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PubMed2002

Chronopathological forms of magnesium depletion with hypofunction or with hyperfunction of the biological clock.

The main mechanisms of the chronopathological forms of magnesium depletion associate a low Mg intake with various dysregulating biorhythms. The differentiation between forms with hyperfunction and forms with hypofunction of the biological clock is seminal and the main marker is the production of melatonin (MT). The clinical forms of the various patterns of the chronopathological forms of Mg depletion may be central or peripheral. The clinical forms with hyperfunction of the biological clock (marker: increase in MT) may associate diverse expressions of nervous hypoexcitability: depression (i.e. Seasonal affective disease); cephalalgias nocturnal, without photophobia (i.e. cluster headaches); dyssomnia LASPS (advanced sleep phase syndrome) particularly]; asthenia and myalgias (i.e. fibromyalgia, chronic fatigue syndrome). The main comorbidity is found with depressive states. The therapy relies on classical bright light phototherapy, sometimes associated with psychoanaleptics. The clinical forms with hypofunction of biological clock (marker: decrease in MT) may associate various signs of nervous hyperexcitability (HEN): anxiety (from generalized anxiety to panic attacks); cephalalgias diurnal with photophobia (mainly migraine); dyssomnia [DSPS (delayed sleep phase syndrome) particularly, jet lag, night work disorders, age related insomnia, sometimes with inappropriate behaviour; photogenic epilepsia, generalized or focal; some clinical forms of chronic fatigue syndrome and fibromyalgia. The main comorbidity is between migraine and epilepsia. The treatment relies on the diverse forms of darkness therapy, possibly with the help of some psycholeptics: anxiolytics and anticonvulsants. The indications of chromatotherapy remain to be validated.

Animals↗
PubMed1996

Forward genetic approaches to circadian clocks in mice.

The study of mammalian circadian rhythms has a rich history of physiological understanding, but the molecular elements of the mammalian clock remain to be discovered. Availability of effective mutagenesis procedures and mouse molecular genetics resources sufficient for the task of positional cloning give cause for hope that the Clock gene, as well as other components of the mammalian circadian system, will be identified soon. The isolation of Clock in a deliberate mutagenesis screen provides an important proof-of-principle that forward genetics can be successfully applied toward the discovery of novel genes underlying complex behaviors in mice.

Animals↗
PubMed1999

Molecular clock mirages.

The hypothesis of the molecular clock proposes that molecular evolution occurs at rates that persist through time and across lineages, for a given gene. The neutral theory of molecular evolution predicts that the clock will be a Poisson process, with equal mean and variance. Experimental data have shown that the variance is typically larger than the mean. Hypotheses have been advanced to account for the hypervariance of molecular evolution. Four recent papers show that none of the predictive hypotheses that have been proposed can be generally maintained. The conclusion is that molecular evolution is dependent on the fickle process of natural selection. But it is a time-dependent process, so that accumulation of empirical data often yields an approximate clock, as a consequence of the expected convergence of large numbers.

Animals↗
PubMed2005

Four well-constrained calibration points from the vertebrate fossil record for molecular clock estimates.

Recent controversy about the use of the vertebrate fossil record for external calibration of molecular clocks centers on two issues, the number of dates used for calibration and the reliability of the fossil calibration date. Viewing matters from a palaeontological perspective, we propose three qualitative, phylogenetic criteria that can be used within a comparative framework for the selection of well-constrained calibration dates from the vertebrate fossil record. On the basis of these criteria, we identify three highly suitable new fossil calibration dates for molecular clock estimates: the lungfish-tetrapod split (between 419 and 408 Ma), the bird-crocodile split (between 251 and 243 Ma), and the alligator-caiman split (between 71 and 66 Ma). Together with our previously suggested bird-lizard split (between 252 and 257 Ma), these four fossil dates span a range of very different ages. They are, in our opinion, more suitable for molecular clock calibration than the traditionally used mammal-bird split, which is less well constrained. We plea for closer interactions between paleontologists and molecular biologists in studying the timescale of vertebrate evolution.

Animals↗
PubMed1992

A mammalian molecular clock?

The molecular clock hypothesis remains controversial more than a quarter of a century after it was first proposed. A variety of approaches have been applied to testing the molecular clock in mammals. In many of these studies apparent refutation of the molecular clock has been based on false assumptions about the pattern of mammalian evolution. With a few exceptions there now appears to be little evidence for variation in the rate of molecular evolution among mammalian lineages, although comparison of more genes and proteins among a greater variety of mammalian orders is needed before a definitive conclusion can be reached on the issue.

Animals↗
PubMed2004

Scoring clock tests for dementia screening: a comparison of two scoring methods.

OBJECTIVE: To compare the dementia screening performance of two scoring systems of the clock drawing test. METHODS: A sample of 1199 elderly subjects was administered the clock drawing test as part of a study on aging and dementia. The clock drawings were scored using published criteria for the two scoring systems that were compared. Additionally, a selection of 103 drawings was scored by three different raters to evaluate inter-rater agreement within each of the two methods. For a selection of 473 drawings the final diagnosis on the presence or absence of dementia was known. For these drawings accuracy for the detection of dementia was compared between the two methods. RESULTS: The four-item scoring system (Kappa 0.76; sensitivity 0.97; specificity 0.32; PPV 0.53; NPV 0.93) was found to be a little more reliable and as accurate as the six-item scoring system (Kappa 0.67; sensitivity 0.96; specificity 0.42; PPV 0.56; NPV 0.94). CONCLUSION: Since both scoring systems showed largely similar results, primary care physicians and other health care providers should be encouraged to use the four-item scoring checklist as it is easier and requires less time than the more elaborate checklist of the six-item system.

Aged↗
PubMed1999

Staying in plastic containers interferes with the orientation of clock-shifted homing pigeons.

Staying in plastic containers ventilated with natural air during transport and while waiting at the release site was found to affect the initial orientation of pigeons, Columba livia f. domestica, that were exposed to a 6-h clock-shift. The deflection from the mean direction of controls was significantly smaller, and the mean vector length was significantly shorter, than that of clock-shifted pigeons transported in conventional wooden cages. This effect was most pronounced when the birds stayed in plastic containers for the first and second time. Nonshifted control birds seemed to be largely unaffected by plastic containers. There was no influence on homing performance, which suggests a transient nature of the effect. Since the clock-shifted birds had access to the same orientational cues as the controls, we suggest that their sun compass was impaired by stress. We discuss general implications of this container effect, particularly in relation to some cases of olfactory deprivation where containers have been used and stress-induced side-effects cannot be excluded. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed2002

Population dynamics of clock-controlled biological species: models and why circadian rhythms are circadian.

Conventional models of population dynamics of biological species do not take into account the fact that activity of most living organisms is under control of biological clocks, which are oscillators with periods near 1 day, 1 year, and so on. Here proposed are new categories of population dynamics models which are combinations of Lotka-Volterra type of equations (as a simplest example; in fact, an arbitrary type may be used) and equations of the biological oscillators. Such models may be particularly useful in addressing to those problems which are inaccessible with conventional models. A simple example of such models with distributed clock periods is proposed and studied numerically and analytically to consider why periods of biological rhythms are not precisely one day or one year, etc., as is often questioned. For this purpose, a notion of survival index is introduced to measure the degree of success in survival. It turns out that clock periods equal or close to that of the milieu are not necessarily advantageous for survival and can even lead to extinction; survival is then most successful at the edge of entrainment. This may provide a clue to answer the question. It is also found that survival is difficult for those species which cannot be entrained by the environmental cycle.

Animals↗
PubMed1994

Illuminating the clock: circadian photobiology.

Light and circadian (daily) clocks are intimately related. Undoubtedly, the daily light/dark cycle has played a key role in the evolution of these oscillators. Now, light and dark signals synchronize these internal timekeepers to the precisely 24 h environmental cycle. Light also affects the period and amplitude of circadian rhythms. The expression of some 'light-responsive' genes are regulated by an intertwining of clock and light control mechanisms. These genes may help us to understand the evolution of circadian rhythmicity and can be employed as tools to identify and clone other genes which encode components of clock mechanisms or of their entrainment pathways.

Circadian Rhythm↗
PubMed1993

Reduced light sensitivity of the circadian clock in a hypopigmented mouse mutant.

Pink-eyed dilution (p/p) is a recessive mutation in mice which results in reduced pigmentation of the retinal pigment epithelium, as well as alterations in visual pathways and function. We investigated whether this mutation also affects light information reaching the circadian clock. Entrainment to a 12 h light 12 h dark cycle and the free-running period in constant darkness were not affected by this mutation. Phase shifts in response to 1 h light pulses consisting of bright white light at either circadian time 16 or 24 also did not differ between mutant and wild-type C57BL/6J mice. However, when 5 min, 502 nm light pulses of 1.2 x 10(-1) microW/cm2 or 4 x 10(-2) microW/cm2 were given at circadian time 16, the mutant mice responded with significantly smaller phase shifts than the wild-type mice. When animals were transferred to constant light, the free-running period of wild-type mice was longer than that of mutant mice, a finding which is consistent with a sensitivity difference between mutant and wild-type mice. Horseradish peroxidase tracing of retinal innervation of the hypothalamic suprachiasmatic nuclei (SCN)--the location of a circadian pacemaker--revealed a reduced innervation of the SCN in mutant mice compared with wild-type mice. The total volume of the SCN, as determined by neutral red stain, was also reduced in mutant mice, although not to as great an extent as the retinal innervation. Taken together, these results indicate that while basic characteristics of circadian clock function are not altered by the pink-eyed dilution mutation, the sensitivity of the clock to light is reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

A simple quantitative model of the molecular clock.

We present the ideas, and their motivation, at the basis of a simple model of nucleic acid evolution: the stationary Markov process, or Markov clock. After a brief review of its relevant mathematical properties, the Markov clock is applied to nucleotide sequences from mitochondrial and nuclear genes of different species. Particular emphasis is given to the necessity of carrying out a correct statistical analysis, which allows us to check quantitatively the applicability of our model. We find evidence that the Markov clock ticks in many different processes, and that its limitations can be understood in terms of a simple idea that we call the "base-drift" hypothesis. This hypothesis correlates the deviations from the stationarity of the Markov process to the evolutionary distance dAB(p) of two species A and B, relative to the process P. We conclude by discussing the implications of our findings for future work.

Animals↗
PubMed1987

On the molecular evolutionary clock.

The conceptual framework surrounding the origin of the molecular evolutionary clock and circumstances of this origin are described. In regard to the quest for the best available molecular clocks, a return to protein clocks is conditionally recommended. On the basis of recent data and certain considerations, it is pointed out that the realm of neutrality in evolution is probably less extensive than is now commonly thought, in the three distinct senses of the term neutrality--neutrality as nonfunctionality of mutations, neutrality as equifunctionality of mutations, and neutrality as a mode of fixation of mutations. The possibility is raised that complex sets of interacting components forming a system that is bounded with respect to its environment may quite generally display an intrinsic trend to a quasi-clockwise evolutionary behavior.

Biological Evolution↗
PubMed1981

Precision of the Gonyaulax circadian clock.

Under constant conditions, the circadian bioluminescent glow rhythm in populations (10(5) cells) of Gonyaulax polyedra is accurate to within 2 min/day. On successive days following the transfer to constant conditions, however, the glow exhibits a progressively broader waveform, implying that individual clocks in the population are drifting out of synchrony. Analysis of the glow waveform suggests that the standard deviation in circadian period among individual clocks is about 18 min and that the period of a given clock varies by less than this from one day to the next.

Animals↗
PubMedDate not supplied

Phase of the circadian clock is accurately transferred from mother to daughter cells in the dinoflagellate Gonyaulax polyedra.

In the first cycle following transfer from a 12 h light-12 h dark cycle (LD12:12) to constant darkness (DD), the standard deviation in circadian phase among individual clocks in populations of Gonyaulax polyedra is approximately 60 min. When a culture is transferred to constant light conditions (LL) from an LD 12:12 cycle, the standard deviation increases in the first 2-3 d, but then remains unchanged, suggesting a lack of observable desynchronization in LL after the transient period. The synchrony in a cell population is preserved even after several cell divisions. The results indicate that variations in period among cells are small, that the period of an individual clock does not fluctuate randomly from day to day, and that the circadian phase of a mother cell is faithfully passed to the clocks of the daughter cells.

Animals↗
PubMed2006

A mathematical investigation of a Clock and Wavefront model for somitogenesis.

Somites are transient blocks of cells that form sequentially along the antero-posterior axis of vertebrate embryos. They give rise to the vertebrae, ribs and other associated features of the trunk. In this work we develop and analyse a mathematical formulation of a version of the Clock and Wavefront model for somite formation, where the clock controls when the boundaries of the somites form and the wavefront determines where they form. Our analysis indicates that this interaction between a segmentation clock and a wavefront can explain the periodic pattern of somites observed in normal embryos. We can also show that a simplification of the model provides a mechanism for predicting the anomalies resulting from perturbation of the wavefront.

Algorithms↗
PubMed1996

Tryptophan hydroxylase mRNA levels are regulated by the circadian clock, temperature, and cAMP in chick pineal cells.

Chick pineal cells contain a circadian oscillator that derives rhythmic synthesis and secretion of melatonin even in dispersed cell culture. Here, we demonstrate that the mRNA encoding tryptophan hydroxylase (TPH), the first enzyme in the melatonin synthetic pathway, is expressed rhythmically under the control of the circadian clock. TPH message levels doubled between early day and early night, under both cyclic lightning and constant lightning conditions. The amplitude of the TPH mRNA rhythm was increased to 4-fold by culturing the cells at 43.3 degrees C for 48 h instead of 36.7 degrees C. Addition of forskolin to the cultures in early day produced a modest increase (50%) in TPH message levels but had no effect at other times. Because TPH mRNA are regulated by the endogenous pineal circadian clock, this provides a valuable system in which the molecular mechanism of clock control of gene expression.

Animals↗
PubMed1989

Midazolam, a short-acting benzodiazepine, resets the circadian clock of the hamster.

Treatment with the short-acting benzodiazepine, triazolam, has been found to induce changes in both behavioral and endocrine circadian rhythms in hamsters. The objective of this study was to determine if these effects of triazolam could be generalized to other short-acting benzodiazepines. Therefore, the effects of midazolam on the biological clock of the hamster were examined in detail. A phase-response curve and a dose-response curve were measured to determine the effects of a single intraperitoneal injection of midazolam on the circadian clock of hamsters free-running in constant light. Midazolam injections produced maximal phase advances at circadian time (CT) 6 and 9 and maximal phase delays at CT 15 and 21. Doses of 2.5 mg or larger produced phase shifts that were significantly different from those produced by the vehicle controls. In addition, the phase-shifting effects of midazolam were completely blocked by administration of the benzodiazepine receptor antagonist, RO 15-1788, indicating that the phase-shifting actions of midazolam are mediated via benzodiazepine receptors. These results indicate that the previously reported effects of triazolam on the circadian clock can be generalized to other short-acting benzodiazepines.

Animals↗
PubMed1989

'Clock' and 'motor' components in absolute coordination of rhythmic movements.

Human subjects swung, through motions at the two wrists, hand-held pendulums of variable mass and length. Within a pair, the two pendulums could be of the same or different magnitude. The subjects were required to produce a coordinated state in which the two rhythmic units oscillated at a single common period. Fifty-four conditions of absolute coordination, that is, 54 different pairs of wrist-pendulum systems, were investigated for each of three subjects in the course of six sessions. Each condition of absolute coordination was conducted in the out of phase mode and at the single most comfortable period. The period variances of the right and left systems in the 162 instances of absolute coordination were analysed according to a method that assumes that a timekeeper function and a motor implementation function contribute independently to the variance in the periodic timing of a rhythmic movement. The major findings were that in absolute coordination: (a) a system's 'motor' variance, but not its 'clock' variance, depended on the deviation of the period of absolute coordination tau from the system's characteristic period; (b) right and left 'clock' variances were related and (c) neither the 'motor' variances nor the 'clock' variances were affected by deviations in the mean phase relation from 180 degrees. The results were discussed in terms of their implications for interpreting von Holst's notions of maintenance tendency and magnetic effect and, more generally, the neural and dynamical basis of absolute coordination.

Adult↗