Journal of Biological Rhythms最新文献

{"title":"Performance of Blood-Based Biomarkers for Human Circadian Pacemaker Phase: Training Sets Matter As Much As Feature-Selection Methods.","authors":"Carla S Möller-Levet, Simon N Archer, Derk-Jan Dijk","doi":"10.1177/07487304251358950","DOIUrl":"10.1177/07487304251358950","url":null,"abstract":"<p><p>Biomarkers are valuable tools in a wide range of human health areas including circadian medicine. Valid, low-burden, multivariate molecular approaches to assess circadian phase at scale in people living and working in the real world hold promise for translating basic circadian knowledge to practical applications. However, standards for the development and evaluation of these circadian biomarkers have not yet been established, even though several publications report such biomarkers and claim that the methods are universal. Here, we present a basic exploration of some of the determinants and confounds of blood-based biomarker development for suprachiasmatic nucleus (SCN) phase by reanalysing publicly available data sets. We compare performance of biomarkers based on three feature-selection methods: Partial Least Squares Regression, ZeitZeiger, and Elastic Net, as well as performance of a standard set of clock genes. We explore the effects of training sample size and the impact of the experimental protocols from which training samples are drawn and on which performance is tested. Approaches based on small sample sizes used for training are prone to poor performance due to overfitting. Performance to some extent depends on the feature-selection method, but at least as much on the experimental conditions from which the biomarker training samples were drawn. Performance of biomarkers developed under baseline conditions does not necessarily translate to protocols that mimic real-world scenarios such as shiftwork in which sleep may be restricted or desynchronized from the endogenous circadian SCN phase. The molecular features selected by the various approaches to develop biomarkers for the SCN phase show very little overlap although the processes associated with these features have common themes with response to steroid hormones, that is, cortisol being the most prominent. Overall, the findings indicate that establishment of circadian biomarkers should be guided by established biomarker-development concepts and foundational principles of human circadian biology.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"506-527"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12572356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jules Verne: A Literary Pioneer of Chronobiology.","authors":"Diego A Golombek","doi":"10.1177/07487304251369951","DOIUrl":"10.1177/07487304251369951","url":null,"abstract":"","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"503-505"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>miR-124</i> acts During <i>Drosophila</i> Development to Determine the Phase of Adult Circadian Behavior.","authors":"Yongliang Xia, Chenghao Chen, Patrick Emery","doi":"10.1177/07487304251361579","DOIUrl":"10.1177/07487304251361579","url":null,"abstract":"<p><p>The circadian clock enables organisms to optimize their metabolism, physiology, and behavior with the time-of-day. However, circadian rhythms benefit organisms only if they are properly synchronized with the day/night cycle; circadian misalignment can have detrimental effects on animals' wellbeing and survival. We previously showed that in <i>Drosophila</i>, loss of the microRNA <i>miR-124</i> advances the phase of circadian evening locomotor activity by several hours under constant darkness conditions. Interestingly, we now report that loss of <i>miR-124</i> also delays morning activity under a light/dark cycle with a short photoperiod. We recapitulated these opposite phase phenotypes by eliminating <i>miR-124</i> during larval development, but not when this microRNA is lost during pupation to adulthood. The loss of <i>miR-124</i> results in significant miswiring within the circadian neural network and severely alters neural activity rhythms in the ventral Lateral Neurons (s-LNvs) and the posterior Dorsal Neurons 1 (DN1ps), which control the timing of morning and evening activity. Silencing the s-LNvs in <i>miR-124</i> mutant flies restores the phase of evening activity, while activating the DN1ps rescues the phases of both morning and evening activities. Our findings thus reveal the pivotal role of <i>miR-124</i> in sculpting the <i>Drosophila</i> circadian neural network during development and its long-lasting impact on circuit activity and adult circadian behavior.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"574-593"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian Control of Pulmonary Endothelial Signaling Occurs via the NADPH Oxidase 2-NLRP3 Pathway.","authors":"Shaon Sengupta, Yool Lee, Jian Qin Tao, Isha Akolia, Natalia Louneva, Kaitlyn Forrest, Oindrila Paul, Thomas G Brooks, Gregory R Grant, Amita Sehgal, Shampa Chatterjee","doi":"10.1177/07487304251363656","DOIUrl":"10.1177/07487304251363656","url":null,"abstract":"<p><p>Circadian rhythms are endogenous oscillations that occur with a 24-h periodicity and support organismal homeostasis. While the role of the circadian clock in systemic vasculature is well known, its role in pulmonary vasculature, specifically in the pulmonary endothelium, has remained unexplored. We hypothesized that the circadian clock directly regulates pulmonary endothelium to control lung inflammation. Using pulmonary artery segments and endothelial cells isolated from lungs of mPer2luciferase transgenic mice, we monitored circadian rhythms and observed that lipopolysaccharide (LPS) treatment disrupted rhythmicity. This disruption was mediated by reactive oxygen species (ROS) generated via NADPH oxidase 2 (NOX2). Remarkably, the pharmacologic inhibition of NOX2 before LPS exposure restored circadian rhythmicity in the pulmonary endothelium. In wild-type (WT) mice, LPS activated a NOX2-NLRP3 signaling axis that drove inflammation as evidenced by increased polymorphonuclear neutrophil (PMN) accumulation and intercellular adhesion molecule-1 (ICAM-1) expression on the pulmonary endothelium. In contrast, disruption of the clock using two different clock mutants (<i>Bmal</i>1^-/- and <i>Cry1/2</i>^-/-) resulted in a sustained baseline elevation of PMN and ICAM-1, which changed minimally with LPS. This effect was attributed to aberrant activation of the NLRP3 inflammasome at baseline in the clock mutants, as supported by lung transcriptomic data and reversal of the phenotype with an NLRP3 inhibitor. Importantly, these findings also reveal an intriguing bidirectional relationship: while the circadian clock modulates inflammatory responses, inflammatory stimuli in turn alter circadian rhythmicity via the NOX2 pathway. Together, our results identify a novel mechanism by which circadian control of pulmonary endothelial inflammation may be leveraged to mitigate the consequences of clock disruption in lung disease.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"555-573"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12499374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clock-Dependent Phosphorylation of CikA Regulates Its Activity.","authors":"Cigdem Sancar, Susan S Golden","doi":"10.1177/07487304251338156","DOIUrl":"10.1177/07487304251338156","url":null,"abstract":"<p><p>In the cyanobacterial circadian clock, a core oscillator comprising the proteins KaiA, KaiB, and KaiC keeps time based on a rhythmic phosphorylation of KaiC, and histidine protein kinases relay temporal information from the KaiABC complex to regulate gene expression. The kinases SasA and CikA engage directly with the oscillator and are responsible for modulating the phosphorylation and dephosphorylation throughout the circadian day of the response-regulator transcription factor RpaA; the phosphorylation state of RpaA in turn determines circadian gene expression. We recently showed that either CikA or SasA can drive rhythmic phosphorylation and DNA binding of RpaA in an in vitro system. However, when SasA is absent in vivo, a bioluminescence reporter gene shows a very low expression and amplitude rhythm, indicating CikA kinase activity is not sufficient to activate gene expression. We questioned why CikA cannot serve as a robust kinase for RpaA in the absence of SasA in the cell. Here, we investigated post-translational modifications of CikA and found KaiC-dependent phosphorylation sites of CikA that dramatically affect its activity. Phosphomimetic mutants of these sites showed that the phosphorylated version of CikA is not functional. Our data show that inverse correlation of KaiC levels and these inhibitory phosphorylation sites can explain the lower CikA activity in a SasA knockout background. We conclude that these phosphorylation sites act as a rheostat for CikA activity and are regulated by KaiC levels.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"455-467"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated Batch Processing of Diurnal Cardiac Activity: Comparison of Fully Automated Batch- to Gold-Standard Manual Processing.","authors":"Maximilian Schmausser, Christoph Hoog Antink, Michael Kaess, Julian Koenig","doi":"10.1177/07487304251348516","DOIUrl":"10.1177/07487304251348516","url":null,"abstract":"<p><p>The analysis of long-term variation patterns in heart rate (HR) and heart rate variability (HRV) provides insights into autonomic nervous system function beyond short-term recordings taken under resting or experimental conditions. Yet, traditional processing pipelines often require time- and labor-intensive visual inspection of electrocardiography (ECG) data and manual artifact removal. This study evaluated the performance of 3 code-based fully automated batch-processing pipelines-<i>NeuroKit2</i>, <i>RHRV</i>, and <i>Systole</i>-against the manual gold standard utilizing Kubios for both (diurnal) HR and HRV estimates derived from raw 48-h ECG recordings. Results illustrate that while automated pipelines yield HR estimates in good agreement to the gold standard (<i>r</i> = 0.91-0.99; α = 0.90-0.99), HRV estimates exhibit greater deviations (<i>r</i> = 0.66-0.87; α = 0.76-0.90). Cosinor analyses of diurnal HR patterns indicate strong consistency between Kubios and NeuroKit2 (<i>r</i> = 0.94-0.99; α = 0.97-0.99), but weaker correlations with RHRV and Systole (<i>r</i> = 0.58-0.87; α = 0.63-0.93). HRV cosinor parameters showed even larger discrepancies, with parameter-dependent correlations ranging from <i>r</i> = 0.41 to 0.86 and Cronbach's alphas from α = 0.59 to 0.91. Findings suggest that automated batch processing of ECG data for analyzing diurnal variation patterns in HR and HRV produces results that show moderate to good agreement with the gold standard including visual inspection and manual processing. However, caution is warranted, as existing toolboxes and pipelines may lead to different results.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"468-479"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for Internal Misalignment of Circadian Rhythms in Youth With Emerging Mood Disorders.","authors":"Joanne S Carpenter, Jacob J Crouse, Mirim Shin, Emiliana Tonini, Gabrielle Hindmarsh, Zsofi de Haan, Frank Iorfino, Rebecca Robillard, Sharon Naismith, Elizabeth M Scott, Ian B Hickie","doi":"10.1177/07487304251349408","DOIUrl":"10.1177/07487304251349408","url":null,"abstract":"<p><p>Despite evidence for links between circadian dysfunction and mood disorders, previous research has largely reported on single biological markers of circadian alignment. The available evidence on relationships between 2 internal phase markers (e.g., dim light melatonin onset [DLMO] and peak cortisol concentration) suggests these signals may be temporally misaligned in major depressive disorder with greater misalignment associated with more severe depressive symptoms. This study aimed to examine multiple circadian phase markers to determine whether any youth with emerging mood disorders present with clear evidence of internal circadian misalignment, and whether the degree of circadian misalignment is correlated with more severe mood symptoms. Cross-sectional data from 69 youth presenting for mental health care (20.6 ± 3.8 years; 39% male) and 19 healthy controls (24.0 ± 3.6 years; 53% male) included actigraphy monitoring; overnight in-lab measurement of 3 phase markers: DLMO, salivary cortisol peak (CORT), and core body temperature nadir (TEMP); and depressive symptoms (Hamilton Depression Rating Scale). Abnormal phase angles between 2 phase markers were defined as ±2 standard deviations beyond the control mean. In those with emerging mood disorders, earlier TEMP relative to other phase markers (DLMO, CORT, sleep midpoint) was associated with higher depressive symptoms. Sixteen individuals (23%) with emerging mood disorders had abnormal phase angles between at least 1 pair of phase markers, consistent with internal misalignment of the circadian system. The internal misalignment subgroup had later DLMO on average, however presented with a diverse range of individual phase angle abnormalities. Diverse disruptions of circadian alignment occur in youth with mental ill-health. The relative timing of core body temperature and melatonin rhythms may be key circadian features linked to depressive symptoms. Longitudinal research is needed to establish whether correction of circadian misalignment is relevant to treatment of mood syndromes in youth with evidence of disrupted circadian systems.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"424-440"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12426331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Hard Day's Night: The Circadian Beatles.","authors":"Diego A Golombek","doi":"10.1177/07487304251365297","DOIUrl":"10.1177/07487304251365297","url":null,"abstract":"","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"409-410"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asymmetric Velocity Response Curves to Light and the Intrinsic Period of the Human Circadian Pacemaker.","authors":"Anne C Skeldon, Imran M Usmani, Derk-Jan Dijk","doi":"10.1177/07487304251355454","DOIUrl":"10.1177/07487304251355454","url":null,"abstract":"","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"421-423"},"PeriodicalIF":2.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"It's Not Just Light: Assessing the Intrinsic Period of the Human Circadian Pacemaker Under Dim Light Conditions Should Include Non-Photic Influences.","authors":"Melissa A St Hilaire, Charles A Czeisler, Elizabeth B Klerman","doi":"10.1177/07487304251355451","DOIUrl":"10.1177/07487304251355451","url":null,"abstract":"<p><p>Response to: \"Mathematical Analysis of Light-sensitivity Related Challenges in Assessment of the Intrinsic Period of the Human Circadian Pacemaker\".</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"414-420"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}