotypes of patients with delayed sleep-wake phase disorder (DSWPD) and non-24-hour sleep-wake rhythm disorder (N24SWD), two different circadian rhythm sleep disorders (CRSDs) by measuring clock gene expression rhythms in fibroblast cells derived from individual patients. Bmal1-luciferase (Bmal1-luc) expression rhythms were measured in the primary fibroblast cells derived from skin biopsy samples of patients with DSWPD and N24SWD, as well as control subjects. The period length of the Bmal1-luc rhythm (in vitro period) was distributed normally and was 22.80±0.47 (mean±s.d.) h in control-derived fibroblasts. The in vitro periods in DSWPD-derived fibroblasts and N24SWD-derived fibroblasts were 22.67±0.67 h and 23.18±0.70 h, respectively. The N24SWD group showed a significantly longer in vitro period than did the control or DSWPD group. Furthermore, in vitro period was associated with response to chronotherapy in the N24SWD group. Longer in vitro periods were observed in the non-responders (mean±s.d.: 23.59±0.89 h) compared with the responders (mean±s.d.: 22.97±0.47 h) in the N24SWD group. Our results indicate that prolonged circadian periods contribute to the onset and poor treatment outcome of N24SWD. In vitro rhythm assays could be useful for predicting circadian phenotypes and clinical prognosis in patients with CRSDs.

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

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    Sam-Moon Kim

    2016-05-01

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

  20. Dynamical feedback between circadian clock and sucrose availability explains adaptive response of starch metabolism to various photoperiods

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    Francois Gabriel Feugier

    2013-01-01

    Full Text Available Plants deal with resource management during all their life. During the day they feed on photosynthetic carbon, sucrose, while storing a part into starch for night use. Careful control of carbon partitioning, starch degradation and sucrose export rates is crucial to avoid carbon starvation, insuring optimal growth whatever the photoperiod. Efficient regulation of these key metabolic rates can give an evolutionary advantage to plants. Here we propose a model of adaptive starch metabolism in response to various photoperiods. We assume the three key metabolic rates to be circadian regulated in leaves and that their phases of oscillations are shifted in response to sucrose starvation. We performed gradient descents for various photoperiod conditions to find the corresponding optimal sets of phase shifts that minimize starvation. Results at convergence were all consistent with experimental data: i diurnal starch profile showed linear increase during the day and linear decrease at night; ii shorter photoperiod tended to increase starch synthesis speed while decreasing its degradation speed during the longer night; iii sudden early dusk showed slower starch degradation during the longer night. Profiles that best explained observations corresponded to circadian regulation of all rates. This theoretical study would establish a framework for future research on feedback between starch metabolism and circadian clock as well as plant productivity.

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

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    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.

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

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    Rich, Tyvin A

    2007-04-01

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

  3. Circadian rhythmicity of active GSK3 isoforms modulates molecular clock gene rhythms in the suprachiasmatic nucleus.

    Science.gov (United States)

    Besing, Rachel C; Paul, Jodi R; Hablitz, Lauren M; Rogers, Courtney O; Johnson, Russell L; Young, Martin E; Gamble, Karen L

    2015-04-01

    The suprachiasmatic nucleus (SCN) drives and synchronizes daily rhythms at the cellular level via transcriptional-translational feedback loops comprising clock genes such as Bmal1 and Period (Per). Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, phosphorylates at least 5 core clock proteins and shows diurnal variation in phosphorylation state (inactivation) of the GSK3β isoform. Whether phosphorylation of the other primary isoform (GSK3α) varies across the subjective day-night cycle is unknown. The purpose of this study was to determine if the endogenous rhythm of GSK3 (α and β) phosphorylation is critical for rhythmic BMAL1 expression and normal amplitude and periodicity of the molecular clock in the SCN. Significant circadian rhythmicity of phosphorylated GSK3 (α and β) was observed in the SCN from wild-type mice housed in constant darkness for 2 weeks. Importantly, chronic activation of both GSK3 isoforms impaired rhythmicity of the GSK3 target BMAL1. Furthermore, chronic pharmacological inhibition of GSK3 with 20 µM CHIR-99021 enhanced the amplitude and shortened the period of PER2::luciferase rhythms in organotypic SCN slice cultures. These results support the model that GSK3 activity status is regulated by the circadian clock and that GSK3 feeds back to regulate the molecular clock amplitude in the SCN. © 2015 The Author(s).

  4. Development of a circadian light source

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    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.

  5. Circadian typology and sensation seeking in adolescents.

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    Muro, Anna; Gomà-i-Freixanet, Montserrat; Adan, Ana

    2012-12-01

    The relationship of circadian typology with personality has been largely studied in adults, but there are few studies exploring such relationship in adolescents. Adolescence has been associated with a greater tendency to eveningness preference, sleeping problems, poorer academic achievement, earlier substance use, or risky behaviors, and it is suggested that this association might be mediated by personality factors. Given the relevance of identifying the behavioral outcomes of young evening types to detect and prevent health problems, the present study aimed to explore, for the first time, the relationship between sensation seeking and circadian typology in an adolescent sample of 688 students (51.45% boys) from 12 to 16 yrs old. They answered the Spanish versions of the Morningness-Eveningness Scale for Children (MESC) and the Junior Sensation Seeking Scale (J-SSS), which includes four subscales measuring Thrill and Adventure Seeking, Experience Seeking, Disinhibition, and Boredom Susceptibility. Analyses showed that boys obtained significantly higher scores than girls on J-SSS total score and all subscales except Boredom Susceptibility, whereas evening-type adolescents of both sexes scored significantly higher than neither types and than morning types on J-SSS total score. These results indicate that evening-type adolescents show a greater desire for varied, new, complex, and intense sensations, and they are ready for experiencing more risks than morning types. The implications of this study suggest the need of being aware of individual differences in the SS trait in evening-type adolescents, as well as taking into account the wide variety of behaviors associated with it, either prosocial or antisocial, to design better preventive health and academic programs.

  6. Circadian phase resetting via single and multiple control targets.

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    Neda Bagheri

    2008-07-01

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

  7. Sleep and circadian rhythm disruption in neuropsychiatric illness.

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    Jagannath, Aarti; Peirson, Stuart N; Foster, Russell G

    2013-10-01

    Sleep and circadian rhythm disruption (SCRD) is a common feature in many neuropsychiatric diseases including schizophrenia, bipolar disorder and depression. Although the precise mechanisms remain unclear, recent evidence suggests that this comorbidity is not simply a product of medication or an absence of social routine, but instead reflects commonly affected underlying pathways and mechanisms. For example, several genes intimately involved in the generation and regulation of circadian rhythms and sleep have been linked to psychiatric illness. Further, several genes linked to mental illness have recently been shown to also play a role in normal sleep and circadian behaviour. Here we describe some of the emerging common mechanisms that link circadian rhythms, sleep and SCRD in severe mental illnesses. A deeper understanding of these links will provide not only a greater understanding of disease mechanisms, but also holds the promise of novel avenues for therapeutic intervention. Copyright © 2013. Published by Elsevier Ltd.

  8. Metabolic Compensation and Circadian Resilience in Prokaryotic Cyanobacteria

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    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

  9. Escaping Circadian Regulation: An Emerging Hallmark of Cancer?

    Science.gov (United States)

    El-Athman, Rukeia; Relógio, Angela

    2018-03-28

    Alterations of circadian clock genes are associated with patient survival, tumor stage, and clinical subtype across various cancer types, highlighting the importance of timing in cancer treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Introduction: circadian rhythm and its disruption: impact on reproductive function.

    Science.gov (United States)

    Casper, Robert F; Gladanac, Bojana

    2014-08-01

    Almost all forms of life have predictable daily or circadian rhythms in molecular, endocrine, and behavioral functions. In mammals, a central pacemaker located in the suprachiasmatic nuclei coordinates the timing of these rhythms. Daily light exposure that affects the retina of the eye directly influences this area, which is required to align endogenous processes to the appropriate time of day. The present "Views and Reviews" articles discuss the influence of circadian rhythms, especially nightly secretion of melatonin, on reproductive function and parturition. In addition, an examination is made of problems that arise from recurrent circadian rhythm disruption associated with changes in light exposure patterns common to modern day society. Finally, a possible solution to prevent disruptions in circadian phase markers by filtering out short wavelengths from nocturnal light is reviewed. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. CIRCAD: Automated Analysis of Circadian Core Temperature Data

    National Research Council Canada - National Science Library

    Doherty, Tammy

    2000-01-01

    .... Use of the CIRCAD program, described in this report, dramatically reduces the amount of time required for circadian data analyses and provides the capability to quickly implement and test new analytical methods...

  12. Sleep structure in blindness is influenced by circadian desynchrony

    DEFF Research Database (Denmark)

    Aubin, Sébrina; Jennum, Poul; Nielsen, Tore

    2018-01-01

    We examined the structure, duration and quality of sleep, including non-rapid eye movement sleep and rapid eye movement sleep, in 11 blind individuals without conscious light perception and 11 age- and sex-matched sighted controls. Because blindness is associated with a greater incidence of free......-running circadian rhythms, we controlled for circadian phase by a measure of melatonin onset timing. When circadian rhythm was entrained and melatonin onset occurred at normal times, sleep structure did not differ between blind and sighted individuals. On the other hand, an abnormal timing of the circadian phase......, including delayed, shifted and unclassifiable melatonin onsets, led to larger rapid eye movement sleep latencies and increased wake times. No differences were observed for stages of non-rapid eye movement sleep, either between congenital and late blind and sighted individuals, or across the different...

  13. 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.

  14. Circadian and pharmacological regulation of casein kinase I in the ...

    Indian Academy of Sciences (India)

    2008-12-31

    Dec 31, 2008 ... formed in strict accordance with NIH rules for animal care and maintenance. ... date and a mammalian protease inhibitor cocktail (Sigma,. Cat. No. P8340; dilution ..... 1998 Circadian behavior and plasticity of light-induced ...

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Federica Gilardi

    2014-03-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  18. PPARα deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPARγ activation in the liver

    International Nuclear Information System (INIS)

    Oishi, Katsutaka; Uchida, Daisuke; Ohkura, Naoki; Horie, Shuichi

    2010-01-01

    Research highlights: → PPARα deficiency augments a ketogenic diet-induced circadian PAI-1 expression. → Hepatic expressions of PPARγ and PCG-1α are induced by a ketogenic diet. → PPARγ antagonist attenuates a ketogenic diet-induced PAI-1 expression. → Ketogenic diet advances the phase of circadian clock in a PPARα-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor α (PPARα) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPARα-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPARα-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPARα target genes such as Cyp4A10 and FGF21 was damped in PPARα-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPARα-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPARα activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPARγ and its coactivator PCG-1α were more effectively induced in PPARα-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPARγ antagonist, in both WT and PPARα-null mice. PPARγ activation seems to be involved in KD-induced hypofibrinolysis by augmenting PAI-1 gene expression

  19. System identification of the Arabidopsis plant circadian system

    Science.gov (United States)

    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.

  20. Circadian modulation of complex learning in diurnal and nocturnal Aplysia

    OpenAIRE

    Lyons, Lisa C.; Rawashdeh, Oliver; Katzoff, Ayelet; Susswein, Abraham J.; Eskin, Arnold

    2005-01-01

    Understanding modulation of memory, as well as the mechanisms underlying memory formation, has become a key issue in neuroscience research. Previously, we found that the formation of long-term, but not short-term, memory for a nonassociative form of learning, sensitization, was modulated by the circadian clock in the diurnal Aplysia californica. To define the scope of circadian modulation of memory, we examined an associative operant learning paradigm, learning that food is inedible (LFI). Si...

  1. 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...

  2. 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...

  3. Associations between circadian and stress response cortisol in children

    OpenAIRE

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

    2017-01-01

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

  4. 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 “...

  5. Maternal feeding controls fetal biological clock.

    Directory of Open Access Journals (Sweden)

    Hidenobu Ohta

    Full Text Available BACKGROUND: It is widely accepted that circadian physiological rhythms of the fetus are affected by oscillators in the maternal brain that are coupled to the environmental light-dark (LD cycle. METHODOLOGY/PRINCIPAL FINDINGS: To study the link between fetal and maternal biological clocks, we investigated the effects of cycles of maternal food availability on the rhythms of Per1 gene expression in the fetal suprachiasmatic nucleus (SCN and liver using a transgenic rat model whose tissues express luciferase in vitro. Although the maternal SCN remained phase-locked to the LD cycle, maternal restricted feeding phase-advanced the fetal SCN and liver by 5 and 7 hours respectively within the 22-day pregnancy. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that maternal feeding entrains the fetal SCN and liver independently of both the maternal SCN and the LD cycle. This indicates that maternal-feeding signals can be more influential for the fetal SCN and particular organ oscillators than hormonal signals controlled by the maternal SCN, suggesting the importance of a regular maternal feeding schedule for appropriate fetal molecular clockwork during pregnancy.

  6. Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload

    Energy Technology Data Exchange (ETDEWEB)

    Pardo Andreu, G.L. [Centro de Quimica Farmaceutica, Departamento de Investigaciones Biomedicas, Ciudad de La Habana (Cuba); Inada, N.M.; Vercesi, A.E. [Universidade Estadual de Campinas, Departamento de Patologia Clinica, Faculdade de Ciencias Medicas, Campinas, SP (Brazil); Curti, C. [Universidade de Sao Paulo, Departamento de Fisica e Quimica, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, SP (Brazil)

    2009-01-15

    One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21{+-}4 to 130{+-}7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H{sup +} leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria. (orig.)

  7. Comparison of coupled and uncoupled load simulations on a jacket support structure

    DEFF Research Database (Denmark)

    Haselbach, Philipp Ulrich; Natarajan, Anand; Jiwinangun, Randi Gusto

    2013-01-01

    In this article, a comparison of the moments and forces at the joints of a jacket structure is made between fully coupled aerohydroelastic simulations in HAWC2 and uncoupled load predictions in the finite element software Abaqus. The jacket sub structure is modelled in moderate deep waters of 50m...... structure similar to the Upwind reference jacket is developed in the Abaqus environment, to which is added the transition piece and tower. The aeroelastic loads determined in normal operating conditions of the turbine is integrated and centralized as nodal forces and moments acting at the tower top...... in Abaqus. The fully coupled simulation is implemented and performed in HAWC2. In the uncoupled case, the loads (wave loads and tower base loads) are analysed by an implicit structural Finite Element Analysis (Abaqus 6.11-1). A subroutine is used as a preprocessor generating a beam element model and linking...

  8. Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle

    DEFF Research Database (Denmark)

    Fernström, Maria; Tonkonogi, Michail; Sahlin, Kent

    2004-01-01

    Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting...... respiration or state 3). Protein expression of UCP3 and ANT was measured with Western blotting. After endurance training, .VO2peak, citrate synthase activity (CS), state 3 respiration and ANT increased by 24, 47, 40 and 95%, respectively (all P ... mitochondrial resistance to Ca2+ overload but does not influence UCR or protein expression of UCP3 and ANT. The increased Ca2+ resistance may prevent mitochondrial degradation and the mechanism needs to be further explored....

  9. Temperature controls oxidative phosphorylation and reactive oxygen species production through uncoupling in rat skeletal muscle mitochondria.

    Science.gov (United States)

    Jarmuszkiewicz, Wieslawa; Woyda-Ploszczyca, Andrzej; Koziel, Agnieszka; Majerczak, Joanna; Zoladz, Jerzy A

    2015-06-01

    Mitochondrial respiratory and phosphorylation activities, mitochondrial uncoupling, and hydrogen peroxide formation were studied in isolated rat skeletal muscle mitochondria during experimentally induced hypothermia (25 °C) and hyperthermia (42 °C) compared to the physiological temperature of resting muscle (35 °C). For nonphosphorylating mitochondria, increasing the temperature from 25 to 42 °C led to a decrease in membrane potential, hydrogen peroxide production, and quinone reduction levels. For phosphorylating mitochondria, no temperature-dependent changes in these mitochondrial functions were observed. However, the efficiency of oxidative phosphorylation decreased, whereas the oxidation and phosphorylation rates and oxidative capacities of the mitochondria increased, with increasing assay temperature. An increase in proton leak, including uncoupling protein-mediated proton leak, was observed with increasing assay temperature, which could explain the reduced oxidative phosphorylation efficiency and reactive oxygen species production. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Classical-processing and quantum-processing signal separation methods for qubit uncoupling

    Science.gov (United States)

    Deville, Yannick; Deville, Alain

    2012-12-01

    The Blind Source Separation problem consists in estimating a set of unknown source signals from their measured combinations. It was only investigated in a non-quantum framework up to now. We propose its first quantum extensions. We thus introduce the Quantum Source Separation field, investigating both its blind and non-blind configurations. More precisely, we show how to retrieve individual quantum bits (qubits) only from the global state resulting from their undesired coupling. We consider cylindrical-symmetry Heisenberg coupling, which e.g. occurs when two electron spins interact through exchange. We first propose several qubit uncoupling methods which typically measure repeatedly the coupled quantum states resulting from individual qubits preparations, and which then statistically process the classical data provided by these measurements. Numerical tests prove the effectiveness of these methods. We then derive a combination of quantum gates for performing qubit uncoupling, thus avoiding repeated qubit preparations and irreversible measurements.

  11. Derivatives of Rhodamine 19 as Mild Mitochondria-targeted Cationic Uncouplers*

    Science.gov (United States)

    Antonenko, Yuri N.; Avetisyan, Armine V.; Cherepanov, Dmitry A.; Knorre, Dmitry A.; Korshunova, Galina A.; Markova, Olga V.; Ojovan, Silvia M.; Perevoshchikova, Irina V.; Pustovidko, Antonina V.; Rokitskaya, Tatyana I.; Severina, Inna I.; Simonyan, Ruben A.; Smirnova, Ekaterina A.; Sobko, Alexander A.; Sumbatyan, Natalia V.; Severin, Fedor F.; Skulachev, Vladimir P.

    2011-01-01

    A limited decrease in mitochondrial membrane potential can be beneficial for cells, especially under some pathological conditions, suggesting that mild uncouplers (protonophores) causing such an effect are promising candidates for therapeutic uses. The great majority of protonophores are weak acids capable of permeating across membranes in their neutral and anionic forms. In the present study, protonophorous activity of a series of derivatives of cationic rhodamine 19, including dodecylrhodamine (C12R1) and its conjugate with plastoquinone (SkQR1), was revealed using a variety of assays. Derivatives of rhodamine B, lacking dissociable protons, showed no protonophorous properties. In planar bilayer lipid membranes, separating two compartments differing in pH, diffusion potential of H+ ions was generated in the presence of C12R1 and SkQR1. These compounds induced pH equilibration in liposomes loaded with the pH probe pyranine. C12R1 and SkQR1 partially stimulated respiration of rat liver mitochondria in State 4 and decreased their membrane potential. Also, C12R1 partially stimulated respiration of yeast cells but, unlike the anionic protonophore FCCP, did not suppress their growth. Loss of function of mitochondrial DNA in yeast (grande-petite transformation) is known to cause a major decrease in the mitochondrial membrane potential. We found that petite yeast cells are relatively more sensitive to the anionic uncouplers than to C12R1 compared with grande cells. Together, our data suggest that rhodamine 19-based cationic protonophores are self-limiting; their uncoupling activity is maximal at high membrane potential, but the activity decreases membrane potentials, which causes partial efflux of the uncouplers from mitochondria and, hence, prevents further membrane potential decrease. PMID:21454507

  12. Excitation contraction uncoupling by high intracellular [Ca2+] in frog skeletal muscle: a voltage clamp study.

    Science.gov (United States)

    Olivera, J Fernando; Pizarro, Gonzalo

    2016-10-01

    Raising the intracellular [Ca 2+ ] ([Ca 2+ ] i ) was previously found to produce uncoupling between the electrical depolarization of the transverse tubules and contraction in skinned muscle fibers. Here we study the effect of elevated [Ca 2+ ] i in voltage clamped cut fibers of frog skeletal muscle to establish how the charge movement, a measure of the activation of the dihydropyridine receptors (DHPR)-voltage sensors, and Ca 2+ release, a consequence of the opening of the ryanodine receptor (RyR)-release channels, were affected. [Ca 2+ ] i was raised by various procedures (pharmacological release from the sarcoplasmic reticulum, application of high [Ca 2+ ] i intracellular solution, permeabilization of the plasma membrane by a Ca 2+ ionophore) all of which produced impairment of excitation-contraction coupling. The charge movement was reduced from 20.2 ± 1.24 to 9.9 ± 0.94 nC/μF meanwhile the Ca 2+ release flux was reduced from 13.5 + 0.7 to 2.2 ± 0.3 μM/ms (n = 33). This suggests that a significant fraction of the DHPRs that remained functional, could not activate RyRs, and were therefore presumably disconnected. These results are broadly consistent with the original reports in skinned fibers. Uncoupling was prevented by the addition to the intracellular solution of the protease inhibitor leupeptin. In approximately 40 % of the uncoupled cells we observed that the [Ca 2+ ] i transient continued to rise after the voltage clamp pulse was turned off. This loss of control by membrane voltage suggests that the uncoupled release channels might have another mechanism of activation, likely by Ca 2+ .

  13. Augmenting energy expenditure by mitochondrial uncoupling: a role of AMP-activated protein kinase

    Czech Academy of Sciences Publication Activity Database

    Klaus, S.; Keipert, S.; Rossmeisl, Martin; Kopecký, Jan

    2012-01-01

    Roč. 7, č. 3 (2012), s. 369-386 ISSN 1555-8932 R&D Projects: GA MZd(CZ) NS10528; GA MŠk(CZ) 7E10059; GA MŠk(CZ) OC08008 Institutional research plan: CEZ:AV0Z50110509 Keywords : adipose tissue * skeletal muscle * uncoupling protein * transgenic mice * insulin sensitivity Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.329, year: 2012

  14. Triglyceride-lowering effect of respiratory uncoupling in white adipose tissue

    Czech Academy of Sciences Publication Activity Database

    Rossmeisl, Martin; Kovář, J.; Syrový, Ivo; Flachs, Pavel; Bobková, D.; Kolář, František; Poledne, R.; Kopecký, Jan

    2005-01-01

    Roč. 13, č. 5 (2005), s. 835-844 ISSN 1071-7323 R&D Projects: GA ČR(CZ) GP303/03/P127; GA ČR(CZ) GA303/02/1220 Institutional research plan: CEZ:AV0Z5011922 Keywords : adipose tissue * uncoupling protein * lipoprotein lipase Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.972, year: 2005

  15. 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 

  16. 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

  17. 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.

  18. Circadian Disruption Changes Gut Microbiome Taxa and Functional Gene Composition.

    Science.gov (United States)

    Deaver, Jessica A; Eum, Sung Y; Toborek, Michal

    2018-01-01

    Disrupted circadian rhythms and alterations of the gut microbiome composition were proposed to affect host health. Therefore, the aim of this research was to identify whether these events are connected and if circadian rhythm disruption by abnormal light-dark (LD) cycles affects microbial community gene expression and host vulnerability to intestinal dysfunction. Mice were subjected to either a 4-week period of constant 24-h light or of normal 12-h LD cycles. Stool samples were collected at the beginning and after the circadian rhythm disruption. A metatranscriptomic analysis revealed an increase in Ruminococcus torques , a bacterial species known to decrease gut barrier integrity, and a decrease in Lactobacillus johnsonii , a bacterium that helps maintain the intestinal epithelial cell layer, after circadian rhythm disruption. In addition, genes involved in pathways promoting host beneficial immune responses were downregulated, while genes involved in the synthesis and transportation of the endotoxin lipopolysaccharide were upregulated in mice with disrupted circadian cycles. Importantly, these mice were also more prone to dysfunction of the intestinal barrier. These results further elucidate the impact of light-cycle disruption on the gut microbiome and its connection with increased incidence of disease in response to circadian rhythm disturbances.

  19. [Study on feeding behavior patterns of rats on cariogenic diet].

    Science.gov (United States)

    Sasaki, Y

    1989-03-01

    The feeding behavior patterns of Jcl:Wistar rats fed on commercial stock diet and cariogenic diet (Diet #2000) were investigated with the newly developed autorecording system. They were caged separately under a regular light-dark cycle (L:D = 12:12). The results and conclusion were as follows. All rats have a circadian feeding rhythm, and 70-85% of feeding frequency were observed during the dark period. The group on the commercial stock diet showed a dual-peak pattern of feeding at 20:30 and 4:00. On the other hand, the cariogenic diet groups showed a more frequent feeding pattern during the dark period. The feeding frequency increased from 1:00 to 3:00 in the high sucrose diet group and more frequent feeding was observed. From these results, it was suggested that dental caries in the rats was caused by not only the local effect of sucrose in the mouth but also by the changing patterns of feeding behavior with cariogenic diet.

  20. Muscle Mitochondrial Uncoupling Dismantles Neuromuscular Junction and Triggers Distal Degeneration of Motor Neurons

    Science.gov (United States)

    Dupuis, Luc; Gonzalez de Aguilar, Jose-Luis; Echaniz-Laguna, Andoni; Eschbach, Judith; Rene, Frédérique; Oudart, Hugues; Halter, Benoit; Huze, Caroline; Schaeffer, Laurent; Bouillaud, Frédéric; Loeffler, Jean-Philippe

    2009-01-01

    Background Amyotrophic lateral sclerosis (ALS), the most frequent adult onset motor neuron disease, is associated with hypermetabolism linked to defects in muscle mitochondrial energy metabolism such as ATP depletion and increased oxygen consumption. It remains unknown whether muscle abnormalities in energy metabolism are causally involved in the destruction of neuromuscular junction (NMJ) and subsequent motor neuron degeneration during ALS. Methodology/Principal Findings We studied transgenic mice with muscular overexpression of uncoupling protein 1 (UCP1), a potent mitochondrial uncoupler, as a model of muscle restricted hypermetabolism. These animals displayed age-dependent deterioration of the NMJ that correlated with progressive signs of denervation and a mild late-onset motor neuron pathology. NMJ regeneration and functional recovery were profoundly delayed following injury of the sciatic nerve and muscle mitochondrial uncoupling exacerbated the pathology of an ALS animal model. Conclusions/Significance These findings provide the proof of principle that a muscle restricted mitochondrial defect is sufficient to generate motor neuron degeneration and suggest that therapeutic strategies targeted at muscle metabolism might prove useful for motor neuron diseases. PMID:19404401

  1. Kidney transplantation restored uncoupled bone turnover in end-stage renal disease.

    Science.gov (United States)

    Kawarazaki, Hiroo; Shibagaki, Yugo; Kido, Ryo; Nakajima, Ichiro; Fuchinoue, Shohei; Ando, Katsuyuki; Fujita, Toshiro; Fukagawa, Masafumi; Teraoka, Satoshi; Fukumoto, Seiji

    2012-07-01

    While kidney transplantation (KTx) reverses many disorders associated with end-stage renal disease (ESRD), patients who have received KTx often have chronic kidney disease and bone and mineral disorder (CKD-MBD). However, it is unknown how bone metabolism changes by KTx. Living donor-KTx recipients (n = 34) at Tokyo Women's Medical University were prospectively recruited and the levels of bone-specific alkaline phosphatase (BAP) and serum cross-linked N-telopeptides of Type 1 collagen (NTX) were measured before, 6 and 12 months after transplantation. Before KTx, serum BAP was within the reference range in more than half of patients while NTX was high in most patients. Serum NTX was higher in patients with longer dialysis durations compared to that with shorter durations before KTx. However, there was no difference in serum BAP between these patients. After KTx, BAP increased while NTX decreased along with the decline of PTH. In addition, the numbers of patients who showed high BAP and NTX were comparable after KTx. These results suggest that bone formation is suppressed and uncoupled with bone resorption in patients with ESRD and this uncoupling is restored by KTx. Further studies are necessary to clarify the mechanism of bone uncoupling in patients with ESRD.

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

    OpenAIRE

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

    2012-01-01

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

  3. A Ketone Ester Diet Increases Brain Malonyl-CoA and Uncoupling Proteins 4 and 5 while Decreasing Food Intake in the Normal Wistar Rat*

    Science.gov (United States)

    Kashiwaya, Yoshihiro; Pawlosky, Robert; Markis, William; King, M. Todd; Bergman, Christian; Srivastava, Shireesh; Murray, Andrew; Clarke, Kieran; Veech, Richard L.

    2010-01-01

    Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mm and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD+]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain l-glutamate by 15–20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain. PMID:20529850

  4. A ketone ester diet increases brain malonyl-CoA and Uncoupling proteins 4 and 5 while decreasing food intake in the normal Wistar Rat.

    Science.gov (United States)

    Kashiwaya, Yoshihiro; Pawlosky, Robert; Markis, William; King, M Todd; Bergman, Christian; Srivastava, Shireesh; Murray, Andrew; Clarke, Kieran; Veech, Richard L

    2010-08-20

    Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mm and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD(+)]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain L-glutamate by 15-20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain.

  5. Circadian rhythms in blood pressure in free-ranging three-toed sloths (Bradypus variegatus

    Directory of Open Access Journals (Sweden)

    Duarte D.P.F.

    2003-01-01

    Full Text Available Blood pressure (BP profiles were monitored in nine free-ranging sloths (Bradypus variegatus by coupling one common carotid artery to a BP telemetry transmitter. Animals moved freely in an isolated and temperature-controlled room (24ºC with 12/12-h artificial light-dark cycles and behaviors were observed during resting, eating and moving. Systolic (SBP and diastolic (DBP blood pressures were sampled for 1 min every 15 min for 24 h. BP rhythm over 24 h was analyzed by the cosinor method and the mesor, amplitude, acrophase and percent rhythm were calculated. A total of 764 measurements were made in the light cycle and 721 in the dark cycle. Twenty-four-hour values (mean ± SD were obtained for SBP (121 ± 22 mmHg, DBP (86 ± 17 mmHg, mean BP (MBP, 98 ± 18 mmHg and heart rate (73 ± 16 bpm. The SBP, DBP and MBP were significantly higher (unpaired Student t-test during the light period (125 ± 21, 88 ± 15 and 100 ± 17 mmHg, respectively than during the dark period (120 ± 21, 85 ± 17 and 97 ± 17 mmHg, respectively and the acrophase occurred between 16:00 and 17:45 h. This circadian variation is similar to that observed in cats, dogs and marmosets. The BP decreased during "behavioral sleep" (MBP down from 110 ± 19 to 90 ± 19 mmHg at 21:00 to 8:00 h. Both feeding and moving induced an increase in MBP (96 ± 17 to 119 ± 17 mmHg at 17:00 h and 97 ± 19 to 105 ± 12 mmHg at 15:00 h, respectively. The results show that conscious sloths present biphasic circadian fluctuations in BP levels, which are higher during the light period and are mainly synchronized with feeding.

  6. The circadian clock modulates anti-cancer properties of curcumin

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  7. 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.

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

    Science.gov (United States)

    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

  9. Non-circadian expression masking clock-driven weak transcription rhythms in U2OS cells.

    Directory of Open Access Journals (Sweden)

    Julia Hoffmann

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  11. Control of Circadian Behavior by Transplanted Suprachiasmatic Nuclei and by the Tau Gene

    National Research Council Canada - National Science Library

    Menaker, Micahel

    1997-01-01

    The mammalian retina was found to contain an independent circadian oscillator which regulates the synthesis of melatonin and has effects, through a presently unknown pathway, on the circadian rhythm...

  12. Impacts of nurses’ circadian rhythm sleep disorders, fatigue, and depression on medication administration errors

    Directory of Open Access Journals (Sweden)

    Abdelbaset M. Saleh

    2014-01-01

    Conclusions: Medication administration errors, fatigue and depression were all significantly affected by circadian sleep disorders. An administration’s control of work flow to provide convenient sleep hours will help in improving sleep circadian rhythms and consequently minimize these problems.

  13. 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.

  14. Feeding Your Baby

    Medline Plus

    Full Text Available ... care Is it safe? Labor & birth Postpartum care Baby Caring for your baby Feeding your baby Family ... community Home > Baby > Feeding your baby Feeding your baby E-mail to a friend Please fill in ...

  15. Feeding Your Baby

    Medline Plus

    Full Text Available ... our online community Home > Baby > Feeding your baby Feeding your baby E-mail to a friend Please ... been added to your dashboard . Time to eat! Feeding your baby helps her grow healthy and strong. ...

  16. Breastfeeding vs. Formula Feeding

    Science.gov (United States)

    ... for Educators Search English Español Breastfeeding vs. Formula Feeding KidsHealth / For Parents / Breastfeeding vs. Formula Feeding What's ... work with a lactation specialist. All About Formula Feeding Commercially prepared infant formulas are a nutritious alternative ...

  17. Feeding tube insertion - gastrostomy

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002937.htm Feeding tube insertion - gastrostomy To use the sharing features on this page, please enable JavaScript. A gastrostomy feeding tube insertion is the placement of a feeding ...

  18. Animal Feeding Operations

    Science.gov (United States)

    ... type=”submit” value=”Submit” /> Healthy Water Home Animal Feeding Operations Recommend on Facebook Tweet Share Compartir ... of Concentrated Animal Feeding Operations (CAFOs) What are Animal Feeding Operations (AFOs)? According to the United States ...

  19. 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.

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

    Science.gov (United States)

    Ushirogawa, H; Abe, Y; Tomioka, K

    1997-10-01

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

  1. Protein phosphatase dependent circadian regulation of intermediate-term associative memory

    OpenAIRE

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    M.A. Quera Salva

    2012-04-01

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

  3. 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.

  4. 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

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

    Science.gov (United States)

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

    2017-08-01

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

  6. Neurogenetics of Drosophila circadian clock: expect the unexpected.

    Science.gov (United States)

    Jarabo, Patricia; Martin, Francisco A

    2017-12-01

    Daily biological rhythms (i.e. circadian) are a fundamental part of animal behavior. Numerous reports have shown disruptions of the biological clock in neurodegenerative disorders and cancer. In the latter case, only recently we have gained insight into the molecular mechanisms. After 45 years of intense study of the circadian rhtythms, we find surprising similarities among species on the molecular clock that governs biological rhythms. Indeed, Drosophila is one of the most widely used models in the study of chronobiology. Recent studies in the fruit fly have revealed unpredicted roles for the clock machinery in different aspects of behavior and physiology. Not only the central pacemaker cells do have non-classical circadian functions but also circadian genes work in other cells and tissues different from central clock neurons. In this review, we summarize these new evidences. We also recapitulate the most basic features of Drosophila circadian clock, including recent data about the inputs and outputs that connect the central pacemaker with other regions of the brain. Finally, we discuss the advantages and drawbacks of using natural versus laboratory conditions.

  7. Towards assessing the impact of circadian lighting in elderly housing from a holistic perspective

    DEFF Research Database (Denmark)

    Sen, Sumit; Flyvholm, Anton; Xylakis, Emmanouil

    2017-01-01

    Circadian lighting has the potential to be used as a welfare technology, and improve the health and well-being of the general public. A research-based dynamic circadian lighting scheme can be developed using LED lighting. Testing and evaluating circadian lighting however requires a holistic...

  8. Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells.

    Science.gov (United States)

    Shikata, Yuki; Kiga, Masaki; Futamura, Yushi; Aono, Harumi; Inoue, Hiroyuki; Kawada, Manabu; Osada, Hiroyuki; Imoto, Masaya

    2017-04-01

    The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated nonactin, an antibiotic mitochondrial uncoupler, as a hit compound. Nonactin, as well as other mitochondrial uncouplers, induced apoptosis selectively in β-catenin mutated tumor cells. Significant tumor regression was observed in the β-catenin mutant HCT 116 xenograft model, but not in the β-catenin wild type A375 xenograft model, in response to daily administration of nonactin in vivo. Furthermore, we found that expression of an active mutant form of β-catenin induced a decrease in the glycolysis rate. Taken together, our results demonstrate that tumor cells with mutated β-catenin depend on mitochondrial oxidative phosphorylation for survival. Therefore, they undergo apoptosis in response to mitochondrial dysfunction following the addition of mitochondrial uncouplers, such as nonactin. These results suggest that targeting mitochondria is a potential chemotherapeutic strategy for tumor cells that harbor β-catenin mutations. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  9. PER1 Phosphorylation Specifies Feeding Rhythm in Mice

    Directory of Open Access Journals (Sweden)

    Zhiwei Liu

    2014-06-01

    Full Text Available Organization of circadian behavior, physiology, and metabolism is important for human health. An S662G mutation in hPER2 has been linked to familial advanced sleep-phase syndrome (FASPS. Although the paralogous phosphorylation site S714 in PER1 is conserved in mice, its specific function in circadian organization remains unknown. Here, we find that the PER1S714G mutation accelerates the molecular feedback loop. Furthermore, hPER1S714G mice, but not hPER2S662G mice, exhibit peak time of food intake that is several hours before daily energy expenditure peaks. Both the advanced feeding behavior and the accelerated clock disrupt the phase of expression of several key metabolic regulators in the liver and adipose tissue. Consequently, hPER1S714G mice rapidly develop obesity on a high-fat diet. Our studies demonstrate that PER1 and PER2 are linked to different downstream pathways and that PER1 maintains coherence between the circadian clock and energy metabolism.

  10. Relationship between circadian typology and big five personality domains.

    Science.gov (United States)

    Tonetti, Lorenzo; Fabbri, Marco; Natale, Vincenzo

    2009-02-01

    We explored the relationship between personality, based on the five-factor model, and circadian preference. To this end, 503 participants (280 females, 223 males) were administered the Morningness-Eveningness Questionnaire (MEQ) and the self-report version of the Big Five Observer (BFO) to determine circadian preference and personality features, respectively. Morning types scored significantly higher than evening and intermediate types on the conscientiousness factor. Evening types were found to be more neurotic than morning types. With reference to the big five personality model, our data, together with those of all the previous studies, indicate that the conscientiousness domain is the one that best discriminates among the three circadian types. Results are discussed with reference to neurobiological models of personality.

  11. Circadian regulation of hormone signaling and plant physiology.

    Science.gov (United States)

    Atamian, Hagop S; Harmer, Stacey L

    2016-08-01

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

  12. 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

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

    Science.gov (United States)

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

    2014-01-01

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

  14. 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.

  15. Antioxidant and regulatory role of mitochondrial uncoupling protein UCP2 in pancreatic beta-cells

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Olejár, Tomáš; Smolková, Katarína; Ježek, Jan; Dlasková, Andrea; Plecitá-Hlavatá, Lydie; Zelenka, Jaroslav; Špaček, Tomáš; Engstová, Hana; Reguera Pajuelo, David; Jabůrek, Martin

    2014-01-01

    Roč. 63, Suppl.1 (2014), S73-S91 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GAP305/12/1247; GA ČR(CZ) GPP304/10/P204; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : mitochondria * uncoupling protein UCP2 * pancreatic beta-cells * reactive oxygen species * glucose-stimulated insulin secretion Subject RIV: EA - Cell Biology Impact factor: 1.293, year: 2014

  16. Synchronization of uncoupled excitable systems induced by white and coloured noise

    International Nuclear Information System (INIS)

    Zambrano, Samuel; Marino, Ines P; Seoane, Jesus M; Sanjuan, Miguel A F; Euzzor, Stefano; Geltrude, Andrea; Meucci, Riccardo; Arecchi, Fortunato T

    2010-01-01

    We study, both numerically and experimentally, the synchronization of uncoupled excitable systems due to a common noise. We consider two identical FitzHugh-Nagumo systems, which display both spiking and non-spiking behaviours in chaotic or periodic regimes. An electronic circuit provides a laboratory implementation of these dynamics. Synchronization is tested with both white and coloured noise, showing that coloured noise is more effective in inducing synchronization of the systems. We also study the effects on the synchronization of parameter mismatch and of the presence of intrinsic (not common) noise, and we conclude that the best performance of coloured noise is robust under these distortions.

  17. Inhibition of electron transfer and uncoupling effects by emodin and emodinanthrone in Escherichia coli.

    Science.gov (United States)

    Ubbink-Kok, T; Anderson, J A; Konings, W N

    1986-07-01

    The anthraquinones emodin (1,3,delta-trihydroxy-6-methylanthraquinone) and emodinanthrone (1,3,8-trihydroxy-6-methylanthrone) inhibited respiration-driven solute transport at micromolar concentrations in membrane vesicles of Escherichia coli. This inhibition was enhanced by Ca ions. The inhibitory action on solute transport is caused by inhibition of electron flow in the respiratory chain, most likely at the level between ubiquinone and cytochrome b, and by dissipation of the proton motive force. The uncoupling action was confirmed by studies on the proton motive force in beef heart cytochrome oxidase proteoliposomes. These two effects on energy transduction in cytoplasmic membranes explain the antibiotic properties of emodin and emodinanthrone.

  18. Hydroperoxy fatty acid cycling mediated by mitochondrial uncoupling protein UCP2

    Czech Academy of Sciences Publication Activity Database

    Jabůrek, Martin; Miyamoto, S.; Di Mascio, P.; Garlid, K. D.; Ježek, Petr

    2004-01-01

    Roč. 279, č. 51 (2004), s. 53097-53102 ISSN 0021-9258 R&D Projects: GA AV ČR IAA5011106; GA MŠk LZ1K03002; GA ČR GA204/04/0495 Grant - others:NIH(US) TW01487; NIH(US) DK 56273; FAPESP(BR) CHPq; Programa de Apoio aos Nucleos de Excelencia(BR) PRONEX/FINEP Institutional research plan: CEZ:AV0Z5011922 Keywords : uncoupling protein * fatty acid hydroperoxides * reactive oxygen species Subject RIV: CE - Biochemistry Impact factor: 6.355, year: 2004

  19. Light and Cognition: Roles for Circadian Rhythms, Sleep, and Arousal

    Science.gov (United States)

    Fisk, Angus S.; Tam, Shu K. E.; Brown, Laurence A.; Vyazovskiy, Vladyslav V.; Bannerman, David M.; Peirson, Stuart N.

    2018-01-01

    Light exerts a wide range of effects on mammalian physiology and behavior. As well as synchronizing circadian rhythms to the external environment, light has been shown to modulate autonomic and neuroendocrine responses as well as regulating sleep and influencing cognitive processes such as attention, arousal, and performance. The last two decades have seen major advances in our understanding of the retinal photoreceptors that mediate these non-image forming responses to light, as well as the neural pathways and molecular mechanisms by which circadian rhythms are generated and entrained to the external light/dark (LD) cycle. By contrast, our understanding of the mechanisms by which lighting influences cognitive processes is more equivocal. The effects of light on different cognitive processes are complex. As well as the direct effects of light on alertness, indirect effects may also occur due to disrupted circadian entrainment. Despite the widespread use of disrupted LD cycles to study the role circadian rhythms on cognition, the different experimental protocols used have subtly different effects on circadian function which are not always comparable. Moreover, these protocols will also disrupt sleep and alter physiological arousal, both of which are known to modulate cognition. Studies have used different assays that are dependent on different cognitive and sensory processes, which may also contribute to their variable findings. Here, we propose that studies addressing the effects of different lighting conditions on cognitive processes must also account for their effects on circadian rhythms, sleep, and arousal if we are to fully understand the physiological basis of these responses. PMID:29479335

  20. Circadian profile of cardiac autonomic nervous modulation in healthy subjects

    DEFF Research Database (Denmark)

    Bonnemeier, Hendrik; Richardt, Gert; Potratz, Jürgen

    2003-01-01

    UNLABELLED: Circadian Profile of Heart Rate Variability. INTRODUCTION: Although heart rate variability (HRV) has been established as a tool to study cardiac autonomic activity, almost no data are available on the circadian patterns of HRV in healthy subjects aged 20 to 70 years. METHODS AND RESULTS...... higher in men. Younger men also exhibited significantly higher values...... parasympathetic activity. The significant gender-related difference of HRV decreases with aging. These findings emphasize the need to determine age-, gender-, and nycthemeral-dependent normal ranges for HRV assessment....

  1. 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.

  2. 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.

  3. Explicit thin-lens solution for an arbitrary four by four uncoupled beam transfer matrix

    Energy Technology Data Exchange (ETDEWEB)

    Balandin, V. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Orlov, S. [Moscow State Univ. (Russian Federation). Faculty of Computational Mathematics and Cybernetics

    2011-10-15

    In the design of beam transport lines one often meets the problem of constructing a quadrupole lens system that will produce desired transfer matrices in both the horizontal and vertical planes. Nowadays this problem is typically approached with the help of computer routines, but searching for the numerical solution one has to remember that it is not proven yet that an arbitrary four by four uncoupled beam transfer matrix can be represented by using a finite number of drifts and quadrupoles (representation problem) and the answer to this questions is not known not only for more or less realistic quadrupole field models but also for the both most commonly used approximations of quadrupole focusing, namely thick and thin quadrupole lenses. In this paper we make a step forward in resolving the representation problem and, by giving an explicit solution, we prove that an arbitrary four by four uncoupled beam transfer matrix actually can be obtained as a product of a finite number of thin-lenses and drifts. (orig.)

  4. Mitochondrial Hormesis in Pancreatic β Cells: Does Uncoupling Protein 2 Play a Role?

    Directory of Open Access Journals (Sweden)

    Ning Li

    2012-01-01

    Full Text Available In pancreatic β cells, mitochondrial metabolism translates glucose sensing into signals regulating insulin secretion. Chronic exposure of β cells to excessive nutrients, namely, glucolipotoxicity, impairs β-cell function. This is associated with elevated ROS production from overstimulated mitochondria. Mitochondria are not only the major source of cellular ROS, they are also the primary target of ROS attacks. The mitochondrial uncoupling protein UCP2, even though its uncoupling properties are debated, has been associated with protective functions against ROS toxicity. Hormesis, an adaptive response to cellular stresses, might contribute to the protection against β-cell death, possibly limiting the development of type 2 diabetes. Mitochondrial hormesis, or mitohormesis, is a defense mechanism observed in ROS-induced stress-responses by mitochondria. In β cells, mitochondrial damages induced by sublethal exogenous H2O2 can induce secondary repair and defense mechanisms. In this context, UCP2 is a marker of mitohormesis, being upregulated following stress conditions. When overexpressed in nonstressed naïve cells, UCP2 confers resistance to oxidative stress. Whether treatment with mitohormetic inducers is sufficient to restore or ameliorate secretory function of β cells remains to be determined.

  5. Understanding uncoupling in the multiredox centre P450 3A4-BMR model system.

    Science.gov (United States)

    Degregorio, Danilo; Sadeghi, Sheila J; Di Nardo, Giovanna; Gilardi, Gianfranco; Solinas, Sandro P

    2011-01-01

    Understanding the uncoupling at the haem active site and/or at the level of multidomain electron transfer is an important element in cytochrome P450 chemistry. Here a chimeric model system consisting of human cytochrome P450 3A4 and the soluble reductase domain of CYP102A1 from Bacillus megaterium (BMR) is used to study the relationship between electron transfer and the coupling efficiency in substrate monoxygenation. Several regulatory features were considered. FAD and FMN added to apoenzyme in oversaturating concentrations influence neither formaldehyde production nor coupling efficiency. The optimal conditions of coupling efficiency depended only on the NADPH concentration. The pH (8.0) and ionic strength (50 mM potassium phosphate) were found to modulate the level of coupling, indicating an influence over the formation of a productive interaction between the BMR and the haem domain. Overall, uncoupling is found to be an intrinsic property of the haem domain, and the covalent linkage of the reductase in a single polypeptide chain has little influence over the activity coupled to product formation.

  6. Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan.

    Science.gov (United States)

    Wolkow, Catherine A; Iser, Wendy B

    2006-05-01

    Uncoupling proteins (UCPs), which dissipate the mitochondrial proton gradient, have the ability to decouple mitochodrial respiration from ATP production. Since mitochondrial electron transport is a major source of free radical production, it is possible that UCP activity might impact free radical production. Free radicals can react with and damage cellular proteins, DNA and lipids. Accumulated damage from oxidative stress is believed to be a major contributor to cellular decline during aging. If UCP function were to impact mitochondrial free radical production, then one would expect to find a link between UCP activity and aging. This theory has recently been tested in a handful of organisms whose genomes contain UCP1 homologs. Interestingly, these experiments indicate that UCP homologs can affect lifespan, although they do not support a simple relationship between UCP activity and aging. Instead, UCP-like proteins appear to have a variety of effects on lifespan, and on pathways implicated in lifespan regulation. One possible explanation for this complex picture is that UCP homologs may have tissue-specific effects that complicate their effects on aging. Furthermore, the functional analysis of UCP1 homologs is incomplete. Thus, these proteins may perform functions in addition to, or instead of, mitochondrial uncoupling. Although these studies have not revealed a clear picture of UCP effects on aging, they have contributed to the growing knowledge base for these interesting proteins. Future biochemical and genetic investigation of UCP-like proteins will do much to clarify their functions and to identify the regulatory networks in which they are involved.

  7. Uncoupling Protein 2: A Key Player and a Potential Therapeutic Target in Vascular Diseases

    Directory of Open Access Journals (Sweden)

    Giorgia Pierelli

    2017-01-01

    Full Text Available Uncoupling protein 2 (UCP2 is an inner mitochondrial membrane protein that belongs to the uncoupling protein family and plays an important role in lowering mitochondrial membrane potential and dissipating metabolic energy with prevention of oxidative stress accumulation. In the present article, we will review the evidence that UCP2, as a consequence of its roles within the mitochondria, represents a critical player in the predisposition to vascular disease development in both animal models and in humans, particularly in relation to obesity, diabetes, and hypertension. The deletion of the UCP2 gene contributes to atherosclerosis lesion development in the knockout mice, also showing significantly shorter lifespan. The UCP2 gene downregulation is a key determinant of higher predisposition to renal and cerebrovascular damage in an animal model of spontaneous hypertension and stroke. In contrast, UCP2 overexpression improves both hyperglycemia- and high-salt diet-induced endothelial dysfunction and ameliorates hypertensive target organ damage in SHRSP. Moreover, drugs (fenofibrate and sitagliptin and several vegetable compounds (extracts from Brassicaceae, berberine, curcumin, and capsaicin are able to induce UCP2 expression level and to exert beneficial effects on the occurrence of vascular damage. As a consequence, UCP2 becomes an interesting therapeutic target for the treatment of common human vascular diseases.

  8. Thyroid hormone affects secretory activity and uncoupling protein-3 expression in rat harderian gland.

    Science.gov (United States)

    Chieffi Baccari, Gabriella; Monteforte, Rossella; de Lange, Pieter; Raucci, Franca; Farina, Paola; Lanni, Antonia

    2004-07-01

    The effects of T(3) administration on the rat Harderian gland were examined at morphological, biochemical, and molecular levels. T(3) induced hypertrophy of the two cell types (A and B) present in the glandular epithelium. In type A cells, the hypertrophy was mainly due to an increase in the size of the lipid compartment. The acinar lumina were filled with lipoproteic substances, and the cells often showed an olocrine secretory pattern. In type B cells, the hypertrophy largely consisted of a marked proliferation of mitochondria endowed with tightly packed cristae, the mitochondrial number being nearly doubled (from 62 to 101/100 microm(2)). Although the average area of individual mitochondria decreased by about 50%, the total area of the mitochondrial compartment increased by about 80% (from 11 to 19/100 microm(2)). This could be ascribed to T(3)-induced mitochondrial proliferation. The morphological and morphometric data correlated well with our biochemical results, which indicated that mitochondrial respiratory activity is increased in hyperthyroid rats. T(3), by influencing the metabolic function of the mitochondrial compartment, induces lipogenesis and the release of secretory product by type A cells. Mitochondrial uncoupling proteins 2 and 3 were expressed at both mRNA and protein levels in the euthyroid rat Harderian gland. T(3) treatment increased the mRNA levels of both uncoupling protein 2 (UCP2) and UCP3, but the protein level only of UCP3. A possible role for these proteins in the Harderian gland is discussed.

  9. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects

    International Nuclear Information System (INIS)

    Fox, P.T.; Raichle, M.E.

    1986-01-01

    Coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2 ) was studied using multiple sequential administrations of 15 O-labeled radiotracers and positron emission tomography. In the resting state an excellent correlation between CBF and CMRO 2 was found when paired measurements of CBF and CMRO 2 from multiple (30-48) brain regions were tested in each of 33 normal subjects. Regional uncoupling of CBF and CMRO 2 was found, however, during neuronal activation induced by somatosensory stimulation. Stimulus-induced focal augmentation of cerebral blood flow (29% mean) far exceeded the concomitant local increase in tissue metabolic rate (mean, 5%), when resting-state and stimulated-state measurements were obtained in each of 9 subjects. Stimulus duration had no significant effect on response magnitude or on the degree of CBF-CMRO 2 uncoupling observed. Dynamic, physiological regulation of CBF by a mechanism (neuronal or biochemical) dependent on neuronal firing per se, but independent of the cerebral metabolic rate of oxygen, is hypothesized

  10. Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation.

    Science.gov (United States)

    Zhang, Jun-Xia; Qu, Xin-Liang; Chu, Peng; Xie, Du-Jiang; Zhu, Lin-Lin; Chao, Yue-Lin; Li, Li; Zhang, Jun-Jie; Chen, Shao-Liang

    2018-05-01

    Uncoupled endothelial nitric oxide synthase (eNOS) produces O 2 - instead of nitric oxide (NO). Earlier, we reported rapamycin, an autophagy inducer and inhibitor of cellular proliferation, attenuated low shear stress (SS) induced O 2 - production. Nevertheless, it is unclear whether autophagy plays a critical role in the regulation of eNOS uncoupling. Therefore, this study aimed to investigate the modulation of autophagy on eNOS uncoupling induced by low SS exposure. We found that low SS induced endothelial O 2 - burst, which was accompanied by reduced NO release. Furthermore, inhibition of eNOS by L-NAME conspicuously attenuated low SS-induced O 2 - releasing, indicating eNOS uncoupling. Autophagy markers such as LC3 II/I ratio, amount of Beclin1, as well as ULK1/Atg1 were increased during low SS exposure, whereas autophagic degradation of p62/SQSTM1 was markedly reduced, implying impaired autophagic flux. Interestingly, low SS-induced NO reduction could be reversed by rapamycin, WYE-354 or ATG5 overexpression vector via restoration of autophagic flux, but not by N-acetylcysteine or apocynin. eNOS uncoupling might be ascribed to autophagic flux blockade because phosphorylation of eNOS Thr495 by low SS or PMA stimulation was also regulated by autophagy. In contrast, eNOS acetylation was not found to be regulated by low SS and autophagy. Notably, although low SS had no influence on eNOS Ser1177 phosphorylation, whereas boosted eNOS Ser1177 phosphorylation by rapamycin were in favor of the eNOS recoupling through restoration of autophagic flux. Taken together, we reported a novel mechanism for regulation of eNOS uncoupling by low SS via autophagy-mediated eNOS phosphorylation, which is implicated in geometrical nature of atherogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Timing Matters: Circadian Rhythm in Sepsis, Obstructive Lung Disease, Obstructive Sleep Apnea, and Cancer.

    Science.gov (United States)

    Truong, Kimberly K; Lam, Michael T; Grandner, Michael A; Sassoon, Catherine S; Malhotra, Atul

    2016-07-01

    Physiological and cellular functions operate in a 24-hour cyclical pattern orchestrated by an endogenous process known as the circadian rhythm. Circadian rhythms represent intrinsic oscillations of biological functions that allow for adaptation to cyclic environmental changes. Key clock genes that affect the persistence and periodicity of circadian rhythms include BMAL1/CLOCK, Period 1, Period 2, and Cryptochrome. Remarkable progress has been made in our understanding of circadian rhythms and their role in common medical conditions. A critical review of the literature supports the association between circadian misalignment and adverse health consequences in sepsis, obstructive lung disease, obstructive sleep apnea, and malignancy. Circadian misalignment plays an important role in these disease processes and can affect disease severity, treatment response, and survivorship. Normal inflammatory response to acute infections, airway resistance, upper airway collapsibility, and mitosis regulation follows a robust circadian pattern. Disruption of normal circadian rhythm at the molecular level affects severity of inflammation in sepsis, contributes to inflammatory responses in obstructive lung diseases, affects apnea length in obstructive sleep apnea, and increases risk for cancer. Chronotherapy is an underused practice of delivering therapy at optimal times to maximize efficacy and minimize toxicity. This approach has been shown to be advantageous in asthma and cancer management. In asthma, appropriate timing of medication administration improves treatment effectiveness. Properly timed chemotherapy may reduce treatment toxicities and maximize efficacy. Future research should focus on circadian rhythm disorders, role of circadian rhythm in other diseases, and modalities to restore and prevent circadian disruption.

  12. Expression profiling of skeletal muscle following acute and chronic β2-adrenergic stimulation: implications for hypertrophy, metabolism and circadian rhythm

    Directory of Open Access Journals (Sweden)

    Lynch Gordon S

    2009-09-01

    Full Text Available Abstract Background Systemic administration of β-adrenoceptor (β-AR agonists has been found to induce skeletal muscle hypertrophy and significant metabolic changes. In the context of energy homeostasis, the importance of β-AR signaling has been highlighted by the inability of β1-3-AR-deficient mice to regulate energy expenditure and susceptibility to diet induced obesity. However, the molecular pathways and gene expression changes that initiate and maintain these phenotypic modulations are poorly understood. Therefore, the aim of this study was to identify differential changes in gene expression in murine skeletal muscle associated with systemic (acute and chronic administration of the β2-AR agonist formoterol. Results Skeletal muscle gene expression (from murine tibialis anterior was profiled at both 1 and 4 hours following systemic administration of the β2-AR agonist formoterol, using Illumina 46K mouse BeadArrays. Illumina expression profiling revealed significant expression changes in genes associated with skeletal muscle hypertrophy, myoblast differentiation, metabolism, circadian rhythm, transcription, histones, and oxidative stress. Differentially expressed genes relevant to the regulation of muscle mass and metabolism (in the context of the hypertrophic phenotype were further validated by quantitative RT-PCR to examine gene expression in response to both acute (1-24 h and chronic administration (1-28 days of formoterol at multiple timepoints. In terms of skeletal muscle hypertrophy, attenuation of myostatin signaling (including differential expression of myostatin, activin receptor IIB, phospho-Smad3 etc was observed following acute and chronic administration of formoterol. Acute (but not chronic administration of formoterol also significantly induced the expression of genes involved in oxidative metabolism, including hexokinase 2, sorbin and SH3 domain containing 1, and uncoupling protein 3. Interestingly, formoterol

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

    Science.gov (United States)

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Leila M. Guissoni Campos

    2018-02-01

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

  15. Improved circadian sleep-wake cycle in infants fed a day/night dissociated formula milk.

    Science.gov (United States)

    Cubero, J; Narciso, D; Aparicio, S; Garau, C; Valero, V; Rivero, M; Esteban, S; Rial, R; Rodríguez, A B; Barriga, C

    2006-06-01

    On the basis of the circadian nutritional variations present in breast milk, and of the implications for the sleep/wake cycle of the nutrients present in infant formula milks, we designed a formula milk nutritionally dissociated into a Day/Night composition. The goal was to improve the bottle-fed infant's sleep/wake circadian rhythm. A total of 21 infants aged 4-20 weeks with sleeping difficulties were enrolled in the three-week duration study. The sleep analysis was performed using an actimeter (Actiwatch) placed on an ankle of each infant to uninterruptedly record movements during the three weeks. The dissociated Day milk, designed to be administered from 06:00 to 18:00, contained low levels of tryptophan (1.5g/100g protein) and carbohydrates, high levels of proteins, and the nucleotides Cytidine 5 monophosphate, Guanosine 5 monophosphate and Inosine 5 monophosphate. The dissociated Night milk, designed to be administered from 18.00 to 06.00, contained high levels of tryptophan (3.4g/100g protein) and carbohydrates, low levels of protein, and the nucleotides Adenosine 5 monophosphate and Uridine 5 monophosphate. Three different milk-feeding experiments were performed in a double-blind procedure covering three weeks. In week 1 (control), the infants received both by day and by night a standard formula milk; in week 2 (inverse control), they received the dissociated milk inversely (Night/Day instead of Day/Night); and in week 3, they received the Day/Night dissociated formula concordant with the formula design. When the infants were receiving the Day/Night dissociated milk in concordance with their environment, they showed improvement in all the nocturnal sleep parameters analyzed: total hours of sleep, sleep efficiency, minutes of nocturnal immobility, nocturnal awakenings, and sleep latency. In conclusion, the use of a chronobiologically adjusted infant formula milk seems to be effective in improving the consolidation of the circadian sleep/wake cycle in bottle

  16. PSD-95 uncoupling from NMDA receptors by Tat-N-dimer ameliorates neuronal depolarisation in cortical spreading depression

    DEFF Research Database (Denmark)

    Kucharz, Krzysztof; Søndergaard Rasmussen, Ida; Bach, Anders

    2017-01-01

    during the first hour after i.v. injection. The Tat-N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO2) responses were preserved. During cortical spreading depression, the Tat-N-dimer reduced the average amplitude...... depression on cortical blood flow and CMRO2 We suggest that uncoupling of PSD-95 from NMDA receptors reduces overall neuronal excitability and the amplitude of the spreading depolarisation wave. These findings may be of interest for understanding the neuroprotective effects of the nNOS/PSD-95 uncoupling...

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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...

  2. Organization of Circadian Behavior Relies on Glycinergic Transmission.

    Science.gov (United States)

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

    2017-04-04

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

  3. 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

  4. Transcripts from the Circadian Clock: Telling Time and Season

    NARCIS (Netherlands)

    K. Brand (Karl)

    2011-01-01

    textabstractWe all know it when we wake mere moments before an alarm clock is scheduled to wake us: our body clock made the alarm clock redundant. This phenomenon is driven by an endogenous timer known as the biological, or circadian clock. Each revolution of the Earth about its own axis produces

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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

  7. Studies on circadian rhythm disturbances and melatonin in delirium

    NARCIS (Netherlands)

    de Jonghe, A.-M.

    2014-01-01

    The circadian sleep/wake rhythm disturbances that are seen in delirium and the role of melatonin supplementation provide a new angle in delirium research. More research is needed to determine the role of melatonin in the pathophysiological mechanisms of delirium and to determine whether the

  8. 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

  9. Circadian Rhythm Shapes the Gut Microbiota Affecting Host Radiosensitivity.

    Science.gov (United States)

    Cui, Ming; Xiao, Huiwen; Luo, Dan; Zhang, Xin; Zhao, Shuyi; Zheng, Qisheng; Li, Yuan; Zhao, Yu; Dong, Jiali; Li, Hang; Wang, Haichao; Fan, Saijun

    2016-10-26

    Modern lifestyles, such as shift work, nocturnal social activities, and jet lag, disturb the circadian rhythm. The interaction between mammals and the co-evolved intestinal microbiota modulates host physiopathological processes. Radiotherapy is a cornerstone of modern management of malignancies; however, it was previously unknown whether circadian rhythm disorder impairs prognosis after radiotherapy. To investigate the effect of circadian rhythm on radiotherapy, C57BL/6 mice were housed in different dark/light cycles, and their intestinal bacterial compositions were compared using high throughput sequencing. The survival rate, body weight, and food intake of mice in diverse cohorts were measured following irradiation exposure. Finally, the enteric bacterial composition of irradiated mice that experienced different dark/light cycles was assessed using 16S RNA sequencing. Intriguingly, mice housed in aberrant light cycles harbored a reduction of observed intestinal bacterial species and shifts of gut bacterial composition compared with those of the mice kept under 12 h dark/12 h light cycles, resulting in a decrease of host radioresistance. Moreover, the alteration of enteric bacterial composition of mice in different groups was dissimilar. Our findings provide novel insights into the effects of biological clocks on the gut bacterial composition, and underpin that the circadian rhythm influences the prognosis of patients after radiotherapy in a preclinical setting.

  10. 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

  11. Circadian rhythm gene regulation in the housefly, Musca domestica

    Czech Academy of Sciences Publication Activity Database

    Codd, V.; Doležel, David; Stehlík, Jan; Piccin, A.; Garner, K. J.; Racey, S. N.; Straatman, K. R.; Louis, E. J.; Costa, R.; Šauman, Ivo; Kyriacou, C. P.; Rosato, E.

    2007-01-01

    Roč. 177, č. 3 (2007), s. 1539-1551 ISSN 0016-6731 R&D Projects: GA ČR GA204/04/0862; GA MŠk 2B06129 Institutional research plan: CEZ:AV0Z50070508 Keywords : circadian * evolution * Diptera Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.001, year: 2007

  12. 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

  13. Circadian regulation of epithelial functions in the intestine

    Czech Academy of Sciences Publication Activity Database

    Pácha, Jiří; Sumová, Alena

    2013-01-01

    Roč. 208, č. 1 (2013), s. 11-24 ISSN 1748-1708 R&D Projects: GA ČR(CZ) GAP303/10/0969; GA ČR(CZ) GAP303/11/0668 Institutional support: RVO:67985823 Keywords : circadian rhythms * intestine * colon * proliferation * digestion * intestinal transport Subject RIV: ED - Physiology Impact factor: 4.251, year: 2013

  14. Chamber-dependent circadian expression of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Georg, Birgitte; Jørgensen, Henrik L

    2010-01-01

    Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) have important local functions within the myocardium, where they protect against accelerated fibrosis. As circadian expression of cardiac natriuretic peptides could be of importance in local cardiac protection against disease, we...

  15. 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.

  16. Disrupting circadian rhythms in rats induces retrograde amnesia

    NARCIS (Netherlands)

    Fekete, Mátyás; Ree, J.M. van; Niesink, Raymond J.M.; Wied, D. de

    1985-01-01

    Disrupting circadian organization in rats by phase-shifting the illumination cycle or by exposure to a reversed day/night cycle or to continuous light, resulted in retrograde amnesia for passive avoidance behavior. This retrograde amnesia induced by phase-shifting lasted at least 2 days, and

  17. Circadian secretion patterns of ß-endorphin and leucine enkephalin

    Directory of Open Access Journals (Sweden)

    E. H. de Wet

    1992-07-01

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

  18. 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.

  19. Peripheral circadian clocks are diversely affected by adrenalectomy

    Czech Academy of Sciences Publication Activity Database

    Soták, Matúš; Bryndová, Jana; Ergang, Peter; Vagnerová, Karla; Kvapilová, Pavlína; Vodička, Martin; Pácha, Jiří; Sumová, Alena

    2016-01-01

    Roč. 33, č. 5 (2016), s. 520-529 ISSN 0742-0528 R&D Projects: GA ČR(CZ) GA13-08304S Institutional support: RVO:67985823 Keywords : adrenalectomy * circadian rhythms * corticosterone * peripheral clock Subject RIV: ED - Physiology Impact factor: 2.562, year: 2016

  20. Circadian changes in long noncoding RNAs in the pineal gland

    DEFF Research Database (Denmark)

    Coon, Steven L; Munson, Peter J; Cherukuri, Praveen F

    2012-01-01

    Long noncoding RNAs (lncRNAs) play a broad range of biological roles, including regulation of expression of genes and chromosomes. Here, we present evidence that lncRNAs are involved in vertebrate circadian biology. Differential night/day expression of 112 lncRNAs (0.3 to >50 kb) occurs in the ra...

  1. Phase analysis of circadian-related genes in two tissues

    Directory of Open Access Journals (Sweden)

    Li Leping

    2006-02-01

    Full Text Available Abstract Background Recent circadian clock studies using gene expression microarray in two different tissues of mouse have revealed not all circadian-related genes are synchronized in phase or peak expression times across tissues in vivo. Instead, some circadian-related genes may be delayed by 4–8 hrs in peak expression in one tissue relative to the other. These interesting biological observations prompt a statistical question regarding how to distinguish the synchronized genes from genes that are systematically lagged in phase/peak expression time across two tissues. Results We propose a set of techniques from circular statistics to analyze phase angles of circadian-related genes in two tissues. We first estimate the phases of a cycling gene separately in each tissue, which are then used to estimate the paired angular difference of the phase angles of the gene in the two tissues. These differences are modeled as a mixture of two von Mises distributions which enables us to cluster genes into two groups; one group having synchronized transcripts with the same phase in the two tissues, the other containing transcripts with a discrepancy in phase between the two tissues. For each cluster of genes we assess the association of phases across the tissue types using circular-circular regression. We also develop a bootstrap methodology based on a circular-circular regression model to evaluate the improvement in fit provided by allowing two components versus a one-component von-Mises model. Conclusion We applied our proposed methodologies to the circadian-related genes common to heart and liver tissues in Storch et al. 2, and found that an estimated 80% of circadian-related transcripts common to heart and liver tissues were synchronized in phase, and the other 20% of transcripts were lagged about 8 hours in liver relative to heart. The bootstrap p-value for being one cluster is 0.063, which suggests the possibility of two clusters. Our methodologies can

  2. p38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-uncoupling in obesity.

    Science.gov (United States)

    Yu, Yi; Rajapakse, Angana G; Montani, Jean-Pierre; Yang, Zhihong; Ming, Xiu-Fen

    2014-07-18

    Endothelial nitric oxide synthase (eNOS)-uncoupling links obesity-associated insulin resistance and type-II diabetes to the increased incidence of cardiovascular disease. Studies have indicated that increased arginase is involved in eNOS-uncoupling through competing with the substrate L-arginine. Given that arginase-II (Arg-II) exerts some of its biological functions through crosstalk with signal transduction pathways, and that p38 mitogen-activated protein kinase (p38mapk) is involved in eNOS-uncoupling, we investigated here whether p38mapk is involved in Arg-II-mediated eNOS-uncoupling in a high fat diet (HFD)-induced obesity mouse model. Obesity was induced in wild type (WT) and Arg-II-deficient (Arg-II(-/-)) mice on C57BL/6 J background by high-fat diet (HFD, 55% fat) for 14 weeks starting from age of 7 weeks. The entire aortas were isolated and subjected to 1) immunoblotting analysis of the protein level of eNOS, Arg-II and p38mapk activation; 2) arginase activity assay; 3) endothelium-dependent and independent vasomotor responses; 4) en face staining of superoxide anion and NO production with Dihydroethidium and 4,5-Diaminofluorescein Diacetate, respectively, to assess eNOS-uncoupling. To evaluate the role of p38mapk, isolated aortas were treated with p38mapk inhibitor SB203580 (10 μmol/L, 1 h) prior to the analysis. In addition, the role of p38mapk in Arg-II-induced eNOS-uncoupling was investigated in cultured human endothelial cells overexpressing Arg-II in the absence or presence of shRNA against p38mapk. HFD enhanced Arg-II expression/activity and p38mapk activity, which was associated with eNOS-uncoupling as revealed by decreased NO and enhanced L-NAME-inhibitable superoxide in aortas of WT obese mice. In accordance, WT obese mice revealed decreased endothelium-dependent relaxations to acetylcholine despite of higher eNOS protein level, whereas Arg-II(-/-) obese mice were protected from HFD-induced eNOS-uncoupling and endothelial dysfunction, which

  3. Circadian activity rhythms for mothers with an infant in ICU

    Directory of Open Access Journals (Sweden)

    Shih-Yu eLee

    2010-12-01

    Full Text Available Circadian rhythms influence sleep and wakefulness. Circadian activity rhythms (CAR are altered in individuals with dementia or seasonal affective disorder. To date, studies exploring CAR and sleep in postpartum women are rare. The purpose of this report is to describe relationships between CAR, sleep disturbance, and fatigue among 72 first-time mothers during their 2nd week postpartum while their newborn remain hospitalized in intensive care unit (ICU. Seventy two mothers were included in this secondary data analysis sample from three separate studies. Participants completed the General Sleep Disturbance Scale (GSDS, Numerical Rating Scale for Fatigue (NRS-F, and a sleep diary. The objective sleep data included total sleep time (TST, wake after sleep onset (WASO, and CAR determined by the circadian quotient (amplitude/mesor averaged from at least 48-hours of wrist actigraphy monitoring. The TST of mothers who self-reported as poor sleepers was 354 minutes (SEM= 21.9, with a mean WASO of 19.5% (SEM= 2.8. The overall sleep quality measured by the GSDS was clinically, significantly disrupted (M= 5.5, SD= 1.2. The mean score for morning fatigue was 5.8 (SD= 2.0, indicating moderate fatigue severity. The CAR was .62 (SEM= .04, indicating poor synchronization. The self-reported good sleepers (GSDS < 3 had better CAR (M= .71, SEM= .02 than poor sleepers (GSDS > 3 (t [70] = 2.0, p< .05. A higher circadian equation was associated with higher TST (r= .83, p<.001, less WASO (r= -.50, p< .001, lower self-reported sleep disturbance scores (r= -.35, p= .01, and less morning fatigue (r= -.26. Findings indicate that mothers with a hospitalized infant have both nocturnal sleep problems and disturbed circadian activity rhythms. Factors responsible for these sleep and rhythm disturbances, the adverse effects on mother’s physical and mental well-being, and mother-infant relationship require further study.

  4. 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

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

    Miyoshi, Yashuhiro

    1993-01-01

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

  7. Oxidase uncoupling in heme monooxygenases: Human cytochrome P450 CYP3A4 in Nanodiscs

    Energy Technology Data Exchange (ETDEWEB)

    Grinkova, Yelena V.; Denisov, Ilia G.; McLean, Mark A. [Departments of Biochemistry and Chemistry, University of Illinois, 505 South Goodwin Avenue (United States); Sligar, Stephen G., E-mail: s-sligar@illinois.edu [Departments of Biochemistry and Chemistry, University of Illinois, 505 South Goodwin Avenue (United States)

    2013-01-25

    Highlights: ► Substantial reducing equivalents are lost in human P450 CYP3A4 via an oxidase channel. ► Substrate binding has a pronounced effect on uncoupling in cytochrome P450. ► Anionic phospholipids improve the overall coupling in CYP3A4 Nanodiscs. -- Abstract: The normal reaction mechanism of cytochrome P450 operates by utilizing two reducing equivalents to reduce atmospheric dioxygen, producing one molecule of water and an oxygenated product in an overall stoichiometry of 2 electrons:1 dioxygen:1 product. However, three alternate unproductive pathways exist where the intermediate iron–oxygen states in the catalytic cycle can yield reduced oxygen products without substrate metabolism. The first involves release of superoxide from the oxygenated intermediate while the second occurs after input of the second reducing equivalent. Superoxide rapidly dismutates and hence both processes produce hydrogen peroxide that can be cytotoxic to the organism. In both cases, the formation of hydrogen peroxide involves the same overall stoichiometry as oxygenases catalysis. The key step in the catalytic cycle of cytochrome P450 involves scission of the oxygen–oxygen bond of atmospheric dioxygen to produce a higher valent iron-oxo state termed “Compound I”. This intermediate initiates a radical reaction in the oxygenase pathway but also can uptake two additional reducing equivalents from reduced pyridine nucleotide (NADPH) and the flavoprotein reductase to produce a second molecule of water. This non-productive decay of Compound I thus yields an overall oxygen to NADPH ratio of 1:2 and does not produce hydrocarbon oxidation. This water uncoupling reaction provides one of a limited means to study the reactivity of the critical Compound I intermediate in P450 catalysis. We measured simultaneously the rates of NADPH and oxygen consumption as a function of substrate concentration during the steady-state hydroxylation of testosterone catalyzed by human P450 CYP3A4

  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. 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

  10. 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.

  11. Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

    Science.gov (United States)

    Berghella, Libera; Ferraro, Elisabetta

    2012-01-01

    Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

  12. Fatty Acids are Key in 4-Hydroxy-2-Nonenal-Mediated Activation of Uncoupling Proteins 1 and 2

    Czech Academy of Sciences Publication Activity Database

    Malingriaux, E. A.; Rupprecht, A.; Gille, L.; Jovanovic, O.; Ježek, Petr; Jabůrek, Martin; Pohl, E. E.

    2013-01-01

    Roč. 8, č. 10 (2013), e77786 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP302/10/0346 Institutional support: RVO:67985823 Keywords : mitochondrial uncoupling proteins * 4-hydroxy-2-nonenal * fatty acids Subject RIV: EA - Cell Biology Impact factor: 3.534, year: 2013

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

    Directory of Open Access Journals (Sweden)

    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

  14. Feeding Your Baby

    Medline Plus

    Full Text Available ... for your baby Feeding your baby Family health & safety Complications & Loss Pregnancy complications Preterm labor & premature birth ... for your baby Feeding your baby Family health & safety Complications & Loss Pregnancy complications Preterm labor & premature birth ...

  15. Feeding Your Baby

    Medline Plus

    Full Text Available ... questions Email sign up Join our online community Home > Baby > Feeding your baby Feeding your baby E- ... We're working to radically improve the health care they receive. We're pioneering research to find ...

  16. Feeding Your Baby

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    Full Text Available ... fitness Prenatal care Is it safe? Labor & birth Postpartum care Baby Caring for your baby Feeding your ... fitness Prenatal care Is it safe? Labor & birth Postpartum care Baby Caring for your baby Feeding your ...

  17. Feeding Your Baby

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    Full Text Available ... Home > Baby > Feeding your baby Feeding your baby E-mail to a friend Please fill in all fields. Please enter a valid e-mail address. Your information: Your recipient's information: Your ...

  18. Feeding tube - infants

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007235.htm Feeding tube - infants To use the sharing features on this page, please enable JavaScript. A feeding tube is a small, soft, plastic tube placed ...

  19. Gastrostomy feeding tube - bolus

    Science.gov (United States)

    Feeding - gastrostomy tube - bolus; G-tube - bolus; Gastrostomy button - bolus; Bard Button - bolus; MIC-KEY - bolus ... KEY, 3 to 8 weeks after surgery. These feedings will help your child grow strong and healthy. ...

  20. Feeding Your Baby

    Medline Plus

    Full Text Available ... Frequently asked questions Email sign up Join our online community Home > Baby > Feeding your baby Feeding your baby E-mail to a friend Please fill in all fields. Please enter a ...

  1. Feeding Your Baby

    Medline Plus

    Full Text Available ... Frequently asked questions Email sign up Join our online community March for Babies Nacersano Share Your Story ... Frequently asked questions Email sign up Join our online community Home > Baby > Feeding your baby Feeding your ...

  2. Variable ATP yields and uncoupling of oxygen consumption in human brain

    DEFF Research Database (Denmark)

    Gjedde, Albert; Aanerud, Joel; Peterson, Ericka

    2011-01-01

    normalized the metabolic rate to the population average of that region. Coefficients of variation ranged from 10 to 15% in the different regions of the human brain and the normalized regional metabolic rates ranged from 70% to 140% of the population average for each region, equal to a two-fold variation......The distribution of brain oxidative metabolism values among healthy humans is astoundingly wide for a measure that reflects normal brain function and is known to change very little with most changes of brain function. It is possible that the part of the oxygen consumption rate that is coupled...... to ATP turnover is the same in all healthy human brains, with different degrees of uncoupling explaining the variability of total oxygen consumption among people. To test the hypothesis that about 75% of the average total oxygen consumption of human brains is common to all individuals, we determined...

  3. Mediator binding to UASs is broadly uncoupled from transcription and cooperative with TFIID recruitment to promoters.

    Science.gov (United States)

    Grünberg, Sebastian; Henikoff, Steven; Hahn, Steven; Zentner, Gabriel E

    2016-11-15

    Mediator is a conserved, essential transcriptional coactivator complex, but its in vivo functions have remained unclear due to conflicting data regarding its genome-wide binding pattern obtained by genome-wide ChIP Here, we used ChEC-seq, a method orthogonal to ChIP, to generate a high-resolution map of Mediator binding to the yeast genome. We find that Mediator associates with upstream activating sequences (UASs) rather than the core promoter or gene body under all conditions tested. Mediator occupancy is surprisingly correlated with transcription levels at only a small fraction of genes. Using the same approach to map TFIID, we find that TFIID is associated with both TFIID- and SAGA-dependent genes and that TFIID and Mediator occupancy is cooperative. Our results clarify Mediator recruitment and binding to the genome, showing that Mediator binding to UASs is widespread, partially uncoupled from transcription, and mediated in part by TFIID. © 2016 The Authors.

  4. Design of an achromatic and uncoupled medical gantry for radiation therapy

    International Nuclear Information System (INIS)

    Tsoupas, N.; Kayran, D.; Litvinenko, V.; MacKay, W.W.

    2011-01-01

    We are presenting the layout and the optics of a beam line to be used as a medical gantry in radiation therapy. The optical properties of the gantry's beam line are such as to make the beam line achromatic and uncoupled. These two properties make the beam spot size, which is delivered and focused by the gantry, on the tumor of the patient, independent of the angular orientation of the gantry. In this paper we present the layout of the magnetic elements of the gantry, and also present the theoretical basis for the optics design of such a gantry. A medical gantry, as it is used in the radiation treatment of cancer patients, is the last part of the beam optical system, of the accelerator complex, which delivers and focuses the beam on the tumor. The curved line shown in figure 1 is a schematic diagram of a gantry which can rotate about a horizontal axis. The particle beam (green arrow in fig. 1) enters the gantry, and is guided by the gantry on the tumor (red spot in fig. 1). As the gantry rotates about the axis shown in figure 1, the beam exiting the gantry always lies on a plane normal to the rotation axis at the point of the icocenter. Thus the gantry facilitates the ability of the beam delivery system, to deliver the beam at the tumor, which is placed at the icocenter, from any angle on this vertical plane, which is normal to the rotation angle of the gantry as stated earlier. The gantry consists of dipoles and quadrupoles elements whose median symmetry plane lies on a plane which contains the rotation axis of the gantry. In this paper we define this plane as the 'plane of the gantry'. As the beam is transported along the axis of rotation of the gantry and before it enters the gantry, it is focused by 'normal' quadrupoles and experiences no linear beam coupling. Subsequently the beam enters the gantry, and is transported by the gantry to the delivery point which is the tumor. The transported beam at the tumor is still linearly uncoupled as long as the plane of the

  5. Uncoupling proteins (UCP) in unicellular eukaryotes: true UCPs or UCP1-like acting proteins?

    Science.gov (United States)

    Luévano-Martínez, Luis Alberto

    2012-04-05

    Uncoupling proteins belong to the superfamily of mitochondrial anion carriers. They are apparently present throughout the Eukarya domain in which only some members have an established physiological function, i.e. UCP1 from brown adipose tissue is involved in non-shivering thermogenesis. However, the proteins responsible for the phenotype observed in unicellular organisms have not been characterized. In this report we analyzed functional evidence concerning unicellular UCPs and found that true UCPs are restricted to some taxonomical groups while proteins conferring a UCP1-like phenotype to fungi and most protists are the result of a promiscuous activity exerted by other mitochondrial anion carriers. We describe a possible evolutionary route followed by these proteins by which they acquire this promiscuous mechanism. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  6. Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis.

    Science.gov (United States)

    Cerqueira, Fernanda M; Laurindo, Francisco R M; Kowaltowski, Alicia J

    2011-03-31

    Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR). Since treatment of mice with dinitrophenol (DNP) promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

  7. Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis.

    Directory of Open Access Journals (Sweden)

    Fernanda M Cerqueira

    2011-03-01

    Full Text Available Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR. Since treatment of mice with dinitrophenol (DNP promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

  8. Acceptably aware during general anaesthesia: 'dysanaesthesia'--the uncoupling of perception from sensory inputs.

    Science.gov (United States)

    Pandit, Jaideep J

    2014-07-01

    This review makes the case for 'dysanaesthesia', a term encompassing states of mind that can arise in the course of anaesthesia during surgery, characterised by an uncoupling of sensation and perceptual experience. This is reflected in a macroscopic, functional model of anaesthetically-relevant consciousness. Patients in this state can be aware of events but in a neutral way, not in pain, sometimes personally dissociated from the experiences. This makes events associated with surgery peripheral to their whole experience, such that recall is less likely and if it exists, makes any spontaneous report of awareness unlikely. This state of perception-sensation uncoupling is therefore broadly acceptable (a minimum requirement for acceptable anaesthesia) but since it is likely a dose-related phenomenon, may also represent a precursor for awareness with adverse recall. This hypothesis uniquely explains the often inconsistent responses seen during the experimental paradigm of the 'isolated forearm technique', wherein apparently anaesthetised patients exhibit a positive motor response to verbal command, but no spontaneous movement to surgery. The hypothesis can also explain the relatively high incidence of positive response to relatively direct questions for recall (e.g., using the Brice questionnaire; ∼1:500; the vast majority of these being neutral reports) versus the very low incidence of spontaneous reports of awareness (∼1:15,000; a higher proportion of these being adverse recollections). The hypothesis is consistent with relevant notions from philosophical discussions of consciousness, and neuroscientific evidence. Dysanaesthesia has important implications for research and also for the development of appropriate monitoring. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Chimera states in a multilayer network of coupled and uncoupled neurons

    Science.gov (United States)

    Majhi, Soumen; Perc, Matjaž; Ghosh, Dibakar

    2017-07-01

    We study the emergence of chimera states in a multilayer neuronal network, where one layer is composed of coupled and the other layer of uncoupled neurons. Through the multilayer structure, the layer with coupled neurons acts as the medium by means of which neurons in the uncoupled layer share information in spite of the absence of physical connections among them. Neurons in the coupled layer are connected with electrical synapses, while across the two layers, neurons are connected through chemical synapses. In both layers, the dynamics of each neuron is described by the Hindmarsh-Rose square wave bursting dynamics. We show that the presence of two different types of connecting synapses within and between the two layers, together with the multilayer network structure, plays a key role in the emergence of between-layer synchronous chimera states and patterns of synchronous clusters. In particular, we find that these chimera states can emerge in the coupled layer regardless of the range of electrical synapses. Even in all-to-all and nearest-neighbor coupling within the coupled layer, we observe qualitatively identical between-layer chimera states. Moreover, we show that the role of information transmission delay between the two layers must not be neglected, and we obtain precise parameter bounds at which chimera states can be observed. The expansion of the chimera region and annihilation of cluster and fully coherent states in the parameter plane for increasing values of inter-layer chemical synaptic time delay are illustrated using effective range measurements. These results are discussed in the light of neuronal evolution, where the coexistence of coherent and incoherent dynamics during the developmental stage is particularly likely.

  10. A novel high-throughput assay for islet respiration reveals uncoupling of rodent and human islets.

    Directory of Open Access Journals (Sweden)

    Jakob D Wikstrom

    Full Text Available The pancreatic beta cell is unique in its response to nutrient by increased fuel oxidation. Recent studies have demonstrated that oxygen consumption rate (OCR may be a valuable predictor of islet quality and long term nutrient responsiveness. To date, high-throughput and user-friendly assays for islet respiration are lacking. The aim of this study was to develop such an assay and to examine bioenergetic efficiency of rodent and human islets.The XF24 respirometer platform was adapted to islets by the development of a 24-well plate specifically designed to confine islets. The islet plate generated data with low inter-well variability and enabled stable measurement of oxygen consumption for hours. The F1F0 ATP synthase blocker oligomycin was used to assess uncoupling while rotenone together with myxothiazol/antimycin was used to measure the level of non-mitochondrial respiration. The use of oligomycin in islets was validated by reversing its effect in the presence of the uncoupler FCCP. Respiratory leak averaged to 59% and 49% of basal OCR in islets from C57Bl6/J and FVB/N mice, respectively. In comparison, respiratory leak of INS-1 cells and C2C12 myotubes was measured to 38% and 23% respectively. Islets from a cohort of human donors showed a respiratory leak of 38%, significantly lower than mouse islets.The assay for islet respiration presented here provides a novel tool that can be used to study islet mitochondrial function in a relatively high-throughput manner. The data obtained in this study shows that rodent islets are less bioenergetically efficient than human islets as well as INS1 cells.

  11. Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival

    KAUST Repository

    Lambert, Hélène Perreten

    2014-09-18

    Brain activity is energetically costly and requires a steady and highly regulated flow of energy equivalents between neural cells. It is believed that a substantial share of cerebral glucose, the major source of energy of the brain, will preferentially be metabolized in astrocytes via aerobic glycolysis. The aim of this study was to evaluate whether uncoupling proteins (UCPs), located in the inner membrane of mitochondria, play a role in setting up the metabolic response pattern of astrocytes. UCPs are believed to mediate the transmembrane transfer of protons, resulting in the uncoupling of oxidative phosphorylation from ATP production. UCPs are therefore potentially important regulators of energy fluxes. The main UCP isoforms expressed in the brain are UCP2, UCP4, and UCP5. We examined in particular the role of UCP4 in neuron-astrocyte metabolic coupling and measured a range of functional metabolic parameters including mitochondrial electrical potential and pH, reactive oxygen species production, NAD/NADH ratio, ATP/ADP ratio, CO2 and lactate production, and oxygen consumption rate. In brief, we found that UCP4 regulates the intramitochondrial pH of astrocytes, which acidifies as a consequence of glutamate uptake, with the main consequence of reducing efficiency of mitochondrial ATP production. The diminished ATP production is effectively compensated by enhancement of glycolysis. This nonoxidative production of energy is not associated with deleterious H2O2 production. We show that astrocytes expressing more UCP4 produced more lactate, which is used as an energy source by neurons, and had the ability to enhance neuronal survival.

  12. Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5

    Directory of Open Access Journals (Sweden)

    Viggiano E

    2016-07-01

    Full Text Available Emanuela Viggiano,1,2 Vincenzo Monda,1 Antonietta Messina,1 Fiorenzo Moscatelli,3 Anna Valenzano,3 Domenico Tafuri,4 Giuseppe Cibelli,3 Bruno De Luca,1 Giovanni Messina,1,3 Marcellino Monda1 1Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Second University of Naples, Naples, 2Department of Medicine, University of Padua, Padua, 3Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 4Department of Motor Sciences and Wellness, University of Naples “Parthenope”, Naples, Italy Abstract: Depression of electrocorticogram propagating over the cortex surface results in cortical spreading depression (CSD, which is probably related to the pathophysiology of stroke, epilepsy, and migraine. However, preconditioning with CSD produces neuroprotection to subsequent ischemic episodes. Such effects require the expression or activation of several genes, including neuroprotective ones. Recently, it has been demonstrated that the expression of the uncoupling proteins (UCPs 2 and 5 is amplified during brain ischemia and their expression exerts a long-term effect upon neuron protection. To evaluate the neuroprotective consequence of CSD, the expression of UCP-5 in the brain cortex was measured following CSD induction. CSD was evoked in four samples of rats, which were sacrificed after 2 hours, 4 hours, 6 hours, and 24 hours. Western blot analyses were carried out to measure UCP-5 concentrations in the prefrontal cortices of both hemispheres, and immunohistochemistry was performed to determine the localization of UCP-5 in the brain cortex. The results showed a significant elevation in UCP-5 expression at 24 hours in all cortical strata. Moreover, UCP-5 was triggered by CSD, indicating that UCP-5 production can have a neuroprotective effect. Keywords: cortical spreading depression, neuroprotective effect, uncoupling protein-5

  13. PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPAR{gamma} activation in the liver

    Energy Technology Data Exchange (ETDEWEB)

    Oishi, Katsutaka, E-mail: k-ooishi@aist.go.jp [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Uchida, Daisuke [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki (Japan); Ohkura, Naoki [Department of Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa (Japan); Horie, Shuichi [Department of Clinical Biochemistry, Kagawa Nutrition University, Sakado, Saitama (Japan)

    2010-10-15

    Research highlights: {yields} PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression. {yields} Hepatic expressions of PPAR{gamma} and PCG-1{alpha} are induced by a ketogenic diet. {yields} PPAR{gamma} antagonist attenuates a ketogenic diet-induced PAI-1 expression. {yields} Ketogenic diet advances the phase of circadian clock in a PPAR{alpha}-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPAR{alpha}-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPAR{alpha}-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPAR{alpha} target genes such as Cyp4A10 and FGF21 was damped in PPAR{alpha}-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPAR{alpha}-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPAR{alpha} activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPAR{gamma} and its coactivator PCG-1{alpha} were more effectively induced in PPAR{alpha}-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPAR{gamma} antagonist, in both WT and PPAR

  14. Insulin resistance and circadian rhythm of cardiac autonomic modulation

    Directory of Open Access Journals (Sweden)

    Cai Jianwen

    2010-12-01

    Full Text Available Abstract Background Insulin resistance (IR has been associated with cardiovascular diseases (CVD. Heart rate variability (HRV, an index of cardiac autonomic modulation (CAM, is also associated with CVD mortality and CVD morbidity. Currently, there are limited data about the impairment of IR on the circadian pattern of CAM. Therefore, we conducted this investigation to exam the association between IR and the circadian oscillations of CAM in a community-dwelling middle-aged sample. Method Homeostasis models of IR (HOMA-IR, insulin, and glucose were used to assess IR. CAM was measured by HRV analysis from a 24-hour electrocardiogram. Two stage modeling was used in the analysis. In stage one, for each individual we fit a cosine periodic model based on the 48 segments of HRV data. We obtained three individual-level cosine parameters that quantity the circadian pattern: mean (M, measures the overall average of a HRV index; amplitude (Â, measures the amplitude of the oscillation of a HRV index; and acrophase time (θ, measures the timing of the highest oscillation. At the second stage, we used a random-effects-meta-analysis to summarize the effects of IR variables on the three circadian parameters of HRV indices obtained in stage one of the analysis. Results In persons without type diabetes, the multivariate adjusted β (SE of log HOMA-IR and M variable for HRV were -0.251 (0.093, -0.245 (0.078, -0.19 (0.06, -4.89 (1.76, -3.35 (1.31, and 2.14 (0.995, for log HF, log LF, log VLF, SDNN, RMSSD and HR, respectively (all P Conclusion Elevated IR, among non-diabetics significantly impairs the overall mean levels of CAM. However, the  or θ of CAM were not significantly affected by IR, suggesting that the circadian mechanisms of CAM are not impaired. However, among persons with type 2 diabetes, a group clinically has more severe form of IR, the adverse effects of increased IR on all three HRV circadian parameters are much larger.

  15. 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

  16. 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.

  17. Circadian variation in QT dispersion determined from a 12-lead Holter recording

    DEFF Research Database (Denmark)

    Hansen, Stig; Rasmussen, Verner; Larsen, Klaus

    2007-01-01

    Background: QT dispersion is considered to reflect inhomogeneity of myocardial repolarization. Method: The circadian variation of QT interval dispersion was examined in 95 healthy subjects using 24-hour Holter monitoring. Three different methods of lead selection were applied: all 12 leads (QTdisp...... circadian variation using mean values of QTdisp 12, QTdisp 6, or QTdisp 2 obtained every hour, every 2, or every 4 hours, except in QTdisp 6, which demonstrated a significant circadian variation (P ... a significant circadian variation in QTdisp 12 and QTdisp 6 (P circadian variation was seen in QTdisp 2. A subdivision into 10-year age groups revealed that subjects at age >50 years had a significant circadian variation in QTdisp 12 and QTdisp 6, but not in QTdisp 2. Only in males...

  18. Breast-Feeding Twins: Making Feedings Manageable

    Science.gov (United States)

    ... Department of Health and Human Services Office on Women's Health. http://www.womenshealth.gov/publications/our-publications/breastfeeding-guide. Accessed March 11, 2015. Shelov SP, et al. Feeding your ...

  19. Feed safety in the feed supply chain

    Directory of Open Access Journals (Sweden)

    Pinotti, L.

    2011-01-01

    Full Text Available A number of issues have weakened the public's confidence in the quality and wholesomeness of foods of animal origin. As a result farmers, nutritionists, industry and governments have been forced to pay serious attention to animal feedstuff production processes, thereby acknowledging that animal feed safety is an essential prerequisite for human food safety. Concerns about these issues have produced a number of important effects including the ban on the use of processed animal proteins, the ban on the addition of most antimicrobials to farm animals diets for growth‐promotion purposes, and the implementation of feed contaminant regulations in the EU. In this context it is essential to integrate knowledge on feed safety and feed supply. Consequently, purchase of new and more economic sources of energy and protein in animal diets, which is expected to conform to adequate quality, traceability, environmental sustainability and safety standards, is an emerging issue in livestock production system.

  20. SLEEP AND CIRCADIAN RHYTHM DISORDERS IN PARKINSON'S DISEASE.

    Science.gov (United States)

    Gros, Priti; Videnovic, Aleksandar

    2017-09-01

    Sleep disorders are among the most challenging non-motor features of Parkinson's disease (PD) and significantly affect quality of life. Research in this field has gained recent interest among clinicians and scientists and is rapidly evolving. This review is dedicated to sleep and circadian dysfunction associated with PD. Most primary sleep disorders may co-exist with PD; majority of these disorders have unique features when expressed in the PD population. We discuss the specific considerations related to the common sleep problems in Parkinson's disease including insomnia, rapid eye movement sleep behavior disorder, restless legs syndrome, sleep disordered breathing, excessive daytime sleepiness and circadian rhythm disorders. Within each of these sleep disorders, we present updated definitions, epidemiology, etiology, diagnosis, clinical implications and management. Furthermore, areas of potential interest for further research are outlined.

  1. The Effect of Cataract Surgery on Circadian Photoentrainment

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  2. Circadian neuroendocrine physiology and electromagnetic field studies: Precautions and complexities

    International Nuclear Information System (INIS)

    Warman, G.R.; Tripp, H.M.; Harman, V.L.; Arendt, J.

    2003-01-01

    The suppression of melatonin by exposure to low frequency electromagnetic fields (EMFs) 'the melatonin hypothesis' has been invoked as a possible mechanism through which exposure to these fields may result in an increased incidence of cancer. While the effect of light on melatonin is well established, data showing a similar effect due to EMF exposure are sparse and, where present, are often poorly controlled. The current review focuses on the complexities associated with using melatonin as a marker and the dynamic nature of normal melatonin regulation by the circadian neuroendocrine axis. These are issues which the authors believe contribute significantly to the lack of consistency of results in the current literature. Recommendations on protocol design are also made which, if followed, should enable researchers to eliminate or control for many of the confounding factors associated with melatonin being an output from the circadian clock. (author)

  3. Circadian neuroendocrine physiology and electromagnetic field studies: Precautions and complexities

    Energy Technology Data Exchange (ETDEWEB)

    Warman, G.R.; Tripp, H.M.; Harman, V.L.; Arendt, J

    2003-07-01

    The suppression of melatonin by exposure to low frequency electromagnetic fields (EMFs) 'the melatonin hypothesis' has been invoked as a possible mechanism through which exposure to these fields may result in an increased incidence of cancer. While the effect of light on melatonin is well established, data showing a similar effect due to EMF exposure are sparse and, where present, are often poorly controlled. The current review focuses on the complexities associated with using melatonin as a marker and the dynamic nature of normal melatonin regulation by the circadian neuroendocrine axis. These are issues which the authors believe contribute significantly to the lack of consistency of results in the current literature. Recommendations on protocol design are also made which, if followed, should enable researchers to eliminate or control for many of the confounding factors associated with melatonin being an output from the circadian clock. (author)

  4. 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...

  5. The timing of the circadian clock and sleep differ between napping and non-napping toddlers

    OpenAIRE

    Akacem, Lameese D; Simpkin, Charles T; Carskadon, Mary A; Wright, Kenneth P; Jenni, Oskar G; Achermann, Peter; LeBourgeois, Monique K

    2015-01-01

    The timing of the internal circadian clock shows large inter-individual variability across the lifespan. Although the sleep-wakefulness pattern of most toddlers includes an afternoon nap, the association between napping and circadian phase in early childhood remains unexplored. This study examined differences in circadian phase and sleep between napping and non-napping toddlers. Data were collected on 20 toddlers (34.2±2.0 months; 12 females; 15 nappers). Children followed their habitual napp...

  6. 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.

  7. 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...

  8. 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.

  9. Modified-release hydrocortisone to provide circadian cortisol profiles.

    Science.gov (United States)

    Debono, Miguel; Ghobadi, Cyrus; Rostami-Hodjegan, Amin; Huatan, Hiep; Campbell, Michael J; Newell-Price, John; Darzy, Ken; Merke, Deborah P; Arlt, Wiebke; Ross, Richard J

    2009-05-01

    Cortisol has a distinct circadian rhythm regulated by the brain's central pacemaker. Loss of this rhythm is associated with metabolic abnormalities, fatigue, and poor quality of life. Conventional glucocorticoid replacement cannot replicate this rhythm. Our objectives were to define key variables of physiological cortisol rhythm, and by pharmacokinetic modeling test whether modified-release hydrocortisone (MR-HC) can provide circadian cortisol profiles. The study was performed at a Clinical Research Facility. Using data from a cross-sectional study in healthy reference subjects (n = 33), we defined parameters for the cortisol rhythm. We then tested MR-HC against immediate-release hydrocortisone in healthy volunteers (n = 28) in an open-label, randomized, single-dose, cross-over study. We compared profiles with physiological cortisol levels, and modeled an optimal treatment regimen. The key variables in the physiological cortisol profile included: peak 15.5 microg/dl (95% reference range 11.7-20.6), acrophase 0832 h (95% confidence interval 0759-0905), nadir less than 2 microg/dl (95% reference range 1.5-2.5), time of nadir 0018 h (95% confidence interval 2339-0058), and quiescent phase (below the mesor) 1943-0531 h. MR-HC 15 mg demonstrated delayed and sustained release with a mean (sem) maximum observed concentration of 16.6 (1.4) microg/dl at 7.41 (0.57) h after drug. Bioavailability of MR-HC 5, 10, and 15 mg was 100, 79, and 86% that of immediate-release hydrocortisone. Modeling suggested that MR-HC 15-20 mg at 2300 h and 10 mg at 0700 h could reproduce physiological cortisol levels. By defining circadian rhythms and using modern formulation technology, it is possible to allow a more physiological circadian replacement of cortisol.

  10. Circadian rhytm in the house fly (Musca domestica)

    OpenAIRE

    BAZALOVÁ, Olga

    2010-01-01

    In this thesis the expression pattern of five circadian clock genes (cwo, pdp 1{$\\varepsilon$}, ck 1{$\\varepsilon$}, ck 2{$\\beta$} and pdh) was studied in the housefly (Musca domestica). The influence of temperature on the expression pattern of these five genes and of two others genes, per and tim, was examined. The locomotor activity of flies exposed to three different temperature conditions was studied.

  11. Multiple layers of posttranslational regulation refine circadian clock activity in Arabidopsis.

    Science.gov (United States)

    Seo, Pil Joon; Mas, Paloma

    2014-01-01

    The circadian clock is a cellular time-keeper mechanism that regulates biological rhythms with a period of ~24 h. The circadian rhythms in metabolism, physiology, and development are synchronized by environmental cues such as light and temperature. In plants, proper matching of the internal circadian time with the external environment confers fitness advantages on plant survival and propagation. Accordingly, plants have evolved elaborated regulatory mechanisms that precisely control the circadian oscillations. Transcriptional feedback regulation of several clock components has been well characterized over the past years. However, the importance of additional regulatory mechanisms such as chromatin remodeling, protein complexes, protein phosphorylation, and stability is only starting to emerge. The multiple layers of circadian regulation enable plants to properly synchronize with the environmental cycles and to fine-tune the circadian oscillations. This review focuses on the diverse posttranslational events that regulate circadian clock function. We discuss the mechanistic insights explaining how plants articulate a high degree of complexity in their regulatory networks to maintain circadian homeostasis and to generate highly precise waveforms of circadian expression and activity.

  12. 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.

  13. Clinical Trial of the Effect of Exercise on Resetting of the Endogenous Circadian Pacemaker

    National Research Council Canada - National Science Library

    Czeisler, Charles

    2000-01-01

    ...: 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...

  14. Absence of Circadian Rhythms of Preterm Premature Rupture of Membranes and Preterm Placental Abruption

    Science.gov (United States)

    Luque-Fernandez, Miguel Angel; Ananth, Cande V.; Sanchez, Sixto E.; Qiu, Chun-fang; Hernandez-Diaz, Sonia; Valdimarsdottir, Unnur; Gelaye, Bizu; Williams, Michelle A.

    2014-01-01

    Purpose Data regarding circadian rhythm in the onset of spontaneous preterm premature rupture of membranes (PROM) and placental abruption (PA) cases are conflicting. We modeled the time of onset of preterm PROM and PA cases and examined if the circadian profiles varied based on the gestational age at delivery. Methods We used parametric and nonparametric methods, including trigonometric regression in the framework of generalized linear models, to test the presence of circadian rhythms in the time of onset of preterm PROM and PA cases, among 395 women who delivered a singleton between 2009 and 2010 in Lima, Peru. Results We found a diurnal circadian pattern, with a morning peak at 07h:32’ (95%CI:05h:46’ – 09h:18’) among moderate preterm PROM cases (P-value<0.001), and some evidence of a diurnal circadian periodicity among PA cases in term infants (P-value=0.067). However, we did not find evidence of circadian rhythms in the time of onset of extremely or very preterm PROM (P-value=0.259) and preterm PA (P-value=0.224). Conclusions The circadian rhythms of the time of onset of preterm PROM and PA cases varied based on gestational weeks at delivery. While circadian rhythms were presented among moderate preterm PROM and term PA cases, there was no evidence of circadian rhythms among preterm PA and very or extremely preterm PROM cases, underlying other mechanisms associated with the time of onset. PMID:25453346

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

    Science.gov (United States)

    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.

  16. 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.

  17. 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.

  18. 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.

  19. Colour As a Signal for Entraining the Mammalian Circadian Clock

    Science.gov (United States)

    Walmsley, Lauren; Hanna, Lydia; Mouland, Josh; Martial, Franck; West, Alexander; Smedley, Andrew R.; Bechtold, David A.; Webb, Ann R.; Lucas, Robert J.; Brown, Timothy M.

    2015-01-01

    Twilight is characterised by changes in both quantity (“irradiance”) and quality (“colour”) of light. Animals use the variation in irradiance to adjust their internal circadian clocks, aligning their behaviour and physiology with the solar cycle. However, it is currently unknown whether changes in colour also contribute to this entrainment process. Using environmental measurements, we show here that mammalian blue–yellow colour discrimination provides a more reliable method of tracking twilight progression than simply measuring irradiance. We next use electrophysiological recordings to demonstrate that neurons in the mouse suprachiasmatic circadian clock display the cone-dependent spectral opponency required to make use of this information. Thus, our data show that some clock neurons are highly sensitive to changes in spectral composition occurring over twilight and that this input dictates their response to changes in irradiance. Finally, using mice housed under photoperiods with simulated dawn/dusk transitions, we confirm that spectral changes occurring during twilight are required for appropriate circadian alignment under natural conditions. Together, these data reveal a new sensory mechanism for telling time of day that would be available to any mammalian species capable of chromatic vision. PMID:25884537

  20. Colour as a signal for entraining the mammalian circadian clock.

    Directory of Open Access Journals (Sweden)

    Lauren Walmsley

    2015-04-01

    Full Text Available Twilight is characterised by changes in both quantity ("irradiance" and quality ("colour" of light. Animals use the variation in irradiance to adjust their internal circadian clocks, aligning their behaviour and physiology with the solar cycle. However, it is currently unknown whether changes in colour also contribute to this entrainment process. Using environmental measurements, we show here that mammalian blue-yellow colour discrimination provides a more reliable method of tracking twilight progression than simply measuring irradiance. We next use electrophysiological recordings to demonstrate that neurons in the mouse suprachiasmatic circadian clock display the cone-dependent spectral opponency required to make use of this information. Thus, our data show that some clock neurons are highly sensitive to changes in spectral composition occurring over twilight and that this input dictates their response to changes in irradiance. Finally, using mice housed under photoperiods with simulated dawn/dusk transitions, we confirm that spectral changes occurring during twilight are required for appropriate circadian alignment under natural conditions. Together, these data reveal a new sensory mechanism for telling time of day that would be available to any mammalian species capable of chromatic vision.

  1. Impaired clock output by altered connectivity in the circadian network.

    Science.gov (United States)

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

    2007-03-27

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

  2. Circadian pattern of blood pressure in normal pregnancy and preeclampsia.

    Science.gov (United States)

    Gupta, Hem Prabha; Singh, R K; Singh, Urmila; Mehrotra, Seema; Verma, N S; Baranwal, Neelam

    2011-08-01

    AIMS #ENTITYSTARTX00026; To find out the circadian pattern of blood pressure in normotensive pregnant women and in women with preeclampsia. A cross-sectional prospective observational case control study. Blood pressure was sampled in thirty-five normotensive pregnant women (control) and thirty five preeclamptic women (study group) by using non-invasive automatic ambulatory blood pressure monitoring machine for 72 h. Blood pressure (BP) was not constant over 24 h period and it oscillated from time to time in control group. BP was maximum during early part of afternoon. However, in preeclampsia besides quantitative increase in BP, circadian BP oscillations were less pronounced and in around 50% subjects BP was maximum during evening and night hours. Both systolic and diastolic BP showed definite reproducible circadian pattern in both preeclamptic and normotensive pregnant women. This pattern both quantitatively and qualitatively was different in preeclamptic women. Standardized 24 h BP monitoring allows quantitative and qualitative evaluation of hypertensive status and is important for timing and dosing of antihypertensive medications.

  3. Hypercorticism blunts circadian variations of osteocalcin regardless of nutritional status.

    Science.gov (United States)

    Vergély, N; Lafage-Proust, M-H; Caillot-Augusseau, A; Millot, L; Lang, F; Estour, B

    2002-02-01

    Anorexia nervosa (AN) and Cushing's syndrome (CS) are both responsible for osteoporosis. The mechanisms leading to osteoporosis in AN include hypogonadism, nutritional depletion, and in some cases hypercorticism. Osteocalcin circulating level is a serum marker of osteoblastic activity that follows a circadian rhythm (OCR). Serum osteocalcin is decreased in both CS and AN and can be increased with treatment. In this study we analyzed the influence of combined cortisol and nutritional status on osteocalcin levels and its circadian rhythm in these two different models of hypercorticism, one nutritionally replete (CS) and one nutritionally deplete (AN), and we evaluated the effects of their treatment (surgical cure and weight gain, respectively). Before treatment, osteocalcin levels were lower in CS (n = 16) and AN (n = 42) than in controls and in the AN patient subgroup with hypercorticism (n = 13) compared to those without (n = 29). OCR was absent in CS and in AN patients with hypercorticism, whereas their circadian cortisol cycle was maintained. In CS, successful surgical treatment increased osteocalcin levels (n = 5) and restored OCR. In AN, weight gain (n = 13) induced a significant decrease in cortisol levels in hypercortisolic AN patients, and restored normal osteocalcin levels and OCR. In conclusion, we found that hypercorticism was associated with a decrease in osteocalcin levels in nutritionally replete or deplete patients and that OCR was more affected by cortisol levels than by cortisol cycle.

  4. Sleep and circadian rhythm disturbance in bipolar disorder.

    Science.gov (United States)

    Bradley, A J; Webb-Mitchell, R; Hazu, A; Slater, N; Middleton, B; Gallagher, P; McAllister-Williams, H; Anderson, K N

    2017-07-01

    Subjective reports of insomnia and hypersomnia are common in bipolar disorder (BD). It is unclear to what extent these relate to underlying circadian rhythm disturbance (CRD). In this study we aimed to objectively assess sleep and circadian rhythm in a cohort of patients with BD compared to matched controls. Forty-six patients with BD and 42 controls had comprehensive sleep/circadian rhythm assessment with respiratory sleep studies, prolonged accelerometry over 3 weeks, sleep questionnaires and diaries, melatonin levels, alongside mood, psychosocial functioning and quality of life (QoL) questionnaires. Twenty-three (50%) patients with BD had abnormal sleep, of whom 12 (52%) had CRD and 29% had obstructive sleep apnoea. Patients with abnormal sleep had lower 24-h melatonin secretion compared to controls and patients with normal sleep. Abnormal sleep/CRD in BD was associated with impaired functioning and worse QoL. BD is associated with high rates of abnormal sleep and CRD. The association between these disorders, mood and functioning, and the direction of causality, warrants further investigation.

  5. Propylthiouracil, but not other antithyroid treatments, lengthens hamster circadian period

    International Nuclear Information System (INIS)

    Morin, L.P.

    1988-01-01

    Two experiments were performed to evaluate the role of the thyroid gland as a mediator of circadian rhythms in the hamster. In experiment 1, the antithyroid drug propylthiouracil (PTU) lengthened the circadian period (τ), increased thyroid weight, and eliminated detectable thyroxine (T 4 ) and triiodothyronine (T 3 ) from blood. A low-iodine diet greatly reduced T 4 levels but had no effect on T 3 or τ. Treatment with 500 μCi of 131 I failed to alter any parameter of physiology or thythmicity measured. In this experiment, some animals in the low-iodine and PTU groups had greatly reduced testes sizes, and testses size was inversely correlated with change in τ. In experiment 2, T 4 and T 3 levels detected 11 wk after surgical thyroidectomy were significantly less than those found in sham-operated ammals, but concentrations of the two hormones varied widely across the thyroidectomized group. Thyroidectomy did not increase τ either 4 or 11 wk after surgery, nor was there evidence from individuals that level of thyroid function was associated with change in τ. The results from these experiments suggest that diminished thyroid function is not causal of lengthened circadian period

  6. Disruption of Circadian rhythms enhances radiation tolerance in mice

    International Nuclear Information System (INIS)

    Patil, Shrikant L.; Krishna, A.P.; Somashekarappa, H.M.; Patil, Rajashekar K.

    2014-01-01

    Whether an alteration in responses to the radiations depends on the phase of Circadian rhythm, this has been explored previously. The results however have been inconclusive and only survival rate of animals has been considered to represent the effect. Circadian phase has been shown to be critical in many therapeutic procedures. The present study was conducted on control group of mice (12L: 12D), extended day length and night length by imposing 24 hrs of light followed by 24 hrs of darkness, a third group received (8L: 8D) light: day cycles. These regimes were operational for seven days, at the end of seventh day mice from three different groups were exposed to 3 Gy of total body gamma radiation. Survival study, extent of lipid peroxidation and antioxidant status was estimated. Radioresistance was found to be enhanced in mice maintained at 8L: 8D cycle. There was no significant changes observed in mice of time shift group (24L: 24D). The corresponding shift in the acrophase of radioresistance following a sudden time shift supports the effect of disrupted circadian rhythms. (author)

  7. Sleep Deprivation Influences Circadian Gene Expression in the Lateral Habenula.

    Science.gov (United States)

    Zhang, Beilin; Gao, Yanxia; Li, Yang; Yang, Jing; Zhao, Hua

    2016-01-01

    Sleep is governed by homeostasis and the circadian clock. Clock genes play an important role in the generation and maintenance of circadian rhythms but are also involved in regulating sleep homeostasis. The lateral habenular nucleus (LHb) has been implicated in sleep-wake regulation, since LHb gene expression demonstrates circadian oscillation characteristics. This study focuses on the participation of LHb clock genes in regulating sleep homeostasis, as the nature of their involvement is unclear. In this study, we observed changes in sleep pattern following sleep deprivation in LHb-lesioned rats using EEG recording techniques. And then the changes of clock gene expression (Per1, Per2, and Bmal1) in the LHb after 6 hours of sleep deprivation were detected by using real-time quantitative PCR (qPCR). We found that sleep deprivation increased the length of Non-Rapid Eye Movement Sleep (NREMS) and decreased wakefulness. LHb-lesioning decreased the amplitude of reduced wake time and increased NREMS following sleep deprivation in rats. qPCR results demonstrated that Per2 expression was elevated after sleep deprivation, while the other two genes were unaffected. Following sleep recovery, Per2 expression was comparable to the control group. This study provides the basis for further research on the role of LHb Per2 gene in the regulation of sleep homeostasis.

  8. 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.

  9. Circadian Stress Regimes Affect the Circadian Clock and Cause Jasmonic Acid-Dependent Cell Death in Cytokinin-Deficient Arabidopsis Plants[OPEN

    Science.gov (United States)

    Nitschke, Silvia; Cortleven, Anne; Iven, Tim; Havaux, Michel; Schmülling, Thomas

    2016-01-01

    The circadian clock helps plants measure daylength and adapt to changes in the day-night rhythm. We found that changes in the light-dark regime triggered stress responses, eventually leading to cell death, in leaves of Arabidopsis thaliana plants with reduced cytokinin levels or defective cytokinin signaling. Prolonged light treatment followed by a dark period induced stress and cell death marker genes while reducing photosynthetic efficiency. This response, called circadian stress, is also characterized by altered expression of clock and clock output genes. In particular, this treatment strongly reduced the expression of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Intriguingly, similar changes in gene expression and cell death were observed in clock mutants lacking proper CCA1 and LHY function. Circadian stress caused strong changes in reactive oxygen species- and jasmonic acid (JA)-related gene expression. The activation of the JA pathway, involving the accumulation of JA metabolites, was crucial for the induction of cell death, since the cell death phenotype was strongly reduced in the jasmonate resistant1 mutant background. We propose that adaptation to circadian stress regimes requires a normal cytokinin status which, acting primarily through the AHK3 receptor, supports circadian clock function to guard against the detrimental effects of circadian stress. PMID:27354555

  10. Immunoreactivities to three circadian clock proteins in two ground crickets suggest interspecific diversity of the circadian clock structure

    Czech Academy of Sciences Publication Activity Database

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

    2006-01-01

    Roč. 21, č. 2 (2006), s. 118-131 ISSN 0748-7304 Grant - others:Japan Society for the Promotion of Science(JP) JSPS 99L01205; Japan Society for the Promotion of Science(JP) ID No. P 04197 Institutional research plan: CEZ:AV0Z50070508 Keywords : circadian rhythm * photoperiodic clock * cryptochrome (CRY) Subject RIV: ED - Physiology Impact factor: 4.633, year: 2006

  11. Circadian clock-dependent and -independent rhythmic proteomes implement distinct diurnal functions in mouse liver.

    Science.gov (United States)

    Mauvoisin, Daniel; Wang, Jingkui; Jouffe, Céline; Martin, Eva; Atger, Florian; Waridel, Patrice; Quadroni, Manfredo; Gachon, Frédéric; Naef, Felix

    2014-01-07

    Diurnal oscillations of gene expression controlled by the circadian clock underlie rhythmic physiology across most living organisms. Although such rhythms have been extensively studied at the level of transcription and mRNA accumulation, little is known about the accumulation patterns of proteins. Here, we quantified temporal profiles in the murine hepatic proteome under physiological light-dark conditions using stable isotope labeling by amino acids quantitative MS. Our analysis identified over 5,000 proteins, of which several hundred showed robust diurnal oscillations with peak phases enriched in the morning and during the night and related to core hepatic physiological functions. Combined mathematical modeling of temporal protein and mRNA profiles indicated that proteins accumulate with reduced amplitudes and significant delays, consistent with protein half-life data. Moreover, a group comprising about one-half of the rhythmic proteins showed no corresponding rhythmic mRNAs, indicating significant translational or posttranslational diurnal control. Such rhythms were highly enriched in secreted proteins accumulating tightly during the night. Also, these rhythms persisted in clock-deficient animals subjected to rhythmic feeding, suggesting that food-related entrainment signals influence rhythms in circulating plasma factors.

  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. Circadian pacemaking in cells and circuits of the suprachiasmatic nucleus.

    Science.gov (United States)

    Hastings, M H; Brancaccio, M; Maywood, E S

    2014-01-01

    The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal circadian pacemaker of the brain. It co-ordinates the daily rhythms of sleep and wakefulness, as well as physiology and behaviour, that set the tempo to our lives. Disturbance of this daily pattern, most acutely with jet-lag but more insidiously with rotational shift-work, can have severely deleterious effects for mental function and long-term health. The present review considers recent developments in our understanding of the properties of the SCN that make it a robust circadian time-keeper. It first focuses on the intracellular transcriptional/ translational feedback loops (TTFL) that constitute the cellular clockwork of the SCN neurone. Daily timing by these loops pivots around the negative regulation of the Period (Per) and Cryptochrome (Cry) genes by their protein products. The period of the circadian cycle is set by the relative stability of Per and Cry proteins, and this can be controlled by both genetic and pharmacological interventions. It then considers the function of these feedback loops in the context of cytosolic signalling by cAMP and intracellular calcium ([Ca(2+) ]i ), which are both outputs from, and inputs to, the TTFL, as well as the critical role of vasoactive intestinal peptide (VIP) signalling in synchronising cellular clocks across the SCN. Synchronisation by VIP in the SCN is paracrine, operating over an unconventionally long time frame (i.e. 24 h) and wide spatial domain, mediated via the cytosolic pathways upstream of the TTFL. Finally, we show how intersectional pharmacogenetics can be used to control G-protein-coupled signalling in individual SCN neurones, and how manipulation of Gq/[Ca(2+) ]i -signalling in VIP neurones can re-programme the circuit-level encoding of circadian time. Circadian pacemaking in the SCN therefore provides an unrivalled context in which to understand how a complex, adaptive behaviour can be organised by the dynamic activity of a relatively

  14. Biogas feed analysis

    OpenAIRE

    Song, Yuan

    2008-01-01

    Biogas production is regarded as the best energy recovery process from wet organic solid wastes (WOSW). Feed composition, storage conditions and time will influence the compositions of feed to biogas processes. In this study, apple juice from Meierienes Juice factory was used as the model substrates to mimic the liquid phase that can be extracted from fruit or juice industry WOSW. A series of batch experiments were carried out with different initial feed concentrations (0, 1, 2, 5, 10 %) of a...

  15. Breastfeeding is best feeding.

    Science.gov (United States)

    Cutting, W

    1995-02-01

    The traditional practice of breast feeding is the best means to make sure infants grow up healthy. It costs nothing. Breast milk contains antibodies and other substances which defend against disease, especially those linked to poor food hygiene and inadequate water and sanitation. In developing countries, breast fed infants are at least 14 times less likely to die from diarrhea than those who are not breast fed. Urbanization and promotion of infant formula undermine breast feeding. Even though infants up to age 4-6 months should receive only breast milk to remain as healthy as possible, infants aged less than 4-6 months often receive other milks or gruels. Attendance of health workers at delivery and their contact with mother-infant pairs after delivery are ideal opportunities to encourage mothers to breast feed. In fact, if health workers provide mothers skilled support with breast feeding, mothers are more likely to breast feed well and for a longer time. Health workers need counseling skills and firm knowledge of techniques on breast feeding and of how to master common difficulties to help mothers with breast feeding. Listening skills and confidence building skills are also needed. Good family and work place support allows women in paid employment outside the home to continue breast feeding. Breast feeding is very important in emergency situations where access to water, sanitation, food, and health care is limited (e.g., refugee camps). In these situations, health workers should especially be aware of women's ability to breast feed and to support their breast feeding. HIV can be transmitted to nursing infants from HIV infected mothers. Yet one must balance this small risk against the possibility of contracting other serious infections (e.g., diarrhea) through alternative infant feeding, particularly if there is no access to potable water and sanitation.

  16. NUCLEOTIDES IN INFANT FEEDING

    Directory of Open Access Journals (Sweden)

    L.G. Mamonova

    2007-01-01

    Full Text Available The article reviews the application of nucleotides-metabolites, playing a key role in many biological processes, for the infant feeding. The researcher provides the date on the nucleotides in the women's milk according to the lactation stages. She also analyzes the foreign experience in feeding newborns with nucleotides-containing milk formulas. The article gives a comparison of nucleotides in the adapted formulas represented in the domestic market of the given products.Key words: children, feeding, nucleotides.

  17. The Arabidopsis sickle mutant exhibits altered circadian clock responses to cool tempatures and tempature-dependent alternative splicing

    Science.gov (United States)

    The circadian clock allows plants to anticipate and respond to daily changes in ambient temperature. Mechanisms establishing the timing of circadian rhythms in Arabidopsis thaliana through temperature entrainment remain unclear. Also incompletely understood is the temperature compensation mechanism ...

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Infectious waste feed system

    Science.gov (United States)

    Coulthard, E. James

    1994-01-01

    An infectious waste feed system for comminuting infectious waste and feeding the comminuted waste to a combustor automatically without the need for human intervention. The system includes a receptacle for accepting waste materials. Preferably, the receptacle includes a first and second compartment and a means for sealing the first and second compartments from the atmosphere. A shredder is disposed to comminute waste materials accepted in the receptacle to a predetermined size. A trough is disposed to receive the comminuted waste materials from the shredder. A feeding means is disposed within the trough and is movable in a first and second direction for feeding the comminuted waste materials to a combustor.

  20. Uncoupling effect of palmitate is exacerbated in skeletal muscle mitochondria of sea-acclimatized king penguins (Aptenodytes patagonicus).

    Science.gov (United States)

    Rey, Benjamin; Duchamp, Claude; Roussel, Damien

    2017-09-01

    In king penguin juveniles, the environmental transition from a terrestrial to a marine habitat, occurring at fledging, drastically stimulates lipid catabolism and the remodelling of muscle mitochondria to sustain extensive swimming activity and thermoregulation in the cold circumpolar oceans. However, the exact nature of these mechanisms remains only partially resolved. Here we investigated, in vitro, the uncoupling effect of increasing doses of fatty acids in pectoralis muscle intermyofibrillar mitochondria isolated, either from terrestrial never-immersed or experimentally cold water immersed pre-fledging king penguins or from sea-acclimatized fledged penguins. Mitochondria exhibited much greater palmitate-induced uncoupling respiration and higher maximal oxidative capacity after acclimatization to marine life. Such effects were not reproduced experimentally after repeated immersions in cold water, suggesting that the plasticity of mitochondrial characteristics may not be primarily driven by cold exposure per se but by other aspects of sea acclimatization. Copyright © 2017. Published by Elsevier Inc.

  1. Uncoupling of sarcoplasmic reticulum Ca²⁺-ATPase by N-arachidonoyl dopamine. Members of the endocannabinoid family as thermogenic drugs

    DEFF Research Database (Denmark)

    Mahmmoud, Yasser Ahmed; Gaster, Michel

    2013-01-01

    BACKGROUND AND PURPOSE: The sarcoplasmic reticulum Ca²⁺-ATPase (SERCA) plays a role in thermogenesis. The exogenous compound capsaicin increased SERCA-mediated ATP hydrolysis not coupled to Ca²⁺ transport. Here, we have sought to identify endogenous compounds that may function as SERCA uncoupling...... agents. EXPERIMENTAL APPROACH: Using isolated SR vesicles from rabbits, we have screened for endogenous compounds that uncouple SERCA. We have also studied their ability to deplete cytoplasmic ATP from human skeletal muscle cells in culture. KEY RESULTS: Studies on SR vesicles showed that the endogenous......, regardless of the presence of glucose. CONCLUSIONS AND IMPLICATIONS: NADA is an endogenous molecule that may function as SERCA uncoupling agent in vivo. Members of the endocannabinoid family exert concerted actions on several Ca²⁺-handling proteins. Uncoupling of SERCA by exogenous compounds could be a novel...

  2. Undecanesulfonate does not allosterically activate H+ uniport mediated by uncoupling protein-1 in brown adipose tissue mitochondria

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Špaček, Tomáš; Garlid, K.; Jabůrek, Martin

    2006-01-01

    Roč. 38, č. 11 (2006), s. 1965-1974 ISSN 1357-2725 R&D Projects: GA AV ČR(CZ) IAA5011106; GA MŠk(CZ) 1P05ME794 Grant - others:NIH(US) TW01487 Institutional research plan: CEZ:AV0Z50110509 Keywords : uncoupling protein–1 * mitochondria * fatty acid Subject RIV: ED - Physiology Impact factor: 4.804, year: 2006

  3. Dietary Uncoupling of Gut Microbiota and Energy Harvesting from Obesity and Glucose Tolerance in Mice

    OpenAIRE

    Matthew J. Dalby; Alexander W. Ross; Alan W. Walker; Peter J. Morgan

    2017-01-01

    Summary Evidence suggests that altered gut microbiota composition may be involved in the development of obesity. Studies using mice made obese with refined high-fat diets have supported this; however, these have commonly used chow as a control diet, introducing confounding factors from differences in dietary composition that have a key role in shaping microbiota composition. We compared the effects of feeding a refined high-fat diet with those of feeding either a refined low-fat diet or a cho...

  4. Synthesis of mitochondrial uncoupling protein in brown adipocytes differentiated in cell culture

    International Nuclear Information System (INIS)

    Kopecky, J.; Baudysova, M.; Zanotti, F.; Janikova, D.; Pavelka, S.; Houstek, J.

    1990-01-01

    In order to characterize the biogenesis of unique thermogenic mitochondria of brown adipose tissue, differentiation of precursor cells isolated from mouse brown adipose tissue was studied in cell culture. Synthesis of mitochondrial uncoupling protein (UCP), F1-ATPase, and cytochrome oxidase was examined by L-[35S]methionine labeling and immunoblotting. For the first time, synthesis of physiological amounts of the UCP, a key and tissue-specific component of thermogenic mitochondria, was observed in cultures at about confluence (day 6), indicating that a complete differentiation of brown adipocytes was achieved in vitro. In postconfluent cells (day 8) the content of UCP decreased rapidly, in contrast to some other mitochondrial proteins (beta subunit of F1-ATPase, cytochrome oxidase). In these cells, it was possible, by using norepinephrine, to induce specifically the synthesis of the UCP but not of F1-ATPase or cytochrome oxidase. The maximal response was observed at 0.1 microM norepinephrine and the synthesis of UCP remained activated for at least 24 h. Detailed analysis revealed a major role of the beta-adrenergic receptors and elevated intracellular concentration of cAMP in stimulation of UCP synthesis. A quantitative recovery of the newly synthesized UCP in the mitochondrial fraction indicated completed biogenesis of functionally competent thermogenic mitochondria

  5. TGF-beta Sma/Mab signaling mutations uncouple reproductive aging from somatic aging.

    Directory of Open Access Journals (Sweden)

    Shijing Luo

    2009-12-01

    Full Text Available Female reproductive cessation is one of the earliest age-related declines humans experience, occurring in mid-adulthood. Similarly, Caenorhabditis elegans' reproductive span is short relative to its total life span, with reproduction ceasing about a third into its 15-20 day adulthood. All of the known mutations and treatments that extend C. elegans' reproductive period also regulate longevity, suggesting that reproductive span is normally linked to life span. C. elegans has two canonical TGF-beta signaling pathways. We recently found that the TGF-beta Dauer pathway regulates longevity through the Insulin/IGF-1 Signaling (IIS pathway; here we show that this pathway has a moderate effect on reproductive span. By contrast, TGF-beta Sma/Mab signaling mutants exhibit a substantially extended reproductive period, more than doubling reproductive span in some cases. Sma/Mab mutations extend reproductive span disproportionately to life span and act independently of known regulators of somatic aging, such as Insulin/IGF-1 Signaling and Dietary Restriction. This is the first discovery of a pathway that regulates reproductive span independently of longevity and the first identification of the TGF-beta Sma/Mab pathway as a regulator of reproductive aging. Our results suggest that longevity and reproductive span regulation can be uncoupled, although they appear to normally be linked through regulatory pathways.

  6. Widespread uncoupling between transcriptome and translatome variations after a stimulus in mammalian cells

    Directory of Open Access Journals (Sweden)

    Tebaldi Toma

    2012-06-01

    Full Text Available Abstract Background The classical view on eukaryotic gene expression proposes the scheme of a forward flow for which fluctuations in mRNA levels upon a stimulus contribute to determine variations in mRNA availability for translation. Here we address this issue by simultaneously profiling with microarrays the total mRNAs (the transcriptome and the polysome-associated mRNAs (the translatome after EGF treatment of human cells, and extending the analysis to other 19 different transcriptome/translatome comparisons in mammalian cells following different stimuli or undergoing cell programs. Results Triggering of the EGF pathway results in an early induction of transcriptome and translatome changes, but 90% of the significant variation is limited to the translatome and the degree of concordant changes is less than 5%. The survey of other 19 different transcriptome/translatome comparisons shows that extensive uncoupling is a general rule, in terms of both RNA movements and inferred cell activities, with a strong tendency of translation-related genes to be controlled purely at the translational level. By different statistical approaches, we finally provide evidence of the lack of dependence between changes at the transcriptome and translatome levels. Conclusions We propose a model of diffused independency between variation in transcript abundances and variation in their engagement on polysomes, which implies the existence of specific mechanisms to couple these two ways of regulating gene expression.

  7. Calculation of Coupled Vibroacoustics Response Estimates from a Library of Available Uncoupled Transfer Function Sets

    Science.gov (United States)

    Smith, Andrew; LaVerde, Bruce; Hunt, Ron; Fulcher, Clay; Towner, Robert; McDonald, Emmett

    2012-01-01

    The design and theoretical basis of a new database tool that quickly generates vibroacoustic response estimates using a library of transfer functions (TFs) is discussed. During the early stages of a launch vehicle development program, these response estimates can be used to provide vibration environment specification to hardware vendors. The tool accesses TFs from a database, combines the TFs, and multiplies these by input excitations to estimate vibration responses. The database is populated with two sets of uncoupled TFs; the first set representing vibration response of a bare panel, designated as H(sup s), and the second set representing the response of the free-free component equipment by itself, designated as H(sup c). For a particular configuration undergoing analysis, the appropriate H(sup s) and H(sup c) are selected and coupled to generate an integrated TF, designated as H(sup s +c). This integrated TF is then used with the appropriate input excitations to estimate vibration responses. This simple yet powerful tool enables a user to estimate vibration responses without directly using finite element models, so long as suitable H(sup s) and H(sup c) sets are defined in the database libraries. The paper discusses the preparation of the database tool and provides the assumptions and methodologies necessary to combine H(sup s) and H(sup c) sets into an integrated H(sup s + c). An experimental validation of the approach is also presented.

  8. Spatial uncoupling of biodegradation, soil respiration, and PAH concentration in a creosote contaminated soil

    International Nuclear Information System (INIS)

    Bengtsson, Goeran; Toerneman, Niklas; Yang Xiuhong

    2010-01-01

    Hotspots and coldspots of concentration and biodegradation of polycyclic aromatic hydrocarbons (PAHs) marginally overlapped at the 0.5-100 m scale in a creosote contaminated soil in southern Sweden, suggesting that concentration and biodegradation had little spatial co-variation. Biodegradation was substantial and its spatial variability considerable and highly irregular, but it had no spatial autocorrelation. The soil concentration of PAHs explained only 20-30% of the variance of their biodegradation. Soil respiration was spatially autocorrelated. The spatial uncoupling between biodegradation and soil respiration seemed to be governed by the aging of PAHs in the soil, since biodegradation of added 13 C phenanthrene covaried with both soil respiration and microbial biomass. The latter two were also correlated with high concentrations of phospholipid fatty acids (PLFAs) that are common in gram-negative bacteria. However, several of the hotspots of biodegradation coincided with hotspots for the distribution of a PLFA indicative of fungal biomass. - Hotspots of PAH biodegradation in a creosote contaminated soil do not coincide with hotspots of PAH concentration, microbial biomass and respiration.

  9. Seismic Assessment of Buildings: Proposal of a New Modified Uncoupled Modal Response History Analysis

    International Nuclear Information System (INIS)

    Jerez, Sandra; Mebarki, Ahmed

    2010-01-01

    This paper develops a new modified uncoupled modal response history analysis (M-UMRHA) in order to study the seismic behavior of structures. It aims to provide an acceptable accuracy with reduced calculation duration in comparison to complete analysis, i.e. the THA. The proposed method improves the existing UMRHA, developed by Chopra and Goel [1], by considering an energy based approach to build the capacity curve [2] and a pseudo-adaptive feature to account for changes in modal shapes after yielding, motivated by an adaptive method [3]. Validation is made by comparison with NLTHA as well as other simplified methods. Low and medium-rise RC buildings were analyzed under real ground motion records. Results show good estimates of structural parameters and give good correlation between damage and story displacements as well as drifts. Like other simplified methods, accuracy decreases in the inelastic domain. However, this procedure gives acceptable estimates of structural response with a few additional calculations and it has the potential to be used in large scale studies, and probabilistic approaches.

  10. Low-level lasers affect uncoupling protein gene expression in skin and skeletal muscle tissues

    International Nuclear Information System (INIS)

    Canuto, K S; Sergio, L P S; Mencalha, A L; Fonseca, A S; Paoli, F

    2016-01-01

    Wavelength, frequency, power, fluence, and emission mode determine the photophysical, photochemical, and photobiological responses of biological tissues to low-level lasers. Free radicals are involved in these responses acting as second messengers in intracellular signaling processes. Irradiated cells present defenses against these chemical species to avoid unwanted effects, such as uncoupling proteins (UCPs), which are part of protective mechanisms and minimize the effects of free radical generation in mitochondria. In this work UCP2 and UCP3 mRNA gene relative expression in the skin and skeletal muscle tissues of Wistar rats exposed to low-level red and infrared lasers was evaluated. Samples of the skin and skeletal muscle tissue of Wistar rats exposed to low-level red and infrared lasers were withdrawn for total RNA extraction, cDNA synthesis, and the evaluation of gene expression by quantitative polymerase chain reaction. UCP2 and UCP3 mRNA expression was differently altered in skin and skeletal muscle tissues exposed to lasers in a wavelength-dependent effect, with the UCP3 mRNA expression dose-dependent. Alteration on UCP gene expression could be part of the biostimulation effect and is necessary to make cells exposed to red and infrared low-level lasers more resistant or capable of adapting in damaged tissues or diseases. (paper)

  11. Cell Death and Heart Failure in Obesity: Role of Uncoupling Proteins

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    Angélica Ruiz-Ramírez

    2016-01-01

    Full Text Available Metabolic diseases such as obesity, metabolic syndrome, and type II diabetes are often characterized by increased reactive oxygen species (ROS generation in mitochondrial respiratory complexes, associated with fat accumulation in cardiomyocytes, skeletal muscle, and hepatocytes. Several rodents studies showed that lipid accumulation in cardiac myocytes produces lipotoxicity that causes apoptosis and leads to heart failure, a dynamic pathological process. Meanwhile, several tissues including cardiac tissue develop an adaptive mechanism against oxidative stress and lipotoxicity by overexpressing uncoupling proteins (UCPs, specific mitochondrial membrane proteins. In heart from rodent and human with obesity, UCP2 and UCP3 may protect cardiomyocytes from death and from a state progressing to heart failure by downregulating programmed cell death. UCP activation may affect cytochrome c and proapoptotic protein release from mitochondria by reducing ROS generation and apoptotic cell death. Therefore the aim of this review is to discuss recent findings regarding the role that UCPs play in cardiomyocyte survival by protecting against ROS generation and maintaining bioenergetic metabolism homeostasis to promote heart protection.

  12. Hydrodynamical simulations of coupled and uncoupled quintessence models - II. Galaxy clusters

    Science.gov (United States)

    Carlesi, Edoardo; Knebe, Alexander; Lewis, Geraint F.; Yepes, Gustavo

    2014-04-01

    We study the z = 0 properties of clusters (and large groups) of galaxies within the context of interacting and non-interacting quintessence cosmological models, using a series of adiabatic SPH simulations. Initially, we examine the average properties of groups and clusters, quantifying their differences in ΛCold Dark Matter (ΛCDM), uncoupled Dark Energy (uDE) and coupled Dark Energy (cDE) cosmologies. In particular, we focus upon radial profiles of the gas density, temperature and pressure, and we also investigate how the standard hydrodynamic equilibrium hypothesis holds in quintessence cosmologies. While we are able to confirm previous results about the distribution of baryons, we also find that the main discrepancy (with differences up to 20 per cent) can be seen in cluster pressure profiles. We then switch attention to individual structures, mapping each halo in quintessence cosmology to its ΛCDM counterpart. We are able to identify a series of small correlations between the coupling in the dark sector and halo spin, triaxiality and virialization ratio. When looking at spin and virialization of dark matter haloes, we find a weak (5 per cent) but systematic deviation in fifth force scenarios from ΛCDM.

  13. Isoproterenol Increases Uncoupling, Glycolysis, and Markers of Beiging in Mature 3T3-L1 Adipocytes.

    Directory of Open Access Journals (Sweden)

    Colette N Miller

    Full Text Available Beta-adrenergic activation stimulates uncoupling protein 1 (UCP1, enhancing metabolic rate. In vitro, most work has studied brown adipocytes, however, few have investigated more established adipocyte lines such as the murine 3T3-L1 line. To assess the effect of beta-adrenergic activation, mature 3T3-L1s were treated for 6 or 48 hours with or without isoproterenol (10 and 100 μM following standard differentiation supplemented with thyroid hormone (T3; 1 nM. The highest dose of isoproterenol increased lipid content following 48 hours of treatment. This concentration enhanced UCP1 mRNA and protein expression. The increase in UCP1 following 48 hours of isoproterenol increased oxygen consumption rate. Further, coupling efficiency of the electron transport chain was disturbed and an enhancement of glycolytic rate was measured alongside this, indicating an attempt to meet the energy demands of the cell. Lastly, markers of beige adipocytes (protein content of CD137 and gene transcript of CITED1 were also found to be upregulated at 48 hours of isoproterenol treatment. This data indicates that mature 3T3-L1 adipocytes are responsive to isoproterenol and induce UCP1 expression and activity. Further, this finding provides a model for further pharmaceutical and nutraceutical investigation of UCP1 in 3T3-L1s.

  14. The role of uncoupling protein 3 regulating calcium ion uptake into mitochondria during sarcopenia

    Science.gov (United States)

    Nikawa, Takeshi; Choi, Inho; Haruna, Marie; Hirasaka, Katsuya; Maita Ohno, Ayako; Kondo Teshima, Shigetada

    Overloaded mitochondrial calcium concentration contributes to progression of mitochondrial dysfunction in aged muscle, leading to sarcopenia. Uncoupling protein 3 (UCP3) is primarily expressed in the inner membrane of skeletal muscle mitochondria. Recently, it has been reported that UCP3 is associated with calcium uptake into mitochondria. However, the mechanisms by which UCP3 regulates mitochondrial calcium uptake are not well understood. Here we report that UCP3 interacts with HS-1 associated protein X-1 (Hax-1), an anti-apoptotic protein that is localized in mitochondria, which is involved in cellular responses to calcium ion. The hydrophilic sequences within the loop 2, matrix-localized hydrophilic domain of mouse UCP3 are necessary for binding to Hax-1 of the C-terminal domain in adjacent to mitochondrial innermembrane. Interestingly, these proteins interaction occur the calcium-dependent manner. Indeed, overexpression of UCP3 significantly enhanced calcium uptake into mitochondria on Hax-1 endogenously expressing C2C12 myoblasts. In addition, Hax-1 knock-down enhanced calcium uptake into mitochondria on both UCP3 and Hax-1 endogenously expressing C2C12 myotubes, but not myoblasts. Finally, the dissociation of UCP3 and Hax-1 enhances calcium uptake into mitochondria in aged muscle. These studies identify a novel UCP3-Hax-1 complex regulates the influx of calcium ion into mitochondria in muscle. Thus, the efficacy of UCP3-Hax-1 in mitochondrial calcium regulation may provide a novel therapeutic approach against mitochondrial dysfunction-related disease containing sarcopenia.

  15. Functional and immunochemical characterization of a mutant of Escherichia coli energy uncoupled for lactose transport

    International Nuclear Information System (INIS)

    Herzlinger, D.; Carrasco, N.; Kaback, H.R.

    1985-01-01

    Right-side-out cytoplasmic membrane vesicles from Escherichia coli ML 308-22, a mutant ''uncoupled'' for beta-galactoside/H + symport are specifically defective in the ability to catalyze accumulation of methyl 1-thio-beta-D-galactopyranoside (TMG) in the presence of an H + electrochemical gradient (interior negative and alkaline). Furthermore, the rate of carrier-mediated efflux under nonenergized conditions is slow and unaffected by ambient pH from pH 5.5 to 7.5, and TMG-induced H + influx is only about 15% of that observed in vesicles containing wild-type lac permease (ML 308-225). Alternatively, ML 308-22 vesicles bind p-nitrophenyl alpha-D-galactopyranoside and monoclonal antibody 4B1 to the same extent as ML 308-225 vesicles and catalyze facilitated diffusion and equilibrium exchange as well as ML 308-225 vesicles. When entrance counterflow is studied with external substrate at saturating and subsaturating concentrations, it is apparent that the mutation simulates the effects of deuterium oxide. That is, the mutation has no effect on the rate or extent of counterflow when external substrate is saturating but stimulates the efficiency of counterflow when external substrate is below the apparent K/sub m/. Moreover, although replacement of protium with deuterium stimulates counterflow in ML 308-225 vesicles when external substrate is subsaturating, the isotope has no effect on the mutant vesicles under the same conditions

  16. Temporal Uncoupling between Energy Acquisition and Allocation to Reproduction in a Herbivorous-Detritivorous Fish.

    Directory of Open Access Journals (Sweden)

    Francisco Villamarín

    Full Text Available Although considerable knowledge has been gathered regarding the role of fish in cycling and translocation of nutrients across ecosystem boundaries, little information is available on how the energy obtained from different ecosystems is temporally allocated in fish bodies. Although in theory, limitations on energy budgets promote the existence of a trade-off between energy allocated to reproduction and somatic growth, this trade-off has rarely been found under natural conditions. Combining information on RNA:DNA ratios and carbon and nitrogen stable-isotope analyses we were able to achieve novel insights into the reproductive allocation of diamond mullet (Liza alata, a catadromous, widely distributed herbivorous-detritivorous fish. Although diamond mullet were in better condition during the wet season, most reproductive allocation occurred during the dry season when resources are limited and fish have poorer body condition. We found a strong trade-off between reproductive and somatic investment. Values of δ13C from reproductive and somatic tissues were correlated, probably because δ13C in food resources between dry and wet seasons do not differ markedly. On the other hand, data for δ15N showed that gonads are more correlated to muscle, a slow turnover tissue, suggesting long term synthesis of reproductive tissues. In combination, these lines of evidence suggest that L. alata is a capital breeder which shows temporal uncoupling of resource ingestion, energy storage and later allocation to reproduction.

  17. Metformin induces oxidative stress in white adipocytes and raises uncoupling protein 2 levels.

    Science.gov (United States)

    Anedda, Andrea; Rial, Eduardo; González-Barroso, M Mar

    2008-10-01

    Metformin is a drug widely used to treat type 2 diabetes. It enhances insulin sensitivity by improving glucose utilization in tissues like liver or muscle. Metformin inhibits respiration, and the decrease in cellular energy activates the AMP-activated protein kinase that in turn switches on catabolic pathways. Moreover, metformin increases lipolysis and beta-oxidation in white adipose tissue, thereby reducing the triglyceride stores. The uncoupling proteins (UCPs) are transporters that lower the efficiency of mitochondrial oxidative phosphorylation. UCP2 is thought to protect against oxidative stress although, alternatively, it could play an energy dissipation role. The aim of this work was to analyse the involvement of UCP2 on the effects of metformin in white adipocytes. We studied the effect of this drug in differentiating 3T3-L1 adipocytes and found that metformin causes oxidative stress since it increases the levels of reactive oxygen species (ROS) and lowers the aconitase activity. Variations in UCP2 protein levels parallel those of ROS. Metformin also increases lipolysis in these cells although only when the levels of ROS and UCP2 have decreased. Hence, UCP2 does not appear to be needed to facilitate fatty acid oxidation. Furthermore, treatment of C57BL/6 mice with metformin also augmented the levels of UCP2 in epididymal white adipose tissue. We conclude that metformin treatment leads to the overexpression of UCP2 in adipocytes to minimize the oxidative stress that is probably due to the inhibition of respiration caused by the drug.

  18. Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins

    Directory of Open Access Journals (Sweden)

    Khanichi N. Charles

    2017-10-01

    Full Text Available Summary: Deterioration of metabolic health is a hallmark of aging and generally assumed to be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism and accelerates aging; conversely, calorie restriction (CR prevents age-related metabolic diseases and extends lifespan. However, it is unclear whether preservation of metabolic health is sufficient to extend lifespan. We utilized a genetic mouse model lacking Fabp4/5 that confers protection against metabolic diseases and shares molecular and lipidomic features with CR to address this question. Fabp-deficient mice exhibit extended metabolic healthspan, with protection against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly, however, Fabp-deficient mice did not exhibit any extension of lifespan. These data indicate that extension of metabolic healthspan in the absence of CR can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways, at least in laboratory mice. : Deterioration of metabolic health is a hallmark of aging and generally thought to be detrimental to longevity. Charles et al. utilize FABP-deficient mice as a model to demonstrate that the preservation of metabolic health in this model persists throughout life, even under metabolic stress, but does not increase longevity. Keywords: fatty acid binding protein, aging, calorie restriction, metabolic health, inflammation, metaflammation, diabetes, obesity, de novo lipogenesis

  19. Plasma Amino Acids Stimulate Uncoupled Respiration of Muscle Subsarcolemmal Mitochondria in Lean but Not Obese Humans.

    Science.gov (United States)

    Kras, Katon A; Hoffman, Nyssa; Roust, Lori R; Patel, Shivam H; Carroll, Chad C; Katsanos, Christos S

    2017-12-01

    Obesity is associated with mitochondrial dysfunction in skeletal muscle. Increasing the plasma amino acid (AA) concentrations stimulates mitochondrial adenosine triphosphate (ATP) production in lean individuals. To determine whether acute elevation in plasma AAs enhances muscle mitochondrial respiration and ATP production in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in obese adults. Assessment of SS and IMF mitochondrial function during saline (i.e., control) and AA infusions. Eligible participants were healthy lean (body mass index, mass index >30 kg/m2; age 35 ± 3 years; n = 11) subjects. Single trial of saline infusion followed by AA infusion. SS and IMF mitochondria were isolated from muscle biopsies collected at the end of the saline and AA infusions. Mitochondrial respiration and ATP production. AA infusion increased adenosine 5'-diphosphate (ADP)-stimulated respiration and ATP production rates of SS mitochondria in the lean (P lean subjects only (P lean or obese subjects (P > 0.05). Increasing the plasma AA concentrations enhances the capacity for respiration and ATP production of muscle SS, but not IMF, mitochondria in lean individuals, in parallel with increases in uncoupled respiration. However, neither of these parameters increases in muscle SS or IMF mitochondria in obese individuals. Copyright © 2017 Endocrine Society

  20. Mitochondrial uncoupling and the reprogramming of intermediary metabolism in leukemia cells

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    Juliana eVélez

    2013-04-01

    Full Text Available Nearly 60 years ago Otto Warburg proposed, in a seminal publication, that an irreparable defect in the oxidative capacity of normal cells supported the switch to glycolysis for energy generation and the appearance of the malignant phenotype (Warburg, 1956. Curiously, this phenotype was also observed by Warburg in embryonic tissues, and recent research demonstrated that normal stem cells may indeed rely on aerobic glycolysis – fermenting pyruvate to lactate in the presence of ample oxygen - rather than on the complete oxidation of pyruvate in the Krebs cycle - to generate cellular energy (Folmes et al., 2012. However, it remains to be determined whether this phenotype is causative for neoplastic development, or rather the result of malignant transformation. In addition, in light of mounting evidence demonstrating that cancer cells can carry out electron transport and oxidative phosphorylation, although in some cases predominantly using electrons from non-glucose carbon sources (Bloch-Frankenthal et al., 1965, Warburg´s hypothesis needs to be revisited. Lastly, recent evidence suggests that the leukemia bone marrow microenvironment promotes the Warburg phenotype adding another layer of complexity to the study of metabolism in hematological malignancies. In this review we will discuss some of the evidence for alterations in the intermediary metabolism of leukemia cells and present evidence for a concept put forth decades ago by lipid biochemist Feodor Lynen, and acknowledged by Warburg himself, that cancer cell mitochondria uncouple ATP synthesis from electron transport and therefore depend on glycolysis to meet their energy demands (Lynen, 1951;Warburg, 1956.