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1.
Pore-forming toxins (PFTs) are the most common class of bacterial protein toxins and constitute important bacterial virulence factors. The mode of action of PFT is starting to be better understood. In contrast, little is known about the cellular response to this threat. Recent studies reveal that cells do not just swell and lyse, but are able to sense and react to pore formation, mount a defense, even repair the damaged membrane and thus survive. These responses involve a variety of signal-transduction pathways and sophisticated cellular mechanisms such as the pathway regulating lipid metabolism. In this review we discuss the different classes of bacterial PFTs and their modes of action, and provide examples of how the different bacteria use PFTs. Finally, we address the more recent field dealing with the eukaryotic cell response to PFT-induced damage. Received 19 September 2007; received after revision 18 October 2007; accepted 23 October 2007  相似文献   

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ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanical work. During the functioning cycle, the AAA+ motor transits through multiple distinct states. Ring architecture and placement of the catalytic sites at the intersubunit interfaces allow for a unique level of coordination among subunits of the motor. This in turn results in conformational differences among subunits and overall asymmetry of the motor ring as it functions. To date, a large amount of structural information has been gathered for different AAA+ motors, but even for the most characterized of them only a few structural states are known and the full mechanistic cycle cannot be yet reconstructed. Therefore, the first part of this work will provide a broad overview of what arrangements of AAA+ subunits have been structurally observed focusing on diversity of ATPase oligomeric ensembles and heterogeneity within the ensembles. The second part of this review will concentrate on methods that assess structural and functional heterogeneity among subunits of AAA+ motors, thus bringing us closer to understanding the mechanism of these fascinating molecular motors.  相似文献   

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Facilitating the entry of molecules into mammalian cells is of great interest to fields as diverse as cell biology and drug delivery. The discovery of natural protein transduction domains and the development of artificial ones, including polyarginine, provides a means to achieve this goal. Here, we comment on key chemical and biological aspects of cationic peptide internalization, including the physiological relevance of this process. Received 13 April 2006; received after revision 21 May 2006; accepted 2 June 2006  相似文献   

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Cry proteins, produced by Bacillus thuringiensis (Bt), are widely used for the control of insect pests in agriculture as spray products or expressed in transgenic crops, such as maize and cotton. Little was known regarding the mechanism of action of these toxins when the first commercial Bt product was introduced fifty years ago. However, research on the mechanism of action over the last two decades has enhanced our knowledge of toxin interaction with membrane receptors and their effects in insect midgut cells. All this information allowed for the rational design of improved toxins with higher toxicity or toxins that overcome insect resistance, which could compromise Bt use and effectiveness in the field. In this review we discuss and evaluate the different models of the mode of action of Cry toxins, including a discussion about the role of various receptors in toxin action. Received 13 June 2008; received after revision 05 November 2008; accepted 11 November 2008  相似文献   

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P-glycoprotein (P-gp) is an active membrane transporter responsible for cell detoxification against numerous amphiphilic compounds, leading to multidrug resistance in tumor cells. It displays entangled connections with its membrane environment since it recognizes its substrates within the cytosolic leaflet and it also translocates some endogenous lipids to the exoplasmic leaflet. Regarding its relationships with membrane microdomains, ‘lipid rafts’, a literature analysis concludes that (i) P-gp also exists in rafts and non-raft membrane domains, depending on the cell considered, the experimental conditions and the method used to test it; (ii) cholesterol has a positive influence on P-gp function, and this may be a direct effect of the free cholesterol present in membrane or an indirect effect mediated by the cholesterol-enriched microdomains; (iii) when present in rafts, P-gp interacts with protein partners regulating its activity; (iv) P-gp is a lipid translocase that handles the raft-constituting lipids with particular efficiency, and it also influences membrane trafficking in the cell. Received 18 November 2005; received after revision 23 December 2005; accepted 12 January 2006  相似文献   

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This paper analyzes the experiment presented in 2019 by the Event Horizon Telescope (EHT) Collaboration that unveiled the first image of the supermassive black hole at the center of galaxy M87. The intended aim of the paper is to assess whether the EHT Collaboration has made an “inference to the best explanation” (IBE) to conclude that the data effectively confirm the hypothesis that the object at the center of M87 is in fact a supermassive Kerr rotating black hole. I demonstrate that the EHT Collaboration has applied an IBE. It is shown that the hypothesis that at the center of M87 there is a supermassive Kerr rotating black hole was already the best explanation at the time in which the 2017 EHT experiment was conducted. My analysis is intertwined with considerations on realist and empiricist interpretations of IBE, which are used to assess whether the conclusion that the object at the center of M87 is a Kerr rotating black hole implies holding a realist commitment with respect to such object.  相似文献   

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In 1905 the Campos Rodrigues Observatory (CRO) was founded in Lourenço Marques (nowadays Maputo), the capital of Mozambique, by then part of the Portuguese overseas empire. In this paper the inception and early history of the CRO are analysed in the broader context of the interwoven history of the Portuguese and British empires in Africa, and specifically with respect to the scientific relations between Mozambique and South Africa. The equipment, personnel, practices and networks involved in the inception and early development of the CRO are brought into focus in order to illustrate the problems and strategies that shaped the establishment and functioning of this observatory, which was conceived essentially as a symbol of imperial stamina and colonial prowess. It is suggested that by providing a focal point for the development of scientific relations between Mozambique and South Africa, the CRO served both Portuguese ambitions for recognition as an imperial power and the emergence of South African nationalism.  相似文献   

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以WO3,MoO3,Eu2O3,Li2CO3,Y2O3为原料,采用传统的高温固相反应方法制备了一种新的白光LED用红色荧光粉LiEu1-xYx(WO4)0.5(MoO4)1.5(x=0,0.1,0.2,0.3,0.4,0.5,0.6,0.8)系列,利用XRD和荧光光谱仪等对其进行了研究.结果表明这系列荧光粉可以被近紫外光(396nm)和蓝光(466nm)有效激发,发射峰值位于615nm(Eu3+离子的5D0→7F2跃迁)的红光,并且证明了Eu3+离子在晶体结构中占据了非反演对称中心的位置;激发波长与目前广泛使用的蓝光和紫外光LED芯片相符合,因此该系列荧光粉可以用作近紫外辐射的InGaN管芯激发三基色荧光粉系统或者是用来补充蓝光芯片激发的黄色荧光粉系统缺少的红色部分.详细研究了各种助熔剂对该体系荧光粉发光特性的影响.XRD的测量结果表明加入适量的助熔剂有利于LiEu1-xYx(WO4)0.5(MoO4)1.5荧光粉的结晶化,并且不引入杂相.适量的助熔剂的加入可增大该系列荧光粉的相对发光强度,并能有效降低荧光粉的平均粒径.  相似文献   

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Summary A method for the estimation of muscle nucleotides is described. The separation of nucleotides has been accomplished by paper ionophoresis at high voltages, as well as by paper chromatography. Even little changes in the nucleotide content such as the changes in a single muscular contraction can be well observed by this method.A decrease of 0.25 µ M ATP/g/contraction (i.e. about of the normal ATP content) has been observed in a contracted muscle, when compared with the ATP content of the resting muscle.  相似文献   

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以Fecl_3为原料采用浸渍法,获得了载铁活性炭,考察对水中砷的去除能力及影响因素,并对吸附过程进行等温吸附模型和动力学的模拟。实验结果表明,砷去除的最佳条件为:栽铁活性炭平衡振荡5h,pH控制在7。水中常见共存离子除Ca~(2+)外不影响砷的去除效果,ca~(2+)有助于砷的去除。改性炭对砷的吸附能较好的符合Langmuir模型和二级动力学方程,而不符合Freundlich模型,说明这一吸附过程为单分子层吸附。由于活性炭对砷的吸附属于物理吸附,故全过程不引入其他离子,不会对水体造成二次污染。  相似文献   

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应用周国治提出的新溶液模型计算所得的Fe Mn Si中γ和ε相的Gibbs自由能 ,并考虑了Si的影响 ,重新导出了γ和ε相随温度变化的热力学参量 .用最小均方根方法将实验值拟合得到合金γ相的Neel温度与组分浓度 (摩尔分数 )的关系式 :TγN=6 7xFe 5 40xMn xFexMn[76 1 6 89(xFe-xMn) ]- 85 0xSi.计算得到不同组分Fe Mn Si合金马氏体相变的临界驱动力ΔGγ→εc ,即合金在Ms 温度γ和ε相的自由能差 ,例如 ,Fe 2 7.0Mn 6 .0Si合金的ΔGγ→εc =- 1 0 0 .99J/mol,Fe 2 6 .9Mn 3.37Si的ΔGγ→εc =- 1 2 2 .1 1J/mol.ΔGγ→εc 与组分的依赖关系符合低层错能合金中fcc(γ)→hcp(ε)马氏体相变的临界驱动力表达式 ,即ΔGγ→εC =A·γ B ,其中γ是层错能 (SFE) ,A和B为与材料相关的常数 .  相似文献   

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分析了交替分离(AS)算法与交替投影(AP)算法的一些性质. 根据这些分析结果, 提出了将交替分离与交替投影算法有机结合形成所谓ASAP算法, 以克服交替分离算法收敛速度较慢而交替投影算法又易于陷入最大似然代价函数的局部极值的缺陷. 分析了这种结合的逻辑合理性. 计算机仿真也验证了ASAP算法能够以较少的迭代次数得到信号参数较理想的估计.  相似文献   

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分别配制了Bi含量为90,100和110mole%的前驱体,在Pt/Ti/SiO2/Si衬底上制备Bi3.4Ce0.6Ti3O12薄膜,研究前驱体中Bi含量对其微观结构和铁电性能的影响.前驱体中Bi含量增加可以有效地改善薄膜的结晶性能和表面形貌.对Pt/Bi3.4Ce0.6Ti3O12/Pt电容结构进行电学性能测量,发现Bi过量10%的前驱体制备的Bi3.4Ce0.6Ti3O12薄膜具有较好的性能:室温下,在测试频率1kHz时,其介电常数为172,介电损耗为0.033;在测试电场为600kV/cm时,其剩余极化值(2Pr)和矫顽电场(2Ec)分别达到67.1μC/cm2和299.7kV/cm;同时还表现出良好的抗疲劳特性和绝缘性能.  相似文献   

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提出了由模糊子集生成的(λ,T)-模糊理想(滤子)的概念,并且用三角范数的性质及生成理想的概念刻画了(λ,T)-模糊理想(滤子)。研究了由模糊集生成的(λ,T)-模糊理想的逆像在同态映射下与模糊集的逆像生成的(λ,T)-模糊理想是相等的。  相似文献   

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