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Physiology is an integrative science that requires an understanding of the organism as a whole to acquire a deep comprehension of its functions and avoid misconceptions that may impair further learning. Thus it is necessary to develop resources that promote the integrative vision that Physiology requires. Chronobiology is a challenging discipline and one of the least addressed concepts in Physiology curricula. The activity here presented proposes a workshop with a theoretical-practical perspective in the context of the Neuroscience Conferences held annually at our university. All conference presentations are neuroscience-related topics, in combination with practical activities, some of them analyzing variables of the students themselves. We chose to assess this informal teaching scenario to involve the students with a scientific perspective while learning and hoping to increase their appreciation for different topics related to neuroscience. Specifically for this activity on chronobiology, the evaluation was carried out via a survey study including quantitative and qualitative questions and semistructured personal interviews. In general, the results reveal a very positive opinion from students regarding aspects such as the teaching methodology, the organization before and during the activity or the added value of the experience for their future professional performance. Some of the students stated they were more aware of the importance of their circadian system and even changed some of their personal daily routines after the activity. Such positive feedback encourages us to continue working in this theoretical-practical format in the future, as it contributes to improving students' perception of their own learning.

Background & Aims: Assessment of circadian health is confined to adults. However, understanding circadian status of school-aged children is necessary due to its health implications. The aim was to develop 1) a protocol to assess circadian function in school-aged children by combining the best non-invasive tools previously validated in adults; 2) a score to capture circadian function in children including food timing. This protocol will allow to explore gender differences and to compare the circadian function of school-aged children with adults from the same Mediterranean area., Methods: Healthy children (8-12 y) from 3 schools in a Mediterranean area of Spain were recruited (n = 248; 125 males and 123 females). Several non-invasive tools were used: a) 7-day-diaries of food timing and food intake, physical-activity and sleep, b) Munich-chronotype-self-reported-questionnaire; c) cortisol and melatonin saliva determinations; d) 7-day-rhythms of wrist temperature (T), activity (A), position (P) and the integrative variable TAP e) 7-day-light exposure., Results: We have constructed the first school-aged children population for the assessment of circadian function (ONTIME-Jr) and a new circadian score has been developed. Among circadian-related measures, TAP was the most suitable and reliable to determine circadian system characteristics. Circadian function was better in girls than in boys [circadian score (AU) Mean ± SD (girls, 1216 ± 153 vs. 1159 ± 173 boys, P = 0.012)], and also in school-aged children than in adults from the same Mediterranean area (Circadian-Function-Index: children 0.47 ± 0.06 vs. adults 0.45 ± 0.06 P = 0.001)., Conclusions: A new protocol, including TAP and food timing, demonstrated to be reliable in assessing circadian function in children. These non-invasive techniques provide the wherewithal for paediatricians to assess circadian function in clinical practice., Trial Registration: Chronobiology and childhood obesity (ONTIME-Jr: Obesity, Nutrigenetics, Timing and Mediterranean, Junior). ClinicalTrials.gov ID: NCT02895282, October 2014., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Changes in lighting accompany modern urbanization trends and can lead to various pathologies based on circadian disturbances. In this study, we assessed the changes in the circadian rhythm of core body temperature (Tcore) and locomotor activity of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) following exposure to different lighting conditions: extended light phase of the day (16 h–8 h, 20 h–4 h, 24 h–0 h), light pollution, monochromatic light, and bright light therapy. The telemetry data was collected after experimental lighting conditions during periods with standard lighting (12 h of light and 12 h of darkness) and was processed using linear and cosinor analysis. The daily rhythms of rats’ parameters persisted in accordance with the standard lighting regime. Tcore changes were observed in both groups compared to the initial period: in WKY, a decrease in Tcore during the darkness and an increase during the light; in SHR, the opposite trend, with Tcore increased during the darkness and decreased during the light phase of the day. A relationship between Tcore and activity was observed with weak correlation. WKY exhibited more pronounced signs of adaptive variation and desynchronization compared to SHR, which could be associated with a wider range of functional capabilities of the organism without cardiovascular pathology.

Introduction: European mistletoe (Viscum album L.) has been gaining increasing interest in the field of oncology as a clinically relevant adjunctive treatment in many forms of cancer. In the field of phytopharmacology, harvesting time is pivotal. In the last century, a form of metabolomic fingerprinting based on pattern formation was proposed as a way to determine optimal harvesting times to ensure high quality of mistletoe as raw material for pharmaceutical use. In order to further evaluate the information obtained with this metabolomic fingerprinting method, we analysed a large time series of previously undigitised daily mistletoe chromatograms dating back to the 1950s.Methods: These chromatograms were scanned and evaluated using computerized image analysis, resulting in 12 descriptors for each individual chromatogram. We performed a statistical analysis of the data obtained, investigating statistical distributions, cross-correlations and time self-correlations.Results: The analysed dataset spanning about 27 years, contains 19,037 evaluable chromatograms in daily resolution. Based on the distribution and cross-correlation analyses, the 12 descriptors could be clustered into six independent groups describing different aspects of the chromatograms. One descriptor was found to mirror the annual rhythm being well correlated with temperature and a phase shift of 10 days. The time self-correlation analysis showed that most other descriptors had a characteristic self-correlation of ∼50 days, which points to further infradian rhythms (i.e., more than 24 h).Discussion: To our knowledge, this dataset is the largest of its type. The combination of this form of metabolomic fingerprinting with the proposed computer analysis seems to be a promising tool to characterise biological variations of mistletoe. Additional research is underway to further analyse the different rhythms present in this dataset.

The article is an editorial in the journal Frontiers in Physiology, discussing the field of chronobiology and its focus on biological rhythms, particularly circadian rhythms. It emphasizes the importance of studying non-circadian rhythms and using diverse models to understand circadian rhythms in different species. The editorial also highlights the impact of chronobiology on biomedical sciences and the potential for incorporating circadian medicine into healthcare. It features the research of up-and-coming investigators in the field, covering topics such as diet, glucose metabolism, sleep loss, and post-transcriptional mechanisms in regulating circadian rhythms. The editorial pays tribute to the late Steve Brown, a prominent scientist in the field. [Extracted from the article]

Abstract Heart rate variability (HRV) is commonly used in experimental studies to assess sympathetic and parasympathetic activities. The belief that HRV in rodents reflects similar cardiovascular regulations in humans is supported by evidence, and HRV in rats appears to be at least analogous to that in humans, although the degree of influence of the parasympathetic division of the autonomic nervous system (ANS) may be greater in rats than in humans. Experimental studies are based on control or baseline values, on the basis of which the change in ANS activity after a given experimental intervention is assessed, but it is known that the ANS in rats is very sensitive to various stress interventions, such as the manipulation itself, and ANS activity can also differ depending on sex, the time of measurement, and whether the animals are under general anaesthesia. Thus, for correct assessment, changes in ANS activity and their relationship to the observed parameter should be based on whether ANS activity does or does not change but also to what extent the activity is already changed at the start of the experiment. Since rats are considered to be the most suitable model animal for basic cardiovascular research, in this review we point out existing differences in individual HRV frequency parameters at the start of experiments (control, baseline values), taking into account sex in relation to time of measurement and anaesthesia.

Summary: Disruption of circadian rhythms during fetal development may predispose mice to developing heart disease later in life. Here, we report that male, but not female, mice that had experienced chronic circadian disturbance (CCD) in utero were more susceptible to pathological cardiac remodeling compared with mice that had developed under normal intrauterine conditions. CCD-treated males showed ventricular chamber dilatation, enhanced myocardial fibrosis, decreased contractility, higher rates of induced tachyarrhythmia, and elevated expression of biomarkers for heart failure and myocardial remodeling. In utero CCD exposure also triggered sex-dependent changes in cardiac gene expression, including upregulation of the secretoglobin gene, Scgb1a1, in males. Importantly, cardiac overexpression of Scgb1a1 was sufficient to induce myocardial hypertrophy in otherwise naive male mice. Our findings reveal that in utero CCD exposure predisposes male mice to pathological remodeling of the heart later in life, likely as a consequence of SCGB1A1 upregulation.

In the middle of the twentieth century, physiologists interested in human biological rhythms undertook a series of field experiments in natural spaces that they believed could closely approximate conditions of biological timelessness. With the field of rhythms research was still largely on the fringes of the life sciences, natural spaces seemed to offer unique research opportunities beyond what was available to physiologists in laboratory spaces. In particular, subterranean caves and the High Arctic became archetypal 'natural laboratories' for the study of human circadian (daily) rhythms. This paper is explores the field experiments which occurred in these 'timeless spaces'. It considers how scientists understood these natural spaces as suitably 'timeless' for studying circadian rhythms and what their experimental practices can tell us about contemporary physiological notions of biological time, especially its relationship to 'environmentality' (Formosinho et al. in Stud History Philos Sci 91:148–158, 2022). In so doing, this paper adds to a growing literature on the interrelationship of field sites by demonstrating the ways that caves and the Arctic were connected by rhythms scientists. Finally, it will explore how the use of these particular spaces were not just scientific but also political – leveraging growing Cold War anxieties about nuclear fallout and the space race to bring greater prestige and funding to the study of circadian rhythms in its early years. [ABSTRACT FROM AUTHOR]

Medical science does not treat death as an independent physiological phenomenon. It believes that disease is the cause of death and treats both as preventable phenomena. Doctors and relatives nurture a guilt complex when death occurs. The moment of natural death is robbed of its poignancy. There is no cause of death. Death of the physical body is an intrinsic, time governed, built-in ontolytic program. It completes the biologic trajectory of the individual organism which begins at conception and ends with death. In this article, the actual built-in mechanism and operation of the physiological process of death is suggested vis-a-vis biology and medicine. The physical body of an individual is like a biological gadget which is constantly charged with life force received from cosmic energy through the subtle body which is an implement that cannot be objectified in the same way as the gross physical body but is experienced only subjectively by one and all, as mind (antahkaran in Sanskrit and Indian languages, meaning inner instrument, a subtler instrument in contrast to external organs of actions like limbs, tongue, etc. of the physical body). This life force keeps the subtle body and the entire physical body live and functioning. It maintains the body's integrity and internal homeostasis throughout life. The physical body like a gadget has a built-in program which decides how much total capacity, pace and quantum of life force it can use. It is often referred to as breath quota and heartbeat quota, however, they are manifestations and not the mechanism and operation of life and death in the physical body. When the quantum of life force of the physical body is exhausted, the subtle body, a connector for life forces departs, leaving behind the physical body. The vital functions stop and the person is declared dead. It is usually referred to as departure of soul (Pran or Jiva in India) from the physical body in common parlance. This phenomenon of predetermined capacity, pace and fixed quota of life force is operational in all the components of the body. Each cell, each organ, each system and the whole body is a packed unit of bioenergy. They are in structural and functional dynamic homeostasis under constant flux resulting in constant change in the body. The rate of expenditure contributes towards deciding the total life span of the cell, organ, systems and individual. It accounts for the phenomena of cell death, progressive diminution in vitality, change in organ and system functions during life and physical death of an individual at the end. Death is a bio-cosmic phenomenon governed by biological laws. There is variation in life span at the interspecies and intraspecies levels because we measure lifespan of an individual in terms of physical time and not in terms of biological time which is an independent entity, not measurable and predictable as physical time. Everyone lives one full unit of life in terms of biological time which begins at conception and ends with death. The normal distribution of each biological feature, including the biological unit of life, is independent of one another making each individual unique. The biological clock runs at its own dynamic unique pace in every individual. The biological timer starts ticking at conception and stops when the life force quantum is over. When the person dies, the physical body stops functioning and is left behind for others to dispose of. The timing of death is beyond the realm of objective perception and cannot be equated with chronological or physical time. It is a trans-science and trans-technique phenomenon beyond the ken of humankind to alter its mechanism and operation. The article explains the impact of extrinsic and intrinsic diseases, various treatments such as organ transplant, as well as the impact of lifestyle on the biological time scale of an individual. It spells out the difference between natural and unnatural death. With this understanding, death can be appreciated, accepted and respected as a built-in operational intrinsic physiological phenomenon for the end of one's life. It is a must for the survival and healthy continuity of all the species in the biological world including mankind. [ABSTRACT FROM AUTHOR]

The circadian system in mammals ensures adaptation to the light-dark cycle on Earth and imposes 24-h rhythmicity on metabolic, physiological and behavioral processes. The central circadian pacemaker is located in the brain and is entrained by environmental signals called Zeitgebers. From here, neural, humoral and systemic signals drive rhythms in peripheral clocks in nearly every mammalian tissue. During pregnancy, disruption of the complex interplay between the mother’s rhythmic signals and the fetal developing circadian system can lead to long-term health consequences in the offspring. When an infant is born very preterm, it loses the temporal signals received from the mother prematurely and becomes totally dependent on 24/7 care in the Neonatal Intensive Care Unit (NICU), where day/night rhythmicity is usually blurred. In this literature review, we provide an overview of the fetal and neonatal development of the circadian system, and short-term consequences of disruption of this process as occurs in the NICU environment. Moreover, we provide a theoretical and molecular framework of how this disruption could lead to later-life disease. Finally, we discuss studies that aim to improve health outcomes after preterm birth by studying the effects of enhancing rhythmicity in light and noise exposure.

Cryptochromes are flavoproteins related to photolyases that are widespread throughout the plant and animal kingdom. They govern blue light-dependent growth in plants, control circadian rhythms in a light-dependent manner in invertebrates, and play a central part in the circadian clock in vertebrates. In addition, cryptochromes might function as receptors that allow animals to sense the Earth’s magnetic field. As cryptochromes are also present in mammals including humans, the possibility of a magnetosensitive protein is exciting. Here we attempt to provide a concise overview of cryptochromes in mammals. We briefly review their canonical role in the circadian rhythm from the molecular level to physiology, behaviour and diseases. We then discuss their disputed light sensitivity and proposed role in the magnetic sense in mammals, providing three mechanistic hypotheses. Specifically, mammalian cryptochromes could form light-induced radical pairs in particular cellular milieus, act as magnetoreceptors in darkness, or as secondary players in a magnetoreception signalling cascade. Future research can test these hypotheses to investigate if the role of mammalian cryptochromes extends beyond the circadian clock.

Objectives: To characterize bedside 24-h patterns in light exposure in the Neonatal Intensive Care Unit (NICU) and to explore the environmental and individual patient characteristics that influence these patterns in this clinical setting.Methods: We conducted a retrospective cohort study that included 79 very preterm infants who stayed in an incubator with a built-in light sensor. Bedside light exposure was measured continuously (one value per minute). Based on these data, various metrics (including relative amplitude, intradaily variability, and interdaily stability) were calculated to characterize the 24-h patterns of light exposure. Next, we determined the association between these metrics and various environmental and individual patient characteristics.Results: A 24-h light-dark cycle was apparent in the NICU with significant differences in light exposure between the three nurse shifts (p < 0.001), with the highest values in the morning and the lowest values at night. Light exposure was generally low, with illuminances rarely surpassing 75 lux, and highly variable between patients and across days within a single patient. Furthermore, the season of birth and phototherapy had a significant effect on 24-h light-dark cycles, whereas no effect of bed location and illness severity were observed.Conclusion: Even without an official lighting regime set, a 24-h light-dark cycle was observed in the NICU. Various rhythmicity metrics can be used to characterize 24-h light-dark cycles in a clinical setting and to study the relationship between light patterns and health outcomes.

Biological processes and physiological functions in living beings are featured by oscillations with a period of about 24 h (circadian) or cycle at the second and third harmonic (ultradian) of the basic frequency, driven by the biological clock. This molecular mechanism, common to all kingdoms of life, comprising animals, plants, fungi, bacteria, and protists, represents an undoubted adaptive advantage allowing anticipation of predictable changes in the environmental niche or of the interior milieu. Biological rhythms are the field of study of Chronobiology. In the last decade, growing evidence hints that molecular platforms holding up non-trivial quantum phenomena, including entanglement, coherence, superposition and tunnelling, bona fide evolved in biosystems. Quantum effects have been mainly implicated in processes related to electromagnetic radiation in the spectrum of visible light and ultraviolet rays, such as photosynthesis, photoreception, magnetoreception, DNA mutation, and not light related such as mitochondrial respiration and enzymatic activity. Quantum effects in biological systems are the field of study of Quantum Biology. Rhythmic changes at the level of gene expression, as well as protein quantity and subcellular distribution, confer temporal features to the molecular platform hosting electrochemical processes and non-trivial quantum phenomena. Precisely, a huge amount of molecules plying scaffold to quantum effects show rhythmic level fluctuations and this biophysical model implies that timescales of biomolecular dynamics could impinge on quantum mechanics biofunctional role. The study of quantum phenomena in biological cycles proposes a profitable “entanglement” between the areas of interest of these seemingly distant scientific disciplines to enlighten functional roles for quantum effects in rhythmic biosystems.

Summary: The interplay of environmental, social, and behavioral factors influencing human circadian phase in ecological conditions remains elusive. The Uruguayan national dance school END-SODRE operating in two shifts (morning: 8:30–12:30 and night: 20:00–24:00) allowed us to evaluate how social demands, chronotype, environmental light, physical activity, and sleep patterns affected individual circadian phase measured by the onset of the nocturnal increase of melatonin (DLMO) in a single study. The DLMO was 1.5 h earlier in morning-shift dancers (n = 7) compared to night-shift dancers (n = 11). Sleep time and chronotype (only in night-shift dancers) were associated with the circadian phase. In training days, during each participant’s phase-advance and phase-delay time windows, light exposure was similar between morning and night-shift dancers and did not correlate with DLMO. In contrast, the time spent in moderate-vigorous physical activity during each participant’s phase-lag time window was higher in night-shift dancers than in morning-shift dancers and positively correlated with DLMO.

The melatoninergic system comprises the neurohormone melatonin and its molecular targets. The major source of melatonin is the pineal organ where melatonin is rhythmically produced during darkness. In mammals, melatonin biosynthesis is controlled by the central circadian rhythm generator in the suprachiasmatic nucleus (SCN) and photoreceptors in the retina. Melatonin elicits its function principally through two specific receptors called MT1 and MT2. MT1 is highly expressed in the SCN and the hypophysial pars tuberalis (PT), an important interface for control of seasonal functions. The expression of the MT2 is more widespread. The role of the melatoninergic system in the control of seasonal functions, such as reproduction, has been known for more than 4 decades, but investigations on its impact on the circadian system under normal (entrained) conditions started 2 decades later by comparing mouse strains with a fully functional melatoninergic system with mouse strains which either produce insufficient amounts of melatonin or lack the melatonin receptors MT1 and MT2. These studies revealed that an intact melatoninergic system is not required for the generation or maintenance of rhythmic behavior under physiological entrained conditions. As shown by jet lag experiments, the melatoninergic system facilitated faster re-entrainment of locomotor activity accompanied by a more rapid adaptation of the molecular clock work in the SCN. This action depended on MT2. Further studies indicated that the endogenous melatoninergic system stabilizes the locomotor activity under entrained conditions. Notably, these effects of the endogenous melatoninergic system are subtle, suggesting that other signals such as corticosterone or temperature contribute to the synchronization of locomotor activity. Outdoor experiments lasting for a whole year indicate a seasonal plasticity of the chronotype which depends on the melatoninergic system. The comparison between mice with an intact or a compromised melatoninergic system also points toward an impact of this system on sleep, memory and metabolism.

Circadian clocks are an intrinsic element of life that orchestrate appropriately timed daily physiological and behavioural rhythms entrained to the solar cycle, thereby conferring increased fitness. However, it is thought that the first archaic ‘proto-clocks’ evolved in ancient cyanobacteria in a marine environment, where the dominant time cues (zeitgebers) probably would have been lunar-driven and included tidal cycles. To date, non-circadian ‘marine clocks’ have been described with circatidal (~12.4 h), circasemilunar (~14.8 days), and circalunar (~29.5 days) periodicity, mostly studied in accessible but temporally complex intertidal habitats. In contrast to the well-described circadian clock, their molecular machinery is poorly understood, and fundamental mechanisms remain unclear. We propose that a multi-species approach is the most apposite strategy to resolve the divergence that arose from non-circadian clockwork forged in an evolutionary environment with multiple zeitgebers. We review circatidal clock models with a focus on intertidal organisms, for which robust behavioural, physiological, or genetic underpinnings have been explicated, and discuss their relative experimental merits. Developing a comprehensive mechanistic understanding of circatidal clocks should be a priority because it will ultimately contribute to a more holistic understanding of the origins and evolution of chronobiology itself.

Industrialization has greatly changed human lifestyle; work and leisure activities have been moved indoors, and artificial light has been used to illuminate the night. As cyclic environmental cues such as light and feeding become weak and/or irregular, endogenous circadian systems are increasingly being disrupted. These disruptions are associated with metabolic dysfunction, possibly contributing to increased rates of overweight and obesity worldwide. Here, we aimed to investigate how activity-rest rhythms, patterns of light exposure, and levels of urbanization may be associated with body mass index (BMI) in a sample of rural and urban Quilombola communities in southern Brazil. These are characterized as remaining social groups who resisted the slavery regime that prevailed in Brazil. Quilombola communities were classified into five groups according to their stage of urbanization: from rural areas with no access to electricity to highly urbanized communities. We collected anthropometric data to calculate BMI, which was categorized as follows: from ≥ 18.5 kg/m2 to < 25 kg/m2 = normal weight; from ≥ 25 kg/m2 to < 30 kg/m2 = overweight; and ≥ 30 kg/m2 = obese. Subjects were asked about their sleep routines and light exposure on workdays and work-free days using the Munich Chronotype Questionnaire (N = 244 included). In addition, we analyzed actimetry data from 121 participants with seven consecutive days of recordings. Living in more urbanized areas and higher intradaily variability (IV) of activity-rest rhythms were associated with an increased risk of belonging to the overweight or obese group, when controlling for age and sex. These findings are consistent with preclinical data and point to potential strategies in obesity prevention and promotion of healthy metabolic profiles.

Summary: Circadian clocks are important to much of life on Earth and are of inherent interest to humanity, implicated in fields ranging from agriculture and ecology to developmental biology and medicine. New techniques show that it is not simply the presence of clocks, but coordination between them that is critical for complex physiological processes across the kingdoms of life. Recent years have also seen impressive advances in synthetic biology to the point where parallels can be drawn between synthetic biological and circadian oscillators. This review will emphasize theoretical and experimental studies that have revealed a fascinating dichotomy of coupling and heterogeneity among circadian clocks. We will also consolidate the fields of chronobiology and synthetic biology, discussing key design principles of their respective oscillators.

Here we review and extend the equal fitness paradigm (EFP) as an important step in developing and testing a synthetic theory of ecology and evolution based on energy and metabolism. The EFP states that all organisms are equally fit at steady state, because they allocate the same quantity of energy, ~ 22.4 kJ/g/generation to the production of offspring. On the one hand, the EFP may seem tautological, because equal fitness is necessary for the origin and persistence of biodiversity. On the other hand, the EFP reflects universal laws of life: how biological metabolism – the uptake, transformation and allocation of energy – links ecological and evolutionary patterns and processes across levels of organisation from: (1) structure and function of individual organisms, (2) life history and dynamics of populations, and (3) interactions and coevolution of species in ecosystems. The physics and biology of metabolism have facilitated the evolution of millions of species with idiosyncratic anatomy, physiology, behaviour and ecology but also with many shared traits and tradeoffs that reflect the single origin and universal rules of life. [ABSTRACT FROM AUTHOR]

Organisms use circadian rhythms to anticipate and exploit daily environmental oscillations. While circadian rhythms are of clear importance for inhabitants of tropic and temperate latitudes, its role for permanent residents of the polar regions is less well understood. The high Arctic Svalbard ptarmigan shows behavioral rhythmicity in presence of light-dark cycles but is arrhythmic during the polar day and polar night. This has been suggested to be an adaptation to the unique light environment of the Arctic. In this study, we examined regulatory aspects of the circadian control system in the Svalbard ptarmigan by recording core body temperature (Tb) alongside locomotor activity in captive birds under different photoperiods. We show that Tb and activity are rhythmic with a 24-h period under short (SP; L:D 6:18) and long photoperiod (LP; L:D 16:8). Under constant light and constant darkness, rhythmicity in Tb attenuates and activity shows signs of ultradian rhythmicity. Birds under SP also showed a rise in Tb preceding the light-on signal and any rise in activity, which proves that the light-on signal can be anticipated, most likely by a circadian system.

The intrinsic earth magnetic field (geomagnetic field, GMF) provides an essential environmental condition for most living organisms to adapt the solar cycle by rhythmically synchronizing physiological and behavioral processes. However, hypomagnetic field (HMF) of outer space, the Moon, and the Mars differs much from GMF, which poses a critical problem to astronauts during long-term interplanetary missions. Multiple experimental works have been devoted to the HMF effects on circadian rhythm and found that HMF perturbs circadian rhythms and profoundly contributes to health problems such as sleep disorders, altered metabolic as well as neurological diseases. By systemizing the latest progress on interdisciplinary cooperation between magnetobiology and chronobiology, this review sheds light on the health effects of HMF on circadian rhythms by elaborating the underlying circadian clock machinery and molecular processes.

Rest-Activity circadian Rhythm (RAR) can be used as a marker of the circadian timing system. Recent studies investigated the relationship between irregular circadian rhythms and cardiovascular risk factors such as hypertension, obesity, and dyslipidemia. These factors are related to the Metabolic Syndrome (MS), a clustering of metabolic risk factors that increases the risk of several cardiovascular and metabolic diseases. This cross-sectional analysis aimed to explore the RAR characteristics by actigraphy in subjects with MS, particularly in relation to sex and MS parameters, using parametric and non-parametric analyses. Distinguishing the characteristics of RAR based on sex could prove useful as a tool to improve the daily level of activity and set up customized activity programs based on each person’s circadian activity profile. This study showed that female participants exhibited higher values than male participants in the Midline Estimating Statistic of Rhythm (MESOR) (243.3 ± 20.0 vs 197.6 ± 17.9 activity count), Amplitude (184.5 ± 18.5 vs 144.2 ± 17.2 activity count), which measures half of the extent of the rhythmic variation in a cycle, and the most active 10-h period (M10) (379.08 ± 16.43 vs 295.13 ± 12.88 activity count). All these parameters are indicative of a higher daily activity level in women. Female participants also had lower Intradaily Variability (IV) than male participants (0.75 ± 0.03 vs 0.85 ± 0.03 activity count), which indicates a more stable and less fragmented RAR. These preliminary data provide the first experimental evidence of a difference in RAR parameters between male and female people with MS.

Therefore, alternative photopigments sensitive to other wavelengths could, through ipRGCs projections, modulate SCN photic entrainment and, most likely, also non-visual light responses depending on other areas of the brain. Keywords: endogenous rhythmicity; canonical and non-canonical circadian clocks; photic entrainment; non-circadian clocks; COVID-19 EN endogenous rhythmicity canonical and non-canonical circadian clocks photic entrainment non-circadian clocks COVID-19 1 4 4 05/22/21 20210520 NES 210520 Chronobiology is a relatively young and fast evolving research field, which aims at understanding the origin, the mechanisms and the prerogatives of endogenous biological clocks. Chronobiology and COVID-19 Infection from SARS-CoV-2 and the development of COVID-19 disease are very likely to affect circadian clock functioning. Similarly, it has become evident that brain structures other than the suprachiasmatic nuclei (SCN) clock neurons [for example astrocytes within the SCN itself (Hastings et al., [14]), the habenula (Baño-Otálora and Piggins, [3]) and the blood brain barrier (Cuddapah et al., [9])] exhibit clock properties or produce oscillations that modulate SCN outputs in many different ways. [Extracted from the article]

Summary: Circadian rhythm is altered during aging, although the underlying molecular mechanisms remain largely unknown. Here, we used the turquoise killifish as a short-lived vertebrate model to examine the effects of aging on the major circadian network comprising the four mammalian clock protein homologs, Bmal1, Clockb, Cry1b, and Per3, which are highly conserved in the killifish with 50%–85% amino acid sequence identity to their human counterparts. The amplitude of circadian rhythm was smaller in old fish (14 weeks) than in young fish (6 weeks). In old fish brain, the Bmal1 protein level was significantly downregulated. However, the Bmal1 interaction with Clockb and chromatin binding of Bmal1 to its downstream target promoters were retained. Furthermore, Bmal1 was relatively well maintained in the pineal gland compared with other regions of the old fish brain. The results suggest that the circadian clock system in the killifish becomes spatially confined to the pineal gland upon aging.

Current research suggests that mood varies from season to season in some individuals, in conjunction with light-modulated alterations in chronobiologic indices such as melatonin and cortisol. The primary aim of this study was to evaluate the effects of seasonal variations in darkness on mood in depressed antepartum women, and to determine the relationship of seasonal mood variations to contemporaneous blood melatonin and cortisol measures; a secondary aim was to evaluate the influence of seasonal factors on measures of melancholic versus atypical depressive symptoms. We obtained measures of mood and overnight concentrations of plasma melatonin and serum cortisol in 19 depressed patients (DP) and 12 healthy control (HC) antepartum women, during on-going seasonal variations in daylight/darkness, in a cross-sectional design. Analyses of variance showed that in DP, but not HC, Hamilton Depression Rating Scale (HRSD) scores were significantly higher in women tested during seasonally longer versus shorter nights. This exacerbation of depressive symptoms occurred when the dim light melatonin onset, the melatonin synthesis offset, and the time of maximum cortisol secretion (acrophase) were phase-advanced (temporally shifted earlier), and melatonin quantity was reduced, in DP but not HC. Serum cortisol increased across gestational weeks in both the HC and DP groups, which did not differ significantly in cortisol concentration. Nevertheless, serum cortisol concentration correlated positively with HRSD score in DP but not HC; notably, HC showed neither significant mood changes nor altered melatonin and cortisol timing or quantity in association with seasonal variations. These findings suggest that depression severity during pregnancy may become elevated in association with seasonally related phase advances in melatonin and cortisol timing and reduced melatonin quantity that occur in DP, but not HC. Thus, women who experience antepartum depression may be more susceptible than their nondepressed counterparts to phase alterations in melatonin and cortisol timing during seasonally longer nights. Interventions that phase delay melatonin and/or cortisol timing-for example, increased exposure to bright evening light-might serve as an effective intervention for antepartum depressions whose severity is increased during seasonally longer nights.

Sepsis remains a major therapeutic challenge and is associated with a high rate of morbidity and mortality. It is a dynamic condition in which multiple parameters change over time, rendering it difficult to overcome the various injurious responses, which worsen the prognosis in these patients. The prognosis of sepsis is associated with a disbalance of compensatory responses to infectious triggers, part of which can be deleterious. Marked inter- and intra-patient variability characterizes the mechanisms that underlie sepsis progression and determine the response to therapy. In this paper, we review some of the data on the use of chronopharmacological approaches for the treatment of patients with sepsis and discuss the role of the autonomic nervous system in the mechanisms associated with immune response and chronotherapy in these patients. We describe the implementation of an individualized platform that is based on the personalized autonomic nervous system, immune, and chronobiology-derived parameters for generating a patient-tailored therapeutic regimen. The notion of overcoming the deleterious compensatory response in a highly dynamic system in sepsis is presented to ensure an improved response to current therapies.

The aim of this report is to summarize the data documenting the vital nature of well-regulated cellular and organismal circadian rhythms, which are also reflected in a stable melatonin cycle, in supporting optimal health. Cellular fluctuations in physiology exist in most cells of multicellular organisms with their stability relying on the prevailing light:dark cycle, since it regulates, via specialized intrinsically-photoreceptive retinal ganglion cells (ip RGC) and the retinohypothalamic tract, the master circadian oscillator, i.e., the suprachiasmatic nuclei (SCN). The output message of the SCN, as determined by the light:dark cycle, is transferred to peripheral oscillators, so-called slave cellular oscillators, directly via the autonomic nervous system with its limited distribution. and indirectly via the pineal-derived circulating melatonin rhythm, which contacts every cell. Via its regulatory effects on the neuroendocrine system, particularly the hypothalamo-pituitary-adrenal axis, the SCN also has a major influence on the adrenal glucocorticoid rhythm which impacts neurological diseases and psychological behaviors. Moreover, the SCN regulates the circadian production and secretion of melatonin. When the central circadian oscillator is disturbed, such as by light at night, it passes misinformation to all organs in the body. When this occurs the physiology of cells becomes altered and normal cellular functions are compromised. This physiological upheaval is a precursor to pathologies. The deterioration of the SCN/pineal network is often a normal consequence of aging and its related diseases, but in today's societies where manufactured light is becoming progressively more common worldwide, the associated pathologies may also be occurring at an earlier age. [ABSTRACT FROM AUTHOR]

Background: Daylight Saving Time (DST) annually moves clocks 1 hour forward, when daytime is longer than night. Previous studies from medium and high latitude locations have pointed to a disruptive effect of DST on human circadian rhythms. Since Brazil is an equatorial country implementing DST, a different relationship between photic and social synchronisers may interfere with DST effects. Aim: To explore the prevalence and duration of self-reported discomfort related to DST among Brazilian residents (latitude 12–33° S, longditude 39–57° W). It was hypothesised that an elevated prevalence of self-reported discomfort would be found in Brazil, due to the pronounced uncoupling between social and geophysical synchronisers. Subjects and methods: In total, 12 467 volunteers completed a web-based, Brazilian version of Horne-Östberg Morningness-Eveningness Questionnaire, provided demographic information, and answered questions related to DST complaints (discomfort, duration of discomfort). Results: Of the total sample, 45.43% reported no discomfort related to DST, with meaningful proportions for all chronotypes. However, eveningness was most associated with discomfort. About one fourth of the total sample reported discomfort over the whole DST period. Gender interaction is largely supported by these results. Conclusions: DST at low latitude locations may be disruptive for circadian rhythms, since seasonality of sunrise near the equator is negligible or very mild.

During last decades, the way of life in modern societies has deeply modified the temporal adjustment of the circadian system, mainly due to the inappropriate use of artificial lighting and the high prevalence of social jet-lag. Therefore, it becomes necessary to design non-invasive and practical tools to monitor circadian marker rhythms but also its main synchronizer, the light-dark cycle under free-living conditions. The aim of this work was to improve the ambulatory circadian monitoring device (ACM, Kronowise®) capabilities by developing an algorithm that allows to determine light intensity, timing and circadian light stimulation by differentiating between full visible, infrared and circadian light, as well as to discriminate between different light sources (natural and artificial with low and high infrared composition) in subjects under free living conditions. The ACM device is provided with three light sensors: (i) a wide-spectrum sensor (380–1100 nm); (ii) an infrared sensor (700–1100 nm) and (iii) a sensor equipped with a blue filter that mimics the sensitivity curve of the melanopsin photopigment and the melatonin light suppression curve. To calibrate the ACM device, different commercial light sources and sunlight were measured at four different standardized distances with both a spectroradiometer (SPR) and the ACM device. CIE S 026/E:2018 (2018), toolbox software was used to calculate the melanopic stimulation from data recorded by SPR. Although correlation between raw data of luminance measured by ACM and SPR was strong for both full spectrum (r = 0.946, p < 0.0001) and circadian channel (r = 0.902, p < 0.0001), even stronger correlations were obtained when light sources were clustered in three groups: natural, infrared-rich artificial light and infrared-poor artificial light, and their corresponding linear correlations with SPR were considered (r = 0.997, p < 0.0001 and r = 0.998, p < 0.0001, respectively). Our results show that the ACM device provided with three light sensors and the algorithm developed here allow an accurate detection of light type, intensity and timing for full visible and circadian light, with simultaneous monitoring of several circadian marker rhythms that will open the possibility to explore light synchronization in population groups while they maintain their normal lifestyle.

A specific and unique aspect of cardiorespiratory activity can be captured by dividing the heart rate (HR) by the respiration rate (RR), giving the pulse-respiration quotient (PRQ = HR/RR). In this review article, we summarize the main findings of studies using and investigating the PRQ. We describe why the PRQ is a powerful parameter that captures complex regulatory states of the cardiorespiratory system, and we highlight the need to re-introduce the use of this parameter into modern studies about human physiology and pathophysiology. In particular, we show that the PRQ (i) changes during human development, (ii) is time-dependent (ultradian, circadian, and infradian rhythms), (iii) shows specific patterns during sleep, (iv) changes with physical activity and body posture, (v) is linked with psychophysical and cognitive activity, (vi) is sex-dependent, and (vii) is determined by the individual physiological constitution. Furthermore, we discuss the medical aspects of the PRQ in terms of applications for disease classification and monitoring. Finally, we explain why there should be a revival in the use of the PRQ for basic research about human physiology and for applications in medicine, and we give recommendations for the use of the PRQ in studies and medical applications.

Background: Evidence indicates that human circadian rhythm is affected by the intestinal microbiota, and establishment of the circadian rhythm begins during fetal development. However, the relationship between maternal fermented food intake and infant sleep duration has not been previously investigated. In this study, we examined whether dietary consumption of fermented food during pregnancy is associated with infant sleep duration at 1 year of age. Methods: This birth cohort study used data from a nationwide government-funded study called The Japan Environment and Children’s Study (JECS). After exclusions from a dataset comprising 104,065 JECS records, we evaluated 72,624 mother-child pairs where the child was 1 year old. We investigated the association between dietary intake of fermented foods during pregnancy and infant sleep duration of less than 11 h at 1 year of age. Results: Multivariable logistic regression showed that maternal intake of fermented food, especially miso, during the pregnancy was independently associated with reduced risk of infant sleep duration of less than 11 h. Conclusions: Further research, including interventional studies, is warranted to confirm the association between consumption of fermented foods during pregnancy and sufficient infant sleep duration. Trial registration: . [ABSTRACT FROM AUTHOR]

The osmotic stability of the erythrocyte membrane (OSEM) has been associated with changes in lipid profile, blood glucose and blood pressure. Changes in these parameters are very frequent in shift workers, possibly because of the lack of synchronization of biological rhythms, which results in the social jetlag. However, the existence of association between OSEM and circadian misalignment has not been investigated in this population. Therefore, this study investigated whether shift work, sleep time and social jetlag (SJL) are associated with biochemical and hematological variables. A population consisting of 79 men working at night (n = 37) or during the day (n = 42), aged between 21 and 65 years and with a mean BMI of 27.56 ± 4.0 kg/m2, was investigated cross-sectionally in relation to sleep time, SJL, anthropometric (height, weight and waist circumference) and blood variables, with emphasis on the OSEM. SJL was calculated by the absolute difference between the midpoint of sleep on work and rest days. The Generalized Linear Model (GzLM) was used to investigate the existence of associations between SJL and average sleep time in relation to the analyzed variables. Workers without SJL presented lower baseline lysis values of erythrocytes in isotonic medium in relation to workers with SJL. In addition, workers who slept on average less than 6 hours had higher OSEM, and higher total and LDL-cholesterol in relation to those who slept more than 6 hours, regardless of the shift. It is possible that the association of sleep deprivation and SJL with erythrocyte membrane stability is mediated through changes in the lipid profile. [ABSTRACT FROM AUTHOR]

Background: This paper is aimed to (i) develop an innovative classification of COPD, multi-dimensional phenotype, based on a multidimensional assessment; (ii) describe the identified multi-dimensional phenotypes. Methods: An exploratory factor analysis to identify the main classificatory variables and, then, a cluster analysis based on these variables were run to classify the COPD-diagnosed 514 patients enrolled in the STORICO (trial registration number: NCT03105999) study into multi-dimensional phenotypes. Results: The circadian rhythm of symptoms and health-related quality of life, but neither comorbidity nor respiratory function, qualified as primary classificatory variables. Five multidimensional phenotypes were identified: the MILD COPD characterized by no night-time symptoms and the best health status in terms of quality of life, quality of sleep, level of depression and anxiety, the MILD EMPHYSEMATOUS with prevalent dyspnea in the early-morning and day-time, the SEVERE BRONCHITIC with nocturnal and diurnal cough and phlegm, the SEVERE EMPHYSEMATOUS with nocturnal and diurnal dyspnea and the SEVERE MIXED COPD distinguished by higher frequency of symptoms during 24h and worst quality of life, of sleep and highest levels of depression and anxiety. Conclusions: Our results showed that properly collected respiratory symptoms play a primary classificatory role of COPD patients. The longitudinal observation will disclose the discriminative and prognostic potential of the proposed multidimensional phenotype. Trial registration: Trial registration number: , date of registration: 10th April 2017. [ABSTRACT FROM AUTHOR]

Over the last decades, the European hare (Lepus europaeus) has become the subject of many interdisciplinary studies due to the sharp Europe-wide population decline. In European hares, the first stage of life until weaning and the subsequent dispersal have been sparsely studied, in particular, habitat selection, movements and survival rate, as juveniles´ precocial lifestyle is dominated by concealment, motionlessness and inconspicuousness. In this study, free-living juvenile European hares (leverets) were detected systematically by thermography (n = 394), radio-tagged or marked (n = 122) from birth until the fifth week of life to research their habitat usage and pre-dispersal movements. The day-resting places and night locations, as well as the distance moved by leverets with aging, were evaluated by generalized linear mixed effect models. In addition, the habitat preference was assessed by a conservative use-availability analysis. Up to the fifth week of life, 30.5% of all leverets used cultivated areas in the daytime. In contrast, the remaining 69.4% animals inhabitated linear or small planar structures in the daytime, with the edges of field tracks, hedges and some ruderal structures clearly being preferred. At nighttime, 93% of all juveniles, which occupied linear structures in the daytime, used the adjoining fields up to 20 m away from the next linear structure. Nocturnal distances of more than 60 m to the next edge rarely occurred before the end of the pre-weaning phase. The time of day and age have a significant influence on the distance moved by juvenile hares. With increasing age, leverets moved less during the day and roamed further at night. The results are largely consistent with the behavioral patterns found in the few previous studies on pre-weaning European hares and show the importance of hiding places for leverets in early life stages. This study should contribute to a better understanding of behavior in juvenile life-history stages of European hares that may help to identify vulnerable phases in their lifecycle. In addition, the findings can refine existing population models and improve conservation efforts. [ABSTRACT FROM AUTHOR]

Although it is well established that the vertebrate retina contains endogenous circadian clocks that regulate retinal physiology and function during day and night, the processes that the clocks affect and the means by which the clocks control these processes remain unresolved. We previously demonstrated that a circadian clock in the goldfish retina regulates rod-cone electrical coupling so that coupling is weak during the day and robust at night. The increase in rod-cone coupling at night introduces rod signals into cones so that the light responses of both cones and cone horizontal cells, which are post-synaptic to cones, become dominated by rod input. By comparing the light responses of cones, cone horizontal cells and rod horizontal cells, which are post-synaptic to rods, under dark-adapted conditions during day and night, we determined whether the daily changes in the strength of rod-cone coupling could account entirely for rhythmic changes in the light response properties of cones and cone horizontal cells. We report that although some aspects of the day/night changes in cone and cone horizontal cell light responses, such as response threshold and spectral tuning, are consistent with modulation of rod-cone coupling, other properties cannot be solely explained by this phenomenon. Specifically, we found that at night compared to the day the time course of spectrally-isolated cone photoresponses was slower, cone-to-cone horizontal cell synaptic transfer was highly non-linear and of lower gain, and the delay in cone-to-cone horizontal cell synaptic transmission was longer. However, under bright light-adapted conditions in both day and night, cone-to-cone horizontal cell synaptic transfer was linear and of high gain, and no additional delay was observed at the cone-to-cone horizontal cell synapse. These findings suggest that in addition to controlling rod-cone coupling, retinal clocks shape the light responses of cone horizontal cells by modulating cone-to-cone horizontal cell synaptic transmission. [ABSTRACT FROM AUTHOR]

Circadian clocks control the timing of animal behavioral and physiological rhythms. Fruit flies anticipate daily environmental changes and exhibit two peaks of locomotor activity around dawn and dusk. microRNAs are small non-coding RNAs that play important roles in post-transcriptional regulation. Here we identify Drosophila miR-210 as a critical regulator of circadian rhythms. Under light-dark conditions, flies lacking miR-210 (miR-210KO) exhibit a dramatic 2 hrs phase advance of evening anticipatory behavior. However, circadian rhythms and molecular pacemaker function are intact in miR-210KO flies under constant darkness. Furthermore, we identify that miR-210 determines the evening phase of activity through repression of the cell adhesion molecule Fasciclin 2 (Fas2). Ablation of the miR-210 binding site within the 3’ UTR of Fas2 (Fas2ΔmiR-210) by CRISPR-Cas9 advances the evening phase as in miR-210KO. Indeed, miR-210 genetically interacts with Fas2. Moreover, Fas2 abundance is significantly increased in the optic lobe of miR-210KO. In addition, overexpression of Fas2 in the miR-210 expressing cells recapitulates the phase advance behavior phenotype of miR-210KO. Together, these results reveal a novel mechanism by which miR-210 regulates circadian locomotor behavior. [ABSTRACT FROM AUTHOR]

Circadian expression rhythms of clock gene products in the bladder are reportedly hindered by clock gene abnormalities. However, the role of clock gene products in various pathological lower urinary tract conditions is unknown. The present study examined the relationship between clock genes and voiding dysfunction in spontaneous hypertensive rats (SHR). The voluntary voiding behavior study using metabolic cages was performed in 18-weeks old male Wistar rats (control group, n = 36) and SHR (SHR group, n = 36) under 12-h light/12-h dark conditions. Bladders were harvested every 4 h at six time points (n = 6 for each time point for each group), and we analyzed the messenger RNA (mRNA) expression of several clock genes: period 2 (Per2), cryptochrome 2 (Cry2), brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), nuclear receptor subfamily 1, group D, member 1 (Rev-erbα), mechanosensors: transient receptor potential vanilloid channel 1 (TRPV1), TRPV4, Piezo1, and vesicular nucleotide transporter (VNUT) using real-time polymerase chain reaction. Though 24-h urination frequency for both light and dark periods was significantly higher in the SHR group, urine volume per voiding was significantly lower versus control. In controls, urine volume per voiding was significantly lower during the dark period (active phase) than the light period (rest phase); this parameter did not significantly differ between active and rest phases for SHR. SHR bladders showed significantly higher expression of Cry2 and Clock during the active phase compared to controls. In the SHR group, TRPV1, TRPV4, Piezo1, and VNUT mRNA levels were significantly higher during the active phase compared to the control group. We speculate that Cry2 and Clock may be contributing factors in the decrease of bladder capacity during the active phase in SHR through increase of TRPV1, TRPV4, Piezo1, and VNUT expression, but further research will be necessary to elucidate the precise mechanisms. [ABSTRACT FROM AUTHOR]

We propose a multi-scale model to explain the time-of-day effects on learning and memory. We specifically model the circadian variation of hippocampus (HC) dependent long-term potentiation (LTP), depression (LTD), and the fear conditioning paradigm in amygdala. The model we built has both Goodwin type circadian gene regulatory network (GRN) and the conductance model of Morris-Lecar (ML) type to explain the spontaneous firing patterns (SFR) in suprachiasmatic nucleus (SCN). In the conductance model, we also include N-Methyl-D-aspartic acid receptor (NMDAR) to study the circadian dependent changes in LTP/LTD in hippocampus and include both NMDAR and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) dynamics to explain the circadian modulation of fear conditioning paradigm in memory acquisition, recall, and extinction as seen in amygdala. Our multi-scale model captures the essential dynamics seen in the experiments and strongly supports the circadian time-of-the-day effects on learning and memory. [ABSTRACT FROM AUTHOR]

In fish, the circadian clock represents a key regulator of many aspects of biology and is controlled by combinations of abiotic and biotic factors. These environmental factors are frequently manipulated in fish farms as part of strategies designed to maximize productivity. The flatfish turbot, Scophthalmus maximus, represents one of the most important species within the aquaculture sector in Asia and Europe. Despite the strategic importance of this species, the function and regulation of the turbot circadian system remains poorly understood. Here, we have characterized the core circadian clock genes, clock1, per1, per2 and cry1 in turbot and have studied their daily expression in various tissues under a range of lighting conditions and feeding regimes. We have also explored the influence of light and feeding time on locomotor activity. Rhythmic expression of the four core clock genes was observed in all tissues studied under light dark (LD) cycle conditions. Rhythmicity of clock gene expression persisted upon transfer to artificial free running, constant conditions confirming their endogenous circadian clock control. Furthermore, turbot showed daily cycles of locomotor activity and food anticipatory activity (FAA) under LD and scheduled-feeding, with the activity phase as well as FAA coinciding with and being dependent upon exposure to light. Thus, while FAA was absent under constant dark (DD) conditions, it was still detected in constant light (LL). In contrast, general locomotor activity was arrhythmic in both constant darkness and constant light, pointing to a major contribution of light, in concert with the circadian clock, in timing locomotor activity in this species. Our data represents an important contribution to our understanding of the circadian timing system in the turbot and thereby the optimization of rearing protocols and the improvement of the well-being of turbot within fish farming environments. [ABSTRACT FROM AUTHOR]

Although most research on sleep and adolescent health has focused on how long each youth sleeps on average, variability in sleep duration may be just as problematic. Existing findings have been inconsistent and unable to address cause-effect relationships. This study piloted an experimental protocol to induce sleep variability and explore its impact on daytime sleepiness in adolescents. Healthy adolescents aged 14–17 participated in a 3-week, at-home protocol. Sleep was monitored by sleep diaries and actigraphy. Following a run-in period to stabilize wake times (set at 6:30 throughout the protocol), participants were randomly counterbalanced across two 5-night experimental conditions. Bedtimes were consistent at 11:00 during the stable sleep condition (7.5-hour sleep period each night) but changed on alternating nights during the variable sleep condition (ranging from 9:30 to 12:30) so that sleep duration averaged 7.5 hours across the condition with a standard deviation of 1.37 hours. Difficulty waking was assessed each morning and daytime sleepiness was assessed by end-of-condition parent- and adolescent-reports. Of the 20 participants who completed the study, 16 met the predetermined adherence definition. For those who were adherent, there were no differences in overall sleep duration between the stable and variable sleep conditions (p>.05) but adolescents had 58.6 minutes greater night-to-night variation in sleep duration in the variable condition (p < .001). Across all nights, youth reported greater difficulty waking following nights of shorter assigned sleep (p = .004) and greater overall sleepiness during the variable condition (p = .03). It is feasible to experimentally vary how long adolescents sleep on a nightly basis while holding average sleep duration constant. Such a protocol will promote tests of the acute effects of day-to-day changes in sleep duration on health. [ABSTRACT FROM AUTHOR]

Purpose: Responding to emergency alarms is a daily occurrence for personnel in safety-critical occupations, and is associated with negative health outcomes in this population. The purpose of the present study was to determine the acute inflammatory response to an isolated emergency alarm mobilisation in both day and night conditions. Methods: Sixteen healthy males (mean age 25 ± 4 years) spent four days and nights in a sleep laboratory and were required to mobilise to an emergency alarm either during the day (1558 h), or from nocturnal sleep (0358 h). Pro (TNF-α, IL-1β, IL-8, IL-6) and anti-inflammatory (IL-4 and IL-10) cytokine responses to each alarm mobilisation were compared to time-matched control conditions without the alarm and mobilisation stimulus. Results: Analysis revealed no significant drift of cytokine levels at 1400 h across the study (P≥0.139). The plasma concentration of anti-inflammatory cytokine IL-4 was 84% greater in the 2-h sampling period following night alarm mobilisation compared to a night control of gentle awakening (P = 0.049), no other condition-by-time interactions were observed. The majority of inflammatory concentrations did not significantly change between alarm mobilisation and control conditions, in either day or night trials. Conclusions: These findings may reflect the lack of a true emergency (and the perceived stress) for the alarm mobilisation, together with the neutralising effect of different circadian biorhythms on inflammatory cytokine concentrations. [ABSTRACT FROM AUTHOR]

Misalignment of the daily sleep-wake and fasting-feeding cycles with the endogenous circadian timing system is an inevitable consequence of night shift work and is associated with adverse metabolic health effects. However, a detailed characterisation of the effects of night shifts on 24-h rhythms in the metabolome is missing. We performed targeted metabolomic profiling on plasma samples collected every 2 h from healthy human subjects during two 24-h measurement periods at baseline and on the fourth day of a simulated night shift protocol, in which the habitual sleep-wake cycle was delayed by 10 h. Thirty-two out of the 130 detected metabolites showed a 24-h rhythm both at baseline and during the night shift condition. Among these, 75% were driven by sleep-wake and fasting-feeding cycles rather than by the endogenous circadian clock, showing an average phase delay of 8.8 h during the night shift condition. Hence, the majority of rhythmic metabolites were misaligned relative to the endogenous circadian system during the night shift condition. This could be a key mechanism involved in the increased prevalence of adverse metabolic health effects observed in shift workers. On the individual level, the response to the night shift protocol was highly diverse, with phase shifts of rhythmic metabolite profiles ranging from a 0.2-h advance in one subject to a 12-h delay in another subject, revealing an individual metabolomic signature of circadian misalignment. Our findings provide insight into the overall and individual responses of the metabolome to circadian misalignment associated with night schedules and may thereby contribute to the development of individually tailored strategies to minimise the metabolic impacts of shift work. [ABSTRACT FROM AUTHOR]

Environmental circadian disruption (ECD), characterized by repeated or long-term disruption in environmental timing cues which require the internal circadian clock to change its phase to resynchronize with the environment, is associated with numerous serious health issues in humans. While animal and isolated cell models exist to study the effects of destabilizing the relationship between the circadian system and the environment, neither approach provides an ideal solution. Here, we developed an in vitro model which incorporates both elements of a reductionist cellular model and disruption of the clock/environment relationship using temperature as an environmental cue, as occurs in vivo. Using this approach, we have demonstrated that some effects of in vivo ECD can be reproduced using only isolated peripheral oscillators. Specifically, we report exaggerated inflammatory responses to endotoxin following repeated environmental circadian disruption in explanted spleens. This effect requires a functional circadian clock but not the master brain clock, the suprachiasmatic nucleus (SCN). Further, we report that this is a result of cumulative, rather than acute, circadian disruption as has been previously observed in vivo. Finally, such effects appear to be tissue specific as it does not occur in lung, which is less sensitive to the temperature cycles employed to induce ECD. Taken together, the present study suggests that this model could be a valuable tool for dissecting the causes and effects of circadian disruption both in isolated components of physiological systems as well as the aggregated interactions of these systems that occur in vivo. [ABSTRACT FROM AUTHOR]

Risk-taking is a complex form of decision-making that involves calculated assessments of potential costs and rewards that may be immediate or delayed. Thus, making predictions about inter-individual variation in risk-taking due to personality traits, decision styles or other attributes can be difficult. The association of risk-taking with gender is well-supported; males report higher propensity for risk-taking and show higher risk-taking on tasks measuring actual risk-taking behavior. Risk-taking also appears to be associated with circadian phenotypes (chronotypes), with evening-types reporting higher levels of risk-taking—but this association may be confounded by the fact that, in certain age groups, males are more likely to be evening-types. Here, we test for gender by chronotype effects on risk-taking in young adults (n = 610) using a self-reported risk propensity questionnaire, the health domain of the DOSPERT, and a behavioral task measuring risk-taking, the Balloon Analog Risk Task (BART). Our results show that males report and take significantly more risks than females in this population. In addition, evening-type individuals have significantly higher self-reported risk propensity and tend to take more risks on the BART. Interestingly, there is no significant difference in risk propensity or risk-taking behavior across male circadian phenotypes, but evening-type females significantly report and take more risk than female intermediate and morning types. In regression analyses, we found both gender and chronotype predict risk propensity and risk-taking. Path analysis confirms that chronotype has an indirect effect on gender differences in both risk propensity and risk-taking. Furthermore, we found that trait anxiety (STAI) and sleep disturbance (PROMIS), significantly correlate with chronotype and gender in the complete dataset, but do not independently predict differences in female risk-taking. These results suggest that chronotype mediates gender effects on risk-taking and that these effects are driven primarily by morning-type females, but are not related to gender-specific differences in trait anxiety or sleep quality. [ABSTRACT FROM AUTHOR]

Purpose: The circadian clock is entrained to light by the intrinsically photosensitive retinal ganglion cells. Loss of these cells in glaucoma, an eye disease with loss of retinal ganglion cells as its key feature, might thus result in a change in chronotype. We aimed to compare the chronotype between glaucoma patients and healthy subjects. Methods: We sent the Munich ChronoType Questionnaire to 221 glaucoma patients (response rate 81%); controls (primary control group) were primarily their spouses. After exclusion of shift workers and participants who woke-up due to an alarm clock on days off, 159 glaucoma patients (88 early, 21 moderate, 23 severe) and 163 controls remained. We calculated chronotype as the mid-sleep on days off, corrected for workweek accumulated sleep debt (MSFsc). We compared means and variances between groups using Welch’s tests and F-tests, respectively. A secondary control group was recruited from participants in a citizen-science project (n = 17073) who completed an online questionnaire. A resampling method was applied to enable an age- and gender- matched comparison with the glaucoma patients. Results: Compared to the primary control group, glaucoma did not affect the mean MSFsc (controls 3:47; early, moderate, and severe glaucoma 3:40, 3:45, and 3:33, respectively [P = 0.62]). Chronotype variability seemed to increase with increasing disease severity (severe glaucoma versus controls: P = 0.023). The mean MSFsc of the secondary control group was 3:50 (95% confidence interval 3:48 to 3:52); significantly later than that of the glaucoma patients (3:40; P = 0.024). Mean MSFsc did not differ significantly between the control groups (P = 0.42). Conclusions: No clear changes were found in the chronotype as determined by sleep phase in patients with glaucoma, especially not in early and moderate glaucoma. In severe glaucoma, chronotype variability seems to increase, possibly alongside a small advancement. [ABSTRACT FROM AUTHOR]

The balance of sleep and wake is plastic and changes to meet environmental demands. Mechanisms that allow an animal to suppress sleep and maintain waking in potentially adverse situations could serve adaptive functions in evolution. The fruit fly, Drosophila melanogaster, is well poised as a system in which to explore these questions. The environment changes sleep and wake in flies, e.g., starvation induces waking in Drosophila as it does in many animals. Further, the sophisticated neurobiological toolkit available to Drosophila researchers gives the fly a great advantage as a system to investigate the precise neurobiological mechanisms underlying these adaptive changes. In a paper in this issue of PLOS Biology, Yurgel and colleagues elegantly exploit the advantages of the Drosophila model to map starvation-induced wakefulness to a single pair of peptidergic neurons and their partners. [ABSTRACT FROM AUTHOR]

While rods, cones, and intrinsically photosensitive melanopsin-containing ganglion cells (ipRGCs) all drive light entrainment of the master circadian pacemaker of the suprachiasmatic nucleus, recent studies have proposed that entrainment of the mouse retinal clock is exclusively mediated by a UV-sensitive photopigment, neuropsin (OPN5). Here, we report that the retinal circadian clock can be phase shifted by short duration and relatively low-irradiance monochromatic light in the visible part of the spectrum, up to 520 nm. Phase shifts exhibit a classical photon dose-response curve. Comparing the response of mouse models that specifically lack middle-wavelength (MW) cones, melanopsin, and/or rods, we found that only the absence of rods prevented light-induced phase shifts of the retinal clock, whereas light-induced phase shifts of locomotor activity are normal. In a “rod-only” mouse model, phase shifting response of the retinal clock to light is conserved. At shorter UV wavelengths, our results also reveal additional recruitment of short-wavelength (SW) cones and/or OPN5. These findings suggest a primary role of rod photoreceptors in the light response of the retinal clock in mammals. [ABSTRACT FROM AUTHOR]