Circadian Amplitude Research Articles

A simulation-based framework for multi-individual circadian re-entrainment using a single light schedule

Circadian misalignment is experienced by travelers, shift workers, and people with irregular sleep patterns. Circadian misalignment leads to lower cognitive alertness and increases the risk of poor health outcomes. Since the circadian system is highly responsive to light, circadian rhythms can be realigned using lighting interventions in a built environment. However, inter-individual differences pose an unsolved problem in the implementation of such lighting interventions, particularly for individuals in a shared living space. Here, we present a novel method to converge on schedules of light exposure that can align the circadian rhythms of a group of individuals with different intrinsic circadian periods, within an optimal time. We used an experimentally validated limit-cycle oscillator model of the human circadian system to set a target in the phase and amplitude of the circadian oscillator. An iterative process then changes the switching times of a light/dark bang-bang input to minimize the difference in circadian amplitude and phase to arrive at the target. The proposed method successfully generated schedules of light exposures that optimized the time required for re-entrainment of multiple individuals with circadian phase shifts up to 12 h advance or delay. This method offers a novel solution to improve circadian entrainment under the practical constraint of multiple individuals in a shared living space.

Association of circadian rhythms with brain disorder incidents: a prospective cohort study of 72242 participants

Circadian rhythm disruption (CRD) is a shared characteristic of various brain disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and major depression disorder (MDD). Disruption of circadian rhythm might be a risk factor for brain disorder incidents. From 7-day accelerometry data of 72,242 participants in UK Biobank, we derived a circadian relative amplitude variable, which to some extent reflected the degree of circadian rhythm disruption. Records of brain disorder incidents were obtained from a wide range of health outcomes across self-report, primary care, hospital inpatient data, and death data. Using multivariate Cox proportional hazard ratio regression, we created two models adjusting for different covariates. Then, linear correlations between relative amplitude and several brain morphometric measures were examined in participants with brain MRI data. After a median follow-up of around 6.1 years, 72,242 participants were included in the current study (female 54.9%; mean age 62.1 years). Individuals with reduced relative amplitude had increasing risk of all-cause dementia (Hazard ratio 1.23 [95% CI 1.15 to 1.31]), PD (1.33 [1.25 to 1.41]), stroke (1.13 [1.06 to 1.22]), MDD (1.18 [1.13 to 1.23]), and anxiety disorder (1.14 [1.09 to 1.20]) in fully adjusted models. Additionally, significant correlations were found between several cortical regions and white matter tracts and relative amplitude that have been linked to dementia and psychiatric disorders. We confirm CRD to be a risk factor for various brain disorders. Interventions for regulating circadian rhythm may have clinical relevance to reducing the risk of various brain disorders.

Low circadian amplitude and delayed phase are linked to seasonal affective disorder (SAD)

• Symptoms of seasonal affective disorder (SAD) are linked to in-vivo circadian mRNA oscillations. • SAD symptoms are associated with low circadian amplitude and delayed winter phase. • Our computational modeling results link SAD with clock gene variants associated with SAD. • Females and evening chronotypes are at higher risk for SAD. : Symptoms of seasonal affective disorder (SAD) can affect up to 10-20% of individuals in temperate populations and are more common in females. Depressive symptoms within SAD individuals provide a model for investigating how genetic, environmental, and physiological factors interact to influence mood. Winter-type SAD occurs during short photoperiod seasons, suggesting circadian physiology may influence susceptibility to SAD. : Using a longitudinal cross-season design in a Northeastern US population (n=213), we tested how SAD symptoms (SPAQ-GSS) were associated with gender, depression scores (BDI-II), chronotype (MCTQ-MSF), and in-vivo circadian phase and amplitude. In addition, we used computational modeling to simulate whether circadian gene variants reproduce SAD phenotypes across seasons. : We found that high seasonality scores are associated with lower circadian amplitude, delayed circadian phases in winter, and evening chronotypes. Our model reproduces seasonal decreases in amplitude and delayed phases for circadian gene variants associated with SAD. Modeling further suggests that transcriptional increases for variants in Cry1 and Cry2 genes and changes in transcription, phosphorylation and/or degradation rates of Per3 variants may be associated with these seasonal changes. : Our study examined clock gene expression from peripheral tissues which represent circadian rhythms influenced by both intrinsic, physiological and external, environmental factors. The mutant conditions for the modeling study are limited, and many biochemical reaction rates in humans are unknown. : Our study validates previous results linking SAD symptoms with gender, chronotype, and depressive symptoms and provides evidence for potential genetic and physiological mechanisms of SAD—low circadian amplitude and seasonally delayed circadian phase.

LBSUN99 Combination Of Drosophila And Mammalian Genetics Identifies Lcorl As A Novel Regulator Of Metabolism

Abstract Obesity and adult-onset diabetes result from a complex interaction of multiple genetic, environmental, and behavioral factors. The hypothalamus contains multiple nuclei required for the regulation of metabolic homeostasis. One nucleus, termed the ventromedial hypothalamus (VMH), facilitates glucose homeostasis and metabolic adaptations to challenges such as high fat diet (HFD) and exercise. Using a combination of Drosophila and mouse genetics, we uncovered a novel gene network whose function is required for VMH-regulated whole body metabolism. Using Drosophila to rapidly screen orthologs of genes enriched in the mouse VMH, we identified the gene encoding the Ecdysone Induced Protein 93F (E93; human ortholog, Ligand dependent corepressor-like, Lcorl). Adult flies with neural knockdown of E93 are obese and hyperphagic, with increased energy stores, reduced exercise endurance, and dampened circadian amplitude. These findings reveal a novel role of E93 in metabolism. We found that the knockdown of E93 specifically in myoinhibitory peptide (MIP) and GABAergic neurons are sufficient to recapitulate the phenotype seen in a pan-neuronal E93 knockdown. | In mice, we found that Lcorl, the mammalian orthologue of E93, is highly expressed throughout the entire VMH. We used CRISPR/Cas9 to generate mice harboring both a Lcorl KO and a floxed allele to investigate its function in the whole-body and in a tissue specific manner. Lcorl KO mice are viable and fertile. However, they have disruptions in growth, lipid metabolism, and circadian rhythm. Taken together these data reveal that Lcorl is as a novel regulator of energy metabolism and circadian rhythm. Additionally, this study shows the power of combined drosophila and mammalian genetics in uncovering novel regulators of metabolism. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Preliminary evidence that daily light exposure enhances the antibody response to influenza vaccination in patients with dementia

Enhancing lighting conditions in institutions for individuals with dementia improves their sleep, circadian rhythms and well-being. Here, we report first findings that exposure to brighter light during daytime may support the immune response to the annual influenza vaccination. Eighty older institutionalised patients suffering from dementia (54 women and 26 men) continuously wore an activity tracker for 8 weeks to assess individual light exposure and rest-activity cycles. We analysed the patients’ immune response from two blood samples taken before and 4 weeks after the annual influenza vaccination. Individual antibody concentrations to three influenza virus strains (H3N2, H1N1, IB) were quantified via hemagglutination inhibition assays. By quantifying individual light exposure profiles (including daylight), we classified the patients into a low and a high light exposure group based on a median illuminance of 392.6 lux. The two light exposure groups did not differ in cognitive impairment severity, age or gender distribution. However, patients in the high light exposure group showed a significantly greater circadian rest-activity amplitude (i.e., more daytime activity and less nighttime activity) along with a significantly greater antibody titer increase to the H3N2 vaccine than patients in the low light exposure group, despite similar pre-vaccination concentrations. Sufficient seroprotective responses to all three influenza virus strains were attained for ≥75% of participants. These data provide preliminary evidence for a potentially enhanced immune response in patients with dementia when they received more daily light. Future studies are needed to determine whether regular daily light exposure may have beneficial effects on the human immune system, either directly or via a stabilising circadian sleep-wake rhythms.

Endogenous circadian temperature rhythms relate to adolescents' daytime physical activity.

Circadian rhythms relate to multiple aspects of health and wellbeing, including physical activity patterns. Susceptible circadian regulation predisposes to circadian misalignment, poor sleep, sleep deprivation, increased sleepiness, and thereby sedentary behavior. Adolescents’ circadian regulation is particularly vulnerable, and may lead to sedentary behavior. To investigate which factors associate strongest between physical activity (PA) and circadian behavior, we conducted multimodal circadian rhythm analyses. We investigate how individual characteristics of habitual circadian patterns associate with objectively measured PA. We studied 312 adolescents [70% females) (56% with delayed sleep phase (DSP)], mean age 16.9 years. Circadian period length, temperature mesor (estimated 24 h midline) and amplitude (difference between mesor and peak) were measured using distally attached thermologgers (ibutton 1922L, 3-day-measurement). We additionally utilized algorithm-formed clusters of circadian rhythmicity. Sleep duration, timing, DSP, and PA were measured using actigraphs (GeneActiv Original, 10-day-measurement). We found that continuous circadian period length was not associated with PA, but lower mesor and higher amplitude were consistently associated with higher levels of PA as indicated by mean Metabolic Equivalent (METmean) and moderate-to-vigorous PA (MVPA), even when controlling for sleep duration. Separate circadian clusters formed by an algorithm also reflected distinct patterns of PA accordingly. Late sleepers and those with DSP were less likely to engage in MVPA compared to non-DSP and had more sedentary behavior. Adolescents who engage in higher levels or high-intensity PA have better circadian regulation, as measured by different objective methods including distal temperature measurements as well as actigraphy-measured sleep-wake behavior.

Antioxidative and Circadian Rhythm Regulation Effect of Quercus gilva Extract

Herein, water and ethanol extracts were obtained from the leaves, branches, kernels, and pericarp of Quercus gilva and subsequently analyzed for antioxidant activity and circadian rhythm regulation effects. Candidate components that may affect circadian rhythm and antioxidant activity were investigated to discover potential functional materials. Antioxidant activity was analyzed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity assays, showing that the hot water extract exhibited higher activity than that of the ethanol extract. In particular, the branch extract showed high antioxidant activity. By measuring total contents of polyphenols, flavonoids, and tannins, the hot water branch extract showed the highest concentrations, highlighting their significant contribution to the antioxidant activity. Examination of the circadian rhythm regulation of each extract showed that the ethanol extract exhibited greater impacts on the circadian rhythm amplitude compared to the water extract. The branch ethanol extract induced circadian rhythm amplitude changes via clock gene Bmal1 expression regulation. Determination of 12 phenolic compound concentrations showed that the branch ethanol extract contained many phenolic compounds, including catechin. This suggests that these compounds affected circadian rhythm regulation. In conclusion, the hot water branch extract has potential as an natural antioxidant material, while the corresponding ethanol extract has potential as a functional material for regulating circadian rhythm.

Comprehensive Behavioral Analysis of Opsin 3 (Encephalopsin)-Deficient Mice Identifies Role in Modulation of Acoustic Startle Reflex.

Opsin-3 (Opn3, encephalopsin) was the first nonvisual opsin gene discovered in mammals. Since then, several Opn3 functions have been described, and in two cases (adipose tissue, smooth muscle) light sensing activity is implicated. In addition to peripheral tissues, Opn3 is robustly expressed within the central nervous system, for which it derives its name. Despite this expression, no studies have investigated developmental or adult CNS consequences of Opn3 loss-of-function. Here, the behavioral consequences of mice deficient in Opn3 were investigated. Opn3-deficient mice perform comparably to wild-type mice in measures of motor coordination, socialization, anxiety-like behavior, and various aspects of learning and memory. However, Opn3-deficient mice have an attenuated acoustic startle reflex (ASR) relative to littermates. This deficit is not because of changes in hearing sensitivity, although Opn3 was shown to be expressed in auditory and vestibular structures, including cochlear outer hair cells. Interestingly, the ASR was not acutely light-dependent and did not vary between daytime and nighttime trials, despite known functions of Opn3 in photoreception and circadian gene amplitude. Together, these results demonstrate the first role of Opn3 on behavior, although the role of this opsin in the CNS remains largely elusive.

Rhythmic transcription of Bmal1 stabilizes the circadian timekeeping system in mammals

In mammals, the circadian clock consists of transcriptional and translational feedback loops through DNA cis-elements such as E-box and RRE. The E-box-mediated core feedback loop is interlocked with the RRE-mediated feedback loop, but biological significance of the RRE-mediated loop has been elusive. In this study, we established mutant cells and mice deficient for rhythmic transcription of Bmal1 gene by deleting its upstream RRE elements and hence disrupted the RRE-mediated feedback loop. We observed apparently normal circadian rhythms in the mutant cells and mice, but a combination of mathematical modeling and experiments revealed that the circadian period and amplitude of the mutants were more susceptible to disturbance of CRY1 protein rhythm. Our findings demonstrate that the RRE-mediated feedback regulation of Bmal1 underpins the E-box-mediated rhythm in cooperation with CRY1-dependent posttranslational regulation of BMAL1 protein, thereby conferring the perturbation-resistant oscillation and chronologically-organized output of the circadian clock.

Fragmentation, circadian amplitude, and fractal pattern of daily-living physical activity in people with multiple sclerosis: Is there relevant information beyond the total amount of physical activity?

BackgroundPhysical activity is lower in people with multiple sclerosis (pwMS) compared to healthy controls. Previous work focused on studying activity levels or activity volume, but studies of daily-living rest-activity fragmentation patterns, circadian rhythms, and fractal regulation in pwMS are limited. Based on findings in other cohorts, one could suggest that these aspects of daily-living physical activity will provide additional information about the health and well-being of pwMS. Therefore, here, we aimed to (1) identify which fragmentation, fractal, and circadian amplitude measures differ between pwMS and healthy controls, (2) evaluate the relationship between fragmentation, fractal, and circadian amplitude measures and disease severity, and (3) begin to evaluate the added value of those measures, as compared to more conventional measures of physical activity (e.g., mean signal vector magnitude (SVM). A global measure of the overall volume of physical activity). Methods132 people with relapsing-remitting MS (47±11 yrs, 69.7% female, Expanded Disability Status Scale, EDSS, median (IQR): 3 (2–4)) and 90 healthy controls (46±11 yrs, 47.8% female) were asked to wear a 3D accelerometer on their lower back for 7 days. Rest-activity fragmentation, circadian amplitude, fractal regulation, and mean SVM metrics were extracted. PwMS and healthy controls were compared using independent samples t-tests and linear regression, including comparisons adjusted for mean SVM to control for the effect of physical activity volume. Spearman correlations between measures and logistic regressions were used to identify the clinical condition based on the measures that differed significantly after adjusting for SVM. All analyses included adjustments for demographic and clinical parameters (e.g., age, sex). ResultsMultiple measures of activity fragmentation significantly differed between pwMS and healthy controls, reflecting a more fragmented active behavior in pwMS. PwMS had a lower circadian rhythm amplitude, indicating a smaller amplitude in the circadian changes of daily activity, and weaker temporal correlations as based on the fractal analysis. When taking into account physical activity volume, one circadian amplitude measure and one fractal measure remained significantly different in pwMS and controls. Fragmentation measures and circadian amplitude measures were significantly associated with disability level as measured by the EDSS; the association with circadian amplitude remained significant, even after adjusting for the mean SVM. ConclusionThe physical activity patterns of pwMS differ from those of healthy individuals in rest-activity fragmentation, the amplitude of the circadian rhythm, and fractal regulation. Measures describing these aspects of activity provide information that is not captured in the total volume of physical activity and could, perhaps, augment the monitoring of disease progression and evaluation of the response to interventions.

Mediating effect of circadian rhythm between work stress and sleep quality in Chinese shift-working nurses: A cross-sectional survey.

This study examined the mediating effect of circadian rhythm amplitude (LV) and stability (FR) between work stress and sleep quality among Chinese shift-working nurses (SWNs). A cross-sectional study. Three-hundred and seventy-nine nurses working in shifts were investigated by convenient sampling from six hospitals in Shanghai, China. The mediating effect was analysed using the structural equation model with bootstrapping procedures. Work stress could directly affect shift nurses' sleep quality and indirectly affect sleep quality through circadian rhythm amplitude and stability. The total indirect effects of work stress on sleep quality accounted for 36.7% of the total effect. The study revealed that poor sleep quality is very common among SWNs, which deserves attention. The mediating effect of the circadian rhythm provides new insights to improve sleep quality, not only by lightening the work stress but also by improving circadian rhythm in SWNs.

Data-driven modelling captures dynamics of the circadian clock of Neurospora crassa.

Eukaryotic circadian clocks are based on self-sustaining, cell-autonomous oscillatory feedback loops that can synchronize with the environment via recurrent stimuli (zeitgebers) such as light. The components of biological clocks and their network interactions are becoming increasingly known, calling for a quantitative understanding of their role for clock function. However, the development of data-driven mathematical clock models has remained limited by the lack of sufficiently accurate data. Here we present a comprehensive model of the circadian clock of Neurospora crassa that describe free-running oscillations in constant darkness and entrainment in light-dark cycles. To parameterize the model, we measured high-resolution time courses of luciferase reporters of morning and evening specific clock genes in WT and a mutant strain. Fitting the model to such comprehensive data allowed estimating parameters governing circadian phase, period length and amplitude, and the response of genes to light cues. Our model suggests that functional maturation of the core clock protein Frequency causes a delay in negative feedback that is critical for generating circadian rhythms.

ISX-9 potentiates CaMKIIδ-mediated BMAL1 activation to enhance circadian amplitude

Circadian dysregulation associates with numerous diseases including metabolic dysfunction, sleep disorder, depression and aging. Given that declined circadian amplitude is a trait commonly found with compromised health, interventions that design in precluding circadian amplitude from dampening will aid to mitigate complex, circadian-related diseases. Here we identify a neurogenic small molecule ISX-9 that is able to support persistent and higher amplitude of circadian oscillations. ISX-9 improves diurnal metabolic rhythms in middle-aged mice. Moreover, the ISX-9-treated mice show better sleep homeostasis with increased delta power during the day time and higher locomotive activity in the dark period. ISX-9 augments CaMKIIδ expression and increases BMAL1 activity via eliciting CaMKIIδ-mediated phosphorylation on BMAL1 residues S513/S515/S516, accordingly composes a positive feedback effect on enhancing circadian amplitude. CaMKIIδ-targeting, and the use of ISX-9 may serve as decent choices for treating circadian-related disorders.

Homeostatic response to sleep deprivation and circadian rhythmicity are intact in older adults with insomnia.

We examined whether homeostatic sleep drive and circadian rhythmicity differ in older adults with insomnia (OAI) compared to older good sleepers (GS). OAI (n = 37) and GS (n = 30) participated in a 60-h in-lab study with sleep deprivation and constant routine paradigms. Homeostatic sleep drive was assessed by examining the effect of sleep deprivation on delta EEG power and theta EEG power, and repeated sleep latency tests. Circadian rhythm was assessed with salivary melatonin (phase and amplitude), core body temperature (phase, amplitude, and mesor), and sleep latency during a constant routine paradigm. Mixed models were used to assess interactions of group (OAS vs GS) with homeostatic sleep and circadian effects. Compared to GS, OAI showed a greater linear increase in waking theta power during sleep deprivation, but the two groups did not show differential responses to sleep deprivation in delta EEG, or in repeated sleep latency tests. The two groups did not differ in circadian phase or amplitude of melatonin or core body temperature rhythms. OAI had a significantly elevated core body temperature mesor compared to GS. Homeostatic response to sleep deprivation was intact in OAI compared to GS; theta EEG power suggested a greater homeostatic response in OAI. Circadian rhythm amplitude and phase were similar in OAI compared to GS. Elevated body temperature mesor in OAI may indicate elevated physiological arousal. These findings suggest that effective treatments for insomnia in older adults may leverage intact sleep and circadian regulatory mechanisms, rather than repair defective sleep and circadian regulation.

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.

Slow Wave Sleep Deficits in the Flinders Sensitive Line Rodent Model of Depression: Effects of Medial Forebrain Bundle Deep-Brain Stimulation

Major Depressive Disorder (MDD) is an affective disorder typically accompanied by sleep disturbances. Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) is an emerging intervention for treatment-resistant depression, but its effect on sleep has not been closely examined. Here we aimed to characterise sleep deficits in the Flinders sensitive line, an established rodent model of depression, and investigate the consequences of MFB stimulation on sleep-related phenotypes. Rats were implanted with bilateral stimulation electrodes in the MFB, surface electrodes to record electrocorticography and electromyography for sleep scoring and electrodes within the prelimbic cortex, nucleus accumbens (NAc) and dorsal hippocampus. Recordings of sleep and oscillatory activity were conducted prior to and following twenty-four hours of MFB stimulation. Behavioural anti-depressant effects were monitored using the forced swim test. Previously unreported abnormalities in the Flinders sensitive line rats were observed during slow wave sleep, including decreased circadian amplitude of its rhythm, a reduction in slow wave activity and elevated gamma band oscillations. Previously established rapid eye movement sleep deficits were replicated. MFB stimulation had anti-depressant effects on behavioural phenotype, but did not significantly impact sleep architecture; it suppressed elevated gamma activity during slow wave sleep in the electrocorticogram and prelimbic cortex signals. Diverse abnormalities in Flinders sensitive line rats emphasise slow wave sleep as a state of dysfunction in affective disorders. MFB stimulation is able to affect behaviour and sleep physiology without influencing sleep architecture. Gamma modulation may represent a component of antidepressant mechanism.

Bright Light Decreases Peripheral Skin Temperature in Healthy Men: A Forced Desynchrony Study Under Dim and Bright Light (II).

Human thermoregulation is strictly regulated by the preoptic area of the hypothalamus, which is directly influenced by the suprachiasmatic nucleus (SCN). The main input pathway of the SCN is light. Here, thermoregulatory effects of light were assessed in humans in a forced desynchrony (FD) design. The FD experiment was performed in dim light (DL, 6 lux) and bright white light (BL, 1300 lux) in 8 men in a semi-randomized within-subject design. A 4 × 18 h FD protocol (5 h sleep, 13 h wake) was applied, with continuous core body temperature (CBT) and skin temperature measurements at the forehead, clavicles, navel, palms, foot soles and toes. Skin temperature parameters indicated sleep-wake modulations as well as internal clock variations. All distal skin temperature parameters increased during sleep, when CBT decreased. Light significantly affected temperature levels during the wake phase, with decreased temperature measured at the forehead and toes and increased navel and clavicular skin temperatures. These effects persisted when the lights were turned off for sleep. Circadian amplitude of CBT and all skin temperature parameters decreased significantly during BL exposure. Circadian proximal skin temperatures cycled in phase with CBT, while distal skin temperatures cycled in anti-phase, confirming the idea that distal skin regions reflect heat dissipation and proximal regions approximate CBT. In general, we find that increased light intensity exposure may have decreased heat loss in humans, especially at times when the circadian system promotes sleep.

Universal Stress Protein regulates the circadian rhythm of central oscillator genes in Arabidopsis.

Environmental stresses restrict plant growth and development and decrease crop yield. The circadian clock is associated with the ability of a plant to adapt to daily environmental fluctuations and the production and consumption of energy. Here, we investigated the role of Arabidopsis Universal Stress Protein (USP; At3g53990) in the circadian regulation of nuclear clock genes. The Arabidopsis usp knockout mutant line exhibited critically diminished circadian amplitude of the central oscillator CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) but enhanced the amplitude of TIMING OF CAB EXPRESSION 1 (TOC1). However, the expression of USP under the control of its own promoter restored the circadian timing of both genes, suggesting that USP regulates the circadian rhythm of Arabidopsis central clock genes, CCA1 and TOC1.

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.