Journal Of Biological Rhythms[JOURNAL]
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200 papers
Modeling 24-Hour Blood Pressure Rhythms Using Mixed-Effects Cosinor Models.
Khan MTF, Smith DF, Schuler CL … +5 more , DiFrancesco MW, Ruben MD, Rao MB, Amin RS, Hossain MM
J Biol Rhythms · 2026 Jul · PMID 42397040 · Publisher ↗
Single-component cosinor models are commonly used to assess circadian dysregulation in 24 h ambulatory blood pressure (BP) measurements, but they cannot capture more complex or asymmetric circadian patterns. This study e...
Single-component cosinor models are commonly used to assess circadian dysregulation in 24 h ambulatory blood pressure (BP) measurements, but they cannot capture more complex or asymmetric circadian patterns. This study evaluated 4 mixed-effects cosinor models by applying them to systolic and diastolic blood pressure (SBP and DBP) data collected from children with obstructive sleep apnea (OSA) and healthy controls (non-OSA) and compared the estimated circadian parameters between groups. The analysis included 24-h BP monitoring data from 219 age- and gender-matched children (117 controls, 52 with mild OSA, and 50 with moderate-to-severe OSA [MS-OSA]). Mixed-effects cosinor models with 1 to 4 components estimated various circadian parameters: acrophase, amplitude, and time arrived at peak velocity (TAPV). The 3-component mixed-effects cosinor model provided the best fit for SBP and DBP data. The estimated MESOR (midline estimating statistic of rhythm) was 106 mmHg for SBP and 64 mmHg for DBP in the control group; the MS-OSA group had a higher DBP MESOR (66 mmHg). Children with OSA had a dampened early afternoon BP peak and an increased late-evening BP peak. The timing differences for the first BP peak were more pronounced in the morning for SBP, and from morning to mid-day for DBP, particularly in MS-OSA. TAPV occurred in the morning in all models, with slight timing differences in SBP for mild OSA, and in DBP for MS-OSA, compared to controls. Although single-component cosinor models are traditionally used for 24-h BP rhythms, the multi-component mixed-effects models provided a better fit and captured disease-related differences.
Single-Cell RNA Sequencing of Murine Liver Reveals an Aligned Circadian Clock and Cell-Population-Specific Circadian-Regulated Pathways.
Veltri AJ, Nukaya M, Korac K … +2 more , Schwartz PB, Ronnekleiv-Kelly SM
J Biol Rhythms · 2026 Jul · PMID 42397025 · Publisher ↗
The circadian clock is tightly connected to metabolism, which is evident in the various metabolic processes performed by the liver. Perturbation of these processes due to circadian dysregulation leads to liver-specific p...
The circadian clock is tightly connected to metabolism, which is evident in the various metabolic processes performed by the liver. Perturbation of these processes due to circadian dysregulation leads to liver-specific pathology. The liver is composed of multiple cell populations, each with distinct functions contributing to organ homeostasis, but the individual contributions of these populations to circadian clock function are not yet known. Single-cell RNA sequencing provides the opportunity to understand clock function and oscillating gene expression within an organ system at the individual cell population level, allowing for a better understanding of the crosstalk between the circadian clock and metabolic pathways within the liver. Previously, barriers to achieving this goal included both the complexity of generating single-cell RNA-sequencing time series data and the complexity of data analysis. Herein, we established a protocol that enabled the generation of murine liver cell population time series data, as well as a methodological approach to evaluate the core molecular clock and oscillating gene expression in individual cell populations. Using a combination of the normalized coefficient of variation, clock-correlation, and pseudobulk analyses, we found a robust and aligned circadian clock in each of the hepatic cell populations. We then employed a pseudoreplicate/pseudobulk strategy to identify oscillating gene expression, and when benchmarked against bulk RNA-sequencing data, we demonstrated that many metabolic genes were oscillating in several of the cell populations, including non-hepatocyte clusters. Finally, we identified oscillating genes unique to specific cell populations that play critical roles in liver function. The findings in this study provide a critical foundation for understanding clock function and the contributions of oscillating gene function at the individual cell population level in the liver.
Martin Zatz.
Schwartz WJ, Silver R, Wirz-Justice A … +1 more , Zucker I
J Biol Rhythms · 2026 Jul · PMID 42397023 · Publisher ↗
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Thinking About Writing a Cover Letter.
Rosbash M
J Biol Rhythms · 2026 Jul · PMID 42383382 · Full text
First there are the obvious things that go into every cover letter. I try to summarize the main conclusions of the paper, obviously in a different way from the Abstract. Sometimes I just do this in the letter with bullet...
First there are the obvious things that go into every cover letter. I try to summarize the main conclusions of the paper, obviously in a different way from the Abstract. Sometimes I just do this in the letter with bullet points. Second, I try to explain why the editor should pay attention to these conclusions, how they differ from or extend the existing literature in new and/or important ways. Having said “new” and “important,” I need to emphasize that this task is critical, delicate and challenging. It is the same task that authors face in their Abstract and Discussion. How can one highlight the findings without going overboard, without any dishonesty or even excessive exaggeration? This is an ethical imperative of course, but walking along this often thin line can be difficult. If one is excessively mute or quiet about how interesting or novel the work is, the editors as well as the public at large might not pay attention. Gone are the days when Watson and Crick could use British understatement and just say, "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." Of course this understatement accompanied what was arguably the most important paper of the 20th century. I digress obviously. Third, I always try and engage the editor in some personal way. I recognize that a personal connection is likely a different exercise for me than for many practitioners, especially young people: Why? I know many of these editors personally – or at least have interacted with them in the past, often more than once. And some of them know me, usually for the better (but note: not always).
IL-6 Trans-Signaling Is Critical for Integrating Circadian Rhythms and Neuroimmune Responses to LPS Challenge in Mice.
Ambríz-Zárate JS, Báez-Ruiz A, Saderi N … +1 more , Salgado-Delgado RC
J Biol Rhythms · 2026 Jun · PMID 42376984 · Publisher ↗
Immunological homeostasis relies on a sophisticated bidirectional dialogue between the immune and nervous systems, primarily coordinated by cytokine signaling. These peripheral signals access the central nervous system (...
Immunological homeostasis relies on a sophisticated bidirectional dialogue between the immune and nervous systems, primarily coordinated by cytokine signaling. These peripheral signals access the central nervous system (CNS) via circumventricular organs and are integrated within the hypothalamus to mount appropriate homeostatic responses. Given that the immune system is under rigorous circadian control, circadian desynchrony-such as constant light exposure-often compromises this coordination, thereby increasing disease vulnerability. This study investigates the hypothesis that interleukin-6 (IL-6) is a pivotal mediator in this neuroimmune dialogue, specifically examining how astrocytic IL-6 trans-signaling modulates hypothalamic activity following an immune challenge. Utilizing male wild-type (WT) and GFAP-sgp130Fc (TG) mice-the latter genetically engineered to express a soluble gp130 fusion protein that selectively binds the IL-6/sIL-6R complex, thereby acting as a specific decoy receptor to inhibit astrocytic IL-6 trans-signaling without altering classical membrane-bound signaling-we assessed physiological and molecular responses under standard LD cycles and constant light (LL) conditions, the latter serving as a model for circadian desynchronization. Our results reveal that TG mice exhibit compromised circadian patterns and significantly altered thermoregulatory responses to lipopolysaccharide (LPS) compared to WT controls. Notably, TG mice under LL conditions showed a complete abolition of the thermoregulatory response to LPS, identifying a critical failure in homeostatic integration when both astrocytic signaling and circadian organization are impaired. Furthermore, c-Fos immunoreactivity within the suprachiasmatic nucleus and paraventricular nucleus indicated a profound suppression of hypothalamic activation in TG animals. Peripheral analysis of hepatic mRNA (IL-1β, IL-6, TLR4) confirmed genotype- and photoperiod-dependent variations, with TG mice displaying a markedly blunted inflammatory profile. These findings underscore the essential role of astrocytic IL-6 trans-signaling in neuroimmune communication and demonstrate that its absence, coupled with circadian disruption, induces a state of "neuronal deafness" that severely compromises the ability of the CNS to respond to inflammatory challenges.
The Ontogeny of Rhythms in Circadian Clock Gene Expression in Mouse Brain and Neuroimmune Tissues.
Bell KS, Chen R, Weitzner AS … +1 more , Fonken LK
J Biol Rhythms · 2026 Jun · PMID 42306957 · Publisher ↗
The circadian system coordinates daily physiology across nearly all tissues to temporally organize metabolism and maintain homeostasis. In the brain, circadian timing regulates neural activity, cellular function, and neu...
The circadian system coordinates daily physiology across nearly all tissues to temporally organize metabolism and maintain homeostasis. In the brain, circadian timing regulates neural activity, cellular function, and neuroimmune signaling, which is especially important during development. Yet, the ontogeny of circadian regulation during neurodevelopment remains poorly defined. Here, we characterized time-of-day variation in core clock and neuroimmune genes across multiple brain structures during early postnatal development, alongside circulating corticosterone concentrations. Using male and female C57BL mice housed in a standard light-dark cycle [12:12 light (150 lux)/dark (0 lux)], we measured the expression of , , and in the suprachiasmatic nucleus, hippocampus, and medial prefrontal cortex, as well as in neuroimmune tissues (choroid plexus, meninges, and isolated microglia) across postnatal days (PND) 1-24. Across development, rhythms were seen in corticosterone concentrations and all brain regions, with increased amplitudes and gene-specific phase maturation toward adult-like timing by PND 24. Notably, the choroid plexus and meninges exhibited time-of-day differences in clock gene expression by PND 10-24. In contrast, isolated microglia did not display detectable time-of-day differences in clock gene expression; however, microglial phagocytic activity varied by time of day. Together, these findings demonstrate that circadian regulation of the brain emerges during the neonatal period, and the parameters of time-of-day differences are tissue- and gene-specific during development. In addition, functional rhythms may precede or occur independent of detectable transcriptional differences. This work establishes a developmental framework for circadian-neuroimmune interactions, with important implications for neuroimmune development and vulnerability. Given the neuroimmune system's role in shaping brain development, disruptions in these temporal processes may contribute to neurodevelopmental or mood disorders.
Biological Rhythms in Coronavirus Pneumonia Pathogenesis.
Mok H, Gierasch C, Ostendorf E … +14 more , Jaiswal A, Adler AJ, Ganninger A, Wright L, Ganninger A, Fox C, Hyrc K, Shao G, Eubanks A, Patlin B, Arra M, Kumar P, Huss J, Haspel JA
J Biol Rhythms · 2026 Jun · PMID 42304657 · Full text
Night shift work is linked to more severe coronavirus pneumonia, suggesting that host resilience to these pathogens may depend on the timing of exposure. Here, we examined how the time of day influences the severity of c...
Night shift work is linked to more severe coronavirus pneumonia, suggesting that host resilience to these pathogens may depend on the timing of exposure. Here, we examined how the time of day influences the severity of coronavirus pneumonia in mice, using mouse hepatitis virus-1 (MHV-1) as a natural infection model. We found that the timing of infection influenced MHV-1 severity, with the highest mortality, peak viral load, and lung inflammation occurring with midday infection, which corresponds to the mid-rest phase in mice and is comparable with nighttime in humans. The time-of-day dependence in disease severity occurred prominently in males and was sensitive to global disruption of the clock gene . Midday infection correlated with increased MHV-1 binding to and replication within alveolar macrophages (AM). Depleting AMs with clodronate or loading them with neutral liposomes before MHV-1 infection eliminated differences in pneumonia survival and peak viral load related to the timing of infection. These data suggest an immunologic rhythm underlying coronavirus outcomes, in which oscillations in "first contact" interactions between AMs and the virus shape subsequent pneumonia severity.
On Fealty and Fencers in Science.
Herzog ED
J Biol Rhythms · 2026 Jun · PMID 42261986 · Publisher ↗
Abstract loading — click title to view on PubMed.
GIGEM (Group Isolation Gauge Effect Metrics), a Software Suite for Analyzing Social Isolation-induced Sleep Loss and Multi-batch Experiments in .
Doria EI, Hammood F, Yan J … +1 more , Li W
J Biol Rhythms · 2026 Jun · PMID 42261946 · Full text
We introduce Group Isolation Gauge Effect Metrics (GIGEM), a high-throughput software suite for sleep analysis designed to manage large population datasets from multi-batch experiments. In this study, we characterized s...
We introduce Group Isolation Gauge Effect Metrics (GIGEM), a high-throughput software suite for sleep analysis designed to manage large population datasets from multi-batch experiments. In this study, we characterized social isolation-induced sleep phenotypes across 38 Sleep Inbred Panel (SIP) lines after both acute and chronic social isolation. Beyond this specific study, GIGEM is broadly suited for diverse sleep research involving large-scale and multi-batch datasets. GIGEM enabled an extensive analysis of sleep parameters and allowed systematic identification of sleep changes in response to social isolation. Following acute social isolation, SIP line animals showed heterogeneous responses, including sleep loss, sleep gain, and no change in sleep. In contrast, chronic social isolation led to significant sleep loss in nearly all lines, though to varying degrees. While most SIP lines were sensitive to chronic social isolation, a select few were resistant to it. These results were obtained across 38 SIP lines and wild-type controls (totaling 5687 animals). Collectively, our results demonstrate that chronic social isolation-induced sleep loss is a robust yet variable trait and establish GIGEM as a powerful, generalizable tool for sleep phenotyping in large-scale, multi-batch studies.
Defining Clock Neurons Within Distributed Circadian Circuits Through Multiscale Technologies.
Walters B, Garg S, Fernandez DC
J Biol Rhythms · 2026 May · PMID 42175567 · Full text
The mammalian circadian system has traditionally been viewed as a hierarchical network organized around a master pacemaker in the suprachiasmatic nucleus (SCN), which synchronizes peripheral clocks to coordinate daily rh...
The mammalian circadian system has traditionally been viewed as a hierarchical network organized around a master pacemaker in the suprachiasmatic nucleus (SCN), which synchronizes peripheral clocks to coordinate daily rhythms in physiology and behavior. While this framework has provided a foundational model for circadian regulation, recent advances in molecular profiling, circuit tracing, and neuronal manipulation reveal a more complex architecture. Multiple brain regions outside the SCN contain neurons with intrinsic circadian properties that actively participate in processing temporal information, challenging the classical central-peripheral model. These findings raise a fundamental conceptual question: what defines a circadian clock neuron? Here, we synthesize recent molecular, cellular, and systems-level studies to examine the defining features of neurons embedded within brain circadian clocks. By integrating high-resolution molecular profiling with functional circuit analysis, we propose an operational framework for identifying clock neurons across brain circuits. Specifically, we outline four criteria that characterize circadian clock neurons: molecular oscillation, autonomy, physiological rhythmicity, and circuit influence. This framework reflects current experimental capabilities and highlights how multiscale approaches-from single-cell transcriptomics to causal circuit manipulation-are reshaping our understanding of circadian organization in the brain. Clarifying the identity of clock neurons will be essential for mapping distributed circadian circuits and for developing targeted interventions for neurological and neurodegenerative disorders associated with circadian and sleep disruption.
Light-induced Desynchrony of a Multi-oscillatory Circadian System in -deficient Mice.
Takasu NN, Tokuda IT, Uchida H … +3 more , Nakahata Y, Nakamura TJ, Nakamura W
J Biol Rhythms · 2026 May · PMID 42159220 · Publisher ↗
The gene was first identified in as a key regulator of circadian rhythms, with mutations that altered or abolished behavioral rhythmicity. Mammals possess 3 homologs, , , and . Here, we systematically compared the circ...
The gene was first identified in as a key regulator of circadian rhythms, with mutations that altered or abolished behavioral rhythmicity. Mammals possess 3 homologs, , , and . Here, we systematically compared the circadian properties of mice deficient in each gene, singly and in combination, under constant darkness (DD). We analyzed their free-running periods (τ) and phase response curves (PRCs) to 6-h light pulses (6-h LPs). Each -deficient line exhibited distinct circadian characteristics. -deficient mice (including double mutants) showed high-amplitude PRCs with large phase shifts near CT18, consistent with Type 0 resetting. -deficient mice displayed shorter τ and Type 1 PRCs with crossover points near CT17. Remarkably, some -deficient mice lost circadian rhythmicity after a single 6-h LP delivered near the crossover but regained rhythmicity following a second pulse 12 days later. In contrast, mice, which retain , failed to maintain stable rhythms in DD yet transiently reestablished a short-period (~19.5 h) rhythm in response to a 6-h LP. These findings indicate that rhythm loss in -deficient mice does not represent oscillation stop but rather light-induced desynchrony among multiple oscillators that constitute the circadian pacemaker. Collectively, our results demonstrate that sustains oscillator strength, maintains inter-oscillator coupling, and together they ensure the robustness of the mammalian circadian system against strong photic perturbation.
Influence of Diurnal Rhythms and Aging on Pupil Size Changes During Dark Adaptation in Mice.
Iba Y, Yamashita Y, Hasegawa T … +2 more , Masui T, Wada H
J Biol Rhythms · 2026 May · PMID 42159211 · Publisher ↗
During dark adaptation, pupil size changes in association with visual adaptation processes; however, the influence of diurnal phase (daytime vs nighttime) and aging on these changes remains unclear. In this study, we exa...
During dark adaptation, pupil size changes in association with visual adaptation processes; however, the influence of diurnal phase (daytime vs nighttime) and aging on these changes remains unclear. In this study, we examined pupil size changes during dark adaptation across the daytime and nighttime in young, middle-aged, and aged C57BL/6N mice. In young mice, pupil size reached a maximum shortly after the onset of dark adaptation and then gradually decreased during the daytime, whereas it remained dilated during the nighttime. Furthermore, dopamine depletion induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) significantly attenuated the gradual pupillary constriction following pupil dilation during dark adaptation in the daytime, suggesting a possible involvement of dopaminergic signaling in the later phase of the response. In middle-aged mice, pupillary light reflex-evoked constriction was preserved; however, the early (rapid) phase of constriction following the initial dilation during daytime dark adaptation was impaired, whereas the later (delayed) phase remained largely comparable to that in young mice, suggesting age-related alterations in regulatory mechanisms rather than a loss of constriction capacity. Pharmacological analyses further suggested that distinct neural mechanisms may differentially contribute to these temporal phases. In aged mice, maximal pupil dilation during dark adaptation was significantly reduced during both the daytime and nighttime. In addition, aged mice exhibited distinct abnormalities in pupil dilation immediately after the onset of dark adaptation during the nighttime, indicating mechanisms that differ from those observed in middle-aged mice. Together, these results demonstrate that pupillary dynamics during dark adaptation are modulated by diurnal phase and progressively altered with aging. Thus, analysis of pupil dynamics during dark adaptation may provide a useful approach for detecting age-related changes in neural function.
Biological Rhythms of Vital Signs in Newborns in a Neonatal Intensive Care Unit: A Prospective Observational Study.
Amadeu da Rocha V, Bueno M, Aparecida Silva I … +1 more , da Silveira Cruz-Machado S
J Biol Rhythms · 2026 May · PMID 42153342 · Publisher ↗
To characterize the presence and relationships between the rhythms of axillary temperature, heart rate, respiratory rate, blood pressure, and peripheral oxygen saturation, from the first (D1) to the third day of life (D3...
To characterize the presence and relationships between the rhythms of axillary temperature, heart rate, respiratory rate, blood pressure, and peripheral oxygen saturation, from the first (D1) to the third day of life (D3) in newborns (NBs) hospitalized in the neonatal intensive care unit (NICU). Primary, descriptive, nested clinical study within a primary, observational, and prospective clinical study, conducted in the NICU of a public hospital in the city of São Paulo, Brazil. Demographic data and vital signs (axillary temperature, heart rate, respiratory rate, blood pressure, and peripheral oxygen saturation) recorded in clinical charts were collected between the first and third day of life (D1-D3) at 4-h intervals (8 h; 12 h; 16 h; 20 h; 24 h; 4 h). The biological rhythms of the vital signs were analyzed using the Cosinor algorithm. Eighty-eight NBs participated (44 preterm and 44 term). Incipient variability of vital signs was observed in the first days, with reduced amplitudes and unstable phases. There was a correlation between the amplitude of axillary temperature and length of hospital stay in preterm infants, and between the amplitude of diastolic blood pressure and length of stay in term infants, suggesting the clinical potential of variability as a marker of neonatal maturation and clinical vulnerability. Altogether, the findings indicate the presence of early physiological rhythmicity and reinforce the importance of chronosensitive care and the incorporation of chronobiological parameters in clinical management, aiming to optimize the development and outcomes of hospitalized newborns.
Variations in the Timing of Bipolar Mood Cycles Associated With Interactions of the Moon's Synodic, Tropical, and Anomalistic Cycles.
Wehr TA, Avery DH
J Biol Rhythms · 2026 May · PMID 42130202 · Publisher ↗
The Moon's motion around the Earth is complex, governed by interactions among several types of cycles that arise from different aspects of its orbit. The 29.53-day synodic cycle occurs as the Moon passes through new-moon...
The Moon's motion around the Earth is complex, governed by interactions among several types of cycles that arise from different aspects of its orbit. The 29.53-day synodic cycle occurs as the Moon passes through new-moon and full-moon alignments (syzygies) with the Earth and the Sun. The 27.32-day tropical cycle occurs as the Moon moves back and forth between its northernmost and southernmost positions (standstills) relative to the plane of the Earth's equator. The 27.55-day anomalistic cycle occurs as the Moon moves back and forth from its nearest and farthest distances from the Earth (perigees and apogees). The Moon's effects on luminance and gravity at the Earth's surface are greatest at times of syzygies, standstills, and perigees. Here, based on periodogram analyses of 14.5 patient-year records of a circular, rapid cycling type of bipolar disorder, we show that onsets of mania in a given individual can recur in association with 2 or more lunar cycles simultaneously, and with conjunctions of syzygies of the synodic cycle with standstills of the tropical cycle or with perigees of the anomalistic cycle. The results are consistent with the fact that the Moon's effects at the Earth's surface are the result of interactions among all of its constituent cycles, and they highlight the potential importance of long-term longitudinal designs in studies of lunar influence.
A Journey Through Chronotype Changes in University Students.
Domenie ED, Erminelli D, Giusti G … +4 more , Mangini C, Zarantonello L, Costa R, Montagnese S
J Biol Rhythms · 2026 May · PMID 42108751 · Publisher ↗
Chronotype reflects an individual's preferred timing of sleep/daily activities and is typically regarded as a stable trait, though it varies across the lifespan and may fluctuate also over shorter periods of time. Here,...
Chronotype reflects an individual's preferred timing of sleep/daily activities and is typically regarded as a stable trait, though it varies across the lifespan and may fluctuate also over shorter periods of time. Here, we investigate the temporal stability of self-assessed chronotype and its modulation by behavioral advice in a large cohort of University students participating in a 2-arm circadian hygiene education initiative (either encouraging consistency or advancement of sleep, meals, and exercise timing). Students provided demographic and sleep quality information, and repeated chronotype assessments (2-22 months) using the Self-Morningness/Eveningness (Self-ME) question, which offers a choice among 4 categories (definitely morning, morning, evening, definitely evening) and the Ultrashort Munich ChronoType Questionnaire (μMCTQ), which has midsleep and social jetlag as outcomes. Two main samples were analyzed: students completing baseline/2-month follow-up assessments ( = 1902) and students completing baseline/one later assessment, at any time ( = 2820); a subgroup with 3 available assessments ( = 1257) was also examined. Agreement between subsequent Self-ME assessments was good in all samples (0.6 < Cohen's < 0.8), with approximately 70% of students confirming their first assessment at 2 months, with variations (62%-73%) depending on time between assessments and behavioral advice; transitions mostly occurred between adjacent Self-ME categories. Nonetheless, approximately 30% of participants changed category between 2 assessments, and those who moved once were more likely to move again. "Non movers" exhibited more extreme sleep-wake habits. Furthermore, midsleep and social jetlag changed over the calendar year in ways that seemed to reflect the time-course/constraints of the academic year. The 2 circadian hygiene interventions influenced chronotype stability slightly and differently, particularly in morning types, who probably found it easier to comply with the suggestion of advancing sleep-wake timing. In conclusion, chronotype in young adults shows relative stability but is plastic within limits, also in relation to the way it is measured.
RhythmInsight: An Interactive Web Platform for Circadian and Diurnal Rhythmic Analysis and Visualization.
Han G, Wu X, Xiao X … +9 more , Guo T, Li D, Zhang H, Gao D, Li C, Wang A, Chao HW, Jin Y, Chen H
J Biol Rhythms · 2026 May · PMID 42087371 · Publisher ↗
Circadian rhythms are endogenous biological cycles with a period of approximately 24 h that integrate a wide range of physiological and behavioral processes in living organisms. In addition to circadian rhythms, many oth...
Circadian rhythms are endogenous biological cycles with a period of approximately 24 h that integrate a wide range of physiological and behavioral processes in living organisms. In addition to circadian rhythms, many other biological processes also exhibit diurnal (24 h) rhythms driven by external environmental cues. With the significance of circadian and diurnal regulation becoming increasingly recognized, the field of chronobiology is exhibiting unprecedented growth in the life sciences and translational medicine. Over the past 2 decades, a variety of computational methods have been developed to detect and extract rhythmic signals from the time-series data of different species. However, existing rhythmic analysis tools are often fragmented, demand programming expertise, exhibit limited visualization capabilities, and impose inconsistent requirements on data types and sampling intervals. Therefore, there is an urgent need to establish a convenient and comprehensive tool for detecting and analyzing the circadian and diurnal rhythmicity. To meet this demand, RhythmInsight was developed as an open access, web-based platform for comprehensive analysis and visualization of circadian and diurnal rhythms across various species and data types, including physiological, omics, and experimental data. RhythmInsight includes 3 modules: Rhythmic Analysis, Differential Rhythmicity Analysis, and Rhythmic Visualization. The Rhythmic Analysis module incorporates 9 algorithms (JTK_CYCLE, Cosinor, CircaCompare, meta2d, Lomb-Scargle, RAIN, ARSER, Fisher's G-test, and Robust G-test) to detect and characterize rhythmic signals. The Differential Rhythmicity Analysis module, based on CircaCompare, detects and compares rhythmic parameters (amplitude, phase, and the Midline Estimating Statistic of Rhythm) between 2 experimental conditions. The Rhythmic Visualization module provides powerful graphical tools, including line plots, fitted curves, heatmaps, polar plots, and boxplots, for the intuitive visualization of time-dependent trends. By integrating rhythmic algorithmic analysis with interactive visualization, RhythmInsight simplifies the analysis process and enhances accessibility for researchers without programming backgrounds, particularly experimental biologists and early-career scientists. RhythmInsight is freely available at https://RhythmInsight.com.
Is the FEO Food-Entrainable? Reexamining the Classic Fred Stephan Experiment Using Canonical-Clock-Less Triple Knockout Mice.
Taufique SKT, Ehichioya DE, Farah S … +2 more , Shen M, Yamazaki S
J Biol Rhythms · 2026 May · PMID 42080227 · Full text
When nocturnal rodents are subjected to daytime restricted feeding, in which food is only available for a few hours per day, they typically become active a few hours before the onset of the scheduled mealtime. This so-ca...
When nocturnal rodents are subjected to daytime restricted feeding, in which food is only available for a few hours per day, they typically become active a few hours before the onset of the scheduled mealtime. This so-called food-anticipatory activity (FAA) is controlled by an autonomous circadian pacemaker, which is independent from the central circadian pacemaker in the suprachiasmatic nucleus (SCN). Fred Stephan named this pacemaker the food-entrainable oscillator (FEO) because FAA re-entrains to a shifted feeding schedule. We recently developed a method to measure food-seeking nose-poking behavior by an operant feeding device and found that anticipatory food-seeking nose-poking for scheduled daily food availability shifts in parallel with phase-shifted environmental light-dark cycles, raising the possibility that anticipatory food-seeking behavior is controlled by an oscillator entrained to the environmental light-dark cycle. With this possible light-entrainability of the FEO, we revisited Stephan's historical experiment-testing whether the FEO entrains to feeding cycle in the absence of a light-dark cycle without functional SCN-using triple knockout (KO) mice, in which the canonical circadian oscillators in the SCN and peripheral tissues are disabled. KO mice were subjected to restricted feeding under constant darkness. The food-seeking nose-poking activity of a subset of the KO mice indeed occasionally entrained to the feeding cycle and re-entrained to a shifted feeding cycle. Despite our previous study showing that anticipatory food-seeking behavior shifted with the environmental light-dark cycle, these data demonstrate that it can also entrain to the feeding cycle in the absence of an environmental light-dark cycle, supporting Stephan's observation that the FEO is indeed food-entrainable.
A Lentiviral Fluorescent Reporter to Study Circadian Rhythms in Single Cells.
Gabriel CH, Lehmann L, Ahlburg J … +1 more , Kramer A
J Biol Rhythms · 2026 Apr · PMID 42041078 · Publisher ↗
Circadian rhythms-self-sustained, ~24-h oscillations in transcript and protein levels-are generated by a cell-autonomous molecular clock. These rhythms shape how individual cells respond to external signals, influencing...
Circadian rhythms-self-sustained, ~24-h oscillations in transcript and protein levels-are generated by a cell-autonomous molecular clock. These rhythms shape how individual cells respond to external signals, influencing key decisions such as differentiation and apoptosis. However, current tools for visualizing circadian rhythms at the single-cell level often rely on genomic engineering and clonal expansion, limiting their accessibility and applicability. We present fluorescent circadian reporters based on the murine gene, delivered via lentiviral transduction and compatible with time-lapse single-cell microscopy. These reporters produce oscillatory signals that depend on a functional circadian clock and can be used to determine a cell's circadian dynamics parameters, such as circadian phase. Their simple and efficient delivery should make them suitable for a wide variety of cell types, greatly expanding opportunities to study single-cell circadian dynamics and their impact across diverse biological processes and systems.
Chronotype, Race, and Gender.
Refinetti R
J Biol Rhythms · 2026 Apr · PMID 42011859 · Publisher ↗
This letter follows up on an article recently published in the . The authors of the original article used actigraphy data from a sample of 720 participants to show that the mean chronotype of male participants is not sig...
This letter follows up on an article recently published in the . The authors of the original article used actigraphy data from a sample of 720 participants to show that the mean chronotype of male participants is not significantly different from the mean chronotype of female participants but also that the mean chronotype of Black participants is about 20 min later than the mean chronotype of White participants. I reached the same conclusions using a larger data set of 7562 participants from National Health and Nutrition Examination Survey (NHANES) 2013-2014. This corroboration is important because the associations of race and gender with chronotype have been inconsistent in studies in which chronotype was measured with questionnaires rather than with objective rest-activity measures.
RSK: A Pivotal Regulator of Circadian Plasticity at the Neuronal and Behavioral Level.
Theyyassanchery Mani A, Backs V, Werner C … +2 more , Helfrich-Förster C, Raabe T
J Biol Rhythms · 2026 Apr · PMID 41966995 · Publisher ↗
Circadian neuronal plasticity describes daily recurring changes at the level of neuronal morphology, connectivity and synaptic processes. Disturbance of these plastic changes could result in inflexibility of an organism...
Circadian neuronal plasticity describes daily recurring changes at the level of neuronal morphology, connectivity and synaptic processes. Disturbance of these plastic changes could result in inflexibility of an organism to adapt behavior to changing environmental cues. The mitogen activated protein kinases (MAPK)/ERK signaling pathway is involved both in circadian processes and neuronal plasticity. Ribosomal S6 kinases (RSK) act as downstream mediators of ERK signaling with apparently pleiotropic-but sometimes poorly understood- functions in the nervous system. This is illustrated by some major gaps in our understanding of the pathophysiological processes caused by RSK2 mutations in humans that lead to intellectual disabilities. Previous studies described the role of RSK as one regulator of the molecular circadian oscillator. Here we could show that RSK kinase activity is required to control another aspect of circadian rhythmicity, the daily remodeling of the dorsal branching pattern of the small ventral lateral neurons (s-LN) as the central pacemaker cells. Loss of RSK function resulted in more fasciculated and less branched s-LN's in the early morning, which could affect synaptic in- or output connectivity. Increased fasciculation correlated with a reduced number of Bruchpilot sites as a marker for presynapses. Analysis of the expression of the Pigment Dispersing Factor PDF in s-LN's, the most important signaling factor between clock neurons, revealed no evidence of changes in mutants. Consistent with unaffected PDF signaling as a major output from the s-LN's, mutant flies are rhythmic. Their free-running rhythms show even a significantly higher power than those of the wild-type controls. This robustness is at the expense of flexibility to adapt their activity to variations in light conditions. Together with the known role of RSK in olfactory learning and memory processes our results suggest that RSK is required to maintain experience dependent plasticity.
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