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Elementary calcium signaling in arterial smooth muscle 动脉平滑肌中的基本钙信号
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-01-01 DOI: 10.1080/19336950.2019.1688910
Gang Fan, Yingqiu Cui, M. Gollasch, M. Kassmann
ABSTRACT Vascular smooth muscle cells (VSMCs) of small peripheral arteries contribute to blood pressure control by adapting their contractile state. These adaptations depend on the VSMC cytosolic Ca2+ concentration, regulated by complex local elementary Ca2+ signaling pathways. Ca2+ sparks represent local, transient, rapid calcium release events from a cluster of ryanodine receptors (RyRs) in the sarcoplasmic reticulum. In arterial SMCs, Ca2+ sparks activate nearby calcium-dependent potassium channels, cause membrane hyperpolarization and thus decrease the global intracellular [Ca2+] to oppose vasoconstriction. Arterial SMC Cav1.2 L-type channels regulate intracellular calcium stores content, which in turn modulates calcium efflux through RyRs. Cav3.2 T-type channels contribute to a minor extend to Ca2+ spark generation in certain types of arteries. Their localization within cell membrane caveolae is essential. We summarize present data on local elementary calcium signaling (Ca2+ sparks) in arterial SMCs with focus on RyR isoforms, large-conductance calcium-dependent potassium (BKCa) channels, and cell membrane-bound calcium channels (Cav1.2 and Cav3.2), particularly in caveolar microdomains.
外周小动脉血管平滑肌细胞(VSMCs)通过调节其收缩状态参与血压控制。这些适应依赖于VSMC细胞质Ca2+浓度,由复杂的局部基本Ca2+信号通路调节。钙离子火花代表局部的,短暂的,快速的钙释放事件从肌浆网的一群红嘌呤受体(RyRs)。在动脉SMCs中,Ca2+火花激活附近的钙依赖性钾通道,引起膜超极化,从而降低整体细胞内[Ca2+]以对抗血管收缩。动脉SMC Cav1.2 l型通道调节细胞内钙储存含量,进而调节钙通过RyRs外排。在某些类型的动脉中,Cav3.2 t型通道有助于少量扩展Ca2+火花的产生。它们在细胞膜小泡内的定位至关重要。我们总结了动脉SMCs中局部基本钙信号(Ca2+火花)的现有数据,重点关注RyR亚型,大电导钙依赖性钾(BKCa)通道和细胞膜结合钙通道(Cav1.2和Cav3.2),特别是在腔泡微域。
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引用次数: 22
PI3Kα in cardioprotection: Cytoskeleton, late Na+ current, and mechanism of arrhythmias PI3Kα在心脏保护中的作用:细胞骨架、晚期Na+电流和心律失常的机制
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-01-01 DOI: 10.1080/19336950.2019.1697127
P. Zhabyeyev, Xueyi Chen, B. Vanhaesebroeck, G. Oudit
ABSTRACT PI 3-kinase α (PI3Kα) is a lipid kinase that converts phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-triphosphate (PIP3). PI3Kα regulates a variety of cellular processes such as nutrient sensing, cell cycle, migration, and others. Heightened activity of PI3Kα in many types of cancer made it a prime oncology drug target, but also raises concerns of possible adverse effects on the heart. Indeed, recent advances in preclinical models demonstrate an important role of PI3Kα in the control of cytoskeletal integrity, Na+ channel activity, cardioprotection, and prevention of arrhythmias.
PI3Kα (PI3Kα)是一种脂质激酶,可将磷脂酰肌醇4,5-二磷酸(PIP2)转化为磷脂酰肌醇3,4,5-三磷酸(PIP3)。PI3Kα调节多种细胞过程,如营养感知、细胞周期、迁移等。PI3Kα在多种癌症中的活性升高使其成为主要的肿瘤药物靶点,但也引起了对心脏可能产生不良影响的担忧。事实上,临床前模型的最新进展表明,PI3Kα在控制细胞骨架完整性、Na+通道活性、心脏保护和预防心律失常方面发挥了重要作用。
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引用次数: 10
Role of the voltage sensor module in Nav domain IV on fast inactivation in sodium channelopathies: The implication of closed-state inactivation Nav结构域电压传感器模块在钠通道病变快速失活中的作用:闭合状态失活的含义
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-01-01 DOI: 10.1080/19336950.2019.1649521
T. Nakajima, Y. Kaneko, Tommy Dharmawan, M. Kurabayashi
ABSTRACT The segment 4 (S4) voltage sensor in voltage-gated sodium channels (Navs) have domain-specific functions, and the S4 segment in domain DIV (DIVS4) plays a key role in the activation and fast inactivation processes through the coupling of arginine residues in DIVS4 with residues of putative gating charge transfer center (pGCTC) in DIVS1-3. In addition, the first four arginine residues (R1-R4) in Nav DIVS4 have position-specific functions in the fast inactivation process, and mutations in these residues are associated with diverse phenotypes of Nav-related diseases (sodium channelopathies). R1 and R2 mutations commonly display a delayed fast inactivation, causing a gain-of-function, whereas R3 and R4 mutations commonly display a delayed recovery from inactivation and profound use-dependent current attenuation, causing a severe loss-of-function. In contrast, mutations of residues of pGCTC in Nav DIVS1-3 can also alter fast inactivation. Such alterations in fast inactivation may be caused by disrupted interactions of DIVS4 with DIVS1-3. Despite fast inactivation of Navs occurs from both the open-state (open-state inactivation; OSI) and closed state (closed-state inactivation; CSI), changes in CSI have received considerably less attention than those in OSI in the pathophysiology of sodium channelopathies. CSI can be altered by mutations of arginine residues in DIVS4 and residues of pGCTC in Navs, and altered CSI can be an underlying primary biophysical defect of sodium channelopathies. Therefore, CSI should receive focus in order to clarify the pathophysiology of sodium channelopathies.
电压门控钠离子通道(Navs)中的4段(S4)电压传感器具有域特异性功能,而DIV域(DIVS4)中的S4段通过DIVS4中的精氨酸残基与DIVS1-3中假定的门控电荷转移中心(pGCTC)残基的耦合在激活和快速失活过程中起关键作用。此外,Nav DIVS4中的前四个精氨酸残基(R1-R4)在快速失活过程中具有位置特异性功能,这些残基的突变与Nav相关疾病(钠通道病)的多种表型相关。R1和R2突变通常表现为延迟的快速失活,导致功能获得,而R3和R4突变通常表现为延迟的失活恢复和严重的使用依赖的电流衰减,导致严重的功能丧失。相反,Nav DIVS1-3中pGCTC残基的突变也可以改变快速失活。这种快速失活的改变可能是由DIVS4与DIVS1-3的相互作用中断引起的。尽管nav的快速失活发生在开放状态(开放状态失活;OSI)和关闭状态(关闭状态失活;CSI),在钠通道病变的病理生理学中,CSI的变化比OSI的变化受到的关注要少得多。DIVS4中精氨酸残基和nav中pGCTC残基的突变可以改变CSI, CSI的改变可能是钠通道病潜在的原发性生物物理缺陷。因此,为了阐明钠通道病变的病理生理机制,CSI应受到重视。
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引用次数: 11
A Call to Peace: How Third-Party Actors and Frameworks Impacted the Peace Processes of Northern Ireland and Colombia 呼吁和平:第三方行为体和框架如何影响北爱尔兰和哥伦比亚的和平进程
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-12-14 DOI: 10.15385/JCH.2018.3.1.3
Esther K Holm
Northern Ireland and Colombia both serve as excellent case studies on how the end of the Cold War impacted peace processes. Both countries experienced conflicts that begun in the Cold War era and underwent peace processes in the post-Cold War era. As such, studying them reveals characteristics of post-Cold War peace processes. For example, both Northern Ireland and Colombia showcase the important role that third-party actors play in modern conflict mediation. Both countries benefited greatly from mediation conducted by international organization, other countries, and individuals. Furthermore, both countries demonstrate the importance of frameworks in any successful peace negotiation. This paper argues that third-party actors greatly benefit peace processes and that a detailed framework is imperative to a successful peace process.
北爱尔兰和哥伦比亚都是研究冷战结束如何影响和平进程的优秀案例。两国都经历了始于冷战时代的冲突,并在冷战后的时代经历了和平进程。因此,研究它们揭示了冷战后和平进程的特点。例如,北爱尔兰和哥伦比亚都展示了第三方行为体在现代冲突调解中发挥的重要作用。两国都从国际组织、其他国家和个人的调解中受益匪浅。此外,两国都表明了框架在任何成功的和平谈判中的重要性。本文认为,第三方行为体极大地有利于和平进程,一个详细的框架是和平进程成功的必要条件。
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引用次数: 0
21st Century Javelin Catchers: White House Organization and the Chief of Staff 21世纪标枪捕手:白宫组织和办公厅主任
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-12-14 DOI: 10.15385/JCH.2018.3.1.5
Molly Schwall
This research discusses the impact that White House organization has on the roles of chief of staff. The paper begins with an overview of the major models of White House organization and the roles typically performed by chief of staff. By examining the impact of organizational difficulties faced by the chiefs of staff in the presidencies of George W. Bush and Barack Obama through case studies, this research seeks to situate the major roles of chief of staff within White House organization to examine the impact of organization on chief of staff performance. The findings of the case studies suggest that the formalistic model of White House organization best serves the roles of chief of staff by providing clear, delineated lines of organization with specific tasks for White House staffing. The paper concludes by examining the presidency of Donald Trump and the organizational difficulties faced during the first year of his administration.
本研究讨论了白宫组织对办公厅主任角色的影响。本文首先概述了白宫组织的主要模式和办公厅主任通常扮演的角色。通过案例研究,研究了乔治·w·布什和巴拉克·奥巴马总统任期内参谋长所面临的组织困难的影响,本研究试图将白宫组织内参谋长的主要角色定位,以研究组织对参谋长绩效的影响。案例研究的结果表明,白宫组织的形式主义模式最适合办公厅主任的角色,因为它为白宫人员配备提供了明确、划定的组织线和具体任务。本文最后考察了唐纳德·特朗普的总统任期以及他执政第一年面临的组织困难。
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引用次数: 0
The Speech Act of Naming in Context: A Linguistic Study of Naming in the Old Testament 语境中命名的言语行为:旧约中命名的语言学研究
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-12-14 DOI: 10.15385/JCH.2018.3.1.2
L. Yost
This research sought to study the act of naming in the context of the Old Testament using speech act theory. To analyze naming as presented in the Old Testament, I first studied the Hebrew words qārāʾ and šēm, creating from my findings the following extended definition: (naming is) the act of giving a name within particular specified circumstances by one with authority over the name-receiver, whose authority is respected by others such that the name spoken is hence used to identify and represent the receiver. This, along with an understanding of Alston (2000) and the example of Arcadi (2013), shaped a schema of illocutionary rules and conditions that I then tested in nine case studies of naming throughout the Old Testament. Key components include particular circumstances, necessary conditions and authority, and the occurrence within a community. Ultimately, I conclude naming as presented in the Old Testament is in fact a speech act that is subject to particular rules and carries great importance.
本研究试图用言语行为理论来研究旧约背景下的命名行为。为了分析旧约中出现的命名,我首先研究了希伯来语qārā和šēm,根据我的发现创建了以下扩展定义:(命名是)在特定的特定情况下,由一个对名字接受者有权威的人命名的行为,他的权威受到其他人的尊重,因此所说的名字被用来识别和代表接受者。这一点,加上对奥尔斯顿(2000)和阿卡迪(2013)的理解,形成了一个言外之语规则和条件的图式,然后我在整个旧约的九个命名案例研究中进行了测试。关键组成部分包括特定的情况、必要的条件和权力,以及在社区内发生的事件。最后,我得出结论,旧约中的命名实际上是一种言语行为,受特定规则的约束,具有重要意义。
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引用次数: 0
Eyes on the Money: How Realist Economic Policy Facilitates the Modern Surveillance State in the USA and the PRC 金钱的目光:现实主义经济政策如何促进美国和中国的现代监督国家
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-12-14 DOI: 10.15385/JCH.2018.3.1.7
Benjamin Warder
This paper examines the manner in which the United States of America and the People’s Republic of China, as the world’s leading economic superpowers, pursue a generally realist international relations approach to maintaining and securing their bases of economic power, and how this purpose translates into the development and proliferation of Closed Circuit Television (CCTV) camera networks in major cities as a means of protecting those cities as economic hubs crucial to the national economy. Two research questions guide the paper. First, how does each state demonstrate realist policies in the process of securing economic centers and the overall protection of its economy? Second, how does the use of CCTV contribute to the security and functionality of major economic centers in each state? Through a case comparison, the study examines the two countries on the bases of differences in governmental ideological orientation, justification of continued government-operated CCTV proliferation, and likelihood of altering that proliferation by civic means, ultimately concluding that as the international system retains its competitive atmosphere, surveillance state policies will continue to be the norm as national government purpose to maintain bases of global power.
本文考察了美利坚合众国和中华人民共和国作为世界领先的经济超级大国,采取普遍现实主义的国际关系方法来维持和确保其经济实力基础的方式,以及这一目的如何转化为主要城市闭路电视(CCTV)摄像机网络的发展和扩散,作为保护这些城市作为对国民经济至关重要的经济中心的手段。两个研究问题指导论文。首先,每个国家在确保经济中心和全面保护其经济的过程中如何展示现实主义政策?其次,CCTV的使用如何有助于各州主要经济中心的安全和功能?通过案例比较,本研究考察了两国在政府意识形态取向、政府运作的闭路电视继续扩散的理由以及通过公民手段改变这种扩散的可能性方面的差异,最终得出结论:随着国际体系保持其竞争氛围,监控国家政策将继续成为国家政府维持全球权力基础的规范。
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引用次数: 0
Seeing Green Through the Eyes of National Oil Companies: A Comparison of Gazprom’s and Petrobras’ Environmental Sustainability 从国家石油公司的角度看绿色:俄罗斯天然气工业股份公司和巴西石油公司环境可持续性的比较
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-12-14 DOI: 10.15385/jch.2018.3.1.6
J. A. Thompson
The case studies of Gazprom and Petrobras are used to compare the interaction and relation between national oil companies, the state government and environmental policy. Specifically the paper seeks to address how the policy and interaction between the state government and the NOCs affect sustainable development of the preservation of the environment. The methodology used is set out by senior research international scholar, Eduardo Viola. He examines the state government’s position on the climate through three criteria: reduction of greenhouse gas (GHG) emissions, domestic climate policies and the state’s international standing on the issue. The United Nations Framework Convention on Climate Change (UNFCCC) GHG Inventory data, Brazil and Russia’s energy strategies and a third-party newspaper reporter will all be used to compare the two case studies. The research discovers that protection of the natural environment is an area of lesser importance to more predominant state goals of energy development and independence and the foreign policy agendas of legitimizing or leveraging the state’s energy capabilities towards other nations.
通过对俄罗斯天然气工业股份公司和巴西国家石油公司的案例研究,比较了国有石油公司、州政府和环境政策之间的相互作用和关系。具体而言,本文试图解决州政府和国有石油公司之间的政策和互动如何影响环境保护的可持续发展。所使用的方法是由资深国际研究学者Eduardo Viola提出的。他通过三个标准考察了州政府在气候问题上的立场:减少温室气体(GHG)排放、国内气候政策和该州在这个问题上的国际地位。联合国气候变化框架公约(UNFCCC)的温室气体清单数据、巴西和俄罗斯的能源战略以及第三方报纸记者都将被用来比较这两个案例研究。研究发现,与能源发展和独立的国家目标以及使国家能源能力合法化或利用国家能源能力对其他国家的外交政策议程相比,保护自然环境是一个不那么重要的领域。
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引用次数: 0
Public Principles and Economic Legacy 公共原则和经济遗产
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-04-27 DOI: 10.15385/JCH.2018.2.2.2
Stanley G. Schwartz
Abstract 2018 will mark the 60 th anniversary of the publication of Public Principles of Public Debt. The Nobel-prize winning economist’s first book conflicted with the Keynesian orthodoxy of the day, and added fresh ideas to an ongoing debate over the fundamentals of public debt theory. This paper seeks to outline the dialogue among leading economists surrounding public debt since the publication of Public Principles of Public Debt, examining the major schools of thought and their development. The ideas of John Maynard Keynes, James Buchanan, and Richard Barro will receive attention, without neglecting other significant contributions. The paper will conclude by examining current papers in the field of public debt theory, considering them in light of the noted historical ideas. Despite the foundational nature of James Buchanan’s work in public finance, his cautions regarding the assumptions, methodology, incentives, and institutions of public debt, particularly his integration of public choice, are not treated centrally in many ongoing analyses. The empirical nature of much current public debt theory and research has led away from the presuppositional roots of the public debt debate. Renewed awareness of the historical and theoretical realities of public debt theory will be valuable for the field, and can provide reinvigorated application of public choice. This paper works toward those goals, examining the 60 years of public debt theory history since the publication of James Buchanan’s Public Principles of Public Debt and considering current work in the field.
2018年是《公共债务原则》出版60周年。这位获得诺贝尔奖的经济学家的第一本书与当时的正统凯恩斯主义存在冲突,并为正在进行的关于公共债务理论基本原理的辩论增添了新的观点。本文旨在概述自《公共债务的公共原则》出版以来,主要经济学家之间围绕公共债务的对话,考察主要思想流派及其发展。约翰•梅纳德•凯恩斯(John Maynard Keynes)、詹姆斯•布坎南(James Buchanan)和理查德•巴罗(Richard Barro)的思想将受到关注,同时也不会忽视其他重要贡献。最后,本文将考察当前公共债务理论领域的论文,并根据著名的历史思想进行思考。尽管詹姆斯·布坎南在公共财政方面的工作具有基础性,但他对公共债务的假设、方法、激励和制度的警告,特别是他对公共选择的整合,并没有在许多正在进行的分析中得到集中处理。当前许多公共债务理论和研究的实证性质已经偏离了公共债务辩论的预设根源。重新认识公共债务理论的历史和理论现实,对这一领域将是有价值的,并可以为公共选择的应用提供新的活力。本文致力于实现这些目标,考察了自詹姆斯·布坎南(James Buchanan)的《公共债务原则》(public Principles of public debt)出版以来60年的公共债务理论史,并考虑了该领域目前的工作。
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引用次数: 1
A Four-Legged Megalosaurus and Swimming Brontosaurs 四足巨龙和会游泳的雷龙
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2018-04-27 DOI: 10.15385/jch.2018.2.2.5
Jordan C. Oldham
Thomas Kuhn in his famous work The Structure of Scientific Revolutions laid out the framework for his theory of how science changes. At the advent of dinosaur paleontology fossil hunters like Gideon Mantell discovered some of the first dinosaurs like Iguanodon and Megalosaurus. Through new disciples like Georges Cuvier’s comparative anatomy lead early dinosaur paleontologist to reconstruct them like giant reptiles of absurd proportions. This lead to the formation of a new paradigm that prehistoric animals like dinosaurs existed and eventually went extinct. The first reconstructions of dinosaur made them to look like giant counterparts of their modern cousins. Then in 1841, Richard Owen coined the term dinosaur, and put the newly discovered dinosaurs into a special group based on similar morphological characteristics. He reconstructed them to look like giant elephant like reptiles. They were slow, sluggish, and their tales dragged the ground. Then in 1858, William Foulke and Joseph Leidy discovered the dinosaur Hadrosaurus which had morphological characteristics that hindered the animal from being quadrupedal. As a result a new paradigm was formed and some dinosaurs were lifted off the ground. They were reconstructed to look like giant reptilian kangaroos in stance, but they were still considered slow, sluggish, with tails still dragging behind them. This paradigm persisted until the 1960’s when paleontologist John Ostrom realized that there was an anomaly within dinosaur paleontology. The environments that dinosaurs inhabited did not match with the reconstructions of swamp dwelling animals, and dinosaur anatomy also did not match those reconstructions. Ostrom’s discovery and description of Deinonychus with its very bird like skeleton lead him to conclude that dinosaurs were energetic, and probably endothermic. This resulted in a crisis which lead other paleontologist to research this anomaly. More discoveries proved Ostrom’s new paradigm and dinosaur paleontology underwent a scientific revolution from the 1960’s to the 1980’s. Formally termed the dinosaur renaissance this revolution lead to dinosaurs being reconstructed as active, intelligent animals no longer with their tails dragging behind them.
托马斯·库恩在他著名的著作《科学革命的结构》中为他的科学如何变化的理论奠定了框架。在恐龙古生物学出现时,像吉迪恩·曼特尔这样的化石猎人发现了一些最早的恐龙,比如禽龙和巨龙。通过像乔治·居维叶的比较解剖学这样的新信徒,早期的恐龙古生物学家把它们重建成荒诞比例的巨型爬行动物。这导致了一种新的范式的形成,即恐龙等史前动物存在并最终灭绝。对恐龙的第一次重建使它们看起来像它们现代表亲的巨大复制品。1841年,理查德·欧文创造了“恐龙”一词,并根据相似的形态特征将新发现的恐龙归入一个特殊的类群。他把它们重建成像大象一样的爬行动物。他们行动迟缓,步履蹒跚,他们的故事拖着地面。然后在1858年,威廉·福尔克和约瑟夫·莱迪发现了鸭嘴龙,这种恐龙的形态特征阻碍了它成为四足动物。结果形成了一个新的范式,一些恐龙被抬离了地面。它们被重建成站立时像巨型爬行类袋鼠的样子,但它们仍然被认为是缓慢、迟缓的,尾巴仍然拖在身后。这种模式一直持续到20世纪60年代,直到古生物学家约翰·奥斯特罗姆意识到恐龙古生物学中存在一种异常现象。恐龙居住的环境与重建的沼泽动物不匹配,恐龙的解剖结构也与这些重建的恐龙不匹配。奥斯特罗姆对恐爪龙的发现和描述,以及它非常像鸟的骨骼,使他得出这样的结论:恐龙是精力充沛的,而且可能是吸热的。这导致了一场危机,导致其他古生物学家开始研究这种异常现象。更多的发现证实了奥斯特罗姆的新范式,从20世纪60年代到80年代,恐龙古生物学经历了一场科学革命。这场革命被正式称为恐龙复兴,它使恐龙被改造成活跃、聪明的动物,不再拖着尾巴。
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引用次数: 1
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