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At least 919 records · Page 51Linked to original sources
PubMed1992

Pre-natal development of a hypothalamic biological clock.

The available evidence indicates that a biological clock oscillates in the mammalian fetus and that the fetal clock is entrained by redundant circadian signals from the mother. An entrainable biological clock during fetal life helps the developing mammal more readily prepare for life in the outside world. In humans, the early establishment of maternal-infant synchrony may help the infant maximize its responsiveness to the outside world.

Animals↗
PubMed1997

Light-induced resetting of a mammalian circadian clock is associated with rapid induction of the mPer1 transcript.

To understand how light might entrain a mammalian circadian clock, we examined the effects of light on mPer1, a sequence homolog of Drosophila per, that exhibits robust rhythmic expression in the SCN. mPer1 is rapidly induced by short duration exposure to light at levels sufficient to reset the clock, and dose-response curves reveal that mPer1 induction shows both reciprocity and a strong correlation with phase shifting of the overt rhythm. Thus, in both the phasing of dark expression and the response to light mPer1 is most similar to the Neurospora clock gene frq. Within the SCN there appears to be localization of the induction phenomenon, consistent with the localization of both light-sensitive and light-insensitive oscillators in this circadian center.

Animals↗
PubMed2001

Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock.

Mice carrying a null mutation in the Period 1 (mPer1) gene were generated using embryonic stem cell technology. Homozygous mPer1 mutants display a shorter circadian period with reduced precision and stability. Mice deficient in both mPer1 and mPer2 do not express circadian rhythms. While mPER2 regulates clock gene expression at the transcriptional level, mPER1 is dispensable for the rhythmic RNA expression of mPer1 and mPer2 and may instead regulate mPER2 at a posttranscriptional level. Studies of clock-controlled genes (CCGs) reveal a complex pattern of regulation by mPER1 and mPER2, suggesting independent controls by the two proteins over some output pathways. Genes encoding key enzymes in heme biosynthesis are under circadian control and are regulated by mPER1 and mPER2. Together, our studies show that mPER1 and mPER2 have distinct and complementary roles in the mouse clock mechanism.

Animals↗
PubMed1998

Synchronization of timepieces to the atomic clock in an urban emergency medical services system.

STUDY OBJECTIVE: Erroneous time documentation of emergency treatment caused by the variation in the accuracy of timepieces has profound medical, medicolegal, and research consequences. The purpose of this study was to confirm the variation of critical timepiece settings in an urban emergency care system noted in previous studies and to implement and monitor the results of a prospective program to improve time synchronization. METHODS: Timepieces (n = 393) used by firefighters, paramedics, and emergency physicians and nurses were randomly sampled immediately before and at two time intervals (1 and 4 months) after attempted synchronization to the US atomic clock standard. The setting on each timepiece was compared with the atomic clock. From the data, a mathematical simulation estimated the number of time-related documentation errors that would occur in 2,500 simulated cardiac arrest cases using timepieces with accuracy similar to those found in the EMS system before and after attempted synchronization. RESULTS: Before attempted synchronization, the timepieces had a mean error of 2.0 (95% confidence interval 1.8 to 2.3) minutes. One month after attempted synchronization, the mean error decreased significantly to .9(.8 to 1.1) minute. However, it increased to 1.7 (1.5 to 1.9) minutes within 4 months. Mathematical simulation before attempted synchronization predicted that 93% of cardiac arrest cases would contain a documentation error of 2 minutes or more and that 41% of cases would contain a documentation error of 5 minutes or more. Attempted synchronization cut the 2-minute documentation error rate in half and reduced the 5-minute documentation error rate by three fourths. However, the error rates were predicted to return to baseline 4 months after attempted synchronization. CONCLUSION: Emergency medical timepieces are often inaccurate, making it difficult to reconstruct events for medical, medicolegal, or research purposes. Community synchronization of timepieces to the atomic clock can reduce the problem significantly, but the effects of a one-time attempted synchronization event are short-lived.

Death Certificates↗
PubMed1999

Resetting the rat circadian clock by ultra-short light flashes.

We examined the effects that ultra-brief, intense, light flashes have on the rat circadian clock, the suprachiasmatic nucleus of the hypothalamus (SCN). We found that as few as five intense flashes, each 10-micros in duration (1 per s), can produce both phase shifts in free-running activity rhythms and Fos expression in the SCN in rats kept in constant darkness. After pre-exposure to such flashes, phase shifts in response to a continuous light pulse delivered 2 h later were potentiated, but Fos expression in the SCN was decreased as following pre-exposure to continuous light. These results show that flashes induce behavioral and cellular effects indicative of clock resetting similar to those induced by light stimuli of longer duration. Extremely brief but intense, light stimuli may be much more important to clock resetting than had been previously known.

Animals↗
PubMed1999

The effectiveness of light on the circadian clock is linked to its emotional value.

Studies carried out within the primary visual system have shown that neural responses to light stimuli transmitted via the retinogeniculate pathway are significantly altered when these stimuli are made aversive through conditioning. The effect of such aversive conditioning on neural responses to light transmitted within the circadian visual system has not been investigated. In mammals, the principal projection of the circadian visual system, the retinohypothalamic tract, is functionally and anatomically distinct from the primary visual pathway allowing for direct transmission of light from the retina to the suprachiasmatic nucleus of the hypothalamus, the circadian clock. Light transmitted within this pathway is essential for entrainment of circadian rhythms providing the critical stimulus for resetting the circadian clock. We asked whether the response of neural elements within the suprachiasmatic nucleus to a resetting light stimulus would be altered if that stimulus had acquired aversive properties through conditioning. To study this we assessed the effect of a light stimulus made aversive through pairings with footshock on a cellular correlate of clock resetting, the expression of the transcription factor Fos in neurons of the suprachiasmatic nucleus. We show that Fos expression in the suprachiasmatic nucleus in response to light previously paired with footshock is significantly suppressed. This finding provides the first evidence that the effectiveness of a light as a resetting stimulus can be modulated by its conditioned aversive properties.

Animals↗
PubMed1996

Circadian clock neurons in the silkmoth Antheraea pernyi: novel mechanisms of Period protein regulation.

We examined Period (PER) protein regulation in the brain of the silkmoth Antheraea pernyi. PER expression is restricted to the cytoplasm and axons of eight neurons, with no evidence of temporal movement into the nucleus. These neurons appear to be circadian clock cells, because PER and per mRNA are colocalized and their levels oscillate in these cells, Timeless protein immunoreactivity is coexpressed in each PER-positive neuron, and clock protein and mRNA oscillations are all suppressed in these neurons by constant light. A per antisense RNA oscillation was detected that is spatially restricted to PER-expressing cells, suggesting a novel mechanism of PER regulation. PER-positive neurons and their projections are strategically positioned for regulating prothoracicotropic hormone and eclosion hormone, two neurohormones under circadian control. Differences in the molecular details of PER expression and regulation between the brains of silkmoths and fruitflies provide insights into the mechanisms of clock gene regulation.

Animals↗
PubMed1998

A molecular rhythm mediating circadian clock output in Drosophila.

Analysis of the Drosophila lark gene indicates that it encodes an RNA-binding protein that functions as a regulatory element of the circadian clock output pathway controlling adult eclosion. We now demonstrate that the lark RNA-binding protein oscillates in abundance during the circadian cycle; importantly, the phasing of the lark rhythm is consistent with gene-dosage studies, which indicate that the protein behaves as a repressor molecule. The lark protein rhythm persists in constant conditions (continuous darkness and constant temperature) and is eliminated by period gene null mutations, confirming that it is under clock control and suggesting that it acts as an output mechanism that mediates the temporal regulation of adult eclosion. We also show that lark protein oscillates in abundance within a defined group of neuropeptide (CCAP) -containing neurons of the ventral nervous system (VNS), which in other insects are thought to comprise cellular elements of the clock output pathway regulating eclosion.

Animals↗
PubMed2000

Analysis of clock proteins in mouse SCN demonstrates phylogenetic divergence of the circadian clockwork and resetting mechanisms.

The circadian clock in the suprachiasmatic nuclei (SCN) is comprised of a cell-autonomous, autoregulatory transcriptional/translational feedback loop. Its molecular components include three period and two cryptochrome genes. We describe circadian patterns of expression of mPER2 and mPER3 in the mouse SCN that are synchronous to those for mPER1, mCRY1, and mCRY2. Coimmunoprecipitation experiments demonstrate in vivo associations of the SCN mPER proteins with each other and with the mCRY proteins, and of mCRY proteins with mTIM, but no mPER/mTIM interactions. Examination of the effects of weak and strong resetting light pulses on SCN clock proteins highlights a central role for mPER1 in photic entrainment, with no acute light effects on either the mCRY or mTIM proteins. These clock protein interactions and photic responses in mice are divergent from those described in Drosophila.

Animals↗
PubMed2003

Site stripping based on likelihood ratio reduction is a useful tool to evaluate the impact of non-clock-like behavior on viral phylogenetic reconstructions.

The site stripping for clock detection procedure was implemented in the recently developed maximum likelihood framework for estimating evolutionary rates and divergence times in measurably evolving populations. The method was used to investigate the effect of rate variability on estimating divergence times in non-clock-like trees for human immunodeficiency viruses and hepatitis C viruses. We validate our approach by comparing dated coalescent nodes in molecular phylogenies with known dates of transmission. Our method was able to rapidly recover clock-like behavior and to indicate the presence and direction of a bias when estimates of divergence times using the unstripped data were flawed.

Algorithms↗
PubMed2003

The mammalian circadian clock.

Organisms populating the earth are under the steady influence of daily and seasonal changes resulting from the planet's rotation and orbit around the sun. This periodic pattern most prominently manifested by the light-dark cycle has led to the establishment of endogenous circadian timing systems that synchronize biological functions to the environment. The mammalian circadian system is composed of many individual, tissue-specific clocks. To generate coherent physiological and behavioral responses, the phases of this multitude of clocks are orchestrated by the master circadian pacemaker residing in the suprachiasmatic nuclei of the brain. Genetic, biochemical and genomic approaches have led to major advances in understanding the molecular and cellular basis of mammalian circadian clock components and mechanisms.

Animals↗
PubMed2001

Cranial nerve clock. Part 1. A declarative memory paradigm.

RATIONALE AND OBJECTIVES: The authors performed this study to compare a declarative memory paradigm developed to help teach medical students about the cranial nerves with a traditional text-based approach. MATERIALS AND METHODS: The authors designed a clock-based paradigm to help medical students learn about the cranial nerves. To enhance memorization and related brain activation, the paradigm uses visual, spatial, and word associations in the context of an analog clock face. Twenty-one undergraduate students were randomly divided into two groups. Group T viewed traditional text slides, and group C viewed text slides followed by the corresponding cranial clock slides. Subjects were tested before and after these sessions. RESULTS: Group C performed significantly better than group T in learning the names of the cranial nerves and their correct order (P < .011). Recall of name, number, and function was better for 11 of 12 cranial nerves, with statistical significance reached for nerves III (P = .005), V (P = .04), and X (P = .03). CONCLUSION: Alternative teaching strategies may help improve declarative memory.

Cranial Nerves↗
PubMed2003

Shedding light on the circadian clock and the photoperiodic control of flowering.

Recently, notable progress has been made towards understanding the genetic interactions that underlie the function of the circadian clock in plants, and how these functions are related to the seasonal control of flowering time. The LHY/CCA1 and TOC1 genes have been proposed to participate in a negative feedback loop that is part of the central oscillator of the circadian clock. Furthermore, analysis of a flowering-time pathway has suggested how transcriptional regulation by the circadian clock, combined with post-transcriptional regulation by light, could activate proteins that control flowering time in response to appropriate daylengths.

Arabidopsis↗
PubMed1992

A circadian clock in the Limulus brain transmits synchronous efferent signals to all eyes.

A circadian clock in the brain of the horseshoe crab, Limulus polyphemus, has an important role in the function of the peripheral visual system. At night, the clock transmits neural activity to the lateral, ventral, and median eyes via efferent optic nerve fibers. The activity occurs in synchronous bursts (maximum rate of 2 bursts/s) with individual efferent fibers contributing a single spike in each burst. The circadian efferent activity originates in the protocerebrum. Lateral connections synchronize the efferent activity recorded from the two halves of the protocerebrum, suggesting the existence of bilateral circadian oscillators. Circadian efferent activity survives excision of the brain and isolation of the protocerebrum. We conclude that circadian clock and its complex neural circuitry are fundamental components of the Limulus visual system.

Animals↗
PubMed1996

Use of the clock drawing task in the diagnosis of mild and very mild Alzheimer's disease.

The purpose of this study was to examine the utility of the clock drawing task (CDT) in differentiating between patients with mild and very mild Alzheimer's disease (AD) and normal controls. Thirty normal elderly individuals and 30 patients with probable AD were entered into the study and asked, in a standard fashion, to draw a clock from memory. All the clocks were scored according to two previously described standardized scoring systems, and the accuracy of classification into normal or AD groups was determined. Both CDT scales could discriminate between moderate AD and normal aging but lacked sensitivity in the very mild AD cases; mild cases showed intermediate sensitivity. In conclusion, the CDT as a test for AD is insensitive in the early-stage cases, but sensitivity improves with increasing severity of dementia. The CDT is unlikely to be useful in distinguishing between AD in its early stages and normal aging.

Aged↗
PubMed2005

The chlorate-iodine clock reaction.

A clock reaction produced by mixing chlorate and iodine solutions in perchloric acid media is reported. This is the first example of a clock reaction using chlorate as a reagent. Increasing chlorate and acid concentration reduces the induction period. Changing the initial iodine concentration does not affect the length of the induction period. The discovery of this clock reaction opens the possibility that a new family of oscillation reactions can be built using chlorate as reagent.

Journal Article↗
PubMed2006

Peroxyl radical clocks.

A series of peroxyl radical clocks has been developed and calibrated based on the competition between the unimolecular beta-fragmentation (k(beta)) of a peroxyl radical and its bimolecular reaction with a hydrogen atom donor (k(H)). These clocks are based on either methyl linoleate or allylbenzene and were calibrated directly with alpha-tocopherol or methyl linoleate, which have well-established rate constants for reaction with peroxyl radicals (k(H-tocopherol) = 3.5 x 10(6) M(-1) s(-1), k(H-linoleate) = 62 M(-1) s(-1)). This peroxyl radical clock methodology has been successfully applied to determine inhibition and propagation rate constants ranging from 10(0) to 10(7) M(-1) s(-1).

Calibration↗
PubMed2000

Differential effects of auditory and visual signals on clock speed and temporal memory.

The effects of signal modality on duration classification in college students were studied with the duration bisection task. When auditory and visual signals were presented in the same test session and shared common anchor durations, visual signals were classified as shorter than equivalent duration auditory signals. This occurred when auditory and visual signals were presented sequentially in the same test session and when presented simultaneously but asynchronously. Presentation of a single modality signal within a test session, or both modalities but with different anchor durations did not result in classification differences. The authors posit a model in which auditory and visual signals drive an internal clock at different rates. The clock rate difference is due to an attentional effect on the mode switch and is revealed only when the memories for the short and long anchor durations consist of a mix of contributions from accumulations generated by both the fast auditory and slower visual clock rates. When this occurs auditory signals seem longer than visual signals relative to the composite memory representation.

Adult↗