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).     

生物钟机制研究进展

由生物体内源性生物钟所产生的昼夜节律是近年来生命科学的研究热点之一。几种模型生物（蓝细菌、脉孢菌、拟南芥、果蝇、小鼠）的生物钟相关基因相继被克隆和鉴定,为理解昼夜节律的分子机制奠定了基础。振荡器蛋白对其编码基因的负反馈调控可能是不同生物的生物运作普遍机制,在此基础上,不同生物有不尽相同的调控方式;隐色素可能是高等生物的共同生物钟光受体。     

Life's 24-hour clock: molecular control of circadian rhythms in animal cells

Our sleep–wake cycles and many other 24-hour rhythms of behavior and physiology persist in the absence of environmental cues. Genetic and biochemical studies have shown that such rhythms are controlled by internal molecular clocks. These are assembled from the cycling RNA and protein products of a small group of genes that are conserved throughout the animal kingdom.     

昆虫钟基因研究进展

昆虫进化形成了内在的生物钟机制以协调行为、生理及代谢节律与外部环境信号同步,从而更有效地利用资源并获得适应性优势。行为、生理及代谢昼夜调控的协调对于昆虫有效应对可预见的生理上的挑战至关重要。生化过程和代谢变化与外部环境的昼夜节律同步性受基因表达的控制,钟基因在昆虫的重要生理过程如中枢及外围生物钟机制、光周期信号传导、光周期介导的外围组织调控、代谢以及免疫中发挥着重要作用。根据信号转导过程中的作用,昆虫钟基因分为3类——信号输入基因、信号震荡起搏器和信号输出基因,它们通过相互作用形成了复杂的转录-翻译反馈回路并参与调控昆虫昼夜节律和光周期事件。本文针对昆虫钟基因的鉴定、分类和功能,作用分子机制以及研究方法和挑战等方面作了总结,并展望了昆虫钟基因未来的研究方向,这将为昆虫钟基因的进一步功能研究及开发利用提供信息参考。     

生物钟PRR蛋白促进拟南芥幼苗中花青素的合成

生物钟(circadian clock)是激发植物生理特征节律性表达,并使之维持稳定的保守内源调节机制。PRR(PSEUDO-RESPONSE REGULATOR)蛋白家族是生物钟中央振荡器的重要组成部分,调控植物的种子萌发、下胚轴伸长和开花等多种生命过程。花青素(anthocyanin)是植物次生代谢产物,对植物的繁衍、生长发育和抵抗逆境胁迫具有重要作用。该研究以拟南芥(Arabidopsis thaliana)为对象,探讨生物钟PRR蛋白对花青素生物合成的调控功能和分子机制。结果表明：(1)在PRR基因单突变体及多突变体幼苗中,花青素的积累明显降低,某些花青素合成相关基因的表达也显著降低。(2)相反,在PRR5过表达幼苗中,花青素的积累以及某些花青素合成相关基因的表达则显著升高。(3)蛋白相互作用结果显示,PRR5蛋白能与MYB75、TT8、MYB90及MYB113等花青素调控蛋白相互作用,并形成复合物。(4)遗传学分析结果显示,拟南芥PRR5诱导幼苗中花青素的合成依赖于MYB家族花青素调控蛋白。综上认为,生物钟PRR蛋白可能通过PRR5与MYB75、TT8等相互作用,促进拟南芥幼...     

Normal vision can compensate for the loss of the circadian clock

Circadian clocks are thought to be essential for timing the daily activity of animals, and consequently increase fitness. This view was recently challenged for clock-less fruit flies and mice that exhibited astonishingly normal activity rhythms under outdoor conditions. Compensatory mechanisms appear to enable even clock mutants to live a normal life in nature. Here, we show that gradual daily increases/decreases of light in the laboratory suffice to provoke normally timed sharp morning (M) and evening (E) activity peaks in clock-less flies. We also show that the compound eyes, but not Cryptochrome (CRY), mediate the precise timing of M and E peaks under natural-like conditions, as CRY-less flies do and eyeless flies do not show these sharp peaks independently of a functional clock. Nevertheless, the circadian clock appears critical for anticipating dusk, as well as for inhibiting sharp activity peaks during midnight. Clock-less flies only increase E activity after dusk and not before the beginning of dusk, and respond strongly to twilight exposure in the middle of the night. Furthermore, the circadian clock responds to natural-like light cycles, by slightly broadening Timeless (TIM) abundance in the clock neurons, and this effect is mediated by CRY.     

Freerunning and entrained circadian rhythms in activity,eating and drinking in the cat

Abstract

Because cats with pontile lesions exhibit an abnormal behavior that is under photoperiodic control, and because circadian rhythms are implicated in photoperiodic control mechanisms, an effort was made to detect circadian rhythms in the cat. Cats were isolated from all extraneous stimuli in soundproof chambers for extended periods of time. Photocells were used to monitor activity, eating and drinking in different LD cycles, in constant light at two intensities, and in constant dark. Freerunning circadian rhythms were found in the constant conditions, and entrained nocturnal patterns occurred in most of the LD cycles. The higher intensities of ambient illumination disrupted the freerunning rhythms. The freerunning rhythms were always greater than 24 h, ranging from 24.2 to 25 h. Measurements of food intake of cats living in a large colony room, obtained by weighing the food, revealed that a nocturnal pattern of entrainment was not present in the majority of the cats. Instead, most cats in the colony exhibited a random pattern of eating throughout the light and dark period of the LD cycle. However, the variation among the cats in the colony was considerable, extending from nocturnal to diurnal patterns of eating. A diurnal pattern of human activity was present in the colony and may account for the disruption of a basic nocturnal pattern. The presence of circadian rhythms in the cat leads us to consider the coincidence models for photoperiodic induction as possible explanations of the photoperiodic control of the lesion‐induced abnormal behavior.     

Geography of the circadian gene clock and photoperiodic response in western North American populations of the three‐spined stickleback Gasterosteus aculeatus

Controlled laboratory experiments were used to show that Oregon and Alaskan three‐spined stickleback Gasterosteus aculeatus, collected from locations differing by 18° of latitude, exhibited no significant variation in length of the polyglutamine domain of the clock protein or in photoperiodic response within or between latitudes despite the fact that male and female G. aculeatus are photoperiodic at both latitudes. Hence, caution is urged when interpreting variation in the polyglutamine repeat (PolyQ) domain of the gene clock in the context of seasonal activities or in relationship to photoperiodism along geographical gradients.     

昆虫生物钟分子调控研究进展

昆虫生物钟节律的研究是人类了解生物节律的重要途径。昆虫在生理和行为上具有广泛的节律活动,如运动、睡眠、学习记忆、交配、嗅觉等节律活动,其中昼夜活动行为节律的研究广泛而深入。昆虫乃至高等动物普遍具有保守的昼夜节律系统,昼夜生物钟节律主要包括输入系统:用于接受外界光和温度等环境信号并传入核心振荡器,使得生物时钟与环境同步;核心时钟系统:自我维持的昼夜振荡器;输出系统:将生物钟产生的信号传递出去而控制生物行为和生理的节律变化。早期分子和遗传学研究主要关注昼夜节律振荡器的分子机制及神经生物学,阐明了昼夜生物钟节律的主要分子机制及相关神经网络。最近更多的研究关注生物钟信号是如何输入和输出。本文以果蝇运动节律的相关研究为主要内容,围绕生物钟输入系统、振荡器、输出系统这3个组成部分对昆虫生物钟研究进展进行总结。     

生物钟的转录后与翻译后水平调控进展

哺乳动物中的昼夜节律系统由位于下丘脑SCN核内的生物钟主钟和位于多数外周细胞中的子钟组成。在分子水平上,生物钟的节律振荡由生物钟基因及其编码蛋白的转录和翻译形成的自主的反馈环路组成,并接受外界因素的影响与环境周期保持同步。为此,就生物钟的调控机制而言,除了转录水平的基因表达调控外,生物钟转录产物和蛋白质的修饰也可以显著影响生物钟基因的表达时相。讨论了一些转录后与翻译后的修饰作用及其对生物钟的影响,并对其今后的研究方向作了展望。     

Development of model based on clock gene expression of human hair follicle cells to estimate circadian time

ABSTRACT

Considering the effects of circadian misalignment on human pathophysiology and behavior, it is important to be able to detect an individual’s endogenous circadian time. We developed an endogenous Clock Estimation Model (eCEM) based on a machine learning process using the expression of 10 circadian genes. Hair follicle cells were collected from 18 healthy subjects at 08:00, 11:00, 15:00, 19:00, and 23:00 h for two consecutive days, and the expression patterns of 10 circadian genes were obtained. The eCEM was designed using the inverse form of the circadian gene rhythm function (i.e., Circadian Time = F(gene)), and the accuracy of eCEM was evaluated by leave-one-out cross-validation (LOOCV). As a result, six genes (PER1, PER3, CLOCK, CRY2, NPAS2, and NR1D2) were selected as the best model, and the error range between actual and predicted time was 3.24 h. The eCEM is simple and applicable in that a single time-point sampling of hair follicle cells at any time of the day is sufficient to estimate the endogenous circadian time.     

KaiA调控蓝藻生物钟的分子机制研究进展

蓝藻生物钟系统主要包括输入途径、核心振荡器和输出途径3部分,核心振荡器主要由时钟蛋白KaiA、KaiB、KaiC构成。3种蛋白之间的相互作用产生节律信号及调控输入、输出信号进而维持生物振荡的精确与稳定。文中围绕蓝藻生物钟核心振荡器及核心振荡器组成蛋白的结构、功能与相互作用特点,结合本实验室近期取得的研究成果,针对时钟蛋白KaiA调节KaiC的酶活性、介导核心振荡器的时相重置、与CikA竞争KaiB的结合位点等方面近年来的研究进展进行了综述。     

Peripheral circadian clocks are diversely affected by adrenalectomy

Glucocorticoids are considered to synchronize the rhythmicity of clock genes in peripheral tissues; however, the role of circadian variations of endogenous glucocorticoids is not well defined. In the present study, we examined whether peripheral circadian clocks were impaired by adrenalectomy. To achieve this, we tested the circadian rhythmicity of core clock genes (Bmal1, Per1-3, Cry1, RevErbα, Rora), clock-output genes (Dbp, E4bp4) and a glucocorticoid- and clock-controlled gene (Gilz) in liver, jejunum, kidney cortex, splenocytes and visceral adipose tissue (VAT). Adrenalectomy did not affect the phase of clock gene rhythms but distinctly modulated clock gene mRNA levels, and this effect was partially tissue-dependent. Adrenalectomy had a significant inhibitory effect on the level of Per1 mRNA in VAT, liver and jejunum, but not in kidney and splenocytes. Similarly, adrenalectomy down-regulated mRNA levels of Per2 in splenocytes and VAT, Per3 in jejunum, RevErbα in VAT and Dbp in VAT, kidney and splenocytes, whereas the mRNA amounts of Per1 and Per2 in kidney and Per3 in VAT and splenocytes were up-regulated. On the other hand, adrenalectomy had minimal effects on Rora and E4bp4 mRNAs. Adrenalectomy also resulted in decreased level of Gilz mRNA but did not alter the phase of its diurnal rhythm. Collectively, these findings suggest that adrenalectomy alters the mRNA levels of core clock genes and clock-output genes in peripheral organs and may cause tissue-specific modulations of their circadian profiles, which are reflected in changes of the amplitudes but not phases. Thus, the circulating corticosteroids are necessary for maintaining the high-amplitude rhythmicity of the peripheral clocks in a tissue-specific manner.     

哺乳动物生物钟与能量代谢的相关研究进展

生物钟广泛存在于各种生物体中,是生命体的一种内源调节机制。哺乳动物生物钟系统与机体营养代谢和能量平衡有着密切的关系。概述了生物钟系统通过营养途径、限速酶途径、核受体途径对哺乳动物机体代谢活动和能量平衡的调控,以及哺乳动物代谢稳态对生物钟系统的影响,从而为从生物钟调控的角度治疗和防控代谢综合征提供新的思路。