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Abstract Habitual short sleep durations are associated with several cardiovascular diseases. Experimental research generally supports these findings as metrics of arterial function are impaired after complete deprivation of sleep and after longer periods of partial sleep restriction. The acute influence of a single instance of partial sleep restriction (PSR), however, has not been defined. We evaluated arterial structure and function among 32 university‐aged participants on two occasions: once after normal habitual sleep (NS), and again the morning after an acute partial sleep restriction (PSR) intervention involving only 3 h of sleep for a single night. Endothelial function was measured using ultrasonography at the brachial artery via flow‐mediated dilatation (FMD), and a ramp peak oxygen uptake test was used to evaluate cardiorespiratory fitness. Blood samples were collected from a subset of participants to investigate the influence of circulatory factors on cellular mechanisms implicated in endothelial function. Sleep duration was lower after a night of PSR compared to NS (P 0.05). Ex vivo cell culture results aligned with in vivo data, showing that acute PSR does not alter intracellular processes involved in endothelial function. No differences in arterial structure or function were observed between NS and acute PSR in healthy and young participants, and cardiorespiratory fitness does not modulate the arterial response to acute sleep restriction.

Background: Emerging research has suggested sleep to be a modifier of the trajectory of concussion recovery in adolescent and adult populations. Despite the growing recognition of the relationship between sleep and concussion, the mechanisms and physiological processes governing this association have yet to be established. Main Body: Following a concussion, a pathophysiologic cascade of events occurs, characterized by numerous factors including microglia activation, ionic imbalance, and release of excitatory neurotransmitters. Importantly, each of these factors plays a role in the regulation of the sleep-wake cycle. Therefore, dysregulation of sleep following injury may be a function of the diffuse disruption of cerebral functioning in the wake of both axonal damage and secondary physiological events. As the onset of sleep-related symptoms is highly variable following a concussion, clinicians should be aware of when and how these symptoms present. Post-injury changes in sleep have been reported in the acute, sub-acute, and chronic phases of recovery and can prolong symptom resolution, affect neurocognitive performance, and influence mood state. Though these changes support sleep as a modifier of recovery, limited guidance exists for clinicians or their patients in the management of sleep after concussion. This may be attributed to the fact that research has correlated sleep with concussion recovery but has failed to explain why the correlation exists. Sleep is a complex, multifactorial process and the changes seen in sleep that are seen following concussion are the result of interactions amongst numerous processes that regulate the sleep-wake cycle. Short Conclusion: The assessment and management of sleep by identifying and considering the biological, sociological, and psychological interactions of this multifactorial process will allow for clinicians to address the dynamic nature of changes in sleep following concussion. Key Points: Sleep is considered a modifier of recovery from concussion, yet little attention has been given to the overlapping physiologies between sleep and concussion, thereby limiting understanding as to why it effects recovery. Our theoretical model proposes that the neurometabolic cascade modulates sleep-wake physiology across multiple levels via alterations in neurotransmitter release, glymphatic clearance, and extracellular ionic concentration. [ABSTRACT FROM AUTHOR]

The origin of biological rhythms goes back to the very beginning of life. They are observed in the animal and plant world at all levels of organization, from cells to ecosystems. As early as the 18th century, plant scientists were the first to explain the relationship between flowering cycles and environmental cycles, emphasizing the importance of daily light-dark cycles and the seasons. Our temporal structure is controlled by external and internal rhythmic signals. Light is the main synchronizer of the circadian system, as daily exposure to light entrains our clock over 24 hours, the endogenous period of the circadian system being close to, but not exactly, 24 hours. In 1960, a seminal scientific meeting, the Cold Spring Harbor Symposium on Biological Rhythms, brought together all the biological rhythms scientists of the time, a number of whom are considered the founders of modern chronobiology. All aspects of biological rhythms were addressed, from the properties of circadian rhythms to their practical and ecological aspects. Birth of chronobiology dates from this period, with the definition of its vocabulary and specificities in metabolism, photoperiodism, animal physiology, etc. At around the same time, and right up to the present day, research has focused on melatonin, the circadian neurohormone of the pineal gland, with data on its pattern, metabolism, control by light and clinical applications. However, light has a double face, as it has positive effects as a circadian clock entraining agent, but also deleterious effects, as it can lead to chronodisruption when exposed chronically at night, which can increase the risk of cancer and other diseases. Finally, research over the past few decades has unraveled the anatomical location of circadian clocks and their cellular and molecular mechanisms. This recent research has in turn allowed us to explain how circadian rhythms control physiology and health. [ABSTRACT FROM AUTHOR]

Circadian rhythm is defined biochemical, physiological, metabolic and behavioral responses of all living organisms such as bacteria, mammals, fungi and plants within a 24-hour light and dark photoperiod. In plants, circadian rhythm regulates multiple physiological, metabolic and behavioral processes such as stomatal and leaf movements, stem elongation, enzyme activity and aging. Circadian clock genes are known to play a role in regulating the biosynthesis of phytohormones which are involved in many crucial processes such as seed germination, hypocotyl elongation and photosynthesis. Circadian rhythm regulates and optimizes physiological and molecular mechanisms in a diurnal cycle, anticipating seasonal changes and preparing the plant for different environmental conditions in plant. Circadian rhythm also plays a crucial role in the regulation of plant defense against biotic and abiotic stresses. Melon is a diploid species and one of the most important Cucurbitaceae family members. In this study, we aimed to investigate the relationship between different developmental processes and circadian rhythm in melon. The relationship between circadian rhythm and growth, development and resistance in melon a detailed understanding of the relationship will help to improve future agricultural production and ground for further research on tolerance to environmental stresses will be created. [ABSTRACT FROM AUTHOR]

Normally, the sleep–wake cycle is synchronized with the body's circadian rhythm, which in turn is synchronized with the 24-h period of sunlight. Circadian changes in key hormones, particularly cortisol, also tend to follow the body's circadian rhythm, masking their involvement in controlling the transition between sleep and wakefulness. In our work, we study the behavior of an extended mathematical model that describes the dynamics of both switching between sleep and wakefulness and the process of cortisol production, including their mutual influence. The main goal of our work is to evaluate the behavior of such an extended model in the light of the phenomenon of spontaneous internal desynchronization (SID). Our results indicate that the influence of the cortisol subsystem on the switch between sleep and wakefulness depends significantly on the strength of this feedback. In particular, the increased contribution of cortisol leads to desynchronization between the sleep–wake cycle and the circadian rhythm. With random deviations in the speed of the homeostatic process, the action of cortisol, on the one hand, increases the predictability of the behavior of physiological markers of the sleep–wake cycle, and on the other hand, can lead to the appearance of "excesses of activity"—days with early awakening and late falling asleep. [ABSTRACT FROM AUTHOR]

Animal behavior emerges from integration of many processes with different spatial and temporal scales. Dynamical behavioral patterns, including daily and ultradian rhythms and the dynamical microstructure of behavior (i.e., autocorrelations properties), can be differentially affected by external cues. Identifying these patterns is important for understanding how organisms adapt to their environment, yet unbiased methods to quantify dynamical changes over multiple temporal scales are lacking. Herein, we combine a wavelet approach with Detrended Fluctuation Analysis to identify behavioral patterns and evaluate changes over 42-days in mice subjected to different dietary restriction paradigms. We show that feeding restriction alters dynamical patterns: not only are daily rhythms modulated but also the presence, phase and/or strength of ~12h-rhythms, as well as the nature of autocorrelation properties of feed-intake and wheel running behaviors. These results highlight the underlying complexity of behavioral architecture and offer insights into the multi-scale impact of feeding habits on physiology. Wavelet analysis of mice wheel running and feeding time series unveils the impact of food restriction on dynamical patterns beyond circadian rhythms, highlighting the complex nature of mouse behavior across a spectrum of temporal scales. [ABSTRACT FROM AUTHOR]

Objective There are well-described impacts of biological rhythms on human physiology. With the increasing push for routine blood tests for preventative medical care and clinical and physiological research, optimizing effectiveness is paramount. This study aimed to determine whether it is feasible to assess diurnal variations of peripheral lymphocyte prevalence using finger prick blood in a small sample size. Methods Using polychromatic flow cytometry, the prevalence of lymphocytes was assessed using 25 µL fingertip blood samples at 8 AM and 5 PM from 8 participants. Results TH cells and B cells showed significantly higher percentages in the 5 PM samples, whereas NK cells demonstrated a significantly higher morning percentage. T cells, leukocytes, and cytotoxic T cells showed no significant changes. Conclusion The detection of diurnal variations demonstrates that small blood volumes can be used to detect lymphocyte variations. The lower blood volume required provides a new testing method for clinical and research settings. [ABSTRACT FROM AUTHOR]

Identification of the neural circuits in the brain regulating animal behavior and physiology is critical for understanding brain functions and is one of the most challenging goals in neuroscience research. The fruitfly Drosophila melanogaster has often been used to identify the neural circuits involved in the regulation of specific behaviors because of the many neurogenetic tools available to express target genes in particular neurons. Neurons controlling sexual behavior, feeding behavior, and circadian rhythms have been identified, and the number of neurons responsible for controlling these phenomena is small. The search for a few neurons controlling a specific behavior is an important first step to clarify the overall picture of the neural circuits regulating that behavior. We previously found that the clock gene period (per), which is essential for circadian rhythms in Drosophila, is also essential for long-term memory (LTM). We have also found that a very limited number of per-expressing clock neurons in the adult brain are required for the consolidation and maintenance of LTM. In this review, we focus on LTM in Drosophila, introduce the concept of LTM regulation by a few clock neurons that we have recently discovered, and discuss how a few clock neurons regulate Drosophila LTM. [ABSTRACT FROM AUTHOR]

CXCR2 plays diverse and novel roles in cancer, physiology, and viral infection (COVID-19) beyond its widely accepted role in bacterial infections. The pro- or antitumoral action of CXCR2 remains under debate because this varies depending on the cells expressing the receptor. Multiple cell types express CXCR2, including neutrophils and endothelial, immune, stromal, and epithelial cells, but expression validation at the protein and RNA levels is needed. Tissue-specific heterogeneity of CXCR2 expression and function in neutrophils has been clarified with respect to maturation, aging, and the circadian rhythm. The recent availability of structures of CXCR2 bound to ligands or antagonists and the analysis of downstream effectors of CXCR2 should facilitate the design of more potent drugs and a better understanding of CXCR2 signaling function in pathophysiology. Recent findings have modified our understanding of the roles of chemokine receptor CXCR2 and its ligands in cancer, inflammation, and immunity. Studies in Cxcr2 tissue-specific knockout mice show that this receptor is involved in, among other things, cancer, central nervous system (CNS) function, metabolism, reproduction, COVID-19, and the response to circadian cycles. Moreover, CXCR2 involvement in neutrophil function has been revisited not only in physiology but also for its major contribution to cancers. The recent unfolding of the role of CXCR2 in numerous cancers has led to extensive evaluation of multiple CXCR2 antagonists in preclinical and clinical studies. In this review we discuss the potential of targeting CXCR2 for cancer treatment. [ABSTRACT FROM AUTHOR]

Human performance and physiology undergo circadian changes. The safety of driving tends to decrease at night and during the afternoon, and these changes cannot be solely addressed to the decreased visibility. Previous literature reported that circadian rhythmicity plays a role in these changes. A similar phenomenon might occur in semi-automated driving. Also, as physiology undergoes circadian changes, it was suggested that systems of driver state monitoring might have different accuracy during the day and at night. This paper investigated the circadian effect on driving performance and physiology of the driver in simulated semi-automated driving. 53 participants participated in the experiment twice, once during the day and once at night. They drove a driving simulator in the semi-automated driving scenario. Following psychophysiological functions were measured during the experiment: electromyography, electrooculography, electrocardiography, respiration, pulse, blood oxygenation, electrodermal activity, voice, sleepiness, fatigue, readiness to take-over manual control of the vehicles, mental workload, cortisol, and alpha-amylase. There was a significant correlation between circadian phase and sleepiness, fatigue, readiness to take-over manual driving, physical demand, mean autocorrelation of voice, mean noise to harmonics ratio in voice, horizontal eye movements, frequency of frontalis, mean power in frontalis, peak power in frontalis, cortisol level, and driving performance. [ABSTRACT FROM AUTHOR]

Physiological processes are governed by intricate networks of transcriptional and post-translational regulations. Inter-cellular interactions and signaling pathways further modulate the response of the cells to environmental conditions. Understanding the dynamics of these systems in healthy conditions and their alterations in pathologic situations requires a “systems” approach. Computational models allow to formalize and to simulate the dynamics of complex networks. Here, we briefly illustrate, through a few selected examples, how modeling helps to answer non-trivial questions regarding rhythmic phenomena, signaling and decision-making in cellular systems. These examples relate to cell differentiation, metabolic regulation, chronopharmacology and calcium dynamics.

Molecular and physiological determinants of the timing of reproductive events, including the pre-ovulatory LH surge and seasonal fluctuations in fertility, are incompletely understood. We used the Cryptochrome 1-deficient duper mutant to examine the role of this core circadian clock gene in Syrian hamsters. We find that the phase of the LH surge and its stability upon shifts of the light: dark cycle are altered in duper mutants. The intensity of immunoreactive PER1 in GnRH cells of the preoptic area peaks earlier in the day in duper than wild type hamsters. We note that GnRH fibers coursing through the suprachiasmatic nucleus (SCN) contact vasopressin- and VIP-immunoreactive cells, suggesting a possible locus of circadian control of the LH surge. Unlike wild types, duper hamsters do not regress their gonads within 8 weeks of constant darkness, despite evidence of melatonin secretion during the subjective night. In light of the finding that the duper allele is a stop codon in Cryptochrome 1, our results suggest important neuroendocrine functions of this core circadian clock gene.

Light-sensitive neurons are located in the ventral and central core of the suprachiasmatic nucleus (SCN), whereas stably oscillating clock neurons are found mainly in the dorsal shell. Signals between the SCN core and shell are believed to play an important role in light entrainment. Core neurons express vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP), and Neuroglobin (Ngb), whereas the shell neurons express vasopressin (AVP), prokineticin 2, and the VIP type 2 (VPAC2) receptor. In rodents, light has a phase-shifting capacity at night, which induces rapid and transient expression of the EGR1 and FOS in the SCN.Methods: The present study used immunohistochemical staining of FOS, EGR1, and phenotypical markers of SCN neurons (VIP, AVP, Ngb) to identify subtypes/populations of light-responsive neurons at early night.Results: Double immunohistochemistry and cell counting were used to evaluate the number of SCN neurons expressing FOS and EGR1 in the SCN. The number of neurons expressing either EGR1 or FOS was higher than the total number of neurons co-storing EGR1 and FOS. Of the total number of light-responsive cells, 42% expressed only EGR1, 43% expressed only FOS, and 15% expressed both EGR1 and FOS. Light-responsive VIP neurons represented only 31% of all VIP neurons, and EGR1 represents the largest group of light-responsive VIP neurons (18%). VIP neurons expressing only FOS represented 1% of the total light-responsive VIP neurons. 81% of the Ngb neurons in the mouse SCN were light-responsive, and of these neurons expressing only EGR1 after light stimulation represented 44%, whereas 24% expressed FOS. Although most light-responsive neurons are found in the core of the SCN, 29% of the AVP neurons in the shell were light-responsive, of which 8% expressed EGR1, 10% expressed FOS, and 11% co-expressed both EGR1 and FOS after light stimulation.Discussion: Our analysis revealed cell-specific differences in light responsiveness between different peptidergic and Ngb-expressing neurons in different compartments of the mouse SCN, indicating that light activates diverse neuronal networks in the SCN, some of which participate in photoentrainment.

Environmental rhythms such as the daily light-dark cycle selected for endogenous clocks. These clocks predict regular environmental changes and provide the basis for well-timed adaptive homeostasis in physiology and behavior of organisms. Endogenous clocks are oscillators that are based on positive feedforward and negative feedback loops. They generate stable rhythms even under constant conditions. Since even weak interactions between oscillators allow for autonomous synchronization, coupling/synchronization of oscillators provides the basis of self-organized physiological timing. Amongst the most thoroughly researched clocks are the endogenous circadian clock neurons in mammals and insects. They comprise nuclear clockworks of transcriptional/translational feedback loops (TTFL) that generate ∼24 h rhythms in clock gene expression entrained to the environmental day-night cycle. It is generally assumed that this TTFL clockwork drives all circadian oscillations within and between clock cells, being the basis of any circadian rhythm in physiology and behavior of organisms. Instead of the current gene-based hierarchical clock model we provide here a systems view of timing. We suggest that a coupled system of autonomous TTFL and posttranslational feedback loop (PTFL) oscillators/clocks that run at multiple timescales governs adaptive, dynamic homeostasis of physiology and behavior. We focus on mammalian and insect neurons as endogenous oscillators at multiple timescales. We suggest that neuronal plasma membrane-associated signalosomes constitute specific autonomous PTFL clocks that generate localized but interlinked oscillations of membrane potential and intracellular messengers with specific endogenous frequencies. In each clock neuron multiscale interactions of TTFL and PTFL oscillators/clocks form a temporally structured oscillatory network with a common complex frequency-band comprising superimposed multiscale oscillations. Coupling between oscillator/clock neurons provides the next level of complexity of an oscillatory network. This systemic dynamic network of molecular and cellular oscillators/clocks is suggested to form the basis of any physiological homeostasis that cycles through dynamic homeostatic setpoints with a characteristic frequency-band as hallmark. We propose that mechanisms of homeostatic plasticity maintain the stability of these dynamic setpoints, whereas Hebbian plasticity enables switching between setpoints via coupling factors, like biogenic amines and/or neuropeptides. They reprogram the network to a new common frequency, a new dynamic setpoint. Our novel hypothesis is up for experimental challenge.

Cellular circadian rhythms confer temporal organisation upon physiology that is fundamental to human health. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body, but their physiological function is poorly understood. Here, we present a novel biochemical assay for haemoglobin (Hb) oxidation status which relies on a redox‐sensitive covalent haem‐Hb linkage that forms during SDS‐mediated cell lysis. Formation of this linkage is lowest when ferrous Hb is oxidised, in the form of ferric metHb. Daily haemoglobin oxidation rhythms are observed in mouse and human RBCs cultured in vitro, or taken from humans in vivo, and are unaffected by mutations that affect circadian rhythms in nucleated cells. These rhythms correlate with daily rhythms in core body temperature, with temperature lowest when metHb levels are highest. Raising metHb levels with dietary sodium nitrite can further decrease daytime core body temperature in mice via nitric oxide (NO) signalling. These results extend our molecular understanding of RBC circadian rhythms and suggest they contribute to the regulation of body temperature. Synopsis: Red blood cells (RBCs) have circadian rhythms, but their physiological functional is poorly understood. A novel reporter system reveals oscillations of haemoglobin (Hb) oxidation status in vitro and in vivo, which contribute to the rhythmic regulation of body temperature through nitric oxide (NO) signalling.A novel biochemical assay reports Hb oxidation status.Hb oxidation (metHb) is rhythmic in mouse and human RBCs cultured in vitro.Daily variation in redox status is observed in humans in vivo, with highest metHb levels during the rest phase.Increased metHb in RBCs during the rest phase correlates with reduced core body temperature and an increase in peripheral vasodilation due to NO signalling.Manipulation of in vivo metHb status with sodium nitrite causes core body cooling. [ABSTRACT FROM AUTHOR]

Temperature influences animal physiology and behavior. Animals must set an appropriate body temperature to maintain homeostasis and maximize survival. Mammals set their body temperatures using metabolic and behavioral strategies. The daily fluctuation in body temperature is called the body temperature rhythm (BTR). For example, human body temperature increases during wakefulness and decreases during sleep. BTR is controlled by the circadian clock, is closely linked with metabolism and sleep, and entrains peripheral clocks located in the liver and lungs. However, the underlying mechanisms of BTR are largely unclear. In contrast to mammals, small ectotherms, such as Drosophila, control their body temperatures by choosing appropriate environmental temperatures. The preferred temperature of Drosophila increases during the day and decreases at night; this pattern is referred to as the temperature preference rhythm (TPR). As flies are small ectotherms, their body temperature is close to that of the surrounding environment. Thus, Drosophila TPR produces BTR, which exhibits a pattern similar to that of human BTR. In this review, we summarize the regulatory mechanisms of TPR, including recent studies that describe neuronal circuits relaying ambient temperature information to dorsal neurons (DNs). The neuropeptide diuretic hormone 31 (DH31) and its receptor (DH31R) regulate TPR, and a mammalian homolog of DH31R, the calcitonin receptor (CALCR), also plays an important role in mouse BTR regulation. In addition, both fly TPR and mammalian BTR are separately regulated from another clock output, locomotor activity rhythms. These findings suggest that the fundamental mechanisms of BTR regulation may be conserved between mammals and flies. Furthermore, we discuss the relationships between TPR and other physiological functions, such as sleep. The dissection of the regulatory mechanisms of Drosophila TPR could facilitate an understanding of mammalian BTR and the interaction between BTR and sleep regulation. [ABSTRACT FROM AUTHOR]

A rhythmic expression of clock genes occurs within the cells of multiple organs and tissues throughout the body, termed “peripheral clocks.” Peripheral clocks are subject to entrainment by a multitude of factors, many of which are directly or indirectly controlled by the light-entrainable clock located in the suprachiasmatic nucleus of the hypothalamus. Peripheral clocks occur in the gastrointestinal tract, notably the epithelia whose functions include regulation of absorption, permeability, and secretion of hormones; and in the myenteric plexus, which is the intrinsic neural network principally responsible for the coordination of muscular activity in the gut. This review focuses on the physiological circadian variation of major colonic functions and their entraining mechanisms, including colonic motility, absorption, hormone secretion, permeability, and pain signalling. Pathophysiological states such as irritable bowel syndrome and ulcerative colitis and their interactions with circadian rhythmicity are also described. Finally, the classic circadian hormone melatonin is discussed, which is expressed in the gut in greater quantities than the pineal gland, and whose exogenous use has been of therapeutic interest in treating colonic pathophysiological states, including those exacerbated by chronic circadian disruption.

Aging alters the amplitude and phase of centrally regulated circadian rhythms. Here we evaluate whether peripheral circadian rhythmicity in the plasma lipidome is altered by aging through retrospective lipidomics analysis on plasma samples collected in 24 healthy individuals (9 females; mean ± SD age: 40.9 ± 18.2 years) including 12 younger (4 females, 23.5 ± 3.9 years) and 12 middle-aged older, (5 females, 58.3 ± 4.2 years) individuals every 3 h throughout a 27-h constant routine (CR) protocol, which allows separating evoked changes from endogenously generated oscillations in physiology. Cosinor regression shows circadian rhythmicity in 25% of lipids in both groups. On average, the older group has a ~14% lower amplitude and a ~2.1 h earlier acrophase of the lipid circadian rhythms (both, p ≤ 0.001). Additionally, more rhythmic circadian lipids have a significant linear component in addition to the sinusoidal across the 27-h CR in the older group (44/56) compared to the younger group (18/58, p < 0.0001). Results from individual-level data are consistent with group-average results. Results indicate that prevalence of endogenous circadian rhythms of the human plasma lipidome is preserved with healthy aging into middle-age, but significant changes in rhythmicity include a reduction in amplitude, earlier acrophase, and an altered temporal relationship between central and lipid rhythms. Intrinsic circadian rhythm in the human plasma lipidome is preserved during healthy aging, but there is a significant advance in the phase and a reduction in the amplitude of circadian lipid profiles in older compared to younger adults. [ABSTRACT FROM AUTHOR]

Normal and abnormal cardiac rhythms are of key physiological and clinical interest. This introductory article begins from Sylvio Weidmann's key historic 1950s microelectrode measurements of cardiac electrophysiological activity and Singh & Vaughan Williams's classification of cardiotropic targets. It then proceeds to introduce the insights into cardiomyocyte function and its regulation that subsequently emerged and their therapeutic implications. We recapitulate the resulting view that surface membrane electrophysiological events underlying cardiac excitation and its initiation, conduction and recovery constitute the final common path for the cellular mechanisms that impinge upon this normal or abnormal cardiac electrophysiological activity. We then consider progress in the more recently characterized successive regulatory hierarchies involving Ca2+ homeostasis, excitation–contraction coupling and autonomic G-protein signalling and their often reciprocal interactions with the surface membrane events, and their circadian rhythms. Then follow accounts of longer-term upstream modulation processes involving altered channel expression, cardiomyocyte energetics and hypertrophic and fibrotic cardiac remodelling. Consideration of these developments introduces each of the articles in this Phil. Trans. B theme issue. The findings contained in these articles translate naturally into recent classifications of cardiac electrophysiological targets and drug actions, thereby encouraging future iterations of experimental cardiac electrophysiological discovery, and testing directed towards clinical management. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'. [ABSTRACT FROM AUTHOR]

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]

Overnutrition is a risk factor for various human diseases, including neurodegenerative diseases, metabolic disorders, and cancers. Therefore, targeting overnutrition represents a simple but attractive strategy for the treatment of these increasing public health threats. Fasting as a dietary intervention for combating overnutrition has been extensively studied. Fasting has been practiced for millennia, but only recently have its roles in the molecular clock, gut microbiome, and tissue homeostasis and function emerged. Fasting can slow aging in most species and protect against various human diseases, including neurodegenerative diseases, metabolic disorders, and cancers. These centuried and unfading adventures and explorations suggest that fasting has the potential to delay aging and help prevent and treat diseases while minimizing side effects caused by chronic dietary interventions. In this review, recent animal and human studies concerning the role and underlying mechanism of fasting in physiology and pathology are summarized, the therapeutic potential of fasting is highlighted, and the combination of pharmacological intervention and fasting is discussed as a new treatment regimen for human diseases. [ABSTRACT FROM AUTHOR]

Daily light–dark cycles shape the circadian physiology and behaviour of nearly all organisms, with variation in circadian phenotypes having cascading effects on individual fitness, species interactions and species co‐evolution.Recent evidence that circadian rhythms in host immunity and metabolism are synchronised by the gut microbiota suggest that the circadian dynamics of gut microbes are a crucial component of their function. However, there remains little knowledge or understanding of the diurnal dynamics of gut microbiomes in natural populations or the consequences for host physiology and ecology.Here, we summarise the hallmarks of gut microbiota oscillations reported to date and the mechanisms by which they synchronise rhythms in host immunity and metabolism. We outline the consequences for diverse biological processes such as host pathogen susceptibility and seasonal switches in metabolism, and discuss how the breakdown of these circadian interactions, for example during senescence or because of light pollution, may affect wildlife infection risk and disease.We also provide practical guidelines for the measurement of microbial oscillations in wildlife, highlighting that whilst faecal samples of wild animals are rarely available over a 24‐h period, characterising even parts of the gut microbial cycle can be informative.An improved understanding of how gut microbial diurnal rhythms manifest in wildlife is essential to fully comprehend their role in shaping variation in host circadian phenotypes and the consequences for host physiology and ecology. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Circadian rhythms in physiology and behavior allow organisms to anticipate the daily environmental changes imposed by the rotation of our planet around its axis. Although these rhythms eventually manifest at the organismal level, a cellular basis for circadian rhythms has been demonstrated. Significant contributors to these cell-autonomous rhythms are daily cycles in gene expression and protein translation. However, recent data revealed cellular rhythms in other biological processes, including ionic currents, ion transport, and cytosolic ion abundance. Circadian rhythms in ion currents sustain circadian variation in action potential firing rate, which coordinates neuronal behavior and activity. Circadian regulation of metal ions abundance and dynamics is implicated in distinct cellular processes, from protein translation to membrane activity and osmotic homeostasis. In turn, studies showed that manipulating ion abundance affects the expression of core clock genes and proteins, suggestive of a close interplay. However, the relationship between gene expression cycles, ion dynamics, and cellular function is still poorly characterized. In this review, I will discuss the mechanisms that generate ion rhythms, the cellular functions they govern, and how they feed back to regulate the core clock machinery. [ABSTRACT FROM AUTHOR]

Opsins are transmembrane proteins that have a covalent bond with a chromophore 11-cis-retinal in the intracellular region, opsins transiently bind to a G protein, which in turn is alternatively coupled to GTP or GDP. These characteristics allow opsins to function as photopigments and, after reacting with light, they launch the cascade of intracellular communication processes known as phototransduction. Commonly referred to as the starting point of the visual pathway, phototransduction as initiated by opsins, can also mediate physiological processes as varied as taxis, metabolic synchronization, and seasonal migration. This review analyzes such functions performed by opsins in crustaceans, a group with a huge diversity of species that, owing to their plasticity, have been able to invade habitats that other arthropods or terrestrial vertebrates have been unable to occupy. Our analysis emphasizes the way in which opsins take part in crustacean behavioral display under extreme habitat conditions as in the case of cave fauna), as well as in essential ontogenic events. The many functions of opsins have been scarcely investigated due to bias generated by their participation in visual processes. Attention to the non-visual activity of opsins can break new grounds towards an integrative understanding of animal physiology. [ABSTRACT FROM AUTHOR]

Simple Summary: Providing more light in the first days after weaning is a common practice in pig husbandry. This supposedly stimulates feed intake and performance of (smaller) piglets after weaning. Currently, the literature does not agree on whether this is beneficial. Therefore, the effects of extending the lighting schedule on nursery pig performance, health, and behaviour during the entire nursery period were studied. No beneficial effects were seen on performance and behaviour of the pigs. Furthermore, piglets that were exposed to more light showed worse fecal consistency scores on days 7 (LONG: 21 vs. SHORT: 10; p = 0.039), 11 (LONG: 40 vs. SHORT: 14; p = 0.002), 21 (LONG: 21 vs. SHORT: 8; p = 0.008), and 25 (LONG: 26 vs. SHORT: 11; p = 0.015). It could not be excluded that this difference was due to infection, but there was no significant increase in mortality. This study provides evidence that leaving the lights on for the first days after weaning is not beneficial but should be repeated on more farms to get definitive answers. Lighting influences the circadian rhythm and physiology of animals. Yet, the influence of light on nursery pigs is not fully understood and results remain controversial. The present study investigated the effects of a prolonged photoperiod on the performance, health, and behaviour of nursery pigs. This study was conducted in one farm and included 288 hybrid nursery pigs. Long (LONG) and short (SHORT) photoperiod animals were exposed to either 16 or 8 h of light per day, respectively. Performance, health, welfare, and behavioural parameters were monitored during a nursery period of five weeks. Short photoperiod piglets tended to have higher weights at the end of the nursery (LONG: 21.59 vs. SHORT: 22.19 kg; p = 0.064) and higher average daily gain (LONG: 385 vs. SHORT: 403 g/day; p = 0.063) compared to the long photoperiod piglets. The LONG piglets had significantly higher fecal consistency scores (0–100) than the SHORT piglets on days 7 (LONG: 21 vs. SHORT: 10; p = 0.039), 11 (LONG: 40 vs. SHORT: 14; p = 0.002), 21 (LONG: 21 vs. SHORT: 8; p = 0.008), and 25 (LONG: 26 vs. SHORT: 11; p = 0.015). The LONG piglets tended to have a slightly higher incidence of aggressive behaviour (LONG: 2.49% vs. SHORT: 2.36%; p = 0.071). No significant differences were found for the remaining parameters (p > 0.1). Under the present conditions, lengthening the photoperiod during the nursery period did not significantly improve the performance, health, and welfare of the pigs. [ABSTRACT FROM AUTHOR]

Abstract Background Circadian rhythms are important for all aspects of biology; virtually every aspect of biological function varies according to time of day. Although this is well known, variation across the day is also often ignored in the design and reporting of research. For this review, we analyzed the top 50 cited papers across 10 major domains of the biological sciences in the calendar year 2015. We repeated this analysis for the year 2019, hypothesizing that the awarding of a Nobel Prize in 2017 for achievements in the field of circadian biology would highlight the importance of circadian rhythms for scientists across many disciplines, and improve time-of-day reporting. Results Our analyses of these 1000 empirical papers, however, revealed that most failed to include sufficient temporal details when describing experimental methods and that few systematic differences in time-of-day reporting existed between 2015 and 2019. Overall, only 6.1% of reports included time-of-day information about experimental measures and manipulations sufficient to permit replication. Conclusions Circadian rhythms are a defining feature of biological systems, and knowing when in the circadian day these systems are evaluated is fundamentally important information. Failing to account for time of day hampers reproducibility across laboratories, complicates interpretation of results, and reduces the value of data based predominantly on nocturnal animals when extrapolating to diurnal humans.

BACKGROUND: With the development of visceral obesity, against the background of insulin resistance (IR), lipo- and glucose toxicity in tissues progresses, which disrupts the metabolic balance of the body, and is the main factor in the development of type 2 diabetes mellitus (DM2). To date, a growing number of publications highlighting the role of circadian rhythms in the control of gluconeogenesis and lipogenesis. In the context of the development of DM2, the process of rhythm mismatch (desynchronosis) is increasingly mentioned, for the diagnosis of which the calculation of amplitude-phase parameters is used. Thus, the study of circadian rhythm disturbances using amplitude-phase parameters and factors influencing them is of particular interest in individuals with visceral obesity and prediabetes, since the data obtained can be used as markers for preclinical diagnosis of DM2.AIM: To identify significant differences in the parameters (amplitude, acrophase) of circadian rhythms (fasting glycemia, basal body temperature, heart rate) as markers of desynchronosis in groups without carbohydrate metabolism disorders, but with the presence of visceral obesity, prediabetes (impaired fasting glycemia, impaired glucose tolerance test) and DM2 and obesity.MATERIALS AND METHODS: The study was conducted in individuals with visceral obesity, as well as the presence of prediabetes or DM2, with a disease experience of not more than 5 years.In accordance with the study design, every 3 hours during the day, the participants made self-measurements of blood glucose at home (using individual glucometers), basal body temperature (BTT) in the armpit (using a mercury thermometer) and heart rate (HR) ( with the help of an electronic tonometer), with the fixation of the results in self-control diaries. To assess the reliability of the circadian rhythms of the studied indicators, the interpretation of chronobiological parameters (MESORa-Midline Estimating Statistic of Rhytm; amplitude; acrophase) was carried out using a single сosinor analysis.RESULTS: Of the 120 study participants, 73% were women and 27% were men. Mean age of participants was 58.6[52.2;56.7] years, BMI 31.3[29.7;33.9] and presence of visceral obesity WC 100 [93.8;104.7]. When conducting cosinor analysis, the daily rhythms of physiological indicators of fasting glycemia, BTT and heart rate differ from normal already in the group with visceral obesity without carbohydrate metabolism disorders and prediabetes, in the form of a decrease in the amplitude of daily rhythms (p

Introduction: Melatonin (5-methoxy-N-acetyl-tryptamine) is a circadian hormone synthesized and secreted by the pineal gland. In addition to regulating circadian rhythms of many physiological functions, melatonin is involved in regulating autonomic nervous function and blood pressure. Hypothalamus paraventricular nucleus (PVN), receiving melatonin projections from the superchiasmatic nucleus, is a critical brain region to regulate neuroendocrine and cardiovascular function. Here, we determined the synaptic mechanisms involved in the effect of melatonin on the sympathetic outflow and blood pressure.Methods and Results: Microinjection of melatonin into the PVN produced a depressor effect and decreased renal sympathetic nerve activity (RSNA). While microinjection of luzindole, a non-selective melatonin receptor antagonist, into the PVN did not change melatonin-induced sympathoinhibition, GABAA receptor antagonist bicuculline eliminated melatonin-induced sympathoinhibition. Furthermore, melatonin decreased firing rate of retrogradely labeled PVN neurons which project to the rostral ventrolateral medulla (RVLM), an effect was not altered by luzindole but eliminated by bicuculline. Melatonin significantly increased the amplitude of spontaneous and evoked GABAergic inhibitory synaptic currents, as well as GABA-induced currents.Conclusion: These data suggest that melatonin in the PVN suppresses sympathetic vasomotor tone through enhancing GABAA receptor activity. This study provides novel information for understanding the cellular mechanisms involved in the effect of melatonin on regulating blood pressure and sympathetic output.

Heart rate biologging has been successfully used to study wildlife responses to natural and human-caused stressors (e.g., hunting, landscape of fear). Although rarely deployed to inform conservation, heart rate biologging may be particularly valuable for assessing success in wildlife reintroductions. We conducted a case study for testing and validating the use of subcutaneous heart rate monitors in eight captive scimitar-horned oryx (Oryx dammah), a once-extinct species that is currently being restored to the wild. We evaluated biologger safety and accuracy while collecting long-term baseline data and assessing factors explaining variation in heart rate. None of the biologgers were rejected after implantation, with successful data capture for 16–21 months. Heart rate detection accuracy was high (83%–99%) for six of the individuals with left lateral placement of the biologgers. We excluded data from two individuals with a right lateral placement because accuracies were below 60%. Average heart rate for the six scimitar-horned oryx was 60.3 ± 12.7 bpm, and varied by about 12 bpm between individuals, with a minimum of 31 bpm and a maximum of 188 bpm across individuals. Scimitar-horned oryx displayed distinct circadian rhythms in heart rate and activity. Heart rate and activity were low early in the morning and peaked near dusk. Circadian rhythm in heart rate and activity were relatively unchanged across season, but hourly averages for heart rate and activity were higher in spring and summer, respectively. Variation in hourly heart rate averages was best explained by a combination of activity, hour, astronomical season, ambient temperature, and an interaction term for hour and season. Increases in activity appeared to result in the largest changes in heart rate. We concluded that biologgers are safe and accurate and can be deployed in free-ranging and reintroduced scimitar-horned oryx. In addition to current monitoring practices of reintroduced scimitar-horned oryx, the resulting biologging data could significantly aid in 1) evaluating care and management action prior to release, 2) characterizing different animal personalities and how these might affect reintroduction outcomes for individual animals, and 3) identifying stressors after release to determine their timing, duration, and impact on released animals. Heart rate monitoring in released scimitar-horned oryx may also aid in advancing our knowledge about how desert ungulates adapt to extreme environmental variation in their habitats (e.g., heat, drought).

Light entrains the endogenous circadian clocks of organisms to synchronize their behavioral and physiological rhythms with the natural photoperiod. The presence of artificial light at night disrupts these photoperiodic cues and is currently considered to be a major threat to key fitness-related behaviors, including sleep disruption and physiological stress. Research on the ecological influence of forest pest and their natural enemies is lacking. The wood-boring insects significantly damage forest and urban forest ecosystem functions. The parasitic beetles, Dastarcus helophoroides is an important natural enemy of wood-boring insects, especially those in the Cerambycidae family. However, the effect of artificial light at night on the locomotor rhythms and oviposition capacity of D. helophoroides has received little attention. To address this gap, diel changes in the locomotor activity and number of eggs laid by female D. helophoroides was analyzed under different light-dark (LD) cycles and temperatures. The results showed that the 24-h rhythmic of locomotor activity in these beetles was elevated in darkness and reduced under illumination, indicating that they are nocturnal insects. This activity has two major peaks, the evening (1–8 h after lights off) and morning (3.5–12.5 h after lights off) components, reflecting that light mediate regular changes in locomotor activity. Moreover, the circadian rhythms and active percentage were influenced by the illumination duration and temperature, especially constant light and 40°C. Females laid more eggs under the 16 L: 8 D cycles at 30°C than under the other combinations of photoperiod (including constant light and darkness) and temperature. Finally, the potential influence of exposure to four ecologically relevant intensities of artificial light at night (0, 1, 10 or 100 lx) on oviposition capacity was studied. The results showed that lifetime exposure to bright artificial light (1–100 lx) at night decreased the number of eggs laid relative to those laid with no lighting at night. These results demonstrate that chronic exposure to bright artificial light at night may influence the locomotor activity and oviposition capacity of this parasitic beetle.

Integrating thermal physiology with environmental temperature is essential to understanding distributions of species and vulnerability to climate change. Warming tolerance – the difference between an organism's maximum thermal tolerance (Tmax) and maximum habitat temperature (Thab) – is frequently used to integrate organismal sensitivity and environmental exposure. Traditionally, applications of warming tolerance define Tmax and Thab as invariable magnitudes, yet tolerance magnitude depends on exposure duration, and diel temperature cycles expose organisms to a range of temperature magnitudes and durations. How traditional (i.e. acute) estimates of warming tolerance compare to estimates from prolonged exposures remains poorly understood. In this study, magnitude–duration curves for tolerances of one cold‐water, two cool‐water and one warm‐water species of freshwater fish were compiled from the literature and compared to magnitude–duration exposures from 66 streams across the eastern United States. Warming tolerances were estimated for exposure durations spanning 0.01–24 h. Current acute (0.01 h) warming tolerances ranged from median 6.30°C for the cold‐water species to 9.68°C for the warm‐water species. The lowest warming tolerances corresponded to prolonged exposures lasting median 3.85–5.30 h among species and were 2.51–4.38°C lower than acute estimates. Although acute estimates remained positive in historically occupied and unoccupied streams (6.30 versus 2.33°C), estimates based on prolonged exposure were positive at occupied streams of the cold‐water species but transitioned to negative in unoccupied streams (2.19 versus −1.12°C). Acute warming tolerances for the cold‐water species also remained positive under future climate (6.29–4.23°C) but approached zero at prolonged durations (2.19–0.09°C) and transitioned to negative for 47.2% of streams. Results demonstrate that acute measures of Tmax and Thab overestimate warming tolerances and therefore underestimate climate change vulnerability. Integrating magnitude–duration relationships into warming tolerance estimates can elucidate physiological mechanisms underlying species distributions and can improve accuracy of climate change vulnerability assessments. [ABSTRACT FROM AUTHOR]

Background: It is known that the circadian rhythm phase in adults can be advanced in a natural light-dark cycle without electrical lighting. However, the effect of advanced sleep-wake timing according to the natural light-dark cycle on children's circadian phase is unclear. We investigated the effects of approximately 2 weeks of camping life with little access to artificial lighting on children's circadian phases. We also conducted an exploratory examination on the effects of wake time according to natural sunrise time on the manner of the advance of their circadian phases. Methods: Twenty-one healthy children (mean ± SD age, 10.6 ± 1.4 years) participated in a camping program with wake time (4:00) being earlier than sunrise time (EW condition), and 21 healthy children (10.4 ± 1.1 years) participated in a camping program with wake time (5:00) being almost matched to sunrise time (SW condition). Salivary dim light melatonin onset (DLMO) before the camping program and that after approximately 2 weeks of camping were compared. Results: DLMO was advanced by approximately 2 h after the camping program compared with the circadian phase in daily life in both conditions. In addition, the advances in DLMO were significantly correlated with mid-sleep points before the camp in both conditions (EW: r = 0.72, p < 0.01, SW: r = 0.70, p < 0.01). These correlations mean that the phase advance was greater for the children with delayed sleep habits in daily life. Furthermore, in the EW condition, mean DLMO after the camp (18:09 ± 0:33 h) was earlier than natural sunset time and there was no significant decrease in interindividual variability in DLMO. On the other hand, in the SW condition, mean DLMO after the camp (18:43 ± 0:20 h) matched natural sunset time and interindividual variability in DLMO was significantly lower than that before the camp. Conclusions: Camping with advanced sleep and wake timing under natural sunlight advances children's circadian phases. However, DLMO earlier than sunset in an early waking condition may lead to large interindividual variability in the circadian rhythm phase. [ABSTRACT FROM AUTHOR]

The brain has a complex structure composed of hundreds of regions, forming networks to cooperate body functions. Therefore, understanding how various brain regions communicate with each other and with peripheral organs is important to understand human physiology. The suprachiasmatic nucleus (SCN) in the brain is the circadian pacemaker. The SCN receives photic information from the environment and conveys this to other parts of the brain and body to synchronize all circadian clocks. The circadian clock is an endogenous oscillator that generates daily rhythms in metabolism and physiology in almost all cells via a conserved transcriptional–translational negative feedback loop. So, the information flow from the environment to the SCN to other tissues synchronizes locally distributed circadian clocks to maintain homeostasis. Thus, understanding the circadian networks and how they adjust to environmental changes will better understand human physiology. This review will focus on circadian networks mediated by the SCN to understand how the environment, brain, and peripheral tissues form networks for cooperation. [ABSTRACT FROM AUTHOR]

The change in life activities throughout a cycle of approximately 24 h is called the circadian rhythm. Circadian rhythm has an important impact on biological metabolism, digestion, immunity, and other physiological activities, but the circadian rhythm of crustaceans has rarely been studied. In this study, the activity of digestive enzymes (α-amylase, trypsin, and lipase) and immune enzymes (superoxide dismutase, lysozyme, and catalase), as well as the circadian rhythm of the intestinal bacterial community of Exopalaemon carinicauda, were studied. The results showed that the digestive and immune enzyme activities of E. carinicauda changed significantly (p < 0.05) at four time points throughout the day by one-way ANOVA analysis, with the highest value at 24:00 and the lowest value at 12:00. The highest values of alpha diversity and richness were observed in the 24:00 samples, which were significantly higher than those in the other groups (p < 0.05). The principal coordinate analysis (PCoA) results obviously showed that the samples from the same sampling time had higher similarity in the bacterial community structure. Candidatus hepatoplasma had the highest abundance among the intestinal microorganisms at 24:00, and Marinomonas had the highest abundance at 12:00. This study contributed to the understanding of digestive enzyme activity, immune enzyme activity, and the circadian rhythm of the intestinal bacterial community structure in E. carinicauda. It will play an important role in optimizing feeding times and improving digestion and nutrient utilization for E. carinicauda. The results of this study provide a basis for further study on the physiological mechanism of diurnal variation of intestinal flora in crustaceans. [ABSTRACT FROM AUTHOR]

Circadian entrainment in mice relies primarily on photic cues that trigger the transcription of the core clock genes Period1/2 in the suprachiasmatic nucleus (SCN), thus aligning the phase of the clock with the dawn/dusk cycle. It has been shown previously that this pathway is directly regulated by adenosine signalling and that adenosine A2A/A1 receptor antagonists can both enhance photic entrainment and phase shift circadian rhythms of wheel-running behaviour in mice. In this study, we tested the ability of CT1500, a clinically safe adenosine A2A/A1 receptor antagonist to effect circadian entrainment. We show that CT1500 lengthens circadian period in SCN ex vivo preparations. Furthermore, we show in vivo that a single dose of CT1500 enhances re-entrainment to a shifted light dark cycle in a dose-dependent manner in mice and also phase shifts the circadian clock under constant dark with a clear time-of-day related pattern. The phase response curve shows CT1500 causes phase advances during the day and phase delays at dusk. Finally, we show that daily timed administration of CT1500 can entrain the circadian clock to a 24 h rhythm in free-running mice. Collectively, these data support the use of CT1500 in the treatment of disorders of circadian entrainment.

Circadian clocks are ∼24-h timekeepers that control rhythms in almost all aspects of our behavior and physiology. While it is well known that subcellular localization of core clock proteins plays a critical role in circadian regulation, very little is known about the spatiotemporal organization of core clock mRNAs and its role in generating ∼24-h circadian rhythms. Here we describe a streamlined single molecule Fluorescence In Situ Hybridization (smFISH) protocol and a fully automated analysis pipeline to precisely quantify the number and subcellular location of mRNAs of Clock, a core circadian transcription factor, in individual clock neurons in whole mount Drosophila adult brains. Specifically, we used ∼48 fluorescent oligonucleotide probes that can bind to an individual Clock mRNA molecule, which can then be detected as a diffraction-limited spot. Further, we developed a machine learning-based approach for 3-D cell segmentation, based on a pretrained encoder-decoder convolutional neural network, to automatically identify the cytoplasm and nuclei of clock neurons. We combined our segmentation model with a spot counting algorithm to detect Clock mRNA spots in individual clock neurons. Our results demonstrate that the number of Clock mRNA molecules cycle in large ventral lateral clock neurons (lLNvs) with peak levels at ZT4 (4 h after lights are turned on) with ∼80 molecules/neuron and trough levels at ZT16 with ∼30 molecules/neuron. Our streamlined smFISH protocol and deep learning-based analysis pipeline can be employed to quantify the number and subcellular location of any mRNA in individual clock neurons in Drosophila brains. Further, this method can open mechanistic and functional studies into how spatiotemporal localization of clock mRNAs affect circadian rhythms.

RNA‐binding motif protein 3 (RBM3), an outstanding cold shock protein, is rapidly upregulated to ensure homeostasis and survival in a cold environment, which is an important physiological mechanism in response to cold stress. Meanwhile, RBM3 has multiple physiological functions and participates in the regulation of various cellular physiological processes, such as antiapoptosis, circadian rhythm, cell cycle, reproduction, and tumogenesis. The structure, conservation, and tissue distribution of RBM3 in human are demonstrated in this review. Herein, the multiple physiological functions of RBM3 were summarized based on recent research advances. Meanwhile, the cytoprotective mechanism of RBM3 during stress under various adverse conditions and its regulation of transcription were discussed. In addition, the neuroprotection of RBM3 and its oncogenic role and controversy in various cancers were investigated in our review. [ABSTRACT FROM AUTHOR]

The microbial community colonizing the gastrointestinal tract, collectively termed the gut microbiota, is an important element of the host organism due to its impact on multiple aspects of health. The digestion of food, secretion of immunostimulatory molecules, performance of chemical reactions in the intestine, and production of metabolites by the microbiota contribute to host homeostasis and disease. Recent discoveries indicate that these major functions are not constantly performed over the course of a day, but rather undergo diurnal fluctuations due to compositional and biogeographical oscillations in the microbiota. Here, we summarize the characteristics and origins of diurnal microbiome rhythms as well as their functional consequences for the circadian biology of the host. We describe the major known pathways of circadian host-microbiome communication and discuss possible implications of altered diurnal microbiome rhythms for human disease. [ABSTRACT FROM AUTHOR]

Modern lifestyle reduces environmental rhythmicity and may lead to circadian desynchrony. We are exposed to poor day-time lighting indoors and excessive night-time artificial light. We use air-conditioning to reduce ambient temperature cycle, and food is regularly available at all times. These disruptions of daily rhythms may lead to type 2 diabetes mellitus (T2DM), obesity, cardiometabolic diseases (CMD), depression and anxiety, all of which impose major public health and economic burden on societies. Therefore, we need appropriate animal models to gain a better understanding of their etiologic mechanisms, prevention, and management.We argue that the fat sand rat (Psammomys obesus), a diurnal animal model, is most suitable for studying the effects of modern-life conditions. Numerous attributes make it an excellent model to study human health disorders including T2DM, CMD, depression and anxiety. Here we review a comprehensive series of studies we and others conducted, utilizing the fat sand rat to study the underlying interactions between biological rhythms and health. Understanding these interactions will help deciphering the biological basis of these diseases, which often occur concurrently. We found that when kept in the laboratory (compared with natural and semi-wild outdoors conditions where they are diurnal), fat sand rats show low amplitude, nocturnal or arrhythmic activity patterns, dampened daily glucose rhythm, glucose intolerance, obesity and decreased survival rates. Short photoperiod acclimation exacerbates these pathologies and further dampens behavioral and molecular daily rhythms, resulting in CMD, T2DM, obesity, adipocyte dysfunction, cataracts, depression and anxiety. Increasing environmental rhythmicity by morning bright light exposure or by access to running wheels strengthens daily rhythms, and results in higher peak-to-trough difference in activity, better rhythmicity in clock genes expression, lower blood glucose and insulin levels, improved glucose tolerance, lower body and heart weight, and lower anxiety and depression. In summary, we have demonstrated that fat sand rats living under the correspondent of “human modern lifestyle” conditions exhibit dampened behavioral and biological rhythms and develop circadian desynchrony, which leads to what we have named “The Circadian Syndrome”. Environmental manipulations that increase rhythmicity result in improvement or prevention of these pathologies. Similar interventions in human subjects could have the same positive results and further research on this should be undertaken.

Background: Circadian rhythms are important for all aspects of biology; virtually every aspect of biological function varies according to time of day. Although this is well known, variation across the day is also often ignored in the design and reporting of research. For this review, we analyzed the top 50 cited papers across 10 major domains of the biological sciences in the calendar year 2015. We repeated this analysis for the year 2019, hypothesizing that the awarding of a Nobel Prize in 2017 for achievements in the field of circadian biology would highlight the importance of circadian rhythms for scientists across many disciplines, and improve time-of-day reporting. Results: Our analyses of these 1000 empirical papers, however, revealed that most failed to include sufficient temporal details when describing experimental methods and that few systematic differences in time-of-day reporting existed between 2015 and 2019. Overall, only 6.1% of reports included time-of-day information about experimental measures and manipulations sufficient to permit replication. Conclusions: Circadian rhythms are a defining feature of biological systems, and knowing when in the circadian day these systems are evaluated is fundamentally important information. Failing to account for time of day hampers reproducibility across laboratories, complicates interpretation of results, and reduces the value of data based predominantly on nocturnal animals when extrapolating to diurnal humans. [ABSTRACT FROM AUTHOR]

In humans, an adaptable internal biological system generates circadian rhythms that maintain synchronicity of behavior and physiology with the changing demands of the 24-h environment. Development of the circadian system begins in utero and continues throughout the first few years of life. Maturation of the clock can be measured through sleep/wake patterns and hormone secretion. Circadian rhythms, by definition, can persist in the absence of environmental input; however, their ability to adjust to external time cues is vital for adaptation and entrainment to the environment. The significance of these external factors that influence the emergence of a stable circadian clock in the first years of life remain poorly understood. Infants raised in our post-modern world face adverse external circadian signals, such as artificial light and mistimed hormonal cues via breast milk, which may increase interference with the physiological mechanisms that promote circadian synchronization. This review describes the very early developmental stages of the clock and common circadian misalignment scenarios that make the developing circadian system more susceptible to conflicting time cues and temporal disorder between the maternal, fetal, infant, and peripheral clocks. [ABSTRACT FROM AUTHOR]

Obese individuals are at significantly elevated risk of developing cardiovascular disease (CVD). Additionally, obesity has been associated with disrupted circadian rhythm, manifesting in abnormal sleeping and feeding patterns. To date, the mechanisms linking obesity, circadian disruption, and CVD are incompletely understood, and insight into novel mechanistic pathways is desperately needed to improve therapeutic potential and decrease morbidity and mortality. The objective of this study was to investigate the roles of metabolic and circadian disruptions in obesity and assess their contributions in promoting vascular disease. Lean (db/+) and obese (db/db) mice were subjected to 12 weeks of constant darkness to differentiate diurnal and circadian rhythms, and were assessed for changes in metabolism, gene expression, and vascular function. Expression of endothelial nitric oxide synthase (eNOS), an essential enzyme for vascular health, was blunted in obesity and correlated with the oscillatory loss of the novel regulator cezanne (OTUD7B). Lean mice subjected to constant darkness displayed marked reduction in vasodilatory capacity, while endothelial dysfunction of obese mice was not further compounded by diurnal insult. Endothelial gene expression of essential circadian clock components was altered in obesity, but imperfectly phenocopied in lean mice housed in constant darkness, suggesting overlapping but separate mechanisms driving endothelial dysfunction in obesity and circadian disruption. Taken together, these data provide insight into the nature of endothelial circadian rhythm in obesity and suggest a distinct mechanism by which obesity causes a unique circadian defect in the vasculature. [ABSTRACT FROM AUTHOR]

The behavior and physiology of most organisms are temporally coordinated and aligned with geophysical time by a complex interplay between the master and peripheral clocks. Disruption of such rhythmic physiological activities that are hierarchically organized has been linked to a greater risk of developing diseases ranging from cancer to metabolic syndrome. Herein, we summarize the molecular clockwork that is employed by intestinal epithelial cells to anticipate environmental changes such as rhythmic food intake and potentially dangerous environmental stress. We also discuss recent discoveries contributing to our understanding of how a proper rhythm of intestinal stem cells may achieve coherence for the maintenance of tissue integrity. Emerging evidence indicates that the circadian oscillations in the composition of the microbiota may operate as an important metronome for the proper preservation of intestinal physiology and more. Furthermore, in this review, we outline how epigenetic clocks that are based on DNA methylation levels may extensively rewire the clock-controlled functions of the intestinal epithelium that are believed to become arrhythmic during aging. [ABSTRACT FROM AUTHOR]

Melatonin is a special hormone that act as an internal synchronizer of circadian rhythms, the organism physiology and behavior to the environmental day and night and seasons of the year. The present urban society and the industrial production processes as organized should be considered, as both depend on the presence of indoor lights during the night and include the profuse use of electronic devices whose screens are rich in blue wavelength light. Light during the night delays the beginning of the secretory episode of melatonin and blunts its peak, causing chronic hypomelatoninemia. Hypomelatonemia, that causes deprivation of sleep and eating behavior disorders, along with low physical activity, can be the reason of the obesity, «non-infectious epidemic of the 21st century». According to this, the use of melatonin drugs for obesity treatment can be effective. Further prospective, controlled, randomized trials in this area are required to confirm this hypothesis.

Prolonged exposure to chronic sleep restriction (CSR) and shiftwork are both associated with incident hypertension and cardiovascular disease. We hypothesized that the combination of CSR and shiftwork’s rotating sleep schedule (causing recurrent circadian disruption, RCD) would increase blood pressure, renal sodium retention, potassium excretion, and aldosterone excretion. Seventeen healthy participants were studied during a 32-day inpatient protocol that included 20-h “days” with associated scheduled sleep/wake and eating behaviors. Participants were randomly assigned to restricted (1:3.3 sleep:wake, CSR group) or standard (1:2 sleep:wake, Control group) ratios of sleep:wake duration. Systolic blood pressure during circadian misalignment was ∼6% higher in CSR conditions. Renal sodium and potassium excretion showed robust circadian patterns; potassium excretion also displayed some influence of the scheduled behaviors (sleep/wake, fasting during sleep so made parallel fasting/feeding). In contrast, the timing of renal aldosterone excretion was affected predominately by scheduled behaviors. Per 20-h “day,” total sodium excretion increased, and total potassium excretion decreased during RCD without a change in total aldosterone excretion. Lastly, a reduced total renal sodium excretion was found despite constant oral sodium consumption and total aldosterone excretion, suggesting a positive total body sodium balance independent of aldosterone excretion. These findings may provide mechanistic insight into the observed adverse cardiovascular and renal effects of shiftwork.