Journal Of Biological Rhythms[JOURNAL]
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200 papers
Managing Circadian Disruption due to Hospitalization: A Pilot Randomized Controlled Trial of the CircadianCare Inpatient Management System.
Mangini C, Zarantonello L, Formentin C … +10 more , Giusti G, Domenie ED, Ruggerini D, Costa R, Skene DJ, Basso D, Battagliarin L, Di Bella A, Angeli P, Montagnese S
J Biol Rhythms · 2024 Apr · PMID 38153134 · Publisher ↗
The objective of the present study was to test the effects of an inpatient management system (CircadianCare) aimed at limiting the negative impact of hospitalization on sleep by enhancing circadian rhythmicity. Fifty inp...
The objective of the present study was to test the effects of an inpatient management system (CircadianCare) aimed at limiting the negative impact of hospitalization on sleep by enhancing circadian rhythmicity. Fifty inpatients were randomized to either CircadianCare ( = 25; 18 males, 62.4 ± 1.9 years) or standard of care ( = 25; 14 males, 64.5 ± 2.3 years). On admission, all underwent a full sleep-wake evaluation; they then completed daily sleep diaries and wore an actigraph for the whole length of hospitalization. On days 1 (T0), 7 (T1), and 14 (T2, if still hospitalized), salivary melatonin for dim light melatonin onset (DLMO) and 24-h skin temperature were recorded. In addition, environmental noise, temperature, and illuminance were monitored. Patients in the CircadianCare arm followed 1 of 3 schedules for light/dark, meal, and physical activity timings, based on their diurnal preference/habits. They wore short-wavelength-enriched light-emitting glasses for 45 min after awakening and short-wavelength light filter shades from 18:00 h until sleep onset. While the first, primary registered outcome (reduced sleep-onset latency on actigraphy or diary) was not met, based on sleep diaries, there was a trend (0.05 < < 0.1) toward an advance in bedtime for CircadianCare compared to standard of care patients between T0 and T1. Similarly, DLMO time significantly advanced in the small group of patients for whom it could be computed on both occasions, with untreated ones starting from earlier baseline values. Patients sleeping near the window had significantly higher sleep efficiency, regardless of treatment arm. As noise fluctuation increased, so did the number of night awakenings, regardless of treatment arm. In conclusion, the CircadianCare management system showed positive results in terms of advancing sleep timing and the circadian rhythm of melatonin. Furthermore, our study identified a combination of environmental noise and lighting indices, which could be easily modulated to prevent hospitalization-related insomnia.
The Negative Effects of Travel on Student Athletes Through Sleep and Circadian Disruption.
Heller HC, Herzog E, Brager A … +22 more , Poe G, Allada R, Scheer F, Carskadon M, de la Iglesia HO, Jang R, Montero A, Wright K, Mouraine P, Walker MP, Goel N, Hogenesch J, Van Gelder RN, Kriegsfeld L, Mah C, Colwell C, Zeitzer J, Grandner M, Jackson CL, Roxanne Prichard J, Kay SA, Paul K
J Biol Rhythms · 2024 Feb · PMID 37978840 · Full text
Collegiate athletes must satisfy the academic obligations common to all undergraduates, but they have the additional structural and social stressors of extensive practice time, competition schedules, and frequent travel...
Collegiate athletes must satisfy the academic obligations common to all undergraduates, but they have the additional structural and social stressors of extensive practice time, competition schedules, and frequent travel away from their home campus. Clearly such stressors can have negative impacts on both their academic and athletic performances as well as on their health. These concerns are made more acute by recent proposals and decisions to reorganize major collegiate athletic conferences. These rearrangements will require more multi-day travel that interferes with the academic work and personal schedules of athletes. Of particular concern is additional east-west travel that results in circadian rhythm disruptions commonly called jet lag that contribute to the loss of amount as well as quality of sleep. Circadian misalignment and sleep deprivation and/or sleep disturbances have profound effects on physical and mental health and performance. We, as concerned scientists and physicians with relevant expertise, developed this white paper to raise awareness of these challenges to the wellbeing of our student-athletes and their co-travelers. We also offer practical steps to mitigate the negative consequences of collegiate travel schedules. We discuss the importance of bedtime protocols, the availability of early afternoon naps, and adherence to scheduled lighting exposure protocols before, during, and after travel, with support from wearables and apps. We call upon departments of athletics to engage with sleep and circadian experts to advise and help design tailored implementation of these mitigating practices that could contribute to the current and long-term health and wellbeing of their students and their staff members.
Characterizing Gun Violence by Time, Day of the Week, Holidays, and Month in 6 US Cities, 2015-2021.
Klerman EB, Affouf M, Robbins R … +4 more , Iyer JM, Griggs C, Masiakos PT, Sacks CA
J Biol Rhythms · 2024 Feb · PMID 37978837 · Full text
Developing interventions to prevent firearm-related violence and to address its consequences requires an improved understanding of when these violent events are most likely to occur. We explored gunshot events in 6 of th...
Developing interventions to prevent firearm-related violence and to address its consequences requires an improved understanding of when these violent events are most likely to occur. We explored gunshot events in 6 of the most populated cities in the United States by time of day, day of week, holiday/non-holiday, and month using publicly available datasets. In some of these cities, gunshot events occurred most often at nighttime, on holidays and weekends, and during summer months, with significant interaction effects. There were also time-related changes in characteristics of the victims. Primary prevention efforts aimed at curbing firearm-related violence should consider these differential risks.
The Molecular Circadian Clock Is a Target of Anti-cancer Translation Inhibitors.
Berthier A, Gheeraert C, Johanns M … +4 more , Vinod M, Staels B, Eeckhoute J, Lefebvre P
J Biol Rhythms · 2024 Feb · PMID 37872767 · Publisher ↗
Circadian-paced biological processes are key to physiology and required for metabolic, immunologic, and cardiovascular homeostasis. Core circadian clock components are transcription factors whose half-life is precisely r...
Circadian-paced biological processes are key to physiology and required for metabolic, immunologic, and cardiovascular homeostasis. Core circadian clock components are transcription factors whose half-life is precisely regulated, thereby controlling the intrinsic cellular circadian clock. Genetic disruption of molecular clock components generally leads to marked pathological events phenotypically affecting behavior and multiple aspects of physiology. Using a transcriptional signature similarity approach, we identified anti-cancer protein synthesis inhibitors as potent modulators of the cardiomyocyte molecular clock. Eukaryotic protein translation inhibitors, ranging from translation initiation (rocaglates, 4-EGI1, etc.) to ribosomal elongation inhibitors (homoharringtonine, puromycin, etc.), were found to potently ablate protein abundance of REV-ERBα, a repressive nuclear receptor and component of the molecular clock. These inhibitory effects were observed both in vitro and in vivo and could be extended to PER2, another component of the molecular clock. Taken together, our observations suggest that the activity spectrum of protein synthesis inhibitors, whose clinical use is contemplated not only in cancers but also in viral infections, must be extended to circadian rhythm disruption, with potential beneficial or iatrogenic effects upon acute or prolonged administration.
Use of Light Protection Equipment at Night Reduces Time Until Discharge From the Neonatal Intensive Care Unit: A Randomized Interventional Study.
Odebrecht Vergne de Abreu AC, Alves Braga de Oliveira M, Alquati T … +5 more , Tonon AC, de Novaes Reis M, Camargo Rossi A, Sbaraini Bonatto F, Paz Hidalgo M
J Biol Rhythms · 2024 Feb · PMID 37846856 · Publisher ↗
Newborn infants' circadian systems are not completely developed and rely on external temporal cues for synchronizing their biological rhythms to the environment. In neonatal intensive care units (NICUs), lighting is usua...
Newborn infants' circadian systems are not completely developed and rely on external temporal cues for synchronizing their biological rhythms to the environment. In neonatal intensive care units (NICUs), lighting is usually continuous or irregular and infants are exposed to artificial light at night, which can have negative health consequences. Therefore, the aim of this study was to evaluate the impact of the use of individual light protection equipment at night on the development and growth of preterm neonates. Infants born at less than 37 gestational weeks who no longer needed constant intensive care were admitted into a newborn nursery and randomized to either use eye masks at night (intervention, = 21) or not (control, = 20). Infants who used eye protection at night were discharged earlier than those in the control group (8 [5] vs 12 [3.75] days; < 0.05). A greater variation within the day in heart rate was observed in the intervention group, with lower values of beats per minute at 1400 and 2000 h. There was no significant difference in weight gain between groups. In view of our results and of previous findings present in the literature, we suggest that combining a darkened environment at night with individual light protection devices creates better conditions for the development of preterm infants in the NICU. In addition, eye masks are an affordable and simple-to-use tool that can reduce hospitalization costs by decreasing the number of days spent in the NICU.
The Daily Patterns of Emergency Medical Events.
Helander ME, Formica MK, Bergen-Cico DK
J Biol Rhythms · 2024 Feb · PMID 37786272 · Publisher ↗
This study examines population-level daily patterns of time-stamped emergency medical service (EMS) dispatches to establish their situational predictability. Using visualization, sinusoidal regression, and statistical te...
This study examines population-level daily patterns of time-stamped emergency medical service (EMS) dispatches to establish their situational predictability. Using visualization, sinusoidal regression, and statistical tests to compare empirical cumulative distributions, we analyzed 311,848,450 emergency medical call records from the US National Emergency Medical Services Information System (NEMSIS) for years 2010 through 2022. The analysis revealed a robust daily pattern in the hourly distribution of distress calls across 33 major categories of medical emergency dispatch types. Sinusoidal regression coefficients for all types were statistically significant, mostly at the < 0.0001 level. The coefficient of determination ranged from 0.84 and 0.99 for all models, with most falling in the 0.94 to 0.99 range. The common sinusoidal pattern, peaking in mid-afternoon, demonstrates that all major categories of medical emergency dispatch types appear to be influenced by an underlying daily rhythm that is aligned with daylight hours and common sleep/wake cycles. A comparison of results with previous landmark studies revealed new and contrasting EMS patterns for several long-established peak occurrence hours-specifically for chest pain, heart problems, stroke, convulsions and seizures, and sudden cardiac arrest/death. Upon closer examination, we also found that heart attacks, diagnosed by paramedics in the field via 12-lead cardiac monitoring, followed the identified common daily pattern of a mid-afternoon peak, departing from prior generally accepted morning tendencies. Extended analysis revealed that the normative pattern prevailed across the NEMSIS data when reorganized to consider monthly, seasonal, daylight-savings versus civil time, and pre-/post-COVID-19 periods. The predictable daily EMS patterns provide impetus for more research that links daily variation with causal risk and protective factors. Our methods are straightforward and presented with detail to provide accessible and replicable implementation for researchers and practitioners.
Comments on Block et al., Pittendrigh Remembered, 2023.
Rusak B
J Biol Rhythms · 2024 Feb · PMID 37776296 · Publisher ↗
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Circadian Adaptation of Melatonin and Cortisol in Police Officers Working Rotating Shifts.
Kosmadopoulos A, Boudreau P, Kervezee L … +1 more , Boivin DB
J Biol Rhythms · 2024 Feb · PMID 37750410 · Full text
Misalignment of behavior and circadian rhythms due to night work can impair sleep and waking function. While both simulated and field-based studies suggest that circadian adaptation to a nocturnal schedule is slow, the r...
Misalignment of behavior and circadian rhythms due to night work can impair sleep and waking function. While both simulated and field-based studies suggest that circadian adaptation to a nocturnal schedule is slow, the rates of adaptation in real-world shift-work conditions are still largely unknown. The aim of this study was to evaluate the extent of adaptation of 24-h rhythms with 6-sulfatoxymelatonin (aMT6s) and cortisol in police officers working rotating shifts, with a special attention to night shifts. A total of 76 police officers (20 women; aged 32 ± 5.4 years, mean ± SD) from the province of Quebec, Canada, participated in a field study during their 28- or 35-day work cycle. Urine samples were collected for ~32 h before a series of day, evening, and night shifts to assess circadian phase. Before day, evening, and night shifts, 60%-89% of officers were adapted to a day schedule based on aMT6 rhythms, and 71%-78% were adapted based on cortisol rhythms. To further quantify the rate of circadian adaptation to night shifts, initial and final phases were determined in a subset of 37 officers with suitable rhythms for both hormones before and after 3-8 consecutive shifts (median = 7). Data were analyzed with circular and linear mixed-effects models. After night shifts, 30% and 24% of officers were adapted to a night-oriented schedule for aMT6s and cortisol, respectively. Significantly larger phase-delay shifts (aMT6s: -7.3 ± 0.9 h; cortisol: -6.3 ± 0.8 h) were observed in police officers who adapted to night shifts than in non-adapted officers (aMT6s: 0.8 ± 0.9 h; cortisol: 0.2 ± 1.1 h). Consistent with prior research, our results from both urinary aMT6s and cortisol midpoints indicate that a large proportion of police officers remained in a state of circadian misalignment following a series of night shifts in dim-light working environments.
Are We Finding Functional or Merely Statistically Significant Rhythms?
Ananthasubramaniam B
J Biol Rhythms · 2023 Dec · PMID 37609713 · Publisher ↗
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Ambient Temperature Effects on the Spring and Autumn Somatic Growth Trajectory Show Plasticity in the Photoneuroendocrine Response Pathway in the Tundra Vole.
van Dalum MJ, van Rosmalen L, Appenroth D … +5 more , Cazarez Marquez F, Roodenrijs RTM, de Wit L, Hut RA, Hazlerigg DG
J Biol Rhythms · 2023 Dec · PMID 37565646 · Full text
Seasonal mammals register photoperiodic changes through the photoneuroendocrine system enabling them to time seasonal changes in growth, metabolism, and reproduction. To a varying extent, proximate environmental factors...
Seasonal mammals register photoperiodic changes through the photoneuroendocrine system enabling them to time seasonal changes in growth, metabolism, and reproduction. To a varying extent, proximate environmental factors like ambient temperature (T) modulate timing of seasonal changes in physiology, conferring adaptive flexibility. While the molecular photoneuroendocrine pathway governing the seasonal responses is well defined, the mechanistic integration of nonphotoperiodic modulatory cues is poorly understood. Here, we explored the interaction between T and photoperiod in tundra voles, , a boreal species in which the main impact of photoperiod is on postnatal somatic growth. We demonstrate that postweaning growth potential depends on both gestational and postweaning patterns of photoperiodic exposure, with the highest growth potential seen in voles experiencing short (8 h) gestational and long (16 h) postweaning photoperiods-corresponding to a spring growth program. Modulation by T was asymmetric: low T (10 °C) enhanced the growth potential of voles gestated on short photoperiods independent of postweaning photoperiod exposure, whereas in voles gestated on long photoperiods, showing a lower autumn-programmed growth potential, the effect of T was highly dependent on postweaning photoperiod. Analysis of the primary molecular elements involved in the expression of a neuroendocrine response to photoperiod, thyrotropin beta subunit () in the , somatostatin () in the arcuate nucleus, and type 2/3 deiodinase (/) in the mediobasal hypothalamus identified as the most T-sensitive gene across the study, showing increased expression at higher T, while higher T reduced somatostatin expression. Contrastingly and were largely insensitive to T. Overall, these observations reveal a complex interplay between T and photoperiodic control of postnatal growth in , and suggest that integration of T into the control of growth occurs downstream of the primary photoperiodic response cascade revealing potential adaptivity of small herbivores facing rising temperatures at high latitudes.
Vasculature of the Suprachiasmatic Nucleus: Pathways for Diffusible Output Signals.
Yao Y, Green IK, Taub AB … +3 more , Tazebay R, LeSauter J, Silver R
J Biol Rhythms · 2023 Dec · PMID 37553858 · Full text
Transplant studies demonstrate unequivocally that the suprachiasmatic nucleus (SCN) produces diffusible signals that can sustain circadian locomotor rhythms. There is a vascular portal pathway between the SCN and the org...
Transplant studies demonstrate unequivocally that the suprachiasmatic nucleus (SCN) produces diffusible signals that can sustain circadian locomotor rhythms. There is a vascular portal pathway between the SCN and the organum vasculosum of the lamina terminalis in mouse brain. Portal pathways enable low concentrations of neurosecretions to reach specialized local targets without dilution in the systemic circulation. To explore the SCN vasculature and the capillary vessels whereby SCN neurosecretions might reach portal vessels, we investigated the blood vessels (BVs) of the core and shell SCN. The arterial supply of the SCN differs among animals, and in some animals, there are differences between the 2 sides. The rostral SCN is supplied by branches from either the superior hypophyseal artery (SHpA) or the anterior cerebral artery or the anterior communicating artery. The caudal SCN is consistently supplied by the SHpA. The rostral SCN is drained by the preoptic vein, while the caudal is drained by the basal vein, with variations in laterality of draining vessels. In addition, several key features of the core and shell SCN regions differ: Median BV diameter is significantly smaller in the shell than the core based on confocal image measurements, and a similar trend occurs in iDISCO-cleared tissue. In the cleared tissue, whole BV length density and surface area density are significantly greater in the shell than the core. Finally, capillary length density is also greater in the shell than the core. The results suggest three hypotheses: First, the distinct arterial and venous systems of the rostral and caudal SCN may contribute to the in vivo variations of metabolic and neural activities observed in SCN networks. Second, the dense capillaries of the SCN shell are well positioned to transport blood-borne signals. Finally, variations in SCN vascular supply and drainage may contribute to inter-animal differences.
Chronotype and Affective Response to Sleep Restriction and Subsequent Sleep Deprivation.
Cox RC, Ritchie HK, Knauer OA … +3 more , Guerin MK, Stothard ER, Wright KP
J Biol Rhythms · 2024 Feb · PMID 37539684 · Full text
Prior research indicates that sleep restriction, sleep deprivation, and circadian misalignment diminish positive affect, whereas effects on negative affect are inconsistent. One potential factor that may influence an ind...
Prior research indicates that sleep restriction, sleep deprivation, and circadian misalignment diminish positive affect, whereas effects on negative affect are inconsistent. One potential factor that may influence an individual's affective response to sleep restriction, sleep deprivation, and circadian misalignment is chronotype. Later chronotypes generally report higher negative affect and lower positive affect under typical sleep conditions; however, there is mixed evidence for an influence of chronotype on affective responses to sleep restriction and sleep deprivation. The present study examined the effect of chronotype on positive and negative affect during sleep restriction and subsequent total sleep deprivation. Sixteen healthy adults (M = 28.2 years, SD = 11.6 years) were classified as earlier or later chronotypes using multiple chronotype definitions: morningness-eveningness (MEQ), mid-sleep on free days corrected (MSFsc), habitual mid-sleep timing, dim light melatonin onset (DLMO), and phase relationship between DLMO and bedtime. Participants completed a 10-day protocol with one night of sleep restriction and subsequent 28 h total sleep deprivation. Affect was assessed hourly during scheduled wakefulness with the Positive and Negative Affect Schedule (PANAS). Data were analyzed with mixed-model analyses of variance (ANOVAs). During sleep restriction and subsequent sleep deprivation, positive affect decreased and negative affect increased. Across all chronotype measures, relatively later chronotypes demonstrated vulnerability to increased negative affect during sleep loss. The influence of chronotype on positive affect during sleep loss varied by chronotype measure. These findings suggest later chronotypes are more vulnerable to affective impairments during sleep loss and circadian misalignment, even when late chronotype is not extreme.
The SCN-HPA-Periphery Circadian Timing System: Mathematical Modeling of Clock Synchronization and the Effects of Photoperiod on Jetlag Adaptation.
Li Y, Androulakis IP
J Biol Rhythms · 2023 Dec · PMID 37529986 · Full text
Synchronizing the circadian timing system (CTS) to external light/dark cycles is crucial for homeostasis maintenance and environmental adaptation. The CTS is organized hierarchically, with the central pacemaker located i...
Synchronizing the circadian timing system (CTS) to external light/dark cycles is crucial for homeostasis maintenance and environmental adaptation. The CTS is organized hierarchically, with the central pacemaker located in the suprachiasmatic nuclei (SCN) generating coherent oscillations that are entrained to light/dark cycles. These oscillations regulate the release of glucocorticoids by the hypothalamus-pituitary-adrenal (HPA) axis, which acts as a systemic entrainer of peripheral clocks throughout the body. The SCN adjusts its network plasticity in response to variations in photoperiod, leading to changes in the rhythmic release of glucocorticoids and ultimately impacting peripheral clocks. However, the effects of photoperiod-induced variations of glucocorticoids on the synchronization of peripheral clocks are not fully understood, and the interaction between jetlag adaption and photoperiod changes is unclear. This study presents a semi-mechanistic mathematical model to investigate how the CTS responds to changes in photoperiod. Specifically, the study focuses on the entrainment properties of a system composed of the SCN, HPA axis, and peripheral clocks. The results show that high-amplitude glucocorticoid rhythms lead to a more coherent phase distribution in the periphery. In addition, our study investigates the effect of photoperiod exposure on jetlag recovery time and phase shift, proposing different interventional strategies for eastward and westward jetlag. The findings suggest that decreasing photic exposure before jetlag during eastward traveling and after jetlag during westward traveling can accelerate jetlag readaptation. The study provides insights into the mechanisms of CTS organization and potential recovery strategies for transitions between time zones and lighting zones.
Roles for the RNA-Binding Protein Rbp2 in Regulating the Circadian Clock.
McKnight BM, Kang S, Le TH … +10 more , Fang M, Carbonel G, Rodriguez E, Govindarajan S, Albocher-Kedem N, Tran AL, Duncan NR, Amster-Choder O, Golden SS, Cohen SE
J Biol Rhythms · 2023 Oct · PMID 37515350 · Full text
The cyanobacterial circadian oscillator, consisting of KaiA, KaiB, and KaiC proteins, drives global rhythms of gene expression and compaction of the chromosome and regulates the timing of cell division and natural transf...
The cyanobacterial circadian oscillator, consisting of KaiA, KaiB, and KaiC proteins, drives global rhythms of gene expression and compaction of the chromosome and regulates the timing of cell division and natural transformation. While the KaiABC posttranslational oscillator can be reconstituted in vitro, the Kai-based oscillator is subject to several layers of regulation in vivo. Specifically, the oscillator proteins undergo changes in their subcellular localization patterns, where KaiA and KaiC are diffuse throughout the cell during the day and localized as a focus at or near the pole of the cell at night. Here, we report that the CI domain of KaiC, when in a hexameric state, is sufficient to target KaiC to the pole. Moreover, increased ATPase activity of KaiC correlates with enhanced polar localization. We identified proteins associated with KaiC in either a localized or diffuse state. We found that loss of Rbp2, found to be associated with localized KaiC, results in decreased incidence of KaiC localization and long-period circadian phenotypes. Rbp2 is an RNA-binding protein, and it appears that RNA-binding activity of Rbp2 is required to execute clock functions. These findings uncover previously unrecognized roles for Rbp2 in regulating the circadian clock and suggest that the proper localization of KaiC is required for a fully functional clock in vivo.
Connecting the Dots: Potential Interactions Between Sex Hormones and the Circadian System During Memory Consolidation.
Boyd HM, Frick KM, Kwapis JL
J Biol Rhythms · 2023 Dec · PMID 37464775 · Full text
Both the circadian clock and sex hormone signaling can strongly influence brain function, yet little is known about how these 2 powerful modulatory systems might interact during complex neural processes like memory conso...
Both the circadian clock and sex hormone signaling can strongly influence brain function, yet little is known about how these 2 powerful modulatory systems might interact during complex neural processes like memory consolidation. Individually, the molecular components and action of each of these systems have been fairly well-characterized, but there is a fundamental lack of information about how these systems cooperate. In the circadian system, clock genes function as timekeeping molecules that convey time-of-day information on a well-stereotyped cycle that is governed by the suprachiasmatic nucleus. Keeping time is particularly important to synchronize various physiological processes across the brain and body, including those that regulate memory consolidation. Similarly, sex hormones are powerful modulators of memory, with androgens, estrogens, and progestins, all influencing memory consolidation within memory-relevant brain regions like the hippocampus. Despite clear evidence that each system can influence memory individually, exactly how the circadian and hormonal systems might interact to impact memory consolidation remains unclear. Research investigating either sex hormone action or circadian gene function within memory-relevant brain regions has unveiled several notable places in which the two systems could interact to control memory. Here, we bring attention to known interactions between the circadian clock and sex hormone signaling. We then review sex hormone-mediated control of memory consolidation, highlighting potential nodes through which the circadian system might interact during memory formation. We suggest that the bidirectional relationship between these two systems is essential for proper control of memory formation based on an animal's hormonal and circadian state.
Modeling the Effects of Napping and Non-napping Patterns of Light Exposure on the Human Circadian Oscillator.
Stowe SR, LeBourgeois MK, Diniz Behn C
J Biol Rhythms · 2023 Oct · PMID 37427666 · Full text
In early childhood, consolidation of sleep from a biphasic to a monophasic sleep-wake pattern, that is, the transition from sleeping during an afternoon nap and at night to sleeping only during the night, represents a ma...
In early childhood, consolidation of sleep from a biphasic to a monophasic sleep-wake pattern, that is, the transition from sleeping during an afternoon nap and at night to sleeping only during the night, represents a major developmental milestone. Reduced napping behavior is associated with an advance in the timing of the circadian system; however, it is unknown if this advance represents a standard response of the circadian clock to altered patterns of light exposure or if it additionally reflects features of the developing circadian system. Using a mathematical model of the human circadian pacemaker, we investigated the impact of napping and non-napping patterns of light exposure on entrained circadian phases. Simulated light schedules were based on published data from 20 children (34.2 ± 2.0 months) with habitual napping or non-napping sleep patterns (15 nappers). We found the model predicted different circadian phases for napping and non-napping light patterns: both the decrease in afternoon light during the nap and the increase in evening light associated with napping toddlers' later bedtimes contributed to the observed circadian phase difference produced between napping and non-napping light schedules. We systematically quantified the effects on phase shifting of nap duration, timing, and light intensity, finding larger phase delays occurred for longer and earlier naps. In addition, we simulated phase response curves to a 1-h light pulse and 1-h dark pulse to predict phase and intensity dependence of these changes in light exposure. We found the light pulse produced larger shifts compared with the dark pulse, and we analyzed the model dynamics to identify the features contributing to this asymmetry. These findings suggest that napping status affects circadian timing due to altered patterns of light exposure, with the dynamics of the circadian clock and light processing mediating the effects of the dark pulse associated with a daytime nap.
The Associations of Chronotype and Shift Work With Rheumatoid Arthritis.
Butler T, Maidstone JR, Rutter KM … +3 more , McLaughlin TJ, Ray WD, Gibbs EJ
J Biol Rhythms · 2023 Oct · PMID 37382359 · Full text
The circadian clock regulates multiple aspects of human physiology including immunity. People have a circadian preference termed chronotype. Those with an evening preference may be better suited to shift work, but also c...
The circadian clock regulates multiple aspects of human physiology including immunity. People have a circadian preference termed chronotype. Those with an evening preference may be better suited to shift work, but also carry higher risk of adverse health. Shift work leads to misalignment of circadian rhythms and is associated with increased risk of inflammatory disease such as asthma and cancer. Here, we investigate the association between chronotype, shift work, and rheumatoid arthritis (RA). The associations between exposures of shift work and chronotype on risk of RA were studied in up to 444,210 U.K. Biobank participants. Multivariable logistic regression models were adjusted for covariates: age, sex, ethnicity, alcohol intake, smoking history, Townsend Deprivation Index (TDI), sleep duration, length of working week, and body mass index (BMI). After adjusting for covariates, individuals with a morning chronotype had lower odds of having rheumatoid arthritis (RA; odds ratio [OR]: 0.93, 95% confidence interval [CI]: 0.88-0.99) when compared to intermediate chronotypes. The association between morning chronotype and RA persisted with a more stringent RA case definition (covariate-adjusted OR: 0.89, 95% CI: 0.81-0.97). When adjusted for age, sex, ethnicity, and TDI, shift workers had higher odds of RA (OR: 1.22, 95% CI: 1.1-1.36) compared to day workers that attenuated to the null after further covariate adjustment (OR: 1.1, 95% CI: 0.98-1.22). Morning chronotypes working permanent night shifts had significantly higher odds of RA compared to day workers (OR: 1.89, 95% CI: 1.19-2.99). These data point to a role for circadian rhythms in RA pathogenesis. Further studies are required to determine the mechanisms underlying this association and understand the potential impact of shift work on chronic inflammatory disease and its mediating factors.
Meta-analysis of Diurnal Transcriptomics in Mouse Liver Reveals Low Repeatability of Rhythm Analyses.
Brooks TG, Manjrekar A, Mrcˇela A … +1 more , Grant GR
J Biol Rhythms · 2023 Dec · PMID 37382061 · Full text
To assess the consistency of biological rhythms across studies, 57 public mouse liver tissue timeseries totaling 1096 RNA-seq samples were obtained and analyzed. Only the control groups of each study were included, to cr...
To assess the consistency of biological rhythms across studies, 57 public mouse liver tissue timeseries totaling 1096 RNA-seq samples were obtained and analyzed. Only the control groups of each study were included, to create comparable data. Technical factors in RNA-seq library preparation were the largest contributors to transcriptome-level differences, beyond biological or experiment-specific factors such as lighting conditions. Core clock genes were remarkably consistent in phase across all studies. Overlap of genes identified as rhythmic across studies was generally low, with no pair of studies having over 60% overlap. Distributions of phases of significant genes were remarkably inconsistent across studies, but the genes that consistently identified as rhythmic had acrophase clustering near ZT0 and ZT12. Despite the discrepancies between single-study analyses, cross-study analyses found substantial consistency. Running compareRhythms on each pair of studies identified a median of only 11% of the identified rhythmic genes as rhythmic in only 1 of the 2 studies. Data were integrated across studies in a joint and individual variance estimate (JIVE) analysis, which showed that the top 2 components of joint within-study variation are determined by time of day. A shape-invariant model with random effects was fit to the genes to identify the underlying shape of the rhythms, consistent across all studies, including identifying 72 genes with consistently multiple peaks.
Impact of Simulated Rotating Shift Work on Mammary Tumor Development in the Mouse Model for Breast Cancer.
Streng AA, Van Dycke KCG, van Oostrom CTM … +8 more , Salvatori DCF, Hulsegge G, Chaves I, Roenneberg T, Zander SAL, van Steeg H, van der Horst GTJ, van Kerkhof LWM
J Biol Rhythms · 2023 Oct · PMID 37357746 · Publisher ↗
Epidemiological studies associate night shift work with increased breast cancer risk. However, the underlying mechanisms are not clearly understood. To better understand these mechanisms, animal models that mimic the hum...
Epidemiological studies associate night shift work with increased breast cancer risk. However, the underlying mechanisms are not clearly understood. To better understand these mechanisms, animal models that mimic the human situation of different aspects of shift work are needed. In this study, we used "timed sleep restriction" (TSR) cages to simulate clockwise and counterclockwise rotating shift work schedules and investigated predicted sleep patterns and mammary tumor development in breast tumor-prone female mice. We show that TSR cages are effective in disturbing normal activity and estimated sleep patterns. Although circadian rhythms were not shifted, we observed effects of the rotating schedules on sleep timing and sleep duration. Sleep loss during a simulated shift was partly compensated after the shift and also partly during the free days. No effects were observed on body weight gain and latency time of breast cancer development. In summary, our study shows that the TSR cages can be used to model shift work in mice and affect patterns of activity and sleep. The effect of disturbing sleep patterns on carcinogenesis needs to be further investigated.
Circadian Regulation of the Neuroimmune Environment Across the Lifespan: From Brain Development to Aging.
Chen R, Routh BN, Gaudet AD … +1 more , Fonken LK
J Biol Rhythms · 2023 Oct · PMID 37357738 · Full text
Circadian clocks confer 24-h periodicity to biological systems, to ultimately maximize energy efficiency and promote survival in a world with regular environmental light cycles. In mammals, circadian rhythms regulate myr...
Circadian clocks confer 24-h periodicity to biological systems, to ultimately maximize energy efficiency and promote survival in a world with regular environmental light cycles. In mammals, circadian rhythms regulate myriad physiological functions, including the immune, endocrine, and central nervous systems. Within the central nervous system, specialized glial cells such as astrocytes and microglia survey and maintain the neuroimmune environment. The contributions of these neuroimmune cells to both homeostatic and pathogenic demands vary greatly across the day. Moreover, the function of these cells changes across the lifespan. In this review, we discuss circadian regulation of the neuroimmune environment across the lifespan, with a focus on microglia and astrocytes. Circadian rhythms emerge in early life concurrent with neuroimmune sculpting of brain circuits and wane late in life alongside increasing immunosenescence and neurodegeneration. Importantly, circadian dysregulation can alter immune function, which may contribute to susceptibility to neurodevelopmental and neurodegenerative diseases. In this review, we highlight circadian neuroimmune interactions across the lifespan and share evidence that circadian dysregulation within the neuroimmune system may be a critical component in human neurodevelopmental and neurodegenerative diseases.
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