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Roles of Arpin in cell migration and DNA repair
No full textAu front de migration, la protrusion de la membrane appelée lamellipode est générée par la polymérisation de l'actine branchée par Arp2/3. Ce processus est orchestré par la petite GTPase Rac1 capable d'activer le complexe WAVE et d'exposer son domaine WCA nécessaire pour l'activation d'Arp2/3. Différentes boucles de rétroaction positive soutiennent l'activité de Rac1 et stabilisent le lamellipode. Rac1 active aussi l’inhibiteur d'Arp2/3, Arpin, créant une boucle de rétroaction négative. Comme WAVE, Arpin possède un motif A à son extrémité C-terminale, pour lequel il existe deux sites d’interaction à la surface d’Arp2/3. Au lieu d’empêcher la formation de lamellipode, Arpin régule sa durée de vie et, ainsi, contrôle la persistance de la migration cellulaire. Récemment, une nouvelle fonction d'Arp2/3 dans la recombinaison homologue (HDR) a été rapportée.Dans ma thèse, je me suis attaché à mieux comprendre les rôles et les régulations d'Arpin dans la cellule. Nous avons identifié de nouveaux partenaires d'interaction d'Arpin, les Tankyrases 1 et 2. En interrompant spécifiquement l’interaction des Tankyrases ou d’Arp2/3 avec Arpin, j’ai montré que ces deux interactions sont nécessaires pour l’activité d'Arpin dans la régulation de la migration cellulaire. En collaboration, nous avons étudié les mécanismes d'interaction d'Arpin avec le complexe Arp2/3 et montré qu’Arpin se lie à un seul site sur Arp2/3, au niveau de la sous-unité Arp3. Outre le motif A, l’interaction nécessite un motif C non identifié auparavant, similaire au domaine C des activateurs d’Arp2/3. Deuxièmement, j'ai montré que la déplétion d'Arpin stimulait l'efficacité de la HDR mais favorisait l'accumulation des sites de réparation d’ADN dans le noyau. Arpin, ainsi, pourrait jouer un rôle régulateur dans la réparation de l’ADN.At the leading edge, membrane protrusions called lamellipodia are driven by Arp2/3-mediated actin polymerization. This process is orchestrated by the small GTPase Rac1 that activates the WAVE complex by exposing its WCA domain. Different positive feedback loops sustain Rac1 activity and stabilize lamellipodia. Strikingly, Rac1 also activates an Arp2/3 inhibitory protein, Arpin, thus creating a negative feedback loop. Like WAVE, Arpin possesses an A motif at its C-terminus, for which two binding sites at the surface of Arp2/3 are predicted. Arpin does not prevent lamellipodia from forming but rather regulates their lifetime and, thus, control the persistence of cell migration. Recently, a new Arp2/3 function during DNA repair has been reported, specifically in homology directed recombination (HDR).During my PhD I sought to better understand the roles and regulations of Arpin in the cell. We identified new Arpin interaction partners, Tankyrases 1 and 2. By specifically impairing Tankyrase or Arp2/3 binding to Arpin we demonstrated that both the interactions are required for full Arpin activity in the regulation of cell migration. In collaboration, we studied the mechanisms of Arpin interaction with the Arp2/3 complex and showed that Arpin binds to a single site at the surface of Arp2/3, interacting specifically with the Arp3 subunit. This interaction requires a previously unidentified C helix motif at the C-terminus of Arpin, similar to the C domain of Arp2/3 activators. In addition, I demonstrated that Arpin depletion increases HDR efficiency but also promotes accumulation of DSB foci in the cell nuclei. Arpin, thus, could play a regulatory role in DNA repair
Rôles d’Arpin dans la migration cellulaire et la réparation de l’ADN
No full textAt the leading edge, membrane protrusions called lamellipodia are driven by Arp2/3-mediated actin polymerization. This process is orchestrated by the small GTPase Rac1 that activates the WAVE complex by exposing its WCA domain. Different positive feedback loops sustain Rac1 activity and stabilize lamellipodia. Strikingly, Rac1 also activates an Arp2/3 inhibitory protein, Arpin, thus creating a negative feedback loop. Like WAVE, Arpin possesses an A motif at its C-terminus, for which two binding sites at the surface of Arp2/3 are predicted. Arpin does not prevent lamellipodia from forming but rather regulates their lifetime and, thus, control the persistence of cell migration. Recently, a new Arp2/3 function during DNA repair has been reported, specifically in homology directed recombination (HDR).During my PhD I sought to better understand the roles and regulations of Arpin in the cell. We identified new Arpin interaction partners, Tankyrases 1 and 2. By specifically impairing Tankyrase or Arp2/3 binding to Arpin we demonstrated that both the interactions are required for full Arpin activity in the regulation of cell migration. In collaboration, we studied the mechanisms of Arpin interaction with the Arp2/3 complex and showed that Arpin binds to a single site at the surface of Arp2/3, interacting specifically with the Arp3 subunit. This interaction requires a previously unidentified C helix motif at the C-terminus of Arpin, similar to the C domain of Arp2/3 activators. In addition, I demonstrated that Arpin depletion increases HDR efficiency but also promotes accumulation of DSB foci in the cell nuclei. Arpin, thus, could play a regulatory role in DNA repair.Au front de migration, la protrusion de la membrane appelée lamellipode est générée par la polymérisation de l'actine branchée par Arp2/3. Ce processus est orchestré par la petite GTPase Rac1 capable d'activer le complexe WAVE et d'exposer son domaine WCA nécessaire pour l'activation d'Arp2/3. Différentes boucles de rétroaction positive soutiennent l'activité de Rac1 et stabilisent le lamellipode. Rac1 active aussi l’inhibiteur d'Arp2/3, Arpin, créant une boucle de rétroaction négative. Comme WAVE, Arpin possède un motif A à son extrémité C-terminale, pour lequel il existe deux sites d’interaction à la surface d’Arp2/3. Au lieu d’empêcher la formation de lamellipode, Arpin régule sa durée de vie et, ainsi, contrôle la persistance de la migration cellulaire. Récemment, une nouvelle fonction d'Arp2/3 dans la recombinaison homologue (HDR) a été rapportée.Dans ma thèse, je me suis attaché à mieux comprendre les rôles et les régulations d'Arpin dans la cellule. Nous avons identifié de nouveaux partenaires d'interaction d'Arpin, les Tankyrases 1 et 2. En interrompant spécifiquement l’interaction des Tankyrases ou d’Arp2/3 avec Arpin, j’ai montré que ces deux interactions sont nécessaires pour l’activité d'Arpin dans la régulation de la migration cellulaire. En collaboration, nous avons étudié les mécanismes d'interaction d'Arpin avec le complexe Arp2/3 et montré qu’Arpin se lie à un seul site sur Arp2/3, au niveau de la sous-unité Arp3. Outre le motif A, l’interaction nécessite un motif C non identifié auparavant, similaire au domaine C des activateurs d’Arp2/3. Deuxièmement, j'ai montré que la déplétion d'Arpin stimulait l'efficacité de la HDR mais favorisait l'accumulation des sites de réparation d’ADN dans le noyau. Arpin, ainsi, pourrait jouer un rôle régulateur dans la réparation de l’ADN
Rôles d’Arpin dans la migration cellulaire et la réparation de l’ADN
No full textAt the leading edge, membrane protrusions called lamellipodia are driven by Arp2/3-mediated actin polymerization. This process is orchestrated by the small GTPase Rac1 that activates the WAVE complex by exposing its WCA domain. Different positive feedback loops sustain Rac1 activity and stabilize lamellipodia. Strikingly, Rac1 also activates an Arp2/3 inhibitory protein, Arpin, thus creating a negative feedback loop. Like WAVE, Arpin possesses an A motif at its C-terminus, for which two binding sites at the surface of Arp2/3 are predicted. Arpin does not prevent lamellipodia from forming but rather regulates their lifetime and, thus, control the persistence of cell migration. Recently, a new Arp2/3 function during DNA repair has been reported, specifically in homology directed recombination (HDR).During my PhD I sought to better understand the roles and regulations of Arpin in the cell. We identified new Arpin interaction partners, Tankyrases 1 and 2. By specifically impairing Tankyrase or Arp2/3 binding to Arpin we demonstrated that both the interactions are required for full Arpin activity in the regulation of cell migration. In collaboration, we studied the mechanisms of Arpin interaction with the Arp2/3 complex and showed that Arpin binds to a single site at the surface of Arp2/3, interacting specifically with the Arp3 subunit. This interaction requires a previously unidentified C helix motif at the C-terminus of Arpin, similar to the C domain of Arp2/3 activators. In addition, I demonstrated that Arpin depletion increases HDR efficiency but also promotes accumulation of DSB foci in the cell nuclei. Arpin, thus, could play a regulatory role in DNA repair.Au front de migration, la protrusion de la membrane appelée lamellipode est générée par la polymérisation de l'actine branchée par Arp2/3. Ce processus est orchestré par la petite GTPase Rac1 capable d'activer le complexe WAVE et d'exposer son domaine WCA nécessaire pour l'activation d'Arp2/3. Différentes boucles de rétroaction positive soutiennent l'activité de Rac1 et stabilisent le lamellipode. Rac1 active aussi l’inhibiteur d'Arp2/3, Arpin, créant une boucle de rétroaction négative. Comme WAVE, Arpin possède un motif A à son extrémité C-terminale, pour lequel il existe deux sites d’interaction à la surface d’Arp2/3. Au lieu d’empêcher la formation de lamellipode, Arpin régule sa durée de vie et, ainsi, contrôle la persistance de la migration cellulaire. Récemment, une nouvelle fonction d'Arp2/3 dans la recombinaison homologue (HDR) a été rapportée.Dans ma thèse, je me suis attaché à mieux comprendre les rôles et les régulations d'Arpin dans la cellule. Nous avons identifié de nouveaux partenaires d'interaction d'Arpin, les Tankyrases 1 et 2. En interrompant spécifiquement l’interaction des Tankyrases ou d’Arp2/3 avec Arpin, j’ai montré que ces deux interactions sont nécessaires pour l’activité d'Arpin dans la régulation de la migration cellulaire. En collaboration, nous avons étudié les mécanismes d'interaction d'Arpin avec le complexe Arp2/3 et montré qu’Arpin se lie à un seul site sur Arp2/3, au niveau de la sous-unité Arp3. Outre le motif A, l’interaction nécessite un motif C non identifié auparavant, similaire au domaine C des activateurs d’Arp2/3. Deuxièmement, j'ai montré que la déplétion d'Arpin stimulait l'efficacité de la HDR mais favorisait l'accumulation des sites de réparation d’ADN dans le noyau. Arpin, ainsi, pourrait jouer un rôle régulateur dans la réparation de l’ADN
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
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