TOR

TOR
  • 文章类型: Journal Article
    为了应对压力,真核生物通过磷酸化eIF2α激活整合应激反应(ISR),以促进促存活效应基因的翻译,如酵母中的GCN4。补充ISR是雷帕霉素(TOR)通路的靶标,它规范了eIF4E功能。这里,我们在酿酒酵母中没有eIF4E的情况下探索翻译控制。有趣的是,我们发现eIF4E的丢失导致GCN4翻译的去抑制。此外,我们发现GCN4翻译的去抑制既不伴随eIF2α磷酸化也不伴随引发剂三元复合物(TC)的减少。我们的数据表明,当eIF4E水平耗尽时,GCN4翻译通过一种独特的机制去抑制,该机制可能涉及小核糖体亚基由于eIF4A的局部浓度增加而进行更快的扫描。总的来说,我们的研究结果表明,eIF4F成分的相对水平是核糖体动力学的关键,并可能在基因表达的翻译控制中发挥重要作用.
    In response to stress, eukaryotes activate the integrated stress response (ISR) via phosphorylation of eIF2α to promote the translation of pro-survival effector genes, such as GCN4 in yeast. Complementing the ISR is the target of rapamycin (TOR) pathway, which regulates eIF4E function. Here, we probe translational control in the absence of eIF4E in Saccharomyces cerevisiae. Intriguingly, we find that loss of eIF4E leads to de-repression of GCN4 translation. In addition, we find that de-repression of GCN4 translation is accompanied by neither eIF2α phosphorylation nor reduction in initiator ternary complex (TC). Our data suggest that when eIF4E levels are depleted, GCN4 translation is de-repressed via a unique mechanism that may involve faster scanning by the small ribosome subunit due to increased local concentration of eIF4A. Overall, our findings suggest that relative levels of eIF4F components are key to ribosome dynamics and may play important roles in translational control of gene expression.
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  • 文章类型: Journal Article
    匿名网络,其主要目的是保护用户身份,作为增强网络安全和匿名性的工具,已经越来越突出。尽管如此,这些网络已经成为对抗事务和可疑攻击流量来源的平台。为了抵御互联网上不可预测的对手,检测匿名网络流量已经成为一种必要性。许多识别匿名流量的监督方法都利用了机器学习策略。然而,许多需要访问工程数据集和复杂的体系结构来提取所需的信息。由于匿名网络流量对流量分析的抵制以及公开可用数据集的稀缺,当涉及到匿名流量检测时,这些方法可能需要提高训练效率并实现更高的性能。本研究利用特征工程技术来提取模式信息,并对匿名流量的静态痕迹的特征重要性进行排名。为了有效地利用这些模式属性,我们开发了一个强化学习框架,包括四个关键组成部分:状态,行动,奖励,和状态转换。设计了一种轻量级系统来对匿名和非匿名网络流量进行分类。随后,提出了两个微调阈值来代替二元分类系统中的传统标签。该系统将识别匿名网络流量,而不依赖于标记的数据。实验结果强调,该系统可以识别匿名流量,准确率超过80%(当基于模式信息时)。
    Anonymous networks, which aim primarily to protect user identities, have gained prominence as tools for enhancing network security and anonymity. Nonetheless, these networks have become a platform for adversarial affairs and sources of suspicious attack traffic. To defend against unpredictable adversaries on the Internet, detecting anonymous network traffic has emerged as a necessity. Many supervised approaches to identify anonymous traffic have harnessed machine learning strategies. However, many require access to engineered datasets and complex architectures to extract the desired information. Due to the resistance of anonymous network traffic to traffic analysis and the scarcity of publicly available datasets, those approaches may need to improve their training efficiency and achieve a higher performance when it comes to anonymous traffic detection. This study utilizes feature engineering techniques to extract pattern information and rank the feature importance of the static traces of anonymous traffic. To leverage these pattern attributes effectively, we developed a reinforcement learning framework that encompasses four key components: states, actions, rewards, and state transitions. A lightweight system is devised to classify anonymous and non-anonymous network traffic. Subsequently, two fine-tuned thresholds are proposed to substitute the traditional labels in a binary classification system. The system will identify anonymous network traffic without reliance on labeled data. The experimental results underscore that the system can identify anonymous traffic with an accuracy rate exceeding 80% (when based on pattern information).
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  • 文章类型: Journal Article
    巨自噬/自噬是细胞用来应对有害条件的策略,例如营养缺乏。吞噬细胞,自噬体的前体,在内质网(ER)上启动和扩展。然而,吞噬细胞和完整的自噬体是如何与内质网连接的,目前尚不完全清楚.我们最近公布了两个结构之间的基于RABGTPase的连接。RABC1是RABC/RAB18GTPases的植物成员。我们的生化和显微镜数据表明,RABC1促进自噬响应营养饥饿,但不是在ER压力下。在营养饥饿的条件下,活性RABC1与ER上的ATG18a相互作用,控制ATG18a与ER的关联。随后,活性RABC1被关闭,允许扩大的吞噬团或自噬体从ER分离。我们的工作确定了植物细胞中RABGTP酶介导的自噬过程,为在不断变化的环境中提高作物生产力打开一扇门。
    Macroautophagy/autophagy is a strategy cells use to cope with detrimental conditions, e.g. nutrient deficiency. Phagophores, the precursors to autophagosomes, are initiated and expanded on the endoplasmic reticulum (ER). However, how phagophores and completed autophagosomes are linked to the ER remains incompletely understood. We recently unveiled a RAB GTPase-based linkage between the two structures. RABC1 is a plant member of RABC/RAB18 GTPases. Our biochemical and microscopy data indicated that RABC1 promotes autophagy in response to nutrient starvation, but not under ER stress. Under nutrient-starvation conditions, active RABC1 interacts with ATG18a on the ER, controlling the association of ATG18a to the ER. Subsequently, active RABC1 is turned off allowing expanded phagophores or autophagosomes to detach from the ER. Our work identifies a RAB GTPase-mediated autophagy process in plant cells, opening a door for improving crop productivity in the changing environment.
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  • 文章类型: Journal Article
    了解代谢表现的局限性是解释过去的关键,生活的现在和未来。我们调查了活跃飞行的果蝇的耐热性是否因细胞大小和环境中氧气量的个体差异而受到影响。我们在与雷帕霉素(TOR)/胰岛素途径相关的细胞大小控制中使用了两种功能丧失突变的突变体,与对照相比,在不同的身体组织中显示出减少的(突变型rictorΔ2)或增加的(突变型Mnt1)细胞大小。苍蝇在常氧和缺氧下暴露于温度的稳定升高,直到它们崩溃。响应于每种突变类型以及在缺氧条件下,最高临界温度降低。雌性,它们的细胞比雄性大,耐热性低于男性。总之,细胞周期控制途径中的突变,细胞大小的差异和氧气可用性的差异影响耐热性,但是关于细胞大小和组织氧合在代谢表现中的作用的现有理论只能部分解释我们的结果。对身体细胞组成如何影响新陈代谢的更好理解可能取决于研究模型的发展,这些模型有助于将各种干扰生理参数与细胞大小的专有影响分开。本文是“代谢率变化的进化意义”主题的一部分。
    Understanding metabolic performance limitations is key to explaining the past, present and future of life. We investigated whether heat tolerance in actively flying Drosophila melanogaster is modified by individual differences in cell size and the amount of oxygen in the environment. We used two mutants with loss-of-function mutations in cell size control associated with the target of rapamycin (TOR)/insulin pathways, showing reduced (mutant rictorΔ2) or increased (mutant Mnt1) cell size in different body tissues compared to controls. Flies were exposed to a steady increase in temperature under normoxia and hypoxia until they collapsed. The upper critical temperature decreased in response to each mutation type as well as under hypoxia. Females, which have larger cells than males, had lower heat tolerance than males. Altogether, mutations in cell cycle control pathways, differences in cell size and differences in oxygen availability affected heat tolerance, but existing theories on the roles of cell size and tissue oxygenation in metabolic performance can only partially explain our results. A better understanding of how the cellular composition of the body affects metabolism may depend on the development of research models that help separate various interfering physiological parameters from the exclusive influence of cell size. This article is part of the theme issue \'The evolutionary significance of variation in metabolic rates\'.
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  • 文章类型: Journal Article
    水稻产量约占农业利用的淡水资源的一半,导致淹没稻田的甲烷(CH4)等温室气体排放。为了应对这一挑战,环保和经济有效的节水技术已在水稻种植中广泛采用。然而,在水稻中实施节水处理(WST)与高达50%的大量产量损失以及氮利用效率(NUE)的降低有关。在这项研究中,我们发现在WST条件下,水稻中雷帕霉素(TOR)信号通路的靶标受到了损害。通过多聚体谱分析偶联转录组测序(polysome-seq)分析,我们观察到与TOR活性下调相关的WST的全球翻译显著减少.分子,生物化学,遗传分析揭示了对阳性TOR-S6K-RPS6和阴性TOR-MAF1模块对WST下翻译抑制的影响的新见解。有趣的是,铵通过增强TOR信号传导表现出更大的缓解WST下生长限制的能力,同时促进了铵和氮分配的吸收和利用。我们进一步证明,TOR通过5'非翻译区(5'UTR)在翻译水平上调节铵转运蛋白AMT1;1以及氨基酸通透酶APP1和二肽转运蛋白NPF7.3。总的来说,这些发现表明,增强TOR信号可以通过调节蛋白质合成和NUE的过程来减轻WST导致的水稻产量损失。本研究将有助于选育提高水肥利用率的水稻新品种。
    Rice production accounts for approximately half of the freshwater resources utilized in agriculture, resulting in greenhouse gas emissions such as methane (CH4) from flooded paddy fields. To address this challenge, environmentally friendly and cost-effective water-saving techniques have become widely adopted in rice cultivation. However, the implementation of water-saving treatments (WSTs) in paddy-field rice has been associated with a substantial yield loss of up to 50% as well as a reduction in nitrogen use efficiency (NUE). In this study, we discovered that the target of rapamycin (TOR) signaling pathway is compromised in rice under WST. Polysome profiling-coupled transcriptome sequencing (polysome-seq) analysis unveiled a substantial reduction in global translation in response to WST associated with the downregulation of TOR activity. Molecular, biochemical, and genetic analyses revealed new insights into the impact of the positive TOR-S6K-RPS6 and negative TOR-MAF1 modules on translation repression under WST. Intriguingly, ammonium exhibited a greater ability to alleviate growth constraints under WST by enhancing TOR signaling, which simultaneously promoted uptake and utilization of ammonium and nitrogen allocation. We further demonstrated that TOR modulates the ammonium transporter AMT1;1 as well as the amino acid permease APP1 and dipeptide transporter NPF7.3 at the translational level through the 5\' untranslated region. Collectively, these findings reveal that enhancing TOR signaling could mitigate rice yield penalty due to WST by regulating the processes involved in protein synthesis and NUE. Our study will contribute to the breeding of new rice varieties with increased water and fertilizer utilization efficiency.
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  • 文章类型: Journal Article
    钾(K)是植物生长必需的常量营养素,它在土壤中的可用性差异很大,要求植物应对和适应不断变化的钾营养状况。我们在这里表明,植物生长速率与培养基中的钾状态密切相关,这种依赖钾的生长是由高度保守的营养传感器介导的,雷帕霉素靶蛋白(TOR)。进一步的研究将TOR复合物(TORC)途径与低K反应信号网络联系起来,该网络由钙调磷酸酶B样蛋白(CBL)和CBL相互作用激酶(CIPK)组成。在高K条件下,TORC通过TOR的调节相关蛋白(RAPTOR)-CIPK相互作用迅速激活并关闭CBL-CIPK低K应答途径。相比之下,低K状态激活CBL-CIPK模块,进而通过磷酸化RAPTOR抑制TORC,导致TORC的解离和失活。TORC和CBL-CIPK模块的相互调节协调植物对环境中K营养状况的响应和适应。
    Potassium (K) is an essential macronutrient for plant growth, and its availability in the soil varies widely, requiring plants to respond and adapt to the changing K nutrient status. We show here that plant growth rate is closely correlated with K status in the medium, and this K-dependent growth is mediated by the highly conserved nutrient sensor, target of rapamycin (TOR). Further study connected the TOR complex (TORC) pathway with a low-K response signaling network consisting of calcineurin B-like proteins (CBL) and CBL-interacting kinases (CIPK). Under high K conditions, TORC is rapidly activated and shut down the CBL-CIPK low-K response pathway through regulatory-associated protein of TOR (RAPTOR)-CIPK interaction. In contrast, low-K status activates CBL-CIPK modules that in turn inhibit TORC by phosphorylating RAPTOR, leading to dissociation and thus inactivation of the TORC. The reciprocal regulation of the TORC and CBL-CIPK modules orchestrates plant response and adaptation to K nutrient status in the environment.
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  • 文章类型: Journal Article
    随着互联网的兴起,人们越来越关注用户的匿名性。匿名通信网络(ACN)旨在保护网络中用户的身份隐私。作为典型的ACN,Tor通过一系列中继节点中继用户数据来实现用户匿名性。然而,由于多个节点之间的网络流量传输,这将导致更高的延迟。本文提出了一种基于端口的匿名通信网络(PBACN)来解决这一问题。首先,提出了一种路径构建算法。该算法描述了通过划分通信路径信息来构建路径,这可以降低被对手发现的可能性。其次,设计了一种基于端口的源路由寻址方法。在从源到目标的数据传输过程中,每个节点可以通过解析地址到每个节点的端口直接转发数据。此方法消除了对表查找的需要,降低路由的复杂性。最后,我们提出了一种基于熵的度量来衡量不同ACN的匿名性。在实验评价方面,我们定量分析了各种ACN的匿名性和端到端延迟。实验结果表明,与Tor相比,我们提出的方法将端到端延迟减少了约25%。当对手分数是20%时,PBACN可以将匿名度提高约4%。
    With the rise of the internet, there has been an increasing focus on user anonymity. Anonymous communication networks (ACNs) aim to protect the identity privacy of users in the network. As a typical ACN, Tor achieves user anonymity by relaying user data through a series of relay nodes. However, this results in higher latency due to the transmission of network traffic between multiple nodes. This paper proposes a port-based anonymous communication network (PBACN) to address this issue. First, we propose a path construction algorithm. This algorithm describes constructing paths by partitioning the communication path information, which can reduce the probability of being discovered by adversaries. Secondly, we design a port-based source routing addressing method. During data transmission from the source to the destination, each node can directly forward the data by resolving the address into the port of each node. This method eliminates the need for table lookups, reducing the complexity of routing. Lastly, we propose an entropy-based metric to measure the anonymity of different ACNs. In terms of experimental evaluation, we quantitatively analyze the anonymity and end-to-end delay of various ACNs. The experimental results show that our proposed method reduces end-to-end delay by approximately 25% compared to Tor. When the adversary fraction is 20%, PBACN can improve the anonymity degree by approximately 4%.
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  • 文章类型: Journal Article
    高度保守的TOR信号通路对于协调真核生物的细胞生长与细胞周期机制至关重要。萌芽酵母中的两种TOR复合物之一,TORC1,整合环境线索,促进细胞生长。当细胞生长时,他们需要复制他们的染色体,在有丝分裂中分离它们,在胞质分裂过程中分裂它们的所有成分,最后将母细胞和子细胞物理上分开,开始一个新的细胞周期。为了保持细胞大小稳态和染色体稳定性,至关重要的是,控制生长的机制与细胞周期相联系和协调。连续的高和低TORC1活性时期将参与适当的细胞周期进程。这里,我们回顾了已知的分子机制,通过它TORC1调节细胞周期的发芽酵母酿酒酵母,已被广泛用作模型生物,以了解其哺乳动物直系同源的作用,mTORC1.
    The highly conserved TOR signaling pathway is crucial for coordinating cellular growth with the cell cycle machinery in eukaryotes. One of the two TOR complexes in budding yeast, TORC1, integrates environmental cues and promotes cell growth. While cells grow, they need to copy their chromosomes, segregate them in mitosis, divide all their components during cytokinesis, and finally physically separate mother and daughter cells to start a new cell cycle apart from each other. To maintain cell size homeostasis and chromosome stability, it is crucial that mechanisms that control growth are connected and coordinated with the cell cycle. Successive periods of high and low TORC1 activity would participate in the adequate cell cycle progression. Here, we review the known molecular mechanisms through which TORC1 regulates the cell cycle in the budding yeast Saccharomyces cerevisiae that have been extensively used as a model organism to understand the role of its mammalian ortholog, mTORC1.
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  • 文章类型: Journal Article
    巨自噬/自噬是一个高度保守的分解代谢过程,对于细胞应激反应和维持细胞内的平衡至关重要。自噬功能异常与多种疾病的发病机制有关。包括某些神经退行性疾病,糖尿病,代谢性疾病,和癌症。细胞面临不同的代谢挑战,例如氮气的限制,碳,以及磷酸盐和铁等矿物质,需要整合复杂的代谢信息。细胞利用传感器的信号转导网络,传感器,以及协调自噬反应执行的效应器,伴随着营养饥饿状况的严重程度。这篇综述介绍了当前对细胞如何通过各种营养依赖性信号通路调节自噬启动的机制理解。强调酵母研究的结果,我们探索了营养依赖性自噬调节的新原理,在各种代谢应激条件下显着塑造应激诱导的自噬反应。
    Macroautophagy/autophagy is a highly conserved catabolic process vital for cellular stress responses and maintaining equilibrium within the cell. Malfunctioning autophagy has been implicated in the pathogenesis of various diseases, including certain neurodegenerative disorders, diabetes, metabolic diseases, and cancer. Cells face diverse metabolic challenges, such as limitations in nitrogen, carbon, and minerals such as phosphate and iron, necessitating the integration of complex metabolic information. Cells utilize a signal transduction network of sensors, transducers, and effectors to coordinate the execution of the autophagic response, concomitant with the severity of the nutrient-starvation condition. This review presents the current mechanistic understanding of how cells regulate the initiation of autophagy through various nutrient-dependent signaling pathways. Emphasizing findings from studies in yeast, we explore the emerging principles that underlie the nutrient-dependent regulation of autophagy, significantly shaping stress-induced autophagy responses under various metabolic stress conditions.
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  • 文章类型: Journal Article
    植物根部探索土壤中的水分和养分,从而决定植物适应性和农业产量,以及确定地面下部结构,水位,和全球碳封存。土壤的殖民需要碳和能源的投资,但是糖和能量信号如何与根分支整合是未知的。这里,我们通过结合遗传和化学调节信号通路表明糖小分子信号,海藻糖-6-磷酸(T6P)通过主激酶SNF1相关激酶-1(SnRK1)和雷帕霉素靶(TOR)以及植物激素生长素的参与来调节根分支。通过侧根(LR)建立细胞中的遗传靶向和通过前信号T6P前体的光活化释放来增加T6P水平,这表明T6P通过协同抑制SnRK1和激活TOR来增加根分支。生长素,LR编队的主调节器,通过转录下调LR细胞中的T6P降解剂磷酸海藻糖磷酸酶B来影响T6P功能。我们的结果揭示了LR形成的调节能量平衡网络,该网络将“糖信号”T6P与生长素下游的SnRK1和TOR联系起来。
    Plant roots explore the soil for water and nutrients, thereby determining plant fitness and agricultural yield, as well as determining ground substructure, water levels, and global carbon sequestration. The colonization of the soil requires investment of carbon and energy, but how sugar and energy signaling are integrated with root branching is unknown. Here, we show through combined genetic and chemical modulation of signaling pathways that the sugar small-molecule signal, trehalose-6-phosphate (T6P) regulates root branching through master kinases SNF1-related kinase-1 (SnRK1) and Target of Rapamycin (TOR) and with the involvement of the plant hormone auxin. Increase of T6P levels both via genetic targeting in lateral root (LR) founder cells and through light-activated release of the presignaling T6P-precursor reveals that T6P increases root branching through coordinated inhibition of SnRK1 and activation of TOR. Auxin, the master regulator of LR formation, impacts this T6P function by transcriptionally down-regulating the T6P-degrader trehalose phosphate phosphatase B in LR cells. Our results reveal a regulatory energy-balance network for LR formation that links the \'sugar signal\' T6P to both SnRK1 and TOR downstream of auxin.
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