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Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.

BACKGROUND: The primary objective of this randomized controlled trial (RCT) is to establish the effectiveness of time-restricted eating (TRE) compared with the Mediterranean diet for people with bipolar disorder (BD) who have symptoms of sleep disorders or circadian rhythm sleep-wake disruption. This work builds on the growing evidence that TRE has benefits for improving circadian rhythms. TRE and Mediterranean diet guidance will be offered remotely using self-help materials and an app, with coaching support. METHODS: This study is an international RCT to compare the effectiveness of TRE and the Mediterranean diet. Three hundred participants will be recruited primarily via social media. Main inclusion criteria are: receiving treatment for a diagnosis of BD I or II (confirmed via DIAMOND structured diagnostic interview), endorsement of sleep or circadian problems, self-reported eating window of ≥ 12 h, and no current mood episode, acute suicidality, eating disorder, psychosis, alcohol or substance use disorder, or other health conditions that would interfere with or limit the safety of following the dietary guidance. Participants will be asked to complete baseline daily food logging for two weeks and then will be randomly allocated to follow TRE or the Mediterranean diet for 8 weeks, during which time, they will continue to complete daily food logging. Intervention content will be delivered via an app. Symptom severity interviews will be conducted at baseline; mid-intervention (4 weeks after the intervention begins); end of intervention; and at 6, 9, and 15 months post-baseline by phone or videoconference. Self-rated symptom severity and quality of life data will be gathered at those timepoints, as well as at 16 weeks post baseline. To provide a more refined index of whether TRE successfully decreases emotional lability and improves sleep, participants will be asked to complete a sleep diary (core CSD) each morning and complete six mood assessments per day for eight days at baseline and again at mid-intervention. DISCUSSION: The planned research will provide novel and important information on whether TRE is more beneficial than the Mediterranean diet for reducing mood symptoms and improving quality of life in individuals with BD who also experience sleep or circadian problems. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06188754.

BACKGROUND: Although research on the implementation of evidence-based psychological treatments (EBPTs) has advanced rapidly, research on the sustainment of implemented EBPTs remains limited. This is concerning, given that EBPT activities and benefits regularly decline post-implementation. To advance research on sustainment, the present protocol focuses on the third and final phase-the Sustainment Phase-of a hybrid type 2 cluster-randomized controlled trial investigating the implementation and sustainment of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for patients with serious mental illness and sleep and circadian problems in community mental health centers (CMHCs). Prior to the first two phases of the trial-the Implementation Phase and Train-the-Trainer Phase-TranS-C was adapted to fit the CMHC context. Then, 10 CMHCs were cluster-randomized to implement Standard or Adapted TranS-C via facilitation and train-the-trainer. The primary goal of the Sustainment Phase is to investigate whether adapting TranS-C to fit the CMHC context predicts improved sustainment outcomes. METHODS: Data collection for the Sustainment Phase will commence at least three months after implementation efforts in partnering CMHCs have ended and may continue for up to one year. CMHC providers will be recruited to complete surveys (N = 154) and a semi-structured interview (N = 40) on sustainment outcomes and mechanisms. Aim 1 is to report the sustainment outcomes of TranS-C. Aim 2 is to evaluate whether manipulating EBPT fit to context (i.e., Standard versus Adapted TranS-C) predicts sustainment outcomes. Aim 3 is to test whether provider perceptions of fit mediate the relation between treatment condition (i.e., Standard versus Adapted TranS-C) and sustainment outcomes. Mixed methods will be used to analyze the data. DISCUSSION: The present study seeks to advance our understanding of sustainment predictors, mechanisms, and outcomes by investigating (a) whether the implementation strategy of adapting an EBPT (i.e., TranS-C) to the CMHC context predicts improved sustainment outcomes and (b) whether this relation is mediated by improved provider perceptions of treatment fit. Together, the findings may help inform more precise implementation efforts that contribute to lasting change. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05956678 . Registered on July 21, 2023.

Circadian clocks evolved in diverse organisms as an adaptation to the daily swings in ambient light and temperature that derive from Earth's rotation. These timing systems, based on intracellular molecular oscillations, synchronize organisms' behavior and physiology with the 24-h environmental rhythm. The cyanobacterial clock serves as a special model for understanding circadian rhythms because it can be fully reconstituted in vitro. This review summarizes recent advances that leverage new biochemical, biophysical, and mathematical approaches to shed light on the molecular mechanisms of cyanobacterial Kai proteins that support the clock, and their homologues in other bacteria. Many questions remain in circadian biology, and the tools developed for the Kai system will bring us closer to the answers.

• Sleep and circadian problems are often comorbid with mental disorders. • Sleep and circadian problems are mechanistic contributors to mental disorders. • TranS-C treats sleep and circadian problems across mental disorders via one protocol. • TranS-C is grounded in basic sleep and circadian science and existing EBPTs. • TranS-C includes cognitive-behavioral therapy for insomnia (CBT-I) The transdiagnostic intervention for sleep and circadian dysfunction (TranS-C) was developed to provide one protocol that treats a range of sleep and circadian problems across a range of mental disorders. The focus of TranS-C includes, and goes beyond, categorically defined sleep and circadian disorders to facilitate healthy sleep along empirically derived "sleep health" dimensions. In this State of the Science review, we highlight key advantages of a transdiagnostic approach to sleep and circadian problems, including (a) the potential to better understand and treat comorbidity between various sleep and circadian problems and mental disorders, as well as the potential to better understand and treat the heterogeneous sleep and circadian problems that are present within a specific mental disorder; (b) the opportunity to explore the hypothesis that sleep and circadian problems are an important transdiagnostic mechanism in the multifactorial maintenance of mental disorders; (c) the potential to transfer breakthroughs made across siloed areas of research and practice; (d) its suitability for dissemination into a broad range of settings, particularly lower resource settings; and (e) the opportunity to improve a range of important outcomes. We also explain the theoretical underpinnings of TranS-C, including the two-process model of sleep regulation and the Sleep Health Framework. TranS-C includes cognitive-behavioral therapy for insomnia (CBT-I) and we offer recommendations for when to use CBT-I versus TranS-C. The process for developing TranS-C is discussed along with outcome data, applications to underserved communities, and future directions for research. [ABSTRACT FROM AUTHOR]

During adolescence major shifts in sleep and circadian systems occur with a notable circadian phase delay. Yet, the circadian influence on pain during early adolescence is largely unknown. Using 2 years of data from the Adolescent Brain Cognitive Development study, we investigated the impact of chronotype on pain incidence, moderate-to-severe pain, and multiregion pain 1 year later in U.S. adolescents. Based on the Munich ChronoType Questionnaire, chronotype was calculated as the midpoint between sleep onset and offset on free days, corrected for sleep debt over the week. Adolescents reported pain presence over the past month, and if present, rated pain intensity (0-10 numerical rating scale; ≥ 4 defined as moderate-to-severe pain) and body site locations (Collaborative Health Outcomes Information Registry Body Map; ≥2 regions defined as multiregion pain). Three-level random intercept logistic regression models were specified for each pain outcome, adjusting for baseline sociodemographic and developmental characteristics. Among 5991 initially pain-free adolescents (mean age 12.0 years, SD 0.7), the mean chronotype was 3:59 am (SD 97 minutes), and the 1-year incidence of pain, moderate-to-severe pain, and multiregional pain was 24.4%, 15.2%, and 13.5%, respectively. Each hour later chronotype at baseline was associated with higher odds of developing any pain (odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.01, 1.11), moderate-to-severe pain (OR = 1.10, 95% CI = 1.05-1.17), and multiregion pain (OR = 1.08, 95% CI = 1.02-1.14) during 1-year follow-up. In this diverse U.S. adolescent sample, later chronotype predicted higher incidence of new-onset pain. [ABSTRACT FROM AUTHOR]

The optimal timing of sexual behaviours across a daily cycle can form a key component of mating and reproductive success. However, few studies have explored circadian rhythms in mating behaviour within the context of sexual selection and sexual conflict. Here we characterized circadian patterns in female receptivity to mating and the frequency of male mating and courtship behaviours in freely interacting captive groups of red junglefowl, Gallus gallus , in outdoor enclosures. We showed that patterns of male sexual behaviour and female resistance to mating attempts differ between the morning and evening during a 10-day mating trial. Females progressively reduced their level of resistance to male mating attempts during the early hours of the morning and progressively increased their resistance in the evening. Males did not match their mating frequencies to female receptivity and initiated mating attempts more often in the evening, but tended to perform more courtship displays in the morning. The pattern of male behaviour was associated with social status, such that dominant males courted females more often than subordinates, particularly in the morning. However, we did not find strong evidence that male social status was associated with different timing strategies. These results demonstrate circadian patterns in multiple sexual behaviours in red junglefowl, with potential consequences for sexual selection in this species and welfare management in domestic populations of closely related fowl. • Sexual selection may target individual variation in circadian behaviour. • Sex differences in the optimal timing of behaviours can drive sexual conflict. • We quantified circadian patterns in sexual behaviour in a polygynandrous bird. • Males courted more in the morning and female resistance was highest in the evening. • Male social status was not associated with different timing strategies. [ABSTRACT FROM AUTHOR]

Circadian rhythms are important biological contributors to health. Rest activity rhythms (RAR) are emerging as biomarkers of circadian behavior that are associated with chronic disease when abnormal. RAR have not yet been characterized in chronic kidney diseases (CKD). Leveraging the National Health and Nutrition Examination Survey (2011–2014), patients with CKD (n = 1114; Mean [95% CI]: Age, 50 [58–61] y; 52% female) were compared with non-CKD individuals (n = 5885; Age, 47 [46–48] y; 52% female). Actigraphy data were processed for RAR parameters including rhythmic strength (amplitude), the rhythm adjusted mean (mesor), the timing of peak activity (acrophase), activity regularity (inter-daily stability), and activity fragmentation (intra-daily variability). Cox regression was performed to assess RAR parameters for the prediction of all-cause mortality. Compared to non-CKD adults, patients with CKD had a lower rhythmic amplitude and mesor, and exhibited greater fragmentation and less day-to-day stability in RAR (ps < 0.001). Among CKD patients, a lower rhythmic amplitude (HR [95% CI]: 0.88 [0.82–0.96]; p < 0.001), a lower rhythm adjusted mean (0.87 [0.81–0.95]; p = 0.002), and a higher daily activity fragmentation (1.87 [1.10–3.18]; p = 0.023) were associated with an increased risk of all-cause mortality. Patients with CKD showed dampened rhythmic amplitudes and greater fragmentation of activity that were associated with a higher risk of all-cause mortality. These findings demonstrate a relationship between circadian disruption and prognosis in patients with CKD. [ABSTRACT FROM AUTHOR]

Background: In this case series, results from daily visual exposure to intense polychromatic light of 2000 to 4000 LUX is presented. Bright light treatment is a standard procedure for treating seasonal affective disorder and prodromal Parkinson's disease with high success. With the post-encephalitic symptoms of long-COVID closely approximating those of prodromal Parkinson's disease, we treated insomnia and sleep-related parameters in these patients, including total sleep, number of awakenings, tendency to fall back to sleep, and fatigue, to determine whether mending sleep could improve quality of life. Case presentation: We present three female and two male Caucasian patients aged 42–70 years with long-COVID that persisted from 12 weeks to 139 weeks after contracting coronavirus disease. Conclusion: A light presentation protocol was adapted for long-COVID that not only restored sleep in all patients, but also unexpectedly repaired the depression, anxiety, and cognitive changes (brain fog) as well. A robust pattern of recovery commencing 4–5 days after treatment and was maintained for weeks to months without relapse. These preliminary findings represent a novel, minimally invasive approach for managing the most debilitating symptoms of long-COVID, making it an ideal candidate for the drug hypersensitive, post-encephalitic brain. That a compromised circadian mechanism seen in Parkinson's disease may also underlie post-encephalitic long-COVID implicates a compromised role of the circadian system in these disorders. [ABSTRACT FROM AUTHOR]

The cardiac conduction system in large carnivores, such as the African lion (Panthera leo), represents a significant knowledge gap in both veterinary science and in cardiac electrophysiology. Short QT intervals have been reported from zoo‐kept, anaesthetized lions, and our goal was to record the first ECGs from wild, conscious lions roaming freely, and compare them to zoo‐kept lions under the hypothesis that short QT is unique to zoo‐kept lions. Macroscopic and histological examinations were performed on heart tissue removed from nine healthy zoo lions. ECGs were recorded from the nine anaesthetized zoo‐kept lions, and from 15 anaesthetized and conscious wild lions in Africa. Our histological and topographical description of the lion's heart matched what has previously been published. In conscious lions, the ECG recordings revealed a mean heart rate of 70 ± 4 beats/min, with faster heart rates during the night. PQ and QT intervals were heart rate dependent in the conscious lions. Interestingly, QT intervals recorded in wild lions were markedly longer than QT intervals from zoo lions (398 ± 40 vs. 297 ± 9 ms, respectively; P < 0.0001). Anaesthesia or heart rate did not account for this difference. We provide a comprehensive description of the cardiac anatomy and electrophysiology of wild and zoo‐kept lions. QT intervals were significantly shorter in zoo lions, suggesting functional disparities in cardiac electrophysiology between wild and zoo‐kept lions, potentially related to physical fitness. These findings underscore the plasticity of cardiac electrophysiology and may be of value when reintroducing endangered species into the wild and when managing lions in human care. [ABSTRACT FROM AUTHOR]

Gastrointestinal vagal afferents play an important role in communicating food related information from the gut to the brain. This information initiates vago‐vagal reflexes essential for gut functions, including gut motility and secretions. These afferents also play a role in energy homeostasis, signalling the arrival, amount and nutrient composition of a meal to the central nervous system where it is processed ultimately leading to termination of a meal. Vagal afferent responses to food related stimuli demonstrate a high degree of plasticity, responding to short term changes in nutritional demand, such as the fluctuations that occur across a 24‐hr or in response to a fast, as well as long term changes in energy demand, such as occurs during pregnancy. This plasticity is disrupted in disease states, such as obesity or chronic stress where there is hypo‐ and hypersensitivity of these afferents, respectively. Improved understanding of the plasticity of these afferents will enable identification of new treatment options for diseases associated with vagal afferent function. [ABSTRACT FROM AUTHOR]

Seasonal daylength, or circadian photoperiod, is a pervasive environmental signal that profoundly influences physiology and behavior. In mammals, the central circadian clock resides in the suprachiasmatic nuclei (SCN) of the hypothalamus where it receives retinal input and synchronizes, or entrains, organismal physiology and behavior to the prevailing light cycle. The process of entrainment induces sustained plasticity in the SCN, but the molecular mechanisms underlying SCN plasticity are incompletely understood. Entrainment to different photoperiods persistently alters the timing, waveform, period, and light resetting properties of the SCN clock and its driven rhythms. To elucidate novel candidate genes for molecular mechanisms of photoperiod plasticity, we performed RNA sequencing on whole SCN dissected from mice raised in long (light:dark [LD] 16:8) and short (LD 8:16) photoperiods. Fewer rhythmic genes were detected in mice subjected to long photoperiod, and in general, the timing of gene expression rhythms was advanced 4-6 h. However, a few genes showed significant delays, including Gem. There were significant changes in the expression of the clock-associated gene Timeless and in SCN genes related to light responses, neuropeptides, gamma aminobutyric acid (GABA), ion channels, and serotonin. Particularly striking were differences in the expression of the neuropeptide signaling genes Prokr2 and Cck, as well as convergent regulation of the expression of 3 SCN light response genes, Dusp4, Rasd1, and Gem. Transcriptional modulation of Dusp4 and Rasd1 and phase regulation of Gem are compelling candidate molecular mechanisms for plasticity in the SCN light response through their modulation of the critical NMDAR-MAPK/ERK-CREB/CRE light signaling pathway in SCN neurons. Modulation of Prokr2 and Cck may critically support SCN neural network reconfiguration during photoperiodic entrainment. Our findings identify the SCN light response and neuropeptide signaling gene sets as rich substrates for elucidating novel mechanisms of photoperiod plasticity. Data are also available at http://circadianphotoperiodseq.com/, where users can view the expression and rhythmic properties of genes across these photoperiod conditions. [ABSTRACT FROM AUTHOR]

The circadian system coordinates multiple behavioral outputs to ensure proper temporal organization. Timing information underlying circadian regulation of behavior depends on a molecular circadian clock that operates within clock neurons in the brain. In Drosophila and other organisms, clock neurons can be divided into several molecularly and functionally discrete subpopulations that form an interconnected central clock network. It is unknown how circadian signals are coherently generated by the clock network and transmitted across output circuits that connect clock cells to downstream neurons that regulate behavior. Here, we have exhaustively investigated the contribution of clock neuron subsets to the control of two prominent behavioral outputs in Drosophila : locomotor activity and feeding. We have used cell-specific manipulations to eliminate molecular clock function or induce electrical silencing either broadly throughout the clock network or in specific subpopulations. We find that clock cell manipulations produce similar changes in locomotor activity and feeding, suggesting that overlapping central clock circuitry regulates these distinct behavioral outputs. Interestingly, the magnitude and nature of the effects depend on the clock subset targeted. Lateral clock neuron manipulations profoundly degrade the rhythmicity of feeding and activity. In contrast, dorsal clock neuron manipulations only subtly affect rhythmicity but produce pronounced changes in the distribution of activity and feeding across the day. These experiments expand our knowledge of clock regulation of activity rhythms and offer the first extensive characterization of central clock control of feeding rhythms. Despite similar effects of central clock cell disruptions on activity and feeding, we find that manipulations that prevent functional signaling in an identified output circuit preferentially degrade locomotor activity rhythms, leaving feeding rhythms relatively intact. This demonstrates that activity and feeding are indeed dissociable behaviors, and furthermore suggests that differential circadian control of these behaviors diverges in output circuits downstream of the clock network. [ABSTRACT FROM AUTHOR]

Daylight plays a crucial role in human health, and as research into its effects expands, it is essential for designers to estimate the non-image-forming impacts of various daylighting and lighting strategies. This allows them to create indoor environments that are both pleasant and comfortable. To support this, daylight measurements were taken in five Chinese cities, focusing on spectral power distribution, correlated color temperature, and illuminance. The study calculated the non-image-forming effects of daylight exposure using metrics like melanopic Equivalent Daylight Illuminance and Circadian Light. A key finding was the development of the action factor SAI, which estimates the potential non-image-forming effects of light in built environments. This factor serves as a proxy for understanding how non-image-forming effects relate to correlated color temperatures. Additionally, the research suggests the possibility of creating a time-variational daylighting and lighting strategy with four distinct periods of non-image-forming effects throughout a 24 h day. These insights could be valuable for architects and designers in optimizing indoor lighting systems. [ABSTRACT FROM AUTHOR]

Technological advances have led to a modern-day lighting and smartphone revolution, with artificial light exposure at night increasing to levels never before seen in the evolutionary history of living systems on Earth. Light as a pollutant, however, remains largely unrecognized, and the reproductive effects of light pollution are mostly if not entirely unconsidered. This is despite the reproductive system being intricately linked to metabolism and the circadian system, both of which can be disturbed even by low levels of light. Here, we aim to change this perspective by reviewing the physiological and pathophysiological mechanisms by which light exposure alters the intricate hormonal, metabolic and reproductive networks that are relevant to reproductive toxicology. Nascent human studies have recently identified the photoreceptors responsible for the light dose relationship with melatonin suppression and circadian re-entrainment, directly shown the association between the alignment of light-dark cycles with activity-rest cycles on metabolic health and provided proof-of-principle that properly timed blue light-enriched and blue light-depleted delivery can accelerate circadian re-entrainment. With these advances, there is now a need to consider testicular effects of light pollution. [ABSTRACT FROM AUTHOR]

Primary cilia are dynamic sensory organelles that continuously undergo structural modifications in response to environmental and cellular signals, many of which exhibit rhythmic patterns. Building on our previous findings of rhythmic cilia-related gene expression in diurnal primates (baboon), this study extends the investigation to the nocturnal mouse brain to identify circadian patterns of cilia gene expression across brain regions. We used computational techniques and transcriptomic data from four publicly available databases, to examine the circadian expression of cilia-associated genes within six brain areas: brainstem, cerebellum, hippocampus, hypothalamus, striatum, and suprachiasmatic nucleus. Our analysis reveals that a substantial proportion of cilia transcripts exhibit circadian rhythmicity across the examined regions, with notable overrepresentation in the striatum, hippocampus, and cerebellum. We also demonstrate region-specific variations in the abundance and timing of circadian cilia genes' peaks, indicating an adaptation to the distinct physiological roles of each brain region. Additionally, we show that the rhythmic patterns of cilia transcripts are shifted under various physiological and pathological conditions, including modulation of the dopamine system, high-fat diet, and epileptic conditions, indicating the adaptable nature of cilia transcripts' oscillation. While limited to a few mouse brain regions, our study provides initial insights into the distinct circadian patterns of cilia transcripts and highlights the need for future research to expand the mapping across wider brain areas to fully understand the role of cilia's spatiotemporal dynamics in brain functions. [ABSTRACT FROM AUTHOR]

The European corn borer (Ostrinia nubilalis) is an agricultural pest and burgeoning model for research on speciation, seasonal adaptation and insect resistance management. Although previous work in O. nubilalis has identified genes associated with differences in life cycle, reproduction, and resistance to Bt toxins, the general lack of a robust gene‐editing protocol for O. nubilalis has been a barrier to functional validation of candidate genes. Here, we demonstrate an efficient and practical methodology for heritable gene mutagenesis in O. nubilalis using the CRISPR/Cas9 genome editing system. Precise loss‐of‐function (LOF) mutations were generated at two circadian clock genes, period (per) and pigment‐dispersing factor receptor (pdfr), and a developmental gene, prothoracicotropic hormone (ptth). Precluding the need for a visible genetic marker, gene‐editing efficiency remained high across different single guide RNAs (sgRNA) and germline transmission of mutations to F1 offspring approached 100%. When single or dual sgRNAs were injected at a high concentration, gene‐specific phenotypic differences in behaviour and development were identified in F0 mutants. Specifically, F0 gene mutants demonstrated that PER, but not PDFR, is essential for normal timing of eclosion. PTTH F0 mutants were significantly heavier and exhibited a higher incidence of diapause. This work will accelerate future studies of gene function in O. nubilalis and facilitate the development of similar screens in other Lepidopteran and non‐model insects. [ABSTRACT FROM AUTHOR]

Adequate sleep duration has recently been recognized as a major determinant of cardiovascular health by the American Heart Association. This is a significant step toward recognizing sleep as a major lifestyle factor and pillar of health, along with physical activity and nutrition. However, healthy sleep is not only a matter of duration. Other dimensions, such as timing, regularity, efficiency, satisfaction with sleep, and daytime alertness are also deemed important to consider. We have designed a systematic review protocol according to the PRISMA-P guidelines with the objective of determining which sleep dimensions are predictors of all-cause mortality and major adverse cardiovascular events (MACE; cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and unstable angina requiring hospitalization), and whether or not the use of multiple dimensions of sleep yields superior predictive value to the use of sleep duration alone in predicting the above-mentioned outcomes. We will implement a systematic search strategy in 10 databases with independentmanual screening by two reviewers. The aim is to comprehensively identify longitudinal studies which have examined the relationship between sleep duration and at least one other dimension of sleep andmortality orMACE.Meta-analysis will be performed after data extraction to address these objectives quantitatively. We anticipate that several sleep dimensions beyond sleep duration have been studied in relationship to all-cause mortality and MACE, and that a combination of multiple sleep dimensions can better predict these outcomes than sleep duration alone. Such findings would lay important groundwork to establish multidimensional sleep health as a major determinant of cardiovascular health. [ABSTRACT FROM AUTHOR]

Plants exploit phenotypic plasticity to adapt their growth and development to prevailing environmental conditions. Interpretation of light and temperature signals is aided by the circadian system, which provides a temporal context. Phenotypic plasticity provides a selective and competitive advantage in nature but is obstructive during large-scale, intensive agricultural practices since economically important traits (including vegetative growth and flowering time) can vary widely depending on local environmental conditions. This prevents accurate prediction of harvesting times and produces a variable crop. In this study, we sought to restrict phenotypic plasticity and circadian regulation by manipulating signaling systems that govern plants' responses to environmental signals. Mathematical modeling of plant growth and development predicted reduced plant responses to changing environments when circadian and light signaling pathways were manipulated. We tested this prediction by utilizing a constitutively active allele of the plant photoreceptor phytochrome B, along with disruption of the circadian system via mutation of EARLY FLOWERING3. We found that these manipulations produced plants that are less responsive to light and temperature cues and thus fail to anticipate dawn. These engineered plants have uniform vegetative growth and flowering time, demonstrating how phenotypic plasticity can be limited while maintaining plant productivity. This has significant implications for future agriculture in both open fields and controlled environments. Plants utilize phenotypic plasticity to adapt to prevailing environmental conditions. This work demonstrates that manipulation of phytochrome B- and EARLY FLOWERING3-regulated signaling pathways can limit phenotypic plasticity with respect to light and temperature signals. This has implications for future crop development by enabling consistent plant growth and development despite the effects of climate change. [ABSTRACT FROM AUTHOR]

The circadian rhythms are ubiquitous and confer an adaptive advantage to an individual/population by synchronising its daily activity to its surroundings. Circadian rhythms are controlled by self-sustained oscillator and they continue to oscillate in constant condition. Locomotor activity is one such robust self sustained oscillation. It is essential/crucial for an organism's survival such as feeding, mate choice, escape from the predator, etc. The present investigations were made to understand the effect of Mucuna pruriens and Glycyrrhiza glabra on locomotor behaviour of the Drosophila melanogaster (Oregon K strain) and vestigial wing mutant flies. Locomotor activity rhythms were assayed in D. melanogaster and vestigial wing mutant flies using Drosophila activity monitor and the amount of activity was measured. The results revealed that the Mucuna pruriens and Glycyrrhiza glabra treated flies showed increased activity when compared to control flies, between treated groups, higher concentration treated flies showed maximum activity than lower concentration treated flies. Statistical analysis showed that there is a significant difference in the locomotor activity among control and treated groups of D. melanogaster and vestigial wing mutant of Mucuna pruriens seed and Glycyrrhiza glabra root extract. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the effects of melatonin administration on oxidative stress and behavioral responses immediately (1-h) post-packing and 16-h post-packing circadian rhythms in donkeys during hot-dry conditions. Twenty healthy pack donkeys (15 males and five non-pregnant females), aged 2–3 years with average weight of 93 ± 2.7 kg were divided into two groups randomly. Melatonin was administered at a dose of 10 mg per donkey for 7 days to group 1 donkeys (packing + melatonin) that were subjected to packing (load-carrying), group 2 (packing–melatonin) donkeys were packed only without melatonin administration. The donkeys trekked covering 20 km, three times during the one week experiment, one day apart. Meteorological parameters were recorded during the study period. Serum harvested from the blood sample collected from each donkey before and after packing was analysed for oxidative stress biomarkers. Behavioral parameters were evaluated using the focal animal sampling technique for 1 h immediately (1-h) after packing and at expiration of 16-h post-packing, covering 27-h period at 3-h intervals. Melatonin reduced oxidative stress by preventing reduction in catalase activity and total antioxidant capacity in packing + melatonin donkeys. Melatonin exerted anti-stress effects on behavioral activities in the treated donkeys post-packing by significantly reducing (P < 0.05) the percent duration of grooming, walking and standing, but significantly increasing (P < 0.05) the percent duration of feeding, compared to the control donkeys. In conclusion, melatonin exerted beneficial effects against stresses due to packing and heat, and influenced the circadian rhythms of behavioral activities. Its administration may reduce the risk of negative effects of environmental heat stress and stress due to packing in donkeys during hot-dry conditions. • Melatonin reduced oxidative stress by preventing reduction in catalase activity and total antioxidant capacity in donkeys immediately after packing. • Melatonin exerted its antioxidant effect in the treated donkeys by decreasing the concentration of malondialdehyde concentration post-packing. • The anti-stress effects of melatonin were exerted on behavioral activities in donkeys post-packing by reducing significantly (P < 0.05) percent duration of grooming, walking and standing. • Melatonin increased significantly (P < 0.05) percent duration of feeding in donkeys. [ABSTRACT FROM AUTHOR]

Abstract Background In this case series, results from daily visual exposure to intense polychromatic light of 2000 to 4000 LUX is presented. Bright light treatment is a standard procedure for treating seasonal affective disorder and prodromal Parkinson’s disease with high success. With the post-encephalitic symptoms of long-COVID closely approximating those of prodromal Parkinson’s disease, we treated insomnia and sleep-related parameters in these patients, including total sleep, number of awakenings, tendency to fall back to sleep, and fatigue, to determine whether mending sleep could improve quality of life. Case presentation We present three female and two male Caucasian patients aged 42–70 years with long-COVID that persisted from 12 weeks to 139 weeks after contracting coronavirus disease. Conclusion A light presentation protocol was adapted for long-COVID that not only restored sleep in all patients, but also unexpectedly repaired the depression, anxiety, and cognitive changes (brain fog) as well. A robust pattern of recovery commencing 4–5 days after treatment and was maintained for weeks to months without relapse. These preliminary findings represent a novel, minimally invasive approach for managing the most debilitating symptoms of long-COVID, making it an ideal candidate for the drug hypersensitive, post-encephalitic brain. That a compromised circadian mechanism seen in Parkinson’s disease may also underlie post-encephalitic long-COVID implicates a compromised role of the circadian system in these disorders.

Abstract Background Poor memory for treatment is associated with poorer treatment adherence and poorer patient outcomes. The memory support intervention (MSI) was developed to improve patient memory for treatment with the goal of improving patient outcomes. The aim of this study protocol is to conduct a confirmatory efficacy trial to test whether a new, streamlined, and potent version of the MSI improves outcomes for midlife and older adults. This streamlined MSI is comprised of constructive memory supports that will be applied to a broader range of treatment content. The platform for this study is the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C). We will focus on midlife and older adults who are low income and experiencing mobility impairments. Methods Participants (N = 178) will be randomly allocated to TranS-C + MSI or TranS-C alone. Both intervention arms include eight 50-min weekly sessions. Assessments will be conducted at pre-treatment, post-treatment, 6-, and 12-month follow-up (6FU and 12FU). Aim 1 will compare the effects of TranS-C + MSI versus TranS-C alone on sleep and circadian functioning, daytime functioning, well-being, and patient memory. Aim 2 will test whether patient memory for treatment mediates the relationship between treatment condition and patient outcomes. Aim 3 will evaluate if previously reported poor treatment response subgroups will moderate the relationship between treatment condition and (a) patient memory for treatment and (b) treatment outcome. Exploratory analyses will compare treatment condition on (a) patient adherence, patient-rated treatment credibility, and patient utilization of treatment contents, and (b) provider-rated acceptability, appropriateness, and feasibility. Discussion This study has the potential to provide evidence for (a) the efficacy of a new simplified version of the MSI for maintaining health, well-being, and functioning, (b) the wider application of the MSI for midlife and older adults and to the treatment of sleep and circadian problems, and (c) the efficacy of the MSI for sub-groups who are likely to benefit from the intervention. Trial registration ClinicalTrials.gov NCT05986604. Registered on 2 August 2023.

Abstract Primary cilia are dynamic sensory organelles that continuously undergo structural modifications in response to environmental and cellular signals, many of which exhibit rhythmic patterns. Building on our previous findings of rhythmic cilia-related gene expression in diurnal primates (baboon), this study extends the investigation to the nocturnal mouse brain to identify circadian patterns of cilia gene expression across brain regions. We used computational techniques and transcriptomic data from four publicly available databases, to examine the circadian expression of cilia-associated genes within six brain areas: brainstem, cerebellum, hippocampus, hypothalamus, striatum, and suprachiasmatic nucleus. Our analysis reveals that a substantial proportion of cilia transcripts exhibit circadian rhythmicity across the examined regions, with notable overrepresentation in the striatum, hippocampus, and cerebellum. We also demonstrate region-specific variations in the abundance and timing of circadian cilia genes’ peaks, indicating an adaptation to the distinct physiological roles of each brain region. Additionally, we show that the rhythmic patterns of cilia transcripts are shifted under various physiological and pathological conditions, including modulation of the dopamine system, high-fat diet, and epileptic conditions, indicating the adaptable nature of cilia transcripts’ oscillation. While limited to a few mouse brain regions, our study provides initial insights into the distinct circadian patterns of cilia transcripts and highlights the need for future research to expand the mapping across wider brain areas to fully understand the role of cilia’s spatiotemporal dynamics in brain functions.

The optimal timing of transition from vegetative to floral reproductive phase is critical for plant productivity and agricultural yields. Light plays a decisive role in regulating this transition. The B‐box (BBX) family of transcription factors regulates several light‐mediated developmental processes in plants, including flowering. Here, we identify a previously uncharacterized group II BBX family member, BBX13/COL15, as a negative regulator of flowering under long‐day conditions. BBX13 is primarily expressed in the leaf vasculature, buds, and flowers, showing a similar spatial expression pattern to the major flowering time regulators CO and FT. bbx13 mutants flower early, while BBX13‐overexpressors exhibit delayed flowering under long days. Genetic analyses showed that BBX13 acts upstream to CO and FT and negatively regulates their expression. BBX13 physically interacts with CO and inhibits the CO‐mediated transcriptional activation of FT. In addition, BBX13 directly binds to the CORE2 motif on the FT promoter, where CO also binds. Chromatin immunoprecipitation data indicates that BBX13 reduces the in vivo binding of CO on the FT promoter. Through luciferase assay, we found that BBX13 inhibits the CO‐mediated transcriptional activation of FT. Together, these findings suggest that BBX13/COL15 represses flowering in Arabidopsis by attenuating the binding of CO on the FT promoter. Summary statement: BBX13, a previously uncharacterized protein in the B‐Box family of transcription factors, negatively regulates flowering time in Arabidopsis thaliana. BBX13 physically and genetically interacts with CO and inhibits the CO‐mediated transcriptional activation of FT. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is linked to lifestyle exposures. However, changes in the CRC rates among younger populations remain poorly understood and suggest the existence of yet unidentified factor(s) that may contribute to colon carcinogenesis. Here, we investigated the potential role of time of eating in the risk of pre-cancerous colonic neoplasms (tubular adenoma: TA). Methods: We enrolled 663 participants undergoing screening colonoscopies. Data on food timing, dietary intake, sleep/wake patterns, and chronotype were collected through structured questionnaires. Late eating was defined as the consumption of food or snack within a 3-hour window of sleep onset for at least four days a week. Pathology reports confirmed the histology of colonic polyps, and adenomas were further classified into risk categories. Results: A total of 644 patients met criteria for our study. There were 270 (42.2%) participants classified as late eaters. Compared to non-late eaters, the odds of TA were higher in late eaters (OR = 1.46, 95% CI = 1.05–2.03, p = 0.023), an association which was strengthened after adjusting for multiple confounders (OR 1.98, 95% CI 1.19–3.28, p = 0.008). Late eating remained an independent risk factor for high-risk as well as multiple TAs. Conclusion: This study proposes late eating as a risk factor for colon tubular adenomas and underscores the potential role of less studied forms of circadian disruption imposed by time of eating in the development of colon neoplastic formation. [ABSTRACT FROM AUTHOR]

Background: Human circadian clocks are synchronized daily with the external light-dark cycle and entrained to the 24-hour day. There is increasing evidence that a lack of synchronization and circadian entrainment can lead to adverse health effects. Beyond vision, light plays a critical role in modulating many so-called non-visual functions, including sleep-wake cycles, alertness, mood and endocrine functions. To assess (and potentially optimize) the impact of light on non-visual functions, it is necessary to know the exact 'dose' (i.e. spectral irradiance and exposure duration at eye level) of 24-hour light exposures, but also to include metadata about the lighting environment, individual needs and resources. Problem statement: To address this problem, a new assessment tool is needed that uses existing metrics to provide metadata and information about light quality and quantity from all sources. In this commentary, we discuss the need to develop an evidence-based integrative lighting score that is tailored to specific audiences and lighting environments. We will summarize the most compelling evidence from the literature and outline a future plan for developing such a lighting score using internationally accepted metrics, stakeholder and user feedback. Conclusion: We propose a weighting system that combines light qualities with physiological and behavioral effects, and the use of mathematical modelling for an output score. Such a scoring system will facilitate a holistic assessment of a lighting environment, integrating all available light sources. [ABSTRACT FROM AUTHOR]

Background: This study investigates the impact of blue light-emitting diode (LED) lighting on the physiological responses of Wistar rats. The circadian system plays a vital role in regulating physiological functions, allowing organisms to anticipate and adapt to environmental rhythms. The synchronization of endogenous circadian clocks with external cues, such as light-dark cycles, is essential for optimal performance. However, emerging technologies, like blue LED lighting, present new challenges to circadian rhythms, highlighting the need for continued research in this area. Methods: The study, approved by the Animal Ethics Committee, involved a total of 12 male Wistar rats, which were divided into two groups: a Control group and a blue light (BL) treated group, each consisting of six rats. The BL model was established by subjecting the rats to 12 h of BL exposure daily for a period of 3 months. Half of the rats were sacrificed at the end of this period, while the remaining rats were transitioned to normal light (NL) conditions for another 3 months before being euthanized. Blood and tissue samples were collected for analysis, including measurements of body weight, blood glucose, insulin, melatonin, lipid profile, as well as messenger RNA expression by reverse transcription-polymerase chain reaction and global DNA methylation by enzyme-linked immunosorbent assay. Results: The study found that BL exposure led to a higher monthly increase in body weight, elevated blood glucose levels, and decreased insulin and melatonin levels compared to controls. BL also caused a decrease in total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein. Gene expression analysis revealed downregulation of Period1, Cryptochrome1, and brain and muscle arnt-like protein 1 (Bmal1) in blood and hypothalamus, with significant upregulation upon returning to NL conditions. BL exposure induced hypermethylation in DNA sequences, which partially reverted after returning to NL conditions. Conclusion: Our study reveals the broad impact of BL/artificial light contributing to a higher incidence of obesity and metabolic disorders. With the rise of blue-rich LED lighting, more research is needed to understand its long-term effects on health. This study contributes to a deeper understanding of the intricate relationship between BL exposure and metabolic health, emphasizing the importance of informed decisions regarding lighting technologies to mitigate potential health risks.

Abstract Several different signaling pathways that regulate cell proliferation and differentiation are initiated by binding of ligands to cell-surface and membrane-bound enzyme-linked receptors, such as receptor tyrosine kinases and serine-threonine kinases. They prompt phosphorylation of tyrosine and serine-threonine residues and initiate downstream signaling pathways and priming of intracellular molecules that convey the signal in the cytoplasm and nucleus, with transcriptional activation of specific genes enriching cell growth and survival-related cascades. These cell processes are rhythmically driven by molecular clockworks endowed in every cell type and when deregulated play a crucial role in cancer onset and progression. Growth factors and their matching receptor-dependent signaling are frequently overexpressed and/or dysregulated in many cancer types. In this review we focus on the interplay between biological clocks and Growth Factor Receptor-dependent signaling in the context of carcinogenesis.

Abstract Background More than one in two older people wake up several times a night to urinate. Far from being a minor inconvenience, nocturia is associated with poor health outcomes. Given the importance of sleep as a foundation for resilience and healthy ageing, nocturia may promote the development of frailty, which is inextricably linked to physical decline, disability, and mortality. The aim of this scoping review was to collate published evidence on the relationship between nocturia and frailty, using the methodological framework of Arksey and O'Malley, together with the Joanna Briggs Institute methodology as guidance (OSF registration: osf.io/d5ct7). Methods Relevant publications were retrieved via PubMed, Embase, the Cochrane Library and Google Scholar. The Rayyan tool was used to facilitate the screening process. Data were extracted by two independent reviewers. 250 publications were initially identified, of which 87 met the eligibility criteria. Results Most of the evidence came from cross-sectional studies, most of which had been published within the last 5 years. The researchers were diverse, with 27% having a geriatric background. Only few publications established a clear association between nocturia and frailty. Other topics included: the association between nocturia and poor sleep quality and duration; the association between sleep and frailty; the association between frailty, multimorbidity, and age-related changes in the lower urinary tract. Conclusion The findings emphasize the increasing interest and interdisciplinary nature of research into the relationship between frailty, nocturia, lower urinary tract symptoms, and sleep disturbances. Further research is required to enhance understanding, establish causality, and identify potential therapeutic approaches.

Light-at-night is known to produce a wide variety of behavioral outcomes including promoting anxiety, depression, hyperactivity, abnormal sociability, and learning and memory deficits. Unfortunately, we all live in a 24-h society where people are exposed to light-at-night or light pollution through nightshift work - the need for all-hours emergency services - as well as building and street-lights, making light-at-night exposure practically unavoidable. Additionally, the increase in screentime (tvs and smart devices) during the night also contributes to poorer sleep and behavioral impairments. Compounding these factors is the fact that adolescents tend to be "night owls" and prefer an evening chronotype compared to younger children and adults, so these teenagers will have a higher likelihood of being exposed to light-at-night. Making matters worse is the prevalence of high-school start times of 8 am or earlier - a combination of too early school start times, light exposure during the night, and preference for evening chronotypes is a recipe for reduced and poorer sleep, which can contribute to increased susceptibility for behavioral issues for this population. As such, this mini-review will show, using both human and rodent model studies, how light-at-night affects behavioral outcomes and stress responses, connecting photic signaling and the circadian timing system to the hypothalamic-pituitary adrenal axis. Additionally, this review will also demonstrate that adolescents are more likely to exhibit abnormal behavior in response to light-at-night due to changes in development and hormone regulation during this time period, as well as discuss potential interventions that can help mitigate these negative effects. [ABSTRACT FROM AUTHOR]

Chronotype is an established concept designed to capture the internal clock's phase in real-life conditions. It is vital in many aspects of daily life and can interfere considerably with numerous factors in a given population. Recognizing nonmodifiable and modifiable factors is crucial for identifying covariates of interest when studying the link between chronotype and health status. To date, chronotype and its related factors have not been extensively investigated. The present study aimed to explore the association of chronotypes with meal frequency, physical activity, and demographic factors among the Saudi population. This cross-sectional web-based questionnaire involved 1369 adults (aged 18 years and above) from the general public in Saudi Arabia and was conducted between March and May 2019. Chronotype was assessed using the reduced version of the original Horne and Ostberg morningness-eveningness questionnaire (MEQ). Meal frequencies and demographics data (age, gender, marital status, place of residence, educational level, employment status, income) were obtained. Physical activity level was also obtained using the international physical activity questionnaire. The MEQ scores group individuals into three categories: morning-type, neither-type, and evening-type. The neither-type individuals represented 41.6% (95% confidence interval [CI], 37.5% − 45.6%) of the study population, followed by the morning-type (34.1%; 95% [CI], 29.8% − 38.4%), then the evening-type (24.3%, 95% [CI], 19.6% − 28.9%). Chronotype was significantly associated with age, marital status, employment status and monthly income (All p < 0.05). Significant associations between chronotype with meal frequencies (number of meals per day, breakfast frequency, lunch frequency, and dinner frequency) and physical activity were also observed (All p < 0.05). This study highlights that meal frequencies and physical activity levels are associated with chronotype distribution. Furthermore, demographics, including age, marital status, employment status, and income, were associated with chronotype distribution. [ABSTRACT FROM AUTHOR]

The hypothalamic–pituitary–adrenal axis is an extremely dynamic system with a combination of both circadian and ultradian oscillations. This state of 'continuous dynamic equilibration' provides a platform that is able to anticipate events, is sensitive in its response to stressors, remains robust during perturbations of both the internal and external environments and shows plasticity to adapt to a changed environment. In this review, we describe these oscillations of glucocorticoid (GC) hormones and why they are so important for GC‐dependent gene activation in the brain and liver, and their consequent effects on the regulation of synaptic and memory function as well as appetite control and metabolic regulation. Abnormalities of mood, appetite and metabolic regulation are well‐known consequences of GC therapy, and we suggest that the pattern of GC treatment and hormone replacement should be a much higher priority for endocrinologists and the pharmaceutical industry. One of the major impediments to our research on the importance of these cortisol rhythms in our patients has been our inability to measure repeated levels of hormones across the day in patients in their home or work surroundings. We describe how new wearable methodologies now allow the measurement of 24‐h cortisol profiles – including during sleep – and will enable us to define physiological normality and allow us both to develop better diagnostic tests and inform, at an individual patient level, how to improve replacement therapy. [ABSTRACT FROM AUTHOR]

Glowworms are the bioluminescent larvae of a group of dipteran insects related to fungus gnats. They require sheltered, consistently moist conditions and are found in aggregations on the walls and ceilings of caves and near streams in wet forests where they attract flying insects as prey. The Waitomo Glowworm Cave in New Zealand receives many thousands of visitors each year to see the colony of the glowworm, Arachnocampa luminosa. The cave climate is managed to ensure the glowworms are not harmed by influxes of dry air, as happened in the 1970s. To monitor the population and warn of catastrophic population declines, time‐lapse photographic monitoring of the glowworm population began in 2011 using a permanent, fixed camera. Photographs are taken 30 min apart. The population exhibits synchronised diurnal cycles of bioluminescence intensity. The time of the acrophase (the peak) of the diurnal cycle varied seasonally between 5 pm in early southern spring and 8 pm in summer. Cross‐correlation analyses with cave and water temperatures incorporating time lags suggest that this annual cycle could be related to changes in the composition or density of prey insects. Annual cycles also occur in the number of glowing larvae and their overall intensity. In most years, the numbers are lowest in winter and increase in spring to produce the brightest display through summer. The summer peak is not seen every year and autocorrelation of the 13‐year time series of count shows signs of a 3‐ to 4‐year cycle beyond the annual periodicity. The availability of prey in the cave chamber could influence the annual cycles in glowworm density, underscoring the need for a deeper knowledge of the bionomics of prey species, mainly Chironomidae (non‐biting midges). The photographic monitoring has proven to be a useful component of the management of the glowworm population. [ABSTRACT FROM AUTHOR]

In mammals, seasonal opportunities and challenges are anticipated through programmed changes in physiology and behavior. Appropriate anticipatory timing depends on synchronization to the external solar year, achieved through the use of day length (photoperiod) as a synchronizing signal. In mammals, nocturnal production of melatonin by the pineal gland is the key hormonal mediator of photoperiodic change, exerting its effects via the hypothalamopituitary axis. In this review/perspective, we consider the key developments during the history of research into the seasonal synchronizer effect of melatonin, highlighting the role that the pars tuberalis–tanycyte module plays in this process. We go on to consider downstream pathways, which include discrete hypothalamic neuronal populations. Neurons that express the neuropeptides kisspeptin and (Arg)(Phe)–related peptide‐3 (RFRP‐3) govern seasonal reproductive function while neurons that express somatostatin may be involved in seasonal metabolic adaptations. Finally, we identify several outstanding questions, which need to be addressed to provide a much thorough understanding of the deep impact of melatonin upon seasonal synchronization. [ABSTRACT FROM AUTHOR]

Background: Circadian health refers to individuals' well-being and balance in terms of their circadian rhythm. It is influenced by external cues. In adults, a close relationship between circadian-related alterations and obesity has been described. However, studies in children are scarce, and circadian health and its association with obesity have not been evaluated globally. We aimed to assess whether circadian health differed between children with and without obesity as determined by a global circadian score (GCS) in a school-age population. Methods: Four hundred and thirty-two children (7–12 years) were recruited in Spain. Non-invasive tools were used to calculate the GCS: (1) 7-day rhythm of wrist temperature (T), activity (A), position (P), an integrative variable that combines T, A, and P (TAP); (2) cortisol; and (3) 7-day food and sleep records. Body mass index, body fat percentage, waist circumference (WC), melatonin concentration, and cardiometabolic marker levels were determined. Results: Circadian health, as assessed by the GCS, differed among children with obesity, overweight, and normal weight, with poorer circadian health among children with obesity. Children with obesity and abdominal obesity had 3.54 and 2.39 greater odds of having poor circadian health, respectively, than did those with normal weight or low WC. The percentage of rhythmicity, a marker of the robustness of the TAP rhythm, and the amplitude, both components of the GCS, decreased with increasing obesity. Different lifestyle behaviors were involved in the association between circadian health and obesity, particularly protein intake (P = 0.024), physical activity level (P = 0.076) and chronotype (P = 0.029). Conclusions: The GCS can capture the relationship between circadian health and obesity in school-age children. Protein intake, physical activity level, and chronotype were involved in this association. Early intervention based on improving circadian health may help to prevent childhood obesity. [ABSTRACT FROM AUTHOR]

Lactate is not only the energy substrate of neural cells, but also an important signal molecule in brain. In modern societies, disturbed circadian rhythms pose a global challenge. Therefore, exploring the influence of circadian period on lactate and its metabolic kinetics is essential for the advancement of neuroscientific research. In the present study, the different groups of mice (L: 8:00 a.m.; D: 20:00 p.m.; SD: 20:00 p.m. with 12 h acute sleep deprivation) were infused with [3-13C] lactate through the lateral tail vein for a duration of 2 min. After 30-min lactate metabolism, the animals were euthanized and the tissues of brain and liver were obtained and extracted, and then, the [1H-13C] NMR technology was employed to investigate the kinetic information of lactate metabolism in different brain regions and liver to detect the enrichment of various metabolic kinetic information. Results revealed the fluctuating lactate concentrations in the brain throughout the day, with lower levels during light periods and higher levels during dark periods. Most metabolites displayed strong sensitivity to circadian rhythm, exhibiting significant day-night variations. Conversely, only a few metabolites showed changes after acute sleep deprivation, primarily in the temporal brain region. Interestingly, in contrast to brain lactate metabolism, liver lactate metabolism exhibited a significant increase following acute sleep deprivation. This study explored the kinetics of lactate metabolism, hinted at potential clinical implications for disorders involving circadian rhythm disturbances, and providing a new research basis for clinical exploration of brain and liver lactate metabolism. [ABSTRACT FROM AUTHOR]

In mammals, intrinsic 24 h or circadian rhythms are primarily generated by the suprachiasmatic nuclei (SCN). Rhythmic daily changes in the transcriptome and proteome of SCN cells are controlled by interlocking transcription‐translation feedback loops (TTFLs) of core clock genes and their proteins. SCN cells function as autonomous circadian oscillators, which synchronize through intercellular neuropeptide signalling. Physiological and behavioural rhythms can be severely disrupted by genetic modification of a diverse range of genes and proteins in the SCN. With the advent of next generation sequencing, there is unprecedented information on the molecular profile of the SCN and how it is affected by genetically targeted alteration. However, whether the expression of some genes is more readily affected by genetic alteration of the SCN is unclear. Here, using publicly available datasets from recent RNA‐seq assessments of the SCN from genetically altered and control mice, we evaluated whether there are commonalities in transcriptome dysregulation. This was completed for four different phases across the 24 h cycle and was augmented by Gene Ontology Molecular Function (GO:MF) and promoter analysis. Common differentially expressed genes (DEGs) and/or enriched GO:MF terms included signalling molecules, their receptors, and core clock components. Finally, examination of the JASPAR database indicated that E‐box and CRE elements in the promoter regions of several commonly dysregulated genes. From this analysis, we identify differential expression of genes coding for molecules involved in SCN intra‐ and intercellular signalling as a potential cause of abnormal circadian rhythms. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the effects of time of day on technical and physical performance parameters in young female tennis players. A sample of 12 recreational tennis players (age 24.2 ± 3.8 years) were randomly distributed into two groups. After having their demographics (age, experience, chronotypes), they were measured for body mass, body temperature, serve accuracy, serve speed, countermovement jump, grip strength, agility, and linear speed by counterbalancing method on two different days and at two different times of the day (09:00 and 16:30). The main results revealed that the players had significantly (p < 0.01) higher body temperature and greater values in the grip strength test during the afternoon session in comparison to the morning session. On the other hand, no significant differences (p > 0.05) were observed for other physical and technical performance parameters. The findings may highlight that time of day has no significant effects on several tennis-related performance determinants in female recreational players. [ABSTRACT FROM AUTHOR]

Circadian rhythms are a ubiquitous feature throughout the organism. Accumulating evidence suggests that the dysfunction of circadian rhythms due to genetic mutations or environmental factors contributes to the genesis and progress of multiple diseases. The physiological homeostasis of the ocular surface, like any other tissue or organ, is also orchestrated by circadian rhythms. In this review, we summarize the molecular clocks and the expression of clock-controlled genes in the mammalian ocular surface. Based on the circadian expression of these genes, we conclude the diurnal oscillations of cellular biological activities in the mammalian ocular surface. Moreover, we evaluate the factors entraining circadian oscillators in the ocular surface. Finally, we further discuss the latest development of the close correlation between circadian rhythms and ocular health. Briefly, this review aimed to synthesize the previous studies to aid in understanding the importance of circadian rhythms in the ocular surface and the possible opportunities for circadian rhythm-based interventional strategies to restore the homeostasis of the ocular surface. [ABSTRACT FROM AUTHOR]

Avian long-distance migration requires refined programming to orchestrate the birds' movements on annual temporal and continental spatial scales. Programming is particularly important as long-distance movements typically anticipate future environmental conditions. Hence, migration has long been of particular interest in chronobiology. Captivity studies using a proxy, the shift to nocturnality during migration seasons (i.e., migratory restlessness), have revealed circannual and circadian regulation, as well as an innate sense of direction. Thanks to rapid development of tracking technology, detailed information from free-flying birds, including annual-cycle data and actograms, now allows relating this mechanistic background to behaviour in the wild. Likewise, genomic approaches begin to unravel the many physiological pathways that contribute to migration. Despite these advances, it is still unclear how migration programmes are integrated with specific environmental conditions experienced during the journey. Such knowledge is imminently important as temporal environments undergo rapid anthropogenic modification. Migratory birds as a group are not dealing well with the changes, yet some species show remarkable adjustments at behavioural and genetic levels. Integrated research programmes and interdisciplinary collaborations are needed to understand the range of responses of migratory birds to environmental change, and more broadly, the functioning of timing programmes under natural conditions. [ABSTRACT FROM AUTHOR]

Decades have now passed since Colin Pittendrigh first proposed a model of a circadian clock composed of two coupled oscillators, individually responsive to the rising and setting sun, as a flexible solution to the challenge of behavioral and physiological adaptation to the changing seasons. The elegance and predictive power of this postulation has stimulated laboratories around the world in searches to identify and localize such hypothesized evening and morning oscillators, or sets of oscillators, in insects, rodents, and humans, with experimental designs and approaches keeping pace over the years with technological advances in biology and neuroscience. Here, we recount the conceptual origin and highlight the subsequent evolution of this dual oscillator model for the circadian clock in the mammalian suprachiasmatic nucleus; and how, despite our increasingly sophisticated view of this multicellular pacemaker, Pittendrigh's binary conception has remained influential in our clock models and metaphors. [ABSTRACT FROM AUTHOR]

Preliminary evidence suggests that evening chronotype is related to poorer efficacy of selective serotonin reuptake inhibitors. It is unknown whether this is specific to particular medications, self-rated chronotype, or efficacy. In the Australian Genetics of Depression Study (n = 15,108; 75% women; 18–90 years; 68% with ≥1 other lifetime diagnosis), a survey recorded experiences with 10 antidepressants, and the reduced Morningness-Eveningness Questionnaire was used to estimate chronotype. A chronotype polygenic score was calculated. Age- and sex-adjusted regression models (Bonferroni-corrected) estimated associations among antidepressant variables (how well the antidepressant worked [efficacy], duration of symptom improvement, side effects, discontinuation due to side effects) and self-rated and genetic chronotypes. The chronotype polygenic score explained 4% of the variance in self-rated chronotype (r = 0.21). Higher self-rated eveningness was associated with poorer efficacy of escitalopram (odds ratio [OR] = 1.04; 95% CI, 1.02 to 1.06; p =.000035), citalopram (OR = 1.03; 95% CI, 1.01 to 1.05; p =.004), fluoxetine (OR = 1.03; 95% CI, 1.01 to 1.05; p =.001), sertraline (OR = 1.02; 95% CI, 1.01 to 1.04; p =.0008), and desvenlafaxine (OR = 1.03; 95% CI, 1.01 to 1.05; p =.004), and a profile of increased side effects (80% of those recorded; ORs = 0.93–0.98), with difficulty getting to sleep the most common. Self-rated chronotype was unrelated to duration of improvement or discontinuation. The chronotype polygenic score was only associated with suicidal thoughts and attempted suicide (self-reported). While our measures are imperfect, and not of circadian phase under controlled conditions, the model coefficients suggest that dysregulation of the phenotypic chronotype relative to its genetic proxy drove relationships with antidepressant outcomes. The idea that variation in circadian factors influences response to antidepressants was supported and encourages exploration of circadian mechanisms of depressive disorders and antidepressant treatments. [ABSTRACT FROM AUTHOR]

Although costly to maintain, protein homeostasis is indispensable for normal cellular function and long-term health. In mammalian cells and tissues, daily variation in global protein synthesis has been observed, but its utility and consequences for proteome integrity are not fully understood. Using several different pulse-labelling strategies, here we gain direct insight into the relationship between protein synthesis and abundance proteome-wide. We show that protein degradation varies in-phase with protein synthesis, facilitating rhythms in turnover rather than abundance. This results in daily consolidation of proteome renewal whilst minimising changes in composition. Coupled rhythms in synthesis and turnover are especially salient to the assembly of macromolecular protein complexes, particularly the ribosome, the most abundant species of complex in the cell. Daily turnover and proteasomal degradation rhythms render cells and mice more sensitive to proteotoxic stress at specific times of day, potentially contributing to daily rhythms in the efficacy of proteasomal inhibitors against cancer. Our findings suggest that circadian rhythms function to minimise the bioenergetic cost of protein homeostasis through temporal consolidation of protein turnover. Synopsis: Protein homeostasis is costly to maintain but indispensable for normal cellular function and must be maintained in the face of daily rhythms in global protein production. Here, various pulse-labelling strategies are used to investigate the relationship between protein synthesis and abundance proteome-wide over circadian timescales. Fraction- and time-resolved pulse-SILAC shows rhythmic degradation occurs in phase with protein synthesis at the global level, facilitating daily variation in protein turnover whilst minimising changes in protein abundance. Global protein synthesis, degradation, and turnover is highest during the 6-8 hours following maximal production of the clock protein PER2. Nascent ribosomes assemble with a 24-hour oscillation, peaking after the highest PER2 reporter expression, without corresponding rhythmic changes in ribosomal abundance. The cellular and mouse organismal response to proteotoxic stress conditions varies based on the time of administration. Protein homeostasis is maintained by daily rhythms in protein synthesis and degradation rates. [ABSTRACT FROM AUTHOR]

Background: The disruption of the circadian clock is associated with inflammatory and immunological disorders. BMAL2, a critical circadian protein, forms a dimer with CLOCK, activating transcription. Extracellular cold-inducible RNA-binding protein (eCIRP), released during sepsis, can induce macrophage endotoxin tolerance. We hypothesized that eCIRP induces BMAL2 expression and promotes macrophage endotoxin tolerance through triggering receptor expressed on myeloid cells-1 (TREM-1). Methods: C57BL/6 wild-type (WT) male mice were subjected to sepsis by cecal ligation and puncture (CLP). Serum levels of eCIRP 20 h post-CLP were assessed by ELISA. Peritoneal macrophages (PerM) were treated with recombinant mouse (rm) CIRP (eCIRP) at various doses for 24 h. The cells were then stimulated with LPS for 5 h. The levels of TNF-α and IL-6 in the culture supernatants were assessed by ELISA. PerM were treated with eCIRP for 24 h, and the expression of PD-L1, IL-10, STAT3, TREM-1 and circadian genes such as BMAL2, CRY1, and PER2 was assessed by qPCR. Effect of TREM-1 on eCIRP-induced PerM endotoxin tolerance and PD-L1, IL-10, and STAT3 expression was determined by qPCR using PerM from TREM-1-/- mice. Circadian gene expression profiles in eCIRP-treated macrophages were determined by PCR array and confirmed by qPCR. Induction of BMAL2 activation in bone marrow-derived macrophages was performed by transfection of BMAL2 CRISPR activation plasmid. The interaction of BMAL2 in the PD-L1 promoter was determined by computational modeling and confirmed by the BIAcore assay. Results: Serum levels of eCIRP were increased in septic mice compared to sham mice. Macrophages pre-treated with eCIRP exhibited reduced TNFa and IL-6 release upon LPS challenge, indicating macrophage endotoxin tolerance. Additionally, eCIRP increased the expression of PD-L1, IL-10, and STAT3, markers of immune tolerance. Interestingly, TREM-1 deficiency reversed eCIRPinduced macrophage endotoxin tolerance and significantly decreased PD-L1, IL-10, and STAT3 expression. PCR array screening of circadian clock genes in peritoneal macrophages treated with eCIRP revealed the elevated expression of BMAL2, CRY1, and PER2. In eCIRP-treated macrophages, TREM-1 deficiency prevented the upregulation of these circadian genes. In macrophages, inducible BMAL2 expression correlated with increased PD-L1 expression. In septic human patients, blood monocytes exhibited increased expression of BMAL2 and PD-L1 in comparison to healthy subjects. Computational modeling and BIAcore assay identified a putative binding region of BMAL2 in the PD-L1 promoter, suggesting BMAL2 positively regulates PD-L1 expression in macrophages. Conclusion: eCIRP upregulates BMAL2 expression via TREM-1, leading to macrophage endotoxin tolerance in sepsis. Targeting eCIRP to maintain circadian rhythm may correct endotoxin tolerance and enhance host resistance to bacterial infection. [ABSTRACT FROM AUTHOR]

Resveratrol is a polyphenol known to have metabolic as well as circadian effects. However, there is little information regarding the metabolic and circadian effect of resveratrol on muscle cells. We sought to investigate the metabolic impact of resveratrol throughout the circadian cycle to clarify the associated signaling pathways. C2C12 myotubes were incubated with resveratrol in the presence of increasing concentrations of glucose, and metabolic and clock proteins were measured for 24 h. Resveratrol led to SIRT1, AMPK and PP2A activation. Myotubes treated with increasing glucose concentrations showed higher activation of the mTOR signaling pathway. However, resveratrol did not activate the mTOR signaling pathway, except for P70S6K and S6. In accordance with the reduced mTOR activity, resveratrol led to advanced circadian rhythms and reduced levels of pBMAL1 and CRY1. Resveratrol increased myogenin expression and advanced its rhythms. In conclusion, resveratrol activates the SIRT1-AMPK-PP2A axis, advances circadian rhythms and induces muscle development. [ABSTRACT FROM AUTHOR]

Several different signaling pathways that regulate cell proliferation and differentiation are initiated by binding of ligands to cell-surface and membrane-bound enzyme-linked receptors, such as receptor tyrosine kinases and serine-threonine kinases. They prompt phosphorylation of tyrosine and serine-threonine residues and initiate downstream signaling pathways and priming of intracellular molecules that convey the signal in the cytoplasm and nucleus, with transcriptional activation of specific genes enriching cell growth and survival-related cascades. These cell processes are rhythmically driven by molecular clockworks endowed in every cell type and when deregulated play a crucial role in cancer onset and progression. Growth factors and their matching receptor-dependent signaling are frequently overexpressed and/or dysregulated in many cancer types. In this review we focus on the interplay between biological clocks and Growth Factor Receptor-dependent signaling in the context of carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: More than one in two older people wake up several times a night to urinate. Far from being a minor inconvenience, nocturia is associated with poor health outcomes. Given the importance of sleep as a foundation for resilience and healthy ageing, nocturia may promote the development of frailty, which is inextricably linked to physical decline, disability, and mortality. The aim of this scoping review was to collate published evidence on the relationship between nocturia and frailty, using the methodological framework of Arksey and O'Malley, together with the Joanna Briggs Institute methodology as guidance (OSF registration: osf.io/d5ct7). Methods: Relevant publications were retrieved via PubMed, Embase, the Cochrane Library and Google Scholar. The Rayyan tool was used to facilitate the screening process. Data were extracted by two independent reviewers. 250 publications were initially identified, of which 87 met the eligibility criteria. Results: Most of the evidence came from cross-sectional studies, most of which had been published within the last 5 years. The researchers were diverse, with 27% having a geriatric background. Only few publications established a clear association between nocturia and frailty. Other topics included: the association between nocturia and poor sleep quality and duration; the association between sleep and frailty; the association between frailty, multimorbidity, and age-related changes in the lower urinary tract. Conclusion: The findings emphasize the increasing interest and interdisciplinary nature of research into the relationship between frailty, nocturia, lower urinary tract symptoms, and sleep disturbances. Further research is required to enhance understanding, establish causality, and identify potential therapeutic approaches. [ABSTRACT FROM AUTHOR]

Introduction: Neurologic circadian influences, including sleep/wake transitions, processes (e.g., hormonal variation), and behavioral patterns (e.g., consumption of food and oral medications), may affect seizure patterns. Specific circadian patterns of seizures have been reported depending on type, onset location, and severity; however, data on patterns for patients with seizure clusters and effectiveness of rescue therapy by time of day are limited. Methods: We conducted post hoc analyses using patient diary data from the phase 3 safety study of diazepam nasal spray, which is indicated for acute treatment of seizure clusters in patients with epilepsy aged =6 years. Patients were administered age- and weight-based doses; second doses could be administered if needed to control a seizure cluster. We assessed clock timing of seizure-cluster onset along with second-dose use as a proxy for effectiveness. Treatment-emergent adverse events were recorded. Results: Seizure-cluster onset was observed to be generally highest during mornings and late evenings and lowest in the early evening and middle of the night. Second-dose use was not consistently associated with a specific time of day. The safety profile was consistent with that expected from previous studies of diazepam nasal spray. Conclusion: These results suggest that diazepam nasal spray can be effectively administered at any time of day. [ABSTRACT FROM AUTHOR]

This review highlights recent findings on biological rhythms and discusses their implications for the management and production of domestic animals. Biological rhythms provide temporal coordination between organs and tissues in order to anticipate environmental changes, orchestrating biochemical, physiological and behavioural processes as the right process may occur at the right time. This allows animals to adapt their internal physiological functions, such as sleep-wake cycles, body temperature, hormone secretion, food intake and regulation of physical performance to environmental stimuli that constantly change. The study and evaluation of biological rhythms of various physiological parameters allows the assessment of the welfare status of animals. Alteration of biological rhythms represents an imbalance of the state of homeostasis that can be found in different management conditions. [ABSTRACT FROM AUTHOR]