Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Biological Clocks”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed1970

Stable circadian rhythms as a property of cell populations.

Our paper analyzes the main difficulties which the theory of circadian rhythms encounters in an attempt to explain the mechanisms of biological clocks. It is shown that the assumption of a small concentration of the enzymes involved in the cell-clock mechanism allows explaining such well-known properties of biological clocks as: 1) a large period of the circadian oscillation; 2) insignificant energy consumption; 3) insensitivity to inhibitors; 4) temperature independence; 5) initiation of circadian oscillations in response to a short single external impulse; 6) a limited possibility of synchronization by periodic external factors. It is shown also that the self-oscillating clock mechanism may exist at the level of cell populations. This mechanism is considered to be a temperature-dependent component of the circadian clocks in multicellular organisms.

Cell Physiological Phenomena↗
PubMedDate not supplied

[Aspects of chronobiological effects of ethanol].

Circadian rhythms regulate various life processes in plants, animals and in humans. These rhythms are generated by an endogenous mechanism called the biological clock. It has been known that there is circadian variability of receptors susceptibility to drugs and circadian changes of drugs kinetics. Biological effects of ethanol raise interest of many researchers due to consequences of its use. Effects of ethanol on various ion channels and receptors suggest that its action may also depend on circadian rhythms and may modulate action of the biological clock. Experimental studies on animals and humans have shown that circadian variability influences hypnotic and hypothermic effects of ethanol, cortisol levels, ethanol pharmacokinetics and ethanol intake. Chronic ethanol administration influence thyroid and sex hormones excretion, stimulate the HPA axis and changes various circadian rhythms (of sleep, motor activity and food intake). Changes in circadian ethanol effects may have significance for toxicity and interaction with drugs. Disturbances of circadian rhythms in alcohol-dependent patients may case therapeutic problems.

Alcoholic Beverages↗
PubMed2004

Melatonin desensitizes endogenous MT2 melatonin receptors in the rat suprachiasmatic nucleus: relevance for defining the periods of sensitivity of the mammalian circadian clock to melatonin.

The hormone melatonin phase shifts circadian rhythms generated by the mammalian biological clock, the suprachiasmatic nucleus (SCN) of the hypothalamus, through activation of G protein-coupled MT2 melatonin receptors. This study demonstrated that pretreatment with physiological concentrations of melatonin (30-300 pM or 7-70 pg/mL) decreased the number of hMT2 melatonin receptors heterologously expressed in mammalian cells in a time and concentration-dependent manner. Furthermore, hMT2-GFP melatonin receptors heterologously expressed in immortalized SCN2.2 cells or in non-neuronal mammalian cells were internalized upon pretreatment with both physiological (300 pM or 70 pg/mL) and supraphysiological (10 nM or 2.3 ng/mL) concentrations of melatonin. The decrease in MT2 melatonin receptor number induced by melatonin (300 pM for 1 h) was reversible and reached almost full recovery after 8 h; however, after treatment with 10 nM melatonin full recovery was not attained even after 24 h. This recovery process was partially protein synthesis dependent. Furthermore, exposure to physiological concentrations of melatonin (300 pM) for a time mimicking the nocturnal surge (8 h) desensitized functional responses mediated through melatonin activation of endogenous MT2 receptors, i.e., stimulation of protein kinase C (PKC) in immortalized SCN2.2 cells and phase shifts of circadian rhythms of neuronal firing in the rat SCN brain slice. We conclude that in vivo the nightly secretion of melatonin desensitizes endogenous MT2 melatonin receptors in the mammalian SCN thereby providing a temporally integrated profile of sensitivity of the mammalian biological clock to a melatonin signal.

Animals↗
PubMed1988

The relationship of red cell enzymes to red cell life-span.

Red cells are replaced before they become senescent. It is probable that red cell destruction is controlled by a biologic clock, essentially independent of metabolism, rather than by metabolic failure. The appearance of neo-antigens on the external surface of the red cell could be this "clock."

Biological Clocks↗
PubMed1970

Extraoptic celestial orientation in the southern cricket frog Acris gryllus.

Celestial orientation and setting of the biological clock in the southern cricket frog Acris gryllus can be cued by light stimuli received by extraoptic receptors in the brain. These extraoptic photoreceptors may also be used in learning new orientational directions. A mechanism for a light-activated biological clock is discussed.

Animals↗
PubMed2003

Integration of molecular rhythms in the mammalian circadian system.

The discovery of clock genes and the general principles of their oscillation have made research on biological clocks a highly interesting field in the life sciences. As in other species, the mammalian circadian core oscillator is thought to be composed of an autoregulatory transcription-(post)translation-based feedback loop involving a set of clock genes. The production, phosphorylation, ubiquitination and proteasome-dependent degradation of clock proteins has a key role in generating the clock oscillation. The generation of internal clock time occurs in the hypothalamic suprachiasmatic nucleus (SCN), where clock gene oscillation in each neuron is coupled and amplified. These well synchronized oscillatory signals are spread into the whole brain and to peripheral organs which contain peripheral clocks. The important feature of the circadian system is that the rhythm of gene transcription of dock genes in the SCN reflects the behavioural rhythm almost perfectly. Investigations on biological clocks present the fascinating prospect of analysing the integrational mechanism of 'time' from genes to the living organism.

Animals↗
PubMed2000

Orchestrated transcription of key pathways in Arabidopsis by the circadian clock.

Like most organisms, plants have endogenous biological clocks that coordinate internal events with the external environment. We used high-density oligonucleotide microarrays to examine gene expression in Arabidopsis and found that 6% of the more than 8000 genes on the array exhibited circadian changes in steady-state messenger RNA levels. Clusters of circadian-regulated genes were found in pathways involved in plant responses to light and other key metabolic pathways. Computational analysis of cycling genes allowed the identification of a highly conserved promoter motif that we found to be required for circadian control of gene expression. Our study presents a comprehensive view of the temporal compartmentalization of physiological pathways by the circadian clock in a eukaryote.

Arabidopsis↗
PubMed1999

The mPer2 gene encodes a functional component of the mammalian circadian clock.

Circadian rhythms are driven by endogenous biological clocks that regulate many biochemical, physiological and behavioural processes in a wide range of life forms. In mammals, there is a master circadian clock in the suprachiasmatic nucleus of the anterior hypothalamus. Three putative mammalian homologues (mPer1, mPer2 and mPer3) of the Drosophila circadian clock gene period (per) have been identified. The mPer genes share a conserved PAS domain (a dimerization domain found in Per, Arnt and Sim) and show a circadian expression pattern in the suprachiasmatic nucleus. To assess the in vivo function of mPer2, we generated and characterized a deletion mutation in the PAS domain of the mouse mPer2 gene. Here we show that mice homozygous for this mutation display a shorter circadian period followed by a loss of circadian rhythmicity in constant darkness. The mutation also diminishes the oscillating expression of both mPer1 and mPer2 in the suprachiasmatic nucleus, indicating that mPer2 may regulate mPer1 in vivo. These data provide evidence that an mPer gene functions in the circadian clock, and define mPer2 as a component of the mammalian circadian oscillator.

Animals↗
PubMed2005

Human intestinal circadian clock: expression of clock genes in colonocytes lining the crypt.

Biological clock components have been detected in many epithelial tissues of the digestive tract of mammals (oral mucosa, pancreas, and liver), suggesting the existence of peripheral circadian clocks that may be entrainable by food. Our aim was to investigate the expression of main peripheral clock genes in colonocytes of healthy humans and in human colon carcinoma cell lines. The presence of clock components was investigated in single intact colonic crypts isolated by chelation from the biopsies of 25 patients (free of any sign of colonic lesions) undergoing routine colonoscopy and in cell lines of human colon carcinoma (Caco2 and HT29 clone 19A). Per-1, per-2, and clock mRNA were detected by real-time RT-PCR. The three-dimensional distributions of PER-1, PER-2, CLOCK, and BMAL1 proteins were recorded along colonic crypts by immunofluorescent confocal imaging. We demonstrate the presence of per-1, per-2, and clock mRNA in samples prepared from colonic crypts of 5 patients and in all cell lines. We also demonstrate the presence of two circadian clock proteins, PER-1 and CLOCK, in human colonocytes on crypts isolated from 20 patients (15 patients for PER-1 and 6 for CLOCK) and in colon carcinoma cells. Establishing the presence of clock proteins in human colonic crypts is the first step toward the study of the regulation of the intestinal circadian clock by nutrients and feeding rhythms.

ARNTL Transcription Factors↗
PubMed1999

Different circadian oscillators control Ca(2+) fluxes and lhcb gene expression.

Circadian biological clocks control many biological events, but the pathways by which these events are controlled are largely unknown. Based on a model suggesting that cytosolic-free calcium levels control the expression of the Lhcb gene in plants, we tested whether the circadian oscillation of free calcium is responsible for driving the rhythm of Lhcb expression. We found that these rhythms free-run with different periods in tobacco seedlings in constant conditions. Moreover, robust oscillations of Lhcb promoter activity continued in undifferentiated tobacco calli in the absence of Ca(2+) oscillations. Therefore, these two circadian rhythms are not linked hierarchically. These data provide evidence for separate circadian pacemakers controlling molecular events in plants.

Aequorin↗
PubMed2005

Keep time, stay healthy.

Recent studies reveal that sleep loss in humans leads to metabolic disorders. A new study reports the development of metabolic syndrome in mice with altered circadian timing brought about by a mutation in a gene that functions in the biological clock. An intriguing and unanswered question is the relation between a healthy biological clock and normal appetite and weight regulation.

Animals↗
PubMedDate not supplied

[The effect of continuous illumination and an inverse rhythm (light-darkness) on fibrinolysis].

The studies of chronobiology on biological phenomena revealed the existence of a human internal mechanism ("biological clock") which controls biological events according to each function of the body. Most of the programmed and genetically fixed rhythms can be changed and synchronized by external factors. Starting from these data and from our previous studies which emphasised an intradian rhythm of the proteolytic blood coagulation and fibrinolytic systems we observed the behaviour of the fibrinolytic system in modified environmental conditions (continuous illumination and inversed day-night rhythm). Our experiments were performed on 180 Wistar rats both male and female, submitted to continuous illumination and inversed rhythm for 1, 3 and 5 weeks. We studied plasma fibrinolytic activity (PFA) through euglobulin lysis time (ELT) at three different moments of the day: 8:30, 18:30 and 8:30 the next day. The study revealed intradian variations of PFA regardless of the type and time of submission. Thus: continuous illumination for 1, 3, 5 weeks determined a decrease of PFA (prolonged ELT) during the second part of the day, less important at 5 weeks. Inversed day-night rhythm for 1 and 3 weeks determined the same intradian behaviour of PFA but less important than continuous illumination. PFA variations in our experimental conditions suggest an alteration of its biological rhythm.

Animals↗
PubMed2006

A novel neuronal cell line derived from the ventrolateral region of the suprachiasmatic nucleus.

The suprachiasmatic nucleus of the anterior hypothalamus is the center of an internal biological clock in mammals. Glutamate is the neurotransmitter of retino-hypothalamic tract responsible for mediating the circadian actions of light in rodents. N-methyl-d-aspartate receptors, particularly NR2B subunit are reported to be principally involved in photic resetting of the biological clock in vivo and in slice culture. But, the precise cellular mechanisms of the resetting are not elucidated, because no adequate neuronal cell lines derived from the suprachiasmatic nucleus have been established. We established a neuronal cell line, N14.5, derived from the suprachiasmatic nucleus of a transgenic rat harboring the temperature-sensitive simian virus 40 large T-antigen gene. When the cells were cultured at 39 degrees C, the morphological features were turned fibroblastic into neuronal round cell body with neurite extensions. These cells showed immunoreactivities for neuronal markers (betaIII-tubulin, microtubule-associated protein 2 and TAU2) and as well as for vasoactive intestinal peptide which is expressed in the ventrolateral region of the suprachiasmatic nucleus. The cells expressed N-methyl-d-aspartate receptors, particularly NR1 and NR2B subunits as revealed by quantitative PCR. N-methyl-d-aspartate activated phosphorylation of p44/42 mitogen-activated protein kinase and increased expression level of Per1 and Per2 mRNA. These results suggest that the N14.5 is a novel neuronal cell line derived from the ventrolateral region of the suprachiasmatic nucleus, and that N-methyl-d-aspartate receptors expressed in the cells are a functional receptor. The N14.5 cells may be a useful tool to elucidate numerous chronobiological processes, especially resetting mechanism induced by an external light signal.

Animals↗
PubMed1999

Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms.

Many biochemical, physiological and behavioural processes show circadian rhythms which are generated by an internal time-keeping mechanism referred to as the biological clock. According to rapidly developing models, the core oscillator driving this clock is composed of an autoregulatory transcription-(post) translation-based feedback loop involving a set of 'dock' genes. Molecular clocks do not oscillate with an exact 24-hour rhythmicity but are entrained to solar day/night rhythms by light. The mammalian proteins Cryl and Cry2, which are members of the family of plant blue-light receptors (cryptochromes) and photolyases, have been proposed as candidate light receptors for photoentrainment of the biological clock. Here we show that mice lacking the Cryl or Cry2 protein display accelerated and delayed free-running periodicity of locomotor activity, respectively. Strikingly, in the absence of both proteins, an instantaneous and complete loss of free-running rhythmicity is observed. This suggests that, in addition to a possible photoreceptor and antagonistic clock-adjusting function, both proteins are essential for the maintenance of circadian rhythmicity.

Animals↗
PubMed2005

Entrainment of the human circadian system by light.

The periodic light-dark cycle is the dominant environmental synchronizer used by humans to entrain to the geophysical 24-h day. Entrainment is a fundamental property of circadian systems by which the period of the internal clock (tau) is synchronized to the period of the entraining stimuli (T cycle). An important aspect of entrainment in humans is the maintenance of an appropriate phase relationship between the circadian system, the timing of sleep and wakefulness, and environmental time (a.k.a. the phase angle of entrainment) to maintain wakefulness throughout the day and consolidated sleep at night. In this article, we review these concepts and the methods for assessing circadian phase and period in humans, as well as discuss findings on the phase angle of entrainment in healthy adults. We review findings from studies that examine how the phase, intensity, duration, and spectral characteristics of light affect the response of the human biological clock and discuss studies on entrainment in humans, including recent studies of the minimum light intensity required for entrainment. We briefly review conditions and disorders in which failure of entrainment occurs. We provide an integrated perspective on circadian entrainment in humans with respect to recent advances in our knowledge of circadian period and of the effects of light on the biological clock in humans.

Biological Clocks↗
PubMed1994

Age-related, sex-related, and seasonal changes of plasma lipoprotein concentrations in trout.

Seasonal variability in physiological parameters can be attributed to seasonal variations in environmental factors and/or to the consequence of the presence of endogenous circannual rhythms. In the current study we have measured plasma levels of lipids and of the different lipoprotein classes in fasting trout (Oncorhynchus mykiss) between the ages of 5 and 44 months. Independent of age and sexual maturity, a circannual variation in the low density lipoprotein concentration between 250 and 1300 mg/dl was demonstrated in both sexes. These seasonal fluctuations might be controlled by an endogenous biological clock synchronized by the photoperiod. The lipoprotein profile of trout is dominated by high density lipoproteins as early as the first months of life. Their concentration increases progressively during sexual maturation from about 1200 mg/dl in juveniles to about 2500 mg/dl during spermiation or at the moment of ovulation. This increase is highly significantly correlated with the increased concentration of testosterone occurring in both sexes during sexual maturation. The concentration of very low density lipoproteins increases substantially, from about 150 mg/dl to a maximal concentration of 800 mg/dl in females and 1100 mg/dl in males, during the deposit phase of lipid reserves which precedes the rapid increase in the gonadosomatic ratio. In the course of rapid ovarian growth, vitellogenin appears in the plasma of females and reaches a concentration of 2200 mg/dl 1 month before ovulation. From these results it is concluded that season and reproductive cycle are the two main factors affecting basal plasma lipid and lipoprotein levels in trout. Environmental factors such as photoperiod or endocrine factors such as the concentration of steroid hormones can be correlated and/or involved in the regulation of these quantitative variations. These results also suggest the presence of an endogenous biological clock able to exert an independent effect on plasma lipid and lipoprotein levels.

Age Factors↗
PubMed2005

Mouse intestinal cryptdins exhibit circadian oscillation.

The innate immunity utilizes a plethora of antibacterial polypeptides, known as defensins, to combat ingested bacteria. Mouse enteric defensins (cryptdins) are produced and secreted constitutively but are overexpressed in instances of infection and/or inflammation. Our objective was to determine whether the biological clock plays a role in cryptdin expression under healthy conditions. Analysis of cryptdin 1 and cryptdin 4 expression in the ileum and jejunum of the small intestine of FVB/N mice around the circadian cycle revealed oscillation that peaked at the end of the dark phase. To eliminate the possibility that cryptdin oscillation stems from food intake, we analyzed cryptdin expression under fasting conditions and found oscillation but with a 3 h phase-shift. Comparison of cryptdin expression in two mouse strains (C57BL/6 vs. FVB/N) revealed higher levels in C57BL/6, a mouse strain that is highly susceptible to enteric infection, due, most likely, to impaired cryptdin maturation. The results of this study indicate the involvement of the biological clock in regulating cryptdin expression in the small intestine and reinforce the capacity of food to act as a zeitgeber (synchronizer). With the assumption of similar control in humans, our results may imply that defensin expression peaks during the day.

Animals↗
PubMed2005

Late-night presentation of an auditory stimulus phase delays human circadian rhythms.

Although light is considered the primary entrainer of circadian rhythms in humans, nonphotic stimuli, including exercise and melatonin also phase shift the biological clock. Furthermore, in birds and nonhuman mammals, auditory stimuli are effective zeitgebers. This study investigated whether a nonphotic auditory stimulus phase shifts human circadian rhythms. Ten subjects (5 men and 5 women, ages 18-72, mean age +/- SD, 44.7 +/- 21.4 yr) completed two 4-day laboratory sessions in constant dim light (<20 lux). They received two consecutive presentations of either a 2-h auditory or control stimulus from 0100 to 0300 on the second and third nights (presentation order of the stimulus and control was counterbalanced). Core body temperature (CBT) was collected and stored in 2-min bins throughout the study and salivary melatonin was obtained every 30 min from 1900 to 2330 on the baseline and poststimulus/postcontrol nights. Circadian phase of dim light melatonin onset (DLMO) and of CBT minimum, before and after auditory or control presentation was assessed. The auditory stimulus produced significantly larger phase delays of the circadian melatonin (mean +/- SD, -0.89 +/- 0.40 h vs. -0.27 +/- 0.16 h) and CBT (-1.16 +/- 0.69 h vs. -0.44 +/- 0.27 h) rhythms than the control. Phase changes for the two circadian rhythms also positively correlated, indicating direct effects on the biological clock. In addition, the auditory stimulus significantly decreased fatigue compared with the control. This study is the first demonstration of an auditory stimulus phase-shifting circadian rhythms in humans, with shifts similar in size and direction to those of other nonphotic stimuli presented during the early subjective night. This novel stimulus may be a useful countermeasure to facilitate circadian adaptation after transmeridian travel or shift work.

Acoustic Stimulation↗