Calcium-binding proteins in the circadian centers of the common marmoset (Callithrix jacchus) and the rock cavy (Kerodon rupestris) brains

The hypothalamic suprachiasmatic nucleus (SCN) and the thalamic intergeniculate leaflet (IGL) are considered to be the main centers of the mammalian circadian timing system. In primates, the IGL is included as part of the pregeniculate nucleus (PGN), a cell group located mediodorsally to the dorsal lateral geniculate nucleus. This work was carried out to comparatively evaluate the immunohistochemical expression of the calcium-binding proteins calbindin D-28k (CB), parvalbumin (PV), and calretinin (CR) into the circadian brain districts of the common marmoset and the rock cavy. In both species, although no fibers, terminals or perikarya showed PV-immunoreaction (IR) into the SCN, CB-IR perikarya labeling was detected throughout the SCN rostrocaudal extent, Seeming to delimit its cytoarchitectonic borders. CR-IR perikarya and neuropil were noticed into the ventral and dorsal portions of the SCN, lacking immunoreactivity in the central core of the marmoset and filling the entire nucleus in the rockcavy. The PGN of the marmoset presented a significant number of CB-, PV-, and CR-IR perikarya throughout the nucleus. The IGL of the rocky cavy exhibited a prominent CB- and CR-IR neuropil, showing similarity to the pattern found in other rodents. By comparing with literature data from other mammals, the results of the present study suggest that CB, PV, and CR are differentially distributed into the SCN and IGL among species. They may act either in concert or in a complementary manner in the SCN and IGL, so as to participate in specific aspects of the circadian regulation. (c) 2008 Elsevier Inc. All rights reserved.

Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression

Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variations in myocardial biology. We, therefore, generated a cardiomyocyte-specific circadian clock mutant (CCM) mouse to test this hypothesis. At 12 wk of age, CCM mice exhibit normal myocardial contractile function in vivo, as assessed by echocardiography. Radiotelemetry studies reveal attenuation of heart rate diurnal variations and bradycardia in CCM mice (in the absence of conduction system abnormalities). Reduced heart rate persisted in CCM hearts perfused ex vivo in the working mode, highlighting the intrinsic nature of this phenotype. Wild-type, but not CCM, hearts exhibited a marked diurnal variation in responsiveness to an elevation in workload (80 mmHg plus 1 mu M epinephrine) ex vivo, with a greater increase in cardiac power and efficiency during the dark (active) phase vs. the light (inactive) phase. Moreover, myocardial oxygen consumption and fatty acid oxidation rates were increased, whereas cardiac efficiency was decreased, in CCM hearts. These observations were associated with no alterations in mitochondrial content or structure and modest mitochondrial dysfunction in CCM hearts. Gene expression microarray analysis identified 548 and 176 genes in atria and ventricles, respectively, whose normal diurnal expression patterns were altered in CCM mice. These studies suggest that the cardiomyocyte circadian clock influences myocardial contractile function, metabolism, and gene expression.

Longitudinal study of the spectral composition of behavioral rhythms in the rat

Four. male Wistar rats were housed in pairs of siblings, on LD 12:12h and 22 degrees C + 2 degrees C. Food and water were provided ad libitum. Behavior was videotaped from the 1st to the 3rd month of life. In each age-bracket the spectral composition of rhythmic expressions of the following behavioral categories was analyzed: rest, eat, drink, cage exploration, self-grooming, and social interaction. Rats maintained a stable rank order of time engaged in different behaviors through development, despite modification of time spent in grooming, drinking and social interaction as they got older. Spectral composition of behaviors followed a general ontogenetic pattern: ultradian frequencies of 12-h and 8-h were the strongest in the 1st month and circadian periodicity was predominant in the 3rd month. The increase of circadian power compared with ultradian power components agrees with literature findings. To our knowledge, self-grooming and social interaction have not been investigated before in this context. The similarities between siblings suggest the mutual influence of partners and/ or the existence of genetic factors. Ongoing studies are examining the importance of the social surroundings in which animals develop to the acquisition of adult rhythmic pattern.

Modeling the Emergence of Circadian Rhythms in a Clock Neuron Network

Circadian rhythms in pacemaker cells persist for weeks in constant darkness, while in other types of cells the molecular oscillations that underlie circadian rhythms damp rapidly under the same conditions. Although much progress has been made in understanding the biochemical and cellular basis of circadian rhythms, the mechanisms leading to damped or self-sustained oscillations remain largely unknown. There exist many mathematical models that reproduce the circadian rhythms in the case of a single cell of the Drosophila fly. However, not much is known about the mechanisms leading to coherent circadian oscillation in clock neuron networks. In this work we have implemented a model for a network of interacting clock neurons to describe the emergence (or damping) of circadian rhythms in Drosophila fly, in the absence of zeitgebers. Our model consists of an array of pacemakers that interact through the modulation of some parameters by a network feedback. The individual pacemakers are described by a well-known biochemical model for circadian oscillation, to which we have added degradation of PER protein by light and multiplicative noise. The network feedback is the PER protein level averaged over the whole network. In particular, we have investigated the effect of modulation of the parameters associated with (i) the control of net entrance of PER into the nucleus and (ii) the non-photic degradation of PER. Our results indicate that the modulation of PER entrance into the nucleus allows the synchronization of clock neurons, leading to coherent circadian oscillations under constant dark condition. On the other hand, the modulation of non-photic degradation cannot reset the phases of individual clocks subjected to intrinsic biochemical noise.

Daily rhythms of native Brazilians in summer and winter

Access to electricity, granting relative independence of human activity on the dark phase of the day, has been pointed out as an important cause for the absence of seasonal changes in the daily rhythms of humans living in urban areas. Featuring a population of adult Guarani natives living without access to electricity, the present naturalistic study was designed to explore possible effects of different natural photoperiods and temperature on human circadian rhythms. We compared time series of wrist temperature (WT) and motor activity in winter and summer, respectively, 01 24 individuals aged 18 to 80. Twenty-four-hour rhythms of WT showed lower amplitudes and higher mean levels in summer, with no significant seasonal differences in acrophase. In contrast, rest-activity (RA) rhythms exhibited a significantly later rest on-and offset in summer, but no seasonal changes in duration, amplitude and mean level. We furthermore identified a phase advance of both the WT acrophase and rest onset with increasing age of the individuals. We concluded that in our study the effect of different seasons was reflected in the amplitude and mean level of the WT rhythm, as well the onset of nighttime rest, which was delayed in summer. (C) 2011 Elsevier Inc. All rights reserved.

Studies of biological rhythms in responses to influenza infection and vaccination

Three studies examined seasonal or circadian variations in selected responses to influenza infection or vaccination. The first, a seroepidemiologic study, evaluated temporal patterns of antibody titers to influenza A/Texas. Human umbilical cord bloods were sampled over a two-year period when the virus was not present in the community. No endogenous seasonal pattern was detected. The second study included three experiments on circadian rhythms in mice. Neither susceptibility nor protection from inactivated or attenuated vaccine varied significantly according to time of administration. A slight effect, however, was suggested with inactivated vaccine. Three human vaccine trials comprised the third study. Outcome variables included rise in antibody titer, final antibody titer, incidence of adverse reactions, and protection from community infection. Patterns in antibody response and protection variables were inconsistent, and generally not clinically significant. Local reactions to inactivated vaccine were more frequent if injections were received in the afternoon as compared to morning. This was true to adults that had been previously vaccinated. ^

A contribution to the deterministic modelling of circadian rhythms in cell proliferation activity

This paper presents a deterministic continuous model of proliferative cell activity. The classical series of connected compartments is revisited along with a simple mathematical treatment of two hypotheses: constant transit times and harmonic Ts. Several examples are presented to support these ideas, both taken from previous literature and recent experiences with the fish Carassius auratus, developed at the Junta de Energía Nuclear, Madrid, Spain.

The protein kinase CK2 is involved in regulation of circadian rhythms in Arabidopsis

A wide range of processes in plants, including expression of certain genes, is regulated by endogenous circadian rhythms. The circadian clock-associated 1 (CCA1) and the late elongated hypocotyl (LHY) proteins have been shown to be closely associated with clock function in Arabidopsis thaliana. The protein kinase CK2 can interact with and phosphorylate CCA1, but its role in the regulation of the circadian clock remains unknown. Here we show that plants overexpressing CKB3, a regulatory subunit of CK2, display increased CK2 activity and shorter periods of rhythmic expression of CCA1 and LHY. CK2 is also able to interact with and phosphorylate LHY in vitro. Additionally, overexpression of CKB3 shortened the periods of four known circadian clock-controlled genes with different phase angles, demonstrating that many clock outputs are affected. This overexpression also reduced phytochrome induction of an Lhcb gene. Finally, we found that the photoperiodic flowering response, which is influenced by circadian rhythms, was diminished in the transgenic lines, and that the plants flowered earlier on both long-day and short-day photoperiods. These data demonstrate that CK2 is involved in regulation of the circadian clock in Arabidopsis.

Phytochrome B and the Regulation of Circadian Ethylene Production in Sorghum1

The sorghum (Sorghum bicolor L. Moench) cultivar 58M, which contains the null mutant phytochrome B gene, shows reduced photoperiodic sensitivity and exhibits a shade-avoidance phenotype. Ethylene production by seedlings of wild-type and phytochrome B mutant cultivars was monitored every 3 h, and both cultivars were found to produce ethylene in a circadian rhythm, with peak production occurring during the day. The phytochrome B mutant produces rhythmic peaks of ethylene with approximately 10 times the amplitude of the wild-type counterpart with the same period and diurnal timing. The source of the mutant's additional ethylene is the shoot. The diurnal rhythm can be produced with either light or temperature cycles; however, both light and temperature cycles are required for circadian entrainment. The temperature signal overrides the light signal in the production of diurnal rhythms, because seedlings grown under thermoperiods reversed with the photoperiod produced ethylene peaks during the warm nights. To examine the effect of extreme shading on ethylene production, seedlings were grown under dim, far-red-enriched light. This treatment duplicated the phytochrome B mutant's shade-avoidance phenotype in the wild type and caused the wild type to produce ethylene peaks similar to those observed in the mutant. The results confirm that phytochrome B is not required for proper function of circadian timing, but it may be involved in modulating physiological rhythms driven by the biological clock oscillator.

Circannual rhythms of maturation in the female rainbow trout and their entrainment by changes in photoperiod

The importance of endogenous rhythms in the photoperiodic control of the annual reproduction cycle in female rainbow trout was investigated. The effect of photoperiod regimes on the different stages of maturation was assessed by recording the timing of ovulation and from quantifying associated changes in serum oestradiol-17,testosterone and total calcium. Maintained under constant 6L:18D and constant temperature for up to four years, rainbow trout exhibited an endogenous rhythm of maturation with a periodicity of approximately one year. This rhythm of maturation appears to be driven by an autonomous circannual oscillator or clock which can be dissociated from the neuroendocrine mechanisms controlling gonadal maturation. Under conditions of constant 18L:6D or LL the periodicity of the maturation rhythm was 5.5-6 months; it is suggested that this periodicity may be caused by a splitting or uncoupling of at least two circannual clocks involved in the control of maturation. Abrupt changes in the length of the photoperiod act as a zeitgeber to entrain the endogenous rhythm of maturation. Whether the timing of maturation is advanced or delayed depends primarily on the direction of the change in photoperiod and its timing in relation to the phase of the rhythm, with the magnitude of the alteration in photoperiod having only a supplementary effect. The effect of specific changes in photoperiod on the entrainment of the maturation cycle can be described in terms of a phase-response curve. Photic information is transduced, probably by the pineal gland, into a daily rhythm of melatonin; exposure of rainbow trout to skeleton and resonance photoperiod regimes indicated that daylength measurement is effected by endogenous circadian clock(s) rather than by hour-glass mechanisms. A gating mechanism is closely associated with the circannual clock which determines the timing of onset of maturation in virgin female rainbow trout, only allowing fish that have attained a threshold stage of development to undergo gonadal maturation. Collectively the results support the hypothesis that the female rainbow trout exhibits an endogenous circannual rhythm of maturation which can be entrained by changes in photoperiod.

Circadian gene variants and susceptibility to type 2 diabetes:a pilot study

Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants.

Circadian rhythm disruption and post-surgical recovery

Circadian rhythms, patterns of each twenty-four hour period, are found in most bodily functions. The biological cycles of between 20 and 28 hours have a profound effect on an individual's mood, level of performance, and physical well being. Loss of synchrony of these biological rhythms occurs with hospitalization, surgery and anesthesia. The purpose of this comparative, correlational study was to determine the effects of circadian rhythm disruption in post-surgical recovery. Data were collected during the pre-operative and post-operative periods in the following indices: body temperature, blood pressure, heart rate, urine cortisol level and locomotor activity. The data were analyzed by cosinor analysis for evidence of circadian rhythmicity and disruptions throughout the six day study period which encompassed two days pre-operatively, two days post-operatively, and two days after hospital discharge. The sample consisted of five men and five women who served as their own pre-surgical control. The surgical procedures were varied. Findings showed evidence of circadian disruptions in all subjects post-operatively, lending support for the hypotheses.

Cross-talk and regulatory interactions between the essential response regulator RpaB and cyanobacterial circadian clock output

The response regulator RpaB (regulator of phycobilisome associated B), part of an essential two-component system conserved in cyanobacteria that responds to multiple environmental signals, has recently been implicated in the control of cell dimensions and of circadian rhythms of gene expression in the model cyanobacterium Synechococcus elongatus PCC 7942. However, little is known of the molecular mechanisms that underlie RpaB functions. In this study we show that the regulation of phenotypes by RpaB is intimately connected with the activity of RpaA (regulator of phycobilisome associated A), the master regulator of circadian transcription patterns. RpaB affects RpaA activity both through control of gene expression, a function requiring an intact effector domain, and via altering RpaA phosphorylation, a function mediated through the N-terminal receiver domain of RpaB. Thus, both phosphorylation cross-talk and coregulation of target genes play a role in the genetic interactions between the RpaA and RpaB pathways. In addition, RpaB∼P levels appear critical for survival under light:dark cycles, conditions in which RpaB phosphorylation is environmentally driven independent of the circadian clock. We propose that the complex regulatory interactions between the essential and environmentally sensitive NblS-RpaB system and the SasA-RpaA clock output system integrate relevant extra- and intracellular signals to the circadian clock.

Circadian Phase Control - Genetic Algorithm and Non-linear Control Approach

This paper deals with the phase control for Neurospora circadian rhythm. The nonlinear control, given by tuning the parameters (considered as controlled variables) in Neurospora dynamical model, allows the circadian rhythms tracking a reference one. When there are many parameters (e.g. 3 parameters in this paper) and their values are unknown, the adaptive control law reveals its weakness since the parameters converging and control objective must be guaranteed at the same time. We show that this problem can be solved using the genetic algorithm for parameters estimation. Once the unknown parameters are known, the phase control is performed by chaos synchronization technique.

Circadian Rhythm And Profile In Patients With Juvenile Myoclonic Epilepsy And Temporal Lobe Epilepsy.

This study intended to compare the circadian rhythm and circadian profile between patients with juvenile myoclonic epilepsy (JME) and patients with temporal lobe epilepsy (TLE). We enrolled 16 patients with JME and 37 patients with TLE from the Outpatient Clinic of UNICAMP. We applied a questionnaire about sleep-wake cycle and circadian profile. Fourteen (87%) out of 16 patients with JME, and 22 out of 37 (59%) patients with TLE reported that they would sleep after seizure (p < 0.05). Three (19%) patients with JME, and 17 (46%) reported to be in better state before 10:00 AM (p < 0.05). There is no clear distinct profile and circadian pattern in patients with JME in comparison to TLE patients. However, our data suggest that most JME patients do not feel in better shape early in the day.