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At least 793 records · Page 44Linked to original sources
PubMed2001

Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome.

Recent progress in biological clock research has facilitated genetic analysis of circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24). We analyzed the human period3 (hPer3) gene, one of the human homologs of the Drosophila clock-gene period (Per), as a possible candidate for rhythm disorder susceptibility. All of the coding exons in the hPer3 gene were screened for polymorphisms by a PCR-based strategy using genomic DNA samples from sleep disorder patients and control subjects. We identified six sequence variations with amino acid changes, of which five were common and predicted four haplotypes of the hPer3 gene. One of the haplotypes was significantly associated with DSPS (Bonferroni's corrected P = 0.037; odds ratio = 7.79; 95% CI 1.59-38.3) in our study population. Our results suggest that structural polymorphisms in the hPer3 gene may be implicated in the pathogenesis of DSPS.

Adolescent↗
PubMed1997

Multiple circadian-regulated elements contribute to cycling period gene expression in Drosophila.

A new regulatory element necessary for the correct temporal expression of the period (per) gene was identified by monitoring real-time per expression in living individual flies carrying two different period-luciferase transgenes. luciferase RNA driven from only the per promoter was not sufficient to replicate the normal pattern of per RNA cycling; however, a per-luc fusion RNA driven from a transgene containing additional per sequences cycled identically to endogenous per. The results indicate the existence of at least two circadian-regulated elements--one within the promoter and one within the transcribed portion of the per gene. Phase and amplitude analysis of both per-luc transgenes revealed that normal per expression requires the regulation of these elements at distinct phases and suggests a mechanism by which biological clocks sustain high-amplitude feedback oscillations.

Animals↗
PubMed1994

Dosage compensation of the period gene in Drosophila melanogaster.

The period (per) gene is located on the X chromosome of Drosophila melanogaster. Its expression influences biological clocks in this fruit fly, including the one that subserves circadian rhythms of locomotor activity. Like most X-linked genes in Drosophila, per is under the regulatory control of gene dosage compensation. In this study, we assessed the activity of altered or augmented per+ DNA fragments in transformants. Relative expression levels in male and female adults were inferred from periodicities associated with locomotor behavioral rhythms, and by histochemically assessing beta-galactosidase levels in transgenics carrying different kinds of per-lacZ fusion genes. The results suggest that per contains multipartite regulatory information for dosage compensation within the large first intron and also within the 3' half of this genetic locus.

Animals↗
PubMed1996

A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans.

A variety of mechanisms have been proposed to explain the extension of adult life span (Age) seen in several mutants in Caenorhabditis elegans (age-1: an altered aging rate; daf-2 and daf-23: activation of a dauer-specific longevity program; spe-26: reduced fertility; clk-1: an altered biological clock). Using an assay for ultraviolet (UV) resistance in young adult hermaphrodites (survival after UV irradiation), we observed that all these Age mutants show increased resistance to UV. Moreover, mutations in daf-16 suppressed the UV resistance as well as the increased longevity of all the Age mutants. In contrast to the multiple mechanisms initially proposed, these results suggest that a single, daf-16-dependent pathway, specifies both extended life span and increased UV resistance. The mutations in daf-16 did not alter the reduced fertility of spe-26 and interestingly a daf-16 mutant is more fertile than wild type. We propose that life span and some aspects of stress resistance are jointly negatively regulated by a set of gerontogenes (genes whose alteration causes life extension) in C. elegans.

Animals↗
PubMed1997

Prospective study of the determinants of age at menopause.

The authors prospectively studied the effect of demographic, reproductive, stress-related, and health behavior factors measured at study entry on age of natural menopause in 185 healthy US women. At study entry, women were 42.5-47.5 years old and premenopausal. After a baseline examination (1983-1985), women were followed for 7-9 years, during which time they reported on a monthly basis their menstrual status and whether they were taking hormones. Menopausal age was defined as age at the last menstrual period prior to stopping menstruation for 12 months (and not taking hormones). Estimated median age at menopause was 51.5 years for the whole sample. Median age at menopause was earlier for women who reported irregular menstrual cycles at study entry (50.2 years), were African-American (49.3 years), were smokers (50.6 years), or were currently on a weight reduction diet (50.5 years). Psychosocial stress was predictive of an even earlier median age at menopause in African Americans (48.4 years) and in those with irregular cycles at baseline (49.4 years). Results suggest that premenopausal women in their forties who are experiencing irregular menstrual cycles, are smokers, are dieting, or are African-American are likely to reach menopause earlier than their contemporaries. African-American women may have a different "biological clock" than white women, especially when under stress, or they may experience more stress of longer duration.

Adult↗
PubMed1994

A cytosolic sperm factor triggers calcium oscillations and membrane hyperpolarizations in human oocytes.

Intracellular free Ca2+ concentrations ([Ca2+]i) and membrane potentials were measured in mature human oocytes. Injection of cytosolic extracts made from human or hamster spermatozoa triggered oscillations in [Ca2+]i in human oocytes similar to those described previously in mouse and hamster oocytes. In contrast, injection of carrier buffer caused no [Ca2+]i increase and injection of Ca(2+)-containing solutions caused only a single [Ca2+]i transient. Injection of human sperm extracts also triggered [Ca2+]i oscillations in mature mouse oocytes. The [Ca2+]i oscillations in human oocytes were accompanied by hyperpolarizations in membrane potential. Perfusing oocytes with the sulphydryl reagent thimerosal also caused oscillations in the free [Ca2+]i concentration simultaneously with membrane potential hyperpolarizations. These data suggest that human oocytes possess a similar mechanism for generating [Ca2+]i oscillations to those described in other mammalian oocytes and a membrane potential response similar to that seen previously specifically in hamster oocytes. The data also support the view that human oocytes are activated at fertilization by diffusion of a protein from the spermatozoa into the ooplasm after gamete membrane fusion.

Animals↗
PubMed2001

Light response of the circadian waves of the APRR1/TOC1 quintet: when does the quintet start singing rhythmically in Arabidopsis?

We previously identified a novel class of proteins, named A:rabidopsis pseudo-response regulators (APRRs), each of which (APRR1/TOC1, APRR3, APRR5, APRR7, APRR9) has an intriguing structural design containing an N-terminal pseudo-receiver domain and a C-terminal CONSTANS motif. Expression of these APRR1/TOC1 family members is under the control of a coordinate circadian rhythm at the level of transcription such that the APRR-mRNAs start accumulating sequentially after dawn with 2 to 3 h intervals in the order of APRR9-->APRR7-->APRR5-->APRR3-->APRR1/TOC1 in a given 24 h photo-period. Based on these data, we previously proposed that these sequential and rhythmic events of transcription, termed 'circadian waves of APRR1/TOC1 quintet', may be a basis of a presumed Arabidopsis biological clock (named 'bar code clock') [Matsushika et al. (2000) Plant and Cell Physiol. 41: 1002]. Here we further characterized the event of circadian waves, by demonstrating that certain light stimuli are crucial determinants to induce the robust circadian waves, and accordingly, the first-boosted and light-induced APRR9 appears to be primarily responsible for this light response of the circadian waves. Also, as such a light stimulus, a red light pulse that is presumably perceived by phytochromes appears to be sufficient to induce (or synchronize) the APRR1/TOC1 circadian waves.

Arabidopsis↗
PubMed2003

A Link between circadian-controlled bHLH factors and the APRR1/TOC1 quintet in Arabidopsis thaliana.

APRR1 (ARABIDPSIS PSUEDO-RESPONSE REGULATOR 1) (or TOC1, TIMING OF CAB EXPRESSION 1) is believed to be a crucial component of biological clocks of Arabidopsis thaliana. Nevertheless, its molecular function remains to be fully elucidated. Based on the results of yeast two-hybrid and in vitro binding assays, we previously showed that APRR1/TOC1 interacts with certain bHLH factors (i.e. PIF3 and PIL1, which are PHYTOCHROME INTERACTING FACTOR 3 and its homolog (PIF3-LIKE 1), respectively). To critically examine the relevance of PIL1 with reference to the function of APRR1/TOC1, T-DNA insertion mutants were isolated for PIL1. No phenotype was observed for such homozygous pil1 mutants, in terms of circadian-associated events in plants. We then examined more extensively a certain set of bHLH factors, which are considerably similar to PIL1 in their structural designs. The results of extensive analyses of such bHLH factors (namely, HFR1, PIL2, PIF4, PIL5 and PIL6) in wild-type and APRR1-overexressing (APRR1-ox) transgenic lines provided us with several new insights into a link between APRR1/TOC1 and these bHLH factors. In yeast two-hybrid assays, APRR1/TOC1 showed the ability to interact with these proteins (except for HFR1), as well as PIL1 and PIF3. Among them, it was found that the expressions of PIF4 and PIL6 were regulated in a circadian-dependent manner, exhibiting free-running robust rhythms. The expressions of PIF4 and PIL6 were regulated also by light in a manner that their transcripts were rapidly accumulated upon exposure of etiolated seedlings to light. The light-induced expressions of PIF4 and PIL6 were severely impaired in APRR1-ox transgenic lines. Taken together, here we propose the novel view that these bHLH factors (PIF4 and PIL6) might play roles, in concert with APRR1/TOC1, in the integration of light-signals to control both circadian and photomorphogenic processes.

Arabidopsis↗
PubMed1987

Four congenitally blind children with circadian sleep-wake rhythm disorder.

Four congenitally blind children aged 4-12 years, with severe or moderate mental retardation, were chronobiologically studied. Three of them showed a free-running rhythm of sleep-wake, and the fourth showed an irregular sleep-wake rhythm. To entrain their sleep-wake rhythm to a 24-h rhythm, several trials based on chronotherapy were performed. The free-running rhythms in the three children were considered their own endogenous rhythms, revealed through some disorder in the mechanism synchronizing the endogenous rhythm to the normal 24-h environmental rhythm. The irregular sleep-wake rhythm in the fourth child may have been the result of immaturity or failure of the pacemaker of the circadian rhythm. Because of their severe mental retardation, all the children were lacking in social time cues, which are the most potent "Zeitgebers" for human biological clocks.

Blindness↗
PubMed1998

Expression of an oscillating interferon-gamma receptor in the suprachiasmatic nuclei.

The suprachiasmatic nuclei serve as the dominant circadian pacemaker in the mammalian brain, regulating daily behavioral, physiological and hormonal rhythms. In the ventrolateral parts of these nuclei, the receptor for the key immunoregulatory molecule interferon-gamma (IFN-gamma) was detected in the rat brain. The cellular localization of the IFN-gamma receptor corresponded to neuronal elements. Expression of the receptor followed a diurnal rhythm with a peak at zeitgeber time 15. This peak coincided with an enhanced expression of janus kinase 1 and 2 as well as the signal transducer and activator of transcription 1, which constitute the main intracellular signaling pathway of IFN-gamma. This is the first study to show expression of the receptor of an immune modulatory molecule in the pacemaker of the biological clock, which, thus, may be influenced by immune system signal molecules.

Animals↗
PubMed2000

Serotonin depletion decreases light induced c-fos in the rat suprachiasmatic nucleus.

The suprachiasmatic nucleus (SCN) is the locus of the biological clock in mammals. Daily light cycles entrain the endogenous circadian rhythms in mammals through direct and indirect neural pathways from the retinae to the suprachiasmatic nucleus. We have studied the effect of serotonin depletion on the photic induction of the early response gene c-fas in the SCN of rats. Serotonin depletion, verified by immunohistochemistry, produced a significant decrease (42%) in the number of c-FOS positive cells in the ventrolateral portion of the SCN. These results support the involvement of serotonin as a mediator of photic information to the SCN through the retinal projection to the dorsal raphe nucleus.

Animals↗
PubMed2003

Circadian and photic regulation of ERK, JNK and p38 in the hamster SCN.

Circadian rhythms are entrained by light-activated signal transduction pathways in the biological clock. Among these, circadian and photic control of mouse suprachiasmatic ERK MAP kinase activation has been reported. In this paper we extend these results to hamsters and to the two other major members of the MAPK family: JNK and p38. The three kinases are rhythmically phosphorylated under light-dark and constant conditions, with maximal values during the day or subjective day. Light pulses during the subjective night induce rapid activation of the three enzymes, suggesting that the three MAP kinases might be implicated in mammalian photic entrainment.

Animals↗
PubMed1998

Transcutaneous electrical nerve stimulation (TENS) improves circadian rhythm disturbances in Alzheimer disease.

In patients with Alzheimer disease (AD), an irregular day-night rhythm with behavioral restlessness during the night makes a strong demand on caregivers and is among the most important reasons for institutionalization. A dysfunctioning circadian timing system is supposed to underlie the disturbance or at least to contribute to it. The disturbance improves with increased environmental light, which, through the retinohypothalamic tract, activates the suprachiasmatic nucleus (SCN), the biological clock of the brain. Because recent studies have indicated both direct and indirect spinal projections to the SCN, we investigated whether excitation of spinal neurons by means of transcutaneous electrical nerve stimulation (TENS) could also improve circadian rhythm disturbances in AD patients. The actigraphically obtained rest-activity rhythm of 14 AD patients showed an improvement in its coupling to Zeitgeber after TENS treatment but not after placebo treatment.

Afferent Pathways↗
PubMed1993

Sleep-wake cycle in human African trypanosomiasis.

Sleeping sickness patients are classically described as sleepy by day and restless by night. Prior to this study, we had objectively confirmed this description by recording 24-h sleep patterns in a patient with human African trypanosomiasis. We report 24-h polysomnographic recordings (EEG, electrooculogram, electromyogram, electrocardiogram, and nasal, buccal, and thoracic respiratory traces) performed on two eight-channel electroencephalographs in eight patients with untreated sleeping sickness at an early stage of meningoencephalitis. As in our previously reported patient, there was no hypersomnia. The patients presented mainly a disorganization of the circadian alternation of sleeping and waking, with no or little alteration in the states of vigilance at this early stage of the disease. The disorganization was proportional to the degree of severity of the clinical symptoms. It may be due to an alteration in biological clock mechanisms.

Adolescent↗
PubMed2004

Directed molecular transport in an oscillating symmetric channel.

A mechanism responsible for the directed transport and molecular separation in a symmetric channel is proposed. We found that under the action of spatial harmonic oscillations of the channel, the system exhibits a directed transport in either direction, presenting multiple current reversals as the amplitude and/or frequency of the oscillations are varied. The particles of different masses may be forced to move with different velocities in the same or in the opposite directions by properly adjusting driving parameters. The directed transport can be produced in both directions even in the absence of thermal noise; the latter can speed up or slow down the transport depending on the system parameters.

Biological Clocks↗
PubMed2004

Phase transition and selection in a four-species cyclic predator-prey model.

We study a four-species ecological system with cyclic dominance whose individuals are distributed on a square lattice. Randomly chosen individuals migrate to one of the neighboring sites if it is empty or invade this site if occupied by their prey. The cyclic dominance maintains the coexistence of all four species if the concentration of vacant sites is lower than a threshold value. Above the threshold, a symmetry breaking ordering occurs via growing domains containing only two neutral species inside. These two neutral species can protect each other from the external invaders (predators) and extend their common territory. According to our Monte Carlo simulations the observed phase transition seems to be equivalent to those found in spreading models with two equivalent absorbing states although the present model has continuous sets of absorbing states with different portions of the two neutral species. The selection mechanism yielding symmetric phases is related to the domain growth process with wide boundaries where the four species coexist.

Animals↗
PubMed2004

Spreading of families in cyclic predator-prey models.

We study the spreading of families in two-dimensional multispecies predator-prey systems, in which species cyclically dominate each other. In each time step randomly chosen individuals invade one of the nearest sites of the square lattice eliminating their prey. Initially all individuals get a family name which will be carried on by their descendants. Monte Carlo simulations show that the systems with several species (N=3,4,5) are asymptotically approaching the behavior of the voter model, i.e., the survival probability of families, the mean size of families, and the mean-square distance of descendants from their ancestor exhibits the same scaling behavior. The scaling behavior of the survival probability of families has a logarithmic correction. In case of the voter model this correction depends on the number of species, while cyclic predator-prey models behave like the voter model with infinite species. It is found that changing the rates of invasions does not change this asymptotic behavior. As an application a three-species system with a fourth-species intruder is also discussed.

Animals↗
PubMed2004

Transitions and transport for a spatially periodic stochastic system with locally coupled oscillators.

In this paper, with a special model, we investigate the spatially periodic stochastic system with locally coupled oscillators subject to a constant force F. A nonequilibrium second-order phase transition is found when F=0. This phase transition is reentrant when the additive noise is weak. With varying the constant force F, a continuous or discontinuous transition between the states with positive and negative mean fields (mu>0 and mu<0) is observed, which is not a phase transition. The mean field or current sometimes exhibits hysteresis as a function of F. With the variation of the force F, when hysteresis of the mean field or current versus F appears, a nonzero probability current with definite direction will occur at the point F=0. The correlation between the additive and multiplicative noises has an effect on the transitions and the transport.

Animals↗