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At least 469 records · Page 26Linked to original sources
PubMed2006

Developmental control in animals and a biological role for DNA charge transfer.

A model is developed based on data from diverse lines of inquiry, describing the possible role of charge transfer in the timing and coordination of DNA replication and gene expression in eukaryotic cells. Emphasis is placed on a possible electrical process which participates in the simultaneous base-pair opening in many regions of DNA preceding replication, and a similar coordination of gene expression by simultaneous generation of base-pair openings around promoter and transcriptional start sites. This process could have the character of an ultradian biological clock. There is no specific evidence for such a process, but the argument is presented that such a process is neither unphysical nor unbiological, and its postulation would act as a first-iteration road map for explaining the coordinated nature of eukaryotic organism development.

Animals↗
PubMed2002

Biorhythms and possible central regulation of magnesium status, phototherapy, darkness therapy and chronopathological forms of magnesium depletion.

Biological clock and magnesium status are linked. Central magnesium regulation may be hypothetized. Balanced magnesium status is requested to obtain efficiency of suprachiasmatic nuclei and of pineal gland. Conventional bright light therapy appears as a speedy and efficient antidepressant medication useful for the treatment of various types of depression, and of non migrainous headaches also. Although decrease in melatonin production seems accessory, increases of serotonergy and perhaps of Reactive Oxygen Species constitute the main mechanisms of action. Chromatotherapy emphazizes the effects of short exposure to specific colors. Although the increased production of melatonin constitutes the best marker of darkness, it is only an accessory mechanism of its action. The psycholeptic sedative effects of darkness, like those of magnesium, rely on direct membraneous and oxidant actions, neural mediated effects (i.e. stimulation of inhibitory neuromodulators such as GABA and taurine), and on antagonism of neuroactive gases (CO and NO). Darkness therapyper se, partial substitutive therapy with melatonin and with their mimicking agents (Mg, L-Tryptophan,Taurine) apply to all the chronopathological forms of magnesium depletion with decreased production of melatonin: sleep disorders, migraine, chronic fatigue syndrome, fibromyalgia, some forms of asthma and of sudden infant death syndrome. Further research should assess the importance of the chronopathological forms of magnesium depletion in the physiopathology of these disorders.

Biological Clocks↗
PubMed1984

A mechanism of mania and the chemistry of dreams: a hypothesis.

A suggested cause of mania is asynchrony of two biologic clocks that are involved with the sleep-waking mechanism. Increased norepinephrine in the synaptic clefts of the locus ceruleus could quicken the pace of one clock. That same increase in norepinephrine is a possible inducer of euphoria and hyperactivity in mania. The action of melatonin and/or vasotocin on the dorsal raphe nucleus may induce the hallucinatory behavior in mania. Lithium corrects the psychosis by inhibiting adenylate cyclase and slowing the circadian rhythm.

Biological Clocks↗
PubMed2000

Phase-dependent responses of Per1 and Per2 genes to a light-stimulus in the suprachiasmatic nucleus of the rat.

Single brief and discrete light treatments are sufficient to reset the overt mammalian rhythms of nocturnal rodents. In the present study, we examined the phase-dependent response of the mammalian clock genes, Per1 and Per2, to a brief strong light-stimulus (1000 lux) in the circadian oscillator center, the suprachiasmatic nucleus (SCN) of rats. Light-induced elevation of Per1 mRNA was observed through the subjective night (CT16, CT20 and CT0 (=CT24)) with a marked peak at the subjective dawn (CT0). However, the light influence was very limited for the induction of Per2; only weak elevation of Per2 mRNA was detected at CT16. The effect of light-stimulus on the Per1 gene was transient, and the effect was restricted to ventrolateral SCN neurons in both CT0 and CT16 after light exposure. Since it is known that these rats show a light-induced behavioral phase-shift throughout the subjective night with being strongest at subjective dawn, the present results suggest that the transient induction of Per1 in ventrolateral SCN neurons is a critical step in the resetting of the biological clock to environmental light-dark schedule.

Animals↗
PubMed2005

Time keeping by the quail's eye: circadian regulation of melatonin production.

Previous studies have shown that eye removal disrupts the circadian body temperature and activity rhythms of Japanese quail supporting the hypothesis that the eyes act as pacemakers within the quail circadian system. Furthermore, the putative ocular pacemakers are coupled to the rest of the circadian system via neural and hormonal outputs. Although the neural pathway has yet to be identified, experiments suggest that the daily rhythm of ocular melatonin synthesis and release is the hormonal output. We sought to strengthen the hypothesis that the eyes are the loci of circadian pacemakers, and that melatonin output is involved, by examining melatonin secretion in cultured quail retinas. Using an in vitro flow-through system we demonstrated that (1) isolated retinal tissue could exhibit a rhythm of melatonin release, (2) the rhythm of melatonin synthesis is directly entrainable by 24-h light-dark cycles, and (3) supplementation of the culture medium with serotonin is necessary for robust, rhythmic production of melatonin in constant darkness. These results show definitively that the eyes are the loci of a biological clock and, in light of previous studies showing the disruptive effects of blinding on the circadian system, strengthen the hypothesis that the ocular clock is a circadian pacemaker that can affect the rest of the circadian system via the cyclic synthesis and release of melatonin. The quail retina is proving to be a valuable in vitro model for investigating properties of circadian pacemakers.

5-Hydroxytryptophan↗
PubMed2000

Effect of genistein on the temporal coordination of cleavage and compaction in mouse preimplantation embryos.

Initially, we investigated the effect of genistein, an inhibitor of protein tyrosine kinases, on compaction of the mouse embryo since tyrosine phosphorylation of the cadherin-catenins complex was suggested to down-regulate its adhesive function. Genistein prevented cleavage from the 2- to the 4-cell stage in a concentration-dependent manner. The next cleavage is inhibited at all concentrations used. Time course of intercellular flattening is however identical for both control 8-cell embryos and 4-cell arrested embryos. This confirms that compaction takes place according to a biological clock that does not depend on completion of the third cell cycle. Our results also suggest that, since, in contrast to genistein, protein kinases C modulators are known to cause a premature compaction, diacylglycerol-dependent kinases but not protein tyrosine kinases might be upregulators of compaction.

Actins↗
PubMedDate not supplied

Replicative senescence and the art of counting.

The idea that aging is largely the result of (endogenous) stress appears to be at odds with the concept of biological 'clocks', which seem to programme and terminate cellular aging processes. Here, data are reviewed that show that telomeres, the major clock identified in human cells so far, do in fact measure stress and damage accumulation much more than simple mitotic time. Telomere shortening is significantly stress-dependent due to a telomere-specific damage repair deficiency. This identifies telomere-driven human cell replicative senescence as a stress response with high potential importance for human aging.

Biological Clocks↗
PubMed1995

Suppression of PERIOD protein abundance and circadian cycling by the Drosophila clock mutation timeless.

The timeless mutation (tim) leads to loss of circadian behavioral rhythms in Drosophila melanogaster. The effects of tim on rhythmicity involve interactions with period (per), a second essential clock gene, as the tim mutation suppresses circadian oscillations of per transcription and blocks nuclear localization of a PER reporter protein. In the present study it was found that the tim mutant constitutively produces a low level of PER protein that is comparable with that produced late in the day by wild-type flies. In addition, it was shown that tim suppresses circadian cycling of PER protein abundance and circadian regulation of PER phosphorylation. Transfer of wild-type flies to constant light also suppressed cycling of PER abundance and phosphorylation and produced constitutively low levels of PER. In the tim mutant there was no additional effect of constant light on PER. These results suggest that constant light and the tim mutation produce related changes in the underlying biological clock. We further suggest that the multiple effects of tim are due to a primary effect on per expression at the posttranscriptional level. The effects of tim on behavioral rhythms and per RNA cycling are therefore likely to involve effects on PER protein through previously proposed feedback mechanisms.

Animals↗
PubMed1991

Regularly scheduled voluntary exercise synchronizes the mouse circadian clock.

Circadian rhythm entrainment has long been thought to depend exclusively on periodic cues in the external environment. However, evidence now suggests that appropriately timed vigorous activity may also phase shift the circadian clock. Previously it was not known whether levels of exercise/activity associated with spontaneous behavior provided sufficient feedback to phase shift or synchronize circadian rhythms. The present study investigated this issue by monitoring the sleep-wake, drinking, and wheel-running circadian rhythms of mice (Mus musculus) during unrestricted access to running wheels and when free wheel rotation was limited to either 12- or 6-h intervals with a fixed period of 24 h. Wheel rotation was controlled remotely. Mice spontaneously ran in wheels during scheduled access, and free-running sleep-wake and drinking circadian rhythms became entrained to scheduled exercise in 11 of 15 animals. However, steady-state entrainment was achieved only when exercise commenced several hours into the subjective night. The temporal placement of running during entrainment was related (r = 0.7003, P less than 0.02) to free-running period before entrainment. Mice with a free-running period less than 23.0 h did not entrain but exhibited relative coordination between free-running variables and the wheel availability schedule. Thus the circadian timekeeping system responds to temporal feedback arising from the timing of volitional exercise/activity, suggesting that the biological clock not only is responsive to periodic geophysical events in the external environment but also derives physiological feedback from the spontaneous activity behaviors of the organism.

Animals↗
PubMed2002

Magnesium deficit and sudden infant death syndrome (SIDS): SIDS due to magnesium deficiency and SIDS due to various forms of magnesium depletion: possible importance of the chronopathological form.

Sudden Infant Death Syndrome (SIDS) might be due to the fetal consequences of a Mg maternal deficiency, which might be prevented by simple atoxic nutritional Mg intake by the mother. Various stresses in the pregnant women or in the infant may transform a simple Mg deficiency into Mg depletion which may not be cured by nutritional Mg supplement, but requires a correction of its causal dysregulation. Beside the well established risk factors in baby care and in the environment, it is important to stress the possible role of a primary hypofunction of the biological clock. This may be treated by darkness therapy: total light deprivation at night for the infant and atoxic nutritional Mg supplement for the pregnant women. The place in the prevention of SIDS of Mg therapy for the infant and of the use of melatonin, L-tryptophan and taurine is now uncertain yet.

Adult↗
PubMedDate not supplied

The use of adenoviral vectors and ex vivo transduced neurotransplants: towards promotion of neuroregeneration.

Regeneration of injured axons following injury depends on a delicate balance between growth-promoting and growth-inhibiting factors. Overexpression of neurotrophin genes seems a promising strategy to promote regeneration. Trophic genes can be overexpressed at the site of injury at the axonal stumps, or at the perikaryal level of the injured neuron. Transduction of the neural cells can be achieved by applying adenoviral vectors, either directly in vivo or-in the case of neurotransplantation as an ex vivo approach. In both cases it would create a more permissive environment for axonal growth and therefore in functional regeneration. In this article, the feasibility of the use of adenoviral vectors in several neuroregeneration models--in particularly in spinal cord lesion models and the biological clock transplantation model--is illustrated. The results show that the adenoviral vectors can be a powerful tool to study the effects of overexpression of genes in an in vivo paradigm of nerve regeneration or nerve outgrowth. The potential use of adenoviral vectors and ex vivo transduced neurotransplants is discussed.

Adenoviridae↗
PubMedDate not supplied

Comparison of the spontaneous behaviour of four strains of female mice with different physiological properties.

The behaviour of four strains of virgin and lactating mice with different physiological characteristics (SHN, SLN, GR/A and C3H/He) were compared. In virgin, the motor activity, determined by Supermex, was high in all strains shortly after the start of the test, especially in GR/A. In this strain, the high activity continued longer and was also observed before the dark phase. In both the entire 48 hours and the last 24 hours of measurement, GR/A showed higher activity than the other strains during the light phase, but not during the dark phase. These data suggest that GR/A is more sensitive and thus has lower adaptability to a new environment than the other strains and that the biological clock of this strain differs from the others. The frequency and the period in or out of the nest as estimated by a video monitor were smaller and longer, respectively, in SLN than in the other strains. However, no relationship was found between the pattern of behaviour at lactation and the pup growth as an index of lactational performance.

Animals↗
PubMed2006

The metabolic syndrome: a brain disease?

The incidence of obesity with, as consequence, a rise in associated diseases such as diabetes, hypertension and dyslipidemia--the metabolic syndrome--is reaching epidemic proportions in industrialized countries. Here, we provide a hypothesis that the biological clock which normally prepares us each morning for the coming activity period is altered due to a modern life style of low activity during the day and late-night food intake. Furthermore, we review the anatomical evidence supporting the proposal that an unbalanced autonomic nervous system output may lead to the simultaneous occurrence of diabetes type 2, dyslipidemia, hypertension and visceral obesity.

Autonomic Nervous System↗
PubMed1990

Effect of different light-dark schedules on survival from heart failure.

Our earlier work showed that life in constant light prolonged life for hamsters with an inherited cardiomyopathy when compared to littermates spending their lives in 24 hour days (lights on 12 hr each day). This study was designed to begin evaluating the mechanism for this effect. 4-5.5 month old cardiomyopathic hamsters (CMHs) were placed on one of 5 different light-dark (LD) schedules for the remainder of their lives: (1) LD 12:12 (moderate total light exposure, short photoperiodic effect, 24 hr daylength); (2) LD 12:13 (same total light as LD 12:12, long photoperiodic effect, non-24 hr daylength); (3) LD 6:30 (less total light than LD 12:12, long photoperiodic effect, non-24 hr daylength); (4) LD 18:6 (more total light than LD 12:12, long photoperiodic effect, 24 hr daylength); (5) constant light (high total light exposure, long photoperiodic effect, non-24 hr daylength). CMHs living on the first two non-24 hr schedules lived longer than LD 12:12 controls. This study therefore suggests that manipulating the biological clock can have positive therapeutic consequences. However, in contrast to our earlier studies, hamsters living in constant light were not protected--perhaps because the hamsters began the treatment later in their lives or because their inherited disease was less severe than had been the case in hamsters used in previous studies. Defining the conditions that diminish or enhance the photobiological effect is an important challenge for future research.

Animals↗
PubMed1980

Thymus-endocrine interactions during ageing.

The hypotesis of the thymus acting as biological clock for ageing is revisited. On the basis of data on the endocrine action of the gland, the age-dependent involution of the thymus is postulated to play a fundamental role on the deterioration of the immunological as well as the endocrine functions. Data either on beta-adrenergic responsiveness to Isoproterenol or on hormonal balance, tested on animal model with different degree of thymus efficiency, support this hypothesis.

Aging↗
PubMed1996

Disrupted melatonin-secretion during alcohol withdrawal.

1. The synthesis of the pineal hormone, melatonin, is under adrenergic control. The brain's rhythm generating system (suprachiasmatic nucleus and associated systems) which is synchronised by the light-dark cycle controls norepinephrine release from the sympathetic nerve terminal resulting in cAMP accumulation. Increased cAMP leads to induction of the rate-limiting enzyme, N-acetyltransferase and synthesis of melatonin. The pineal exhibits a circadian rhythm with highest blood levels of the hormone being present during the night. The circadian rhythm of melatonin production provides important time-of-day and time-of-year information and, as a result, this hormonal cycle drives other 24-hour rhythms as well as seasonal cycles of reproduction, at least in photoperiodic mammals. 2. Chronic alcoholics were withdrawn from alcohol during a continued period of 4 days and nights. Blood samples were drawn from an indwelling venous catheter and sleep was monitored with polysomnography. No medication was used. No alcohol intake was allowed after admission. Bright light treatment was applied during day 3 of the study. 3. During the 4 days of alcohol-withdrawal the night time melatonin-secretion was disrupted. More than 50% of the patients had a very low secretion (< 30 pg/ml) which did not normalize during the study period. Psychopathology, sleep quality and sleep architecture improved significantly. The melatonin secretion pattern showed low values throughout the study. This low melatonin secretion might reflect the long lasting toxic influence of alcohol on the biological clock and/or a direct inhibitory effect on pineal function. These are different effects, although interrelated. 4. Ethanol has a direct inhibitory effect on pineal melatonin synthesis. A well-recognized action of ethanol is its ability to permeate and perturb the structure of cell membranes and may be related to its lipophilic properties. The changes in membrane fluidity seem to last longer than the study period of 4 days.

Adult↗
PubMed2003

Breathing around the clock: an overview of the circadian pattern of respiration.

This article reviews human and animal studies about the circadian patterns of physiological variables involved with the respiratory function. Some measures reflecting the mechanical properties of the lungs, such as functional residual capacity, forced expiratory volumes and airway resistance, change periodically with the time of the day. Also resting pulmonary ventilation (V(E)), tidal volume, and breathing rate follow circadian patterns. In humans, these patterns occur independently of the daily changes in activity, whereas, to some extent, they are linked to changes in the state of arousal. Differently, in some rodents, the circadian oscillations of the breathing pattern occur independently of the daily rhythms of either activity or state of arousal. Recent measurements of the breathing pattern for unlimited periods of time in undisturbed animals have indicated that the circadian changes occur in close temporal phase with those of oxygen consumption, carbon dioxide production, and body temperature. However, none of these variables can fully explain the circadian pattern of breathing, the origin of which remains unclear. Both in humans and in rats the V(E) responses to hypercapnia or hypoxia differ at various times of the day. In rats, the daily differences in V(E) responses are buffered by changes in metabolic rate, such that, unlike humans, the hyperventilation (defined as the increase in ventilation-metabolism ratio) remains constant throughout the 24 h. The presence of a biological clock is a major advantage in the adaptation to the environment, although it forces some variables to deviate periodically from their mean value. In humans, these deviations become apparent in conditions of hypoxia. Hence, a daily time-window exists in which the respiratory system is less capable of responding to challenges, a factor which may contribute to the findings that some cardio-respiratory symptoms and diseases peak at particular times of the day.

Animals↗
PubMed1980

Diurnal cycles in serotonin acetyltransferase activity and cyclic GMP content of cultured chick pineal glands.

Levels of serotonin N-acetyltransferase (NAT: acetul CoA:arylamine N-acetyltransferase; EC 2.1.1.5.) activity in the chick pineal gland exhibit a marked diurnal variation in birds kept under a diurnal cycle of ilumination. Activity begins to rise rapidly at the start of the dark phase of the cycle and reaches maximum levels at mid-dark phase about 25-fold greater than the minimum basal level at mid-light phase. Thereafter, the level of activity declines to the basal level about the start of the light phase. This diurnal cycle in chick pineal NAT activity found in vivo has recently been reproduced in vitro with intact glands incubated in organ culture. The mechanism of the 'biological clock' which regulates these variations in level of chick pineal NAT activity is unknown. However, I now report that chick pineal glands cultured under a diurnal cycle of illumination exhibit a diurnal cycle in content of cyclic GMP which roughly parallels the cycles in NAT activity. In contrast, there was no correlation between variations in pineal content of cyclic AMP and in level of NAT activity.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗