A new role for cryptochrome in a Drosophila circadian oscillator

Cryptochromes are flavin/pterin-containing proteins that are involved in circadian clock function in Drosophila and mice. In mice, the cryptochromes Cry1 and Cry2 are integral components of the circadian oscillator within the brain and contribute to circadian photoreception in the retina. In Drosophila, cryptochrome (CRY) acts as a photoreceptor that mediates light input to circadian oscillators in both brain and peripheral tissue. A Drosophila cry mutant, cryb, leaves circadian oscillator function intact in central circadian pacemaker neurons but renders peripheral circadian oscillators largely arrhythmic. Although this arrhythmicity could be caused by a loss of light entrainment, it is also consistent with a role for CRY in the oscillator. A peripheral oscillator drives circadian olfactory responses in Drosophila antennae. Here we show that CRY contributes to oscillator function and physiological output rhythms in the antenna during and after entrainment to light-dark cycles and after photic input is eliminated by entraining flies to temperature cycles. These results demonstrate a photoreceptor-independent role for CRY in the periphery and imply fundamental differences between central and peripheral oscillator mechanisms in Drosophila.     

The ELF3 zeitnehmer regulates light signalling to the circadian clock

The circadian system regulates 24-hour biological rhythms and seasonal rhythms, such as flowering. Long-day flowering plants like Arabidopsis thaliana, measure day length with a rhythm that is not reset at lights-off, whereas short-day plants measure night length on the basis of circadian rhythm of light sensitivity that is set from dusk, early flowering 3 (elf3) mutants of Arabidopsis are aphotoperiodic and exhibit light-conditional arrhythmias. Here we show that the elf3-7 mutant retains oscillator function in the light but blunts circadian gating of CAB gene activation, indicating that deregulated phototransduction may mask rhythmicity. Furthermore, elf3 mutations confer the resetting pattern of short-day photoperiodism, indicating that gating of phototransduction may control resetting. Temperature entrainment can bypass the requirement for normal ELF3 function for the oscillator and partially restore rhythmic CAB expression. Therefore, ELF3 specifically affects light input to the oscillator, similar to its function in gating CAB activation, allowing oscillator progression past a light-sensitive phase in the subjective evening. ELF3 provides experimental demonstration of the zeitnehmer ('time-taker') concept.     

Light acts directly on organs and cells in culture to set the vertebrate circadian clock

The expression of clock genes in vertebrates is widespread and not restricted to classical clock structures. The expression of the Clock gene in zebrafish shows a strong circadian oscillation in many tissues in vivo and in culture, showing that endogenous oscillators exist in peripheral organs. A defining feature of circadian clocks is that they can be set or entrained to local time, usually by the environmental light-dark cycle. An important question is whether peripheral oscillators are entrained to local time by signals from central pacemakers such as the eyes or are themselves directly light-responsive. Here we show that the peripheral organ clocks of zebrafish are set by light-dark cycles in culture. We also show that a zebrafish-derived cell line contains a circadian oscillator, which is also directly light entrained.     

The ELF4 gene controls circadian rhythms and flowering time in Arabidopsis thaliana

Many plants use day length as an environmental cue to ensure proper timing of the switch from vegetative to reproductive growth. Day-length sensing involves an interaction between the relative length of day and night, and endogenous rhythms that are controlled by the plant circadian clock. Thus, plants with defects in circadian regulation cannot properly regulate the timing of the floral transition. Here we describe the gene EARLY FLOWERING 4 (ELF4), which is involved in photoperiod perception and circadian regulation. ELF4 promotes clock accuracy and is required for sustained rhythms in the absence of daily light/dark cycles. elf4 mutants show attenuated expression of CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), a gene that is thought to function as a central oscillator component. In addition, elf4 plants transiently show output rhythms with highly variable period lengths before becoming arrhythmic. Mutations in elf4 result in early flowering in non-inductive photoperiods, which is probably caused by elevated amounts of CONSTANS (CO), a gene that promotes floral induction.     

Circadian rhythm and light regulate opsin mRNA in rod photoreceptors

Disk membranes in the outer segment of rod photoreceptors are continuously renewed, being assembled at the outer segment base, displaced outward by new disks and eventually shed at the tip. In lower vertebrates, disk assembly occurs with a diurnal rhythm with 2-4% of the outer segment length produced daily. We have discovered that in toad and fish retinas the level of mRNA for opsin, the most abundant protein in rod disks, fluctuates with a daily rhythm and is regulated both by light and by a circadian oscillator. The mRNA level rises before light onset, remains high during the light phase of a diurnal cycle and decreases four to tenfold during the dark phase. In constant darkness, mRNA elevation occurs during subjective daytime. At night, rod opsin mRNA can be elevated by exposure to light.     

Creatine accelerates the circadian clock in a unicellular alga

The circadian clock is considered to be a universal feature of eucaryotic organisms, controlling the occurrence and rates of many different aspects of life, ranging from single enzymatic reactions and metabolism to complex behaviours such as activity and rest. Although the nature of the underlying cellular/biochemical oscillator is still unknown, many substances are known to influence either phase or period of circadian rhythms in different organisms. These include D2O, electrolytes and ion channel inhibitors, small organic molecules such as alcohols and aldehydes, inhibitors of protein synthesis and amino-acid analogues. Certain transmitter and neurochemical drugs also influence the circadian clock in higher animals. We report here that the period of free-running circadian rhythms in the unicellular marine alga Gonyaulax polyedra is shortened by extracts from mammalian cells. The effect is dose-dependent, accelerating the circadian clock by as much as 4 hours per day. The substance responsible for this effect has been isolated from bovine muscle and identified as creatine. Authentic creatine has identical biological effects at micromolar concentrations and is known in animal systems for its involvement in cellular energy metabolism. A period shortening substance with similar chemical properties is also present in extracts of Gonyaulax itself.     

非对称动力系统混沌分析的Melnikov方法

以Helmholtz-Duffing双势阱非对称动力系统为研究对象,首先分析了不同非对称参数σ下退化Hamilton系统的势函数与相平面,然后对于受谐和激励的非自治系统根据Melnikov理论推导了系统左右同宿轨道出现混沌运动的阈值条件,最后用数值模拟得到系统的安全池并观察了安全池随激励幅值变化的侵蚀现象,从而验证了解析结果的正确性.理论分析和数值计算表明:0σ1时,系统左半部分受主要影响;σ1时,右半部分受主要影响;Melnikov方法可有效预估非对称系统混沌阈值,并且对于同一非对称参数σ,存在一个临界频率使得系统左右两部分的混沌阈值在这一频率点相等.     

阻挫自旋梯子的纠缠与量子相变

对于具有阻挫作用的反铁磁自旋梯子,采用多体格林函数方法并结合Jordan-Wigner变换,计算系统中近邻双格点的纠缠,分析纠缠的奇异性与量子相变之间关系.发现随着外磁场的变化,纠缠出现奇异即发生量子相变,但在量子相变点纠缠不一定出现奇异,这说明纠缠奇异与量子相变并非一一对应,此外纠缠平台与磁化平台一一对应.     

A cyclic GMP-activated channel in dissociated cells of the chick pineal gland.

Phototransduction in the vertebrate retina is dependent in part on a cyclic GMP-activated ionic channel in the plasma membrane of rods and cones. But other vertebrate cells are also photosensitive. Cells of the chick pineal gland have a photosensitive circadian rhythm in melatonin secretion that persists in dissociated cell culture. Exposure to light causes inhibition of melatonin secretion, and entrainment of the intrinsic circadian oscillator. Chick pinealocytes express several 'retinal' proteins, including arrestin, transducin and a protein similar to the visual pigment rhodopsin. Pinealocytes of lower vertebrates display hyperpolarizing responses to brief pulses of light. Thus it is possible that some of the mechanisms of phototransduction are similar in retinal and pineal photoreceptors. We report here the first recordings of cyclic GMP-activated channels in an extraretinal photoreceptor. Application of GMP, but not cyclic AMP, to excised inside-out patches caused activation of a 15-25 pS cationic channel. These channels may be essential for phototransduction in the chick pineal gland.     

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.     

A circadian oscillator in cultured cells of chicken pineal gland

The activity of serotonin N-acetyltransferase, the key enzyme of melatonin synthesis, shows a marked circadian rhythm in the pineal glands of various animal species. The regulation mechanism of the N-acetyltransferse rhythm in birds is different from that in mammals. N-Acetyltransferase activity in rat pineal gland is controlled by the central nervous system through the sympathetic nerves from the superior cervical ganglion, while in chicken the endogenous oscillator for N-acetyltransferase rhythm is presumably located in the pineal gland. Recently it has been shown that N-acetyltransferase activity oscillates in a circadian manner in the organ culture of chicken pineal glands. When chicken pineal glands were organ-cultured under continuous illumination, the nocturnal increase of enzyme activity was suppressed. These observations suggested that chicken pineal gland contains a circadian oscillator, a photoreceptor and melatonin-synthesising machinery. A central question arises whether the circadian oscillation of N-acetyltransferase activity and its response to environmental lighting are generated within the cell or are emergent properties of interaction between different types of pineal cells. I report here that in the dispersed cell culture of chicken pineal gland, N-acetyltransferase activity exhibits a circadian rhythm and responds to environmental lighting in the same manner as in the organ culture.     

相对论的受驱谐振子混沌：相对论效应和驱动力效应

本文用数值模拟方法研究了相对论效应和驱动力效应对谐振子动力学行为的影响作用.结果表明：相对论效应和驱动力效应的协同作用能使体系的振动频率发生改变,从而使体系产生混沌现象.如果仅存在一种效应,体系就不可能出现混沌.另外,研究还发现体系存在着取决于光速值和驱动力振幅值的混沌区域.在这个混沌区内,光速值和驱动力振幅值的比例约为1∶5.     

高次奇点的指数计算

奇点指数是刻画奇点拓扑性质的一个量，它是一个整数，本利用Cauchy-指标的代数工具就孤立高次奇点，临界奇点分别给出了一组指数计算公式，这是对中计算公式的补充，尤其是对临界奇点指数计算起到了简化作用，也使平面解析向量场的奇点指数计算问题得到完美解决。