Regulation of PEP-Carboxylase by Biological Clock in a CAM Plant

The endogenous circadian rhythm in a crassulacean acid metabolism(CAM) plant Graptopetalum paraguayense was investigated. Phosphoenolpyruvatecarboxylase (PEP-C) takes two forms: the malate-sensitive dayform and the malate-insensitive night form. We monitored thestate of PEP-C by measuring the sensitivity to malate as a parameterof the circadian rhythm. We also measured vacuolar pH and malateconcentration, and contents of oxaloacetate, pyruvate and phosphoenolpyruvate(PEP). A free-running circadian oscillation was observed under continuousdim light (5 klux) after 12 h/12 h light/dark cycles at 20°C.The period of the rhythm was about 20 h. Under continuous light(18 klux), the rhythm was less clear but the length of the periodwas not affected. On the other hand, the rhythms of the vacuolarpH and the malate concentration were evident under the continuouslight, but were not clear under the continuous dim light. Therhythm disappeared in continuous darkness. The content of PEPchanged simultaneously with the transformation of PEP-C duringthe normal day-night cycles and under the continuous light,but stayed at a low level under the continuous dim light. Thisindicated that the transformation of PEP-C was not sufficientto maintain the rhythm in the carbon metabolism. Shift of the timing of the start or end of the dark period priorto the continuous illumination shifted the phase of the PEP-Crhythm without changing the period length significantly. At30°C, the rhythm of PEP-C was less clear, but the periodlength was not affected. These results suggest that the biological clock controls CO₂uptake and day-night CAM cycle through regulation of PEP-C transformation. (Received August 20, 1993; Accepted December 3, 1993)     

光对植物生物钟的调节

植物中的许多生理和生化反应都表现出一种内源的近似于24小时的昼夜节律现象,这些昼夜节律现象受生物钟的调节.高等植物的生物钟系统由输入途径、中央振荡器、输出途径以及一个阀门效应器组成.光信号通过光敏色素和隐花色素进入生物钟,使中央振荡器产生振荡,改变生物钟的输出信号,引起各种生理反应.本文综述了光信号对高等植物生物钟的调节作用和转导途径.     

光对植物生物钟的调节

植物中的许多生理和生化反应都表现出一种内源的近似于24小时的昼夜节律现象,这些昼夜节律现象受生物钟的调节。高等植物的生物钟系统由输入途径、中央振荡器、输出途径以及一个阀门效应器组成。光信号通过光敏色素和隐花色素进入生物钟,使中央振荡器产生振荡,改变生物钟的输出信号,引起各种生理反应。本文综述了光信号对高等植物生物钟的调节作用和转导途径。     

MicroRNA 对获得性免疫的调节作用

微RNA(MicroRNA,miRNA)是一类在转录后水平调节基因表达的大约22 nt的非编 码内源单链RNA.已经表明,它们与许多重要的生理和病理过程相关,包括发育、分化、细胞 凋亡、脂肪代谢、病毒感染和癌症.越来越多的证据表明,miRNA参与了获得性免疫的调节. 有趣的是,不同于开关式的调节,miRNA表现出定量的基因调节,它们能精细调节细胞免疫 反应以响应外界刺激.深入理解miRNAs对获得性免疫的调节作用有助于调节宿主免疫应答和 保护感染组织间的平衡,鉴定免疫调节新靶标和开发基于miRNA的有效疗法.本文综述了miRN A包括病毒miRNA对获得性免疫的调节作用,特别是miRNA在调节免疫活性细胞、T细胞功 能和抗体产生中的作用.     

Mutants of the Biological Clock in CHLAMYDOMONAS REINHARDI

A genetic analysis of the biological clock in Chlamydomonas reinhardi has been initiated. Of six wild-type strains tested (3 mt(+) and 3 mt(-)), five had periods close to 24 hr whereas one had a 21-hr period. Mutants with altered clock period have been isolated. The periods of 3 of these variant strains are temperature compensated. Genetic crosses involving a long-period mutant suggest that a single gene confers the long-period character, and in general clock-period length seems to be a useful phenotypic measure of alterations in the clock due to genetic differences. One phase mutant was found but its behavior was variable and the phase of the rhythm, relative to a light-dark transition which initiates the rhythm, does not seem to be reliable as a parameter of clock differences. No markers have yet been mapped.     

肝细胞核因子的调控作用研究新进展

肝细胞核因子(HNF,Hepatocyte nuclear factor)是调节肝脏基因特异性表达的一类转录因子,主要包括HNF1、HNF3、HNF4和HNF6等,这些转录因子相互作用构成复杂的调控网络。HNF在人体多个重要组织器官如肝、胰、肠、肾等都有不同程度的表达。研究发现,在多种疾病的患者体内,存在着编码这些因子基因的突变,提示HNF与维持及调节人体正常生理功能密不可分。本文旨在对HNF的研究进展作以系统性综述,为研究HNF相关疾病的发生机制并进行有效的干预提供新思路。     

微核糖核酸对血管生成相关因子的调节作用

微核糖核酸(microRNAs,miRNAs)是广泛存在于真核生物中的一类短小的、非编码的单链RNA,由18～25个核苷酸组成,在调节细胞增殖、分化、凋亡和肿瘤发生等多种生物学过程中起重要作用.血管生成过程中受到多种血管生成因子的调控作用,近期研究表明,microRNAs参与血管生成相关因子的调节,进而影响血管生成,然而具体的功能以及作用机制仍需探讨.进一步研究microRNAs对血管生成相关因子的调控作用,为心血管疾病和肿瘤的治疗提供新的理论基础.     

The Biological Clock in Chlamydomonas reinhardi

SYNOPSIS. Chlamydomonas reinhardi has a biological clock regulating phototaxis in dividing and non-dividing cultures; it also can exert some control on growth of continuous cultures. The period length is ∼ 24 hr; it is temperature-compensated and not dependent on the average growth rate. The rhythm can be entrained or phased by light-dark conditions. In dividing cultures a periodic fluctuation in cell number and total protein persists in continuous light.     

Regulation of Flowering Time by MicroRNAs

The shoot apical meristem (SAM) continuously produces lateral organs in plants.Based on the identity of the lateral organs,the life cycle of a plant can be divided into two phases:vegetative and reproductive.The SAM produces leaves during the vegetative phase,whereas it gives rise to flowers in the reproductive phase (reviewed in Poethig,2003).The floral transition,namely the switch from vegetative to reproductive growth,is controlled by diverse endogenous and exogenous cues such as age,hormones,photoperiod,and temperature (reviewed in B(a)urle and Dean,2006;Srikanth and Schmid,2011;Andres and Coupland,2012).The model annual Arabidopsis thaliana has been extensively used for the dissection of the molecular mechanism underlying the floral transition during the last two decades.The molecular and genetic analyses have revealed five flowering time pathways,including age,autonomous,gibberellins (GAs),photoperiod and vernalization (reviewed in Amasino and Michaels,2010).Growing lines of evidence indicate that there are extensive crosstalks,feedback or feed-forward loops between the components within these pathways,and that these multiple floral inductive cues are integrated into a set of floral promoting MADS-box genes including APETALA 1 (AP1),SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1),FRUITFULL (FUL) and LEAFY (LFY) (Amasino and Michaels,2010;Lee and Lee,2010;Srikanth and Schmid,2011).     

microRNAs参与肿瘤干细胞的调节

肿瘤干细胞存在于多种类型肿瘤中,并与肿瘤的发生发展密切相关。肿瘤干细胞和胚胎干细胞在生物学特征上存在许多共同点,如自我更新,多潜能性分化等等。然而,肿瘤干细胞和胚胎干细胞又存在很大差异,主要表现在耐药性、致瘤力和转移活性上。肿瘤干细胞在临床研究中具有不可替代的重要性,然而其分子水平上的调节机制尚未被完整揭示。作为内源性非编码小RNA的一部分,miRNAs在细胞发生发展的调节过程中扮演着重要角色。大量研究表明,miRNAs参与肿瘤干细胞的调节,并参与肿瘤的发生与进展。探索miRNAs在肿瘤干细胞基因表达调控中的作用及作用机制,有助于肿瘤特异性生物学标志物及治疗靶点的确定。本文就miRNAs与肿瘤干细胞调节的相关研究进展进行综述。     

生物钟基因研究新进展

生物钟基因普遍存在于生物界,其作用在于产生和控制昼夜节律的运转。生物钟基因及其编码的蛋白质组成反馈回路,维持振荡系统持续进行并与环境周期保持同步。各级进化水平物种生物钟的基因组成和控制途径有同有异。此文主要介绍蓝细菌、脉孢菌、果蝇、鼠和人昼夜钟的分子运作机制以及研究钟基因的意义和展望。 Abstract:The circadian clock genes,which generate and control the running of the circadian rhythms,exist in organisms ranging from prokaryotes to mammals.The oscillator genes and its coding proteins compose the feedback loops of circadian system.The kind,number and regulating route of clock genes are characterized by living things at different evolution levels.The molecular mechanism of the run of circadian clock genes in cyanobacteria,neurospore,fruit fly,mouse and human being is introduced in this article.     

细胞周期中MicroRNA的调控作用

MicroRNA是近年来发现并热点研究的一类重要的非编码RNA,在干细胞的更新与分化、体细胞性状与数量的维持、甚至肿瘤细胞的恶性增生等生物学过程中都具有重要的调控作用.microRNA通过与靶位点结合而快速有效地降解靶基因mRNA或抑制蛋白的翻译,下调E2F、CDK、cyclin、p21、p27、DNA多聚酶α等关键的细胞周期调控因子的表达,加速或减慢细胞增殖的速度.microRNA对细胞周期的调控还将涉及到微生物感染机体的过程、免疫系统的调控、妊娠期母体的变化、组织的修复、细胞的凋亡与衰老等诸多方面.随着对microRNA调控细胞周期机制的深入研究,microRNA及其靶基因不仅可以作为某些疾病的分子标记物,而且可以用于指导疾病的预防和治疗.     

Global Epigenetic Regulation of MicroRNAs in Multiple Myeloma

Epigenetic changes frequently occur during tumorigenesis and DNA hypermethylation may account for the inactivation of tumor suppressor genes in cancer cells. Studies in Multiple Myeloma (MM) have shown variable DNA methylation patterns with focal hypermethylation changes in clinically aggressive subtypes. We studied global methylation patterns in patients with relapsed/refractory MM and found that the majority of methylation peaks were located in the intronic and intragenic regions in MM samples. Therefore, we investigated the effect of methylation on miRNA regulation in MM. To date, the mechanism by which global miRNA suppression occurs in MM has not been fully described. In this study, we report hypermethylation of miRNAs in MM and perform confirmation in MM cell lines using bisulfite sequencing and methylation-specific PCR (MSP) in the presence or absence of the DNA demethylating agent 5-aza-2′-deoxycytidine. We further characterized the hypermethylation-dependent inhibition of miR-152, -10b-5p and -34c-3p which was shown to exert a putative tumor suppressive role in MM. These findings were corroborated by the demonstration that the same miRNAs were down-regulated in MM patients compared to healthy individuals, alongside enrichment of miR-152-, -10b-5p, and miR-34c-3p-predicted targets, as shown at the mRNA level in primary MM cells. Demethylation or gain of function studies of these specific miRNAs led to induction of apoptosis and inhibition of proliferation as well as down-regulation of putative oncogene targets of these miRNAs such as DNMT1, E2F3, BTRC and MYCBP. These findings provide the rationale for epigenetic therapeutic approaches in subgroups of MM.     

外泌体内mircoRNAs在肝癌中的作用

外泌体是细胞间重要的信息交流介质,包含多种活性分子,如蛋白质、脂类、DNA和微RNA（microRNA, miRNA）等,外泌体可从供体细胞分泌后直接或间接作用于受体细胞,进而影响细胞之间的生命活动。更有意义的是,外泌体内的miRNAs可在血液中稳定存在,且当肿瘤发生时出现异常表达,进而参与肿瘤的发生发展,影响肿瘤患者生存及预后。近年大量研究报道显示,外泌体内miRNAs可作为肝癌诊断的新生物标志物及治疗肝癌的潜在靶标。本文就近年来外泌体内miRNAs在肝癌中的表达及其临床应用进行综述。