Hypothalamic regulation of sleep and circadian rhythms

A series of findings over the past decade has begun to identify the brain circuitry and neurotransmitters that regulate our daily cycles of sleep and wakefulness. The latter depends on a network of cell groups that activate the thalamus and the cerebral cortex. A key switch in the hypothalamus shuts off this arousal system during sleep. Other hypothalamic neurons stabilize the switch, and their absence results in inappropriate switching of behavioural states, such as occurs in narcolepsy. These findings explain how various drugs affect sleep and wakefulness, and provide the basis for a wide range of environmental influences to shape wake-sleep cycles into the optimal pattern for survival.     

Unexpected features of Drosophila circadian behavioural rhythms under natural conditions

Circadian clocks have evolved to synchronize physiology, metabolism and behaviour to the 24-h geophysical cycles of the Earth. Drosophila melanogaster's rhythmic locomotor behaviour provides the main phenotype for the identification of higher eukaryotic clock genes. Under laboratory light-dark cycles, flies show enhanced activity before lights on and off signals, and these anticipatory responses have defined the neuronal sites of the corresponding morning (M) and evening (E) oscillators. However, the natural environment provides much richer cycling environmental stimuli than the laboratory, so we sought to examine fly locomotor rhythms in the wild. Here we show that several key laboratory-based assumptions about circadian behaviour are not supported by natural observations. These include the anticipation of light transitions, the midday 'siesta', the fly's crepuscular activity, its nocturnal behaviour under moonlight, and the dominance of light stimuli over temperature. We also observe a third major locomotor component in addition to M and E, which we term 'A' (afternoon). Furthermore, we show that these natural rhythm phenotypes can be observed in the laboratory by using realistic temperature and light cycle simulations. Our results suggest that a comprehensive re-examination of circadian behaviour and its molecular readouts under simulated natural conditions will provide a more authentic interpretation of the adaptive significance of this important rhythmic phenotype. Such studies should also help to clarify the underlying molecular and neuroanatomical substrates of the clock under natural protocols.     

Spectral sensitivity of human cone photoreceptors

The brain computes visual colour by analysing the relative excitations of three types of retinal cones. Each cone excitation is governed by a spectral sensitivity function which relates the amplitude of the neural response to wavelength at constant light intensity. The spectral sensitivities of human cones are not well characterized. We report measuring the sensitivities by recording electrical responses of human cones to stimuli of different wavelengths. Spectral sensitivities of 'green' and 'red' cones, determined over the entire visible region, show peaks near 530 and 560 nm respectively, and are remarkably similar to those of the old-world monkey Macaca fascicularis. They satisfactorily predict the photopic luminosity function, a measure of the sensitivity of cone-mediated human vision to light of different wavelengths. The kinetics of the light responses of human cones also appeared similar to those of macaque cones: the time to peak response to a dim flash was 50-100 ms and there was a characteristic undershoot during recovery.     

The mPer2 gene encodes a functional component of the mammalian circadian clock.

Circadian rhythms are driven by endogenous biological clocks that regulate many biochemical, physiological and behavioural processes in a wide range of life forms. In mammals, there is a master circadian clock in the suprachiasmatic nucleus of the anterior hypothalamus. Three putative mammalian homologues (mPer1, mPer2 and mPer3) of the Drosophila circadian clock gene period (per) have been identified. The mPer genes share a conserved PAS domain (a dimerization domain found in Per, Arnt and Sim) and show a circadian expression pattern in the suprachiasmatic nucleus. To assess the in vivo function of mPer2, we generated and characterized a deletion mutation in the PAS domain of the mouse mPer2 gene. Here we show that mice homozygous for this mutation display a shorter circadian period followed by a loss of circadian rhythmicity in constant darkness. The mutation also diminishes the oscillating expression of both mPer1 and mPer2 in the suprachiasmatic nucleus, indicating that mPer2 may regulate mPer1 in vivo. These data provide evidence that an mPer gene functions in the circadian clock, and define mPer2 as a component of the mammalian circadian oscillator.     

Rhodopsin-like sensitivity of extra-retinal photoreceptors mediating the photoperiodic response in quail

It has been known for some 50 years that birds use photoreceptors in or near the hypothalamus to mediate the photoperiodic responses that control seasonal breeding. So far, however, attempts to identify the photopigment by determining an action spectrum have failed. The problems stem from the selective filtering of light by the tissues surrounding the photoreceptors and the need to deliver defined amounts of light over the days or weeks required to induce a quantitative measure of photostimulation. Here we have developed a technique which produces a quantitative action spectrum for the photoperiodic response in the Japanese quail; the results indicate the presence of a rhodopsin photopigment with a peak sensitivity of approximately 492 nm. The photoreceptors exhibit a level of sensitivity comparable with that of vertebrate visual pigments. We conclude that the brain photoreceptors of birds are based on a rhodopsin/rhodopsin-like photopigment.     

A benzodiazepine used in the treatment of insomnia phase-shifts the mammalian circadian clock

Between 5 and 20% of the adult population in Western countries suffer from insufficient and/or unsatisfying sleep, often associated with certain psychiatric disorders or with certain types of professional activities (for example, shift workers) and travel schedules (for example, jet lag). The benzodiazepines are at present the drug treatment of choice for the management of anxiety and stress-related conditions as well as insomnia. Benzodiazepines are thought to act by potentiating the action of the neurotransmitter gamma-aminobutyric acid (GABA), a widely distributed transmitter in the central nervous system. The circadian system has a key role in the regulation of the sleep-wake cycle, and at least some forms of insomnia may be the result of a disorder of the circadian sleep-wake rhythm. Similarly, at least some forms of depression may also involve disruption of normal circadian rhythmicity. A central pacemaker for the generation of many circadian rhythms in mammals, including the sleep-wake cycle, appears to be located in the suprachiasmatic nucleus, and recent research indicates that both cell bodies and axons containing GABA are present within the bilaterally paired suprachiasmatic nuclei. These findings raise the possibility that the benzodiazepines, commonly prescribed for sleep and mental disorders, may have an effect on the central circadian pacemaker. Here we report that the acute administration of triazolam, a short-acting benzodiazepine commonly prescribed for the treatment of insomnia, induces a phase-shift in the circadian rhythm of locomotor activity in golden hamsters. This suggests a role for GABA-containing neurones in the mammalian circadian system.     

Diurnal modulation of pacemaker potentials and calcium current in the mammalian circadian clock

The central biological clock of the mammalian brain is located in the suprachiasmatic nucleus. This hypothalamic region contains neurons that generate a circadian rhythm on a single-cell basis. Clock cells transmit their circadian timing signals to other brain areas by diurnal modulation of their spontaneous firing rate. The intracellular mechanism underlying rhythm generation is thought to consist of one or more self-regulating molecular loops, but it is unknown how these loops interact with the plasma membrane to modulate the ionic conductances that regulate firing behaviour. Here we demonstrate a diurnal modulation of Ca2+ current in suprachiasmatic neurons. This current strongly contributes to the generation of spontaneous oscillations in membrane potential, which occur selectively during daytime and are tightly coupled to spike generation. Thus, day-night modulation of Ca2+ current is a central step in transducing the intracellular cycling of molecular clocks to the rhythm in spontaneous firing rate.     

Z25, a novel intronic snoRNA encoded in mammalian nucleolin gene

A novel intronic small nucleolar RNA ( snoRNA) , termed Z25, was identified from mammals by-computer analysis and experimental sequence methods. Z25 is a 69 nucleotides long RNA containing typical boxC/D motifs, terminal stem and an 11-nucleotide sequence complementary to 18S rRNA. In theory, Z25 functions as an RNA guide for the 2'-0-ribose methylation of adenine at position 1678 (human 18S rRNA coordinate) in 18S rRNA. Z25 snoRNA gene was found to be located in the fifth intron of nucleolin gene of human, mouse and rat, demonstrating that the mammalian nucleoline gene is a host gene encoding multiple snoRNAs.     

一种新型叶绿体表达系统的构建

针对目前的叶绿体转基因技术存在载体构建步骤繁琐耗时的问题,建立了一种新型的不需自带启动子的叶绿体表达系统,选择模式植物烟草叶绿体中的假基因作为外源基因的插入位点.通过基因枪转化法获得4株独立的叶绿体转化植株.此新技术可实现叶绿体载体构建的时间、技术成本最小化,从而促进转基因叶绿体的应用.     

一种新型光纤干涉仪的相位噪声及灵敏度分析

为了对微振动信号进行远距离实时检测,提出一种由两低反射率光纤光栅组成的新型双光束光纤干涉仪.给出了采用零差解调技术时干涉系统的散粒噪声和热噪声,并且分析了在不同时间延迟情况下的相位噪声.通过对系统各种噪声的分析,推导出系统的最小探测灵敏度解析表达式.最后根据实验中采用的具体参数,计算出该系统能探测到的最小相位.该干涉仪结构简单、灵敏度高,具有广阔的应用前景.     

一个新的四翼混沌系统的动力学分析

分析了一个具有四翼混沌吸引子混沌系统的平衡点的稳定性、对称性、不变性、耗散性及吸引子的存在性.并通过计算机仿真,讨论了系统的分岔图、Lyapunov指数谱和Poincaré映射等基本动力学特性.结论表明此系统具有丰富的动力学特性.     

矿井通风系统灵敏度分析

从风阻和自然风压两方面考虑,分别对分支风量对风阻的灵敏度以及分支风量对自然风压的灵敏度进行了分析.前者通过求解灵敏度微分方程组,得出灵敏度矩阵,根据矩阵的性质,可以对每一条分支的风流稳定、整个通风网络的稳定作出判断;后者从灵敏度的定义入手,应用线性伴随网路法进行计算,得出灵敏度为自然风压所在分支的动力消耗与i分支中空气动力消耗之比值,为判别风流反向提供了一定的依据.     

一个新分数阶混沌系统的同步和控制

构造了一个具有三个非线性二次项的新分数阶混沌系统,分析了其基本的混沌动力学特性,并应用Laplace变换实现了新系统的混沌控制。基于Lyapunov理论和分数阶混沌系统稳定性理论,得到同时实现新分数阶混沌系统自适应同步和参数辨识的充分条件,并通过数值仿真,验证了结论的正确性。     

一个新的超混沌系统分析与FPGA实现

针对现有超混沌系统的最大Lyapunov指数较小的问题,在三阶Qi系统的基础上,提出了一个具有2个较大的正的Lyapunov指数和较大参数范围的新的超混沌系统,分析了该系统的平衡点及稳定性、Lyapunov指数谱和分形维数、超混沌吸引子的相图等特性,并利用电子设计自动化(electronic design automatic,EDA)技术,借助于计算机的软件现场可编程门阵列 (field programmable gate array,FPGA)平台实现了该系统,实验结果与仿真结果完全一致。     

某涡扇发动机转子系统稳定裕度及其灵敏度分析

某型涡扇发动机转子系统由3个单转子系统构成。将该三转子系统在耦合处分开,把耦合力作为单个转子上的外力,并利用集总参数法和各节点的振动微分方程表达式建立单个转子的振动方程。利用各转子间耦合部件的总体耦合矩阵将单个转子的振动方程耦合在一起,建立了整个三转子系统的振动微分方程。通过求解整个系统的振动微分方程,得到整个系统所有模态的对数衰减率,并进一步求出系统的稳定裕度和其灵敏度。研究结论表明:提高高压转子轴承的阻尼和高压转子的弯曲刚度可以有效提高系统的稳定裕度;联轴器的存在和转子转速的提高都会降低转子系统的稳定裕度。