亲子关系与CLOCK基因rs1801260多态性对学前儿童亲社会行为的交互影响:性别的调节作用

研究探讨了亲子关系与CLOCK基因rs1801260多态性对学前儿童亲社会行为的交互影响及性别的调节作用。以694名学前儿童(M_(年龄)=5.06岁,SD=0.87)及其父母为测试对象,收集儿童的唾液样本进行基因分型,由儿童父母填写亲子关系和儿童亲社会行为量表。研究结果发现,亲子亲密与亲子冲突对亲社会行为的主效应显著。亲子冲突、CLOCK基因rs1801260多态性和性别三重交互影响儿童的亲社会行为,即与携带C等位基因的男孩相比,携带TT基因型的男孩在低亲子冲突下会表现出更多的亲社会行为,在高亲子冲突下则表现出更少的亲社会行为。但亲子冲突与CLOCK基因rs1801260多态性对女孩亲社会行为的交互作用不显著。研究结果为深入理解学前儿童亲社会行为形成的基因-环境交互作用机制提供了证据。

A frequency servo SoC with output power stabilization loop technology for miniaturized atomic clocks

A frequency servo system-on-chip(FS-SoC)featuring output power stabilization technology is introduced in this study for high-precision and miniaturized cesium(Cs)atomic clocks.The proposed power stabilization loop(PSL)technique,incorporating an off-chip power detector(PD),ensures that the output power of the FS-SoC remains stable,mitigating the impact of power fluctuations on the atomic clock's stability.Additionally,a one-pulse-per-second(1PPS)is employed to syn-chronize the clock with GPS.Fabricated using 65 nm CMOS technology,the measured phase noise of the FS-SoC stands at-69.5 dBc/Hz@100 Hz offset and-83.9 dBc/Hz@1 kHz offset,accompanied by a power dissipation of 19.7 mW.The Cs atomic clock employing the proposed FS-SoC and PSL obtains an Allan deviation of 1.7×10^(-11) with 1-s averaging time.

Hypothalamic circuits and aging:keeping the circadian clock updated

Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.

Piperine regulates the circadian rhythms of hepatic clock gene expressions and gut microbiota in high-fat diet-induced obese rats

The interplay between the host circadian clock and microbiota has significant influences on host metabolism processes,and circadian desynchrony triggered by high-fat diet(HFD)is closely related to metabolic disorders.In this study,the modulatory effects of piperine(PIP)on lipid metabolism homeostasis,gut microbiota community and circadian rhythm of hepatic clock gene expressions in obese rats were investigated.The Sprague-Dawley(SD)rats were fed with normal diet(ND),HFD and HFD supplemented with PIP,respectively.After 9 weeks,rats were sacrificed with tissue and fecal samples collected for circadian analysis.Results showed that chronic PIP administration ameliorated the obesity-induced alterations in lipid metabolism and dysregulation of hepatic clock gene expressions in obese rats.The gut microbial communities studied through 16S rRNA sequencing showed that PIP ameliorated the imbalanced nicrobiota and recovered the circadian rhythm of Lactobacillaceae,Desulfovibrionaceae,Paraprevotellaceae,and Lachnospiraceae.The fecal metabolic profiles indicated that 3-dehydroshikimate,cytidine and lithocholyltaurine were altered,which were involved in the amino acid and fatty acid metabolism process.These findings could provide theoretical basis for PIP to work as functional food to alleviate the lipid metabolism disorder,circadian rhythm misalignment,and gut microbiota dysbiosis with wide applications in the food and pharmaceutic industries.

MEMS Huygens Clock Based on Synchronized Micromechanical Resonators

With the continuous miniaturization of electronic devices,microelectromechanical system(MEMS)oscillators that can be combined with integrated circuits have attracted increasing attention.This study reports a MEMS Huygens clock based on the synchronization principle,comprising two synchronized MEMS oscillators and a frequency compensation system.The MEMS Huygens clock improved shorttime stability,improving the Allan deviation by a factor of 3.73 from 19.3 to 5.17 ppb at 1 s.A frequency compensation system based on the MEMS oscillator’s temperature-frequency characteristics was developed to compensate for the frequency shift of the MEMS Huygens clock by controlling the resonator current.This effectively improved the long-term stability of the oscillator,with the Allan deviation improving by 1.6343105 times to 30.9 ppt at 6000 s.The power consumption for compensating both oscillators simultaneously is only 2.85 mW·℃^(-1).Our comprehensive solution scheme provides a novel and precise engineering solution for achieving high-precision MEMS oscillators and extends synchronization applications in MEMS.

A redundant subspace weighting procedure for clock ensemble

A redundant-subspace-weighting(RSW)-based approach is proposed to enhance the frequency stability on a time scale of a clock ensemble.In this method,multiple overlapping subspaces are constructed in the clock ensemble,and the weight of each clock in this ensemble is defined by using the spatial covariance matrix.The superimposition average of covariances in different subspaces reduces the correlations between clocks in the same laboratory to some extent.After optimizing the parameters of this weighting procedure,the frequency stabilities of virtual clock ensembles are significantly improved in most cases.

Flowering-time regulation by the circadian clock:From Arabidopsis to crops

Precise timing of flowering in plants is critical for their growth and reproductive processes.One factor controlling flowering time is the cycle of light and darkness within a day,known as the photoperiod.Plants are classified into long-day,short-day,and day-neutral plants based on light requirements for floral initiation.Although the molecular mechanisms that govern this differentiation remain incompletely understood,studies have consistently shown that the circadian clock plays a central role in regulating photoperiod response across diverse plant species.However,there is a scarcity of reviews describing the regulatory network linking the circadian clock with photoperiodic flowering.This review summarizes that regulatory network,focusing on the distinct roles of clock genes in long-day and short-day plants.We also discuss the strategies of clock gene mutations contributing to geographic variation in longday and short-day crops.

A Yb optical clock with a lattice power enhancement cavity

We construct a power enhancement cavity to form an optical lattice in an ytterbium optical clock.It is demonstrated that the intra-cavity lattice power can be increased by about 45 times,and the trap depth can be as large as 1400Er when laser light with a power of only 0.6 W incident to the lattice cavity.Such high trap depths are the key to accurate evaluation of the lattice-induced light shift with an uncertainty down to~1×10-18.By probing the ytterbium atoms trapped in the power-enhanced optical lattice,we obtain a 4.3 Hz-linewidth Rabi spectrum,which is then used to feedback to the clock laser for the close loop operation of the optical lattice clock.We evaluate the density shift of the Yb optical lattice clock based on interleaving measurements,which is-0.46(62)mHz.This result is smaller compared to the density shift of our first Yb optical clock without lattice power enhancement cavity mainly due to a larger lattice diameter of 344μm.

Physics package based on intracavity laser cooling ^(87)Rb atoms for space cold atom microwave clock

This article proposes a new physics package to enhance the frequency stability of the space cold atom clock with the advantages of a microgravity environment. Clock working processes, including atom cooling, atomic state preparation,microwave interrogation, and transition probability detection, are integrated into the cylindrical microwave cavity to achieve a high-performance and compact physics package for the space cold atom clock. We present the detailed design and ground-test results of the cold atom clock physics package in this article, which demonstrates a frequency stability of 1.2×10^(-12) τ^(-1/2) with a Ramsey linewidth of 12.5 Hz, and a better performance is predicted with a 1 Hz or a narrower Ramsey linewidth in microgravity environment. The miniaturized cold atom clock based on intracavity cooling has great potential for achieving space high-precision time-frequency reference in the future.

A novel small-animal locomotor activity recording device for biological clock research

The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's cover.Then,the RJ25 adaptor relayed the running signal to the main control board.Finally,the main control board was connected to the USB port of the computer with the USB connection.Data were collected using the online-accessible,self-created software Magturning.Through Magturning,generated data were saved and exported in real time.Afterward,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light conditions.In conclusion,this new device can record circadian activity of rodents.Our device is appropriate for interdisciplinary investigations related to biological clock research.

Capsaicin alleviates the hepatic clock gene disruption and gut microbiota dysbiosis in circadian rhythm disorder mouse model

As the body’s internal clock,the circadian rhythm regulates the energy expenditure,appetite,and sleep.There exists a close relationship between the host circadian rhythm and gut microbiota.In this work,a circadian disorder mouse model induced by constant darkness(CD)was constructed to investigate the regulating effects of capsaicin(CAP)on disturbances of metabolism homeostasis and gut microbiota in the respect of circadian rhythm-related mechanisms.Our results indicated that CAP reduced weight gain induced by circadian rhythm disorder in mice by inhibiting fat accumulation in liver and adipose tissue.The rhythmic expressions of circadian clock genes and lipid-metabolism related genes in liver were also recovered by CAP.Microbial study using 16S rRNA sequencing revealed that CAP modulated the gut microbiota richness,diversity and composition,and restored diurnal oscillations of gut microbes at the phylum and family level.These results indicated that CAP could alleviate CD-induced hepatic clock gene disruption and gut microbiota dysbiosis in mice,providing theoretical basis for CAP to be used as a muti-functional ingredient with great healthpromoting effects.

Proposal for a realtime Einstein-synchronization-defined satellite virtual clock

Realization of high performance satellite onboard clock is vital for various positioning, navigation, and timing applications. For further improvement of the synchronization-based satellite time and frequency references, we propose a geosynchronous(GEO) satellite virtual clock concept based on ground–satellite synchronization and present a beacon transponder structure for its implementation(scheduled for launch in 2025), which does not require atomic clocks to be mounted on the satellite. Its high performance relies only on minor modifications to the existing transponder structure of GEO satellites. We carefully model the carrier phase link and analyze the factors causing link asymmetry within the special relativity. Considering that performance of such synchronization-based satellite clocks is primarily limited by the link's random phase noise, which cannot be adequately modeled, we design a closed-loop experiment based on commercial GEO satellites for pre-evaluation. This experiment aims at extracting the zero-means random part of the ground-satellite Ku-band carrier phase via a feedback loop. Ultimately, we obtain a 1σ value of 0.633 ps(two-way link), following the Gaussian distribution. From this result, we conclude that the proposed real-time Einstein-synchronization-defined satellite virtual clock can achieve picosecond-level replication of onboard time and frequency.

A proposal for detecting weak electromagnetic waves around 2.6μm wavelength with Sr optical clock

Infrared signal detection is widely used in many fields.Due to the detection principle,however,the accuracy and range of detection are limited.Thanks to the ultra stability of the^(87)Sr optical lattice clock,external infrared electromagnetic wave disturbances can be responded to.Utilizing the ac Stark shift of the clock transition,we propose a new method to detect infrared signals.According to our calculations,the theoretical detection accuracy in the vicinity of its resonance band of 2.6μm can reach the order of 10-14W,while the minimum detectable signal of common detectors is on the order of 10^(-10)W.

Einstein’s Concept of Clock Synchronization Conflicts with the Second Relativity Postulate

Einstein defined clock synchronization whenever photon pulses with timetags traverse a fixed distance between two clocks with equal time spans ineither direction. Using the second relativity postulate, he found clocksmounted on a rod uniformly moving parallel with the rod’s length cannot besynchronized, but clocks attached to a stationary rod can. He dismissed thisdiscrepancy by claiming simultaneity and clock synchronization were not commonbetween inertial frames, but this paper proves with both Galilean and Lorentztransformations that simultaneity and clock synchronization are preservedbetween inertial frames. His derivation means moving clocks can never besynchronized in a “resting” inertial frame. Ultraprecise atomic clocks intimekeeping labs daily contradict his results. No algebraic error occurred inEinstein’s derivations. The two cases of clocksattached to a rod reveal three major conflicts with the currentsecond postulate. The net velocity between a photon source and detector plusthe “universal” velocity c is mathematically equivalent toEinstein’s clock synchronization method. As the ultraprecise timekeepingcommunity daily synchronizes atomic clocks on the moving Earth withultraprecise time uncertainty well below Einstein’s lowest limit ofsynchronization, the theoretical resolution of the apparent conflict isaccomplished by expanding the second relativity postulate to incorporate thenet velocity between the photon source and detector with the emitted velocity c as components of the total velocity c. This means the magnitudeof the total photon velocity can exceed the speed limit (299792458 m/s) set by the standard velocity c. .

大鼠视交叉上核与松果体中Clock基因转录的昼夜节律性及不同光反应性(英文)

本研究旨在观察和比较视交叉上核(suprachiasmatic nucleus,SCN)与松果体(pineal gland,PG)中Clock基因内源性昼夜转录变化规律以及光照对其的影响。Sprague-Dawley大鼠在持续黑暗(constant darkness,DD)和12 h光照：12 h黑暗交替(12 hour- light：12 hour-dark cycle,LD)光制下分别被饲养8周(n=36)和4周(n=36)后,在一昼夜内每隔4 h采集一组SCN和PG组织(n=6),提取总RNA,用竞争性定量RT-PCR测定不同昼夜时点(circadian times,CT or zeitgeber times,ZT)各样品中Clock基因的mRNA相对表达量,通过余弦法和Clock Lab软件获取节律参数,并经振幅检验是否存在昼夜节律性转录变化。结果如下：(1)SCN中Clock基因mRNA的转录在DD光制下呈现昼低夜高节律性振荡变化(P＜0．05),PG中Clock基因的转录也显示相似的内源性节律外观,即峰值出现于主观夜晚(SCN为CT15,PG为CT18),谷值位于主观白天(SCN为CT3,PG为CT6)(P＞0．05)。(2) LD光制下SCN中Clock基因的转录也具有昼夜节律性振荡(P＜0．05),但与其DD光制下节律外观相比,呈现反时相符律变化(P＜0．05),且其表达的振幅及峰值的mRNA水平均增加(P＜0．05),而PG中Clock基因在LD光制下转录的相应节律参数变化却恰恰相反(P＜0．05)。(3)在LD光制下,光照使PG中Clock基因转录的节律外观反时相于SCN(P＜0．05),即在SCN和PG的峰值分别出现于光照期ZT10和黑暗期ZT17,谷值分别位于黑暗期ZT22和光照期ZT5。结果表明,Clock基因的昼夜转录在SCN和PG中存在同步的内源性节律本质,而光导引在这两个中枢核团调节Clock基因昼夜节律性转录方面有着不同的作用。

山羊clock和cry1基因的克隆及其在大脑和垂体中表达差异的研究

本研究旨在探讨生物钟基因clock和cry1在山羊出生后不同时期的大脑和垂体中的表达差异。在出生后30、60、90和120d共屠宰24只南江黄羊羔羊(公母各12只),取其大脑皮质层和垂体组织样品用于抽提RNA,进行分子克隆和实时荧光定量PCR分析。结果,分离克隆得到了山羊clock基因外显子1到外显子8以及cry1基因外显子6到外显子15的CDS区序列,其长度分别为1 479bp和993bp,其中clock基因部分CDS区序列与绵羊、牛、人和小鼠的对应序列相似性分别为99%、90%、94%和92%,cry1基因部分CDS区序列与绵羊、牛、人和小鼠的对应序列相似性分别为99%、98%、94%和87%。组织表达分析结果表明,性别对clock和cry1基因的表达影响不显著(P>0.05),2个基因在垂体中的mRNA表达量极显著高于大脑中的表达量(P<0.01);在不同时期的垂体组织中,clock和cry1基因表达量均呈现先上升后下降的趋势;在不同时期的大脑组织中,clock基因的表达量趋于波动平衡,呈现上升趋势,cry1基因的相对表达量呈细微的上升趋势。结果提示:clock和cry1基因的CDS区在物种间保守性较高。clock和cry1基因在山羊大脑和垂体组织中起到重要的作用,且其mRNA发育性表达模式具有组织特异性。

CLOCK基因单核苷酸多态性与乳腺癌易感性的病例对照研究

目的：探讨生物钟CLOCK基因的单核苷酸多态性与乳腺癌易感性的关系。方法：采用应用聚合酶链式反应一限制性片断长度多态性（PCR—RFLP）技术检测1499例中国汉族女性乳腺癌患者和1592例正常女性对照者CLOCK基因rs3805151位点的基因型，采用SPSS16．0软件进行数据处理。结果：CLOCK基因CC型、CT型和TT型在病例组和对照组闻的分布差异有统计学意义（x^2=9．712，P=0．008），与CC型相比，杂合型CT可以显著增加乳腺癌的发病风险（OR=1．41，95％CI：1．07～1．87），携带T等位基因（CTrrr）的个体乳腺癌风险增加35％（OR=1．35，95％CI：1．04-1．76）。分层分析显示，携带T等位基因绝经后、无肿瘤家族史者、无乳腺良性病史的个体患乳腺癌风险增加。结论：CLOCK基因rs3805151C〉T可增加乳腺癌发病风险，这一结论有待于进一步通过不同种族人群的关联研究以及功能学研究的证实.

异钩藤碱对血管平滑肌细胞中Baml1、Clock基因表达的调节作用

目的研究异钩藤碱对血管紧张素Ⅱ(AngⅡ)诱导的血管平滑肌细胞(VSMC)中时钟基因(Bmal1、Clock)昼夜节律表达变化的调节作用。方法以AngⅡ诱导胸主动脉平滑肌细胞(A7r5细胞)建立节律变化模型。实验分AngⅡ诱导组、异钩藤碱组、正常对照组。AngⅡ诱导组以终浓度为100 nmol.L-1的AngⅡ诱导24 h,异钩藤碱组加入终浓度为100 nmol.L-1的AngⅡ和12 mg.L-1异钩藤碱处理24 h。采用Real-time PCR方法检测不同时间点VSMC中Bmal1、Clock基因表达水平,比较各组之间节律参数的差异。结果异钩藤碱通过调节AngⅡ诱导的A7r5细胞中的Baml1、Clock基因表达,改变其中值、振幅及峰相位,使A7r5昼夜节律发生改变。结论异钩藤碱对A7r5细胞中Baml1、Clock基因的昼夜节律的表达有调节作用。

生物钟昼夜节律调节基因(CLOCK)在肝癌中高表达且与预后不良相关

目的明确生物钟昼夜节律调节基因(CLOCK)在肝细胞肝癌(HCC)中的表达及对细胞生长的作用。方法采用免疫组织化学染色法检测CLOCK在158例HCC组织及对应癌旁组织中的表达,利用HCC公共数据(共356例)验证CLOCK在HCC组织中的表达变化。单因素统计分析CLOCK表达与HCC患者临床病理特征间的关系,并且采用生存分析法比较CLOCK表达水平高低对HCC患者生存的影响。敲低肝癌Hep G2细胞中CLOCK水平,采用MTS法检测CLOCK对细胞生长的影响。结果 CLOCK在HCC组织高表达,而在356例HCC公共数据中,癌组织中CLOCK表达同样显著上调。按照CLOCK的表达水平,将158例HCC患者分为低表达组和高表达组,单因素分析结果显示,CLOCK在HCC中的表达与肿瘤直径、TNM分期、门脉侵袭有关。CLOCK低表达组HCC患者的总生存时间和无复发生存时间均显著长于高表达组患者。在肝癌Hep G2细胞中,敲低肝癌细胞CLOCK后细胞增殖能力显著降低。结论 CLOCK在HCC中呈高表达趋势,与HCC的恶性程度相关,其表达上调提示HCC患者预后不良,敲低CLOCK显著抑制肝癌细胞生长。

FClock:一种面向SSD的自适应缓冲区管理算法

现有的各种基于闪存的缓冲区管理算法针对闪存读写代价的不对称性进行改进,实际中既存在同一闪存读写代价的不对称性问题,也存在不同闪存不对称性之间的巨大差异性问题,而后者一直没有得到足够的重视.文章提出一种基于闪存硬盘(SSD)的自适应缓冲区管理算法FClock,FClock将数据页组织为两个环形数据结构(CC和DC),分别用于存储缓冲区中的只读数据页和已修改数据页.当需要选择置换页时,FClock使用基于代价的启发式来选择置换页,可在未修改的数据页和已修改的数据页之间进行公平的选择,适用于不同种类的SSD.针对数据库、虚存和文件系统中数据页访问存在高相关性的特点,提出基于"平均命中距离"的访问计数方法来调整数据页的访问频率.基于不同SSD和不同存取模式的实验结果说明,FClock的综合性能优于已有方法.