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npj Biological Timing and Sleep最新文献

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Challenges and opportunities for statistical power and biomarker identification arising from rhythmic variation in proteomics.
Pub Date : 2025-01-01 Epub Date: 2025-01-25 DOI: 10.1038/s44323-024-00020-2
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

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.

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引用次数: 0
Reassessing the involvement of the CREB pathway in the circadian clock of Drosophila melanogaster 重新评估CREB通路在黑腹果蝇生物钟中的作用
Pub Date : 2024-12-04 DOI: 10.1038/s44323-024-00015-z
Anna Katharina Eick, Maite Ogueta, Ralf Stanewsky
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.
生物钟在地球上几乎所有生物中都无处不在,许多关键基因在物种之间高度保守。在哺乳动物视交叉上核中,cAMP反应元件结合蛋白(CREB)通路在将光输入传递给时钟基因的转录过程中起着至关重要的作用。果蝇也表达两种Creb蛋白,CrebA和CrebB,这两种蛋白与生物钟有关。例如,果蝇Creb被认为是神经元兴奋性和时钟基因转录之间的分子联系。在这项研究中,我们对具有时钟细胞特异性CrebA或CrebB突变的果蝇进行了昼夜行为和生物发光测定。令人惊讶的是,我们发现CrebA或CrebB的缺失都不会影响自由奔跑的运动行为、时钟神经元的节律周期振荡或光依赖同步。总之,我们的研究结果质疑了Creb通路在果蝇中保守的昼夜节律作用,并鼓励进一步研究阐明其在昆虫生物钟中的潜在功能。
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引用次数: 0
Light exposure differs by sex in the US, with females receiving less bright light 在美国,不同性别的人接受的光照不同,女性接受的光照较少
Pub Date : 2024-12-04 DOI: 10.1038/s44323-024-00016-y
Danielle A. Wallace
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.
光是昼夜节律系统的主要引导线索,并对健康有其他非昼夜节律的影响。光照模式的性别差异可能导致健康结果的性别差异。2011-2014年美国国家健康与营养调查(NHANES)调查了真实世界的光暴露(通过腕带ActiGraph GT3X+测量),其指标反映了在不同光水平下暴露的持续时间和时间。性别差异采用双样本t检验和线性回归模型进行检验。职业和体育活动相关的因素也被探讨作为影响因素使用线性回归模型调整年龄,季节,和种族/民族。分析纳入了11,314名NHANES参与者(年龄范围:3-80岁以上,52.2%为女性)。结果显示,男性在明亮光线下的时间比女性大约多52%,这种性别差异从童年就开始了。虽然还需要进一步的研究,但这些发现可能是由于室内和室外活动的性别差异。
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引用次数: 0
Sleep and diurnal alternative polyadenylation sites associated with human APA-linked brain disorders 与人类 APA 相关脑部疾病有关的睡眠和昼夜替代多聚腺苷酸位点
Pub Date : 2024-11-01 DOI: 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。
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引用次数: 0
Bridging the gap: examining circadian biology and fatigue alongside work schedules 缩小差距:研究昼夜节律生物学和疲劳与工作时间表的关系
Pub Date : 2024-11-01 DOI: 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。
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引用次数: 0
Insomnia and its treatments—trend analysis and publication profile of randomized clinical trials 失眠症及其治疗方法--随机临床试验的趋势分析和出版概况
Pub Date : 2024-11-01 DOI: 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.
本研究旨在描述失眠症随机对照试验(RCT)的出版概况。我们对有关成人非合并失眠症干预措施的 RCT 进行了系统回顾,共检索到 132 项 RCT,其中 58 项涉及药物治疗,71 项涉及非药物治疗,3 项涉及两种干预措施:其中58项涉及药物治疗,71项涉及非药物治疗,3项涉及两种干预措施。发表论文最多的治疗方法是数字CBT-I(dCBT-I)(35例)、面对面CBT-I(28例)和唑吡坦(22例)。关于 dCBT-I,发表年份的中位数是 2019 年,每年发表 1.13 ± 1.91 篇 RCT。关于唑吡坦,发表年份的中位数为 2008 年,每年发表的 RCT 为 0.71 ± 0.97 篇。关于面对面 CBT-I,中位发表年份为 2018 年,每年发表 0.90 ± 1.14 篇 RCT。现有的研究性临床试验大多是关于非药物干预的,尤其是 CBT-I(大多是在 2000 年代)和 dCBT-I(大多是在最近十年),尽管与药物干预相比,其方法学质量有所下降。这些数据表明,对失眠的非药物干预越来越受到重视。
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引用次数: 0
Melatonin’s role in the timing of sleep onset is conserved in nocturnal mice 褪黑激素在夜行性小鼠睡眠开始时间中的作用是一致的
Pub Date : 2024-11-01 DOI: 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.
在人类和夜间活动的啮齿类动物中,补充褪黑激素可加强非恢复性睡眠节律及其时间调整。值得注意的是,虽然昼行性和夜行性(夜行性)哺乳动物的睡眠周期是相反的,但两者都在昼夜节律钟的控制下于夜间产生褪黑激素。外源性褪黑激素对睡眠和嗜睡的影响相对明确,但其在睡眠中的内源性作用,特别是在睡眠开始(SO)的时间上的作用,仍然鲜为人知。我们在夜间活动的小鼠身上发现,午夜睡眠发作的增加和午夜活动的减少与夜间褪黑激素信号传导有关。此外,我们还发现内源性褪黑激素通过降低唤醒到睡眠转换的阈值来调节睡眠时间。褪黑激素与睡眠时间之间的这种联系可以解释昼夜节律睡眠障碍中睡眠倾向增加以及夜间褪黑激素水平严重降低的患者长期失眠等现象。我们的研究结果表明,褪黑激素在睡眠中的作用在进化过程中得到了保留,从而有效地质疑了褪黑激素不能在夜间哺乳动物的睡眠调节中发挥主要作用的论点,因为夜间哺乳动物的主要活动阶段与褪黑激素的高水平相吻合。
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引用次数: 0
How stepping out helped us tune in: finding space and time to think as an early career researcher 走出如何帮助我们调整:作为一名早期职业研究人员,寻找思考的空间和时间
Pub Date : 2024-10-01 DOI: 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.
从博士后到青年教师的转变令人兴奋,同时也具有独特的挑战性。一方面,博士后可以获得更多的创造自由,并有机会成长为一名独立的科学家。另一方面,随之而来的是越来越多的行政责任、孤独感和工作压力。结果是,在这种环境下,留给创造性思维和反思的时间非常有限。在这里,我们将描述如何通过参加一个让我们跳出常规、一起工作的项目来帮助我们变得更加独立,并重新获得思考的时间。
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引用次数: 0
AAV8-P301L tau expression confers age-related disruptions in sleep quantity and timing AAV8-P301L tau表达会导致与年龄有关的睡眠数量和时间紊乱
Pub Date : 2024-10-01 DOI: 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,&nbsp;Andrew R. Morris,&nbsp;Andrew C. Liu,&nbsp;Jose F. Abisambra,&nbsp;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}
引用次数: 0
Prior-night sleep predicts next-day symptoms over ten days among military personnel with sleep problems 前一晚的睡眠可预测有睡眠问题的军人在十天内第二天出现的症状
Pub Date : 2024-10-01 DOI: 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.
本研究采用远程监控/生态瞬间评估方法来验证前一天晚上的睡眠与第二天症状相关的假设。有睡眠问题的军人(270 人)通过智能手机完成每日睡眠日记和每日两次症状调查,并佩戴商用可穿戴设备十天。在控制年龄和性别的滞后分析中,前一晚的睡眠与第二天的症状密切相关。研究结果支持远程评估睡眠和第二天症状的方法。
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引用次数: 0
期刊
npj Biological Timing and Sleep
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