Depression diagnostics using a nonlinear mathematical oscillatory model.

BACKGROUND AND OBJECTIVES: It is known that long-term stress leads to trauma and very often to depression. Usually, the diagnosis of depression is dealt with by psychiatrists who, based on conversations and questions, diagnose the patient's illness and condition. Unfortunately, this diagnosis is not always reliable. To prevent the development of disease, it is necessary to detect illness in a timely manner. One of the indications of the possibility of the onset of disease is a disturbance in the level of hormones in the body, especially cortisol. The purpose of this study was to develop a mathematical model for cortisol variation resulting from stress which would be useful in making conclusions about depressive states. METHODS: Rapid changes in cortisol concentration, according to ultradian rhythms, which are much faster than the daily circadian rhythm, is modelled as a truly nonlinear oscillator. The mathematical model contains two coupled first order differential equations. The stress is modeled as a pulsating action, described with a periodic trigonometric function, and cortisol production as a cubic nonlinear one. Three models for cortisol variation are considered: 1) the pure nonlinear model, 2) the periodically excited system, 3) and the chaotic system. The results from the study are supported with experimental measurements. RESULTS: Without stress, cortisol variation is of an oscillatory type with a constant steady-state amplitude. Intensive stress causes a resonant phenomenon in cortisol oscillatory variation. The occasion is short and is usually without consequences. For long stress periods deterministic chaos occurs which permanently changes the levels of cortisol. This phenomenon is an indicator of depression. Results from the suggested models are compared with experimentally obtained ones and good quantitative agreement is obtained. CONCLUSIONS: The nonlinear oscillator is a good model for indication of depression. The model provides not only general conclusions, but also individual ones, if personal characteristics are taken into consideration. Response of the model depends not only on the input data related to stress, but also on the system parameters that specify each individual. Findings obtained from this study have implications for the medical diagnosis and treatment of depression.

Fundamentals of sleep regulation: Model and benchmark values for fractal and oscillatory neurodynamics.

Homeostatic, circadian and ultradian mechanisms play crucial roles in the regulation of sleep. Evidence suggests that ratios of low-to-high frequency power in the electroencephalogram (EEG) spectrum indicate the instantaneous level of sleep pressure, influenced by factors such as individual sleep-wake history, current sleep stage, age-related differences and brain topography characteristics. These effects are well captured and reflected in the spectral exponent, a composite measure of the constant low-to-high frequency ratio in the periodogram, which is scale-free and exhibits lower interindividual variability compared to slow wave activity, potentially serving as a suitable standardization and reference measure. Here we propose an index of sleep homeostasis based on the spectral exponent, reflecting the level of membrane hyperpolarization and/or network bistability in the central nervous system in humans. In addition, we advance the idea that the U-shaped overnight deceleration of oscillatory slow and fast sleep spindle frequencies marks the biological night, providing somnologists with an EEG-index of circadian sleep regulation. Evidence supporting this assertion comes from studies based on sleep replacement, forced desynchrony protocols and high-resolution analyses of sleep spindles. Finally, ultradian sleep regulatory mechanisms are indicated by the recurrent, abrupt shifts in dominant oscillatory frequencies, with spindle ranges signifying non-rapid eye movement and non-spindle oscillations - rapid eye movement phases of the sleep cycles. Reconsidering the indicators of fundamental sleep regulatory processes in the framework of the new Fractal and Oscillatory Adjustment Model (FOAM) offers an appealing opportunity to bridge the gap between the two-process model of sleep regulation and clinical somnology.

Seasonal Influence on Salivary Myeloperoxidase Diurnal Variations in Young Healthy Subjects: A Preliminary Study.

BACKGROUND: The interaction between oxidative status markers and biological rhythms is considered particularly important in the pathogenesis of many diseases and more effective therapies. We aimed to determine if the salivary secretion of myeloperoxidase exhibits diurnal variations, and if the potential daily variability differs seasonally. METHODS: The study was performed in Poznan, Poland (52,25°N, 16,58°E) in 10 healthy male volunteers (age median 23.5 years). Whole mixed unstimulated saliva was collected in summer (August) and winter (December) during 36 h at 2-h intervals starting at 6 a.m. on Saturday and ending at 6 p.m. on Sunday, in the domestic setting. The samples were analysed for myeloperoxidase (MPO) and cortisol by immunoassays. The presence of the circadian rhythm of cortisol secretion in saliva confirmed the rhythmicity of the volunteers. RESULTS: For salivary MPO, significantly higher concentrations compared to midnight and noon were observed for 4 a.m. in both summer and winter. Using the cosinor analysis, the variations in salivary MPO levels showed a moderate fit for the 12-h period rhythm (acrophases: in summer 05:37/17:37, in winter 06:16/18:16), without significant differences in the rhythm parameters in summer and winter. However, higher self-reported Global Seasonal Score (which may predispose to seasonal affective disorder) was associated with significantly stronger relative amplitude (RS = 0.811) in winter season only. CONCLUSIONS: In conclusion, our findings suggest the possible ultradian rhythm for MPO in saliva, with two peaks during the day, regardless of the season.

Cardiovascular rhythmicity in overweight and obese children / Ritmicidade cardiovascular em crianças com sobrepeso e obesidade

Abstract Introduction: Obesity is thought to play a role in the disruption of cardiac rhythmicity in obese children, but this is mostly an unexplored field of investigation. We aimed to evaluate the impact of overweight and obesity on circadian and ultradian cardiovascular rhythmicity of prepubertal children, in comparison with normal weight counterparts. Methods: We performed a cross sectional study of 316 children, followed in the birth cohort Generation XXI (Portugal). Anthropometrics and 24-hour ambulatory blood pressure were measured and profiles were examined with Fourier analysis for circadian and ultradian blood pressure (BP) and heart rate (HR) rhythms. Results: Overweight/obese children presented more frequently a non-dipping BP pattern than normal weight counterparts (31.5% vs. 21.6%, p = 0.047). The prevalence of 24-hour mean arterial pressure (MAP) and 8-hour HR rhythmicity was significantly lower in obese children (79.3% vs. 88.0%, p = 0.038 and 33.3% vs. 45.2%, p = 0.031, respectively). The prevalence of the remaining MAP and HR rhythmicity was similar in both groups. No differences were found in the median values of amplitudes and acrophases of MAP and HR rhythms. Discussion: The alterations found in rhythmicity suggest that circadian and ultradian rhythmicity analysis might be sensitive in detecting early cardiovascular dysregulations, but future studies are needed to reinforce our findings and to better understand their long-term implications.

Resumo Introdução: Acredita-se que a obesidade desempenhe um papel na desregulação da ritmicidade cardíaca em crianças obesas, mas esse é um campo de investigação ainda pouco explorado. O objetivo deste trabalho foi avaliar o impacto do sobrepeso e da obesidade na ritmicidade cardiovascular circadiana e ultradiana de crianças pré-púberes, em comparação com crianças com peso normal. Métodos: Realizamos um estudo transversal com 316 crianças, acompanhadas na coorte de nascimentos Geração XXI (Portugal). Foram medidos dados antropométricos e a pressão arterial ambulatorial de 24 horas, e os perfis foram examinados com uma análise de Fourier para ritmos circadianos e ultradianos de pressão arterial (PA) e frequência cardíaca (FC). Resultados: Crianças com sobrepeso/obesidade apresentaram mais frequentemente um padrão de PA não-dipper em comparação com crianças com peso normal (31,5% vs. 21,6%; p = 0,047). A prevalência da pressão arterial média (PAM) de 24 horas e da ritmicidade da FC de 8 horas foi significativamente menor em crianças obesas (79,3% vs. 88,0%; p = 0,038 e 33,3% vs. 45,2%; p = 0,031, respectivamente). A prevalência das restantes ritmicidades da PAM e da FC foi semelhante em ambos os grupos. Não foram encontradas diferenças nos valores medianos das amplitudes e acrofases dos ritmos de PAM e FC. Discussão: As alterações encontradas na ritmicidade sugerem que a análise da ritmicidade circadiana e ultradiana pode ser sensível na detecção de desregulações cardiovasculares precoces, mas são necessários novos estudos para reforçar nossos achados e entender melhor suas implicações a longo prazo.

An auxin-mediated ultradian rhythm positively influences root regeneration via EAR1/EUR1 in Arabidopsis.

Ultradian rhythms have been proved to be critical for diverse biological processes. However, comprehensive understanding of the short-period rhythms remains limited. Here, we discover that leaf excision triggers a gene expression rhythm with ~3-h periodicity, named as the excision ultradian rhythm (UR), which is regulated by the plant hormone auxin. Promoter-luciferase analyses showed that the spatiotemporal patterns of the excision UR were positively associated with de novo root regeneration (DNRR), a post-embryonic developmental process. Transcriptomic analysis indicated more than 4,000 genes including DNRR-associated genes were reprogramed toward ultradian oscillation. Genetic studies showed that EXCISION ULTRADIAN RHYTHM 1 (EUR1) encoding ENHANCER OF ABSCISIC ACID CO-RECEPTOR1 (EAR1), an abscisic acid signaling regulator, was required to generate the excision ultradian rhythm and enhance root regeneration. The eur1 mutant exhibited the absence of auxin-induced excision UR generation and partial failure during rescuing root regeneration. Our results demonstrate a link between the excision UR and adventitious root formation via EAR1/EUR1, implying an additional regulatory layer in plant regeneration.

Phenotypic Interindividual Differences in the Dynamic Structure of Sleep in Healthy Young Adults.

Introduction: Evaluating the dynamic structure of sleep may yield new insights into the mechanisms underlying human sleep physiology. Methods: We analyzed data from a 12-day, 11-night, strictly controlled laboratory study with an adaptation night, 3 iterations of a baseline night followed by a recovery night after 36 h of total sleep deprivation, and a final recovery night. All sleep opportunities were 12 h in duration (22:00-10:00) and recorded with polysomnography (PSG). The PSG records were scored for the sleep stages: rapid eye movement (REM) sleep; non-REM (NREM) stage 1 sleep (S1), stage 2 sleep (S2), and slow wave sleep (SWS); and wake (W). Phenotypic interindividual differences were assessed using indices of dynamic sleep structure - specifically sleep stage transitions and sleep cycle characteristics - and intraclass correlation coefficients across nights. Results: NREM/REM sleep cycles and sleep stage transitions exhibited substantial and stable interindividual differences that were robust across baseline and recovery nights, suggesting that mechanisms underlying the dynamic structure of sleep are phenotypic. In addition, the dynamics of sleep stage transitions were found to be associated with sleep cycle characteristics, with a significant relationship between the length of sleep cycles and the degree to which S2-to-W/S1 and S2-to-SWS transitions were in equilibrium. Discussion: Our findings are consistent with a model for the underlying mechanisms that involves three subsystems - characterized by S2-to-W/S1, S2-to-SWS, and S2-to-REM transitions - with S2 playing a hub-like role. Furthermore, the balance between the two subsystems within NREM sleep (S2-to-W/S1 and S2-to-SWS) may serve as a basis for the dynamic regulation of sleep structure and may represent a novel target for interventions aiming to improve sleep.

Mutual Shaping of Circadian Body-Wide Synchronization by the Suprachiasmatic Nucleus and Circulating Steroids.

Background: Steroids are lipid hormones that reach bodily tissues through the systemic circulation, and play a major role in reproduction, metabolism, and homeostasis. All of these functions and steroids themselves are under the regulation of the circadian timing system (CTS) and its cellular/molecular underpinnings. In health, cells throughout the body coordinate their daily activities to optimize responses to signals from the CTS and steroids. Misalignment of responses to these signals produces dysfunction and underlies many pathologies. Questions Addressed: To explore relationships between the CTS and circulating steroids, we examine the brain clock located in the suprachiasmatic nucleus (SCN), the daily fluctuations in plasma steroids, the mechanisms producing regularly recurring fluctuations, and the actions of steroids on their receptors within the SCN. The goal is to understand the relationship between temporal control of steroid secretion and how rhythmic changes in steroids impact the SCN, which in turn modulate behavior and physiology. Evidence Surveyed: The CTS is a multi-level organization producing recurrent feedback loops that operate on several time scales. We review the evidence showing that the CTS modulates the timing of secretions from the level of the hypothalamus to the steroidogenic gonadal and adrenal glands, and at specific sites within steroidogenic pathways. The SCN determines the timing of steroid hormones that then act on their cognate receptors within the brain clock. In addition, some compartments of the body-wide CTS are impacted by signals derived from food, stress, exercise etc. These in turn act on steroidogenesis to either align or misalign CTS oscillators. Finally this review provides a comprehensive exploration of the broad contribution of steroid receptors in the SCN and how these receptors in turn impact peripheral responses. Conclusion: The hypothesis emerging from the recognition of steroid receptors in the SCN is that mutual shaping of responses occurs between the brain clock and fluctuating plasma steroid levels.

Distinct roles for two Caenorhabditis elegans acid-sensing ion channels in an ultradian clock.

Biological clocks are fundamental to an organism's health, controlling periodicity of behaviour and metabolism. Here, we identify two acid-sensing ion channels, with very different proton sensing properties, and describe their role in an ultradian clock, the defecation motor program (DMP) of the nematode Caenorhabditis elegans. An ACD-5-containing channel, on the apical membrane of the intestinal epithelium, is essential for maintenance of luminal acidity, and thus the rhythmic oscillations in lumen pH. In contrast, the second channel, composed of FLR-1, ACD-3 and/or DEL-5, located on the basolateral membrane, controls the intracellular Ca2+ wave and forms a core component of the master oscillator that controls the timing and rhythmicity of the DMP. flr-1 and acd-3/del-5 mutants show severe developmental and metabolic defects. We thus directly link the proton-sensing properties of these channels to their physiological roles in pH regulation and Ca2+ signalling, the generation of an ultradian oscillator, and its metabolic consequences.

Biological clocks regulate a myriad of processes that occur periodically, from sleeping and waking to how cells use nutrients and energy. One such clock is the one that controls intestinal movements and defecation in the nematode worm Caenorhabditis elegans, which consists of three muscle contractions occurring every 50 seconds. This rhythm is controlled by calcium and proton signalling in the cells of the intestine. The cells of the nematode intestine form a tube, through which gut contents pass. The inside of the tube is acidic, but acidity also plays a role on the outer face of the intestinal tube. In this area, nutrients are distributed and signals are conveyed to other tissues, such as muscles. In fact, acid ­ in the form of protons ­ secreted from the intestinal cells stimulates the muscles that contract in the biological clock that controls the worms' defecation. However, it is poorly understood how the worms control the release of these protons. Kaulich et al. identified two ion channels on the membranes of intestinal cells that become inhibited when the levels of acid surrounding them are high. These channels play distinct roles in controlling the contractions that move the contents of the roundworms' intestines along. The first channel contains a protein called ACD-5, and it is in the membrane of the intestinal cells that faces the inside of the intestinal tube. The second channel is formed by three proteins: FLR-1, ACD-3 and DEL-5. This channel is found on the other side of the intestinal cells, the region where nutrients are distributed and signals are conveyed to the rest of the body. To determine the role of each channel, Kaulich et al. genetically engineered the worms so they would not make the proteins that make up the channels, and imaged the live nematodes to see the effects of removing each channel. The inside of the intestines of worms lacking the ACD-5 containing channel was less acidic than that of normal worms, and the timing of the contractions that control defecation was also slightly altered. Removing the second channel (the one formed by three different proteins), however, had more dramatic effects: the worms were thin, developed more slowly, had less fat tissue and defecated very irregularly. Kaulich et al. imaged live worms to show that the second channel plays a major role in regulating oscillations in acidity both inside and outside cells, as well as controlling calcium levels. This demonstrates that this channel is responsible for the rhythmicity in the contractions that control defecation in the nematodes. Their findings provide important insights towards better understanding proton signalling and the role of acid-sensing ion channels in cellular contexts and biological clocks.

Sexual dimorphism in ultradian and 24h rhythms in plasma levels of growth hormone in Indian walking catfish, Clarias batrachus.

Growth hormone (GH), a key regulator of somatic and reproductive growth in vertebrates, has been extensively studied, although primarily in female fish. Despite numerous reports about sex- and species-specific growth patterns in fish, to our knowledge, there is no report about the 24 h rhythm of plasma GH in male fish. Thus, we aimed to investigate temporal variations in plasma GH levels and the existence of any rhythms therein during the reproductively active months of March to August in the male walking catfish, Clarias batrachus. We also aimed to compare the secretory temporal patterns of GH in male-female specimens of C. batrachus to decipher sexual dimorphism in GH secretions in fish. After 14 days of acclimation to the natural environment, male catfish (N = 240 in total) were sorted and randomly divided into eight groups for study at ZT0 (sunrise ~06:00 h), 3, 6, 9, 12, 15, 18, and 21. During each month, physical parameters like duration of photoperiod and water temperature were measured. Male catfish (n = 40/month) in all eight groups were sampled (n = 5/group) at each time point under the natural time-of-year 24 h light-dark (LD) cycle. Male catfish were anesthetized and blood was collected through a caudal puncture, centrifuged, and plasma isolated. Plasma GH was measured using a competitive homologous enzyme-linked immunosorbent assay. Further, testes were removed, weighed, and the gonadosomatic index (GSI) was calculated. A significant effect of time and season (p ˂ 0.05, two-way ANOVA) on plasma GH level was detected. Cosinor analyses verified the existence of statistically significant (p ˂ 0.05) ultradian (12 h) and 24 h rhythms of plasma GH in male C. batrachus, with the higher values of Mesor (time series mean) and amplitude (one-half peak-to-trough difference) of the periodicities from March to July. Mapping of the acrophases (peak times) showed two ultradian and one 24 h acrophase of GH during the early photophase and early scotophase from March to August. Distinct sexual-dimorphism in plasma GH Mesors and acrophases was noticed between male and female catfish. GSI values of male catfish indicate males mature a little earlier than females in terms of size and reproductive activity. The findings that plasma GH show 24 h and seasonal fluctuations in a sex-specific manner collectively demonstrate the importance of considering the effect of biological 24 h and seasonal time and sex on the GH level in regulating the physiology of somatic growth and reproduction in catfish.

The rhythm of a preterm neonate's life: ultradian oscillations of heart rate, body temperature and sleep cycles.

The objectives are to characterize oscillations of physiological functions such as heart rate and body temperature, as well as the sleep cycle from behavioral states in generally stable preterm neonates during the first 5 days of life. Heart rate, body temperature as well as behavioral states were collected during a daily 3-h observation interval in 65 preterm neonates within the first 5 days of life. Participants were born before 32 weeks of gestational age or had a birth weight below 1500 g; neonates with asphyxia, proven sepsis or malformation were excluded. In total 263 observation intervals were available. Heart rate and body temperature were analyzed with mathematical models in the context of non-linear mixed effects modeling, and the sleep cycles were characterized with signal processing methods. The average period length of an oscillation in this preterm neonate population was 159 min for heart rate, 290 min for body temperature, and the average sleep cycle duration was 19 min. Oscillation of physiological functions as well as sleep cycles can be characterized in very preterm neonates within the first few days of life. The observed parameters heart rate, body temperature and sleep are running in a seemingly uncorrelated pace at that stage of development. Knowledge about such oscillations may help to guide nursing and medical care in these neonates as they do not yet follow a circadian rhythm.

Revealing the hidden reality of the mammalian 12-h ultradian rhythms.

Biological oscillations often cycle at different harmonics of the 24-h circadian rhythms, a phenomenon we coined "Musica Universalis" in 2017. Like the circadian rhythm, the 12-h oscillation is also evolutionarily conserved, robust, and has recently gained new traction in the field of chronobiology. Originally thought to be regulated by the circadian clock and/or environmental cues, recent new evidences support the notion that the majority of 12-h rhythms are regulated by a distinct and cell-autonomous pacemaker that includes the unfolded protein response (UPR) transcription factor spliced form of XBP1 (XBP1s). 12-h cycle of XBP1s level in turn transcriptionally generates robust 12-h rhythms of gene expression enriched in the central dogma information flow (CEDIF) pathway. Given the regulatory and functional separation of the 12-h and circadian clocks, in this review, we will focus our attention on the mammalian 12-h pacemaker, and discuss our current understanding of its prevalence, evolutionary origin, regulation, and functional roles in both physiological and pathological processes.

Glucocorticoid ultradian rhythmicity differentially regulates mood and resting state networks in the human brain: A randomised controlled clinical trial.

Adrenal glucocorticoid secretion into the systematic circulation is characterised by a complex rhythm, composed of the diurnal variation, formed by changes in pulse amplitude of an underlying ultradian rhythm of short duration hormonal pulses. To elucidate the potential neurobiological significance of glucocorticoid pulsatility in man, we have conducted a randomised, double-blind, placebo-controlled, three-way crossover clinical trial on 15 healthy volunteers, investigating the impact of different glucocorticoid rhythms on measures of mood and neural activity under resting conditions by recruiting functional neuroimaging, computerised behavioural tests and ecological momentary assessments. Endogenous glucocorticoid biosynthesis was pharmacologically suppressed, and plasma levels of corticosteroid restored by hydrocortisone replacement in three different regimes, either mimicking the normal ultradian and circadian profile of the hormone, or retaining the normal circadian but abolishing the ultradian rhythm of the hormone, or by our current best oral replacement regime which results in a suboptimal circadian and ultradian rhythm. Our results indicate that changes in the temporal mode of glucocorticoid replacement impact (i) the morning levels of self-perceived vigour, fatigue and concentration, (ii) the diurnal pattern of mood variation, (iii) the within-network functional connectivity of various large-scale resting state networks of the human brain, (iv) the functional connectivity of the default-mode, salience and executive control networks with glucocorticoid-sensitive nodes of the corticolimbic system, and (v) the functional relationship between mood variation and underlying neural networks. The findings indicate that the pattern of the ultradian glucocorticoid rhythm could affect cognitive psychophysiology under non-stressful conditions and opens new pathways for our understanding on the neuropsychological effects of cortisol pulsatility with relevance to the goal of optimising glucocorticoid replacement strategies.

Neonatal irritable sleep-wake rhythm as a predictor of autism spectrum disorders.

Recently, it has been suggested that sleep problems in autism spectrum disorder (ASD) not only are associated symptoms, but may be deeply related to ASD pathogenesis. Common clinical practice relating to developmental disorders, has shown that parents of children with ASD have often stated that it is more difficult to raise children in the neonatal period because these children exhibit sleep problems. This study investigated the possibility that abnormal neonatal sleep-wake rhythms are related to future ASD development. We administered questionnaires to assess parent(s) of children with ASD and controls. A retrospective analysis was conducted among 121 children with ASD (94 male and 27 female children) recruited from the K-Development Support Center for Children (K-ASD), 56 children with ASD (40 male and 16 female children) recruited from the H-Children's Sleep and Development Medical Research Center (H-ASD) and 203 children (104 male and 99 female children) recruited from four nursery schools in T-city (control). Irritable/over-reactive types of sleep-wake rhythms that cause difficulty in raising children, such as 1) frequently waking up, 2) difficulty falling asleep, 3) short sleep hours, and 4) continuous crying and grumpiness, were observed more often in ASD groups than in the control group. Additionally, the number of the mothers who went to bed after midnight during pregnancy was higher in the ASD groups than in the control group. Sleep-wake rhythm abnormalities in neonates may be considerable precursors to future development of ASD. Formation of ultradian and postnatal circadian rhythms should be given more attention when considering ASD development. Although this is a retrospective study, the results suggest that a prospective study regarding this issue may be important in understanding and discovering intervention areas that may contribute to preventing and/or properly treating ASD.

Circahoralian Rhythms of Body Temperature in Mammals and Birds with Different Metabolism Levels.

The time course of intraperitoneal body temperature has been analyzed in two species of mammals (laboratory C57Bl/6 mice and white-breasted hedgehogs (Erinaceus roumanicus) and in two species of passerine birds (common greenfinch Chloris chloris and Japanese quail Coturnix japonica) with different body weights. Similar sets of basic harmonics appearing synchronously in different individuals have been found in the body temperature spectra of the species studied. The level of basal metabolism in those animal species considerably vary; therefore, the period of fluctuations of body temperature in the range of 10-120 min is not determined by the internal characteristics of the body and, presumably, reflects the influence of an external biotropic environmental factor.

Effect of Surgical Removal of Testicles and Adrenal Glands on Ultradian Rhythms of Body Temperature in Male Wistar Rats under Conditions of Constant Illumination.

We have studied body temperature dynamics of mature male Wistar rats maintained under constant illumination after surgical removal of the testicles and adrenal glands. In gonadectomized animals, pronounced increases in body temperature (>0.9°C) were observed every 4-6 h; during the periods 03.35-04.30, 07.35-08.30, 11.35-12.30, 15.35-16.30, 19.35-20.30, and 23.35-00.30, they were recorded 1.5-fold more often than during the rest periods. These results do not significantly differ from the parameters of the control group. Combined removal of the testicles and adrenal glands led to shortening of main period of temperature oscillations to 4-4.5 h and a decrease in its amplitude; pronounced increase in body temperature (>0.5°C) was observed 2.1 times more often during the periods 03.35-04.30, 07.35-08.30, 11.35-12.30, 15.35-16.30, 19.35-20.30, and 23.35-00.30 than in other time intervals. Thus, the removal of the testicles and adrenal glands does not violate the 4-h intraday rhythm of body temperature.

Ultradian Rhythms in the Hypothalamic Arcuate Nucleus Kisspeptin Neurons and Developmental Processes.

Numerous physiological processes in nature have multiple oscillations within 24 h, that is, ultradian rhythms. Compared to the circadian rhythm, which has a period of approximately one day, these short oscillations range from seconds to hours, and the mechanisms underlying ultradian rhythms remain largely unknown. This review aims to explore and emphasize the implications of ultradian rhythms and their underlying regulations. Reproduction and developmental processes show ultradian rhythms, and these physiological systems can be regulated by short biological rhythms. Specifically, we recently uncovered synchronized calcium oscillations in the organotypic culture of hypothalamic arcuate nucleus (ARN) kisspeptin neurons that regulate reproduction. Synchronized calcium oscillations were dependent on voltage-gated ion channel-mediated action potentials and were repressed by chemogenetic inhibition, suggesting that the network within the ARN and between the kisspeptin population mediates the oscillation. This minireview describes that ultradian rhythms are a general theme that underlies biological features, with special reference to calcium oscillations in the hypothalamic ARN from a developmental perspective. We expect that more attention to these oscillations might provide insight into physiological or developmental mechanisms, since many oscillatory features in nature still remain to be explored.

Biological clocks and incremental growth line formation in dentine.

Dentine- and enamel-forming cells secrete matrix in consistent rhythmic phases, resulting in the formation of successive microscopic growth lines inside tooth crowns and roots. Experimental studies of various mammals have proven that these lines are laid down in subdaily, daily (circadian), and multidaily rhythms, but it is less clear how these rhythms are initiated and maintained. In 2001, researchers reported that lesioning the so-called master biological clock, the suprachiasmatic nucleus (SCN), halted daily line formation in rat dentine, whereas subdaily lines persisted. More recently, a key clock gene (Bmal1) expressed in the SCN in a circadian manner was also found to be active in dentine- and enamel- secretory cells. To probe these potential neurological and local mechanisms for the production of rhythmic lines in teeth, we reexamined the role of the SCN in growth line formation in Wistar rats and investigated the presence of daily lines in Bmal1 knockout mice (Bmal1-/- ). In contrast to the results of the 2001 study, we found that both daily and subdaily growth lines persisted in rat dentine after complete or partial SCN lesion in the majority of individuals. In mice, after transfer into constant darkness, daily rhythms continued to manifest as incremental lines in the dentine of each Bmal1 genotype (wild-type, Bmal+/- , and Bmal1-/- ). These results affirm that the manifestation of biological rhythms in teeth is a robust phenomenon, imply a more autonomous role of local biological clocks in tooth growth than previously suggested, and underscore the need further to elucidate tissue-specific circadian biology and its role in incremental line formation. Investigations of this nature will strengthen an invaluable system for determining growth rates and calendar ages from mammalian hard tissues, as well as documenting the early lives of fossil hominins and other primates.

The Inconsistent Nature of Heart Rate Variability During Sleep in Normal Children and Adolescents.

Introduction: Cardiac function is modulated by multiple factors including exogenous (circadian rhythm) and endogenous (ultradian 90-110 min sleep cycle) factors. By evaluating heart rate variability (HRV) during sleep, we will better understand their influence on cardiac activity. The aim of this study was to evaluate HRV in the dark phase of the circadian rhythm during sleep in healthy children and adolescents. Methods: One 3 min segment of pre-sleep electrocardiography (EEG) and 3, 6 min segments of electrocardiography recorded during polysomnography from 75 healthy children and adolescents were sampled during progressive cycles of slow wave sleep (SWS1, SWS2, SWS3). Three, 3 min segments of rapid eye movement sleep (REM) were also assessed, with REM1 marked at the last REM period before awakening. Studies that recorded REM3 prior to SWS3 were used for assessment. HRV variables include the following time domain values: mean NN (average RR intervals over given time), SDNN (Standard Deviation of RR intervals), and RMSSD (root Mean Square of beat-to-beat Differences). Frequency domain values include: low frequency (LF), high frequency (HF), and LF:HF. Results: Mixed linear effects model analysis revealed a significant difference in time and frequency domain values between sleep cycles and stages. Mean NN was lowest (highest heart rate) during pre-sleep then significantly increased across SWS1-3. Mean NN in SWS1 was similar to all REM periods which was significantly lower than both SWS2 and SWS3. SDNN remained at pre-sleep levels until SWS3, and then significantly increased in REM1&2. There was a large drop in LF from pre-sleep to SWS1. As cycles progressed through the night, LF remains lower than awake but increases to awake like levels by REM2. RMSSD and HF were lowest in pre-sleep and increased significantly by SWS1 and remain high and stable across stages and cycles except during the REM3 period where RMSSD decreased. Conclusion: Our results demonstrate that there are considerable changes in the spectral analysis of cardiac function occurring during different sleep stages and between sleep cycles across the night. Hence, time of night and sleep stage need to be considered when reporting any HRV differences.

PSK1 coordinates glucose metabolism and utilization and regulates energy-metabolism oscillation in Saccharomyces cerevisiae.

Energy-metabolism oscillations (EMO) are ultradian biological rhythms observed in in aerobic chemostat cultures of Saccharomyces cerevisiae. EMO regulates energy metabolism such as glucose, carbohydrate storage, O2 uptake, and CO2 production. PSK1 is a nutrient responsive protein kinase involved in regulation of glucose metabolism, sensory response to light, oxygen, and redox state. The aim of this investigation was to assess the function of PSK1 in regulation of EMO. The mRNA levels of PSK1 fluctuated in concert with EMO, and deletion of PSK1 resulted in unstable EMO with disappearance of the fluctuations and reduced amplitude, compared with the wild type. Furthermore, the mutant PSK1Δ showed downregulation of the synthesis and breakdown of glycogen with resultant decrease in glucose concentrations. The redox state represented by NADH also decreased in PSK1Δ compared with the wild type. These data suggest that PSK1 plays an important role in the regulation of energy metabolism and stabilizes ultradian biological rhythms. These results enhance our understanding of the mechanisms of biorhythms in the budding yeast.

Ultradian Rhythms of Body Temperatures in Male Wistar Rats Maintained under Conditions of Constant Illumination.

We studied the dynamics of the body temperature in mature male Wistar rats maintained under condition of constant illumination. It was shown that body temperature under these conditions varied with a 3-5-h period. The daily dynamics of body temperature summed up over 20-23-day intervals showed a 4-h ultradian rhythm with maxima at 3.35-4.30, 7.35-8.30, 11.35-12.30, 15.35-16.30, 19.35-20.30, and 23.35-00.30 h. During these hours, pronounced (>0.9°C) increase in body temperature was observed by 1.6 times more often than in other eriods. Thus, there are periods during the day when the increase in body temperature in rats in the absence of light cues occurs more often than in other periods of the day. Hence, about 4-h ultradian rhythm of body temperature has an external synchronizer that differs from lighting conditions.