Varun Mandi, Haley Miller, Jeongkyung Lee, Young-Hwa Goo, Mousumi Moulik, Ke Ma, Antoni Paul, Vijay K Yechoor, Mariana G Figueiro
{"title":"Modulating light level patterns reduces rest/activity disruption associated with shiftwork.","authors":"Varun Mandi, Haley Miller, Jeongkyung Lee, Young-Hwa Goo, Mousumi Moulik, Ke Ma, Antoni Paul, Vijay K Yechoor, Mariana G Figueiro","doi":"10.1038/s44323-025-00043-3","DOIUrl":"10.1038/s44323-025-00043-3","url":null,"abstract":"<p><p>Long-term exposure to nonstandard work schedules can result in circadian misalignment, which has been linked to a series of maladies. To test whether modulating light patterns reduces shiftwork-induced rest/activity disruptions, 30 male C57BL/6 J mice individually housed in cages outfitted with running wheels were exposed to 6 simulated shiftwork light interventions. Mice experiencing high light levels during shiftwork exhibited a significant decrease in activity compared to low light levels during shiftwork and a conventional 12 L:12D condition, indicating circadian misalignment. In contrast, mice experiencing shiftwork in darkness combined with either modulated evening light pulses or circadian blind, vision-permissive light showed similar levels of rest/activity compared to a 12 L:12D condition, with phasor analysis indicating that their 24-h circadian rest/activity patterns were not misaligned. The results show that exposure to light that permits visibility but is below activation of the circadian system during shiftwork can prevent circadian misalignment.</p>","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":"2 1","pages":"27"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biological rhythms: Living your life, one half-day at a time.","authors":"Patrick Emery, Frédéric Gachon","doi":"10.1038/s44323-025-00037-1","DOIUrl":"10.1038/s44323-025-00037-1","url":null,"abstract":"<p><p>Circadian rhythms play a preeminent role in our life, organizing our physiology and behavior on a daily basis to resonate with our fluctuating environment. However, recent studies reveal that hundreds of mouse and human genes are expressed with a 12-h pattern. We take a close look at mammalian 12-h rhythms, their potential mechanisms and functions, and evidence linking them to circatidal rhythms, which enable marine animals to adapt to tides.</p>","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":"2 1","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The complexity and commonness of the two-process model of sleep regulation from a mathematical perspective.","authors":"Anne C Skeldon, Derk-Jan Dijk","doi":"10.1038/s44323-025-00039-z","DOIUrl":"10.1038/s44323-025-00039-z","url":null,"abstract":"<p><p>The two-process model (2pm) of sleep regulation is a conceptual framework and consists of mathematical equations. It shares similarities with models for cardiac, respiratory and neuronal rhythms and falls within the wider class of coupled oscillator models. The 2pm is related to neuronal mutual inhibition models of sleep-wake regulation. The mathematical structure of the 2pm, in which the sleep-wake cycle is entrained to the circadian pacemaker, explains sleep patterns in the absence of 24 h time cues, in different species and in early childhood. Extending the 2pm with a process describing the response of the circadian pacemaker to light creates a hierarchical entrainment system with feedback which permits quantitative modelling of the effect of self-selected light on sleep and circadian timing. The extended 2pm provides new interpretations of sleep phenotypes and provides quantitative predictions of effects of sleep and light interventions to support sleep and circadian alignment in individuals, including those with neurodegenerative disorders.</p>","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":"2 1","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chronic circadian disruption alters cardiac function and glucose regulation in mice.","authors":"Jenna E J Gearey, Melinda Wang, Michael C Antle","doi":"10.1038/s44323-025-00032-6","DOIUrl":"https://doi.org/10.1038/s44323-025-00032-6","url":null,"abstract":"<p><p>Cardiometabolic disease is a leading cause of death worldwide. One factor that may contribute to the risk, onset, and severity of symptoms is disrupted circadian rhythms. Our study uses two strains of mice to further elucidate this relationship: healthy controls, and a mouse model of insulin resistance with short freerunning periods (~ 22.75 h) and enlarged hearts, raised in either a 24-h or 22.75-h LD cycle. Through glucose and insulin tolerance tests, routine electrocardiograms from one to four months old, and histology, we reveal worse cardiometabolic health outcomes for mice gestated and housed in a mismatched LD cycle compared to those in an LD cycle that matches their endogenous rhythm. This was characterized by heightened blood glucose levels following a glucose or insulin bolus, altered electrophysiological parameters of the cardiac waveform, and increased cardiomyocyte size. Circadian disruption due to work/social schedules or circadian-related disorders in people is often confounded with other unhealthy lifestyles. The present study demonstrates that circadian disruption on its own can lead to adverse health states.</p>","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":"2 1","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matt Spick, Cheryl M Isherwood, Lee A Gethings, Christopher J Hughes, Matthew E Daly, Hana Hassanin, Daan R van der Veen, Debra J Skene, Jonathan D Johnston
{"title":"Challenges and opportunities for statistical power and biomarker identification arising from rhythmic variation in proteomics.","authors":"Matt Spick, Cheryl M Isherwood, Lee A Gethings, Christopher J Hughes, Matthew E Daly, Hana Hassanin, Daan R van der Veen, Debra J Skene, Jonathan D Johnston","doi":"10.1038/s44323-024-00020-2","DOIUrl":"10.1038/s44323-024-00020-2","url":null,"abstract":"<p><p>Time-of-day variation in the molecular profile of biofluids and tissues is a well-described phenomenon, but-especially for proteomics-is rarely considered in terms of the challenges this presents to reproducible biomarker identification. We provide a case study analysis of human circadian and ultradian rhythmicity in proteins, including in the complement and coagulation cascades and apolipoproteins, with PLG, CFAH, ZA2G and ITIH2 demonstrated as rhythmic for the first time. We also show that rhythmicity increases the risk of Type II errors due to the reduction in statistical power from increased variance, and that controlling for rhythmic time-of-day variation improves statistical power and reduces the chances of Type II errors. We recommend that best practice in proteomics study design should account for temporal variation and that time of sampling be reported as part of study metadata. These simple steps can mitigate against both false and missed discoveries, as well as improving reproducibility.</p>","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":"2 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joshua B Benoit, Joy Bose, Oluwaseun M Ajayi, Ashley Webster, Karl Grieshop, David Lewis, Hailie Talbott, Michal Polak
{"title":"Shifted levels of sleep and activity during the night as mechanisms underlying ectoparasite resistance.","authors":"Joshua B Benoit, Joy Bose, Oluwaseun M Ajayi, Ashley Webster, Karl Grieshop, David Lewis, Hailie Talbott, Michal Polak","doi":"10.1038/s44323-025-00031-7","DOIUrl":"10.1038/s44323-025-00031-7","url":null,"abstract":"<p><p>Parasites harm host fitness and are pervasive agents of natural selection capable of driving the evolution of host resistance traits. Previously we demonstrated evolutionary responses to artificial selection for increasing behavioral immunity to <i>Gamasodes queenslandicus</i> mites for <i>Drosophila melanogaster</i>. Here, we report transcriptional shifts in metabolic processes due to selection for mite resistance. We also show decreased starvation resistance and increased use of nutrient reserves in flies from mite-resistant lines. Resistant lines exhibited increased activity, reduced sleep, and elevated oxygen consumption during the night. Using a panel of <i>D. melanogaster</i> lines exhibiting variable sleep durations, we found a positive correlation between mite resistance and reduced sleep. Restraining the activity of artificially selected mite-resistant flies during exposure to parasites reduced their resistance advantage relative to control flies. The results suggest that ectoparasite resistance in this system involves increased activity during the scotophase and metabolic gene expression at the expense of starvation resistance.</p>","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":"2 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S M Ragsdale, J M Radovich, I I Coiduras, W V McCall, S C Grant, C Lee, A Wilber
{"title":"Dual orexin receptor antagonists as promising therapeutics for Alzheimer's disease.","authors":"S M Ragsdale, J M Radovich, I I Coiduras, W V McCall, S C Grant, C Lee, A Wilber","doi":"10.1038/s44323-025-00025-5","DOIUrl":"10.1038/s44323-025-00025-5","url":null,"abstract":"<p><p>We examine the relationship between sleep, glymphatics and Alzheimer's disease (AD), and recent work questioning glymphatic clearance during sleep. We highlight a need for understanding glymphatic and/or other mechanism of clearance during sleep, and review glymphatic flow measurement methods. Further, we explore dual orexin receptor antagonists (DORAs) potential to mitigate AD sleep disturbances and enhance clearance. Further research could elucidate a linkage between DORAs, improved sleep and reducing AD pathophysiology.</p>","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":"2 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The cyanobacterial circadian clock.","authors":"Yong-Gang Chang, Andy LiWang","doi":"10.1038/s44323-025-00042-4","DOIUrl":"10.1038/s44323-025-00042-4","url":null,"abstract":"<p><p>This review summarizes recent advances in understanding the cyanobacterial circadian clock, emphasizing how the KaiA, KaiB, and KaiC proteins generate robust, temperature-compensated rhythms through ordered phosphorylation, conformational switching, and dynamic protein interactions. A comparative analysis of 30 KaiC structures under different states of phosphorylation and nucleotide binding is also presented. Together, these structural and mechanistic insights illuminate fundamental principles of biological timekeeping and evolutionary adaptations in these photosynthetic prokaryotes.</p>","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":"2 1","pages":"26"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Beyond vision: effects of light on the circadian clock and mood-related behaviours.","authors":"Dean Stewart, Urs Albrecht","doi":"10.1038/s44323-025-00029-1","DOIUrl":"https://doi.org/10.1038/s44323-025-00029-1","url":null,"abstract":"<p><p>Light is a crucial environmental factor that influences various aspects of life, including physiological and psychological processes. While light is well-known for its role in enabling humans and other animals to perceive their surroundings, its influence extends beyond vision. Importantly, light affects our internal time-keeping system, the circadian clock, which regulates daily rhythms of biochemical and physiological processes, ultimately impacting mood and behaviour. The 24-h availability of light can have profound effects on our well-being, both physically and mentally, as seen in cases of jet lag and shift work. This review summarizes the intricate relationships between light, the circadian clock, and mood-related behaviours, exploring the underlying mechanisms and its implications for health.</p>","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":"2 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bertold Mariën, Kathryn M Robinson, Manuela Jurca, Ingrid H Michelson, Naoki Takata, Iwanka Kozarewa, Pierre A Pin, Pär K Ingvarsson, Thomas Moritz, Cristian Ibáñez, Ove Nilsson, Stefan Jansson, Steve Penfield, Jun Yu, Maria E Eriksson
{"title":"Nature's Master of Ceremony: The <i>Populus</i> Circadian Clock as Orchestratot of Tree Growth and Phenology.","authors":"Bertold Mariën, Kathryn M Robinson, Manuela Jurca, Ingrid H Michelson, Naoki Takata, Iwanka Kozarewa, Pierre A Pin, Pär K Ingvarsson, Thomas Moritz, Cristian Ibáñez, Ove Nilsson, Stefan Jansson, Steve Penfield, Jun Yu, Maria E Eriksson","doi":"10.1038/s44323-025-00034-4","DOIUrl":"https://doi.org/10.1038/s44323-025-00034-4","url":null,"abstract":"<p><p>Understanding the timely regulation of plant growth and phenology is crucial for assessing a terrestrial ecosystem's productivity and carbon budget. The circadian clock, a system of genetic oscillators, acts as 'Master of Ceremony' during plant physiological processes. The mechanism is particularly elusive in trees despite its relevance. The primary and secondary tree growth, leaf senescence, bud set, and bud burst timing were investigated in 68 constructs transformed into <i>Populus</i> hybrids and compared with untransformed or transformed controls grown in natural or controlled conditions. The results were analyzed using generalized additive models with ordered-factor-smooth interaction smoothers. This meta-analysis shows that several genetic components are associated with the clock. Especially core clock-regulated genes affected tree growth and phenology in both controlled and field conditions. Our results highlight the importance of field trials and the potential of using the clock to generate trees with improved characteristics for sustainable silviculture (e.g., reprogrammed to new photoperiodic regimes and increased growth).</p>","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":"2 1","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}