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}
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":"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}
{"title":"Reassessing the involvement of the CREB pathway in the circadian clock of Drosophila melanogaster","authors":"Anna Katharina Eick, Maite Ogueta, Ralf Stanewsky","doi":"10.1038/s44323-024-00015-z","DOIUrl":"10.1038/s44323-024-00015-z","url":null,"abstract":"Circadian clocks are ubiquitous in almost all organisms on Earth and many key genes are highly conserved among species. In the mammalian suprachiasmatic nucleus, the cAMP response element binding protein (CREB) pathway is known to play a crucial role in conveying light-input to the transcription of clock genes. The fruit fly Drosophila melanogaster also expresses two Creb proteins, CrebA and CrebB, which have been associated with the circadian clock. For example, Drosophila Creb has been suggested to constitute a molecular link between neuronal excitability and clock gene transcription. In this study we subjected flies with clock cell specific CrebA or CrebB mutations to circadian behavioral and bioluminescence assays. Surprisingly, we found that neither loss of CrebA or CrebB did affect free-running locomotor behavior, rhythmic period oscillations in clock neurons, or light-dependent synchronization. In conclusion our findings question the conserved circadian role of the Creb pathway in Drosophila and encourage further studies to elucidate its potential function within insect circadian clocks.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00015-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762903","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":"Light exposure differs by sex in the US, with females receiving less bright light","authors":"Danielle A. Wallace","doi":"10.1038/s44323-024-00016-y","DOIUrl":"10.1038/s44323-024-00016-y","url":null,"abstract":"Light is the primary entraining cue for the circadian system and has other, non-circadian, effects on health. Sex differences in light exposure patterns could drive sex differences in health outcomes. Real-world light exposure (measured with wrist-worn ActiGraph GT3X+) was investigated in the 2011–2014 U.S.-based National Health and Nutrition Examination Survey (NHANES) with metrics reflecting duration in and timing of exposure at different light levels. Sex differences were tested using two-sample t-tests and linear regression models. Occupational and physical activity-related factors were also explored as contributing factors using linear regression models adjusted for age, season, and race/ethnicity. 11,314 NHANES participants (age range: 3–80+, 52.2% females) were included in the analysis. The results show males spending approximately 52% more time in bright light than females, with this sex difference beginning in childhood. While further research is needed, these findings may be due to sex differences in indoor vs. outdoor activities.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00016-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762913","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}
Carlos C. Flores, Nickolas A. Pasetto, Hongyang Wang, Alexander G. Dimitrov, Jon F. Davis, Zhihua Jiang, Christopher J. Davis, Jason R. Gerstner
{"title":"Sleep and diurnal alternative polyadenylation sites associated with human APA-linked brain disorders","authors":"Carlos C. Flores, Nickolas A. Pasetto, Hongyang Wang, Alexander G. Dimitrov, Jon F. Davis, Zhihua Jiang, Christopher J. Davis, Jason R. Gerstner","doi":"10.1038/s44323-024-00012-2","DOIUrl":"10.1038/s44323-024-00012-2","url":null,"abstract":"Disruption of sleep and circadian rhythms are a comorbid feature of many pathologies, and can negatively influence many health conditions, including neurodegenerative disease, metabolic illness, cancer, and various neurological disorders. Genetic association studies linking sleep and circadian disturbances with disease susceptibility have mainly focused on changes in gene expression due to mutations, such as single-nucleotide polymorphisms. The interaction between sleep and/or circadian rhythms with the use of Alternative Polyadenylation (APA) has been largely undescribed, particularly in the context of other disorders. APA generates transcript isoforms by utilizing various polyadenylation sites (PASs) from the same gene affecting its mRNA translation, stability, localization, and subsequent function. Here we identified unique APAs expressed in rat brain over time-of-day, immediately following sleep deprivation, and the subsequent recovery period. From these data, we performed a secondary analysis of these sleep- or time-of-day associated PASs with recently described APA-linked human brain disorder susceptibility genes.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00012-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566005","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}
Malena Mul Fedele, Leandro P. Casiraghi, Santiago A. Plano, Giannina Bellone, Diego A. Golombek, Daniel E. Vigo
{"title":"Bridging the gap: examining circadian biology and fatigue alongside work schedules","authors":"Malena Mul Fedele, Leandro P. Casiraghi, Santiago A. Plano, Giannina Bellone, Diego A. Golombek, Daniel E. Vigo","doi":"10.1038/s44323-024-00011-3","DOIUrl":"10.1038/s44323-024-00011-3","url":null,"abstract":"We compared three different work schedules in a large oil company: 1) two days of 12 h of daytime shifts followed by two consecutive 12 h night shifts, followed by four work-free days (“2 x 2 x 4”), 2) four consecutive 12 h daytime shifts and four consecutive 12 h night shifts, flanked by four work-free days (“4 x 4 x 4”), 3) a non-rotating schedule involving continuous 12 h daytime shifts during 40 days (“fixed 12 h”). We measured wrist-actigraphy, peripheral temperature rhythms, and subjective self-reports regarding fatigue, somnolence, and psycho-affective features. Sleep duration on the resting period was significantly less than the recommended 7 h. The “2 x 2 x 4” schedule resulted in decreased sleep regularity and increased circadian disruption, higher levels of insomnia, increased fatigue impact, lower alertness levels, and heightened symptoms of depression associated with more nocturnal sleep time after diurnal work. Our findings indicate that health and safety vary depending on the type of schedule employed.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00011-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566008","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}
Viviane Akemi Kakazu, Marcia Assis, Andrea Bacelar, Andréia Gomes Bezerra, Giovanna Lira Rosa Ciutti, Silvia Gonçalves Conway, José Carlos Fernandes Galduróz, Luciano F. Drager, Mariana Pery Khoury, Ingrid Porto Araújo Leite, Ygor de Matos Luciano, Dalva Poyares, Sergio Tufik, Gabriel Natan Pires
{"title":"Insomnia and its treatments—trend analysis and publication profile of randomized clinical trials","authors":"Viviane Akemi Kakazu, Marcia Assis, Andrea Bacelar, Andréia Gomes Bezerra, Giovanna Lira Rosa Ciutti, Silvia Gonçalves Conway, José Carlos Fernandes Galduróz, Luciano F. Drager, Mariana Pery Khoury, Ingrid Porto Araújo Leite, Ygor de Matos Luciano, Dalva Poyares, Sergio Tufik, Gabriel Natan Pires","doi":"10.1038/s44323-024-00014-0","DOIUrl":"10.1038/s44323-024-00014-0","url":null,"abstract":"This study aimed to describe the publication profile of randomized controlled trials (RCTs) for insomnia. A systematic review of RCTs regarding interventions for non-comorbid insomnia in adults retrieved 132 RCTs: 58 related to pharmacological treatments, 71 to non-pharmacological treatments, and 3 to both interventions. The treatments with the biggest publication profile were digital CBT-I (dCBT-I) (n = 35), in-person CBT-I (n = 28) and zolpidem (n = 22). Regarding dCBT-I, the median publication year is 2019, with 1.13 ± 1.91 RCTs published per year. Regarding zolpidem, the median publication year is 2008, with 0.71 ± 0.97 RCTs per year. Regarding in-person CBT-I, the median publication year is 2018, with 0.90 ± 1.14 RCTs per year. The majority of the available RCTs are on non-pharmacological interventions, particularly CBT-I (mostly in the 2000s) and dCBT-I (mostly in the last decade), although presenting a reduced methodological quality in comparison to pharmacological interventions. These data suggest an increasing focus on non-pharmacological interventions for insomnia.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00014-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566013","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}
Pureum Kim, Nicholas Garner, Annaleis Tatkovic, Rex Parsons, Prasad Chunduri, Jana Vukovic, Michael Piper, Martina Pfeffer, Marco Weiergräber, Henrik Oster, Oliver Rawashdeh
{"title":"Melatonin’s role in the timing of sleep onset is conserved in nocturnal mice","authors":"Pureum Kim, Nicholas Garner, Annaleis Tatkovic, Rex Parsons, Prasad Chunduri, Jana Vukovic, Michael Piper, Martina Pfeffer, Marco Weiergräber, Henrik Oster, Oliver Rawashdeh","doi":"10.1038/s44323-024-00013-1","DOIUrl":"10.1038/s44323-024-00013-1","url":null,"abstract":"Melatonin supplementation strengthens non‐restorative sleep rhythms and its temporal alignment in both humans and night-active rodents. Of note, although the sleep cycle is reversed in day-active and night-active (nocturnal) mammals, both, produce melatonin at night under the control of the circadian clock. The effects of exogenous melatonin on sleep and sleepiness are relatively clear, but its endogenous role in sleep, particularly, in timing sleep onset (SO), remains poorly understood. We show in nocturnal mice that the increases in mid-nighttime sleep episodes, and the mid-nighttime decline in activity, are coupled to nighttime melatonin signaling. Furthermore, we show that endogenous melatonin modulates SO by reducing the threshold for wake-to-sleep transitioning. Such link between melatonin and SO timing may explain phenomena such as increased sleep propensity in circadian rhythm sleep disorders and chronic insomnia in patients with severely reduced nocturnal melatonin levels. Our findings demonstrate that melatonin’s role in sleep is evolutionarily conserved, effectively challenging the argument that melatonin cannot play a major role in sleep regulation in nocturnal mammals, where the main activity phase coincides with high melatonin levels.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00013-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566009","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}
Manuel Spitschan, Laura Kervezee, Renske Lok, Elise McGlashan, Raymond P. Najjar
{"title":"How stepping out helped us tune in: finding space and time to think as an early career researcher","authors":"Manuel Spitschan, Laura Kervezee, Renske Lok, Elise McGlashan, Raymond P. Najjar","doi":"10.1038/s44323-024-00010-4","DOIUrl":"10.1038/s44323-024-00010-4","url":null,"abstract":"The transition from postdoc to junior faculty is exciting and uniquely challenging. On one hand, it allows for increased creative freedom and the opportunity to grow into an independent scientist. On the other hand, it comes with increasing administrative responsibilities, feelings of isolation, and high pressure to perform. The result is an environment that can leave very limited time for creative thinking and reflection. Here, we describe how participating in a program that allowed us to step out of our routine and work together helped us become more independent—and regain time to think.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00010-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360086","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}