557 research outputs found

    Characterization of the role of the endosomal recycling system for the intracellular transport of the Marburg virus glycoprotein

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    Das Marburg Virus (MARV), das zur Familie der Filoviridae gezählt wird, ist ein Erreger schwerer Fieber mit Letalitätsraten von bis zu 90 %. Das Glykoprotein GP stellt das einzige Oberflächenprotein des MARV dar und daher ist sein korrekter Transport zu den „Budding-Sites“ an der Plasmamembran sowie seine Inkorporation in neue Viruspartikel essentiell für den viralen Infektionszyklus. Das aktuelle Modell beschreibt einen Transport von GP über den klassischen sekretorischen Pfad, der das endoplasmatische Retikulum, den Golgi-Apparat und das trans-Golgi-Netzwerk einschließt. Dennoch sind weder die exakten Transportschritte zwischen dem Golgi-Apparat und der Plasmamembran noch Wirtsfaktoren, die diesen Prozess vermitteln, bekannt. Aus diesem Grund war das Ziel dieser Studie, den post-Golgi-Transport von MARV-GP näher zu charakterisieren und potentielle subzelluläre Kompartimente sowie Wirtsfaktoren zu identifizieren, die die Beförderung von MARV-GP zur Zelloberfläche im Allgemeinen und zu den VP40-reichen „Budding-Sites“ im Besonderen vermitteln. Im ersten Teil dieser Arbeit konnte mittels konfokaler Mikroskopie gezeigt werden, dass MARV-GP mit Markerproteinen von Recycling Endosomen (Transferrin-Rezeptor, GFP-Rab11) sowohl in transient transfizierten als auch in MARV-infizierten Zellen kolokalisiert. Da eine Re-Endozytose von der Plasmamembran ausgeschlossen werden konnte, deuteten diese Ergebnisse auf eine Rolle des endosomalen Recycling-Systems innerhalb des „biosynthetischen“ Transports von GP zwischen dem Golgi-Apparat und der Zelloberfläche. Im zweiten Teil konnte nachgewiesen werden, dass die funktionelle Ablation des endosomalen Recycling-Systems durch die Überexpression einer dominant-negativen Mutante von Myosin Vb (Myosin Vb Tail) zu einer aberranten Verteilung von GP führt, das in der Folge innerhalb oder in der Nähe von perinukleären Myosin Vb Tail-Aggregaten akkumuliert. Infolge einer Blockade des Transports von GP aus dem Golgi-Apparat, konnte weiter aufgedeckt werden, dass GP das Myosin Vb-positive Kompartiment nach Verlassen des Golgi-Apparats erreicht. Die Interferenz des GP-Transports durch das dominant-negative Myosin Vb Tail reduzierte darüber hinaus signifikant die GP-Level an der Zelloberfläche im Allgemeinen und in VP40-reichen Regionen an der Plasmamembran im Besonderen. Im Gegensatz dazu beeinträchtigte die Expression von Myosin Vb Tail weder die Verteilung des MARV Matrixproteins VP40 noch von MARV-NP als Hauptkomponente der viralen Nukleokapside, was für die Nutzung distinkter Transportwege durch MARV-GP und den anderen viralen Strukturproteinen spricht. Überraschenderweise hatte die Inhibition von Rab11, einem bedeutenden Regulator von Myosin Vb, durch die Überexpression dominant-negativer bzw. konstitutiv-aktiver Mutanten oder durch eine siRNA-vermittelte Depletion keinen Einfluss auf die Verteilung oder die Oberflächenexpression von GP, was darauf hindeutet, dass Rab11 nicht essentiell für den Transport von MARV-GP ist. Zusammengefasst sprechen diese Ergebnisse dafür, dass MARV-GP nach dem Verlassen des Golgi-Apparats das Myosin Vb-assoziierte endosomale Recycling-System passiert. Ein korrekter Transport durch das Recycling-System ist substantiell für die Beförderung von GP zur Zelloberfläche sowie zu den VP40-angereicherten Plasmamebranregionen und daher eine wichtige Komponente bei der Bildung der Partikelhülle des MARV.Marburg virus (MARV), belonging to the family Filoviridae, is the causative agent of severe fever with lethality rates of up to 90%. The glycoprotein GP represents the only surface protein of MARV and thus its proper transport to the budding-sites at the plasma membrane and subsequent incorporation into virus particles is essential for the viral infection cycle. Regarding delivery to the cell surface the current model presumes trafficking of GP via the classical secretory pathway involving endoplasmic reticulum, Golgi apparatus and trans-Golgi-network. However, neither the exact transport steps between the Golgi apparatus and the plasma membrane nor host factors regulating trafficking of GP are known. Therefore, the aim of this study was to characterize the post-Golgi transport of MARV-GP and to identify potential subcellular compartments and host factors mediating trafficking of GP to the cell surface in general and to the VP40-enriched budding-sites in particular. In the first part of this thesis, it was shown by confocal microscopy that MARV-GP colocalizes with marker proteins of recycling endosomes (Transferrin receptor, GFP-Rab11) in transiently transfected as well as in MARV-infected cells. Since a re-endocytosis from the plasma membrane could be excluded, these results were a hint for a role of the endosomal recycling system during biosynthetic transport of GP between the Golgi apparatus and the cell surface. In the second part, it was demonstrated that functional ablation of the endosomal recycling system by overexpressing a dominant-negative mutant of Myosin Vb (Myosin Vb Tail) leads to an aberrant distribution of GP which as a consequence accumulates in or near perinuclear Myosin Vb Tail aggregates. By blocking GP exit from the Golgi apparatus, it was further shown that GP enters the Myosin Vb-positive compartment after leaving the Golgi. Furthermore, the interference with GP trafficking by dominant-negative Myosin Vb Tail significantly reduced GP levels at the cell surface in general and targeting of GP to VP40-enriched sites at the plasma membrane in particular. In contrast, distribution of MARV matrix protein VP40 as well as of MARV-NP, the major component of viral nucleocapsids, were not affected by the expression of Myosin Vb Tail pointing towards the use of distinct trafficking pathways by MARV-GP and the other viral structural proteins. Surprisingly, inhibition of Rab11, a major Myosin Vb regulator, by overexpression of dominant-negative or constitutively active mutants or siRNA-mediated knockdown did not perturb GP distribution or surface transport indicating that Rab11 is not essential for MARV-GP transport. In sum, these results suggest that after leaving the Golgi apparatus MARV-GP transits the Myosin Vb-associated endosmal recycling system. A proper transit through the recycling system is critical for GP transport to the cell surface as well as for its targeting to plasma membrane regions enriched in the matrix protein VP40 and therefore an important step during the formation of the MARV envelope

    RETURN ON INVESTMENT IN CORPORATE RESPONSIBILITY: Measuring the Social, Economic, and Environmental Value of Sustainable Business

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    In today’s climate, companies must be economically successful and at the same time take social responsibility. Author Cesar Sandro Saenz Acosta introduces a new SROIM (Social Return on Investment Management) model, to design and measure the social value created by companies. © 2018 Emerald Publishing Limited

    Ermeneutica Sociologica

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    L'autore intende ancorare la sociologia al presupposto che la comprensione dell'essere umano in quanto individuo socialmente definito e costruito risiede nella socialitàThe author intends to anchor the sociology the assumption that the understanding of the human being as an individual socially defined and constructed lies in socializin

    Né qui, né altrove : migration, detention, desertion : a dialogue

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    Sandro Mezzadra teaches the History of Contemporary Political Thought at the University of Bologna. He is an active figure in the alternative globalisation movement in Italy, and has been particularly involved in bringing the question of migration to the centre of political struggle in that movement. Sandro is the author of works such as Diritto di fuga: Migrazioni, cittadinanza, globalizzazione (2001) and (with Fabio Raimondi) Oltre Genova, oltre New York: Tesi sul movimento globale (2001). He is also a member of the editorial collective of DeriveApprodi magazine, one of the chief venues in Italy for the critical analysis of contemporary capitalism. We met in Bologna one foggy January afternoon to discuss the global movement, migration, and border control in Europe and Australia

    The part-time work and job on call in JustEatTakeaway supplementary company agreement for Takeaway.com Express Italy (Just Eat group) riders

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    The comment deals with the part-time work regulation, contained, in particular, in Part II of the JustEatTakeaway supplementary company agreement. The use of this instrument is expected to be massive, considering that it is, in the parties' plans, the common form of work in the company. The author analyses the provisions contained in the collective agreement, especially in the light of the discipline contained in the CCNL Logistica, Trasporto, Merci e Spedizione and in the Protocol signed on 18 July 2018 for the same sector. The author also discusses the rules on overtime and supplementary work and the rules on intermittent work, which are also subject to specific contractual regulations

    Bridging the Boundaries of Science and Technology: Author-Inventors and Quality of Inventions

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    A growing body of research examines the relationship between science and technology by using a social network lens to look at the collaboration networks between authors and inventors. Building on this research, we study how publishing inventors’ (author-inventors’) structural position in scientific (co-authorship) and technological (co-invention) networks affects the quality of their inventions. We probe author-inventors’ characteristics by identifying those who act as cutpoints—i.e., those who play a pivotal role in holding the two networks together. Cutpoints can be connected to more or less cohesive subgroups of the scientific network and hence have access to more or less diverse knowledge bases. The results of the analysis suggest that author-inventors’ structural position—in particular, whether they are cutpoints and belong to more cohesive subgroups of the scientific network—is highly consequential for the quality of the inventions with which they are involved. We tested our hypotheses in the emerging field of nanotechnology. The theoretical and managerial implications of the results are discussed

    <i>Primavera</i> / <i>The Birth of Venus</i> by Sandro Botticelli. Representations, Reinterpretations

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    Tekst pochodzi z pracy magisterskiej pt. &quot;Primavera&quot; i &quot;Narodziny Wenus&quot; Sandro Botticellego. Reinterpretacje, ekfrazy, reprezentacje (promotor: prof. dr hab. Dariusz Czaja), obronionej w IEiAKUJ w roku 2016. Poświęcony jest rozwojowi badań nad obrazem, ponownym odkryciem dzieł Botticellego w kręgach prerafaelitów oraz ich późniejszej reprezentacji w kulturze.The text is composed of an introduction and third chapter of an M.A. dissertation: “Primavera” / “The Birth of Venus” by Sandro Botticelli. Reinterpretations, Ekphrases, Representations (promoter: Prof. Dariusz Czaja), presented at the Institute of Ethnology and Cultural Anthropology, Jagiellonian University, in 2016. The author deals with the development of research focused on the painting, the rediscovery of Botticelli’s works by pre-Raphaelites, and their subsequent representation in culture

    The working time regulation in JustEatTakeaway supplementary company agreement for Takeaway.com Express Italy (Just Eat group) riders

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    Considering that the regulation of the time and the possible economic relevance of the phases of waiting for delivery is a field of discussion still access regarding the work of riders, the Author analyzes, in detail, how the JustEatTakeway supplementary company agreement regulates the working hours of riders. The Author illustrates the discipline contained in the CCNL Logistica,Trasporto, Merci e Spedizione and in the Protocol signed on July 18, 2018 for the same sector, to which the same company agreement in comment refers

    The Topicality of Prehistory. A New Reading of Marx’s Analysis of “So-called Primitive Accumulation”

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    The essay discusses Marx’s analysis of ‘‘so-called primitive accumulation’’ starting from the idea that contemporary global capitalism is characterized by new enclosures and by a set of other processes long considered characteristic of the historical transition to capitalism. A reflection on this temporal short circuit leads the author to an investigation of some of the peculiarities and difficulties of Marx’s method as, for instance, the relationship between the historical and the logical order of exposition. Reading the temporal structures of capitalism against the backdrop of Marx’s analysis of primitive accumulation suggests an emphasis on temporal heterogeneity, on the intertwining of continuity and rupture, of progress and catastrophe, that is far from any ‘‘historicist’’ interpretation of Marx. From this point of view, the author investigates some of the key questions connected to primitive accumulation: the production of labor power as a commodity as a specific and strategic form of the production of subjectivity, the concept of transition, the role of violence in capitalist development, and the relationship between formal and real subsumption of labor under capital

    The distinct roles of subordinate and superordinate group power, conflict, and categorization on intergroup prejudice in a multiethnic Italian terrritory

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    A German-speaking population majority and an Italian-speaking minority have lived in Italian Tyrol, also called “South Tyrol,” an area of northern Italy, for 85 years. In contrast, Trentino, which is adjacent to South Tyrol, has always been an Italian-speaking region. For this latter population, thus, intergroup contact with the population of South Tyrol has been minimal for 85 years. Researchers have shown that intergroup contact forms a condition that can affect levels of intergroup prejudice (S. L. Gaertner et al., 2000). Accordingly, the present author predicted and found differences in prejudice between Trentini participants on the one hand and South Tyrolean participants on the other hand as an effect of the differential level of intergroup contact that these 2 populations experienced. The author also found evidence for his prediction that this effect is mediated by the differential perceptions held by these 2 populations of culturally based intergroup conflict. Further, as hypothesized, because of this latter perception, members of the Italian minority in South Tyrol also perceived the political power of the Trentino–South Tyrol higher order administrative “Region” to be stronger than did members of both the Austrian South Tyrolean and the Trentini majorities. The author discussed implications at the societal level with respect to the role of perceived intergroup conflict for improving intergroup relations
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