Pub Date : 2024-11-01DOI: 10.1038/s44323-024-00012-2
Carlos C. Flores, Nickolas A. Pasetto, Hongyang Wang, Alexander G. Dimitrov, Jon F. Davis, Zhihua Jiang, Christopher J. Davis, Jason R. Gerstner
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.
睡眠和昼夜节律紊乱是许多疾病的并发症，会对许多健康状况产生负面影响，包括神经退行性疾病、代谢性疾病、癌症和各种神经系统疾病。将睡眠和昼夜节律紊乱与疾病易感性联系起来的遗传关联研究主要集中于基因突变（如单核苷酸多态性）导致的基因表达变化。睡眠和/或昼夜节律与交替多腺苷酸化（APA）之间的相互作用在很大程度上尚未被描述，尤其是在其他疾病的背景下。APA 通过利用同一基因的不同多腺苷酸化位点（PAS）产生转录本异构体，从而影响其 mRNA 的翻译、稳定性、定位和后续功能。在这里，我们发现了大鼠大脑在不同时间段、睡眠剥夺后和随后的恢复期所表达的独特 APA。根据这些数据，我们对这些与睡眠或睡眠时间相关的 PAS 与最近描述的与 APA 相关的人类脑部疾病易感基因进行了二次分析。
{"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}
Pub Date : 2024-11-01DOI: 10.1038/s44323-024-00011-3
Malena Mul Fedele, Leandro P. Casiraghi, Santiago A. Plano, Giannina Bellone, Diego A. Golombek, Daniel E. Vigo
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.
我们比较了一家大型石油公司的三种不同工作安排：1）两天 12 小时的白班，然后是连续两次 12 小时的夜班，接着是四天的无工作日（"2 x 2 x 4"）；2）连续四次 12 小时的白班和连续四次 12 小时的夜班，中间是四天的无工作日（"4 x 4 x 4"）；3）40 天内连续 12 小时白班的非轮换时间表（"固定 12 小时"）。我们测量了腕动仪、外周温度节律以及有关疲劳、嗜睡和心理情感特征的主观自我报告。2 x 2 x 4 "时间表导致睡眠规律性降低、昼夜节律紊乱加剧、失眠程度升高、疲劳影响增加、警觉性降低，以及与昼间工作后夜间睡眠时间增加有关的抑郁症状加剧。我们的研究结果表明，健康和安全因采用的时间表类型而异。
{"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}
Pub Date : 2024-11-01DOI: 10.1038/s44323-024-00014-0
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
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.
{"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}
Pub Date : 2024-11-01DOI: 10.1038/s44323-024-00013-1
Pureum Kim, Nicholas Garner, Annaleis Tatkovic, Rex Parsons, Prasad Chunduri, Jana Vukovic, Michael Piper, Martina Pfeffer, Marco Weiergräber, Henrik Oster, Oliver Rawashdeh
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.
{"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}
Pub Date : 2024-10-01DOI: 10.1038/s44323-024-00010-4
Manuel Spitschan, Laura Kervezee, Renske Lok, Elise McGlashan, Raymond P. Najjar
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.
{"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}
Pub Date : 2024-10-01DOI: 10.1038/s44323-024-00009-x
Bryan R. Alava, Andrew R. Morris, Andrew C. Liu, Jose F. Abisambra, Karyn A. Esser
Sleep timing and quantity disturbances persist in tauopathy patients. This has been studied in transgenic models of primary tau neuropathology using traditional electroencephalograms (EEGs) and more recently, the PiezoSleep Mouse Behavioral Tracking System. Here, we generated a primary tauopathy model using an intracerebroventricular injection of human mutant hSyn-P301L-tau, using adeno-associated virus of serotype 8 (AAV8). We discovered distinctions in sleep architecture with altered quantity and timing in AAV8-P301L tau expressing mice of both sexes using the noninvasive PiezoSleep System. The AAV8-P301L tau mice exhibit striking age-related increases in sleep duration specifically at the active phase onset, suggesting a critical and sensitive time-of-day for tauopathy related sleep disturbances to occur. Since our findings show sleep behavior changes at specific transitional periods of the day, tau neuropathology may impact normal diurnal variation in biological processes, which should be explored using the AAV8-P301L tauopathy model.
tau蛋白病患者的睡眠时间和数量障碍持续存在。利用传统脑电图（EEG）和最近的压电睡眠小鼠行为跟踪系统（PiezoSleep Mouse Behavioral Tracking System）在原发性tau神经病理的转基因模型中对此进行了研究。在这里，我们利用 8 号血清型腺相关病毒（AAV8），通过脑室内注射人类突变体 hSyn-P301L-tau，建立了原发性 tau 病模型。我们利用无创压电睡眠系统（PiezoSleep System）发现，在表达 AAV8-P301L tau 的雌雄小鼠中，睡眠结构的数量和时间都发生了改变。AAV8-P301L tau小鼠的睡眠持续时间与年龄相关，特别是在活跃期开始时显著增加，这表明与tauopathy相关的睡眠障碍发生在一天中的一个关键而敏感的时间段。由于我们的研究结果表明睡眠行为在一天中特定的过渡时期会发生变化，因此tau神经病变可能会影响生物过程的正常昼夜变化，这一点应使用AAV8-P301L tau病模型进行探索。
{"title":"AAV8-P301L tau expression confers age-related disruptions in sleep quantity and timing","authors":"Bryan R. Alava, Andrew R. Morris, Andrew C. Liu, Jose F. Abisambra, Karyn A. Esser","doi":"10.1038/s44323-024-00009-x","DOIUrl":"10.1038/s44323-024-00009-x","url":null,"abstract":"Sleep timing and quantity disturbances persist in tauopathy patients. This has been studied in transgenic models of primary tau neuropathology using traditional electroencephalograms (EEGs) and more recently, the PiezoSleep Mouse Behavioral Tracking System. Here, we generated a primary tauopathy model using an intracerebroventricular injection of human mutant hSyn-P301L-tau, using adeno-associated virus of serotype 8 (AAV8). We discovered distinctions in sleep architecture with altered quantity and timing in AAV8-P301L tau expressing mice of both sexes using the noninvasive PiezoSleep System. The AAV8-P301L tau mice exhibit striking age-related increases in sleep duration specifically at the active phase onset, suggesting a critical and sensitive time-of-day for tauopathy related sleep disturbances to occur. Since our findings show sleep behavior changes at specific transitional periods of the day, tau neuropathology may impact normal diurnal variation in biological processes, which should be explored using the AAV8-P301L tauopathy model.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00009-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360083","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}
Pub Date : 2024-10-01DOI: 10.1038/s44323-024-00008-y
Emerson M. Wickwire, Jacob Collen, Vincent F. Capaldi II, Zhiwei Zhao, Scott G. Williams, Connie L. Thomas, Samson Z. Assefa, Jennifer S. Albrecht, Shuo Chen
This study employed remote monitoring/ecological momentary assessment methods to test the hypothesis that prior-night sleep is associated with next-day symptoms. Military personnel with sleep problems (N = 270) completed daily sleep diaries and twice-daily symptom surveys via smartphone and wore a commercial wearable for ten days. In lagged analyses controlling for age and sex, prior-night sleep was robustly associated with next-day symptoms. Findings support remote approaches to assess sleep and next-day symptoms.
{"title":"Prior-night sleep predicts next-day symptoms over ten days among military personnel with sleep problems","authors":"Emerson M. Wickwire, Jacob Collen, Vincent F. Capaldi II, Zhiwei Zhao, Scott G. Williams, Connie L. Thomas, Samson Z. Assefa, Jennifer S. Albrecht, Shuo Chen","doi":"10.1038/s44323-024-00008-y","DOIUrl":"10.1038/s44323-024-00008-y","url":null,"abstract":"This study employed remote monitoring/ecological momentary assessment methods to test the hypothesis that prior-night sleep is associated with next-day symptoms. Military personnel with sleep problems (N = 270) completed daily sleep diaries and twice-daily symptom surveys via smartphone and wore a commercial wearable for ten days. In lagged analyses controlling for age and sex, prior-night sleep was robustly associated with next-day symptoms. Findings support remote approaches to assess sleep and next-day symptoms.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00008-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360084","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}
Pub Date : 2024-09-09DOI: 10.1038/s44323-024-00007-z
Daniel P. Cardinali, Daniel E. Vigo
A circadian disruption, manifested by disturbed sleep and low-grade inflammation, is commonly seen in cardiovascular diseases (CVDs). The decline in plasma melatonin, which is a conserved phylogenetic molecule across all known aerobic creatures, is also a common feature in CVDs. The daily evening pineal melatonin surge synchronizes both the central pacemaker located in the hypothalamic suprachiasmatic nuclei and myriads of cellular clocks in the periphery (“chronobiotic effect”). Melatonin also has cytoprotective properties, acting primarily not only as an antioxidant by buffering free radicals but also by regulating inflammation. In CVDs, exogenous melatonin administration decreases nocturnal hypertension, improves systolic and diastolic blood pressure, reduces the pulsatility index in the internal carotid artery, decreases platelet aggregation, and reduces serum catecholamine levels. Melatonin evokes an increase in parasympathetic activity in the heart. Allometric calculations based on animal research show that melatonin’s cytoprotective benefits in CVDs may require high doses to be fully manifested (in the 100–200 mg/day range). If melatonin is expected to improve health in CVDs, the low doses currently used in clinical trials (i.e., 2–10 mg) are presumably insufficient.
{"title":"Chronobiotic and cytoprotective activity of melatonin in the cardiovascular system. Doses matter","authors":"Daniel P. Cardinali, Daniel E. Vigo","doi":"10.1038/s44323-024-00007-z","DOIUrl":"10.1038/s44323-024-00007-z","url":null,"abstract":"A circadian disruption, manifested by disturbed sleep and low-grade inflammation, is commonly seen in cardiovascular diseases (CVDs). The decline in plasma melatonin, which is a conserved phylogenetic molecule across all known aerobic creatures, is also a common feature in CVDs. The daily evening pineal melatonin surge synchronizes both the central pacemaker located in the hypothalamic suprachiasmatic nuclei and myriads of cellular clocks in the periphery (“chronobiotic effect”). Melatonin also has cytoprotective properties, acting primarily not only as an antioxidant by buffering free radicals but also by regulating inflammation. In CVDs, exogenous melatonin administration decreases nocturnal hypertension, improves systolic and diastolic blood pressure, reduces the pulsatility index in the internal carotid artery, decreases platelet aggregation, and reduces serum catecholamine levels. Melatonin evokes an increase in parasympathetic activity in the heart. Allometric calculations based on animal research show that melatonin’s cytoprotective benefits in CVDs may require high doses to be fully manifested (in the 100–200 mg/day range). If melatonin is expected to improve health in CVDs, the low doses currently used in clinical trials (i.e., 2–10 mg) are presumably insufficient.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00007-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160304","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}
Pub Date : 2024-09-02DOI: 10.1038/s44323-024-00006-0
Olivia J. P. Fraser, Samantha J. Cargill, Steven H. Spoel, Gerben van Ooijen
The rotation of Earth creates a cycle of day and night, leading to predictable changes in environmental conditions. The circadian clock synchronizes an organism with these environmental changes and alters their physiology in anticipation. Prediction of the probable timing of pathogen infection enables plants to prime their immune system without wasting resources or sacrificing growth. Here, we explore the relationship between the immune hormone salicylic acid (SA), and the circadian clock in Arabidopsis. We found that SA altered circadian rhythmicity through the SA receptor and master transcriptional coactivator, NPR1. Reciprocally, the circadian clock gates SA-induced transcript levels of NPR1-dependent immune genes. Furthermore, the clock gene CCA1 is essential for SA-induced immunity to the major bacterial plant pathogen Pseudomonas syringae. These results build upon existing studies of the relationship between the circadian clock and SA signalling and how interactions between these systems produce an effective immune response. Understanding how and why the immune response in plants is linked to the circadian clock is crucial in working towards improved crop productivity.
地球的自转形成了昼夜循环，导致环境条件发生可预测的变化。昼夜节律使生物体与这些环境变化同步，并根据预期改变其生理机能。预测病原体感染的可能时间能让植物在不浪费资源或牺牲生长的情况下启动免疫系统。在这里，我们探讨了免疫激素水杨酸（SA）与拟南芥昼夜节律时钟之间的关系。我们发现，水杨酸通过水杨酸受体和主转录辅激活因子 NPR1 改变了昼夜节律性。与此相对应，昼夜节律钟会控制 SA 诱导的 NPR1 依赖性免疫基因的转录水平。此外，时钟基因 CCA1 对于 SA 诱导的对主要细菌性植物病原体丁香假单胞菌的免疫至关重要。这些结果建立在对昼夜节律时钟和 SA 信号之间的关系以及这些系统之间的相互作用如何产生有效免疫反应的现有研究基础之上。了解植物的免疫反应如何以及为什么与昼夜节律时钟有关，对于提高作物产量至关重要。
{"title":"Crosstalk between salicylic acid signalling and the circadian clock promotes an effective immune response in plants","authors":"Olivia J. P. Fraser, Samantha J. Cargill, Steven H. Spoel, Gerben van Ooijen","doi":"10.1038/s44323-024-00006-0","DOIUrl":"10.1038/s44323-024-00006-0","url":null,"abstract":"The rotation of Earth creates a cycle of day and night, leading to predictable changes in environmental conditions. The circadian clock synchronizes an organism with these environmental changes and alters their physiology in anticipation. Prediction of the probable timing of pathogen infection enables plants to prime their immune system without wasting resources or sacrificing growth. Here, we explore the relationship between the immune hormone salicylic acid (SA), and the circadian clock in Arabidopsis. We found that SA altered circadian rhythmicity through the SA receptor and master transcriptional coactivator, NPR1. Reciprocally, the circadian clock gates SA-induced transcript levels of NPR1-dependent immune genes. Furthermore, the clock gene CCA1 is essential for SA-induced immunity to the major bacterial plant pathogen Pseudomonas syringae. These results build upon existing studies of the relationship between the circadian clock and SA signalling and how interactions between these systems produce an effective immune response. Understanding how and why the immune response in plants is linked to the circadian clock is crucial in working towards improved crop productivity.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00006-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142117954","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}
Pub Date : 2024-08-09DOI: 10.1038/s44323-024-00005-1
Bokai Zhu, Silvia Liu, Natalie L. David, William Dion, Nandini K. Doshi, Lauren B. Siegel, Tânia Amorim, Rosemary E. Andrews, G. V. Naveen Kumar, Hanwen Li, Saad Irfan, Tristan Pesaresi, Ankit X. Sharma, Michelle Sun, Pouneh K. Fazeli, Matthew L. Steinhauser
Mice and many marine organisms exhibit ~12-h ultradian rhythms, however, direct evidence of ~12-h ultradian rhythms in humans is lacking. Here, we performed prospective, temporal transcriptome profiling of peripheral white blood cells from three healthy humans. All three participants independently exhibited robust ~12-h transcriptional rhythms in molecular programs involved in RNA and protein metabolism, with strong homology to circatidal gene programs previously identified in Cnidarian marine species.
{"title":"Evidence for ~12-h ultradian gene programs in humans","authors":"Bokai Zhu, Silvia Liu, Natalie L. David, William Dion, Nandini K. Doshi, Lauren B. Siegel, Tânia Amorim, Rosemary E. Andrews, G. V. Naveen Kumar, Hanwen Li, Saad Irfan, Tristan Pesaresi, Ankit X. Sharma, Michelle Sun, Pouneh K. Fazeli, Matthew L. Steinhauser","doi":"10.1038/s44323-024-00005-1","DOIUrl":"10.1038/s44323-024-00005-1","url":null,"abstract":"Mice and many marine organisms exhibit ~12-h ultradian rhythms, however, direct evidence of ~12-h ultradian rhythms in humans is lacking. Here, we performed prospective, temporal transcriptome profiling of peripheral white blood cells from three healthy humans. All three participants independently exhibited robust ~12-h transcriptional rhythms in molecular programs involved in RNA and protein metabolism, with strong homology to circatidal gene programs previously identified in Cnidarian marine species.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00005-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141922888","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}
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