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At least 775 records · Page 43Linked to original sources
PubMed2000

CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression.

The onset of myocardial infarction occurs frequently in the early morning, and it may partly result from circadian variation of fibrinolytic activity. Plasminogen activator inhibitor-1 activity shows a circadian oscillation and may account for the morning onset of myocardial infarction. However, the molecular mechanisms regulating this circadian oscillation remain unknown. Recent evidence indicates that basic helix-loop-helix (bHLH)/PAS domain transcription factors play a crucial role in controlling the biological clock that controls circadian rhythm. We isolated a novel bHLH/PAS protein, cycle-like factor (CLIF) from human umbilical vein endothelial cells. CLIF shares high homology with Drosophila CYCLE, one of the essential transcriptional regulators of circadian rhythm. CLIF is expressed in endothelial cells and neurons in the brain, including the suprachiasmatic nucleus, the center of the circadian clock. In endothelial cells, CLIF forms a heterodimer with CLOCK and up-regulates the PAI-1 gene through E-box sites. Furthermore, Period2 and Cryptochrome1, whose expression show a circadian oscillation in peripheral tissues, inhibit the PAI-1 promoter activation by the CLOCK:CLIF heterodimer. These results suggest that CLIF regulates the circadian oscillation of PAI-1 gene expression in endothelial cells. In addition, the results potentially provide a molecular basis for the morning onset of myocardial infarction.

ARNTL Transcription Factors↗
PubMed2002

Extracellular superoxide dismutase is a major antioxidant in human fibroblasts and slows telomere shortening.

There is good evidence that telomere shortening acts as a biological clock in human fibroblasts, limiting the number of population doublings a culture can achieve. Oxidative stress also limits the growth potential of human cells, and recent data show that the effect of mild oxidative stress is mediated by a stress-related increased rate of telomere shortening. Thus, fibroblast strains have donor-specific antioxidant defense, telomere shortening rate, and growth potential. We used low-density gene expression array analysis of fibroblast strains with different antioxidant potentials and telomere shortening rates to identify gene products responsible for these differences. Extracellular superoxide dismutase was identified as the strongest candidate, a correlation that was confirmed by Northern blotting. Over-expression of this gene in human fibroblasts with low antioxidant capacity increased total cellular superoxide dismutase activity, decreased the intracellular peroxide content, slowed the telomere shortening rate, and elongated the life span of these cells under normoxia and hyperoxia. These results identify extracellular superoxide dismutase as an important antioxidant gene product in human fibroblasts, confirm the causal role of oxidative stress for telomere shortening, and strongly suggest that the senescence-like arrest under mild oxidative stress is telomere-driven.

Actins↗
PubMed2006

Tel2 is required for activation of the Mrc1-mediated replication checkpoint.

Proteins belonging to the Tel2/Rad-5/Clk-2 family are conserved among eukaryotes and are involved in various cellular processes, such as cell proliferation, telomere maintenance, the biological clock, and the DNA damage checkpoint. However, the molecular mechanisms underlying the functions of these molecules remain largely unclear. Here we report that in the fission yeast, Schizosaccharomyces pombe, Tel2 is required for efficient phosphorylation of Mrc1, a mediator of DNA replication checkpoint signaling, and for activation of Cds1, a replication checkpoint kinase, when DNA replication is blocked by hydroxyurea. In fact, Tel2 is required for survival of replication fork arrest and for the replication checkpoint in cells lacking Chk1, another checkpoint kinase the role of which overlaps that of Cds1 in cell cycle arrest by replication block. In addition, Tel2 plays important roles in entry into S phase and in genome stability. Tel2 is essential for vegetative cell growth, and the tel2Delta strain accumulated cells with 1C DNA content after germination. In the absence of hydroxyurea, Tel2 is vital in the mutant lacking Swi1, a component of the replication fork protection complex, and multiple Rad22 DNA repair foci were frequently observed in Tel2-repressed swi1Delta cells especially at S phase. In contrast, the cds1Deltaswi1Delta mutant did not show such lethality. These results indicate that S. pombe Tel2 plays important roles in the Mrc1-mediated replication checkpoint as well as in the Cds1-independent regulation of genome integrity.

Cell Cycle Proteins↗
PubMed1978

The photoperiodic effect of ahemeral light-dark cycles which entrain circadian rhythms.

1. A 27-h cycle of light and dark provides a greater gonadotrophic stimulus to the laying fowl, as judged by sexual maturity and rate of lay, than a 24-h cycle incorporating the same photoperiod. 2. An hypothesis put forward to account for these effects states that Effective Photoperiod equal p + c - b, where p = actual photoperiod, c = cycle length and b = the period of the endogenous biological clock. 3. Two experiments designed to test this hypothesis have yielded results which are consistent with it. 4. A poultryman who use an ahemeral cycle to alter egg weight or shell thickness and then whishes to transfer his flock back to a 24-h cycle should calculate the difference between the two cycle lengths and then add this quantity to the prevailing photoperiod to find the appropriate amount of light to be used in the 24-h cycle.

Animals↗
PubMedDate not supplied

Does the 'forbidden zone' for sleep onset influence morning shift sleep duration?

Shiftwork researchers have concentrated on the problems on the night shift, and have tended to neglect the truncation of sleep that can occur before morning, or 'early', shifts. We examined the sleep timing and duration between morning shifts of shiftworkers on a variety of shift systems. The extent of morning shift sleep truncation depended very largely on the time at which individuals had to leave home. Further, there was some suggestive evidence that the failure of individuals to compensate by going to sleep earlier was not simply due to social pressures to stay up. Rather it would appear to have depended, at least in part, on the biological clock determined 'forbidden zone' for sleep that occurs shortly before habitual sleep onset.

Adult↗
PubMed1983

How daylight affects reproduction in sheep.

Seasonal patterns of reproduction in New Zealand sheep flocks arise primarily from the annual changes in daily photoperiod. Sheep detect these changes in lighting by means of a built-in biological clock and this information is relayed to the hypothalamic-gonadal axis via the pineal gland. The current level of understanding of the mechanisms which are involved in these processes is briefly reviewed.

Journal Article↗
PubMed2006

Nutritional strategies for football: counteracting heat, cold, high altitude, and jet lag.

Environmental factors often influence the physical and mental performance of football players. Heat, cold, high altitude, and travel across time zones (i.e. leading to jet lag) act as stressors that alter normal physiological function, homeostasis, metabolism, and whole-body nutrient balance. Rather than accepting performance decrements as inevitable, well-informed coaches and players should plan strategies for training and competition that offset environmental challenges. Considering the strength of scientific evidence, this paper reviews recommendations regarding nutritional interventions that purportedly counterbalance dehydration, hyperthermia, hypothermia, hypoxia, acute or chronic substrate deficiencies, sleep loss, and desynchronization of internal biological clocks.

Altitude↗
PubMed2004

New data on the importance of gestational Mg deficiency.

Chronic primary Mg deficiency is frequent. About 20% of the population consumes less than two-thirds of the RDA for Mg. Women, particularly, have low intakes. For example, in France, 23% of women and 18% of men have inadequate intakes. Mg deficiency during pregnancy can induce maternal, fetal, and pediatric consequences that might last throughout life. Studies of gestational Mg deficiency in animals show that Mg deficiency may have marked effects on parturition and postuterine involution. It has interfered with fetal growth and development, and caused morbidity from hematological effects and disturbances in temperature regulation, to teratogenic effects. Emphasis, here, is on effects of chronic clinical gestational Mg deficiency as it affects the infant. Premature labor, contributed to by uterine hyperexcitability caused by chronic maternal Mg deficiency, that can be intensified by stress, gives rise to preterm birth. If the only cause of uterine overactivity is Mg deficiency, its supplementation constitutes nontoxic tocolytic treatment, as an adjuvant treatment, that is devoid of toxicity and enhances efficacy and safety of tocolytic drugs such as beta-2 mimetics. Evidence is considered that Mg deficiency or Mg depletion can contribute to the Sudden Infant Death Syndrome (SIDS). SIDS may be a fetal consequence of maternal Mg deficiency through impaired control of Brown Adipose Tissue (BAT) thermoregulation mechanisms leading to a modified temperature set point. SIDS can result from dysthermias: hypo- or hyperthermic forms. Possibly, simple nutritional Mg supplements might be preventive. Various stresses in an infant can transform simple Mg deficiency into Mg depletion. For example, lying prone can be stressful for the baby, as can parental smoking. The role of chronopathological stress appears to be often neglected, as it constitutes a clinical form of primary hypofunction of the biological clock [with its anatomical and clinical stigma such as reduced production of melatonin (MT) and of its urinary metabolite: 6 Sulfatoxy-Melatonin (6 SMT)]. SIDS might be linked to impaired maturation of both the photoneuroendocrine system and BAT. Prophylaxis of this form of SIDS should include atoxic nutritional Mg therapy for pregnant women with total light deprivation at night for the infant. Consequences of maternal primary Mg deficiency have been inadequately studied. To determine ultimate outcomes of gestational Mg deficiency in infants, a long-term multicenter placebo-controlled prospective study should undertaken on effects of maternal nutritional Mg supplementation on lethality/morbidity in fetus, neonates, infants, children and adults, not only during pregnancy and the baby's first year, but throughout life.

Adult↗
PubMed2006

Sleep biological rhythms in normal infants and those at high risk for SIDS.

The focus of this study was on daytime and nighttime sleep and wakefulness during the peak age for Sudden Infant Death Syndrome (SIDS), two to four months, to determine whether there are differences between at-risk for SIDS (R) and control (C) infants. Such differences may provide insight on the frequent occurrence of SIDS in the early morning hours, when most babies are asleep. This is the only study in which R and C infants were continuously monitored for long periods of time (24-48 h) and then followed and recorded at monthly intervals until the age of 4-6 months. Data analyses indicate that ultradian REM/NREM cyclicity becomes stabilized into a regular pattern at three months of age. Infants at this age convert from a polyphasic sleep/wakefulness pattern to a circadian one. Among the changes that occur is a lengthening of short sleep periods that consolidate at night and wake periods that consolidate in the daytime. The most striking effects are related to sleep state and vary according to age and sex. The lengthening of single sleep and wakeful periods is coupled with the maturation of the brain. The development of the central nervous system facilitates the synchronization of sleeping patterns with external light input and social entrainment. One or more biological clocks or oscillators may be responsible for these REM/NREM patterns and circadian cycles. These differences during the early morning hours, when the occurrence of SIDS peaks, may have important implications for understanding the pathophysiological mechanism of SIDS.

Circadian Rhythm↗
PubMed1999

Physical mapping of porcine seasonality genes.

Seasonal infertility in sows is a problem in the pig industry characterized by delayed onset of puberty in summer and decreased farrowing rate resulting from silent oestrus and aborted pregnancy. Summer infertility is thought to be influenced by heat, sunburn and stress. However, the strongest contributory factor is photoperiod. The difference in seasonality between wild boar and commercial pig breeds suggests that there may be a genetic component to this trait. The maps and associated molecular tools emerging from the pig genome project have created opportunities to examine the genetic component of seasonal infertility. We are identifying and mapping genes that are likely to be involved in biological clock mechanisms and the melatonin pathways as candidate seasonality genes.

Abortion, Veterinary↗
PubMed2000

Mitochondrial oxidative stress plays a key role in aging and apoptosis.

Harman first suggested in 1972 that mitochondria might be the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions. Later in 1980 Miquel and coworkers proposed the mitochondrial theory of cell aging. Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen radicals that exceed the cellular antioxidant defences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported between the rate of mitochondrial production of hydroperoxide and the maximum life span of species. An important change in mitochondrial lipid composition is the age-related decrease found in cardiolipin content. The concurrent enhancement of lipid peroxidation and oxidative modification of proteins in mitochondria further increases mutations and oxidative damage to mitochondrial DNA (mtDNA) in the aging process. The respiratory enzymes containing the defective mtDNA-encoded protein subunits may increase the production of reactive oxygen species, which in turn would aggravate the oxidative damage to mitochondria. Moreover, superoxide radicals produced during mitochondrial respiration react with nitric oxide inside mitochondria to yield damaging peroxynitrite. Treatment with certain antioxidants, such as sulphur-containing antioxidants, vitamins C and E, or the Ginkgo biloba extract EGb 761, protects against the age-associated oxidative damage to mtDNA and the oxidation of mitochondrial glutathione. Moreover, the EGb 761 extract also prevents changes in mitochondrial morphology and function associated with aging of the brain and liver.

Aging↗
PubMed2000

Effect of melatonin on sleep quality of COPD intensive care patients: a pilot study.

Sleep deprivation is extremely common in the intensive care unit (ICU), and this lack of sleep is associated with low melatonin secretion. The objective of the current study was to explore the effect of exogenous melatonin administration on sleep quality in patients hospitalized in the pulmonary intensive care unit (ICU). We performed a double-blind, placebo-controlled study in the pulmonary ICU of a tertiary care hospital. Eight adult patients hospitalized in the pulmonary ICU with respiratory failure caused by exacerbation of chronic obstructive pulmonary disease (COPD) or with pneumonia were studied. Patients received either 3 mg of controlled-release melatonin or a placebo at 22:00, and sleep quality was evaluated by wrist actigraphy. Treatment with controlled-release melatonin dramatically improved both the duration and quality of sleep in this group of patients. Our results suggest that melatonin administration to patients in intensive care units may be indicated as a treatment for sleep induction and resynchronization of the "biologic clock." This treatment may also help in the prevention of the "ICU syndrome" and accelerate the healing process.

Adult↗
PubMed2002

Circadian variation of nitric oxide synthase activity in mouse tissue.

Endogenous nitric oxide (NO) is an important mediator in the processes that control biological clocks and circadian rhythms. The present study was designed to elucidate if NO synthase (NOS) activity in the brain, kidney, testis, aorta, and lungs and plasma NOx levels in mice are controlled by an endogenous circadian pacemaker. Male BALB/c mice were exposed to two different lighting regimens of either light-dark 14:10 (LD) or continuous lighting (LL). At nine different equidistant time points (commencing at 09:00h) blood samples and tissues were taken from mice. The plasma and tissue homogenates were used to measure the levels of NO2 + NO3- (NOx) and total protein. The NOx concentrations were determined by a commercial nitric oxide synthase assay kit, and protein content was assessed in each homogenate tissue sample by the Lowry method. Nitric oxide synthase activity was calculated as pmol/mg protein/h. The resulting patterns were analyzed by the single cosinor method for pre-adjusted periods and by curve-fitting programs to elucidate compound rhythmicity. The NOS activity in kidneys of mice exposed to LD exhibited a circadian rhythm, but no rhythmicity was detected in mice exposed to LL. Aortic NOS activity displayed 24h rhythmicity only in LL. Brain, testis, and lung NOS activity and plasma NOx levels displayed 24h rhythms both in LD and LL. Acrophase values of NOS activity in brain, kidney, testis, and lungs were at midnight corresponding to their behavioral activities. Compound rhythms were also detected in many of the examined patterns. The findings suggest that NOS activity in mouse brain, aorta, lung, and testis are regulated by an endogenous clock, while in kidney the rhythm in NOS activity is synchronized by the exogenous signals.

Animals↗
PubMed2002

Right- and left-brain hemisphere. Rhythm in reaction time to light signals is task-load-dependent: age, gender, and handgrip strength rhythm comparisons.

In healthy mature subjects simple reaction time (SRT) to a single light signal (an easy task) is associated with a prominent rhythm with tau = 24 h of dominant (DH) as well as nondominant (NDH) hand performance, while three-choice reaction time (CRT), a complex task, is associated with tau = 24 h of the DH but tau < 24 h of the NDH. The aims of the study were to assess the influence of age and gender on the difference in tau of the NDH and DH, as it relates to the corresponding cortical hemisphere of the brain, in comparison to the rhythm in handgrip strength. Healthy subjects, 9 (5 M and 4 F) adolescents 10-16 yr of age and 15 (8 M and 7 F) adults 18-67 yr of age, active between 08:00 +/- 1 h and 23:00 +/- 1:30 h and free of alcohol, tobacco, and drug consumption volunteered. Data were gathered longitudinally at home and work 4-7 times daily for 11-20 d. At each test time the following variables were assessed: grip strength of both hands (Dynamometer: Colin-Gentile, Paris, France); single reaction time to a yellow signal (SRT); and CRT to randomized yellow, red, or green signal series with varying instruction from test to test (Psycholog-24: Biophyderm, France). Rhythms in the performance in SRT, CRT, and handgrip strength of both DH and NDH were explored. The sleep-wake rhythm was assessed by sleep-logs, and in a subset of 14 subjects it was also assessed by wrist actigraphy (Mini-Motionlogger: AMI, Ardsley NY). Exploration of the prominent period tau of time series was achieved by a special power spectra analysis for unequally spaced data. Cosinor analysis was used to quantify the rhythm amplitude A and rhythm-adjusted mean M of the power spectral analysis determined trial tau. A 24h sleep-wake rhythm was detected in almost all cases. In adults, a prominent tau of 24 h characterized the performance of the easy task by both the DH and NDH. In adults a prominent tau of 24 h was also detected in the complex CRT task performed by the DH, but for the NDH the tau was < 24 h. This phenomenon was not gender-related but was age-related since it was seldom observed in adolescent subjects. Hand-side differences in the grip strength rhythms in the same individuals were detected, the tau being ultradian rather than circadian in adolescent subjects while in mature subjects the tau frequently differed from that of the rhythm in CRT. These findings further support the hypothesis that functional biological clocks exist in both the left and right hemispheres of the human cortex.

Adolescent↗
PubMed1976

Hibernation and circannual rhythms of food consumption in marmots and ground squirrels.

In order to understand better the evolution and adaptive value of hibernation, ecological aspects and experimental studies of closely related hibernators, the Marmotini, are examined. The central hypothesis is that annual changes in the environment integrate three or, perhaps, four physiological processes: torpor, reporduction, consumption of food, and metabolism. Reproduction occurs promptly after emergence from hibernation. For most species, the breeding season is very short. Although the experimental data are rather meager, no variation in external factors has consistently altered the season of reproduction. Consumption of food and change in weight increases until July or September and then decreases. The large members of the Marmotini store their energy as fat, but small species store their energy as seeds and nuts. Experiments to test the hypothesis that some aspect of the supply, such as fat content, might vary seasonally have produced negative results. Complex experiments on the length of the photoperiod on woodchucks and several species of ground squirrels failed to alter the annual cycle of consumption of food. Animals kept in constant conditions showed a cycle of about 11 months, but woodchucks sent tto Australia changed their cycle in two years to match the seasons of the southern hemisphere. Experiments with temperature and torpor and castration did not alter the annual did not alter the rhythm...

Adipose Tissue↗
PubMedDate not supplied

The evolution of endothermy: role for membranes and molecular activity.

On the basis of the comparative approach and three models of metabolism (endothermic and ectothermic vertebrates, body mass, and mammalian development), we suggest that a few common cellular processes, linked either directly or indirectly to membranes, consume the majority of energy used by most organisms; that membranes act as pacemakers of metabolism through changes in lipid composition, altering membrane characteristics and the working environment of membrane proteins--specifically, that changes in the membrane environment similarly affect the molecular activities (specific rates of activity) of membrane-bound proteins; and that polyunsaturation of membranes increases whereas monounsaturation decreases the activity of membrane proteins. Experiments designed to test this theory using the sodium pump support this supposition. Potential mechanisms considered include fluidity, electrical fields, and related surface area requirements of lipids. In considering the evolution of endothermy in mammals, for example, if the first mammals were small, possibly nocturnal and active organisms, all these factors would favour increased polyunsaturation of membranes. Such changes (from monounsaturated to polyunsaturated membranes) would allow membranes to set the pace of metabolism in the evolution of endothermy.

Animals↗
PubMedDate not supplied

Biological rhythms, medication safety, and women's health.

Biological processes and functions in women are well organized in time, as evidenced by the expression of ultradian (high frequency), circadian ( approximately 24-hour), circamensual ( approximately monthly), and circannual ( approximately yearly) rhythms and by the changes that occur with menarche, reproduction, and menopause. Attributes of women's circamensual structure have been explored in depth, particularly with regard to fertility/infertility and birth control. However, the role of 24-hour and other rhythms in health, disease, and treatment has been little studied. The symptom intensity of a variety of chronic medical conditions is rhythmic, as is the risk of severe events, such as stroke and myocardial infarct (MI). Improving the safety, efficacy, and preventive qualities of medications requires the understanding of how rhythms impact drug pharmacokinetics and pharmacodynamics. The therapeutic and adverse effects of prescription and nonprescription medications widely used by women can vary markedly with the (circadian) time of administration. Circadian rhythm-dependent differences in the safety of medications are particularly relevant to pregnant women; laboratory animal studies show that the fetal toxicity of various treatments varies not only with developmental stage but also with circadian time. Rhythm-dependent differences in the actions of medications are also of great importance to perimenopausal and postmenopausal women, who are advised to ingest prescribed pharmacotherapy for osteopenia and osteoporosis in the morning to minimize the risk of adverse effects and, as a consequence, may elect to take other medications at times not recommended in the instructions for their use. Medication trials must be comprehensive and representative of women and men of different life stages, ethnicities, and likely times (morning vs. evening) of drug use.

Attitude to Health↗