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}
Pub Date : 2024-07-02DOI: 10.1038/s44323-024-00002-4
Shingo Gibo, Yoshifumi Yamaguchi, Elena O. Gracheva, Sviatoslav N. Bagriantsev, Isao T. Tokuda, Gen Kurosawa
Hibernation allows mammals to endure harsh seasons by reducing their basal metabolism and body temperature (Tb) to minimize energy expenditure. During hibernation in small animals such as Syrian hamsters and 13-lined ground squirrels, Tb decreases to an ambient level ( < 5 °C) and remains constant for days to weeks in a physiological condition termed deep torpor. Torpor is interrupted by periods of arousal, during which Tb recovers to a euthermic level (approximately 37 °C), and these torpor–arousal cycles are repeated multiple times during hibernation. However, little is known about the mechanisms governing Tb fluctuations during hibernation. In this study, we employed an unbiased model selection approach to Tb data and revealed that a model incorporating frequency modulation quantitatively reproduced Tb fluctuation during hibernation in Syrian hamsters. We found that an unexpectedly long period of 120–430 days modulates a shorter period of several days. In addition, the aforementioned model reproduced Tb fluctuation in 13-lined ground squirrels, which can undergo repeated hibernation according to intrinsic circannual rhythms in constant laboratory conditions. This is the first quantitative study to demonstrate the concerted action of two endogenous periods, one lasting a few days and the other lasting a year, in the torpor–arousal cycles of distinct mammalian hibernators. We anticipate that our theoretical analysis of Tb fluctuation will be a starting point for quantitative comparisons of hibernation patterns across various hibernating species. Furthermore, quantification of Tb data using models will foster our understanding of the molecular mechanisms of hibernation by revealing the biological processes operating within these periods.
{"title":"Frequency-modulated timer regulates torpor–arousal cycles during hibernation in distinct small mammalian hibernators","authors":"Shingo Gibo, Yoshifumi Yamaguchi, Elena O. Gracheva, Sviatoslav N. Bagriantsev, Isao T. Tokuda, Gen Kurosawa","doi":"10.1038/s44323-024-00002-4","DOIUrl":"10.1038/s44323-024-00002-4","url":null,"abstract":"Hibernation allows mammals to endure harsh seasons by reducing their basal metabolism and body temperature (Tb) to minimize energy expenditure. During hibernation in small animals such as Syrian hamsters and 13-lined ground squirrels, Tb decreases to an ambient level ( < 5 °C) and remains constant for days to weeks in a physiological condition termed deep torpor. Torpor is interrupted by periods of arousal, during which Tb recovers to a euthermic level (approximately 37 °C), and these torpor–arousal cycles are repeated multiple times during hibernation. However, little is known about the mechanisms governing Tb fluctuations during hibernation. In this study, we employed an unbiased model selection approach to Tb data and revealed that a model incorporating frequency modulation quantitatively reproduced Tb fluctuation during hibernation in Syrian hamsters. We found that an unexpectedly long period of 120–430 days modulates a shorter period of several days. In addition, the aforementioned model reproduced Tb fluctuation in 13-lined ground squirrels, which can undergo repeated hibernation according to intrinsic circannual rhythms in constant laboratory conditions. This is the first quantitative study to demonstrate the concerted action of two endogenous periods, one lasting a few days and the other lasting a year, in the torpor–arousal cycles of distinct mammalian hibernators. We anticipate that our theoretical analysis of Tb fluctuation will be a starting point for quantitative comparisons of hibernation patterns across various hibernating species. Furthermore, quantification of Tb data using models will foster our understanding of the molecular mechanisms of hibernation by revealing the biological processes operating within these periods.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00002-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500488","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 : 2024-06-19DOI: 10.1038/s44323-024-00003-3
Mostafa Mortada, Lu Xiong, Paloma Mas
The plant circadian clock regulates daily and seasonal rhythms of key biological processes, from growth and development to metabolism and physiology. Recent circadian research is moving beyond whole plants to specific cells, tissues, and organs. In this review, we summarize our understanding of circadian organization in plants, with a focus on communication and synchronization between circadian oscillators, also known as circadian coupling. We describe the different strengths of intercellular coupling and highlight recent advances supporting interorgan communication. Experimental and mathematical evidence suggests that plants precisely balance both the circadian autonomy of individual cellular clocks and synchronization between neighboring cells and across distal tissues and organs. This complex organization has probably evolved to optimize the specific functions of each cell type, tissue, or organ while sustaining global circadian coordination. Circadian coordination may be essential for proper regulation of growth, development, and responses to specific environmental conditions.
{"title":"Dissecting the complexity of local and systemic circadian communication in plants","authors":"Mostafa Mortada, Lu Xiong, Paloma Mas","doi":"10.1038/s44323-024-00003-3","DOIUrl":"10.1038/s44323-024-00003-3","url":null,"abstract":"The plant circadian clock regulates daily and seasonal rhythms of key biological processes, from growth and development to metabolism and physiology. Recent circadian research is moving beyond whole plants to specific cells, tissues, and organs. In this review, we summarize our understanding of circadian organization in plants, with a focus on communication and synchronization between circadian oscillators, also known as circadian coupling. We describe the different strengths of intercellular coupling and highlight recent advances supporting interorgan communication. Experimental and mathematical evidence suggests that plants precisely balance both the circadian autonomy of individual cellular clocks and synchronization between neighboring cells and across distal tissues and organs. This complex organization has probably evolved to optimize the specific functions of each cell type, tissue, or organ while sustaining global circadian coordination. Circadian coordination may be essential for proper regulation of growth, development, and responses to specific environmental conditions.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00003-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435706","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 : 2024-06-19DOI: 10.1038/s44323-024-00001-5
Aya Honma, Marina Nohara, Sato Honma, Akihiro Homma
This study aims to evaluate the association between sleep-wake rhythm regularity and continuous positive airway pressure (CPAP) adherence. We retrospectively analyzed sleep-wake rhythms with activity monitoring and CPAP adherence among obstructive sleep apnea (OSA) patients newly diagnosed and introduced to CPAP therapy at the Sapporo Hanazono Hospital from January 2018 to June 2022. Among a total of 45 patients, 10 withdrew from CPAP therapy within a year. Nineteen were classified into the good-adherence and 16 into the poor-adherence group. No significant differences were detected among the groups in apnea-hypopnea index (AHI), sleep efficiency, or subjective sleep quality, but a difference was observed in sleep latency, with the CPAP withdrawal group showing higher variability in sleep onset and lower regularity and/or amplitude in circadian behavior activity rhythm than the good-adherence group. Our results suggest that irregularities, particularly in sleep onset, and damped sleep-wake rhythm can be risk factors for CPAP withdrawal.
{"title":"The association between irregularity in sleep-wake rhythm and CPAP adherence","authors":"Aya Honma, Marina Nohara, Sato Honma, Akihiro Homma","doi":"10.1038/s44323-024-00001-5","DOIUrl":"10.1038/s44323-024-00001-5","url":null,"abstract":"This study aims to evaluate the association between sleep-wake rhythm regularity and continuous positive airway pressure (CPAP) adherence. We retrospectively analyzed sleep-wake rhythms with activity monitoring and CPAP adherence among obstructive sleep apnea (OSA) patients newly diagnosed and introduced to CPAP therapy at the Sapporo Hanazono Hospital from January 2018 to June 2022. Among a total of 45 patients, 10 withdrew from CPAP therapy within a year. Nineteen were classified into the good-adherence and 16 into the poor-adherence group. No significant differences were detected among the groups in apnea-hypopnea index (AHI), sleep efficiency, or subjective sleep quality, but a difference was observed in sleep latency, with the CPAP withdrawal group showing higher variability in sleep onset and lower regularity and/or amplitude in circadian behavior activity rhythm than the good-adherence group. Our results suggest that irregularities, particularly in sleep onset, and damped sleep-wake rhythm can be risk factors for CPAP withdrawal.","PeriodicalId":501704,"journal":{"name":"npj Biological Timing and Sleep","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44323-024-00001-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435711","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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