Amplitude Of Circadian Rhythm Research Articles

Circadian patterns of heart rate, respiratory rate and skin temperature in hospitalized COVID-19 patients.

Vital signs follow circadian patterns in both healthy volunteers and critically ill patients, which seem to be influenced by disease severity in the latter. In this study we explored the existence of circadian patterns in heart rate, respiratory rate and skin temperature of hospitalized COVID-19 patients, and aimed to explore differences in circadian rhythm amplitude during patient deterioration. We performed a retrospective study of COVID-19 patients admitted to the general ward of a tertiary hospital between April 2020 and March 2021. Patients were continuously monitored using a wireless sensor and fingertip pulse oximeter. Data was divided into three cohorts: patients who recovered, patients who developed respiratory insufficiency and patients who died. For each cohort, a population mean cosinor model was fitted to detect rhythmicity. To assess changes in amplitude, a mixed-effect cosinor model was fitted. A total of 429 patients were monitored. Rhythmicity was observed in heartrate for the recovery cohort (p<0.001), respiratory insufficiency cohort (p<0.001 and mortality cohort (p = 0.002). Respiratory rate showed rhythmicity in the recovery cohort (p<0.001), but not in the other cohorts (p = 0.18 and p = 0.51). Skin temperature also showed rhythmicity in the recovery cohort (p<0.001), but not in the other cohorts (p = 0.22 and p = 0.12). For respiratory insufficiency, only the amplitude of heart rate circadian pattern increased slightly the day before (1.2 (99%CI 0.16-2.2, p = 0.002)). In the mortality cohort, the amplitude of heart rate decreased (-1.5 (99%CI -2.6- -0.42, p<0.001)) and respiratory rate amplitude increased (0.72 (99%CI 0.27-1.3, p = 0.002) the days before death. A circadian rhythm is present in heart rate of COVID-19 patients admitted to the general ward. For respiratory rate and skin temperature, rhythmicity was only found in patients who recover, but not in patients developing respiratory insufficiency or death. We found no consistent changes in circadian rhythm amplitude accompanying patient deterioration.

Optimized Excess-Green Image Binarization for Accurate Estimation of Lettuce Seedling Leaf-Area in a Plant Factory

Real-time, continuous young seedling-growth measurement improves plant factory stabilization and productivity. Projected leaf area (PLA) based on seedling top-view images is a useful growth index, and easy to measure continuously for large seedling populations. However, it is difficult to automatically determine PLA with a high degree of accuracy, because RGB image color-balance fluctuates with plant growth, leaf movement, and environment. Therefore, we developed a technique for determining PLA on nursery-grown lettuce seedlings. Using a Raspberry Pi 3 microcomputer with a camera module placed above the seedlings, RGB images of 153 seedlings were obtained every 20 min from day 6 to 15 after sowing. Seedling PLA images were obtained by binarization and separation of the leaves from the background. To assess binarization accuracy, we used an Intersection over Union (IoU) index to compare the standard Excess Green (ExG) method, an optimized ExG method (O-ExG), and the artificial neural network U-Net method. Results showed that O-ExG was optimal under the experimental conditions tested. PLA and circadian rhythm amplitude extracted from PLA-image time-series data were independent, implying they can be used together for growth prediction. These findings improve the accuracy of imagebased growth prediction and have practical application in plant factories.

RCAN1 knockout and overexpression recapitulate an ensemble of rest-activity and circadian disruptions characteristic of Down syndrome, Alzheimer’s disease, and normative aging

BackgroundRegulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer’s disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology that appear symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been implicated in facilitating age-related cognitive decline and AD progression. However, no prior studies have assessed whether RCAN1 dysregulation may also promote the age-associated alteration of rest-activity profiles and circadian rhythms, which could in turn contribute to neurodegeneration in DS, AD, and aging.MethodsThe present study examined the impacts of RCAN1 deficiency and overexpression on the photic entrainment, circadian periodicity, intensity and distribution, diurnal patterning, and circadian rhythmicity of wheel running in young (3–6 months old) and aged (9–14 months old) mice of both sexes.ResultsWe found that daily RCAN1 levels in the hippocampus and suprachiasmatic nucleus (SCN) of light-entrained young mice are generally constant and that balanced RCAN1 expression is necessary for normal circadian locomotor activity rhythms. While the light-entrained diurnal period was unaltered, RCAN1-null and RCAN1-overexpressing mice displayed lengthened endogenous (free-running) circadian periods like mouse models of AD and aging. In light-entrained young mice, RCAN1 deficiency and overexpression also recapitulated the general hypoactivity, diurnal rest-wake pattern fragmentation, and attenuated amplitudes of circadian activity rhythms reported in DS, preclinical and clinical AD, healthily aging individuals, and rodent models thereof. Under constant darkness, RCAN1-null and RCAN1-overexpressing mice displayed altered locomotor behavior indicating circadian clock dysfunction. Using the Dp(16)1Yey/+ (Dp16) mouse model for DS, which expresses three copies of Rcan1, we found reduced wheel running activity and rhythmicity in both light-entrained and free-running young Dp16 mice like young RCAN1-overexpressing mice. Critically, these diurnal and circadian deficits were rescued in part or entirely by restoring Rcan1 to two copies in Dp16 mice. We also found that RCAN1 deficiency but not RCAN1 overexpression altered protein levels of the clock gene Bmal1 in the SCN.ConclusionsCollectively, this study’s findings suggest that both loss and aberrant gain of RCAN1 precipitate anomalous light-entrained diurnal and circadian activity patterns emblematic of DS, AD, and possibly aging.

Sex Differences in Pubertal Circadian and Ultradian Rhythmic Development Under Semi-naturalistic Conditions.

Biological rhythms in core body temperature (CBT) provide informative markers of adolescent development under controlled laboratory conditions. However, it is unknown whether these markers are preserved under more variable, semi-naturalistic conditions, and whether CBT may therefore prove useful in a real-world setting. To evaluate this possibility, we examined fecal steroid concentrations and CBT rhythms from pre-adolescence (p26) through early adulthood (p76) in intact male and female Wistar rats under natural light and climate at the Stephen Glickman Field Station for the Study of Behavior, Ecology and Reproduction. Despite greater environmental variability, CBT markers of pubertal onset and its rhythmic progression were comparable with those previously reported in laboratory conditions in female rats and extend actigraphy-based findings in males. Specifically, sex differences emerged in CBT circadian rhythm (CR) power and amplitude prior to pubertal onset and persisted into early adulthood, with females exhibiting elevated CBT and decreased CR power compared with males. Within-day (ultradian rhythm [UR]) patterns also exhibited a pronounced sex difference associated with estrous cyclicity. Pubertal onset, defined by vaginal opening, preputial separation, and sex steroid concentrations, occurred later than previously reported under lab conditions for both sexes. Vaginal opening and increased fecal estradiol concentrations were closely tied to the commencement of 4-day oscillations in CBT and UR power. By contrast, preputial separation and the first rise in testosterone concentration were not associated with adolescent changes to CBT rhythms in male rats. Together, males and females exhibited unique temporal patterning of CBT and sex steroids across pubertal development, with tractable associations between hormonal concentrations, external development, and temporal structure in females. The preservation of these features outside the laboratory supports CBT as a strong candidate for translational pubertal monitoring under semi-naturalistic conditions in females.

Circadian rhythms and some micromorphometric indicators of B16 melanoma

Introduction. Melanoma is one of the most malignant human tumors, originating from melanin-forming tissue. Currently, among the risk factors for the development of malignant neoplasms, including melanoma, light pollution is considered – exposure to light at night. In turn, the violation of circadian rhythm under conditions of light pollution often leads to the occurrence of desynchronosis, which is the cause of the development of a number of diseases, including malignant neoplasms. As a rule, light pollution is accompanied by a decrease in the production of epiphyseal melatonin, which has oncostatic, antitumor and antioxidant effects.The objective of study was to study the morphological features of transplanted B16 melanoma, to establish the micromorphometric indicators of tumor cells and circadian rhythms of some of them for further use as control indicators in the study of the effect of various light regimes and experimental therapy on the morphofunctional state of the body of animals with transplanted melanoma.Methods and materials. The study was conducted on male hybrid mice of the BDF1 line. The animals were divided into 2 equal groups of 25 individuals. The first group served as an intact control, the mice of the second group were transplanted with B16/F10 melanoma. On the 15th day after tumor inoculation, the animals were withdrawn from the experiment at 9.00, 15.00, 21.00 and 3. The mass and volume of the tumor were determined, microscopic, including micromorphometric studies of tumors were performed. Glucose levels were determined in blood plasma. The daily dynamics of the studied parameters was assessed, and for the statistical calculation of the amplitude and acrophase of circadian rhythms, a cosinor analysis was performed.Results. The study of the circadian rhythm of glucose made it possible to reveal its difference in animals with melanoma from that in the control. Changes in the daily rhythmicity of this metabolite, which comprehensively reflects the synchronization of many rhythms with each other, allows us to state a significant change in circadian rhythmostasis in animals with melanoma. As a result of the study, we have established micromorphometric indicators characteristic of B16 melanoma on the 14th day after transplantation. The circadian rhythm of the area of the nucleus and cells, the mitotic index and the absence of a clock for the NCR were established. The difference between the phase-amplitude features of the CR of the area of the nucleus of melanocyte cells from the normal ones was found.Conclusion. The obtained data indicate a change in rhythmostasis in mice with experimental B16 melanoma. The features of the organization of the rhythmicity of the tumor itself can be used in its targeted experimental therapy, taking into account chronobiological features. The results of the study can be used for further studies of the effect of various lighting modes on the morphofunctional state of the animal organism in the pathology under study.

Machine learning and expression analyses reveal circadian clock features predictive of anxiety

Mood disorders, including generalized anxiety disorder, are associated with disruptions in circadian rhythms and are linked to polymorphisms in circadian clock genes. Molecular mechanisms underlying these connections may be direct—via transcriptional activity of clock genes on downstream mood pathways in the brain, or indirect—via clock gene influences on the phase and amplitude of circadian rhythms which, in turn, modulate physiological processes influencing mood. Employing machine learning combined with statistical approaches, we explored clock genotype combinations that predict risk for anxiety symptoms in a deeply phenotyped population. We identified multiple novel circadian genotypes predictive of anxiety, with the PER3(rs17031614)-AG/CRY1(rs2287161)-CG genotype being the strongest predictor of anxiety risk, particularly in males. Molecular chronotyping, using clock gene expression oscillations, revealed that advanced circadian phase and robust circadian amplitudes are associated with high levels of anxiety symptoms. Further analyses revealed that individuals with advanced phases and pronounced circadian misalignment were at higher risk for severe anxiety symptoms. Our results support both direct and indirect influences of clock gene variants on mood: while sex-specific clock genotype combinations predictive of anxiety symptoms suggest direct effects on mood pathways, the mediation of PER3 effects on anxiety via diurnal preference measures and the association of circadian phase with anxiety symptoms provide evidence for indirect effects of the molecular clockwork on mood. Unraveling the complex molecular mechanisms underlying the links between circadian physiology and mood is essential to identifying the core clock genes to target in future functional studies, thereby advancing the development of non-invasive treatments for anxiety-related disorders.

Artificial selections for death‐feigning behavior in beetles show correlated responses in amplitude of circadian rhythms, but the period of the rhythm does not

AbstractOne of the most important survival strategies of organisms is to avoid predators. Studying one of such strategies, namely, death‐feigning behavior, has recently become more common. The success or failure of this antipredator strategy will be affected by the circadian rhythms of both prey and predator because death feigning sometimes has a diurnal rhythm. However, few studies have analyzed the effects of differences in circadian rhythms on predator‐avoidance behavior at the genetic level. Recently, the relationship between genes relating to circadian rhythm and death‐feigning behavior, an antipredator behavior, has been established at the molecular level. Therefore, in this study, we compared three circadian rhythm‐related traits, the free‐running period of rhythms, amplitude of circadian rhythms, and total activity of strains of three Tribolium species that were artificially selected for the death‐feigning duration: short (S‐strains) and long (L‐strains) durations. As a result, the amplitude of circadian rhythms and total activity were significantly different between S‐ and L‐strains, but there was no difference in the free‐running periods of the rhythm between the strains in T. castaneum, T. confusum, and T. freemani. Although the relationship between death‐feigning behavior and activity has been reported for all three species, a genetic relationship between the duration of death feigning and the amplitude of circadian rhythms has been newly found in the present study. It is important to investigate the relationship between antipredator strategies and circadian rhythms at the molecular level in the future.

Evening chronotype as a bipolar feature among patients with major depressive disorder: the results of a pilot factor analysis

Objectives:The bipolar spectrum concept has resulted in a paradigm shift that has affected both the diagnosis and therapy of mood disorders, with bipolarity becoming an indicator of treatment resistance in depression. Evening circadian preference has also been linked to affective disorders. The aim of our study was to confirm the relationship between the severity of depressive symptoms, bipolar features, chronotype, and sleep quality among patients with major depressive disorder.Methods:A group of 55 individuals who were recruited from a mental health outpatient clinic completed the following psychometric tools: a Chronotype Questionnaire comprising morningness-eveningness (ME) and subjective amplitude of the rhythm (AM) scales, the Hypomania Checklist 32 (HCL-32), the Beck Depression Inventory (BDI) and the Pittsburgh Sleep Quality Index (PSQI).Results:Factor analysis identified two latent components, accounting cumulatively for 58% of variables: depressive symptoms (BDI and PSQI) and bipolarity (ME, AM, and HCL-32). After rotation, ME loading in the first factor increased the result to a significant level. The correlation between the two components was very low.Conclusions:Evening chronotype appears to be a bipolarity-related marker, with this relationship being independent of its link to depressive symptoms and sleep quality. Eveningness and high circadian rhythm amplitude may offer promise as diagnostic, prognostic, and therapeutic predictors.

Cross-sectional study of intraocular cataract lens replacement, circadian rest-activity rhythms, and sleep quality in older adults.

Age-related cataract decreases light transmission at the most sensitive spectrum for circadian photoentrainment, with negative ramifications for human health. Here, we assessed whether intraocular lens replacement (IOL) in older patients with previous cataract was associated with increased stability and amplitude of circadian rest-activity rhythms, and improved sleep quality. Our cross-sectional study included sixteen healthy older individuals without ocular diseases (controls; 55-80 years; 63.6 ± 5.6y; 8 women) and 13 patients with previous cataract and bilateral IOL (eight with blue-blocking [BB] lens and five with ultraviolet-only [UV] blocking lens; 55-80 years; 69.9 ± 5.2y; 9 women). The study comprised three weeks of at home rest-activity assessments using wrist-worn actigraphs, and each week preceded a laboratory protocol. Primary outcomes were actigraphy-derived interdaily stability, intradaily variability, and relative amplitude of circadian rest-activity rhythms. Secondary outcomes were actigraphy-assessed sleep quality (i.e. time in bed, sleep duration, sleep efficiency, mean wake bout time and fragmentation index). Patients with IOL had significantly higher interdaily stability ("Group" effect: pFDR =.001), but not intradaily variability ("Group" effect: pFDR = n.s.), and significantly higher relative amplitude of rest-activity rhythms ("Group" effect: pFDR < .001). Moreover, patients with IOL had significantly higher activity levels during the day and lower levels during the evening, as compared to healthy older controls ("Group" effect: pFDR = .03). Analyses of actigraphy-derived sleep parameters yielded no significant differences across groups ("Group" effect: all pFDR > .1). Our cross-sectional study suggests that enhancing spectral lens transmission in patients with cataract may benefit their circadian health.

MiR-455-5p regulates circadian rhythms by accelerating the degradation of Clock mRNA.

Circadian rhythms are approximately 24-hr cycles generated by organisms to adapt to daily rhythms. Core circadian proteins such as CLOCK, BMAL1, PER1/2, and CRY1/2/3 form a transcription-translation feedback loop (TTFL) to maintain circadian rhythms. MicroRNAs are involved in regulating circadian rhythms; however, the detailed mechanisms remain unclear. Here, using miRNA-seq screening, we discovered that the expression level of miR-455 was controlled by CLOCK. Furthermore, miR-455-5p also binds to the 3' untranslated region (3'UTR) of Clock mRNA and regulates its stability. To further study whether such mutual regulation forms a feedback loop to regulate circadian rhythms, we recorded bioluminescence traces of Per2::Luc U2OS cells in real time and confirmed that overexpression of miR-455-5p lengthens the period and attenuates the amplitude of circadian rhythms in synchronized cells (and vice versa). We also discovered that miR-455-5p can function as a Clock modulator to induce a fine-orchestral circadian rhythm in vitro, as well as other known factors such as dexamethasone, horse serum, or temperature. In conclusion, miR-455-5p is essential for maintaining a normal circadian rhythm via regulating Clock mRNA stability. Our study reveals a new mutual regulatory mechanism between CLOCK protein, Clock mRNA, and miR-455-5p, which regulates circadian rhythms in cells.

More Than Morningness: The Effect of Circadian Rhythm Amplitude and Stability on Resilience, Coping, and Sleep Duration.

Self-report tools that measure circadian rhythms have focused primarily on phase. We add to the sparse literature on assessing amplitude and stability. We randomly recruited 1,163 participants who completed several measures. The correlation between the LV scale (amplitude) and FR scale (stability) was −0.12 (p < 0.01). As expected, amplitude was negatively associated with phase (r = −0.64, p < 0.01) while stability showed a weak link with phase (r = 0.07, p < 0.05). Structural equation modeling suggested a close model-fit of the factor structure in the sample (RMSEA = 0.033). The LV scale explained 22% of the variance, while the FR scale explained 23%. Scale reliability was satisfactory for the LV scale (0.68) and good for the FR scale (0.73). Participants with low amplitude or flexible rhythms reported significantly better resilience, coping, and required less daily sleep. We constructed a composite circadian categorical variable to combine the best attributes from the LV and FR scales; participants with both low amplitude and flexible rhythms, reported significantly better resilience, coping, and less sleep need. We found rhythm amplitude decreased with age, while stability remained constant.

Sex-related Changes in Circadian Rhythm of Inflammatory and Oxidative Stress Markers in CKD.

Introduction. Circadian system is deeply involved in renal function. The circadian timing system may be disrupted in chronic kidney disease (CKD) patients. Gender differences in CKD have been reported. This research aimed to investigate the gender differences in the circadian rhythm of inflammatory and oxidant markers of CKD. Methods. Male, intact female, and ovariectomized (OVX) female rats (twenty-four in each group) were randomly assigned to control and CKD groups. The rats were further divided into day (12:00 p.m.) and night (12:00 a.m.) subgroups. Evaluations of each sample were carried out a day after the last day of adenine administration. Results. Final results revealed that the circadian rhythm of plasma melatonin , kidney malondialdehyde (MDA), and transforming growth factor- β (TGF-β) levels in CKD group were the same as the control group. Melatonin and total antioxidant capacity (TAC) levels significantly decreased in the CKD group compared with the control group in day and night subgroups, whereas MDA and TGF-β levels increased. Male group in comparison with the intact female group significantly showed less melatonin and TAC but higher MDA and TGF-β levels which could be due to CKD. Conclusion. Findings of this study represent gender differences in circadian rhythm amplitude of inflammation, melatonin, and oxidative stress in CKD animals, probably in favor of female sex steroids. These findings emphasize on the importance of gender differences in CKD progression; therefore, considerable attention must be paid to gender in the treatment of CKD.Introduction. Circadian system is deeply involved in renal function. The circadian timing system may be disrupted in chronic kidney disease (CKD) patients. Gender differences in CKD have been reported. This research aimed to investigate the gender differences in the circadian rhythm of inflammatory and oxidant markers of CKD. Methods. Male, intact female, and ovariectomized (OVX) female rats (twenty-four in each group) were randomly assigned to control and CKD groups. The rats were further divided into day (12:00 p.m.) and night (12:00 a.m.) subgroups. Evaluations of each sample were carried out a day after the last day of adenine administration. Results. Final results revealed that the circadian rhythm of plasma melatonin , kidney malondialdehyde (MDA), and transforming growth factor- β (TGF-β) levels in CKD group were the same as the control group. Melatonin and total antioxidant capacity (TAC) levels significantly decreased in the CKD group compared with the control group in day and night subgroups, whereas MDA and TGF-β levels increased. Male group in comparison with the intact female group significantly showed less melatonin and TAC but higher MDA and TGF-β levels which could be due to CKD. Conclusion. Findings of this study represent gender differences in circadian rhythm amplitude of inflammation, melatonin, and oxidative stress in CKD animals, probably in favor of female sex steroids. These findings emphasize on the importance of gender differences in CKD progression; therefore, considerable attention must be paid to gender in the treatment of CKD. DOI: 10.52547/ijkd.6242

Точность циркадных часов, здоровье и долголетие

An accurate circadian clock, associated with the precise intrinsic period, tau, can be linked with a definite chronotype and health status. Exemplified by different animal species, and, as we argue herein, may as well be in humans, endogenous tau close enough to 24 hours is associated with higher life expectancy, lower morbidity, and is possibly adhered to moderate morning chronotype. Accurate circadian tau facilitates maintaining a high amplitude of circadian rhythms, a phenotypic trait that is related to health and longevity. Some genetic factors that coordinate tau and ensure circadian clock precision is considered.

Bright daytime light enhances circadian amplitude in a diurnal mammal.

Mammalian circadian rhythms are orchestrated by a master pacemaker in the hypothalamic suprachiasmatic nuclei (SCN), which receives information about the 24 h light-dark cycle from the retina. The accepted function of this light signal is to reset circadian phase in order to ensure appropriate synchronization with the celestial day. Here, we ask whether light also impacts another key property of the circadian oscillation, its amplitude. To this end, we measured circadian rhythms in behavioral activity, body temperature, and SCN electrophysiological activity in the diurnal murid rodent Rhabdomys pumilio following stable entrainment to 12:12 light-dark cycles at four different daytime intensities (ranging from 18 to 1,900 lx melanopic equivalent daylight illuminance). R. pumilio showed strongly diurnal activity and body temperature rhythms in all conditions, but measures of rhythm robustness were positively correlated with daytime irradiance under both entrainment and subsequent free run. Whole-cell and extracellular recordings of electrophysiological activity in ex vivo SCN revealed substantial differences in electrophysiological activity between dim and bright light conditions. At lower daytime irradiance, daytime peaks in SCN spontaneous firing rate and membrane depolarization were substantially depressed, leading to an overall marked reduction in the amplitude of circadian rhythms in spontaneous activity. Our data reveal a previously unappreciated impact of daytime light intensity on SCN physiology and the amplitude of circadian rhythms and highlight the potential importance of daytime light exposure for circadian health.

The role of circadian rhythm stability and amplitude in musculoskeletal disorder prevalence and work-family conflict.

AimThis study aimed to investigate the effect of circadian rhythm stability and amplitude on musculoskeletal disorder prevalence and work–family conflict among nurses.DesignThis cross‐sectional study was conducted on 386 nurses working in three hospitals, in Shahroud, Iran.MethodThe data were collected using the Circadian Rhythm Inventory, Nordic Musculoskeletal Disorders, and Carlson Work‐Family Conflict questionnaires.ResultsThe highest prevalence of musculoskeletal disorders was reported in the lower back (68.4%), upper back (65.5%) and shoulders (53.6%), respectively. No significant relation was found between circadian rhythm stability and amplitude, and musculoskeletal disorders prevalence. The nurses who could not overcome drowsiness reported more Work Interference with Family (WIF), Family Interference with Work (FIW) (time‐based) and FIW (strain‐based) compared to the nurses who overcame drowsiness. In addition, the appropriate nurses for shift work experienced less WIF, FIW (behavioural‐based) and WIF (strain‐based) compared to the nurses who could not work overtime or at night.

Applications of cosinor rhythmometry in pharmacology.

Study design and data analysis are two important aspects relevant to chronopharmacometrics. Blunders can be avoided by recognizing that most physiological variables are circadian periodic. Both ill health and treatment can affect the amplitude, phase, and/or period of circadian (and other) rhythms, in addition to their mean. The involvement of clock genes in molecular pathways related to important physiological systems underlies the bidirectional relationship often seen between circadian rhythm disruption and disease risk. Circadian rhythm characteristics of marker rhythms interpreted in the light of chronobiologic reference values represent important diagnostic tools. A set of cosinor-related programs is presented. They include the least squares fit of multiple-frequency cosine functions to model the time structure of individual records; a cosinor-based spectral analysis to detect periodic signals; the population-mean cosinor to generalize inferences; the chronobiologic serial section to follow the time course of changing rhythm parameters over time; and parameter tests to assess differences among populations. Relative merits of other available cosinor and non-parametric algorithms are reviewed. Parameter tests to compare individual records and a self-starting cumulative sum (CUSUM) make personalized chronotherapy possible, where the treatment of each patient relies on an N-of-1 design. Methods are illustrated in a few examples relevant to endocrinology, cancer and cardiology. New sensing technology yielding large personal data sets is likely to change the healthcare system. Chronobiologic concepts and methods should become an integral part of these evolving systems.

Superoxide is promoted by sucrose and affects amplitude of circadian rhythms in the evening

Plants must coordinate photosynthetic metabolism with the daily environment and adapt rhythmic physiology and development to match carbon availability. Circadian clocks drive biological rhythms which adjust to environmental cues. Products of photosynthetic metabolism, including sugars and reactive oxygen species (ROS), are closely associated with the plant circadian clock, and sugars have been shown to provide metabolic feedback to the circadian oscillator. Here, we report a comprehensive sugar-regulated transcriptome of Arabidopsis and identify genes associated with redox and ROS processes as a prominent feature of the transcriptional response. We show that sucrose increases levels of superoxide (O2-), which is required for transcriptional and growth responses to sugar. We identify circadian rhythms of O2--regulated transcripts which are phased around dusk and find that O2- is required for sucrose to promote expression of TIMING OF CAB1 (TOC1) in the evening. Our data reveal a role for O2- as a metabolic signal affecting transcriptional control of the circadian oscillator in Arabidopsis.

Transgenic rats expressing dominant negative BMAL1 showed circadian clock amplitude reduction and rapid recovery from jet lag.

The circadian rhythms are endogenous rhythms of about 24h, and are driven by the circadian clock. The clock centre locates in the suprachiasmatic nucleus. Light signals from the retina shift the circadian rhythm in the suprachiasmatic nucleus, but there is a robust part of the suprachiasmatic nucleus that causes jet lag after an abrupt shift of the environmental lighting condition. To examine the effect of attenuated circadian rhythm on the duration of jet lag, we established a transgenic rat expressing BMAL1 dominant negative form under control by mouse Prnp-based transcriptional regulation cassette [BMAL1 DN (+)]. The transgenic rats became active earlier than controls, just after light offset. Compared to control rats, BMAL1 DN (+) rats showed smaller circadian rhythm amplitudes in both behavioural and Per2 promoter driven luciferase activity rhythms. A light pulse during the night resulted in a larger phase shift of behavioural rhythm. Furthermore, at an abrupt shift of the light-dark cycle, BMAL1 DN (+) rat showed faster entrainment to the new light-dark cycle compared to controls. The circadian rhythm has been regarded as a limit cycle phenomenon, and our results support the hypothesis that modification of the amplitude of the circadian limit cycle leads to alteration in the length of the phase shift.

Circadian rhythm in critically ill patients: Insights from the eICU Database

ObjectiveTo investigate the circadian variation among critically ill patients and its association with clinical characteristics and survival to hospital discharge in a large population of patients in the intensive care unit (ICU).MethodsCircadian variation was analyzed by fitting cosinor models to hourly blood pressure (BP) measurements in patients of the eICU Collaborative Research Database with an ICU length of stay of at least 3 days. We calculated the amplitude of the 24-hour circadian rhythm and time of the day when BP peaked. We determined the association between amplitude and time of peak BP and severity of illness, medications, mechanical intubation, and survival to hospital discharge.ResultsAmong 23,355 patients (mean age 65 years, 55% male), the mean amplitude of the 24-hour rhythm was 4.5 ± 3.1 mm Hg. Higher APACHE-IV scores, sepsis, organ dysfunction, and mechanical ventilation were associated with a lower amplitude and a shifted circadian rhythm (P < .05 for all). The timing of the BP peak was associated with in-hospital mortality (P < .001). Higher BP amplitude was associated with shorter ICU (2 mm Hg amplitude: 7.0 days, 8 mm Hg amplitude: 6.7 days) and hospital (2 mm Hg amplitude: 11.8 days, 8 mm Hg amplitude: 11.3 days) lengths of stay and lower in-hospital mortality (2 mm Hg amplitude: 18.2%, 8 mm Hg amplitude: 15.2%) (P < .001 for all).ConclusionThe 24-hour rhythm is dampened and phase-shifted in sicker patients and those on mechanical ventilation, vasopressors, or inotropes. Dampening and phase shifting are associated with a longer length of stay and higher in-hospital mortality.

Amplitude of circadian rhythms becomes weaken in the north, but there is no cline in the period of rhythm in a beetle.

Many species show rhythmicity in activity, from the timing of flowering in plants to that of foraging behavior in animals. The free-running periods and amplitude (sometimes called strength or power) of circadian rhythms are often used as indicators of biological clocks. Many reports have shown that these traits are highly geographically variable, and interestingly, they often show latitudinal or longitudinal clines. In many cases, the higher the latitude is, the longer the free-running circadian period (i.e., period of rhythm) in insects and plants. However, reports of positive correlations between latitude or longitude and circadian rhythm traits, including free-running periods, the power of the rhythm and locomotor activity, are limited to certain taxonomic groups. Therefore, we collected a cosmopolitan stored-product pest species, the red flour beetle Tribolium castaneum, in various parts of Japan and examined its rhythm traits, including the power and period of the rhythm, which were calculated from locomotor activity. The analysis revealed that the power was significantly lower for beetles collected in northern areas than southern areas in Japan. However, it is worth noting that the period of circadian rhythm did not show any clines; specifically, it did not vary among the sampling sites, despite the very large sample size (n = 1585). We discuss why these cline trends were observed in T. castaneum.