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Etude des mécanismes associés à la polarité rotationnelle des centrioles dans les cellules animales
No full textLes centrioles sont des structures cellulaires conservées au cours de l'évolution. Ils sont formés par des triplets de microtubules organisés selon une symétrie en 9. Chez les animaux, les centrioles forment le cœur du centrosome, le principal centre d'organisation des microtubules. Les centrosomes sont des acteurs clés de l'organisation cellulaire, essentiels à des processus fondamentaux tels que la division et la polarité cellulaires. Le plus âgé des centrioles au sein du centrosome permet aussi l'assemblage du cil primaire, un organite sensoriel important pour de nombreuses voies de signalisation. Des dysfonctionnements des cils sont impliqués dans une classe de maladies génétiques appelées ciliopathies. Les centrioles sont présents dans tous les principaux groupes eucaryotes, ce qui indique qu'ils ont une origine évolutive commune. Chez nombre d'organismes unicellulaires, les centrioles présentent une asymétrie rotationnelle due à des structures accessoires associées à des triplets spécifiques. Chez l'algue flagellée Chlamydomonas reinhardtii, la protéine Vfl1p contrôle l'asymétrie rotationnelle des centrioles. Dans cette thèse, nous montrons qu'un orthologue de Vfl1p est aussi nécessaire à la polarisation rotationnelle des centrioles dans les cellules multiciliées de la planaire Schmidtea mediterranea. C'est aussi le cas pour VFL3, l'orthologue d'une autre protéine contrôlant la polarité rotationnelle des centrioles chez C. reinhardtii. Chez la planaire, les centrioles sont arrangés en un réseau présentant une asymétrie chirale. Nous avons identifié VFL1 et VFL3 comme étant des composants des centrioles nécessaires à l'établissement de connexions asymétriques entre les centrioles. En effet, ces protéines affectent l'assemblage des appendices centriolaires responsables de l'ancrage des éléments de cytosquelette qui contrôlent la position des centrioles. Nous montrons également que l'orthologue humain de VFL3 est présent au niveau d'appendices centriolaires nécessaires à l'ancrage des microtubules et est nécessaire à cette fonction. Nous réalisons ensuite l'analyse fonctionnelle de l'orthologue humain de VFL1, aussi appelé LRRCC1. Dans le contexte du centrosome humain, les centrioles ne présentent pas d'asymétrie rotationnelle évidente. Le plus âgé des deux centrioles qui composent le centrosome possèdes des appendices organisés selon une symétrie en neuf comme le centriole lui-même. En utilisant une technique d'imagerie super-résolutive appelée expansion microscopy, nous montrons que l'orthologue humain de VFL1 s'associe préférentiellement à deux triplets consécutifs à l'extrémité distale des centrioles, comme cela avait été observé chez C. reinhardtii. VFL1 co-localise partiellement et affecte le recrutement d'un autre composant distal, C2CD3, dont nous montrons qu'il est également localisé de manière asymétrique dans la lumière du centriole. La localisation de VFL1 et C2CD3 dans les centrioles humains rappelle la forme d'une structure filamenteuse présente au même niveau dans les centrioles des flagellés. De plus, la déplétion de VFL1 dans les cellules humaines induit des défauts dans la structure du centriole, l'assemblage du cil primaire et la signalisation par le cil. Ces résultats indiquent que VFL1 coopère avec C2CD3 pour organiser la région distale des centrioles, et confirment le lien entre VFL1 et les ciliopathies suggéré par l'identification il y a quelques années d'une mutation dans le gène LRRCC1 chez deux patients atteints du syndrome de Joubert. Ainsi, nous mettons en évidence que l'asymétrie rotationnelle des centrioles, une propriété ancienne chez les eucaryotes, est conservée au sein du centrosome humain, et est liée à la fonction du cil primaire. L'ensemble de ces résultats apporte un éclairage nouveau sur les bases moléculaires et les fonctions de la polarité rotationnelle des centrioles dans différents contextes biologiques et au cours de l'évolution.Centrioles are evolutionarily conserved cellular structures. In animals, centrioles form the structural core of the centrosome, the main center of microtubule organization. Centrosomes are key players in cell organization, essential for fundamental cellular processes such as division and polarity. The oldest centriole within the centrosome also enables the assembly of the primary cilium, a sensory organelle important for the transduction of many signaling pathways. Cilia dysfunction is implicated in a class of genetic diseases called ciliopathies. Centrioles are present in all major eukaryotic groups, indicating that they have a common evolutionary origin. In many organisms, centrioles exhibit rotational asymmetry due to accessory structures associated with specific triplets. In the flagellated alga Chlamydomonas reinhardtii, the protein Vfl1p (Variable flagella number 1) controls the rotational asymmetry of centrioles. In this thesis, we show that an ortholog of Vfl1p called SMED-VFL1 is also required for rotational polarization of centrioles in multiciliated cells of the planarian Schmidtea mediterranea. This is also the case for VFL3, the ortholog of another protein controlling centriole rotational polarity in C. reinhardtii. In planarians, centrioles are arranged in a pattern generated by a network of centrioles with asymmetric properties. We identified VFL1 and VFL3 as components of centrioles required for the establishment of asymmetric connections between centrioles. These proteins affect the assembly of centriolar appendages responsible for anchoring cytoskeletal elements that control centriole position. We also show that the human orthologue of VFL3 is present at centriolar appendages required for microtubule anchoring and is necessary for this function. We then undertake a functional analysis of the human ortholog of VFL1, also called LRRCC1 (Leucine Rich Repeat and Coiled-Coil containing 1). A mutation in the gene encoding this protein has been linked to a specific ciliopathy, indicating its possible role in primary cilium function. In the context of the human centrosome, the centrioles do not show obvious rotational asymmetry. The older of the two centrioles that make up the centrosome has appendages organized in ninefold symmetry like the centriole itself. Using a super-resolution imaging technique called expansion microscopy, we show that the human ortholog of VFL1 preferentially associates with two consecutive triplets at the distal end of the centrioles, as previously observed in C. reinhardtii. VFL1 partially co-localizes and affects the recruitment of another distal component, C2CD3, which we show is also asymmetrically localized in the centriole lumen. The localization of VFL1 and C2CD3 in human centrioles is reminiscent of the shape of a filamentous structure present at the same level in flagellate centrioles. Furthermore, depletion of VFL1 in human cells induces defects in centriole structure, primary cilium assembly and cilium signaling. These results support that VFL1 cooperates with C2CD3 to organize the distal region of centrioles and confirm the involvement of VFL1 in ciliopathies. Thus, we demonstrate that rotational asymmetry of centrioles, an ancient property in eukaryotes, is conserved within the human centrosome, and is related to primary cilium function. Our results in planarian multiciliated cells also led us to analyze the role of human VFL1 in microtubule anchoring. We observed that VFL1 depletion induces a decrease in microtubule anchoring to the centrosome, in interphase and in mitosis. Together, these results shed new light on the molecular basis and functions of centriole rotational polarity in different biological contexts and during evolution
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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