关于心脏生物钟

哺乳动物心脏活动具有明显的日周期节律现象,分子生物学证实心脏拥有完整的生物钟,具备所有的时钟基因以及时钟输出基因。生物钟节律紊乱和心血管疾病的发生及发展两者之间存在密切关系。如果利用药物纠正时钟基因的异常表达,对于心血管疾病的治疗可能发挥重要作用。     

The biological clock: the bodyguard of temporal homeostasis

In order for any organism to function properly, it is crucial that it be table to control the timing of its biological functions. An internal biological clock, located, in mammals, in the suprachiasmatic nucleus of the hypothalamus (SCN), therefore carefully guards this temporal homeostasis by delivering its message of time throughout the body. In view of the large variety of body functions (behavioral, physiological, and endocrine) as well as the large variety in their preferred time of main activity along the light:dark cycle, it seems logical to envision different means of time distribution by the SCN. In the present review, we propose that even though it presents a unimodal circadian rhythm of general electrical and metabolic activity, the SCN seems to use several sorts of output connections that are active at different times along the light: dark cycle to control the rhythmic expression of different body functions. Although the SCN is suggested to use diffusion of synchronizing factors in the rhythmic control of behavioral functions, it also needs neuronal connections for the control of endocrine functions. The distribution of the time-of-day message to neuroendocrine systems is either directly onto endocrine neurons or via intermediate neurons located in specific SCN targets. In addition, the SCN uses its connections with the autonomic nervous system for spreading its time-of-day message, either by setting the sensitivity of endocrine glands (i.e., thyroid, adrenal, ovary) or by directly controlling an endocrine output (i.e., melatonin synthesis). Moreover, the SCN seems to use different neurotransmitters released at different times along the light: dark cycle for each of the different connection types presented. Clearly, the temporal homeostasis of endocrine functions results from a diverse set of biological clock outputs.     

From biological clock to biological rhythms

The genetic and molecular analysis of circadian timekeeping mechanisms has accelerated as a result of the increasing volume of genomic markers and nucleotide sequence information. Completion of whole genome sequences and the use of differential gene expression technology will hasten the discovery of the clock output pathways that control diverse rhythmic phenomena.     

The aging biological clock in Neurospora crassa

The biological clock affects aging through ras‐1 (bd) and lag‐1, and these two longevity genes together affect a clock phenotype and the clock oscillator in Neurospora crassa. Using an automated cell‐counting technique for measuring conidial longevity, we show that the clock‐associated genes lag‐1 and ras‐1 (bd) are true chronological longevity genes. For example, wild type (WT) has an estimated median life span of 24 days, while the double mutant lag‐1, ras‐1 (bd) has an estimated median life span of 120 days for macroconidia. We establish the biochemical function of lag‐1 by complementing LAG1 and LAC1 in Saccharomyces cerevisiae with lag‐1 in N. crassa. Longevity genes can affect the clock as well in that, the double mutant lag‐1, ras‐1 (bd) can stop the circadian rhythm in asexual reproduction (i.e., banding in race tubes) and lengthen the period of the frequency oscillator to 41 h. In contrast to the ras‐1 (bd), lag‐1 effects on chronological longevity, we find that this double mutant undergoes replicative senescence (i.e., the loss of replication function with time), unlike WT or the single mutants, lag‐1 and ras‐1 (bd). These results support the hypothesis that sphingolipid metabolism links aging and the biological clock through a common stress response     

The biological clock of Chlamydomonas reinhardii in space

The overt circadian rhythm in a wildtype (wt+) and a short period (s-) strain of Chlamydomonas reinhardii has been studied in space using the photoaccumulation behavior as the recorded parameter. The period of the wt+ was 29.6 h, of the s- 21.4 h and did not deviate significantly from ground controls performed exactly at the same time. The phase was delayed in space by 4.2 h in the wt+, but was not altered in the s-. In both strains the amplitudes were significantly higher in space than in the ground controls. During the recording period of 6.5 days the cell density increased in both strains. The survival rate, i.e. the ability to form colonies on agar petri dishes, was higher in space than on ground. The period was in both strains by 1.1 h longer in Florida (Kennedy Space Center) in both the flight and the control samples than in Europe. The significance of these results is discussed with respect to the endogenous nature of the biological clock and the role of the microgravity environment.     

The biological clock modulates the human cortisol response in a multiplicative fashion

Human cortisol levels follow a clear circadian rhythm. We investigated the contribution of alternation of sleep and wakefulness and the circadian clock, using forced desynchrony. Cortisol levels were best described by a multiplication of a circadian and a wake-time component. The human cortisol response is modulated by circadian phase. Exposure to stress at an unnatural phase, as in shift work, is predicted to result in abnormal cortisol levels. Health of shift workers may therefore improve when stress is reduced at times when the clock produces high stress sensitivity.     

Biochemical basis for the biological clock

NADH oxidases at the external surface of plant and animal cells (ECTO-NOX proteins) exhibit stable and recurring patterns of oscillations with potentially clock-related, entrainable, and temperature-compensated period lengths of 24 min. To determine if ECTO-NOX proteins might represent the ultradian time keepers (pacemakers) of the biological clock, COS cells were transfected with cDNAs encoding tNOX proteins having a period length of 22 min or with C575A or C558A cysteine to alanine replacements having period lengths of 36 or 42 min. Here we demonstrate that such transfectants exhibited 22, 36, or 40 to 42 h circadian patterns in the activity of glyceraldehyde-3-phosphate dehydrogenase, a common clock-regulated protein, in addition to the endogenous 24 h circadian period length. The fact that the expression of a single oscillatory ECTO-NOX protein determines the period length of a circadian biochemical marker (60 X the ECTO-NOX period length) provides compelling evidence that ECTO-NOX proteins are the biochemical ultradian drivers of the cellular biological clock.     

昆虫的睡眠与生物钟

近年来 ,越来越多的证据表明昆虫也要睡眠。该文介绍这方面的研究发现 ,包括确定昆虫睡眠的标准以及昆虫与哺乳动物的睡眠在生理机制上的相似性 ,最后阐述了生物钟基因对昆虫睡眠的调节作用     

Maternal feeding controls fetal biological clock

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.     

The genus cecropia: a biological clock to estimate the age of recently disturbed areas in the neotropics

Forest successional processes following disturbance take decades to play out, even in tropical forests. Nonetheless, records of vegetation change in this ecosystem are scarce, increasing the importance of the chronosequence approach to study forest recovery. However, this approach requires accurate dating of secondary forests, which until now was a difficult and/or expensive task. Cecropia is a widespread and abundant pioneer tree genus of the Neotropics. Here we propose and validate a rapid and straightforward method to estimate the age of secondary forest patches based on morphological observations of Cecropia trees. We found that Cecropia-inferred ages were highly correlated with known ages of the forest. We also demonstrate that Cecropia can be used to accurately date disturbances and propose twenty-one species distributed all over the geographical range of the genus as potential secondary forest chronometer species. Our method is limited in applicability by the maximal longevity of Cecropia individuals. Although the oldest chronosequence used in this study was 20 years old, we argue that at least for the first four decades after disturbance, the method described in this study provides very accurate estimations of secondary forest ages. The age of pioneer trees provides not only information needed to calculate the recovery of carbon stocks that would help to improve forest management, but also provides information needed to characterize the initial floristic composition and the rates of species remigration into secondary forest. Our contribution shows how successional studies can be reliably and inexpensively extended without the need to obtain forest ages based on expensive or potentially inaccurate data across the Neotropics.     

The cyanobacterial circadian system: a clock apart

Several new molecular components of the circadian clocks of animals, fungi, and bacteria have been unveiled in the past two years. Enough parts are now identified to indicate that there is more than one way to build a biological clock, although there are parallels in the cycling molecular events among disparate groups of organisms.     

Top-down modeling of hierarchical biological clock mechanisms

Sleep and Biological Rhythms - The behavior of human circadian rhythms could be interpreted within the two-oscillator regime: one for the circadian pacemaker driving temperature/plasma melatonin...     

The biological clock in vertebrate embryogenesis as a mechanism of general control over the developmental organism

The problem of understanding the role of the time factor in embryogenesis is still at the conceptual stage. At the same time, a number of rhythmic processes described in the embryogenesis of animals point to the involvement of a biological clock in this period of ontogenesis. Most of them (biochemical, biophysical, cytological) have been identified during the process of cleavage and have a duration equal to that of a single cleavage division τ₀.