Endogenous Rhythm Research Articles

Validation of the Self-Rating of Biological Rhythm Disorder for Adolescents (SBRDA) Scale by Dim Light Melatonin Onset in Healthy Young Adults.

Understanding the biological rhythms that influence young adult health is vital because the combination of biological changes and a circadian phase delay lead to young adults being at high risk of circadian misalignment. We have previously established a self-rating of biological rhythm disorder for adolescents (SBRDA). However, we did not externally validate the SBRDA against objective measures of biological rhythms such as dim light melatonin onset (DLMO)-the gold standard of the endogenous circadian phase. The purpose of this study was to verify the effectiveness of SBRDA in identifying individuals with biological rhythm disorders. Our participants were 42 (47.2%) boys and 47 (52.8%) girls with an average age of 18.5 ± 1.2 years. Saliva samples were collected from 4 h before bed time to 2 h after sleep every 60 min in a dim-light (<50 lx) laboratory environment. Biological rhythm parameters were assessed using questionnaires, including SBRDA, MEQ, and MCTQ. The mean DLMO time (h) was 22.2 ± 1.9. The DLMO correlated significantly with the SBRDA score (r = 0.33, p < 0.001), MEQ score (r = -0.24, p < 0.05), and MSFsc (r = 0.26, p < 0.05). ROC curve analysis showed that SBRDA was of diagnostic value for biological rhythm disorder (p < 0.05). Our observations demonstrate that SBRDA, which is consistent with MEQ and MCTQ, can be used to reflect endogenous circadian rhythm disorders in young adults. Exposure to dim light may activate melatonin secretion and lead to an earlier peak in young adults with biological rhythm disorder.

Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation

The characteristic endogenous circadian rhythm of plasma glucocorticoid concentrations is made up from an underlying ultradian pulsatile secretory pattern. Recent evidence has indicated that this ultradian cortisol pulsatility is crucial for normal emotional response in man. In this study, we investigate the anatomical transcriptional and cell type signature of brain regions sensitive to a loss of ultradian rhythmicity in the context of emotional processing. We combine human cell type and transcriptomic atlas data of high spatial resolution with functional magnetic resonance imaging (fMRI) data. We show that the loss of cortisol ultradian rhythm alters emotional processing response in cortical brain areas that are characterized by transcriptional and cellular profiles of GABAergic function. We find that two previously identified key components of rapid non-genomic GC signaling – the ANXA1 gene and retrograde endocannabinoid signaling – show most significant differential expression (q = 3.99e−10) and enrichment (fold enrichment = 5.56, q = 9.09e−4). Our results further indicate that specific cell types, including a specific NPY-expressing GABAergic neuronal cell type, and specific G protein signaling cascades underly the cerebral effects of a loss of ultradian cortisol rhythm. Our results provide a biological mechanistic underpinning of our fMRI findings, indicating specific cell types and cascades as a target for manipulation in future experimental studies.

1230: INTENSIVE CARE UNIT USE OF MELATONIN RECEPTOR AGONISTS IMPROVES OUTCOMES IN SEPSIS PATIENTS

Introduction: Delirium aggravates the morbidity and mortality of sepsis patients. Melatonin, the endogenous circadian rhythm regulating hormone, can decrease delirium. Also, melatonin possesses anti-oxidation and anti-inflammation capacity. Of note, the effects of melatonin can be activated by melatonin receptor agonists (such as tasimelteon and ramelteon). Thus, we hypothesized that using melatonin receptor agonists may improve the outcomes of sepsis patients in intensive care unit (ICU). To elucidate further on this issue, we conducted this retrospective study analyzing data retrieved from the Medical Information Mart for Intensive Care (MIMIC) IV database. Methods: Data from the MIMIC IV database were retrieved and analyzed. Only sepsis patients admitted to ICU were included. Patients who stayed in ICU less than 3 days were excluded. Between-group differences in the in-hospital mortality and overall mortality rates were analyzed using the Chi square test. The impacts of ICU use of melatonin receptor agonists on in-hospital mortality and overall mortality in sepsis patients were analyzed using logistic regression analysis. Results: A total of 3943 sepsis patients were included. Among them, 3.78% received melatonin receptor agonists (the Melatonin group, n=149), and ramelteon was the only melatonin receptor agonist these patients received. In addition, 96.22% of the included sepsis patients did not use melatonin receptor agonists (the non-Melatonin group, n=3794) during the entire course of hospitalization. In-hospital mortality rate (20.8% versus 31.0%, p=0.008) and the overall mortality rate (27.5% versus 39.3%%, p=0.004) in the Melatonin group were significantly lower than in the non-Melatonin group. Logistic regression analysis revealed that Melatonin group were associated with significantly lower risks of in-hospital mortality (odd’s ratio [OR]: 0.59, 95% confidence intervals [CI]: 0.39~0.88, p=0.009) and overall mortality (OR: 0.59, 95% CI: 0.41~0.84, p=0.004) comparing to non-Melatonin group. After adjusting for age and gender, the trend remained the same (in-hospital mortality: OR: 0.56, 95% CI: 0.37~0.84, p=0.005; overall mortality: OR: 0.56, 95% CI: 0.38~0.80, p=0.002). Conclusions: ICU use of melatonin receptor agonist ramelteon associated with outcome improvements in sepsis patients.

The Effect of Short-Wavelength White LED Illumination throughout the Night on the Milk Fatty Acid Profile of High-Yielding Dairy Cows.

Fatty acid levels in milk vary between day and night milking. Many dairy cows are still kept under white light-emitting diode (W-LED) illumination throughout the night, although it is known to disrupt endogenous circadian rhythms. We investigated the effects of whole-night W-LED illumination (125 lux) on milk yield and circadian composition, compared to a natural light-dark (LD) cycle of 10 h light. Mid-late lactation cows (n = 34) that were exposed to natural LD cycle showed circadian variation in milk fat composition, characterized by higher health-promoting monounsaturated fatty acid (MUFA; 24.2 ± 0.4 vs. 23.2 ± 0.4 g/100 g fat, p &lt; 0.001) and lower saturated fatty acid levels (71.2 ± 0.4 vs. 72.5 ± 0.4, p &lt; 0.001) at 13:30 h (day milk) than at 03:30 h (night milk). Compared to natural LD (n = 16), W-LED (n = 18) did not affect milk production or milk fat yields, yet abolished the milking time variation in milk fat composition towards a less healthy fatty acid profile. This lowered MUFA levels of day milk (23.8 ± 0.4 vs. 26.7 ± 0.4, p &lt; 0.01). Therefore, W-LED has no commercial advantage over the tested natural LD cycle, and conversely, even shows circadian disruption. Accordingly, a natural LD cycle of 10 h light is preferable over W-LED from the perspective of cost savings, the cows' well-being, and preserving the natural milk fat profile, as the nutritional value of the day milk is slightly higher.

Increased Oxidative Stress Markers in Acute Ischemic Stroke Patients Treated with Thrombolytics.

One of the most common neurological disorders involving oxidative stress is stroke. During a stroke, the balance of redox potential in the cell is disturbed, and, consequently, protein oxidation or other intracellular damage occurs, ultimately leading to apoptosis. The pineal gland hormone, melatonin, is one of the non-enzymatic antioxidants. It not only modulates the perianal rhythm but also has anti-inflammatory properties and protects against stress-induced changes. The focus of this research was to evaluate the concentration of the carbonyl groups and melatonin metabolite in time in patients with acute ischemic stroke that were treated with intravenous thrombolysis. This included a comparison of the functional status of patients assessed according to neurological scales with the control sample comprising healthy people. The studies showed that the serum concentrations of carbonyl groups, which were elevated in patients with ischemic stroke (AIS) in comparison to the control samples, had an impact on the patients' outcome. A urine concentration of the melatonin metabolite, which was lower in patients than controls, was related to functional status after 24 h from cerebral thrombolysis. It shows that determination of carbonyl groups at different time intervals may be an important potential marker of protein damage in patients with AIS treated with cerebral thrombolysis, and that impaired melatonin metabolism induces a low antioxidant protection. Thus, due to the neuroprotective effects of melatonin, attention should also be paid to the design and conduct of clinical trials and hormone supplementation in AIS patients to understand the interactions between exogenous melatonin and its endogenous rhythm, as well as how these relationships may affect patient outcomes.

Endogenous rhythm variation and adaptation to the tidal environment in the freshwater snail, Semisulcospira reiniana

Organisms have endogenous timekeeping system(s) to coordinate their biological processes with environmental cycles, allowing adaptation to external rhythmic changes in their environment. The change in endogenous rhythms could contribute to range expansion in a novel rhythmic environment. We hypothesized that populations of the freshwater snail near estuaries show a circatidal rhythm to synchronize with the tidal cycle. We compared the behavioral and gene expression rhythms between non-tidal and tidal populations of the freshwater snail, Semisulcospira reiniana. Individuals inhabiting tidal areas exhibited a rhythmic activity pattern coordinated with the tidal cycle under both field and laboratory conditions, but individuals inhabiting upstream non-tidal areas showed a circadian activity pattern. The proportion of circadian oscillating genes was greater in non-tidal than in tidal individuals, while that of circatidal oscillating genes was greater in tidal than in non-tidal individuals. Additionally, transcriptome-wide population genetic analyses revealed that these two adjacent populations can be clearly distinguished genetically, though the genetic distance was very small. Our results provide evidence of the shift in an endogenous rhythm via range expansion to a novel rhythmic environment. The changes in a small number of genes and/or phenotypic plasticity may contribute to the difference in the endogenous rhythms between non-tidal and tidal populations.

Social jetlag and risk of depression: Results from the Korea National Health and Nutrition Examination Survey

BackgroundSocial jetlag, which is the mismatch between endogenous rhythm and social timing, is prevalent among the working population. Social jetlag may result in mood changes; however, evidence of relationship between social jetlag and depressive disorders has not been fully verified. Hence, this study aimed to investigate the association between social jetlag and depressive symptoms in a representative working population of South Korea. MethodsThis study included 5447 Korean employees in the Korea National Health and Nutrition Examination Survey. Social jetlag was calculated as the difference between the midpoint of sleep time on weekdays and free days. Depressive symptoms were assessed using Patient Health Questionnaire-9. Multiple logistic regression was used to estimate the odds ratio after adjusting for confounding factors. Moreover, social jetlag and continuous depression scores were evaluated using linear regression and generalized additive models. ResultsThe proportion of the participants who had >2 h of social jetlag was 10.26 %. Depressive symptoms increased as social jetlag increased. Multiple logistic regression analysis showed that the adjusted OR (95 % confidence interval) for 1 to 2 h of social jetlag was 1.355 (0.891–2.059) and for >2 h was 1.859 (1.084–3.187), which <1 h was reference. LimitationsThis study used a cross-sectional design and measurements were based on self-reported scales. ConclusionThis study found that social jetlag and depressive symptoms were significantly related in the Korean working population.

Variability of Helioclimate Factors and Applicability to the Emergency Service Population of the Northern Region

The purpose of this study was to study the influence of the variability of weather and heliophysical factors on the appeal to the Ambulance service for different groups of nosologies in the population of the Russian North. Information about calls to the emergency medical service of Khanty-Mansiysk was obtained from the database of calls for the period from 2001 to 2021 by disease classes (ICD-10). To assess the dynamics of weather factors, data from the All-Russian Research Institute of Hydrometeorological Information and materials from the weather station of Khanty-Mansiysk were used. The dynamics of air temperature; barometric pressure; relative humidity; baric trend; maximum wind speed; weight oxygen content in the air are analyzed. Data on the relative daily number of sunspots are obtained from the materials of the Royal Observatory of Belgium. The average daily values of the level of planetary geomagnetic activity, expressed by the Ap index, are copied from the website of the National Center for Geophysical Data of the USA (Boulder). Mathematical processing was carried out using wavelet analysis. The graph of temperature fluctuations for the period from 2001 to 2021 shows a significant circadian cyclicity and a semi-annual rhythm with a high level of trend. Significant rhythms of barometric pressure with a period of 5 years, 1 year and rhythms close to semi-annual, seasonal and near-monthly are observed. Humidity changes significantly in the circadian and intra-annual rhythms. The baric tendency has significant rhythms: 3 years, 1 year, 6, 3, 2 months. Changes in the maximum wind speed do not have a circadian rhythm, but intra-annual monthly variations are observed. The value of the weight oxygen content has circadian; two-year, five-year; two- and near-monthly rhythms. The relative number of sunspots (W) for the period from 2001 to 2021 is characterized by a five-, two-year and circadian rhythm. When considering the variations of the number W for the period from 1818 to 2017, in addition to the classic eleven-year, annual and near-monthly, rhythms with a period of 42.5 years, 18.1 years and 2.1 years are found. The index of planetary geomagnetic activity (Ar) has a rhythm with a period of 4 years, two-year and near-annual. The significance of all rhythms is p=0.001. When analyzing fluctuations in geomagnetic activity from 1932 to 2016, long-term rhythms are added: 35.00 years; 16.06 years; 10.88 years; semi-annual and three-month rhythms. Despite numerous hypotheses of the search for cosmobiological harmony in the form of evolutionary synchronisms, rhythmic cascades, golden section, the problem of the interaction of exogenous natural rhythms and endogenous rhythms of the human body remains largely unresolved. Comparison of the results of various studies is difficult due to methodological and mathematical approaches. With observation periods of 100-200 years or more, a long-period component is monitored, and in clinical studies (from a day to a week), short-period components are detected. Changing the background in the form of helioclimatic and social variations also does not add accuracy. The use of various methods of time series analysis involves obtaining information of different resolution levels (Fourier transform, SWANN, wavelet analysis). Nevertheless, the results obtained track the classical rhythms of solar and geomagnetic activity with periods of about eleven years, a year and a month. There is also a 35-year-old rhythm, a 42.5-year-old rhythm close to the 44.16-year rhythm identified by Bezrukova A.Ya., at 18.1 years (long-period components of the lunar tide) and other intra-annual rhythms with periods from two weeks to 9 months. The effect of helioclimatic factors on human health indicates the absence of constant coherence (in our case, the consistency of these processes over time, manifested when they are combined), due to the presence of a large number of mega- and mesorhythms, which is manifested by amplitude and phase desynchronization of heliogeophysical indicators and health status.

Circadian secretion rhythm of GLP-1 and its influencing factors.

Circadian rhythm is an inherent endogenous biological rhythm in living organisms. However, with the improvement of modern living standards, many factors such as prolonged artificial lighting, sedentarism, short sleep duration, intestinal flora and high-calorie food intake have disturbed circadian rhythm regulation on various metabolic processes, including GLP-1 secretion, which plays an essential role in the development of various metabolic diseases. Herein, we focused on GLP-1 and its circadian rhythm to explore the factors affecting GLP-1 circadian rhythm and its potential mechanisms and propose some feasible suggestions to improve GLP-1 secretion.

Keeping an eye on circadian time in clinical research and medicine.

Daily rhythms are observed in humans and almost all other organisms. Most of these observed rhythms reflect both underlying endogenous circadian rhythms and evoked responses from behaviours such as sleep/wake, eating/fasting, rest/activity, posture changes and exercise. For many research and clinical purposes, it is important to understand the contribution of the endogenous circadian component to these observed rhythms. The goal of this manuscript is to provide guidance on best practices in measuring metrics of endogenous circadian rhythms in humans and promote the inclusion of circadian rhythms assessments in studies of health and disease. Circadian rhythms affect all aspects of physiology. By specifying minimal experimental conditions for studies, we aim to improve the quality, reliability and interpretability of research into circadian and daily (i.e., time-of-day) rhythms and facilitate the interpretation of clinical and translational findings within the context of human circadian rhythms. We describe protocols, variables and analyses commonly used for studying human daily rhythms, including how to assess the relative contributions of the endogenous circadian system and other daily patterns in behaviours or the environment. We conclude with recommendations for protocols, variables, analyses, definitions and examples of circadian terminology. Although circadian rhythms and daily effects on health outcomes can be challenging to distinguish in practice, this distinction may be important in many clinical settings. Identifying and targeting the appropriate underlying (patho)physiology is a medical goal. This review provides methods for identifying circadian effects to aid in the interpretation of published work and the inclusion of circadian factors in clinical research and practice.

Objective Diagnosis of Circadian Rhythm Disorders.

Circadian sleep-wake disorders are common. Because they represent conflict between the timing of the patient's endogenous rhythms and desired timing of sleep, the presenting complaints may include both difficulty of sleep initiation or maintenance and undesired or unplanned daytime or early evening sleepiness. Therefore, circadian disorders may be misdiagnosed as either a primary insomnia or a hypersomnia disorder, depending on which complaint is more troublesome for the patient. Objective information about sleep and wake patterns over long periods is crucial for accurate diagnosis. Actigraphy provides long-term information about the rest/activity pattern about an individual. However, caution should be applied in interpretation of the results because the information provided only includes information of movements, and activity is only an indirect circadian phase marker. Timing of light and melatonin therapy is critical for successful treatment of circadian rhythm disorders. Therefore, results of actigraphy are useful and should be used in conjunction with additional measurements, including 24 hours sleep-wake history, sleep log, and melatonin measurements.

Shaping overnight consolidation via slow-oscillation closed-loop targeted memory reactivation

Sleep constitutes a privileged state for new memories to reactivate and consolidate. Previous work has demonstrated that consolidation can be bolstered experimentally either via delivery of reminder cues (targeted memory reactivation [TMR]) or via noninvasive brain stimulation geared toward enhancing endogenous sleep rhythms. Here, we combined both approaches, controlling the timing of TMR cues with respect to ongoing slow-oscillation (SO) phases. Prior to sleep, participants learned associations between unique words and a set of repeating images (e.g., car) while hearing a prototypical image sound (e.g., engine starting). Memory performance on an immediate test vs. a test the next morning quantified overnight memory consolidation. Importantly, two image sounds were designated as TMR cues, with one cue delivered at SO UP states and the other delivered at SO DOWN states. A novel sound was used as a TMR control condition. Behavioral results revealed a significant reduction of overnight forgetting for words associated with UP-state TMR compared with words associated with DOWN-state TMR. Electrophysiological results showed that UP-state cueing led to enhancement of the ongoing UP state and was followed by greater spindle power than DOWN-state cueing. Moreover, UP-state (and not DOWN-state) cueing led to reinstatement of target image representations. Together, these results unveil the behavioral and mechanistic effects of delivering reminder cues at specific phases of endogenous sleep rhythms and mark an important step for the endeavor to experimentally modulate memories during sleep.

Temperature synchronisation of circadian rhythms in primary human airway epithelial cells from children

IntroductionCellular circadian rhythms regulate immune pathways and inflammatory responses that mediate human disease such as asthma. Circadian rhythms in the lung may also contribute to exacerbations of chronic diseases such...

Endogenous Diurnal Patterns of Adrenal and Gonadal Hormones During a 24-Hour Constant Routine After Simulated Shift Work.

Night-shift work causes circadian misalignment, predicts the development of metabolic diseases, and complicates the interpretation of hormone measurements. To investigate endogenous circadian rhythms, dissociated from behavioral and environmental confounds, in adrenal and gonadal steroids after simulated shift work. Fourteen healthy adults (ages 25.8 ± 3.2 years) were randomized to 3 days of night or day (control) shift work followed by a constant routine protocol designed to experimentally unveil rhythms driven endogenously by the central circadian pacemaker. Blood was sampled every 3 hours for 24 hours during the constant routine to concurrently obtain 16 Δ4 steroid profiles by mass spectrometry. Cosinor analyses of these profiles provided mesor (mean abundance), amplitude (oscillation magnitude), and acrophase (peak timing). Night-shift work marginally increased cortisol by 1 μg/dL (P = 0.039), and inactive/weak derivatives cortisone (P = 0.003) and 18-hydroxycortisol (P < 0.001), but did not alter the mesor of potent androgens testosterone and 11-ketotestosterone. Adrenal-derived steroids, including 11-ketotestosterone (P < 0.01), showed robust circadian rhythmicity after either day- or night-shift work. In contrast, testosterone and progesterone showed no circadian pattern after both shift work conditions. Night-shift work did not alter the amplitude or acrophase of any of the steroid profiles. Experimental circadian misalignment had minimal effects on steroidogenesis. Adrenal steroids, but not gonadal hormones, showed endogenous circadian regulation robust to prior shift schedule. This dichotomy may predispose night-shift workers to metabolic ill health. Furthermore, adrenal steroids, including cortisol and the main adrenal androgen 11-ketostosterone, should always be evaluated during the biological morning whereas assessment of gonadal steroids, particularly testosterone, is dependent on the shift-work schedule.

Egr1 plays a major role in the transcriptional response of white adipocytes to insulin and environmental cues.

It is believed that insulin regulates metabolic functions of white adipose tissue primarily at the post-translational level via the PI3K-Akt-mediated pathway. Still, changes in transcription also play an important role in the response of white adipocytes to insulin and environmental signals. One transcription factor that is dramatically and rapidly induced in adipocytes by insulin and nutrients is called Early Growth Response 1, or Egr1. Among other functions, it directly binds to promoters of leptin and ATGL stimulating the former and inhibiting the latter. Furthermore, expression of Egr1 in adipocytes demonstrates cell autonomous circadian pattern suggesting that Egr1 not only mediates the effect of insulin and nutrients on lipolysis and leptin production but also, coordinates insulin action with endogenous circadian rhythms of adipose tissue.

Chronobiology of epilepsy and sudden unexpected death in epilepsy

Epilepsy is a neurological disease characterized by spontaneous, unprovoked seizures. Various insults render the brain hyperexcitable and susceptible to seizure. Despite there being dozens of preventative anti-seizure medications available, these drugs fail to control seizures in nearly 1 in 3 patients with epilepsy. Over the last century, a large body of evidence has demonstrated that internal and external rhythms can modify seizure phenotypes. Physiologically relevant rhythms with shorter periodic rhythms, such as endogenous circadian rhythms and sleep-state, as well as rhythms with longer periodicity, including multidien rhythms and menses, influence the timing of seizures through poorly understood mechanisms. The purpose of this review is to discuss the findings from both human and animal studies that consider the effect of such biologically relevant rhythms on epilepsy and seizure-associated death. Patients with medically refractory epilepsy are at increased risk of sudden unexpected death in epilepsy (SUDEP). The role that some of these rhythms play in the nocturnal susceptibility to SUDEP will also be discussed. While the involvement of some of these rhythms in epilepsy has been known for over a century, applying the rhythmic nature of such phenomenon to epilepsy management, particularly in mitigating the risk of SUDEP, has been underutilized. As our understanding of the physiological influence on such rhythmic phenomenon improves, and as technology for chronic intracranial epileptiform monitoring becomes more widespread, smaller and less invasive, novel seizure-prediction technologies and time-dependent chronotherapeutic seizure management strategies can be realized.

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.

Differences in pigment circadian rhythmicity in green- and red-leafed tree species in the sun and shade

Light flux and quality are crucial factor for setting endogenous plant circadian rhythms. Evaluating the daily rhythmicity of leaf chlorophyll content is an effective method to monitor the plant physiological endogenous clock in response to environmental signals such as light availability/quality. Here, we used a leaf-clip sensor to monitor diurnal rhythms in the content of chlorophyll and flavonoids such as flavonols and anthocyanins in three green- (Ailanthus altissima, Tilia platyphyllos and Platanus × acerifolia) and two red-leafed (Acer platanoides cv. Crimson King and Prunus cerasifera var. pissardii) tree species, adapted to sun (L) or shade (S). Significant differences in chlorophyll content (Chl) and its variations during the day were observed among treatments in all the analyzed species. S-plants had more Chl than L-plants irrespective of leaf color, and Chl variations were more distinct during the day than in L-plants. In particular, contents were lowest in the morning (9:00) and in the middle of the day (at 12:00 and 15:00), and the highest at dusk (21:00). The less evident trends in Chl variation in L-plants were attributed to a decrease in Chl content in high light, which likely masked any increases in the shaded counterparts during the afternoon. Daily flavonol levels did not vary no notably during the day. In sun-exposed red leaves, anthocyanins partially screened mesophyll cells from incident light, and its levels were similar to the Chl dynamics in the shaded counterparts. This study provides new bases for further work on endogenous rhythms of plant pigments and improves our understanding of plant physiology in the context of day/night rhythmicity.

The biological clock enhancer nobiletin ameliorates steatosis in genetically obese mice by restoring aberrant hepatic circadian rhythm.

Nonalcoholic fatty liver disease (NAFLD) is associated with disruption of homeostatic lipid metabolism, but underlying processes are poorly understood. One possible mechanism is impairment in hepatic circadian rhythm, which regulates key lipogenic mediators in the liver and whose circadian oscillation is diminished in obesity. Nobiletin enhances biological rhythms by activating RAR-related orphan receptor nuclear receptor, protecting against metabolic syndrome in a clock-dependent manner. The effect of nobiletin in NAFLD is unclear. In this study, we investigate the clock-enhancing effects of nobiletin in genetically obese (db/db) PER2::LUCIFERASE reporter mice with fatty liver. We report microarray expression data suggesting hepatic circadian signaling is impaired in db/db mice with profound hepatic steatosis. Circadian PER2 activity, as assessed by mRNA and luciferase assay, was significantly diminished in liver of db/db PER2::LUCIFERASE reporter mice. Continuous animal monitoring systems and constant dark studies suggest the primary circadian defect in db/db mice lies within peripheral hepatic oscillators and not behavioral rhythms or the master clock. In vitro, nobiletin restored PER2 amplitude in lipid-laden PER2::LUCIFERASE reporter macrophages. In vivo, nobiletin dramatically upregulated core clock gene expression, hepatic PER2 activity, and ameliorated steatosis in db/db PER2::LUCIFERASE reporter mice. Mechanistically, nobiletin reduced serum insulin levels, decreased hepatic Srebp1c, Acaca1, Tnfα, and Fgf21 expression, but did not improve Plin2, Plin5, or Cpt1, suggesting nobiletin attenuates steatosis in db/db mice via downregulation of hepatic lipid accumulation. These data suggest restoring endogenous rhythm with nobiletin resolves steatosis in obesity, proposing that hypothesis that targeting the biological clock may be an attractive therapeutic strategy for NAFLD.NEW & NOTEWORTHY NAFLD is the most common chronic liver disease, but underlying mechanisms are unclear. We show here that genetically obese (db/db) mice with fatty liver have impaired hepatic circadian rhythm. Hepatic Per2 expression and PER2 reporter activity are diminished in db/db PER2::LUCIFERASE mice. The biological clock-enhancer nobiletin restores hepatic PER2 in db/db PER2::LUCIFERASE mice, resolving steatosis via downregulation of Srebp1c. These studies suggest targeting the circadian clock may be beneficial strategy in NAFLD.

The only constant is change: Endogenous circadian rhythms of soil microbial activities

Soil microbial community rhythms are a foundational mechanism that underpins soil microbial ecological processes, but evidence of endogenous circadian rhythms in these communities which are regulated by microbial molecular oscillations is lacking. In this study we used soil total and potentially active microbial communities to explore endogenous circadian rhythms excluded diurnal environmental fluctuations. Even though the communities were sampled from constantly dark, flooded paddy soil conditions, the potentially active microbial community structures were significantly different between the surface soil's ‘day’ and ‘night’. Seven taxa were identified as circadian indicators from the presence of circadian clock genes. The circadian indicators contributed to endogenous circadian rhythms by regulating community diversity, species interactions, and community assembly. These findings emphasize the importance of diurnal-scale perspective in understanding microbial ecological processes and, more practically, in the design of microbial ecology experiments.