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Clock
Kinds of Clock Terms modified by Clock Selected AbstractsCONCORDANCE OF THE CIRCADIAN CLOCK WITH THE ENVIRONMENT IS NECESSARY TO MAXIMIZE FITNESS IN NATURAL POPULATIONSEVOLUTION, Issue 4 2008Kevin J. Emerson The ubiquity of endogenous, circadian (daily) clocks among eukaryotes has long been held as evidence that they serve an adaptive function, usually cited as the ability to properly time biological events in concordance with the daily cycling of the environment. Herein we test directly whether fitness is a function of the matching of the period of an organism's circadian clock with that of its environment. We find that fitness, measured as the per capita expectation of future offspring, a composite measure of fitness incorporating both survivorship and reproduction, is maximized in environments that are integral multiples of the period of the organism's circadian clock. Hence, we show that organisms require temporal concordance between their internal circadian clocks and their external environment to maximize fitness and thus the long-held assumption is true that, having evolved in a 24-h world, circadian clocks are adaptive. [source] CALIBRATING A MOLECULAR CLOCK FROM PHYLOGEOGRAPHIC DATA: MOMENTS AND LIKELIHOOD ESTIMATORSEVOLUTION, Issue 10 2003Michael J. Hickerson Abstract We present moments and likelihood methods that estimate a DNA substitution rate from a group of closely related sister species pairs separated at an assumed time, and we test these methods with simulations. The methods also estimate ancestral population size and can test whether there is a significant difference among the ancestral population sizes of the sister species pairs. Estimates presented in the literature often ignore the ancestral coalescent prior to speciation and therefore should be biased upward. The simulations show that both methods yield accurate estimates given sample sizes of five or more species pairs and that better likelihood estimates are obtained if there is no significant difference among ancestral population sizes. The model presented here indicates that the larger than expected variation found in multitaxa datasets can be explained by variation in the ancestral coalescence and the Poisson mutation process. In this context, observed variation can often be accounted for by variation in ancestral population sizes rather than invoking variation in other parameters, such as divergence time or mutation rate. The methods are applied to data from two groups of species pairs (sea urchins and Alpheus snapping shrimp) that are thought to have separated by the rise of Panama three million years ago. [source] Characterization of two members of the cryptochrome/photolyase family from Ostreococcus tauri provides insights into the origin and evolution of cryptochromesPLANT CELL & ENVIRONMENT, Issue 10 2010MARC HEIJDE ABSTRACT Cryptochromes (Crys) are blue light receptors believed to have evolved from the DNA photolyase protein family, implying that light control and light protection share a common ancient origin. In this paper, we report the identification of five genes of the Cry/photolyase family (CPF) in two green algae of the Ostreococcus genus. Phylogenetic analyses were used to confidently assign three of these sequences to cyclobutane pyrimidine dimer (CPD) photolyases, one of them to a DASH-type Cry, and a third CPF gene has high homology with the recently described diatom CPF1 that displays a bifunctional activity. Both purified OtCPF1 and OtCPF2 proteins show non-covalent binding to flavin adenine dinucleotide (FAD), and additionally to 5,10-methenyl-tetrahydrofolate (MTHF) for OtCPF2. Expression analyses revealed that all five CPF members of Ostreococcus tauri are regulated by light. Furthermore, we show that OtCPF1 and OtCPF2 display photolyase activity and that OtCPF1 is able to interact with the CLOCK:BMAL heterodimer, transcription factors regulating circadian clock function in other organisms. Finally, we provide evidence for the involvement of OtCPF1 in the maintenance of the Ostreococcus circadian clock. This work improves our understanding of the evolutionary transition between photolyases and Crys. [source] CLOCK: Calling time on bipolar disorderPROGRESS IN NEUROLOGY AND PSYCHIATRY, Issue 4 2007Mark Greener Mark Greener reports on the development of an animal model that may help elucidate the mechanism of action of drugs that exert an effect on circadian rhythm in conditions such as mania, which are thought to be linked in part to disruption of the rhythm of life. Copyright © 2007 Wiley Interface Ltd [source] CALIBRATION OF MOLECULAR CLOCKS AND THE BIOGEOGRAPHIC HISTORY OF CRYPTERONIACEAE: A REPLY TO MOYLEEVOLUTION, Issue 8 2004Elena Conti No abstract is available for this article. [source] Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2002Caroline Kopp Abstract A limited set of genes, Clock, Bmal1, mPer1, mPer2, mCry1 and mCry2, has been shown to be essential for the generation of circadian rhythms in mammals. It has been recently suggested that circadian genes might be involved in sleep regulation. We investigated the role of mPer1 and mPer2 genes in the homeostatic regulation of sleep by comparing sleep of mice lacking mPER1 (mPer1 mutants) or a functional mPER2 (mPer2 mutants), and wild-type controls (WT) after 6 h of sleep deprivation (SD). Our main result showed that after SD, all mice displayed the typical increase of slow-wave activity (SWA; EEG power density between 0.75 and 4 Hz) in nonREM sleep, reflecting the homeostatic response to SD. This increase was more prominent over the frontal cortex as compared to the occipital cortex. The genotypes did not differ in the effect of SD on the occipital EEG, while the effect on the frontal EEG was initially diminished in both mPer mutants. Differences between the genotypes were seen in the 24-h distribution of sleep, reflecting especially the phase advance of motor activity onset observed in mPer2 mutants. While the daily distribution of sleep was modulated by mPer1 and mPer2 genes, sleep homeostasis reflected by the SWA increase after 6-h SD was preserved in the mPer mutants. The results provide further evidence for the independence of the circadian and the homeostatic components underlying sleep regulation. [source] Daily Meal Timing is Not Necessary for Resetting the Main Circadian Clock by Calorie RestrictionJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2008J. Mendoza In rodents, entrainment and/or resetting by feeding of the central circadian clock, the suprachiasmatic nucleus (SCN), is more efficient when food cues arise from a timed calorie restriction. Because timed calorie restriction is associated with a single meal each day at the same time, its resetting properties on the SCN possibly depend on a combination of meal time-giving cues and hypocaloric conditions per se. To exclude any effect of daily meal timing in resetting by calorie restriction, the present study employed a model of ultradian feeding schedules, divided into six meals with different durations of food access (6 × 8-min versus 6 × 12-min meal schedule) every 4 h over the 24-h cycle. The effects of such an ultradian calorie restriction were evaluated on the rhythms of wheel-running activity (WRA) and body temperature (Tb) in rats. The results indicate that daily/circadian rhythms of WRA and Tb were shifted by a hypocaloric feeding distributed in six ultradian short meals (i.e. 6 × 8-min meal schedule), showing both phase advances and delays. The magnitude of phase shifts was positively correlated with body weight loss and level of day-time behavioural activity. By contrast, rats fed daily with six ultradian meals long enough (i.e. 6 × 12-min meal schedule) to prevent body weight loss, showed only small, if any, phase shifts in WRA and Tb rhythms. The results obtained reveal the potency of calorie restriction to reset the SCN clock without synchronisation to daily meal timing, highlighting functional links between metabolism, calorie restriction and the circadian timing system. [source] Photic Regulation of mt1 Melatonin Receptors in the Siberian Hamster Pars Tuberalis and Suprachiasmatic Nuclei: Involvement of the Circadian Clock and Intergeniculate LeafletJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2000Schuster In the Siberian hamster suprachiasmatic nuclei and pars tuberalis of the pituitary, high affinity mt1 melatonin receptors are present. We have previously shown that night applied light pulse induced an increase in mt1 mRNA expression in the suprachiasmatic nuclei of this species, independently of the endogenous melatonin. Here, we report the photic regulation of melatonin receptor density and mRNA expression in the suprachiasmatic nuclei and pars tuberalis of pinealectomized Siberian hamsters and the implication in this control of either the circadian clock or the intergeniculate leaflet. The results show that: (1) A 1-h light pulse, delivered during the night, induces a transitory increase in mt1 mRNA expression in the suprachiasmatic nuclei and pars tuberalis. After 3 h this increase has totally disappeared (suprachiasmatic nuclei) or is greatly reduced (pars tuberalis). (2) The melatonin receptor density, in the suprachiasmatic nuclei, is not affected by 1 or 3 h of light, while it is strongly increased in the pars tuberalis. (3) In hamsters kept in constant darkness, the mt1 mRNA rise is gated to the subjective night in the suprachiasmatic nuclei and pars tuberalis. In contrast, the light-induced increase in melatonin binding is also observed in the subjective day in the pars tuberalis. (4) intergeniculate leaflet lesion totally inhibits the mt1 mRNA expression rise in the suprachiasmatic nuclei, while it has no effect on the light-induced increase in mt1 mRNA in the pars tuberalis. However, the light-induced increase in melatonin receptor density is totally prevented by the intergeniculate leaflet lesion in the pars tuberalis. These results show that: (1) the photic regulations of mt1 mRNA expression and receptor density are independent of each other in both the suprachiasmatic nuclei and pars tuberalis; and (2) the circadian clock and the intergeniculate leaflet are implicated in the photic regulation of melatonin receptors but their level of action differs totally between the suprachiasmatic nuclei and pars tuberalis. [source] Sirtuins, melatonin and circadian rhythms: building a bridge between aging and cancerJOURNAL OF PINEAL RESEARCH, Issue 1 2010Brittney Jung-Hynes Abstract:, Histone deacetylases (HDAC) have been under intense scientific investigation for a number of years. However, only recently the unique class III HDAC, sirtuins, have gained increasing investigational momentum. Originally linked to longevity in yeast, sirtuins and more specifically, SIRT1 have been implicated in numerous biological processes having both protective and/or detrimental effects. SIRT1 appears to play a critical role in the process of carcinogenesis, especially in age-related neoplasms. Similarly, alterations in circadian rhythms as well as production of the pineal hormone melatonin have been linked to aging and cancer risk. Melatonin has been found act as a differentiating agent in some cancer cells and to lower their invasive and metastatic status. In addition, melatonin synthesis and release occurs in a circadian rhythm fashion and it has been linked to the core circadian machinery genes (Clock, Bmal1, Periods, and Cryptochromes). Melatonin has also been associated with chronotherapy, the timely administration of chemotherapy agents to optimize trends in biological cycles. Interestingly, a recent set of studies have linked SIRT1 to the circadian rhythm machinery through direct deacetylation activity as well as through the nicotinamide adenine dinucleotide (NAD+) salvage pathway. In this review, we provide evidence for a possible connection between sirtuins, melatonin, and the circadian rhythm circuitry and their implications in aging, chronomodulation, and cancer. [source] Alcohol Consumption and the Body's Biological ClockALCOHOLISM, Issue 8 2005Rainer Spanagel This review summarizes new findings on the bidirectional interactions between alcohol and the clock genes, underlying the generation of circadian rhythmicity. At the behavioral level, both adult and perinatal ethanol treatments alter the free-running period and light response of the circadian clock in rodents; genetic ethanol preference in alcohol-preferring rat lines is also associated with alterations in circadian pacemaker function. At the neuronal level, it has been shown that ethanol consumption alters the circadian expression patterns of period (per) genes in various brain regions, including the suprachiasmatic nucleus. Notably, circadian functions of ,-endorphin,containing neurons that participate in the control of alcohol reinforcement become disturbed after chronic alcohol intake. In turn, per2 gene activity regulates alcohol intake through its effects on the glutamatergic system through glutamate reuptake mechanisms and thereby may affect a variety of physiological processes that are governed by our internal clock. In summary, a new pathologic chain has been identified that contributes to the negative health consequences of chronic alcohol intake. Thus, chronic alcohol intake alters the expression of per genes, and, as a consequence, a variety of neurochemical and neuroendocrine functions become disturbed. Further steps in this pathologic chain are alterations in physiological and immune functions that are under circadian control, and, as a final consequence, addictive behavior might be triggered or sustained by this cascade. [source] Influence of Temperature on the Liver Circadian Clock in the Ruin Lizard Podarcis siculaMICROSCOPY RESEARCH AND TECHNIQUE, Issue 7 2007Manuela Malatesta Abstract Reptiles represent an interesting animal model to investigate the influence of temperature on molecular circadian clocks. The ruin lizard Podarcis sicula lives in a continental climate and it is subjected to wide range of environmental temperatures during the course of the year. As consequence, ruin lizard daily activity pattern includes either the hibernation or periods of inactivity determined by hypothermia. Here we showed the rhythmic expression of two clock genes, lPer2 and lClock, in the liver of active lizards exposed to summer photo-thermoperiodic conditions. Interestingly, the exposition of lizards to hypothermic conditions, typical of winter season, induced a strong dampening of clock genes mRNA rhythmicity with a coincident decrease of levels. We also examined the qualitative and quantitative distribution of lPER2 and lCLOCK protein in different cellular compartments during the 24-h cycle. In the liver of active lizards both proteins showed a rhythmic expression profile in all cellular compartments. After 3 days at 6°C, some temporal fluctuations of the lCLOCK and lPER2 are still detectable, although, with some marked modifications in respect to the values detected in the liver of active lizards. Besides demonstrating the influence of low temperature on the lizard liver circadian oscillators, present results could provide new essential information for comparative studies on the influence of temperature on the circadian system across vertebrate classes. Microsc. Res. Tech., 2007. © 2007 Wiley-Liss, Inc. [source] Immunocytochemical analysis of the circadian clock protein in mouse hepatocytesMICROSCOPY RESEARCH AND TECHNIQUE, Issue 5 2003Manuela Malatesta Abstract Many biochemical, physiological, and behavioral processes in organisms ranging from prokaryotes to humans exhibit circadian rhythms, defined as cyclic oscillations of about 24 hours. The mechanism of the cellular circadian clock relies on interlocking positive and negative transcriptional/translational feedback loops based on the regulated expression of several genes. Clock is one of these genes and its transcript, CLOCK protein, is a transcription factor belonging to the bHLH-PAS family. In mammals the clock gene is expressed in several tissues, including the liver. In the present study, we analyzed by means of quali-quantitative immunoelectron microscopy the fine intracellular distribution of the CLOCK protein in mouse hepatocytes during the daily cycle. We demonstrated that CLOCK protein is mostly located in the cell nucleus, where it accumulates on perichromatin fibrils, representing the in situ form of nascent pre-mRNA, while condensed chromatin and nucleoli contain lower amounts of protein. Moreover, we found that CLOCK protein shows circadian oscillations in these nuclear compartments, peaking in late afternoon. At this time the hepatic transcriptional rate reaches the maximal level, thus suggesting an important role of CLOCK protein in the regulation of liver gene expression. Microsc. Res. Tech. 61:414,418, 2003. © 2003 Wiley-Liss, Inc. [source] Genetics of personalities: no simple answers for complex traitsMOLECULAR ECOLOGY, Issue 4 2010BARBARA TSCHIRREN Identifying the genes that underlie phenotypic variation in natural populations, and assessing the consequences of polymorphisms at these loci for individual fitness are major objectives in evolutionary biology. Yet, with the exception of a few success stories, little progress has been made, and our understanding of the link between genotype and phenotype is still in its infancy. For example, although body length in humans is largely genetically determined, with heritability estimates greater than 0.8, massive genome-wide association studies (GWAS) have only been able to account for a very small proportion of this variation (Gudbjartsson et al. 2008). If it is so difficult to explain the genetics behind relatively ,simple' traits, can we envision that it will at all be possible to find genes underlying complex behavioural traits in wild non-model organisms? Some notable examples suggest that this can indeed be a worthwhile endeavour. Recently, the circadian rhythm gene Clock has been associated with timing of breeding in a wild blue tit population (Johnsen et al. 2007; Liedvogel et al. 2009) and the Pgi gene to variation in dispersal and flight endurance in Glanville fritillary butterflies (Niitepold et al. 2009). A promising candidate gene for influencing complex animal personality traits, also known as behavioural syndromes (Sih et al. 2004), is the dopamine receptor D4 (DRD4) gene. Within the last decade, polymorphisms in this gene have been associated with variation in novelty seeking and exploration behaviour in a range of species, from humans to great tits (Schinka et al. 2002; Fidler et al. 2007). In this issue, Korsten et al. (2010) attempt to replicate this previously observed association in wild-living birds, and test for the generality of the association between DRD4 and personality across a number of European great tit populations. [source] Many but not all Genes in Chlamydomonas reinhardtii are Regulated by the Circadian ClockPLANT BIOLOGY, Issue 6 2001S. Jacobshagen Abstract: Total RNA from autotrophic Chlamydomonas reinhardtii cultures grown in constant dim light and 17 °C constant temperature was subjected to Northern blot analyses. The mRNAs for cytochrome c, ,-tubulin, HSP70B (a chloroplastic heat shock protein of the 70 kD family), chloroplastic fructose-bisphosphate aldolase, and GAS3 (a "gamete-specific" protein of unknown function with high expression in gametes but low expression in vegetative cells) each exhibit a clear circadian rhythm in abundance. The rhythms differ significantly in phase and amplitude. The findings show that the genes for cytochrome c and ,-tubulin indeed are regulated by the circadian clock, as previously suggested. Experiments with cultures grown at 27 °C instead of 17 °C further revealed that the rhythms in mRNA abundance for HSP70B, chloroplastic aldolase, and GAS3 also occur with a similar period at the higher temperature. Thus, the rhythms conform to the criterion of temperature compensation for the period and therefore represent true circadian rhythms. In contrast, the combined amount of mRNA for ubiquitin 52 amino acid fusion protein and ubiquitin 78 to 81 amino acid fusion protein stays constant under both temperature conditions. Because the combined amount of mRNA for the ubiquitin fusion proteins was previously shown to cycle under diurnal conditions when cell division activity is high, our data suggest a regulation of these genes by the cell division cycle and not the circadian clock. In summary, our data, together with several other reports, suggest that the circadian clock regulates many but not all genes in Chlamydomonas reinhardtii. [source] Rock Around the Clock in the Middle Ear CleftTHE LARYNGOSCOPE, Issue 6 2002Sady Selaimen da Costa MD First page of article [source] Clock drawing from the occupational therapy adult perceptual screening test: Its correlation with demographic and clinical factors in the stroke populationAUSTRALIAN OCCUPATIONAL THERAPY JOURNAL, Issue 3 2010Deirdre M. Cooke Background/aim:,The aim of this study was to explore the relationships between clock drawing ability following stroke, and key clinical variables including cognition, functional independence, side and type of stroke, educational level and age. Methods:,One hundred and ninety-seven people with stroke were recruited from 12 hospital and rehabilitation facilities. The participants' scores from the Clock Drawing Test in the Occupational Therapy Adult Perceptual Screening Test were the dependent variables and were entered into logistic regression with Functional Independence Measure motor scores, side of stroke, Oxfordshire Classification System of Stroke, educational level and age as independent variables. Correlation with the Mini-Mental State Examination was analysed independently, due to its strong correlation with other variables. Results:,The Mini-Mental State Examination correlated significantly with the Clock Drawing Test ( Exp (B) = 0.826, P < 0.001). In the multivariate analysis, a significant relationship was found with age (Exp ( B) = 1.052, P < 0.001), Functional Independence Measure , motor (Exp (B) = 0.984, P = 0.030) and side of stroke (Exp (B) = 0.384, P = 0.003). Age demonstrated the strongest correlation with the Clock Drawing Test ability and the greatest decline was from approximately 70 years of age. Conclusions:,The Clock Drawing Test may be a useful and quick screen of cognitive impairments following stroke. Age-related decline must be considered and it is essential that clinicians use this only as a strategy to determine whether a more comprehensive assessment is required. [source] Cooperative Effects on Radical Recombination in CYP3A4-Catalyzed Oxidation of the Radical Clock ,-ThujoneCHEMBIOCHEM, Issue 4 2009Yongying Jiang Dr. Abstract Tick tock: The timing of the ,-thujone radical clock (see scheme) can be specifically altered by an allosteric effector. Progesterone, a well-documented CYP3A4 allosteric effector, was found to increase the yield of the unrearranged, C4-derived product of ,-thujone oxidation at the expense of the combined yields of all the rearranged C4-oxidized metabolites. The results demonstrate that the apparent radical recombination rate in the CYP3A4 hydroxylation of ,-thujone is accelerated by the progesterone hetereotropic cooperativity. [source] Synchronization of the Fungal and the Plant Circadian Clock by LightCHEMBIOCHEM, Issue 16 2008László Kozma-Bognár Abstract Circadian clocks are endogenous time keeping devices that provide temporal control of physiology in accordance with predicted daily changes in the environment. Photoentrainment is the process that synchronizes circadian clocks-and thereby clock-controlled gene expression and physiology-to the environmental day/night cycles. Light is primarily detected by specialized photoreceptors that are coupled,directly or through other signaling components,to the rhythm-generating oscillator. As a consequence, the expression, the activity or the stability of oscillator components are altered, resulting in a change of phase and/or pace of the oscillator. In this review our present knowledge about light absorption/transduction and light-induced modifications of oscillator components in Neurospora crassa and Arabidopsis thaliana is summarized. These systems provide a basis for understanding the molecular mechanisms of entrainment in the fungal and plant circadian systems. [source] Joseph S. Takahashi, Fred W. Turek and Robert Y.Moore (eds): Circadian Clocks (Handbook of Behavioral Neurobiology, Vol 12)GENES, BRAIN AND BEHAVIOR, Issue 3 2002W.J. Schwartz [source] Comparing clock tests for dementia screening: naïve judgments vs formal systems,what is optimal?INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 1 2002James M. Scanlan Abstract Background Clock drawing tests (CDTs) vary in format, scoring, and complexity. Herein, we compared the dementia screening performance of seven CDT scoring systems and the judgements of untrained raters. Methods 80 clock drawings by subjects of known dementia status were selected, 20 from each of four categories (Consortium to Establish a Registry for Alzheimer's disease [CERAD] defined normal, mild, moderate, and severe abnormality). An expert rater scored all clocks using published criteria for seven systems. Additionally, 20 naïve raters judged clocks as either normal or abnormal, without formal instructions. Clocks were then classified by drawers' dementia status for comparison of dementia detection across systems. Results Naïve and formal CDT systems showed 90,100% agreement in CERAD normal, moderate and severe categories, but poor agreement (mean,=,39%) for mildly impaired clocks. When CDT systems were compared for accurate dementia classification, the Mendez and CERAD systems correctly identified the greatest proportion of subjects (84,85%), and Wolf-Klein the smallest (58%). The better systems correctly identified>,70% of mildly demented individuals (CDR,=,1). In contrast, medical records from patients' personal physicians correctly identified only 24% of the mildly demented. Strikingly, naïve raters' CDT judgements were as effective as five of the seven CDT systems in dementia identification. Conclusions While the Mendez system was the most accurate overall, it was not significantly better than CERAD, which had simpler scoring rules. Untrained raters discriminated normal from abnormal clocks with acceptable accuracy for community screening purposes. Results suggest that, if used, most CDT systems would improve personal physicians' dementia recognition in difficult to detect mildly demented subjects. Copyright © 2002 John Wiley & Sons, Ltd. [source] Second Millennium Babylonian Water Clocks: a physical studyCENTAURUS, Issue 3 2000C. Michel-Nozières First page of article [source] Clock synchronization in Cell/B.E. tracesCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 14 2009M. Biberstein Abstract Cell/B.E. is a heterogeneous multicore processor that was designed for the efficient execution of parallel and vectorizable applications with high computation and memory requirements. The transition to multicores introduces the challenge of providing tools that help programmers tune the code running on these architectures. Tracing tools, in particular, often help locate performance problems related to thread and process communication. A major impediment to implementing tracing on Cell is the absence of a common clock that can be accessed at low cost from all cores. The OS clock is costly to access from the auxiliary cores and the hardware timers cannot be simultaneously set on all the cores. In this paper, we describe an offline trace analysis algorithm that assigns wall-clock time to trace records based on their thread-local time stamps and event order. Our experiments on several Cell SDK workloads show that the indeterminism in assigning wall-clock time to events is low, on average 20,40 clock ticks (translating into 1.4,2.8,µs on the system used in our experiments). We also show how various practical problems, such as the imprecision of time measurement, can be overcome. Copyright © 2009 John Wiley & Sons, Ltd. [source] Role of orexins in the hypothalamic-pituitary-ovarian relationshipsACTA PHYSIOLOGICA, Issue 3 2010P. Silveyra Abstract Appropriate nutritional and vigilance states are needed for reproduction. In previous works, we described the influence of the hormonal milieu of proestrus on the orexinergic system and we found that orexin receptor 1 expression in the hypothalamus, but not other neural areas, and the adenohypophysis was under the influence of oestradiol and the time of the day. Information from the sexual hormonal milieu of proestrous afternoon impacts on various components of the orexinergic system and alertness on this particular night of proestrus would be of importance for successful reproduction. In this review, we summarize the available experimental data supporting the participation of orexins in the hypothalamic-pituitary-ovarian relationships. All together, these results suggest a role of the orexinergic system as an integrative link among vital functions such as reproduction, food intake, alertness and the inner biological clock. [source] Moral Education Between Hope and Hopelessness: The Legacy of Janusz KorczakCURRICULUM INQUIRY, Issue 1 2008SARA EFRAT EFRON ABSTRACT The responsibility for addressing morality and moral education in the current moral climate is a daunting task for conscientious educators. What educational response can extricate us from the debilitating feelings of hopelessness and helplessness as we are confronted by horrific terrorist actions, controversial use of military might, displays of corruption and greed and a growing general tension and anxiety? At this demoralizing juncture of uncertainty and doubt, the figure of Janusz Korczak (1878,1942), a Jewish-Polish educator, looms large. For more than 30 years, Korczak devoted his life to educating orphaned Jewish and non-Jewish children. He stayed with the Jewish children to the end as they all perished in a concentration camp. At a time when the surrounding society surrendered to fascism, anti-Semitism, and self-destruction, Korczak encouraged individual autonomy and caring relationships within the context of a community where a vision of justice and trust was an integral part of life. The orphanages he directed were democratic, self-ruled communities, where the children had their own parliament, court, and newspaper. This article describes the principles and the actualization of Korczak's moral education and explores how Korczak reconciled the differences between the ethical world he created in his institutions and the surrounding immoral society. The example set by Korczak's educational praxis serves as an inspiring model of school life across the boundaries of time and place and touches our need to believe in education's responsibility to strive and struggle for a better world, even when it seems an unattainable goal. And the hour shall come when a man will know himself, respect, and love. And the hour shall come in history's clock when man shall know the place of good, the place of evil, the place of pleasure, and the place of pain. (Korczak, 1978, p. 237) [source] Sharp developmental thresholds defined through bistability by antagonistic gradients of retinoic acid and FGF signalingDEVELOPMENTAL DYNAMICS, Issue 6 2007Albert Goldbeter Abstract The establishment of thresholds along morphogen gradients in the embryo is poorly understood. Using mathematical modeling, we show that mutually inhibitory gradients can generate and position sharp morphogen thresholds in the embryonic space. Taking vertebrate segmentation as a paradigm, we demonstrate that the antagonistic gradients of retinoic acid (RA) and Fibroblast Growth Factor (FGF) along the presomitic mesoderm (PSM) may lead to the coexistence of two stable steady states. Here, we propose that this bistability is associated with abrupt switches in the levels of FGF and RA signaling, which permit the synchronized activation of segmentation genes, such as mesp2, in successive cohorts of PSM cells in response to the segmentation clock, thereby defining the future segments. Bistability resulting from mutual inhibition of RA and FGF provides a molecular mechanism for the all-or-none transitions assumed in the "clock and wavefront" somitogenesis model. Given that mutually antagonistic signaling gradients are common in development, such bistable switches could represent an important principle underlying embryonic patterning. Developmental Dynamics 236:1495,1508, 2007. © 2007 Wiley-Liss, Inc. [source] Circadian clock and cell cycle gene expression in mouse mammary epithelial cells and in the developing mouse mammary glandDEVELOPMENTAL DYNAMICS, Issue 1 2006Richard P. Metz Abstract Mouse mammary epithelial cells (HC-11) and mammary tissues were analyzed for developmental changes in circadian clock, cellular proliferation, and differentiation marker genes. Expression of the clock genes Per1 and Bmal1 were elevated in differentiated HC-11 cells, whereas Per2 mRNA levels were higher in undifferentiated cells. This differentiation-dependent profile of clock gene expression was consistent with that observed in mouse mammary glands, as Per1 and Bmal1 mRNA levels were elevated in late pregnant and lactating mammary tissues, whereas Per2 expression was higher in proliferating virgin and early pregnant glands. In both HC-11 cells and mammary glands, elevated Per2 expression was positively correlated with c-Myc and Cyclin D1 mRNA levels, whereas Per1 and Bmal1 expression changed in conjunction with ,- casein mRNA levels. Interestingly, developmental stage had differential effects on rhythms of clock gene expression in the mammary gland. These data suggest that circadian clock genes may play a role in mouse mammary gland development and differentiation. Developmental Dynamics 235:263,271, 2006. © 2005 Wiley-Liss, Inc. [source] Circadian changes in Drosophila motor terminalsDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2007Kerstin I. Mehnert Abstract In Drosophila melanogaster, as in most other higher organisms, a circadian clock controls the rhythmic distribution of rest/sleep and locomotor activity. Here we report that the morphology of Drosophila flight neuromuscular terminals changes between day and night, with a rhythm in synaptic bouton size that continues in constant darkness, but is abolished during aging. Furthermore, arrhythmic mutations in the clock genes timeless and period also disrupt this circadian rhythm. Finally, these clock mutants also have an opposing effect on the nonrhythmic phenotype of neuronal branching, with tim mutants showing a dramatic hyperbranching morphology and per mutants having fewer branches than wild-type flies. These unexpected results reveal further circadian as well as nonclock related pleiotropic effects for these classic behavioral mutants. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] The relationship between melatonin and cortisol rhythms: clinical implications of melatonin therapyDRUG DEVELOPMENT RESEARCH, Issue 3 2005N. Zisapel Abstract Disturbances in circadian rhythm have been linked to chronic diseases such as insomnia, hypertension, diabetes, and depression. Here we review recent studies on the age-related changes in cortisol and melatonin rhythms and then present descriptive statistics on our preliminary findings on the rectification of the cortisol rhythms by melatonin therapy in elderly patients with insomnia. In adults, the melatonin onset typically occurs during low cortisol secretion. Administration of exogenous melatonin around dusk will shift the phase of the human circadian clock to earlier hours (advance phase shift) leading to phase advances in circadian rhythms (e.g., sleep, endogenous melatonin, cortisol). With aging, the production of melatonin declines and is shifted to later hours while the production of cortisol increases and its peak occurs earlier in the night. In a randomized placebo-controlled crossover study with 8 patients with insomnia aged 55 years and older, a group characterized by low and delayed melatonin production, administration of prolonged-release melatonin in the evening was able to rectify the early onset cortisol production. This delay in nocturnal cortisol onset may explain in part the improvement in sleep quality in elderly patients with insomnia, in schizophrenics, and in depressed patients. Support of circadian pacemaker function by melatonin may provide a new strategy in the treatment of disorders related to impairments in the internal temporal order. The clinical benefit from a decrease in cortisol during the early part of the night may lie beyond the improvement of sleep into a better control of blood pressure, metabolism, and mood. Drug Dev. Res. 65:119,125, 2005. © 2005 Wiley-Liss, Inc. [source] The profound influence of the Late Pliocene Panamanian uplift on the exchange, diversification, and distribution of New World birdsECOGRAPHY, Issue 2 2010Brian Tilston Smith Separated throughout most of the Cenozoic era, North and South America were joined during the mid-Pliocene when the uplift of Panama formed a land bridge between these two continents. The fossil record indicates that this connection allowed an unprecedented degree of inter-continental exchange to occur between unique, previously isolated biotic assemblages, a phenomenon now recognized as the "Great American Biotic Interchange". However, a relatively poor avian fossil record has prevented our understanding the role of the land bridge in shaping New World avian communities. To address the question of avian participation in the GABI, we compiled 64 avian phylogenetic studies and applied a relaxed molecular clock to estimate the timing of trans-isthmus diversification events. Here, we show that a significant pulse of avian interchange occurred in concert with the isthmus uplift. The avian exchange was temporally consistent with the well understood mammalian interchange, despite the presumed greater vagility of birds. Birds inhabiting a variety of habitats and elevational zones responded to the newly available corridor. Within the tropics, exchange was equal in both directions although between extratropical and tropical regions it was not. Avian lineages with Nearctic origins have repeatedly invaded the tropics and radiated throughout South America; whereas, lineages with South American tropical origins remain largely restricted to the confines of the Neotropical region. This previously unrecognized pattern of asymmetric niche conservatism may represent an important and underappreciated contributor to the latitude diversity gradient. [source] Ecological implications of plants' ability to tell the timeECOLOGY LETTERS, Issue 6 2009Víctor Resco Abstract The circadian clock (the endogenous mechanism that anticipates diurnal cycles) acts as a central coordinator of plant activity. At the molecular and organism level, it regulates key traits for plant fitness, including seed germination, gas exchange, growth and flowering, among others. In this article, we explore current evidence on the effect of the clock for the scales of interest to ecologists. We begin by synthesizing available knowledge on the effect of the clock on biosphere,atmosphere interactions and observe that, at least in the systems where it has been tested, the clock regulates gas exchange from the leaf to the ecosystem level, and we discuss its implications for estimates of the carbon balance. Then, we analyse whether incorporating the action of the clock may help in elucidating the effects of climate change on plant distributions. Circadian rhythms are involved in regulating the range of temperatures a species can survive and affects plant interactions. Finally, we review the involvement of the clock in key phenological events, such as flowering time and seed germination. Because the clock may act as a common mechanism affecting many of the diverse branches of ecology, our ultimate goal is to stimulate further research into this pressing, yet unexplored, topic. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||