Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CLOCK”

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 631 records · Page 35Linked to original sources
PubMed2002

The circadian gene Clock is required for the correct early expression of the head specific gene Otx2.

The circadian cycle is a universal molecular mechanism for imposing cyclical control on cellular processes. Here we have examined the role of one of the crucial circadian genes, Clock, in early Xenopus development. We show that a dominant negative version of Clock can block the function of the endogenous Clock gene. Doing so during early development reduces Otx2 expression in a highly specific manner and results in anterior defects. Together with previous work (Green et al. (2001) Mech. Dev. 105-110), these results suggest that a positive regulatory loop exists between Clock and Otx2.

Animals↗
PubMed2003

Intrinsic role of polysialylated neural cell adhesion molecule in photic phase resetting of the Mammalian circadian clock.

The suprachiasmatic nuclei (SCN), the location of the mammalian circadian clock, are one of the few adult brain regions that express the highly polysialylated form of neural cell adhesion molecule (PSA-NCAM). A role for the polysialic acid (PSA) component of PSA-NCAM, which is known to promote tissue plasticity, has been reported for photic entrainment of circadian rhythmicity in vivo. The in vivo results, however, do not discriminate between PSA acting upstream or downstream of the glutamatergic synapses that convey photic information to the SCN. To address this key issue, we exploited an in vitro rat brain slice preparation that retains robust circadian function. As in the intact SCN, PSA levels in the isolated SCN are rhythmic, with higher levels during the early subjective day and lower levels during subjective night. Importantly, bath application of glutamate to SCN slices rapidly and transiently increases PSA levels during both the subjective day and night. Pretreating the slices with endoneuraminidase, which selectively removes PSA from NCAM and thereby prevents this increase, abolishes glutamate- and optic chiasm stimulation-induced phase delays of the SCN circadian neuronal activity rhythm. These results support the hypothesis that PSA expression in the SCN is controlled by both the circadian clock and photic input to the clock and that expression of PSA in the SCN is critical for photic-like phase shifts of the clock. Together, these results establish that such actions of PSA are manifested downstream from presynaptic retinohypothalamic terminals and therefore are intrinsic to the SCN itself.

Animals↗
PubMed2003

[Research advances on mammalian circadian clock-related genes].

Circadian rhythms,generated by endogenous biological clocks,regulate physiological activities autonomously. It is one of the focuses in life science in recent years. The researches on the mechanism of mammalian circadian clock have been developed at the molecular level. Some clock-related genes are cloned and identified in succession. The core mechanism for the master circadian clock consists of interaction between the positive and negative transcription and translation feedback loops. The peripheral tissues cultured in vitro exhibit circadian rhythms as well. These give clues to further research.

Animals↗
PubMed2006

Circadian expression of clock genes in the rat eye and brain.

The light sensing system in the eye directly affects the circadian oscillator in the mammalian suprachiasmatic nucleus (SCN). To investigate this relationship in the rat, we examined the circadian expression of clock genes in the SCN and eye tissue during a 24 h day/night cycle. In the SCN, rPer1 and rPer2 mRNAs were expressed in a clear circadian rhythm like rCry1 and rCry2 mRNAs, whereas the level of BMAL1 and CLOCK mRNAs decreased during the day and increased during the night with a relatively low amplitude. It seems that the clock genes of the SCN may function in response to a master clock oscillation in the rat. In the eye, the rCry1 and rCry2 were expressed in a circadian rhythm with an increase during subjective day and a decrease during subjective night. However, the expression of Opn4 mRNA did not exhibit a clear circadian pattern, although its expression was higher in daytime than at night. This suggests that cryptochromes located in the eye, rather than melanopsin, are the major photoreceptive system for synchronizing the circadian rhythm of the SCN in the rat.

Animals↗
PubMed1995

[Role of biological clock in human pathology].

Most of the vegetative, hormonal and behavioural functions of the human organism operate under the biological control of a circadian clock which responds to environmental and social stimuli, synchronizing the organism's physiology to daily and seasonal rhythms. The underlying anatomic structures are located in the suprachiasmatic nucleus and the pineal gland. Although the precise physiologic mechanisms involved are still under study, melatonin is known to play a major role. Normal function of the circadian clock is disrupted in jet-lag, night-shift work, and blindness as well as in rare cases of lesions to the pineal gland leading to a shift in biological rhythms including hormone secretion and control of body temperature, for example. Several signs of impaired function have been identified: various types of sleep disorders, memory and concentration impairment, dysphoria, asthenia, irritability. Seasonal recurrence of such signs and frequent depressive complications are also suggestive of a disorder in the circadian clock. Knowledge of specific clinical signs and biological parameters will undoubtedly lead to the discovery of other disease states dependant on the circadian clock and to the development of therapeutic strategies capable of regulating the organism's chronobiology.

Biological Clocks↗
PubMed1997

A comparison of the clock drawing test and the Pfeiffer Short Portable Mental Status Questionnaire in a geropsychiatry clinic.

Wolf-Klein and colleagues' clock drawing test (CDT) performance was compared with Pfeiffer's Short Portable Mental Status Questionnaire (Pfeiffer) scores in 145 outpatient geropsychiatry patients. Although normal CDT results were almost always associated with normal Pfeiffer scores, 21% of Pfeiffer normal individuals drew abnormal clocks. Age, but not gender or education, was significantly associated with this finding. Almost all the Pfeiffer normal subjects who drew abnormal clocks were diagnosed with primary psychiatric disorders (85%) or neurologically based organic mood and anxiety disorders (12%); only one (3%) had dementia. We suggest the discrepant performance between the CDT and Pfeiffer may result from psychiatric illness. Contributing to this may be CDT sensitivity to executive skills dysfunction. This dyscontrol can occur in patients with dementia and other neurological disorders, but also presents in some primary mental disorders. Older age may heighten this impairment. In a typical geropsychiatry clinic, the CDT will not have high specificity for Alzheimer's disease as reported by Wolf-Klein and her colleagues. This results from the presence of many patients with primary psychopathology, some of whom will draw abnormal clocks, and a limited number with dementia-particularly Alzheimer's disease. Abnormal CDT results of geropsychiatry outpatients must therefore be interpreted carefully. Additional conclusions regarding the study results are discussed.

Aged↗
PubMed2000

Genetic polymorphism at the CLOCK gene locus and major depression.

Genetic analysis in both mouse and Drosophila has indicated that the product of the CLOCK gene is an essential component of a circadian rhythm timing system. A single nucleotide polymorphism (SNP), T3111C, in the 3' flanking region of the human CLOCK gene has been identified. Homozygotes or heterozygotes for the 3111C allele have been reported to have higher mean scores on a measure of evening preference for activity (vs. morning preference) than subjects homozygous for the 3111T allele. Since major depression is hypothesized to be closely linked to circadian rhythms, we explored whether this polymorphism might be related to susceptibility to major depression. We also ascertained allele frequency in an African-American control population, to begin to evaluate population variation at this locus. CLOCK T3111C allele frequencies were determined in 280 European American (EA) subjects, 143 with a history of major depression and 137 screened controls, and in 58 African American (AA) screened control subjects, using a polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) method. There was no significant difference between EA depressed and control subjects in allele frequency. There was a significant difference in allele frequency between EA and AA subjects, demonstrating a potential for population stratification. In none of these groups were significant deviations from Hardy-Weinberg equilibrium found. The present data do not support an association between CLOCK gene alleles at the T3111C locus and major depression.

Alleles↗
PubMed2000

Comparison of a clock drawing test in elderly schizophrenia and Alzheimer's disease patients: a preliminary study.

The objective of this study was to compare between the quantitative and qualitative aspects of a clock drawing test in elderly schizophrenic and Alzheimer's disease (AD) patients. Three independent raters performed a retrospective analysis of the clock drawing item from the Cambridge Cognitive Examination (CAMCOG), in long-term open wards of a public psychiatric hospital and an outpatient psychogeriatric clinic. The study group comprised 21 elderly schizophrenic patients ('graduates') and 21 AD patients matched for gender and education, and cognitive impairment confirmed by a Folstein mini-mental state examination (MMSE) score of 18-23. The Clock Drawing Interpretation Scale (CDIS) was the measure used. Schizophrenic patients were significantly younger than AD patients (63.5 versus 81.3 years, p<0.0001), however, similar concerning gender, education, MMSE and CAMCOG scores. CDIS scores were not correlated with age in eight group. Inter-rater reliability was high (range 0.84-0.97). No significant differences between patient groups were found in mean CDIS total scores. A CDIS specific item analysis revealed that schizophrenic patients were significantly less impaired than AD patients on three out of 20 items: Number 7 (most symbols are aligned in a clockwise or a rightward direction). Number 8 (all symbols are totally within a closure figure), and Number 13 (numbers do not go beyond 12). Although schizophrenic patients and AD patients had similar total scores on the clock drawing test, they differed on specific test items related to spatial/planning deficit and preservation.

Aged↗
PubMed1995

Interaction between the circadian clocks of mother and fetus.

In mammals, a unidirectional communication exists between the biological clocks of the mother and fetus. As a biological clock begins oscillating in the suprachiasmatic nuclei of the fetus, redundant circadian signals entrain the fetal clock to the prevailing light-dark cycle. Recent studies have revealed an activatable dopamine system within the fetal hypothalamus which may serve as a final common pathway by which maternal signals entrain the fetus. An entrained biological clock during fetal life makes the developing mammal better prepared for life in the outside world.

Animals↗
PubMed2002

Ten-Point Clock Test: a correlation analysis with other neuropsychological tests in dementia.

BACKGROUND: Neuropsychology can be useful for differentiating patients with fronto-temporal dementia (FTD) from those with Alzheimer disease (AD) and those with Vascular Dementia (VaD). OBJECTIVES: The purpose of this study was twofold: to explore possible employment of the Ten-Point Clock Test in early identification of different types of cognitive distribution and to relate to its execution to other specific impairment, bound to the selected pathology. METHOD: We compared 30 patients with FLD, to a group of 30 probable-AD patients accordingly to the NINCDS-ADRDA criteria, and to a group of 30 probable VaD patients, according to the NINDS-AIREN criteria. RESULTS: AD group showed the worst results in Clock Drawing Test. On the contrary, FLD group did produce the worst performances in Proverb Interpretation Tasks. VaD worst performance was that of phonological fluency. Our data seem to demonstrate that in mild dementia, stated by the MMSE score (around 22) and confirmed by the data derived from the other neuropsychological evaluation, the Clock Drawing Test is quite sensitive to detect cognitive impairment, even if of different origins. CONCLUSIONS: Ten-Point Clock Test is a strong tool, in order to identify early forms of Alzheimer, and to help differential diagnosis when frontal or vascular dementia have been taken into account. More data will be necessary to give to this speculative interpretation, a neuroimaging and neuroanatomical support. However, this report may encourage the wider use of this parametric test, easily applicable and well accepted by the population in order to implement data concerning cognitive disruption.

Aged↗
PubMed2002

Can clock drawing test help to differentiate between dementia of the Alzheimer's type and vascular dementia? A preliminary study.

OBJECTIVES: the purpose of this preliminary study was to determine if clock drawing performance may help to differentiate between dementia of the Alzheimer's type (DAT) and vascular dementia (VD) patients. METHODS: eighty-eight community-dwelling outpatients were comprehensively evaluated and met DSM-IV criteria for DAT or VD. Cognitive evaluation included the Mini-Mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG). CAMCOG derived clock drawings were blindly evaluated by the same investigator, according to Freedman's method for clock drawing, and a total score as well as subscores (contour, numbers, hands and center) were determined. RESULTS: There were no significant differences between DAT and VD patients in terms of demographic (age, gender, education) and cognitive (MMSE score, CAMCOG score) characteristics. On the average, the VD group showed slightly poorer performance on each of the clock drawing test (CDT) measures studied. With application of the Bonferroni correction, only Freedman's total score and hands subscore were statistically different between groups (p<0.003, p<0.004, respectively). Stepwise logistic regression analyses showed that the only significant variable was Freedman's total score (B=-0.273, p=0.005). Stepwise discriminant analysis identified Freedman's total score as the only significant predictor of diagnosis (Wilkes' lambda=0.903, p=0.003). This model correctly classified 65.9% overall into the respective DAT and VD groups. CONCLUSIONS: CDT scored according to a comprehensive technique may be of value in differentiating DAT from VD patients. We hypothesize that the classificatory ability of Freedman's method might be attributed to its presumed sensitivity to impaired executive functioning which is more pronounced in VD compared with DAT patients.

Aged↗
PubMed1998

Modelling migration: the clock-and-compass model can explain the distribution of ringing recoveries.

The aim of the present study was to test whether the directional distributions found in ringing recoveries could be explained if night-migrating passerines use only a simple clock-and-compass strategy during autumn migration. I developed a mathematical model that predicts the expected directional distributions as a function of distance covered by birds using a clock-and-compass strategy. The predictions were compared with data from natural migration: all ringing recoveries of pied flycatchers, Ficedula hypoleuca, ringed in Scandinavia and recovered elsewhere in Europe and North Africa within the same autumn. The predictions of the model correlated strongly with the distribution of ringing recoveries. This suggests that at least young pied flycatchers, and perhaps night-migrating passerines in general, use a simple clock-and-compass strategy to reach their wintering area. If so, all the prerequisites (a compass and an internal clock) that they need to orient during migration seem to be known at present, at least at the behavioural level, and navigational abilities or any elusive map-sense are not needed for migration. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1994

Control of lhc gene transcription by the circadian clock in Chlamydomonas reinhardtii.

Transcription of nuclear lhc genes has been shown to be under circadian clock control in angiosperms. but many aspects of this regulation have not been elucidated. Unicellular organisms, such as the green alga Chlamydomonas reinhardtii, offer significant advantages for the study of cellular clocks. Therefore, we have asked whether lhc gene expression is regulated by a circadian clock in C. reinhardtii. The mRNA for a photosystem I chlorophyll a/b apoprotein showed a strong diurnal rhythm in cells growing under 12 h/12 h light/dark (LD) cycles; the mRNA accumulated and then declined during the light period reaching very low levels at mid-dark. A similar diurnal pattern was documented for rbcS mRNA. In LD-grown cells shifted to continuous light, the ca. 24 h rhythm of lhca1 mRNA continued for at least 2 cycles. In LD-grown cells shifted to continuous darkness the rhythm of lhca1, but not rbcS2, mRNA also continued, although at lower absolute levels than in LD-grown cells. Also, in the cells shifted to continuous dark, the lhca1 mRNA rhythm persisted in the absence of significant cell division. Pulse-labelling with 32PO4 and sensitivity to actinomycin D demonstrated that control of lhca1 (and rbcS) is mainly transcriptional. However, it was also shown that the half-life of lhca1 mRNA (and rbcS2) is short (1-2 h) and may also vary somewhat during a cycle. We conclude that a cellular, circadian clock regulates lhca1 transcription in C. reinhardtii.

Animals↗
PubMed1985

Dating of the human-ape splitting by a molecular clock of mitochondrial DNA.

A new statistical method for estimating divergence dates of species from DNA sequence data by a molecular clock approach is developed. This method takes into account effectively the information contained in a set of DNA sequence data. The molecular clock of mitochondrial DNA (mtDNA) was calibrated by setting the date of divergence between primates and ungulates at the Cretaceous-Tertiary boundary (65 million years ago), when the extinction of dinosaurs occurred. A generalized least-squares method was applied in fitting a model to mtDNA sequence data, and the clock gave dates of 92.3 +/- 11.7, 13.3 +/- 1.5, 10.9 +/- 1.2, 3.7 +/- 0.6, and 2.7 +/- 0.6 million years ago (where the second of each pair of numbers is the standard deviation) for the separation of mouse, gibbon, orangutan, gorilla, and chimpanzee, respectively, from the line leading to humans. Although there is some uncertainty in the clock, this dating may pose a problem for the widely believed hypothesis that the pipedal creature Australopithecus afarensis, which lived some 3.7 million years ago at Laetoli in Tanzania and at Hadar in Ethiopia, was ancestral to man and evolved after the human-ape splitting. Another likelier possibility is that mtDNA was transferred through hybridization between a proto-human and a proto-chimpanzee after the former had developed bipedalism.

Animals↗
PubMed2002

[Corneal neural paralysis after block excision including the 3 and 9 o'clock meridian].

PURPOSE: Corneal innervation is mainly supported by the long posterior ciliary nerves. Anatomically, the long ciliary nerves run with the long ciliary arteries at 3 and 9 o'clock. The aim of this retrospective study was to find out if block excision of anterior uveal tumors or epithelial ingrowth located at the 3 or 9 o'clock position of the limbal circumference causes corneal neuroparalysis. PATIENTS AND METHODS: Between 1980 and May 1999, a total of 151 block excisions were performed in our department (92 block excisions because of anterior uveal tumors and 59 because of cystic epithelial ingrowth to the anterior chamber). In 27 patients, anterior uveal tumors or cystic epithelial ingrowth were located at the 3 or 9 o'clock position of the limbal circumference (14 patients with cystic epithelial ingrowth and 13 patients with anterior uveal tumors). Mean age of all patients was 54.4 +/- 15.7 years at the time of surgery. Mean diameter of the block excision was 10.7 +/- 4.5 mm for tumor-patients and 9.0 +/- 1.2 mm for patients with anterior chamber cysts. Mean follow-up time was 93.6 +/- 43 months. RESULTS: Only 1 of 27 patients exhibited a moderate neuroparalytic corneal ulcer during the follow-up time. In the remaining 26 patients, no signs of clinically relevant corneal neuroparalysis such as epithelial disorders or neuroparalytic ulcers were found. CONCLUSION: Block excision of tumors or cystic epithelial ingrowth located at the 3 or 9 o'clock position of the limbal circumference did not lead to severe neuroparalytic disorders of the host cornea. This may be an important factor in postoperative management of patients undergoing block excision and corneoscleral grafting.

Adult↗
PubMed2003

Dissociation between the circadian rhythm of locomotor activity and the pineal clock in the Japanese newt.

The circadian locomotor activity rhythm of the Japanese newt has been thought to be driven by a putative brain oscillator(s) subordinate to the pineal clock. The existence of mutual coupling between the pineal clock and the brain oscillator(s) in vivo was examined. We covered the newt's skull with aluminum foil and simultaneously reversed the light-dark cycle, thereby allowing the pineal organ to be exposed to constant darkness while the rest of the animal was exposed to the reversed light-dark cycle. In control animals, whose heads were covered with transparent plastic, the rhythm of synaptic ribbon number in the pineal photoreceptor cells was entrained to the reversed light-dark cycle. Rhythms from newts whose heads were shielded, however, were similar to those observed in the unoperated newts kept under constant darkness. The locomotor activity rhythms of both head-covered animals and control animals were entrained to the reversed light-dark cycle. These data suggest that extrapineal photoreception can entrain the putative brain oscillator(s), but not the pineal clock. Thus, at least in an aspect of photic entrainment, there seems to be little or no mutual coupling between the pineal clock and the putative brain oscillator(s) in the circadian system of the Japanese newt.

Animals↗
PubMed2003

Response regulator homologues have complementary, light-dependent functions in the Arabidopsis circadian clock.

TIMING OF CAB EXPRESSION 1 ( TOC1) functions with CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) in a transcriptional feedback loop that is important for the circadian clock in Arabidopsis thaliana (L.) Heynh. TOC1 and its four paralogues, the Arabidopsis PSEUDO-RESPONSE REGULATOR (PRR) genes, are expressed in an intriguing daily sequence. This was proposed to form a second feedback loop, similar to the interlocking clock gene circuits in other taxa. We show that prr9 and prr5 null mutants have reciprocal period defects for multiple circadian rhythms, consistent with subtly altered expression patterns of CCA1 and TOC1. The period defects are conditional on light quality and combine additively in double-mutant plants. Thus PRR9 and PRR5 modulate light input to the circadian clock but are neither uniquely required for rhythm generation nor form a linear series of mutual PRR gene regulation.

Arabidopsis↗
PubMed1999

Circadian clock-regulated expression of an RNA-binding protein in Arabidopsis: characterisation of a minimal promoter element.

The Atgrp7 transcript encodes a clock-regulated, glycine-rich, RNA-binding protein in Arabidopsis thaliana and shows a circadian variation in steady-state abundance. Constitutive overexpression of its product, AtGRP7, in transgenic Arabidopsis plants depresses the oscillations of the endogenous Atgrp7 transcript, indicating that both the transcript and the protein are part of a clock-regulated negative feedback circuit. Here we characterise the upstream region of the Atgrp7 gene in order to begin to dissect the molecular basis of this oscillating autoregulatory feedback loop. Fusion of a 1.5-kb promoter fragment to the beta-glucuronidase (gus) reporter gene leads to circadian oscillations in the level of the gus transcript in transgenic Arabidopsis plants, with highest levels in the evening, indicating that transcription of the Atgrp7 gene is rhythmically activated by the endogenous circadian clock. A 265-bp fragment upstream of the transcription start site is necessary for high-amplitude Atgrp7 cycling. Within this region, a 56-bp clock-responsive element that confers a low-amplitude circadian oscillation (approximately threefold) with peak abundance in the early evening maps between positions -112 and -57. Another element necessary for augmenting the amplitude of the oscillation lies between -178 and -264. Genetic crosses between a line bearing a promoter-gus fusion and plants that overexpress AtGRP7 show that the promoter by itself does not mediate the negative feedback of AtGRP7 on the oscillations of its own transcript.

Arabidopsis↗