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At least 685 records · Page 38Linked to original sources
PubMed1999

The physical imperative in circadian rhythm: a cytoskeleton-related physically resettable clock mechanism hypothesis.

Organisms maintaining circadian rhythmicity are responding to physical constraint of a 24-hour cycle. Time-cue sensing is fundamental to the clock existence, and entrainment of circadian rhythm is indeed accessible to a wide variety of geophysical stimuli. Light-dark and temperature changes are the main time-cues. Additional physical forces such as barometric pressure, electrostatic and electromagnetic fields and gravity force, display a daily cyclic behavior and can function as secondary time-cues. A conceptual framework that contains explanations to all circadian properties including cell autonomous, environmental responsiveness and self-sustained character, is still lacking. It is argued that clock responsiveness to external cues is central to the cellular clock mechanism, and therefore, the nature of the time-cues and the pathways that enable the cell to respond to physical stimuli are of central importance. A role for cytoskeleton in clock entrainment mechanism is suggested in light of cytoskeleton's major involvement in cellular mechanotransduction.

Animals↗
PubMed2005

The central and basolateral nuclei of the amygdala exhibit opposite diurnal rhythms of expression of the clock protein Period2.

There is considerable evidence that circadian rhythms in mammals can be modulated by emotional state, but how emotional state modulates specific circadian outputs is poorly understood. We analyzed the expression of the circadian clock protein Period2 (PER2) in three regions of the limbic forebrain known to play key roles in emotional regulation, the central nucleus of the amygdala (CEA), the basolateral amygdala (BLA), and the dentate gyrus (DG). We report here that cells in all three regions exhibit daily rhythms in expression of PER2 that are under the control of the master clock, the suprachiasmatic nucleus (SCN). The rhythm in the CEA and the rhythms in the BLA and DG are diametrically opposite in phase and are differentially affected by adrenalectomy. Adrenalectomy completely abolished the PER2 rhythm in the CEA but had no effect on the PER2 rhythms in the BLA and DG. We previously reported a rhythm in PER2 expression in the oval nucleus of the bed nucleus of the stria terminalis that is identical in phase and sensitivity to adrenalectomy to that found in the CEA. Together, these findings show that key structures of the limbic forebrain exhibit daily oscillations in clock gene expression that are controlled not only by input from the SCN but, importantly, by hormonal and neurochemical changes that normally accompany motivational and emotional states. Thus, cells within these areas are strategically positioned to integrate the inputs from the SCN and emotional states to modulate circadian rhythms downstream from the SCN clock.

Adrenalectomy↗
PubMed2005

Origin of the Eumetazoa: testing ecological predictions of molecular clocks against the Proterozoic fossil record.

Molecular clocks have the potential to shed light on the timing of early metazoan divergences, but differing algorithms and calibration points yield conspicuously discordant results. We argue here that competing molecular clock hypotheses should be testable in the fossil record, on the principle that fundamentally new grades of animal organization will have ecosystem-wide impacts. Using a set of seven nuclear-encoded protein sequences, we demonstrate the paraphyly of Porifera and calculate sponge/eumetazoan and cnidarian/bilaterian divergence times by using both distance [minimum evolution (ME)] and maximum likelihood (ML) molecular clocks; ME brackets the appearance of Eumetazoa between 634 and 604 Ma, whereas ML suggests it was between 867 and 748 Ma. Significantly, the ME, but not the ML, estimate is coincident with a major regime change in the Proterozoic acritarch record, including: (i) disappearance of low-diversity, evolutionarily static, pre-Ediacaran acanthomorphs; (ii) radiation of the high-diversity, short-lived Doushantuo-Pertatataka microbiota; and (iii) an order-of-magnitude increase in evolutionary turnover rate. We interpret this turnover as a consequence of the novel ecological challenges accompanying the evolution of the eumetazoan nervous system and gut. Thus, the more readily preserved microfossil record provides positive evidence for the absence of pre-Ediacaran eumetazoans and strongly supports the veracity, and therefore more general application, of the ME molecular clock.

Animals↗
PubMed2001

Erratic overdispersion of three molecular clocks: GPDH, SOD, and XDH.

The neutrality theory predicts that the rate of neutral molecular evolution is constant over time, and thus that there is a molecular clock for timing evolutionary events. It has been observed that the variance of the rate of evolution is generally larger than expected according to the neutrality theory, which has raised the question of how reliable the molecular clock is or, indeed, whether there is a molecular clock at all. We have carried out an extensive investigation of three proteins, glycerol-3-phosphate dehydrogenase (GPDH), superoxide dismutase (SOD), and xanthine dehydrogenase (XDH). We have observed that (i) the three proteins evolve erratically through time and across lineages and (ii) the erratic patterns of acceleration and deceleration differ from locus to locus, so that one locus may evolve faster in one than another lineage, whereas the opposite may be the case for another locus. The observations are inconsistent with the predictions made by various subsidiary hypotheses proposed to account for the overdispersion of the molecular clock.

Amino Acid Substitution↗
PubMed1982

Prothoracic glands of the saturniid moth Samia cynthia ricini possess a circadian clock controlling gut purge timing.

In the moth Samia cynthia ricini, timing of the release of prothoracicotropic hormone is controlled by a circadian clock in the cephalic organ (brain); while this hormone release is necessary for gut purge, the final timing of this event is controlled by a circadian clock in the prothoracic glands that gates release of ecdysone. The photoreceptor of the prothoracic gland clock(s) is extraocular and evidently in the glands themselves. Demonstration that the clock and its photoreceptor are in the prothoracic glands is based on a mixture of localized illuminations and the transplantation of glands from one larva to another.

Journal Article↗
PubMed1995

Genes that control a temperature-compensated ultradian clock in Caenorhabditis elegans.

Substantial progress has been made in understanding the genetic basis of temperature-compensated circadian clocks. Ultradian rhythms, with a period shorter than 24 h, are at least as widespread as circadian rhythms. We have initiated genetic analysis of defecation behavior, which is controlled by an ultradian clock in Caenorhabditis elegans. The defecation motor program is activated every 45 sec, and this rhythm is temperature compensated. We describe mutations in 12 genes that either shorten or lengthen the cycle period. We find that most of these mutations also disrupt temperature compensation, suggesting that this process is an integral part of the clock. These genes open the way for molecular genetic dissection of this ultradian clock.

Activity Cycles↗
PubMed1996

Identification of a novel vertebrate circadian clock-regulated gene encoding the protein nocturnin.

Photoreceptors of the Xenopus laevis retina are the site of a circadian clock. As part of a differential display screen for rhythmic gene products in this system, we have identified a photoreceptor-specific mRNA expressed in peak abundance at night. cDNA cloning revealed an open reading frame encoding a putative 388 amino acid protein that we have named "nocturnin" (for night-factor). This protein has strong sequence similarity to the C-terminal domain of the yeast transcription factor, CCR4, as well as a leucine zipper-like dimerization motif. Nocturnin mRNA levels exhibit a high amplitude circadian rhythm and nuclear run-on analysis indicates that it is controlled by the retinal circadian clock at the level of transcription. Our observations suggest that nocturnin may function through protein-protein interaction either as a component of the circadian clock or as a downstream effector of clock function.

Amino Acid Sequence↗
PubMed2003

p38 mitogen-activated protein kinase regulates oscillation of chick pineal circadian clock.

Extracellular signal-regulated kinase (ERK) and p38 are members of the mitogen-activated protein kinase (MAPK) family, and in some cases these kinases serve for closely related cellular functions within a cell. In a wide range of animal clock structures, ERK plays an important role in the circadian time-keeping mechanism. Here we found that immunoreactivity to p38 protein was uniformly distributed among cells in the chick pineal gland. On the other hand, a constant level of activated p38 was detected over the day, predominantly in the follicular and parafollicular pinealocytes that are potential circadian clock-containing cells. Chronic application of SB203580, a selective and reversible inhibitor of p38, to the cultured chick pineal cells markedly lengthened the period of the circadian rhythm of the melatonin release (up to 28.7 h). Noticeably, despite no significant temporal change of activated p38 level, a 4-h pulse treatment with SB203580 delayed the phase of the rhythm only when delivered during the subjective day. These results indicate a time-of-day-specific role of continuously activated p38 in the period length regulation of the chick pineal clock and suggest temporally separated regulation of the clock by two MAPKs, nighttime-activated ERK and daytime-working p38.

Animals↗
PubMed2005

A role for glycogen synthase kinase-3beta in the mammalian circadian clock.

The Drosophila shaggy gene product is a mammalian glycogen synthase kinase-3beta (GSK-3beta) homologue that contributes to the circadian clock of the Drosophila through TIMELESS phosphorylation, and it regulates nuclear translocation of the PERIOD/TIMELESS heterodimer. We found that mammalian GSK-3beta is expressed in the suprachiasmatic nucleus and liver of mice and that GSK-3beta phosphorylation exhibits robust circadian oscillation. Rhythmic GSK-3beta phosphorylation is also observed in serum-shocked NIH3T3 cells. Exposing serum-shocked NIH3T3 cells to lithium chloride, a specific inhibitor of GSK-3beta, increases GSK-3beta phosphorylation and delays the phase of rhythmic clock gene expression. On the other hand, GSK-3beta overexpression advances the phase of clock gene expression. We also found that GSK-3beta interacts with PERIOD2 (PER2) in vitro and in vivo. Recombinant GSK-3beta can phosphorylate PER2 in vitro. GSK-3beta promotes the nuclear translocation of PER2 in COS1 cells. The present data suggest that GSK-3beta plays important roles in mammalian circadian clock.

ARNTL Transcription Factors↗
PubMed2006

Period2 expression pattern and its role in the development of the pineal circadian clock in zebrafish.

In zebrafish, pineal arylalkylamine-N-acetyltransferase (zfaanat2) mRNA expression begins at 22 h post-fertilization (hpf), and the clock-controlled rhythm of its transcript begins on the third day of development. Here we describe the role of light and of the clock gene, period2 (zper2) in the development of this rhythm. In 1-day-old zebrafish embryos, zper2 expression is transiently up-regulated by light in the pineal gland and, to a lesser extent, in other areas of the brain. Expression of zper2 that was not affected by light occurred in the olfactory placode and lactotroph cells of the pituitary primordium. Circadian analysis of pineal zfaanat2 mRNA expression indicated that light exposure is required for proper development of the circadian clock-controlled rhythmic expression of this gene. Knockdown of zPER2 using antisense technology abolished the effect of light on development of the zfaanat2 rhythm in the pineal gland, corroborating the role of zper2 in light entrainment of the circadian oscillator in zebrafish. Further analysis of zper2 expression at earlier stages of development revealed that light exposure at the blastula to mid-segmentation stages also caused a transient increase in zper2 expression. At mid-segmentation, before pineal differentiation, light-induced zper2 expression was enhanced in pineal progenitor cells. Thus, a possible role for early photoreception and light-induced zper2 expression in the development of clock-controlled rhythms remains to be investigated.

Animals↗
PubMed2003

Testing a molecular clock without an outgroup: derivations of induced priors on branch-length restrictions in a Bayesian framework.

We propose a Bayesian method for testing molecular clock hypotheses for use with aligned sequence data from multiple taxa. Our method utilizes a nonreversible nucleotide substitution model to avoid the necessity of specifying either a known tree relating the taxa or an outgroup for rooting the tree. We employ reversible jump Markov chain Monte Carlo to sample from the posterior distribution of the phylogenetic model parameters and conduct hypothesis testing using Bayes factors, the ratio of the posterior to prior odds of competing models. Here, the Bayes factors reflect the relative support of the sequence data for equal rates of evolutionary change between taxa versus unequal rates, averaged over all possible phylogenetic parameters, including the tree and root position. As the molecular clock model is a restriction of the more general unequal rates model, we use the Savage-Dickey ratio to estimate the Bayes factors. The Savage-Dickey ratio provides a convenient approach to calculating Bayes factors in favor of sharp hypotheses. Critical to calculating the Savage-Dickey ratio is a determination of the prior induced on the modeling restrictions. We demonstrate our method on a well-studied mtDNA sequence data set consisting of nine primates. We find strong support against a global molecular clock, but do find support for a local clock among the anthropoids. We provide mathematical derivations of the induced priors on branch length restrictions assuming equally likely trees. These derivations also have more general applicability to the examination of prior assumptions in Bayesian phylogenetics.

Animals↗
PubMed2004

Explosive radiations and the reliability of molecular clocks: island endemic radiations as a test case.

The reliability of molecular clocks has been questioned for several key evolutionary radiations on the basis that the clock might run fast in explosive radiations. Molecular date estimates for the radiations of metazoan phyla (the Cambrian explosion) and modern orders of mammals and birds are in many cases twice as old as the palaeontological evidence would suggest. Could some aspect of explosive radiations speed the molecular clock, making molecular date estimates too old? Here we use 19 independent instances of recent explosive radiations of island endemic taxa as a model system for testing the proposed influence of rapid adaptive radiation on the rate of molecular evolution. These radiations are often characterized by many of the potential mechanisms for fast rates in explosive radiations--such as small population size, elevated speciation rate, rapid rate of morphological change, release from previous ecological constraints, and adaptation to new niches--and represent a wide variety of species, islands, and genes. However, we find no evidence of a consistent increase in rates in island taxa compared to their mainland relatives, and therefore find no support for the hypothesis that the molecular clock runs fast in explosive radiations.

Adaptation, Biological↗
PubMed2004

Molecular clock fork phylogenies: closed form analytic maximum likelihood solutions.

Maximum likelihood (ML) is increasingly used as an optimality criterion for selecting evolutionary trees, but finding the global optimum is a hard computational task. Because no general analytic solution is known, numeric techniques such as hill climbing or expectation maximization (EM) are used in order to find optimal parameters for a given tree. So far, analytic solutions were derived only for the simplest model-three-taxa, two-state characters, under a molecular clock. Quoting Ziheng Yang, who initiated the analytic approach,"this seems to be the simplest case, but has many of the conceptual and statistical complexities involved in phylogenetic estimation."In this work, we give general analytic solutions for a family of trees with four-taxa, two-state characters, under a molecular clock. The change from three to four taxa incurs a major increase in the complexity of the underlying algebraic system, and requires novel techniques and approaches. We start by presenting the general maximum likelihood problem on phylogenetic trees as a constrained optimization problem, and the resulting system of polynomial equations. In full generality, it is infeasible to solve this system, therefore specialized tools for the molecular clock case are developed. Four-taxa rooted trees have two topologies-the fork (two subtrees with two leaves each) and the comb (one subtree with three leaves, the other with a single leaf). We combine the ultrametric properties of molecular clock fork trees with the Hadamard conjugation to derive a number of topology dependent identities. Employing these identities, we substantially simplify the system of polynomial equations for the fork. We finally employ symbolic algebra software to obtain closed formanalytic solutions (expressed parametrically in the input data). In general, four-taxa trees can have multiple ML points. In contrast, we can now prove that each fork topology has a unique(local and global) ML point.

Animals↗
PubMedDate not supplied

Ambulance, fire, and police dispatch times compared with the atomic clock.

OBJECTIVES: To quantify any differences between the times used by public safety answering points (PSAPs) in a multijurisdictional county compared with the atomic clock and to determine whether there was consistency in any time differences. METHODS: All 25 ambulance, fire, and police PSAPs were contacted by telephone. The current time in hours, minutes, and seconds on the dispatch center's timepiece was requested. The atomic clock time was simultaneously recorded. Time differences between the reported and atomic clock times were calculated and the absolute values were used to calculate the mean difference. The procedure was repeated one week later. Consistency in time deviation was evaluated by subtracting the time differences between weeks 1 and 2 for each center. RESULTS: All 25 centers were contacted and three declined to participate. Time differences ranged from -551 to 117 seconds (mean difference: 61.2 +/- 120.3) for week 1 and -103 to 79 seconds (mean difference: 36.9 +/- 33.4) for week 2. Time deviations between weeks 1 and 2 were: 0 seconds for one center, 1 to 30 seconds for 12 centers, 31 to 60 seconds for four centers, and more than 60 seconds for five centers. CONCLUSIONS: The maximum time difference between dispatch center and atomic clock times was 551 seconds. This difference may be clinically significant for time-dependent research, quality improvement tasks, or medical legal reviews when multiple PSAPs are involved. Lack of consistency in time deviation over one week suggests systematic adjustment for these differences may not be possible.

Ambulances↗
PubMed2006

Circadian rhythmicity and photoperiodism in the pitcher-plant mosquito: can the seasonal timer evolve independently of the circadian clock?

The two major rhythms of the biosphere are daily and seasonal; the two major adaptations to these rhythms are the circadian clock, mediating daily activities, and the photoperiodic timer, mediating seasonal activities. The mechanistic connection between the circadian clock and the photoperiodic timer remains unresolved. Herein, we show that the rhythmic developmental response to exotic light:dark cycles, usually used to infer a causal connection between the circadian clock and the photoperiodic timer, has evolved independently of the photoperiodic timer in the pitcher-plant mosquito Wyeomyia smithii across the climatic gradient of eastern North America from Florida to Canada and from the coastal plain to the mountains. We conclude that the photoperiodic timing of seasonal events can evolve independently of the daily circadian clock.

Animals↗
PubMed2000

Circadian clock-protein expression in cyanobacteria: rhythms and phase setting.

The cyanobacterial gene cluster kaiABC encodes three essential circadian clock proteins: KaiA, KaiB and KaiC. The KaiB and KaiC protein levels are robustly rhythmical, whereas the KaiA protein abundance undergoes little if any circadian oscillation in constant light. The level of the KaiC protein is crucial for correct functioning of the clock because induction of the protein at phases when the protein level is normally low elicits phase resetting. Titration of the effects of the inducer upon phase resetting versus KaiC level shows a direct correlation between induction of the KaiC protein within the physiological range and significant phase shifting. The protein synthesis inhibitor chloramphenicol prevents the induction of KaiC and blocks phase shifting. When the metabolism is repressed by either translational inhibition or constant darkness, the rhythm of KaiC abundance persists; therefore, clock protein expression has a preferred status under a variety of conditions. These data indicate that rhythmic expression of KaiC appears to be a crucial component of clock precession in cyanobacteria.

Bacterial Proteins↗
PubMed1978

Genetic and physiological characteristics of a slow-growing circadian clock mutant of Neurospora crassa.

A circadian clock mutant of Neurospora crassa with a period length of about 25.8 hours (4 hr longer than wild type) has been isolated after mutagenesis of the band strain. This mutant, called frq-5, segregates as a single nuclear gene, maps near the centromere on linkage group III, and is unlinked to four previously described clock mutants clustered on linkage group VII R (Feldman and Hoyle 1973, 1976). frq-5 differs from the other clock mutants in at least two other respects: (1) it is recessive in heterokaryons, and (2) it grows at about 60% the rate of the parent band strain on both minimal and complete media. Double mutants between frq-5 and each of the other clock mutants show additivity of period length--two long period mutants produce a double mutant whose period length is longer than either of the two single mutants, while a long and a short period double mutant has an intermediate period length. Although slow growth and long periodicity of frq-5 have segregated together among more than 300 progeny, slow growth per se is not responsible for the long period, since all the double mutants have the slow growth characteristic of frq-5, but have period lengths both shorter and longer than wild type.

Circadian Rhythm↗
PubMed2006

Molecular components of the mammalian circadian clock.

Circadian rhythms are approximately 24-h oscillations in behavior and physiology, which are internally generated and function to anticipate the environmental changes associated with the solar day. A conserved transcriptional-translational autoregulatory loop generates molecular oscillations of 'clock genes' at the cellular level. In mammals, the circadian system is organized in a hierarchical manner, in which a master pacemaker in the suprachiasmatic nucleus (SCN) regulates downstream oscillators in peripheral tissues. Recent findings have revealed that the clock is cell-autonomous and self-sustained not only in a central pacemaker, the SCN, but also in peripheral tissues and in dissociated cultured cells. It is becoming evident that specific contribution of each clock component and interactions among the components vary in a tissue-specific manner. Here, we review the general mechanisms of the circadian clockwork, describe recent findings that elucidate tissue-specific expression patterns of the clock genes and address the importance of circadian regulation in peripheral tissues for an organism's overall well-being.

Animals↗