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Ruolo delle proteine del tegumento nelle interazioni tra il virus dell’Herpes simplex di tipo1 e il pathway dei Multivesicular bodies
Full text linkMany enveloped viruses complete their replication cycle by forming vesicles that bud from cellular membranes of different origin, but separation of virion from host membranes is not a trivial or spontaneous step. Several enveloped RNA viruses, such as retroviruses, rhabdoviruses, filoviruses, arenaviruses, and, probably, also ortho and paramyxoviruses, solve such a problem by coopting factors that cells usually employ during the formation of vesicles within specific endosome-derived organelles: the multivesicular bodies (MVBs). Actually, enveloped RNA viruses budding and formation of MVBs intraluminal vesicles are analogous processes: in
both cases membranes must curve and bud away from (rather than into) the cytoplasm. Indeed, a productive infection requires that all the components necessary for the formation of infectious particles localize to the membrane at the site where budding will take place. To that end, RNA viruses evolved two possible strategies: the presence of special sequences named Late domains (L-domains) in their structural proteins and/or their ubiquitylation. In any case proteins involved are recruited to the MVBs pathway. Much less is known about herpesviruses and, in
general, enveloped DNA viruses. In fact, even if the initial steps of the herpetic infection are quite well-known, the cellular site of assembly and pericapsid’s acquisition as well as the nature of the membranes involved in viral budding are not clear yet.
The aim of this work was to elucidate the molecular mechanisms behind essential steps of herpesvirus replication, such as assembly and budding from infected cells. In particular, we used the -herpesvirus HSV-1 as a model. Two recent works pointed
out a possible role of MVBs in HSV-1 replication: both virus gress and intracellular trafficking and maturation of the essential glycoprotein gB require functional biogenesis of MVBs. On the basis of those considerations, we evaluated whether MVBs membranes could be the recruiting site of other main structural proteins, such as the tegumental ones, in order to identify those organelles as the pericapsid’s acquisition and final assembly site of the viral particles.
Most of all, we focused on four HSV-1 tegumental proteins: VP1/2, VP13/14, VP16 and VP22. Especially, we observed that both VP1/2 and VP16 possess sequences belonging to the L-domains motifs and that both VP1/2 and VP16 localize at the
MVBs membranes. We also proved the interaction between the PSAP motif of theprotein and Tsg101, its cellular partner. We supposed that the recruitment of VP1/2 to the MVBs can be due, at least partially, to such interaction. Vice versa, the reason
for the localization of VP16 are not as clear. We demonstrated that VP16 does not show any direct interactions between its PPLY motif and the corresponding cellular partners, the members of the Nedd4 ubiqutin-ligases family. Moreover, our data revealed that VP16 is not even ubiquitylated, a post-translational modification that would ensure its sorting to the MVBs. Supposing that its recruitment to the MVBs was indirect and due to other viral proteins, we verified two of the interactions ascribed to VP16 and other tegument proteins in the literature, especially those related to VP13/14 and VP22. We confirmed that VP16 direct interacts with VP22, in the absence of other viral factors, but not with VP13/14. Still, that interaction did
not explain the intracellular localization of VP16 that could require viral and/or cellular factors other than those examined. Last, by a deeper investigation of both VP22 and VP13/14, we demonstrated that each of those proteins is ubiquitylated and
that the ubiquitylation of VP13/14 is specific for the targeting to the MVBs pathway.
Concluding, our data showed that at least four HSV-1 tegumental proteins are recruited to the MVBs or own the necessary features for such an intracellular localization, that are L-domains or ubiquitin conjugation. So it is possible to suppose
that MVBs could provide the appropriate platform for the tegument assembly and the acquisition of the pericapsid as well as a possible exit from the infected cell.Molti virus dotati di envelope completano il proprio ciclo replicativo formando delle vescicole che gemmano attraverso membrane cellulari di varia natura, ma la scissione del virione da tali membrane non è un passaggio semplice o spontaneo. Per
quel che riguarda diversi virus a RNA, tra cui retrovirus, rabdovirus, filovirus, arenavirus e, presumibilmente, orto- e paramixovirus, tale problema è stato risolto mediante il reclutamento di fattori normalmente utilizzati dalla cellula durante la formazione di vescicole interne a specifici organelli membranosi derivati dagli endosomi: i multivesicular bodies (MVB). In effetti, la gemmazione dei virus a RNA dotati di envelope e la formazione delle vescicole interne ai MVB sono
processi analoghi: in entrambi i casi si verifica una curvatura della membrana in allontanamento dal citoplasma. Affinché un’infezione possa considerarsi produttiva, quindi, è necessario che tutti i componenti utili alla formazione della particella siano convogliati a livello della membrana in cui si verificherà l’evento di gemmazione. A questo scopo, i virus a RNA hanno evoluto due possibili strategie: la presenza di particolari sequenze note come Late domain (L-domain) all’interno delle proprie proteine strutturali e/o la loro ubiquitinazione; in entrambi i casi le
proteine coinvolte vengono reclutate nel pathway dei MVB. Molto meno è noto, invece, per quel che riguarda gli herpesvirus e, più in generale, i virus a DNA dotati di envelope. Infatti, se da un lato le fasi iniziali dell’infezione erpetica sono piuttosto conosciute, dall’altro rimangono aperte alcune controversie riguardanti il sito cellulare di assemblaggio e acquisizione del pericapside nonché la natura delle membrane implicate nella gemmazione della particella virale dalla cellula infetta.
Lo scopo di questo lavoro è stato quello di contribuire al chiarimento dei meccanismi molecolari dell’assemblaggio e della gemmazione degli herpesvirus, prendendo come modello il virus dell’herpes simplex di tipo 1 (HSV-1). In particolar modo, due
lavori pubblicati nell’ultimo periodo hanno evidenziato un possibile ruolo dei MVB nel ciclo replicativo di HSV-1 sottolineando l’importanza di una corretta biogenesi di tali organelli per garantire la gemmazione virale e il corretto trafficking intracellulare di una proteina virale essenziale, quale la glicoproteina B. Sulla base di tali riscontri si è deciso di valutare se le membrane dei MVB costituissero il sito di
reclutamento di altre importanti proteine strutturali, quali quelle del tegumento, cosìda poter identificare tali organelli come il sito di acquisizione del pericapside e di assemblaggio definitivo della particella virale.
Nel presente lavoro ci siamo focalizzati soprattutto su quattro proteine del tegumento di HSV-1: VP1/2, VP13/14, VP16 e VP22. In particolar modo, abbiamo dimostrato che VP1/2 e VP16 presentano al proprio interno sequenze riconducibili a L-domain
noti e che sia VP1/2 che VP16 localizzano a livello delle membrane dei MVB. Il reclutamento di VP1/2 a livello di tali organelli può essere attribuito, almeno in parte, all’interazione tra il dominio PSAP in essa contenuto e la proteina Tsg101, suo
partner cellulare, con cui abbiamo dimostrato l’associazione. Viceversa, le cause della localizzazione di VP16 non sono altrettanto chiare. Infatti, abbiamo dimostrato che VP16 non presenta alcuna interazione diretta tra il dominio PPLY in essa
presente e i corrispondenti partner cellulari, i membri della famiglia delle ubiquitino-ligasi Nedd4. Inoltre, in base ai nostri dati, la medesima proteina non risulta nemmeno ubiquitinata, modifica post-traduzionale che ne garantirebbe il direzionamento ai MVB. Nell’ipotesi che il suo reclutamento ai MVB sia di tipo
indiretto e dovuto all’azione di altre proteine virali, abbiamo quindi verificato alcune tra le interazioni riportate in letteratura per quel che riguarda VP16 e le altre proteine del tegumento, in particolare VP13/14 e VP22. Dai nostri esperimenti è emerso che VP16 interagisce direttamente con VP22, in assenza di altri fattori virali, ma non con VP13/14. Tuttavia, nemmeno il legame con VP22 è risultato tale da giustificare la localizzazione intracellulare di VP16, che quindi potrebbe richiedere fattori virali e/o cellulari diversi da quelli analizzati. Infine, mediante studi più approfonditi su VP22 e VP13/14, abbiamo dimostrato che entrambi tali proteine risultano ubiquitinate e che, nel caso specifico di VP13/14, tale ubiquitinazione è del tipo generalmente responsabile del direzionamento di una proteina al pathway dei MVB.
In conclusione, i nostri dati dimostrano che almeno quattro proteine del tegumento sono effettivamente reclutate ai MVB o possiedono le caratteristiche necessarie ad una simile localizzazione, quali la presenza di L-domain o la coniugazione
all’ubiquitina. E’ quindi possibile supporre che tali organelli, oltre a rappresentare una potenziale via d’uscita dalla cellula infettata, possano fornire anche la “piattaforma” cellulare adatta al completamento dell’assemblaggio del tegumento e all’acquisizione del pericapside da parte della particella virale
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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