William J Schwartz, Rae Silver, Anna Wirz-Justice, Irving Zucker
{"title":"Martin Zatz.","authors":"William J Schwartz, Rae Silver, Anna Wirz-Justice, Irving Zucker","doi":"10.1177/07487304261457261","DOIUrl":"10.1177/07487304261457261","url":null,"abstract":"","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261457261"},"PeriodicalIF":3.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375757","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}
Md Tareq Ferdous Khan, David F Smith, Christine L Schuler, Mark W DiFrancesco, Marc D Ruben, Marepalli B Rao, Raouf S Amin, Md Monir Hossain
{"title":"Modeling 24-Hour Blood Pressure Rhythms Using Mixed-Effects Cosinor Models.","authors":"Md Tareq Ferdous Khan, David F Smith, Christine L Schuler, Mark W DiFrancesco, Marc D Ruben, Marepalli B Rao, Raouf S Amin, Md Monir Hossain","doi":"10.1177/07487304261459486","DOIUrl":"10.1177/07487304261459486","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261459486"},"PeriodicalIF":3.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375817","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}
Anthony J Veltri, Manabu Nukaya, Ksenija Korac, Patrick B Schwartz, Sean M Ronnekleiv-Kelly
{"title":"Single-Cell RNA Sequencing of Murine Liver Reveals an Aligned Circadian Clock and Cell-Population-Specific Circadian-Regulated Pathways.","authors":"Anthony J Veltri, Manabu Nukaya, Ksenija Korac, Patrick B Schwartz, Sean M Ronnekleiv-Kelly","doi":"10.1177/07487304261453628","DOIUrl":"10.1177/07487304261453628","url":null,"abstract":"<p><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.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261453628"},"PeriodicalIF":3.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375891","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":"Thinking About Writing a Cover Letter.","authors":"Michael Rosbash","doi":"10.1177/07487304261461324","DOIUrl":"10.1177/07487304261461324","url":null,"abstract":"","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261461324"},"PeriodicalIF":3.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13326739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360940","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}
Josué S Ambríz-Zárate, Adrián Báez-Ruiz, Nadia Saderi, Roberto C Salgado-Delgado
{"title":"IL-6 Trans-Signaling Is Critical for Integrating Circadian Rhythms and Neuroimmune Responses to LPS Challenge in Mice.","authors":"Josué S Ambríz-Zárate, Adrián Báez-Ruiz, Nadia Saderi, Roberto C Salgado-Delgado","doi":"10.1177/07487304261459132","DOIUrl":"10.1177/07487304261459132","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261459132"},"PeriodicalIF":3.0,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351977","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":"On Fealty and Fencers in Science.","authors":"Erik D Herzog","doi":"10.1177/07487304261456978","DOIUrl":"https://doi.org/10.1177/07487304261456978","url":null,"abstract":"","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261456978"},"PeriodicalIF":2.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204997","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}
Orsolya Kiss, Marie Gombert-Labedens, Alan Taitz, Fiona C Baker
{"title":"Menstrual Cycle Temperature Dynamics and Their Association With Conception: A Within- and Between-Person Analysis.","authors":"Orsolya Kiss, Marie Gombert-Labedens, Alan Taitz, Fiona C Baker","doi":"10.1177/07487304251409583","DOIUrl":"10.1177/07487304251409583","url":null,"abstract":"<p><p>Temperature regulation across the menstrual cycle follows predictable rhythmic changes driven by reproductive hormones, particularly the thermogenic effect of progesterone in the luteal phase. While basal body temperature has long been used to identify ovulatory cycles, it is less clear how detailed features of the temperature rhythm, including its strength (amplitude) and timing (phase), relate to the likelihood of conception, especially when accounting for individual variability in cycle length and age. Here, we aimed to examine associations between menstrual temperature rhythm characteristics and conception likelihood using both between-person and within-person analyses. We analyzed daily temperature data from 423 women (19-40 years) contributing 4682 cycles, who were participants in a multi-country study about fertility conducted between 1992 and 1996 (\"Fertili\" dataset). Cycle-level temperature fluctuations were modeled using linear mixed-effects models (GLMMs) with cosine and sine terms scaled to each cycle's length, from which amplitude and phase parameters were derived. At the level of consecutive cycle-series (sessions), GLMMs assessed whether rhythm features, mean temperature, cycle length, cycle regularity, and age predicted conception. Within-person analyses compared pre-conceptive and non-conceptive cycles from the same individual, restricted to cycles with sexual intercourse during the fertile window. Temperature showed a robust oscillatory pattern across the menstrual cycle. At the session level, higher mean temperature was associated with greater conception likelihood in the pre-conceptive cycles, and phase in temperature rhythms tended to be beneficial, particularly in longer cycles. A 3-way interaction revealed that conception was most likely in cycles following shorter cycles (≤35 days) when temperature rhythms were both high in amplitude and well-timed in phase, whereas in longer cycles, rhythm timing appeared to play a larger role than amplitude alone. Within-person comparisons showed that larger temperature phase occurred more often in pre-conceptive cycles than in cycles not followed by conception. Both the magnitude and timing of menstrual temperature rhythms carry information about potential for conception beyond the detection of a post-ovulatory rise. Conception appears most likely when strong rhythmicity aligns optimally with the fertile window in typical length cycles.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"356-365"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052156","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>dlmoR</i>: An Open-Source R Package for the Dim-Light Melatonin Onset (DLMO) Hockey-Stick Method.","authors":"Salma M Thalji, Manuel Spitschan","doi":"10.1177/07487304251389994","DOIUrl":"10.1177/07487304251389994","url":null,"abstract":"<p><p>The dim-light melatonin onset (DLMO) is a commonly used circadian marker indicating the start time of evening melatonin synthesis in humans. Several quantitative techniques have been developed to determine DLMO from melatonin time series, including fixed- or variable-threshold techniques and the hockey-stick method developed by Danilenko et al (2014). Here, we introduce <i>dlmoR</i>, an open-source (MIT License) implementation of the hockey-stick method written in R. Our clean-room implementation follows the original algorithm description, supported by iterative validation against the existing binary executable. We benchmarked <i>dlmoR</i> on 112 melatonin time series data sets from two independent studies and found high agreement with the reference implementation: mean discrepancies were <math><mrow><mo>-</mo><mn>1</mn><mo>.</mo><mn>482</mn><mo>±</mo><mn>21</mn><mo>.</mo><mn>7</mn></mrow></math> min for the Heinrichs and Spitschan (2025) data set and <math><mrow><mn>1</mn><mo>.</mo><mn>165</mn><mo>±</mo><mn>28</mn><mo>.</mo><mn>5</mn></mrow></math> min for the Blume et al. (2024) data set, with circular correlation coefficients of 0.964 and 0.986, respectively. Paired <i>t</i>-tests (<math><mrow><mi>p</mi><mo>></mo><mn>0</mn><mo>.</mo><mn>05</mn></mrow></math>) indicated no systematic difference or bias between methods. Beyond reproducing the hockey-stick algorithm, <i>dlmoR</i> adds capabilities absent from the original executable, including interactive visual diagnostics and bootstrapped confidence intervals, offering qualitative and quantitative views of estimation uncertainty. It supports programmatic, reproducible analysis of melatonin profiles, including batch processing and parameter manipulation. Leveraging this flexibility, we evaluated the sensitivity of the hockey-stick algorithm to controlled changes in sampling schedules, threshold levels, data completeness, and noise. Moderate changes, such as small timing jitter, limited data loss, or modest threshold shifts, kept estimates stable within ±10 min, whereas pronounced alterations to sampling schedules, large multi-point deletions, or substantial threshold changes delayed estimates by over 40 min or prevented estimation. This analysis reveals fundamental limitations in the algorithm's internal mechanics, particularly in how it identifies the onset window and models the melatonin rise, and underscores the need for new uncertainty-aware approaches to DLMO estimation.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"301-323"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180064","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}
Raquel Galan, Gemma Castaño-Vinyals, Elisa Rubio-Garcia, Rubén Lopez-Aladid, Ana Espinosa, Kyriaki Papantoniou, Mariona Bustamante, Parveen Bhatti, Camille Lassale, Cristina Márquez, Ana Alfaro, Climent Casals-Pascual, Manolis Kogevinas, Barbara N Harding
{"title":"The Effect of Night Shift Work on the Gut Microbiome Diversity: The EXPONIT Study.","authors":"Raquel Galan, Gemma Castaño-Vinyals, Elisa Rubio-Garcia, Rubén Lopez-Aladid, Ana Espinosa, Kyriaki Papantoniou, Mariona Bustamante, Parveen Bhatti, Camille Lassale, Cristina Márquez, Ana Alfaro, Climent Casals-Pascual, Manolis Kogevinas, Barbara N Harding","doi":"10.1177/07487304251408152","DOIUrl":"10.1177/07487304251408152","url":null,"abstract":"<p><p>Night shift work may alter the gut microbiome through mechanisms involving circadian misalignment, sleep disturbance, and changes in dietary behavior. However, existing studies on this topic have been limited in sample size and scope. We analyzed stool samples from 240 participants (mean age 42 years, 80% women), of whom 53% were night shift workers. Gut microbiota composition was assessed using 16S rRNA gene sequencing to derive measures of relative abundance, alpha diversity, and beta diversity. Associations between night shift work and microbial composition and alpha diversity were examined using generalized linear models with a Gamma distribution and log link for alpha diversity and Aitchison distance for beta diversity. The effect of night shift work on microbiome genera abundance was evaluated using MaAsLin2 analysis. Models were adjusted for age, sex, and educational level. We also explored potential interactions by sleep quality, diet, and chronotype. There were no overall significant differences in alpha or beta diversity between day and night shift workers, but participants with less than 15 years of night work showed slightly higher Abundance-based Coverage Estimator than non-night workers. Interaction with sleep quality was observed (<i>p</i>-value: 0.01). Among participants with poor sleep quality, night shift work was significantly associated with lower alpha diversity (exp(β): 0.93, 95% CI: 0.87-0.99, <i>p</i>-value: 0.02). Day shift workers showed high relative abundance of <i>Ruminococcus</i>, while night shift workers had increased <i>Escherichia-Shigella</i> at descriptive level, none of which remain statistically significant after false discovery rate. Our findings indicate that night shift work may influence gut microbiome diversity, especially in individuals with poor sleep quality. Future research should explore the long-term health consequences of these microbial changes.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"344-355"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046722","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}
Riya Mirchandaney, Delainey L Wescott, Margaret C Kuzemchak, Allysa D Quick, Kathryn Guo, Duncan B Clark, Daniel J Buysse, Greg J Siegle, Meredith L Wallace, Brant P Hasler
{"title":"Circadian Timing Moderates Diurnal Positive Affect Rhythms in Adolescents.","authors":"Riya Mirchandaney, Delainey L Wescott, Margaret C Kuzemchak, Allysa D Quick, Kathryn Guo, Duncan B Clark, Daniel J Buysse, Greg J Siegle, Meredith L Wallace, Brant P Hasler","doi":"10.1177/07487304251408573","DOIUrl":"10.1177/07487304251408573","url":null,"abstract":"<p><p>In adult samples, tightly-controlled laboratory studies indicate the presence of circadian rhythms in positive (and negative) affect. Naturalistic studies also suggest the presence of diurnal positive affect rhythms in adults, the characteristics (acrophase, mesor, and amplitude) of which vary by self-report circadian preference-greater evening preference is associated with later acrophase, lower mesor, and lower amplitude in positive affect. We examined the extent to which diurnal affect rhythms are associated with 4 different measures of circadian timing, including dim light melatonin onset, in a sample of high-school adolescents who reported at least one drink of alcohol in their lifetime (<i>N</i> = 126, 17.3 ± 0.87 years, 55.6% female). Cosinor models found support for robust diurnal rhythms in positive, but not negative, affect. The overall modeled positive affect rhythm had an acrophase at 3:39 PM, a mesor of 9.77, and an amplitude of 1.61. Later circadian timing was associated with later acrophase in positive affect rhythms across the following measures: circadian preference (3:00 PM vs 4:20 PM, <i>p</i> < .001), chronotype (3:20 PM vs 4:11 PM, <i>p</i> = .014), and actigraphy-based midsleep (3:08 PM vs 4:16 PM, <i>p</i> = .014). We did not find significant associations between circadian phase (dim light melatonin onset) and positive affect rhythms. We also explored weekday-weekend differences in positive affect rhythms, finding significantly higher mesor (9.71 vs 9.99, <i>p</i> = .004) and lower amplitude (1.69 vs 1.26, <i>p</i> = .008) on the weekends than weekdays. In sum, compared to their peers, adolescents with later sleep and circadian timing experience a delayed peak in positive affect during the day, which may have consequences for behavioral activation and depressed mood. These findings underscore the importance of considering the role of sleep and circadian factors in affective processes during adolescence.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"366-379"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099923","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}