1,720,984 research outputs found

    Midbody inheritance, degradation and functions

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    Citokinesis is a final stage of cell division, during which, the mother cell divides, leaving two newly formed daughter cells connected by a thin intercellular bridge (ICB). During abscission of this ICB, the central spindle microtubules are compacted into a protein-rich structure, known as a midbody (MB). Until recently, it was thought that post-mitotic MBs are discarded into the extracellular space where they are degraded immediately following cytokinesis. However, recent studies have shown that MBs are prone to accumulate and persist for a long time in cancer stem cell and cancer cell populations, indi-cating that it may have some post-mitotic functions. Furthermore, it was shown that post-mitotic MBs might function as signalling platforms and determine the stemness and aggressiveness of cancer cells. The abscission of the ICB can occur on one side of the MB (asymmetric abscission), leading to the inheritance of post-mitotic MB only by one daughter cell. Alternatively, when ICB is cut on both sides of the MB (symmetric abscission), the MB is discarded into the extracellular space where it is gradually degraded or internalized by the surrounding cells. The functional consequences of inherited post-mitotic MB in comparison with internalized extracellular post-mitotic MB remains undetermined. How cells retain, accumulate and degrade post-mitotic MB, remains elusive. Although the post-mitotic MB functions become clearer over time, there is still no clear definition of how these intercellular structures accumulate and get degraded once they are inherited or internalized by cancer cells. Moreover, the mechanisms governing post-mitotic MB internalization as well as functional consequences of MB accumulation to cancer cells proliferation and oncogenic potential still need to be determined

    The Art of “Cut and Run”: The Role of Rab14 GTPase in Regulating N-Cadherin Shedding and Cell Motility

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    Linford et al. define a Rab14-mediated endocytic recycling pathway that controls proteolytic N-cadherin cleavage by transporting ADAM10 protease to the plasma membrane. When this pathway is disrupted, diminished ADAM10-dependent N-cadherin shedding leads to increased cell-cell adhesion and inhibition of cell motility

    Regulation of ESCRT-III assembly and membrane scission activity in the budding yeast Saccharomyces cerevisiae

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    The sequential recruitment and assembly of endosomal sorting complexes required for transport (ESCRTs) at the endosomal membrane mediate the selection and clustering of cargoes into vesicles that bud into the lumen of the endosome. In addition to regulating this sorting process at endosomes, in mammalian cells ESCRTs are additionally required for the budding of many types of enveloped viruses, as well as the separation of cells during cytokinesis. These processes share a topologically similar membrane scission event facilitated by regulated ESCRT-III assembly at the cytoplasmic surface of the membrane to promote the formation and scission of internal vesicles. The Snf7 subunit of ESCRT-III in yeast binds directly to an auxiliary protein, Bro1. Like ESCRT-III, Bro1 is required for the formation of intralumenal vesicles at endosomes, but its role in membrane scission has remained uncharacterized. We show that overexpression of Bro1, or its N-terminal Bro1 domain that binds Snf7, enhances the stability of ESCRT-III. Bro1 binding to the Snf7 subunit of ESCRT-III additionally inhibits Vps4-mediated disassembly of ESCRT-III complexes in vivo and in vitro. This stabilization effect correlates with a reduced frequency in the budding of intralumenal vesicles within endosomes, and the appearance of vesicle budding profiles, vesicles that have not yet separated from the limiting endosomal membrane, as observed by electron microscopy and 3-D electron tomography. These results implicate Bro1 as a regulator of ESCRT-III assembly state, and additionally suggest that Vps4-mediated disassembly of the ESCRT-III complex is important for vesicle membrane scission. We also observed that deletion of ESCRT-III proteins Snf7 or Vps24, or overexpression of Bro1 or the Bro1 domain causes the accumulation of budded yeast cells by flow cytometry. While these proteins have been shown to participate in cell abscission in mammalian cells, a role for these proteins in cell division has not been established in yeast. Our findings suggest that ESCRT-III and Bro1 participate in the abscission step of cytokinesis in yeast, implicating them as conserved effectors of membrane scission

    Polarized endocytic transport ,The roles of Rab11 and Rab11-FIPs in regulating cell polarity

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    Endocytic transport plays a vital role in the establishment and maintenance of cell polarity. Many studies have demonstrated that endosome-dependent protein targeting is required for polarization of epithelial cells and neurons. Endocytic transport regulates several highly polarized cellular events, such as cell motility and division. Rab11 GTPase has been shown to be a master regulator of protein transport via recycling endosomes, and many recent studies have focused on the molecular machinery that mediates Rab11-dependent endocytic protein transport in polarized cells. This mini-review describes the recent advances in identifying and characterizing the role of Rab11 and its effector proteins that play important roles in polarized endocytic sorting and transport

    Regulation of ESCRT-III Assembly and Membrane Scission Activity in the Budding Yeast Saccharomyces cerevisiae

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    The sequential recruitment and assembly of endosomal sorting complexes required for transport (ESCRTs) at the endosomal membrane mediate the selection and clustering of cargoes into vesicles that bud into the lumen of the endosome. In addition to regulating this sorting process at endosomes, in mammalian cells ESCRTs are additionally required for the budding of many types of enveloped viruses, as well as the separation of cells during cytokinesis. These processes share a topologically similar membrane scission event facilitated by regulated ESCRT-III assembly at the cytoplasmic surface of the membrane to promote the formation and scission of internal vesicles. The Snf7 subunit of ESCRT-III in yeast binds directly to an auxiliary protein, Bro1. Like ESCRT-III, Bro1 is required for the formation of intralumenal vesicles at endosomes, but its role in membrane scission has remained uncharacterized. We show that overexpression of Bro1, or its N-terminal Bro1 domain that binds Snf7, enhances the stability of ESCRT-III. Bro1 binding to the Snf7 subunit of ESCRT-III additionally inhibits Vps4-mediated disassembly of ESCRT-III complexes in vivo and in vitro. This stabilization effect correlates with a reduced frequency in the budding of intralumenal vesicles within endosomes, and the appearance of vesicle budding profiles, vesicles that have not yet separated from the limiting endosomal membrane, as observed by electron microscopy and 3-D electron tomography. These results implicate Bro1 as a regulator of ESCRT-III assembly state, and additionally suggest that Vps4-mediated disassembly of the ESCRT-III complex is important for vesicle membrane scission. We also observed that deletion of ESCRT-III proteins Snf7 or Vps24, or overexpression of Bro1 or the Bro1 domain causes the accumulation of budded yeast cells by flow cytometry. While these proteins have been shown to participate in cell abscission in mammalian cells, a role for these proteins in cell division has not been established in yeast. Our findings suggest that ESCRT-III and Bro1 participate in the abscission step of cytokinesis in yeast, implicating them as conserved effectors of membrane scission

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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