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Circadian Disruption Impacts Fetal Development in Mice Using High-Frequency Ultrasound. 高频超声对小鼠胎儿发育的影响
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-20 eCollection Date: 2024-01-01 DOI: 10.5334/jcr.249
Samantha M Britz, Shay Nelson, Kylie M Earhart, James K Pru, Emily E Schmitt

The developmental origins of health and disease theory suggests that environmental exposures during early life, particularly during prenatal life, can greatly influence health status later in life. Irregular light-dark cycles, such as those experienced during shift work, result in the repeated disruption of circadian rhythms, which negatively impacts physiological and behavioral cycles. The purpose of our study was to assess parameters in the developing mouse embryo and fetus using high frequency ultrasound when exposed to circadian disruption. Pregnant female mice were subjected to a seven-hour advanced circadian disrupted protocol or remained on a normal 12/12 light-dark cycle throughout pregnancy. Significant differences were observed in placental length (p = 0.00016), placental thickness (p = 0.0332), and stomach diameter (p = 0.0186) at E14.5-18.5. These findings suggest that circadian disruption in pregnant dams, mimicking shift work, alters embryonic and fetal development in specific organs in utero.

健康和疾病理论的发育起源表明,生命早期,特别是产前生活期间的环境暴露可以极大地影响生命后期的健康状况。不规律的明暗周期,如轮班工作期间的经历,导致昼夜节律的反复中断,这对生理和行为周期产生负面影响。我们的研究目的是在暴露于昼夜节律中断时,使用高频超声评估发育中的小鼠胚胎和胎儿的参数。怀孕的雌性小鼠在怀孕期间接受提前7小时的昼夜节律中断方案,或保持正常的12/12光暗周期。妊娠14.5 ~ 18.5时,胎盘长度(p = 0.00016)、胎盘厚度(p = 0.0332)、胃直径(p = 0.0186)差异均有统计学意义。这些发现表明,模仿轮班工作的怀孕水坝的昼夜节律中断改变了子宫内特定器官的胚胎和胎儿发育。
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引用次数: 0
Circadian Temperature in Moderate to Severe Acute Stroke Patients. 中度至重度急性中风患者的昼夜温差。
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI: 10.5334/jcr.241
Jakob Ginsbak Notland, Helle K Iversen, Poul Jennum, Anders S West

Background: Stroke patients often present circadian disruption due to multiple causes e.g., primary disease, comorbidities, medication, immobilization, reduced daylight entrainment and sleep disturbances.

Objective: To investigate the circadian rhythm of temperature in forehead skin in patients with moderate to severe stroke admitted for rehabilitation.

Methods: A physiologic study in form of a secondary analysis of a former randomized study. In total 27 patients with moderate to severe stroke were included between May 1st 2014, and June 1st 2015. Circadian temperature was collected approx. seven days after admission at the acute stroke unit by a skin surface temperature probe as part of a Polysomnography (PSG) measurement.

Results: Temperature variations show no circadian rhythm (Type 3 tests of fixed effects by SAS, p = 0.1610). The median temperature variance did fluctuate, but not significantly, and the small changes in circadian temperature variance did not follow the normal temperature variance.

Conclusion: Patients with moderate to severe stroke show an abrogated circadian rhythm of temperature. There is an unmet need to understand the mechanisms for this, significance for stroke outcome and treatment.

背景:由于多种原因,如原发疾病、并发症、药物、固定、日照减少和睡眠障碍等,脑卒中患者通常会出现昼夜节律紊乱:脑卒中患者常常因多种原因导致昼夜节律紊乱,如原发疾病、并发症、药物、固定、日照减少和睡眠障碍等:研究中重度脑卒中康复患者前额皮肤温度的昼夜节律:方法:通过对之前一项随机研究的二次分析,进行生理学研究。2014年5月1日至2015年6月1日期间,共有27名中重度中风患者被纳入研究。作为多导睡眠图(PSG)测量的一部分,通过皮肤表面温度探头收集入院后七天左右的昼夜体温:结果:体温变化未显示昼夜节律(通过 SAS 进行固定效应的类型 3 检验,p = 0.1610)。中位数体温方差确实有波动,但并不明显,昼夜节律体温方差的微小变化并不遵循正常体温方差:结论:中重度脑卒中患者的体温昼夜节律减弱。结论:中重度脑卒中患者的体温昼夜节律失调,其机制、对脑卒中预后和治疗的意义尚待了解。
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引用次数: 0
Timely Questions Emerging in Chronobiology: The Circadian Clock Keeps on Ticking 时间生物学中出现的及时问题:昼夜节律钟滴答作响
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-02 DOI: 10.5334/jcr.237
Sangeeta Chawla, John S O'Neill, Marina I. Knight, Yuqing He, Lei Wang, Erik Maronde, Sergio Gil Rodríguez, Gerben van Ooijen, Eduardo Garbarino-Pico, Eva Wolf, O. Dkhissi-Benyahya, Anjoom Nikhat, Shaon Chakrabarti, Shawn D. Youngstedt, Natalie Zi-Ching Mak, Ignacio Provencio, Henrik Oster, Namni Goel, Mario Caba, Maria Oosthuizen, Giles E. Duffield, Christopher Chabot, Seth J. Davis
Chronobiology investigations have revealed much about cellular and physiological clockworks but we are far from having a complete mechanistic understanding of the physiological and ecological implications. Here we present some unresolved questions in circadian biology research as posed by the editorial staff and guest contributors to the Journal of Circadian Rhythms. This collection of ideas is not meant to be comprehensive but does reveal the breadth of our observations on emerging trends in chronobiology and circadian biology. It is amazing what could be achieved with various expected innovations in technologies, techniques, and mathematical tools that are being developed. We fully expect strengthening mechanistic work will be linked to health care and environmental understandings of circadian function. Now that most clock genes are known, linking these to physiological, metabolic, and developmental traits requires investigations from the single molecule to the terrestrial ecological scales. Real answers are expected for these questions over the next decade. Where are the circadian clocks at a cellular level? How are clocks coupled cellularly to generate organism level outcomes? How do communities of circadian organisms rhythmically interact with each other? In what way does the natural genetic variation in populations sculpt community behaviors? How will methods development for circadian research be used in disparate academic and commercial endeavors? These and other questions make it a very exciting time to be working as a chronobiologist.
昼夜节律生物学研究已经揭示了许多关于细胞和生理时钟的知识,但我们还远远没有从机制上完全理解其对生理和生态的影响。在此,我们介绍《昼夜节律杂志》的编辑人员和特约撰稿人在昼夜节律生物学研究中提出的一些尚未解决的问题。这些观点并不全面,但却反映了我们对时间生物学和昼夜节律生物学新趋势的广泛观察。通过正在开发的技术、工艺和数学工具的各种预期创新,我们可以取得令人惊叹的成就。我们完全可以预见,加强机制研究工作将与医疗保健和环境对昼夜节律功能的理解联系起来。现在,大多数时钟基因已经为人所知,要将这些基因与生理、新陈代谢和发育特征联系起来,就需要进行从单分子到陆地生态尺度的研究。这些问题有望在未来十年内找到真正的答案。细胞水平的昼夜节律钟在哪里?时钟如何通过细胞耦合产生生物体水平的结果?昼夜节律生物群落如何有节奏地相互影响?种群中的自然遗传变异如何影响群落行为?昼夜节律研究方法的开发将如何用于不同的学术和商业活动?这些问题以及其他问题使得现在成为一名昼夜节律生物学家非常令人兴奋。
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引用次数: 0
Reflections on Several Landmark Advances in Circadian Biology 对昼夜节律生物学若干里程碑式进展的思考
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-01 DOI: 10.5334/jcr.236
Sangeeta Chawla, Henrik Oster, Giles E. Duffield, Erik Maronde, Mario E Guido, Christopher Chabot, O. Dkhissi-Benyahya, Ignacio Provencio, Namni Goel, Shawn D. Youngstedt, Natalie Zi-Ching Mak, Mario Caba, Anjoom Nikhat, Shaon Chakrabarti, Lei Wang, Seth J. Davis
Circadian Biology intersects with diverse scientific domains, intricately woven into the fabric of organismal physiology and behavior. The rhythmic orchestration of life by the circadian clock serves as a focal point for researchers across disciplines. This retrospective examination delves into several of the scientific milestones that have fundamentally shaped our contemporary understanding of circadian rhythms. From deciphering the complexities of clock genes at a cellular level to exploring the nuances of coupled oscillators in whole organism responses to stimuli. The field has undergone significant evolution lately guided by genetics approaches. Our exploration here considers key moments in the circadian-research landscape, elucidating the trajectory of this discipline with a keen eye on scientific advancements and paradigm shifts.
昼夜节律生物学与不同的科学领域相互交叉,错综复杂地交织在生物体生理学和行为学的结构之中。昼夜节律钟对生命节奏的协调是各学科研究人员关注的焦点。这篇回顾性文章深入探讨了从根本上影响我们当代对昼夜节律认识的几个科学里程碑。从破译细胞水平时钟基因的复杂性,到探索整个生物体对刺激反应中耦合振荡器的细微差别。这一领域在遗传学方法的指导下经历了重大演变。我们在此探讨了昼夜节律研究领域的关键时刻,通过对科学进步和范式转变的敏锐观察,阐明了这一学科的发展轨迹。
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引用次数: 0
Abnormalities of Rest-Activity and Light Exposure Rhythms Associated with Cognitive Function in Patients with Mild Cognitive Impairment (MCI). 与轻度认知功能障碍(MCI)患者认知功能相关的休息-活动和光照节律异常。
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-28 eCollection Date: 2023-01-01 DOI: 10.5334/jcr.227
Seong Jae Kim, Jung Hie Lee, Jae-Won Jang, Hee Seo Jung, In Bum Suh

We aimed to examine the difference in rest-activity rhythm (RAR) and light exposure rhythm (LER) between patients with mild cognitive impairment (MCI) and normal controls (NC), and to verify their relationships with cognitive functions. The neuropsychological battery was administered to participants above 50 years old. The MCI diagnosis was made according to Petersen's criteria. Ten patients with MCI (77.90 ± 6.95 years) and eight NC (74.75 ± 5.06 years) were studied. Actigraphy (Actiwatch 2; Philips Respironics) was recorded at home for 5 days. RAR and LER variables, including interdaily stability (IS), intradaily variability (IV) and relative amplitude, were calculated using nonparametric analyses. The associations between cognitive performance and RAR and LER variables were explored using generalized linear models. There were no significant differences in RAR or LER variables between MCI and NC. There was a significant main effect of RAR-IS on the Stroop Color and Word Test (SCWT), indicating a positive relationship between RAR stability and SCWT performance. There was a significant group by RAR-IS interaction on Trail Making Test-A, indicating a negative relationship in MCI compared to NC. There was a significant group by LER-IV interaction on the Boston Naming Test, indicating a positive relationship in MCI compared to NC. There was no disruption in RAR and LER in patients with MCI. Our study showed that circadian rhythm abnormality was associated with a decline in executive function. However, circadian rhythm abnormality was not associated with declines in processing speed and language function in patients with MCI, implying an altered pathophysiology compared to NC.

我们的目的是研究轻度认知障碍(MCI)患者和正常对照组(NC)在休息-活动节律(RAR)和光照节律(LER)方面的差异,并验证它们与认知功能的关系。对 50 岁以上的参与者进行了神经心理测试。MCI 的诊断依据彼得森标准。研究对象包括 10 名 MCI 患者(77.90 ± 6.95 岁)和 8 名 NC 患者(74.75 ± 5.06 岁)。患者在家中进行了为期 5 天的活动量记录(Actiwatch 2; Philips Respironics)。采用非参数分析法计算了 RAR 和 LER 变量,包括日间稳定性(IS)、日内变异性(IV)和相对振幅。使用广义线性模型探讨了认知表现与 RAR 和 LER 变量之间的关联。MCI 和 NC 之间的 RAR 和 LER 变量无明显差异。RAR-IS对Stroop颜色和词语测验(SCWT)有明显的主效应,表明RAR稳定性与SCWT成绩之间存在正相关。RAR-IS对Trail Making Test-A的组间交互作用显着,表明与NC相比,MCI患者的RAR-IS与Trail Making Test-A呈负相关。在 "波士顿命名测试 "中,LER-IV 的组间交互作用非常明显,表明与 NC 相比,MCI 与 LER-IV 呈正相关。在MCI患者中,RAR和LER没有发生紊乱。我们的研究表明,昼夜节律异常与执行功能下降有关。然而,昼夜节律异常与MCI患者处理速度和语言功能的下降无关,这意味着与NC相比,MCI患者的病理生理学发生了改变。
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引用次数: 0
The Alarm Clock Against the Sun: Trends in Google Trends Search Activity Across the Transitions to and from Daylight Saving Time. 对抗太阳的闹钟:谷歌趋势搜索活动在夏令时与夏令时之间的过渡趋势。
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-29 eCollection Date: 2023-01-01 DOI: 10.5334/jcr.230
Esther Dingena Domenie, Lisa Zarantonello, Chiara Mangini, Chiara Formentin, Gianluca Giusti, Domenico Ruggerini, Paola Cusumano, Alberto Biscontin, Rodolfo Costa, Sara Montagnese

The human circadian timing system depends on the light/dark cycle as its main cue to synchronize with the environment, and thus with solar time. However, human activities depend also on social time, i.e. the set of time conventions and restrictions dictated by society, including Daylight Saving Time (DST), which adds an hour to any degree of desynchrony between social and solar time. Here, we used Google Trends as a data source to analyze diurnal variation, if any, and the daily peak in the relative search volume of 26 Google search queries in relation to the transitions to/from DST in Italy from 2015 to 2020. Our search queries of interest fell into three categories: sleep/health-related, medication and random non sleep/health-related. After initial rhythm and phase analysis, 11 words were selected to compare the average phase of the 15 days before and after the transition to/from DST. We observed an average phase advance after the transition to DST, and a phase delay after the transition to civil time, ranging from 25 to 60 minutes. Advances or delays shorter than 60 minutes, which were primarily observed in the sleep/health-related category, may suggest that search timing for these queries is at least partially driven by the endogenous circadian rhythm. Finally, a significant trend in phase anticipation over the years was observed for virtually all words. This is most likely related to an increase in age, and thus in earlier chronotypes, amongst Google users.

人类的昼夜节律计时系统主要依靠光/暗周期来与环境同步,从而与太阳时同步。然而,人类活动也依赖于社会时间,即社会规定的一系列时间惯例和限制,包括夏令时(DST),它使社会时间和太阳时之间的任何不同步程度都增加了一个小时。在此,我们使用谷歌趋势作为数据源,分析昼夜变化(如果有的话),以及与 2015 年至 2020 年意大利夏令时转换有关的 26 个谷歌搜索查询的日相对搜索量峰值。我们感兴趣的搜索查询分为三类:与睡眠/健康相关、药物和随机非睡眠/健康相关。经过初步的节奏和相位分析后,我们选择了 11 个词来比较转入/转出夏令时前后 15 天的平均相位。我们观察到,在过渡到夏令时后,平均相位提前,而在过渡到民用时间后,相位延迟,从 25 分钟到 60 分钟不等。提前或延迟时间短于 60 分钟的情况主要出现在睡眠/健康相关类别中,这可能表明这些查询的搜索时间至少部分受内生昼夜节律的影响。最后,几乎在所有词中都观察到了多年来相位预测的显著趋势。这很可能与谷歌用户的年龄增长有关,因此也与较早的昼夜节律有关。
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引用次数: 0
Correlation Analysis Between Time Awareness and Morningness-Eveningness Preference. 时间意识与晨昏偏好的相关性分析。
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-11 eCollection Date: 2023-01-01 DOI: 10.5334/jcr.225
Reimi Sogawa, Fuminori Ono, Masahiko Terao, Shunta Nagano, Junko Kawabe, Koichi Node, Makoto Akashi

The circadian clock is adjusted by light inputs via the retinohypothalamic tract. Because environmental light is controllable for modern humans at the individual's preference although under social schedules, individual differences in time-related psychology and behavior may be associated with morningness-eveningness preference (M-E preference). To examine this hypothesis, we used the Time Management Scale and Time Anxiety Scale to quantify time-related psychology and behavior. These scales aim to evaluate "awareness of effective time management and utilization" and "anxiety about uncontrollable time schedule and unexpected time-related outcome", respectively. According to our correlation analysis using mid-sleep time as a marker for M-E preference, we obtained results supporting our hypothesis in the correlation between the M-E preference values and the Time Management Scale scores, with larger "time estimation" and "taking each moment as it comes" scores associated with more morningness and eveningness, respectively. Considering that modern humans likely become night owls under artificial light conditions, it appears plausible that lower awareness of time management leads to more eveningness.

昼夜节律时钟是通过视网膜下丘脑束的光输入来调节的。由于环境光对现代人类来说是可以根据个人偏好控制的,尽管在社会时间表下,与时间相关的心理和行为的个体差异可能与晨昏偏好(M-E偏好)有关。为了验证这一假设,我们使用了时间管理量表和时间焦虑量表来量化与时间相关的心理和行为。这些量表旨在分别评估“有效时间管理和利用的意识”和“对无法控制的时间表和意外的时间相关结果的焦虑”。根据我们使用睡眠中期时间作为M-E偏好标记的相关性分析,我们获得的结果支持了我们关于M-E偏好值与时间管理量表分数之间相关性的假设,较大的“时间估计”和“顺其自然”分数分别与更多的早晨和夜晚相关。考虑到现代人可能会在人造光条件下变成夜猫子,时间管理意识的降低似乎会导致更均匀。
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引用次数: 0
Circadian Oscillation Pattern of Endoplasmic Reticulum Quality Control (ERQC) Components in Human Embryonic Kidney HEK293 Cells. 人胚胎肾HEK293细胞内质网质量控制(ERQC)成分的昼夜振荡模式。
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.5334/jcr.219
Yalcin Erzurumlu, Deniz Catakli, Hatice Kubra Dogan

The circadian clock regulates the "push-pull" of the molecular signaling mechanisms that arrange the rhythmic organization of the physiology to maintain cellular homeostasis. In mammals, molecular clock genes tightly arrange cellular rhythmicity. It has been shown that this circadian clock optimizes various biological processes, including the cell cycle and autophagy. Hence, we explored the dynamic crosstalks between the circadian rhythm and endoplasmic reticulum (ER)-quality control (ERQC) mechanisms. ER-associated degradation (ERAD) is one of the most important parts of the ERQC system and is an elaborate surveillance system that eliminates misfolded proteins. It regulates the steady-state levels of several physiologically crucial proteins, such as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and the metastasis suppressor KAI1/CD82. However, the circadian oscillation of ERQC members and their roles in cellular rhythmicity requires further investigation. In the present study, we provided a thorough investigation of the circadian rhythmicity of the fifteen crucial ERQC members, including gp78, Hrd1, p97/VCP, SVIP, Derlin1, Ufd1, Npl4, EDEM1, OS9, XTP3B, Sel1L, Ufd2, YOD1, VCIP135 and FAM8A1 in HEK293 cells. We found that mRNA and protein accumulation of the ubiquitin conjugation, binding and processing factors, retrotranslocation-dislocation, substrate recognition and targeting components of ERQC exhibit oscillation under the control of the circadian clock. Moreover, we found that Hrd1 and gp78 have a possible regulatory function on Bmal1 turnover. The findings of the current study indicated that the expression level of ERQC components is fine-tuned by the circadian clock and major ERAD E3 ligases, Hrd1 and gp78, may influence the regulation of circadian oscillation by modulation of Bmal1 stability.

昼夜节律钟调节分子信号机制的“推拉”,这些信号机制安排生理节律组织以维持细胞内稳态。在哺乳动物中,分子钟基因紧密地安排着细胞节律。研究表明,这种生物钟可以优化各种生物过程,包括细胞周期和自噬。因此,我们探索了昼夜节律与内质网质量控制(ERQC)机制之间的动态串扰。内质网相关降解(ERAD)是ERQC系统中最重要的部分之一,是一种消除错误折叠蛋白的精细监测系统。它调节几种生理上至关重要的蛋白的稳态水平,如3-羟基-3-甲基戊二酰辅酶a还原酶(HMGCR)和转移抑制因子KAI1/CD82。然而,ERQC成员的昼夜节律振荡及其在细胞节律中的作用需要进一步研究。在本研究中,我们深入研究了HEK293细胞中15个ERQC关键成员的昼夜节律性,包括gp78、Hrd1、p97/VCP、SVIP、Derlin1、Ufd1、Npl4、EDEM1、OS9、XTP3B、Sel1L、Ufd2、YOD1、VCIP135和FAM8A1。我们发现ERQC的泛素偶联、结合和加工因子、逆转录易位-错位、底物识别和靶向成分的mRNA和蛋白质积累在生物钟的控制下表现出振荡。此外,我们发现Hrd1和gp78可能对Bmal1的转换具有调节作用。本研究结果表明,ERQC组分的表达水平受到生物钟的微调,ERAD E3的主要连接酶Hrd1和gp78可能通过调节Bmal1的稳定性来影响昼夜节律振荡的调节。
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引用次数: 0
Discovery and Visualization of Age-Dependent Patterns in the Diurnal Transcriptome of Drosophila. 果蝇昼夜转录组中年龄依赖模式的发现与可视化
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-12-08 eCollection Date: 2022-01-01 DOI: 10.5334/jcr.218
Benjamin Sebastian, Rosalyn M Fey, Patrick Morar, Brittany Lasher, Jadwiga M Giebultowicz, David A Hendrix

Many critical life processes are regulated by input from 24-hour external light/dark cycles, such as metabolism, cellular homeostasis, and detoxification. The circadian clock, which helps coordinate the response to these diurnal light/dark cycles, remains rhythmic across lifespan; however, rhythmic transcript expression is altered during normal aging. To better understand how aging impacts diurnal expression, we present an improved Fourier-based method for detecting and visualizing rhythmicity that is based on the relative power of the 24-hour period compared to other periods (RP24). We apply RP24 to transcript-level expression profiles from the heads of young (5-day) and old (55-day) Drosophila melanogaster, and reveal novel age-dependent rhythmicity changes that may be masked at the gene level. We show that core clock transcripts phase advance during aging, while most rhythmic transcripts phase delay. Transcripts rhythmic only in young flies tend to peak before lights on, while transcripts only rhythmic in old peak after lights on. We show that several pathways, including glutathione metabolism, gain or lose coordinated rhythmic expression with age, providing insight into possible mechanisms of age-onset neurodegeneration. Remarkably, we find that many pathways show very robust coordinated rhythms across lifespan, highlighting their putative roles in promoting neural health. We investigate statistically enriched transcription factor binding site motifs that may be involved in these rhythmicity changes.

许多关键的生命过程都受 24 小时外部光/暗周期输入的调节,如新陈代谢、细胞稳态和解毒。昼夜节律时钟有助于协调对这些昼夜光/暗周期的反应,在整个生命周期中保持节律性;然而,在正常衰老过程中,节律性转录物表达会发生改变。为了更好地了解衰老是如何影响昼夜节律表达的,我们提出了一种基于傅立叶的改进方法来检测和可视化节律性,该方法基于 24 小时周期与其他周期相比的相对功率(RP24)。我们将 RP24 应用于来自幼年(5 天)和老年(55 天)黑腹果蝇头部的转录本级表达谱,并揭示了可能在基因水平上被掩盖的新的年龄依赖性节律变化。我们发现,核心时钟转录本在衰老过程中相位提前,而大多数节律性转录本相位延迟。只有年轻蝇的节律性转录本往往在开灯前达到峰值,而只有老年蝇的节律性转录本在开灯后达到峰值。我们发现,包括谷胱甘肽代谢在内的一些通路会随着年龄的增长而获得或丧失协调的节律性表达,这为我们深入了解老年神经退行性变的可能机制提供了线索。值得注意的是,我们发现许多通路在整个生命周期中都表现出非常强的协调节律,这突显了它们在促进神经健康方面的潜在作用。我们对可能参与这些节律变化的转录因子结合位点基团进行了统计富集研究。
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引用次数: 0
Discovery and Visualization of Age-Dependent Patterns in the Diurnal Transcriptome of Drosophila 果蝇日转录组中年龄依赖模式的发现和可视化
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-04-08 DOI: 10.1101/2022.04.06.487011
Benjamin Sebastian, Rosalyn M. Fey, Patrick Morar, Brittany Lasher, Eileen S. Chow, Jadwiga M. Geibultowicz, D. Hendrix
Many critical life processes are regulated by input from 24-hour external light/dark cycles, such as metabolism, cellular homeostasis, and detoxification. The circadian clock, which helps coordinate the response to these diurnal light/dark cycles, remains rhythmic across lifespan; however, rhythmic transcript expression is altered during normal aging. To better understand how aging impacts diurnal expression, we present an improved Fourier-based method for detecting and visualizing rhythmicity that is based on the relative power of the 24-hour period compared to other periods (RP24). We apply RP24 to transcript-level expression profiles from the heads of young (5-day) and old (55-day) Drosophila melanogaster, and reveal novel age-dependent rhythmicity changes that may be masked at the gene level. We show that core clock transcripts phase advance during aging, while most rhythmic transcripts phase delay. Transcripts rhythmic only in young flies tend to peak before lights on, while transcripts only rhythmic in old peak after lights on. We show that several pathways including glutathione metabolism, gain or lose coordinated rhythmic expression with age providing insight into possible mechanisms of age-onset neurodegeneration. Remarkably, we find that many pathways show very robust coordinated rhythms across lifespan, highlighting their putative roles in promoting neural health. We investigate statistically enriched transcription factor binding site motifs that may be involved in these rhythmicity changes.
许多关键的生命过程都受到24小时外部光/暗周期的输入的调节,如代谢、细胞稳态和解毒。昼夜节律时钟有助于协调对这些昼夜光/暗周期的反应,在整个生命周期中保持节奏;然而,在正常衰老过程中,有节奏的转录物表达发生了改变。为了更好地理解衰老如何影响昼夜表达,我们提出了一种改进的基于傅立叶的方法来检测和可视化节律性,该方法基于24小时周期与其他周期相比的相对功率(RP24)。我们将RP24应用于年轻(5天)和老年(55天)黑腹果蝇头部的转录物水平表达谱,并揭示了可能在基因水平上被掩盖的新的年龄依赖性节律性变化。我们发现,核心时钟转录物在衰老过程中相位提前,而大多数节律转录物相位延迟。只有年轻苍蝇的转录物有节律,往往在开灯前达到峰值,而旧苍蝇的转录产物只有在开灯后达到峰值。我们发现,包括谷胱甘肽代谢在内的几种途径,随着年龄的增长,获得或失去协调的节律表达,从而深入了解年龄发作性神经退行性变的可能机制。值得注意的是,我们发现许多途径在整个生命周期中表现出非常强大的协调节奏,突出了它们在促进神经健康方面的假定作用。我们研究了可能参与这些节律性变化的统计富集的转录因子结合位点基序。
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引用次数: 3
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Journal of Circadian Rhythms
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