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Role of aquaporins in cell proliferation: What else beyond water permeability? 水通道蛋白在细胞增殖中的作用:除了透水性之外还有什么?
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-01-11 DOI: 10.1080/19336950.2016.1139250
Ana Galán‐Cobo, R. Ramírez-Lorca, M. Echevarría
abstract In addition to the extensive data demonstrating the importance of mammalian AQPs for the movement of water and some small solutes across the cell membrane, there is now a growing body of evidence indicating the involvement of these proteins in numerous cellular processes seemingly unrelated, at least some of them in a direct way, to their canonical function of water permeation. Here, we have presented a broad range of evidence demonstrating that these proteins have a role in cell proliferation by various different mechanisms, namely, by allowing fast cell volume regulation during cell division; by affecting progression of cell cycle and helping maintain the balance between proliferation and apoptosis, and by crosstalk with other cell membrane proteins or transcription factors that, in turn, modulate progression of the cell cycle or regulate biosynthesis pathways of cell structural components. In the end, however, after discussing all these data that strongly support a role for AQPs in the cell proliferation process, it remains impossible to conclude that all these other functions attributed to AQPs occur completely independently of their water permeability, and there is a need for new experiments designed specifically to address this interesting issue.
除了大量的数据表明哺乳动物aqp对水和一些小溶质在细胞膜上的运动的重要性外,现在有越来越多的证据表明这些蛋白质参与许多细胞过程,这些过程似乎无关,至少其中一些以直接的方式参与其典型的水渗透功能。在这里,我们提出了广泛的证据,证明这些蛋白质通过各种不同的机制在细胞增殖中发挥作用,即在细胞分裂过程中允许快速的细胞体积调节;通过影响细胞周期进程,帮助维持细胞增殖与凋亡之间的平衡,并与其他细胞膜蛋白或转录因子串扰,进而调节细胞周期进程或调节细胞结构成分的生物合成途径。然而,最后,在讨论了所有这些强有力地支持AQPs在细胞增殖过程中的作用的数据之后,我们仍然不可能得出结论,所有这些归因于AQPs的其他功能都是完全独立于它们的水渗透性而发生的,并且需要专门设计新的实验来解决这个有趣的问题。
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引用次数: 41
Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation 天冬酰胺糖基化对Cav3.2 t型钙通道通透性的调节
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-01-08 DOI: 10.1080/19336950.2016.1138189
Katarína Ondáčová, M. Karmažínová, J. Lazniewska, N. Weiss, Ľ. Lacinová
abstract Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. Currently, little is known about the cellular mechanisms controlling the expression and function of T-type channels. Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. However, the role of N-glycans in the conducting function of T-type channels remains elusive. In the present study, we used human Cav3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states.
低压门控t型钙通道在整个神经系统中表达,在神经元兴奋性的形成中起重要作用。t型通道表达缺陷与包括神经性疼痛和癫痫在内的各种神经疾病有关。目前,对控制t型通道表达和功能的细胞机制知之甚少。天冬酰胺连接的糖基化最近被认为是细胞环境控制t型通道表达的重要信号通路。然而,n -聚糖在t型通道传导功能中的作用尚不清楚。在本研究中,我们使用人类Cav3.2糖基化缺陷通道来评估n-糖基化对通道门控的作用。膜片钳记录的门控电流显示,附着在hCav3.2通道上的n -聚糖对通道电压传感器的功能影响很小。相反,特定天冬酰胺残基上的n -糖基化可能通过增强通道的渗透性和/或孔道的开孔而对通道的传导功能起重要作用。我们的数据表明,调节hCav3.2通道的n -链糖基化可能发挥重要的生理作用,也可能支持在疾病状态下观察到的t型电流的改变。
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引用次数: 26
Regulation of Ca2+ signaling in prostate cancer cells 前列腺癌细胞中Ca2+信号的调控
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-01-08 DOI: 10.1080/19336950.2015.1137176
Tatiana Kilch, S. Kappel, C. Peinelt
AbstractPrecise intracellular Ca2+ signaling is crucial to ensure proper cellular functions. Subsequently, imbalances in Ca2+ signaling, particularly in store-operated Ca2+ entry (SOCE), contribute to several pathophysiological malfunctions in immune diseases and cancer. We lately reported on heteromeric Orai1/Orai3 SOCE channels and transient receptor potential melastatin-4 (TRPM4) channels in prostate cancer cells. We here sum up our findings and provide a model for the regulation of Ca2+ signaling in prostate cancer cells.
精确的细胞内Ca2+信号是保证细胞正常功能的关键。随后,Ca2+信号的不平衡,特别是在储存操作的Ca2+进入(SOCE)中,导致免疫疾病和癌症中的几种病理生理功能障碍。我们最近报道了前列腺癌细胞中异聚的Orai1/Orai3 SOCE通道和瞬时受体电位褪黑素-4 (TRPM4)通道。我们在此总结了我们的发现,并提供了Ca2+信号在前列腺癌细胞中的调节模型。
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引用次数: 11
Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells 正常和骨关节炎人滑液祖细胞中离子通道的表达和功能
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-01-05 DOI: 10.1080/19336950.2015.1116652
K. Bertram, U. Banderali, P. Tailor, R. Krawetz
ABSTRACT Osteoarthritis (OA) is a chronic disease affecting the cartilage of over 15% of Canadians. Synovial fluid mesenchymal progenitor cells (sfMPCs) are present in joints and are thought to contribute to healing. OA sfMPCs have a greater proliferative ability but decreased chondrogenic potential. However, little is known about the factors influencing/regulating the differences between normal and OA sfMPCs. Recently, our lab has shown that sfMPC chondrogenic differentiation in vitro is favorably biased toward a similar osmotic environment as they experience in vivo. The current study now examines the expression and functionality of a variety of ion channels in sfMPCs derived from normal individuals and early OA patients. Results indicated that there is differential ion channel regulation at the functional level and expression level in early OA sfMPCs. All ion channels were upregulated in early OA compared to normal sfMPCs with the exception of KCNMA1 at the mRNA level. At the protein level, TRPV4 was over expressed in early OA sfMPCs, while KCNJ12 and KCNMA1 were unchanged between normal and early OA sfMPCs. At the functional level, the inward rectifying potassium channel was under expressed in early OA sfMPCs, however the membrane potential was unchanged between normal and early OA sfMPCs. In the synovial environment itself, a number of differences in ion concentration between normal and early OA synovial fluid were observed. These findings suggest that normal and OA progenitor cells demonstrate functional differences in how they interact with the synovial ion environment.
骨关节炎(OA)是一种影响超过15%加拿大人软骨的慢性疾病。滑液间充质祖细胞(sfMPCs)存在于关节中,被认为有助于关节愈合。OA sfMPCs具有更强的增殖能力,但软骨形成潜力降低。然而,影响/调节正常和OA sfMPCs差异的因素知之甚少。最近,我们的实验室已经表明,sfMPC在体外的软骨分化倾向于与体内相似的渗透环境。目前的研究正在检查来自正常人和早期OA患者的sfMPCs中各种离子通道的表达和功能。结果表明,早期OA sfMPCs在功能水平和表达水平上存在不同的离子通道调节。与正常sfMPCs相比,早期OA中除KCNMA1 mRNA水平外,所有离子通道均上调。在蛋白水平上,TRPV4在早期OA sfMPCs中过表达,而KCNJ12和KCNMA1在正常和早期OA sfMPCs中没有变化。在功能水平上,向内纠偏钾通道在早期OA sfMPCs中表达不足,但膜电位在正常和早期OA sfMPCs之间没有变化。在滑膜环境本身中,观察到正常和早期OA滑膜液中离子浓度的许多差异。这些发现表明,正常和OA祖细胞在如何与滑膜离子环境相互作用方面表现出功能差异。
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引用次数: 16
Interactions between N and C termini of α1C subunit regulate inactivation of CaV1.2 L-type Ca2+ channel α1C亚基N和C端相互作用调控CaV1.2 l型Ca2+通道失活
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-01-02 DOI: 10.1080/19336950.2015.1108499
Adva Benmocha Guggenheimer, L. Almagor, V. Tsemakhovich, D. R. Tripathy, J. Hirsch, N. Dascal
The modulation and regulation of voltage-gated Ca2+ channels is affected by the pore-forming segments, the cytosolic parts of the channel, and interacting intracellular proteins. In this study we demonstrate a direct physical interaction between the N terminus (NT) and C terminus (CT) of the main subunit of the L-type Ca2+ channel CaV1.2, α1C, and explore the importance of this interaction for the regulation of the channel. We used biochemistry to measure the strength of the interaction and to map the location of the interaction sites, and electrophysiology to investigate the functional impact of the interaction. We show that the full-length NT (amino acids 1-154) and the proximal (close to the plasma membrane) part of the CT, pCT (amino acids 1508-1669) interact with sub-micromolar to low-micromolar affinity. Calmodulin (CaM) is not essential for the binding. The results further suggest that the NT-CT interaction regulates the channel's inactivation, and that Ca2+, presumably through binding to calmodulin (CaM), reduces the strength of NT-CT interaction. We propose a molecular mechanism in which NT and CT of the channel serve as levers whose movements regulate inactivation by promoting changes in the transmembrane core of the channel via S1 (NT) or S6 (pCT) segments of domains I and IV, accordingly, and not as a kind of pore blocker. We hypothesize that Ca2+-CaM-induced changes in NT-CT interaction may, in part, underlie the acceleration of CaV1.2 inactivation induced by Ca2+ entry into the cell.
电压门控Ca2+通道的调节和调节受孔形成段、通道的细胞质部分和相互作用的细胞内蛋白的影响。在本研究中,我们证明了l型Ca2+通道CaV1.2 α1C主要亚基的N端(NT)和C端(CT)之间的直接物理相互作用,并探讨了这种相互作用对通道调节的重要性。我们使用生物化学来测量相互作用的强度并绘制相互作用位点的位置,并使用电生理学来研究相互作用的功能影响。我们发现全长NT(氨基酸1-154)和CT的近端(靠近质膜)部分pCT(氨基酸1508-1669)具有亚微摩尔到低微摩尔亲和力。钙调素(CaM)对这种结合并不是必需的。结果进一步表明,NT-CT相互作用调节通道的失活,Ca2+可能通过与钙调蛋白(CaM)结合,降低NT-CT相互作用的强度。我们提出了一种分子机制,其中通道的NT和CT作为杠杆,其运动通过促进通道的跨膜核心通过S1 (NT)或S6 (pCT)结构域I和IV的变化来调节失活,而不是作为一种孔阻滞剂。我们假设Ca2+- cam诱导的NT-CT相互作用的变化可能在一定程度上是Ca2+进入细胞诱导的CaV1.2失活加速的基础。
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引用次数: 13
Feminist Theory and Technical Communication 女性主义理论与技术传播
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-01-01 DOI: 10.15385/JCH.2016.1.1.5
Olivia Duffus
This essay explores feminism, socially-constructed norms, and the relationship between feminism and technical communication. It argues that undergraduate technical communication programs should include courses that study feminist history and theories as related to the field, claiming that studying feminist theory will improve user-centered design and broaden students' spheres of influence as professionals.
本文探讨了女性主义、社会建构的规范以及女性主义与技术传播的关系。它认为,本科技术交流课程应该包括研究与该领域相关的女权主义历史和理论的课程,声称研究女权主义理论将改善以用户为中心的设计,并扩大学生作为专业人士的影响范围。
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引用次数: 0
Choosing to Choose: The Impact of Technology on Choice 选择:技术对选择的影响
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-01-01 DOI: 10.15385/JCH.2016.1.1.8
Aaron J. Alford
Abstract The development of modern technology has increasingly focused on efficiency over expression. Interfaces limit and scale down human choice and expression. Entertainment and communication now use interfaced technology for even basic human expression, artificially limiting the number of potential choices to the options presented by the interface. The logic of technology has become a totalizing phenomenon, bringing all areas of human life under it purview. According to Heidegger, Ellul, and Flusser, the result of this development is a different way of being-in-the-world for humans. The traditional man has been the constant in production and communication, which the medium and technology have been the variable. The modern man has reversed his orientation towards technology, the man is the variable and the machine is the constant. Building machines no longer appears to serve humanity, but instead has become an end in itself. Due to the methods of technology and quantification of nearly every decision, free choice is becoming more and more difficult to comprehend. As a case study for these arguments, The Stanley Parable examines how media can be used to limit possible choices, and can also be used to encourage new forms of play that counteract the predictability of machines and technical communication through human expression and increased computer literacy.
现代技术的发展越来越注重效率而非表达。界面限制和缩小了人类的选择和表达。娱乐和通信现在甚至使用界面技术来进行基本的人类表达,人为地限制了界面所呈现的潜在选择的数量。技术的逻辑已经成为一种综合现象,将人类生活的所有领域纳入其范围。根据海德格尔、埃卢和弗卢瑟的说法,这种发展的结果是人类以一种不同的方式存在于世界上。在生产和交流中,传统的人是不变的,媒介和技术是可变的。现代人已经扭转了他对技术的取向,人是变量,机器是常量。制造机器似乎不再为人类服务,相反,它本身已经成为一种目的。由于几乎所有决策的技术和量化方法,自由选择正变得越来越难以理解。作为这些争论的一个案例,《斯坦利的寓言》研究了媒体如何被用来限制可能的选择,也可以用来鼓励新的游戏形式,通过人类表达和提高计算机素养来抵消机器和技术交流的可预测性。
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引用次数: 0
AC Power Monitoring System 交流电源监控系统
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-01-01 DOI: 10.15385/jch.2016.1.1.7
Jared L. Newman, Luke M. Tomlinson, Grayson H. Dearing, F. Harmon
Motivated by high energy costs, people and organizations want to cut back on their energy consumption. However, the only feedback consumers typically receive is a monthly bill listing their total electricity usage (in kWh). Some companies have begun developing systems that allow households and organizations to monitor their energy usage for individual circuits. Available systems are expensive so a CU engineering senior design team has designed, fabricated, and tested a system for use at Cedarville University. The AC power monitoring system has the ability to measure energy consumption for each individual circuit in the breaker panel, store the data, and then provide the user with visual feedback on energy usage behavior. The basic system provides the proof of concept for future senior design teams. After more testing is completed, further development of this product will be needed by other senior design teams. Eventually, this energy monitoring system could be expanded to include larger loads such as HVAC systems and refrigeration units. It is also envisioned that future projects might be able to provide the user with suggestions for changing and improving energy usage behavior. Failure prediction of equipment on individual circuits could also stem from this initial project. For this project, it has been clearly shown that the concept is feasible, expandable, and cost-effective.
在高能源成本的激励下,个人和组织都希望减少能源消耗。然而,消费者通常收到的唯一反馈是列出他们总用电量(以千瓦时为单位)的月度账单。一些公司已经开始开发系统,允许家庭和组织监控他们的单个电路的能源使用情况。可用的系统价格昂贵,因此CU工程高级设计团队设计、制造并测试了一个系统,供Cedarville大学使用。交流电源监控系统能够测量断路器面板中每个单独电路的能耗,存储数据,然后向用户提供关于能耗行为的可视化反馈。该基本系统为未来的高级设计团队提供了概念验证。在更多的测试完成后,该产品将需要其他高级设计团队进一步开发。最终,这种能源监测系统可以扩展到包括更大的负荷,如暖通空调系统和制冷装置。未来的项目还可以为用户提供改变和改善能源使用行为的建议。单个电路上设备的故障预测也可能源于这个初始项目。对于这个项目,已经清楚地表明,这个概念是可行的,可扩展的,并且具有成本效益。
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引用次数: 1
Justification by Faith: A "Both-And" Approach 因信称义:一种“兼而有之”的方法
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-01-01 DOI: 10.15385/JCH.2016.1.1.1
Rodrigo N Reis
The Pauline doctrine of justification is a prevailing subject among biblical scholarship today. Especially, as a New Perspective on Pauline literature rises claiming that Luther was wrong in his view of Justification, since he was blinded by his own context forcing it into his interpretation of the Pauline text. Consequently, the reformed view cannot be right since it interprets the doctrine of justification mainly through soteriological lens, whereas the Apostle had only ecclesiological purposes in mind when addressing the subject. In light of the previous thought, the purpose of the article is to criticize the New Perspective’s exclusive method by proposing a “both-end” approach to Justification affirming the soteriological aspects of justification held by Luther, but also pointing out the reality of ecclesiological implications. The article is divided in two main sections. The first section highlights the NPP (New Perspective on Paul) definitions of key terms, such as “Works of the Law”, “the Righteousness of God”, and “Justification”, followed by important observations concerning their view of the terms. The second portion of the article provides three main arguments for Paul’s use of the doctrine of Justification having primarily in mind soteriological purposes. The hope for this work is not to solve the debate between both parties, but to demonstrate that the traditional (reformed) view concerning the doctrine of justification is not absurd, as some would say, and that it is possible to hold a soteriological position and still affirm ecclesiological implications to the Pauline doctrine.
保罗称义的教义是当今圣经学术研究的主流主题。特别是,随着一种新的保罗文学观点的兴起,声称路德的称义观点是错误的,因为他被自己的背景蒙蔽了双眼,迫使他对保罗文本进行解释。因此,改革宗的观点不可能是正确的,因为它主要是通过救赎论的视角来解释称义的教义,而使徒在谈到这个主题时,心中只有教会的目的。在上述思想的基础上,本文的目的是通过提出一种“两端”的称义方法来批判新观点的排他方法,这种方法肯定了路德所持的称义的救赎论方面,但也指出了教会意义的现实。这篇文章分为两个主要部分。第一部分强调了NPP(保罗的新观点)对关键术语的定义,如“行律法”、“神的义”和“称义”,然后是关于他们对这些术语的看法的重要观察。文章的第二部分为保罗使用称义的教义提供了三个主要论点,主要是为了救赎目的。本书的目的不是要解决双方的争论,而是要证明传统的(改革宗的)关于称义教义的观点并不荒谬,就像有些人会说的那样,而且在持救赎论立场的同时,仍然可以肯定保罗教义的教会意义。
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引用次数: 0
Visual Rhetoric: A Case for Visual Literacy in the Classroom 视觉修辞:课堂视觉素养的案例
IF 3.3 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-01-01 DOI: 10.15385/JCH.2016.1.1.9
Kaitlyn J Tomlinson
We live in a visual age in which we find visual information surrounding us on every side. The persuasive power of the visual has long been recognized by scholars, but there is a lack of emphasis in the classroom on how to effectively create an effectively persuasive visual. Professors at the collegiate level need to teach their students to be visually literate, to make them responsible users and creators of images.
我们生活在一个视觉时代,我们发现视觉信息无处不在。视觉的说服力早已被学者们所认识,但在课堂上却缺乏对如何有效地创造有效的说服性视觉的重视。大学水平的教授需要教他们的学生具备视觉素养,使他们成为负责任的图像使用者和创造者。
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引用次数: 3
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