Characterizing the amplitude dynamics of the human core-temperature circadian rhythm using a stochastic-dynamic model

Two measures, amplitude and phase, have been used to describe the characteristics of the endogenous human circadian pacemaker, a biological clock located in the hypothalamus. Although many studies of change in circadian phase with respect to different stimuli have been conducted, the physiologic implications of the amplitude changes (dynamics) of the pacemaker are unknown. It is known that phase changes of the human circadian pacemaker have a significant impact on sleep timing and content, hormone secretion, subjective alertness and neurobehavioral performance. However, the changes in circadian amplitude with respect to different stimuli are less well documented. Although amplitude dynamics of the human circadian pacemaker are observed in physiological rhythms such as plasma cortisol, plasma melatonin and core temperature data, currently methods are not available to accurately characterize the amplitude dynamics from these rhythms. Of the three rhythms core temperature is the only reliable variable that can be monitored continuously in real time with a high sampling rate. To characterize the amplitude dynamics of the circadian pacemaker we propose a stochastic-dynamic model of core temperature data that contains both stochastic and dynamic characteristics. In this model the circadian component that has a dynamic characteristic is represented as a perturbation solution of the van der Pol equation and the thermoregulatory response in the data that has a stochastic characteristic is represented as a first-order autoregressive process. The model parameters are estimated using data with a maximum likelihood procedure and the goodness-of-fit measures along with the associated standard error of the estimated parameters provided inference about the amplitude dynamics of the pacemaker. Using this model we analysed core temperature data from an experiment designed to exhibit amplitude dynamics. We found that the circadian pacemaker recovers slowly to an equilibrium level following amplitude suppression. In humans this reaction to perturbation from equilibrium value has potential physiological implications.     

Functional diversities of two activity components of circadian rhythm in genetical splitting mice (CS strain)

CS mice, an inbred strain, showed two distinctive characteristics in the circadian rhythm of locomotor activity: (1) large variation in the freerunning period, and (2) spontaneous rhythm splitting under continuous darkness. In the splitting rhythm there was a positive correlation between the freerunning period of the evening component and the activity time of the morning component. The phase-shifting effect of a 15-min light pulse was examined on the two activity components of the splitting rhythm. There were significant differences in the amount of light-induced phase response between the two components. A light pulse during the late subjective night induced a phase advance shift only in the morning component, while a light pulse during the early subjective night induced a phase delay shift only in the evening component. These results indicate functional diversities of the two activity components in the circadian locomotor rhythm of CS mice, and suggest that the circadian system in CS mice consists of two mutually coupled oscillators which have different circadian periods and different responsiveness to light. The CS mouse is a useful model to explore a genetic background of oscillator coupling in the circadian system of nocturnal rodents. Accepted: 19 November 1998     

哺乳动物昼夜节律生物钟研究进展

昼夜节律生物钟是一种以近似24小时为周期的自主维持的振荡器,在分子水平上,该振荡器是一个由9个基因组成的转录翻译反馈环路系统。它能受外界环境影响重新设置节律,使自身机体活动处于最佳状态。除了进行自我调节外,生物钟基因还能通过调节代谢途径中特定基因表达而影响机体生理生化过程。在过去的几年里,借用遗传学和分子生物学工具,我们对哺乳动物昼夜节律生物钟的分子基础有了新的认识,本文综述了这一进展,并展望了它们在研究人的昼夜节律行为异常领域的前景。     

Independence of genetic variation between circadian rhythm and development time in the seed beetle, Callosobruchus chinensis

A positive genetic correlation between periods of circadian rhythm and developmental time supports the hypothesis that circadian clocks are implicated in the timing of development. Empirical evidence for this genetic correlation in insects has been documented in two fly species. In contrast, here we show that there is no evidence of genetic correlation between circadian rhythm and development time in the adzuki bean beetle, Callosobruchus chinensis. This species has variation that is explained by a major gene in the expression and period length of circadian rhythm between strains. In this study, we found genetic variation in development time between the strains. The development time was not covaried with either the incidence or the period length of circadian rhythm among the strains. Crosses between strains suggest that development time is controlled by a polygene. In the F₂ individuals from the crosses, the circadian rhythm is attributable to allelic variation in the major gene. Across the F₂ individuals, development time was not correlated with either the expression or the period length of circadian rhythm. Thus, we found no effects of major genes responsible for variation in the circadian rhythm on development time in C. chinensis. Our findings collectively give no support to the hypothesis that the circadian clock is involved in the regulation of development time in this species.     

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

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 the circadian and circatidal rhythms of A. asahinai using RNAi. After injection of double-stranded RNA of per, most crickets did not show the circadian modulation of activity but the circatidal rhythm persisted without a significant difference in the period from controls. Thus, per is functionally involved in the circadian rhythm but plays no role, or a less important role, in the circatidal rhythm. We conclude that the circatidal rhythm in A. asahinai is controlled by a circatidal clock whose molecular mechanism is different from that of the circadian clock.     

松果体昼夜节律生物钟分子机制的研究进展

在各种非哺乳类脊椎动物中 ,松果体起着中枢昼夜节律振荡器的作用。近来 ,在鸟类松果体中相继发现了几种钟基因 ,如Per、Cry、Clock和Bmal等 ,其表达的时间变化规律与哺乳类视交叉上核 (SCN)的非常相似。钟的振荡由其自身调控反馈环路的转录和翻译组成 ,鸟类松果体和哺乳类SCN似乎具有共同的钟振荡基本分子构架 ;若干钟基因产物作为正向或负向调节子影响钟的振荡 ;昼夜性的控时机制同时也需要翻译后事件的参与。这些过程对钟振荡器的稳定性和 /或钟导引的光输入通路有着重要的调控作用     

Waterborne copper disrupts circadian rhythm in red seabream (Pagrus major)

We investigated the effect of copper (Cu) on circadian rhythms in red seabream, Pagrus major, under various concentrations of Cu (10, 20, 30 and 40 μg/L). To examine variability in circadian rhythms, we measured changes in the period 2 (Per2), cryptochrome 1 (Cry1), serotonin and arylalkylamine N-acetyltransferase (AANAT2) proteins. We found that circadian rhythm-related plasma proteins were significantly lower in a high-Cu environment (30–40 μg/L) than in low-Cu concentration (0, 10, or 20 μg/L). Our results indicate that environmental Cu at concentrations greater than 30 μg/L can have deleterious effects on fish circadian rhythms.     

Tubule bundle-inclusions in vacuoles of Tamarix aphylla L. mesophyll cells

Summary Vacuoles of differentiating mesophyll cells of Tamarix aphylla contain an amorphous electron-dense material in which stacks of parallel aligned striations are embedded. Cross-sections of the striations disclosed that they represent profiles of longitudinally sectioned bundles of tubules (tubule outer diameter 9.0 nm, tubule wall thickness 1.8 nm). In advanced mesophyll cell development, the amorphous vacuolar material disappears, whereas the bundles of tubules turn into bundles of double helices (double helix diameter 14.5 nm). Cytochemical treatment of mesophyll cells with the enzymes pepsin and trypsin has revealed that both the bundles of tubules/double helices and the embedding material are constituted of protein. The possible functional role of the vacuolar inclusions is discussed.     

An investigation of circadian rhythm in Escherichia coli

Background: Persuasive evidence for circadian programs in non-photosynthetic bacteria other than cyanobacteria is still lacking, we aimed to investigate the circadian rhythm of specific growth rate in Escherichia coli ATCC 25922, one of the important prokaryotes. Methods: To grow E. coli under different light and dark conditions. When the growth entered into the stationary phase, we stopped the culture and obtained the viable counts by MTT assay every 3 h. The specific growth rates (SGRs) were calculated and analyzed with cosinor method for potential rhythms. Results: Single cosinor method revealed that the SGR of E. coli displayed rhythmic variations with a period of around 24 h both under light/dark cycles and under constant darkness. The best-fitting periods and best-fitting cosine curves were acquired. Conclusions: The SGR of E. coli (ATCC 25922) in a culture medium with limiting substrates in the stationary and death phases displayed rhythmic variations with a period of around 24 h under light/dark cycles and constant darkness conditions.     

The circadian locomotor rhythm of Hemideina thoracica (Orthoptera; Stenopelmatidae): the circadian clock as a population of interacting oscillators

ABSTRACT. The behaviour of the circadian locomotor rhythm of the New Zealand weta, Hemideina thoracica (White), supports the model that the underlying pacemaker consists of a population of weakly coupled oscillators. Certain patterns of locomotor activity, previously demonstrated almost exclusively in vertebrates, are presented here as evidence for the above hypothesis. They include after-effects of various pre-treatments, rhythm-splitting and spontaneous changes in the rhythm. After-effects, which describe the unstable behaviour of free-running circadian rhythms following particular experimental perturbations, have been observed in Hemideina following single light pulses, constant dim light, and laboratory and natural entrainment. Period changes occurred in the activity rhythm after single light pulses of 8-h and 12-h duration (25 lx). Constant dim light (0.1 lx) increased the free-running period (τ) of the activity rhythm, but the after-effect of constant dim light was either an increase or a decrease in τ. After-effects upon both τ and the active phase length of the activity rhythm were found following non-24-h light entrainment cycles with 8-h and 12-h light phases of 25 lx. Qualitative measurements of these after-effects upon τ are presented which reveal a relationship between both the direction and amount of change in τ, and the difference between entrainment cycle length (T) and pre-entrainment free-running period. The after-effect of natural entrainment was an initial short-period free-run (τ < 24h) lasting 5–10 days, generally followed by a rapid period lengthening to τ= 25–26 h. Support for the population model was provided by spontaneous dampening, recovery, and period changes of the rhythm, together with the disruption of the active phase following critical light perturbations, and rhythm-splitting. These Hemideina results are compared with the simulations of the Coupled Stochastic System of Enright (1980).     

No endogenous circadian rhythm in resting plasma Hsp72 concentration in humans

Extra-cellular (e) heat shock protein (Hsp)72 has been shown to be elevated in a number of clinical conditions and has been proposed as a potential diagnostic marker. From a methodological and diagnostic perspective, it is important to investigate if concentrations of eHsp72 fluctuate throughout the day; hence, the purpose of the study was to measure resting concentrations of plasma eHsp72 throughout a 24-h period. Blood samples were taken every hour from 1200-2100 hours and from 0700-1200 hours the following day from seven healthy recreationally active males. Participants remained in the laboratory throughout the trial, performed light sedentary activities and were provided with standardised meals and fluids. Physical activity was quantified throughout by the use of an accelerometer. Ethylenediaminetetraacetic acid blood samples were analysed for eHsp72 concentration using a commercially available high-sensitivity enzyme-linked immunosorbent assay (intra-assay coefficient of variation = 1.4%). One-way repeated measures analysis of variance revealed that measures of physiological stress such as heart rate, systolic and diastolic blood pressure remained stable throughout the trial and subjects remained sedentary throughout (mean activity energy expenditure above resting metabolic rate-35.7 +/- 10.0 kcalh(-1)). Plasma Hsp72 concentration did not fluctuate significantly throughout the day and showed no apparent endogenous circadian rhythm in absolute (P = 0.367) or plasma volume change corrected data (P = 0.380). Individual coefficients of variation ranged from 3.8-7.7% (mean 5.4%). Mean Hsp72 concentration across all subjects and time points was 1.49 +/- 0.08 ngml(-1). These data show that in a rested state, plasma eHsp72 concentration shows no apparent endogenous circadian rhythm.     

Biological rhythms,chronodisruption and chrono-enhancement: The role of physical activity as synchronizer in correcting steroids circadian rhythm in metabolic dysfunctions and cancer

ABSTRACT

Rhythms can be observed at all levels of the biologic integration in humans. The observation that a biological or physiological variable shows a circadian rhythm can be explained by several multifactorial systems including external (exogenous), internal (endogenous) and psychobiological (lifestyle) mechanisms. Our body clock can be synchronized with the environment by external factors, called “synchronizers”, i.e. the light–dark cycle, but it is also negatively influenced by some pathological conditions or factors, called “chronodisruptors,” i.e. aging or low physical activity (PA). The desynchronization of a 24-h rhythm in a chronic manner has been recently defined “chronodisruption” or “circadian disruption.” A very large number of hormonal variables, such as adrenal and gonadal stress steroids, are governed by circadian rhythmicity. Such hormones, in normal conditions, show a peak in the first part of the day, while their typical diurnal fluctuations are totally out of sync in subjects affected by cancer or metabolic diseases, such as obesity, diabetes and metabolic syndrome. In general, a flatter slope with altered peaks in cortisol and testosterone circadian rhythms has been observed in pathological individuals. PA, specifically chronic exercise, seems to play a key role as synchronizer for the whole circadian system in such pathologies even if specific data on steroids circadian pattern are still sparse and contradictory. Recently, it has been proposed that low-intensity chronic PA could be an effective intervention to decrease morning cortisol levels in pathological subjects. The standardization of all confounding factors is needed to reach more clear evidence-based results.     

An observational study on disturbed peripheral circadian rhythms in hemodialysis patients

The quality of life of hemodialysis (HD) patients is hampered by reduced nocturnal sleep quality and excessive daytime sleepiness. In addition to the sleep/wake cycle, levels of circadian biomarkers (e.g. melatonin) are disturbed in end-stage renal disease (ESRD). This suggests impaired circadian clock performance in HD patients, but the underlying mechanism is unknown. In this observational study, diurnal rhythms of sleep, serum melatonin and cortisol concentrations and clock gene mRNA expression are compared between HD patients (n?=?9) and healthy control subjects (n?=?9). In addition, the presence of circulating factors that might affect circadian rhythmicity is tested in vitro with cell culture experiments. Reduced sleep quality (median sleep onset latency [interquartile range] of 23.9 [17.3]?min for patients versus 5.0 [10] minutes for controls, p?<?0.01; mean (± SD) sleep efficiency 70.2?±?8.1% versus 82.9?±?10.9%, p?=?0.02 and mean awake minutes after sleep onset 104.8?±?27.9 versus 54.6?±?41.6 minutes, p?= 0.01) and increased daytime sleepiness (mean Epworth Sleepiness Score of 10.0?±?4.8 versus 3.9?±?2.0, p?<?0.01) were confirmed in HD patients. Reduced nocturnal melatonin concentrations (1 AM: 98.1 [122.9] pmol/L versus 12.5 [44.2] pmol/L, p?= 0.019; 5 AM: 114.0 [131.6] pmol/L versus 11.8 [86.8] pmol/L, p?= 0.031) and affected circadian control of cortisol rhythm and circadian expression of the clock gene REV-ERBα were found. HD patient serum had a higher capacity to synchronize cells in vitro, suggesting an accumulated level of clock resetting compounds in HD patients. These compounds were not cleared by hemodialysis treatment or related to frequently used medications. In conclusion, the abovementioned results strongly suggest a disturbance in circadian timekeeping in peripheral tissues of HD patients. Accumulation of clock resetting compounds possibly contributes to this. Future studies are needed for a better mechanistic understanding of the interaction between renal failure and perturbation of the circadian clock.     

Studies on the expression patterns of the circadian rhythm regulated genes in mango

Mango, an important fruit crop of the tropical and subtropical regions shows alternate bearing in most varieties causing a financial loss to the farmer. Genetic reasons for this undesirable trait have not been studied so far. In our attempts to investigate the genetic reasons for alternate bearing we have initiated studies on genes associated with the induction, repression and regulation of flowering in mango. We have previously identified and characterized FLOWERING LOCUS T (FT) genes that induce flowering and two TERMINAL FLOWER1 (TFL1) genes that repress flowering. In this communication, we have explored the association of GI-FKF1-CDF1-CO module with the regulation of flowering in mango. The role of this module in regulating flowering has been well documented in photoperiod sensitive plants. We have characterized these genes and their expressions during flowering in Ratna variety as also their diurnal fluctuations and tissue specific expressions. The data taken together suggest that GI-FKF1-CDF1-CO module may also be employed by mango in regulating its flowering. Further, we suggest that the temperature dependent flowering in mango is probably associated with the presence of temperature sensitive elements present in the promoter region of one of the GIGANTEA genes that have been shown to be closely associated with floral induction.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12298-021-01053-8.     

肠道菌群昼夜节律与宿主生物节律相互作用的研究进展

为了适应地球昼夜更替对机体的影响,哺乳动物进化出了一套内在的适应性计时机制,由此形成了生物钟系统（circadian clock）。昼夜节律作为该系统中的重要部分可与机体的代谢过程同步变化[1]。肠道菌群作为与机体共生的生物群落,在肠道功能方面发挥着重要作用。对肠道菌群的昼夜节律性波动以及与宿主生物节律之间的相互作用进行研究有重要意义。本文将着重阐述肠道菌群昼夜节律与宿主生物节律的相互作用,以及这种相互作用对宿主代谢的影响。     

Thermoperiodic regulation of the circadian eclosion rhythm in the flesh fly, Sarcophaga crassipalpis

We recorded the eclosion time of the flesh fly, Sarcophaga crassipalpis, at different depths in the outdoor soil and under temperature cycles with various amplitudes in the laboratory, to examine the timing adjustment of eclosion in response to temperature cycles and their amplitudes in the pupal stage. In the soil, most eclosions occurred in the late morning, which was consistent with the eclosion time under pseudo-sinusoidal temperature cycles in the laboratory. The circadian clock controlling eclosion was reset by temperature cycles and free-ran with a period close to 24 h. This clock likely helps pupae eclose at an optimal time even when the soil temperature does not show clear daily fluctuations. The eclosion phase of the circadian clock progressively advanced as the amplitude of the pseudo-sinusoidal temperature cycle decreased. This response allows pupae located at any depth in the soil to eclose at the appropriate time despite the depth-dependent phase delay of the temperature change. In contrast, the abrupt temperature increase in square-wave temperature cycles reset the phase of the circadian clock to the increasing time, regardless of the temperature amplitude. The rapid temperature increase may act as the late-morning signal for the eclosion clock.