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1.
Vinculin was identified as a component of focal adhesions and adherens junctions nearly 40 years ago. Since that time, remarkable progress has been made in understanding its activation, regulation and function. Here we discuss the current understanding of the roles of vinculin in cell–cell and cell–matrix adhesions. Emphasis is placed on the how vinculin is recruited, activated and regulated. We also highlight the recent understanding of how vinculin responds to and transmits force at integrin- and cadherin-containing adhesion complexes to the cytoskeleton. Furthermore, we discuss roles of vinculin in binding to and rearranging the actin cytoskeleton.  相似文献   

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Polarity is a fundamental feature of cells. Protein complexes, including the PAR3–PAR6–aPKC complex, have conserved roles in establishing polarity across a number of eukaryotic cell types. In neurons, polarity is evident as distinct axonal versus dendritic domains. The PAR3, PAR6, and aPKC proteins also play important roles in neuronal polarization. During this process, either aPKC kinase activity, the assembly of the PAR3–PAR6–aPKC complex or the localization of these proteins is regulated downstream of a number of signaling pathways. In turn, the PAR3, PAR6, and aPKC proteins control various effector molecules to establish neuronal polarity. Herein, we discuss the many signaling mechanisms and effector functions that have been linked to PAR3, PAR6, and aPKC during the establishment of neuronal polarity.  相似文献   

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The Wigner–Eckart theorem is central to the application of symmetry principles throughout atomic, molecular, and nuclear physics. Nevertheless, the theorem has a puzzling feature: it is dispensable for solving problems within these domains, since elementary methods suffice. To account for the significance of the theorem, I first contrast it with an elementary approach to calculating matrix elements. Next, I consider three broad strategies for interpreting the theorem: conventionalism, fundamentalism, and conceptualism. I argue that the conventionalist framework is unnecessarily pragmatic, while the fundamentalist framework requires more ontological commitments than necessary. Conceptualism avoids both defects, accounting for the theorem’s significance in terms of how it epistemically restructures the calculation of matrix elements. Specifically, the Wigner–Eckart theorem modularizes and unifies matrix element problems, thereby changing what we need to know to solve them.  相似文献   

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In vertebrates, internal organs are positioned asymmetrically across the left-right (LR) axis, placing them in a defined area within the body. This LR asymmetric placement is a conserved feature of the vertebrate body plan. Events determining LR asymmetry occur during embryonic development, and are regulated by the coordinated action of genetic mechanisms that are evolutionarily conserved among vertebrates. Recent studies using zebrafish have provided new insights into how the Kupffer's vesicle organizer region is generated, and how it relays LR asymmetry information to the lateral plate mesoderm. In this review, we summarize recent advances in zebrafish and describe our current understanding of the mechanisms underlying these processes.  相似文献   

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In 1639–1640 Benedetto Castelli (1577–1643) wrote a treatise on the loadstone which is quite unlike any of its contemporaries. In it are the origins of the notion of elementary magnets sharing a common alignment, the idea that all materials are magnetic in different ways, and the first intimation of the conception of magnetic domains. Castelli did not publish his treatise. Nevertheless his work was noted during his life-time, and may have exerted an influence on the development of magnetic theory in the 17th century. The treatise was published in 1883. Since then, however, it has either been neglected or not appreciated. It deserves being rescued from the neglect of more than three centuries.  相似文献   

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David Wallace has recently argued that the eigenstate–eigenvalue (E–E) link has no place in serious discussions of quantum mechanics on the grounds that, as he claims, the E–E link is an invention of philosophers rather than the community of practicing physicists. This raises an historical question regarding the origin of the link. This paper aims to answer this question by tracing the historical development of the link through six key textbooks of quantum mechanics. In light of the historical evidence from these textbooks, it is argued that Wallace provides insufficient grounds for dismissing the E–E link from discussions of quantum mechanics.  相似文献   

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In his search for a unified field theory that could undercut quantum mechanics, Einstein considered five-dimensional classical Kaluza–Klein theory. He studied this theory most intensively during the years 1938–1943. One of his primary objectives was finding a non-singular particle solution. In the full theory this search got frustrated, and in the x5-independent theory Einstein, together with Pauli, argued it would be impossible to find these structures.  相似文献   

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John Harrison (1693–1776) is regarded as the father of chronometry. During his lifetime, he relentlessly pursued one of humankind's greatest and oldest challenges—that of finding the longitude at sea. In succeeding (according to the rules dictated by an Act of Parliament), he bequeathed to humankind the most accurate portable timekeeper the world had ever seen. It is a remarkable fact that his timekeeper, known today as H4, remains more accurate than the majority of expensive mechanical wristwatches manufactured today. Such accuracy required novel approaches to address the various difficulties that befall all mechanical watches, and Harrison overcame many of these with his own innovations. The reduction or elimination of friction is one such problem with clocks and watches, and from an early age Harrison demonstrated his mastery in this subject. This is typified by his choice of woods in his early clocks, and in later clocks by his ‘grasshopper’ escapement. In the 1750s, Harrison's attention switched from clocks to watches, necessitating a hardwearing, low friction material to be found for the pallets in the escapement of his timekeepers. He found these properties in diamond, and in utilizing this to great effect in H4's escapement, he became one of the first people to use diamond as a high-tech material. This paper describes a scientific investigation into the diamond pallets of H4 using Raman microscopy, X-ray diffraction and optical microscopy, to elucidate why diamond was used rather than a more conventional jewel such as ruby, and to gain some insight into how Harrison might have achieved their unconventional morphology. From the evidence presented here, together with evidence collected from primary sources, it is shown that his use of diamond as a hard, low friction material was nothing other than extraordinary, and should be regarded in the same high esteem as his other technological gifts to the world.  相似文献   

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The vasculature is one of the most dynamic tissues that encounter numerous mechanical cues derived from pulsatile blood flow, blood pressure, activity of smooth muscle cells in the vessel wall, and transmigration of immune cells. The inner layer of blood and lymphatic vessels is covered by the endothelium, a monolayer of cells which separates blood from tissue, an important function that it fulfills even under the dynamic circumstances of the vascular microenvironment. In addition, remodeling of the endothelial barrier during angiogenesis and trafficking of immune cells is achieved by specific modulation of cell–cell adhesion structures between the endothelial cells. In recent years, there have been many new discoveries in the field of cellular mechanotransduction which controls the formation and destabilization of the vascular barrier. Force-induced adaptation at endothelial cell–cell adhesion structures is a crucial node in these processes that challenge the vascular barrier. One of the key examples of a force-induced molecular event is the recruitment of vinculin to the VE-cadherin complex upon pulling forces at cell–cell junctions. Here, we highlight recent advances in the current understanding of mechanotransduction responses at, and derived from, endothelial cell–cell junctions. We further discuss their importance for vascular barrier function and remodeling in development, inflammation, and vascular disease.  相似文献   

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Science Policy News

European science foundation brain research programme 1990–1991  相似文献   

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Fetal alcohol spectrum disorders (FASD) is an umbrella term that describes a diverse set of ethanol-induced defects. The phenotypic variation is generated by numerous factors, including timing and dosage of ethanol exposure as well as genetic background. We are beginning to learn about how the concentration, duration, and timing of ethanol exposure mediate variability within ethanol teratogenesis. However, little is known about the genetic susceptibilities in FASD. Studies of FASD animal models are beginning to implicate a number of susceptibility genes that are involved in various pathways. Here we review the current literature that focuses on the genetic predispositions in FASD.  相似文献   

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The Notch and Wnt pathways are two of only a handful of highly conserved signalling pathways that control cell-fate decisions during animal development (Pires-daSilva and Sommer in Nat Rev Genet 4: 39–49, 2003). These two pathways are required together to regulate many aspects of metazoan development, ranging from germ layer patterning in sea urchins (Peter and Davidson in Nature 474: 635–639, 2011) to the formation and patterning of the fly wing (Axelrod et al in Science 271:1826–1832, 1996; Micchelli et al in Development 124:1485–1495, 1997; Rulifson et al in Nature 384:72–74, 1996), the spacing of the ciliated cells in the epidermis of frog embryos (Collu et al in Development 139:4405–4415, 2012) and the maintenance and turnover of the skin, gut lining and mammary gland in mammals (Clayton et al in Nature 446:185–189, 2007; Clevers in Cell 154:274–284, 2013; Doupe et al in Dev Cell 18:317–323, 2010; Lim et al in Science 342:1226–1230, 2013; Lowell et al in Curr Biol 10:491–500, 2000; van et al in Nature 435:959–963, 2005; Yin et al in Nat Methods 11:106–112, 2013). In addition, many diseases, including several cancers, are caused by aberrant signalling through the two pathways (Bolós et al in Endocr Rev 28: 339–363, 2007; Clevers in Cell 127: 469–480, 2006). In this review, we will outline the two signalling pathways, describe the different points of interaction between them, and cover how these interactions influence development and disease.  相似文献   

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When Bouvet discovered the relationship between the binary arithmetic of Leibniz and the hexagrams of the I ching—in reality only a purely formal correspondence—he sent to Leibniz a woodcut diagram of the Fu-Hsi arrangement, which provides the key to the analogy. This diagram, in a re-drawn version, was first published by Gorai Kinzō in a study of Leibniz's interpretation of the I ching and Confucianism which has been influential in providing, indirectly, the principal source for the accounts of Wilhelm and Needham. Yet this pioneering study of Leibniz's interpretation of the hexagrams is virtually unknown. Even the account of Needham, who saved it from complete obscurity, contains one or two inaccuracies about it and these are repeated by Zacher in his otherwise excellent monograph on Leibniz's binary arithmetic.  相似文献   

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The blood–brain barrier (BBB) is a dynamic structure that maintains the homeostasis of the brain and thus proper neurological functions. BBB compromise has been found in many pathological conditions, including neuroinflammation. Monocyte chemoattractant protein-1 (MCP1), a chemokine that is transiently and significantly up-regulated during inflammation, is able to disrupt the integrity of BBB and modulate the progression of various diseases, including excitotoxic injury and hemorrhage. In this review, we first introduce the biochemistry and biology of MCP1, and then summarize the effects of MCP1 on BBB integrity as well as individual BBB components.  相似文献   

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RNA interference has tremendously advanced our understanding of gene function but recent reports have exposed undesirable side-effects. Recombinant Camelid single-domain antibodies (VHHs) provide an attractive means for studying protein function without affecting gene expression. We raised VHHs against gelsolin (GsnVHHs), a multifunctional actin-binding protein that controls cellular actin organization and migration. GsnVHH-induced delocalization of gelsolin to mitochondria or the nucleus in mammalian cells reveals distinct subpopulations including free gelsolin and actin-bound gelsolin complexes. GsnVHH 13 specifically recognizes Ca2+-activated gelsolin (K d ~10 nM) while GsnVHH 11 binds gelsolin irrespective of Ca2+ (K d ~5 nM) but completely blocks its interaction with G-actin. Both GsnVHHs trace gelsolin in membrane ruffles of EGF-stimulated MCF-7 cells and delay cell migration without affecting F-actin severing/capping or actin nucleation activities by gelsolin. We conclude that VHHs represent a potent way of blocking structural proteins and that actin nucleation by gelsolin is more complex than previously anticipated.  相似文献   

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