1,720,986 research outputs found
Le chaperon d’histones SET/I2PP2A est nécessaire pour prévenir les aneuploïdies dans les ovocytes de souris
No full textLa ségrégation des chromosomes dans l'ovogenèse humaine conduit souvent à des aneuploïdies, c'est-à-dire un nombre erroné de chromosomes dans la cellule. Pour obtenir une ségrégation correcte des chromosomes pendant la méiose, il est essentiel que la cohésion entre les chromatides sœurs soit enlevée des bras chromosomiques pendant la méiose I, pour séparer les chromosomes homologues, puis du centromère pendant la méiose II, pour séparer les chromatides sœurs. Ces deux étapes d'élimination de la cohésion sont effectuées par la même enzyme, la séparase, qui doit être régulée pour éviter les erreurs de ségrégation chromosomique. Je suis intéressée à comprendre comment la « décision » de quelle partie de la cohésion à enlever (des bras ou des centromères) est faite pendant la méiose. Deux modèles ont été proposés pour expliquer comment la cohésion du centromère devient vulnérable à la séparase uniquement en méiose II : par l'effet des forces de traction du fuseau méiotique sur cette région du chromosome, ou par l'action d'un agent déprotecteur, SET/I2PP2A. Dans ce projet, j'ai réfuté ces deux modèles. En plus, en utilisant un knock-out conditionnel de SET dans des ovocytes de souris, j'ai trouvé un nouveau rôle de SET dans la régulation de la ségrégation des chromosomes déjà pendant la première division méiotique. En l'absence de SET, les chromosomes ne parviennent pas à s'aligner ni à séparer correctement les chromosomes homologues, conduisant à des aneuploïdies. SET est nécessaire pour enlever la cohésion sur les bras chromosomiques pendant la méiose I et pour maintenir les mécanismes de correction d'erreurs pleinement fonctionnels.Chromosome segregation in human oogenesis is highly error prone, often leading to aneuploidies—a wrong number of chromosomes in the cell. To achieve correct segregation of chromosomes in meiosis, it is vital that cohesion between sister chromatids is removed in a stepwise manner: from chromosome arms during meiosis I to separate homologous chromosomes, and from a region called the centromere during meiosis II to separate sister chromatids. In meiosis, both these steps of cohesion removal are done by the same enzyme, separase. The effect of separase on chromosome cohesion must be tightly regulated to prevent errors in chromosome segregation. I am interested in understanding how the “decision” of which part of cohesion to remove (from arms or centromeres) is done during meiosis. Two main models were proposed to explain how centromere cohesion becomes vulnerable to separase only in meiosis II: by the effect of pulling forces from the meiotic spindle on this region of the chromosome, or through the action of a deprotective agent, SET, also known as I2PP2A. In this project, I have disproved both these models. I show that spindle tension is not required for correct cohesion removal either in meiosis I or in meiosis II. Using a conditional knockout of SET in mouse oocytes, I found a novel and unexpected role of SET in regulating chromosome segregation already during the first meiotic division: in the absence of SET, chromosomes fail to align at the metaphase plate and to correctly separate homologous chromosomes, which leads to aneuploidy. SET is required to remove cohesion on chromosome arms during meiosis I and to keep the mechanisms of error correction fully functional
Mechanism of chromosomes segregation in mouse oocytes
No full textChez la femme, le risque de concevoir un embryon aneuploïde augmente de façon exponentielle dès 35 ans. La majorité de ces aneuploïdies sont dues à de mauvaises ségrégations des chromosomes lors des deux divisions de méiose dans l'ovocyte. Afin de limiter les erreurs de ségrégation, les divisions méiotiques doivent impérativement se dérouler en deux temps et de manière contrôlée. Un premier aspect de ma thèse a consisté à étudier les mécanismes qui régulent la séparation des chromosomes dans l'ovocyte de souris. J'ai montré que la Cycline A2 joue un rôle essentiel pour la séparation des chromatides s¿urs en méiose II. Au contraire, cette protéine doit impérativement être absente des régions centromériques en méiose I afin d'éviter une séparation précoce des chromatides s¿urs qui conduirait à la formation d'un ovocyte aneuploïde. Dans un seconde temps, mes travaux de thèse ont visé à étudier le mécanisme de surveillance de la première transition métaphase-anaphase appelé SAC (Spindle Assembly Checkpoint). Il a été montré que l'expression d'une protéine du SAC appelée BubR1 décroît naturellement dans les ovocytes avec l'âge maternel. Afin d'analyser les conséquences de cette diminution, j'ai utilisé une lignée de souris totalement délétée pour la protéine BubR1 spécifiquement dans les ovocytes. J'ai montré que la perte totale de BubR1 entraîne plus de 80% d'aneuploïdies dans l'ovocyte dès la première division de méiose. La méiose I est accélérée et les chromosomes homologues se séparent de façon anarchique. De plus, le fuseau méiotique devient instable. La diminution naturelle de BubR1 pourrait ainsi expliquer l'augmentation du nombre d'aneuploïdie avec l'âge maternel.Women in industrialized countries tend to postpone childbearing, leading to a 70% increase intrisomic pregnancies over 20 years. Meiosis in females is error prone, with rates of meiotic chromosome missegregations strongly increasing towards the end of the reproductive lifespan. A strong reduction of BubR1 has been observed in oocytes of women approaching menopause and in ovaries of aged mice, which led to the hypothesis that deterioration of spindle assembly checkpoint fidelity contributes to age-related aneuploidization. However, this idea has remained controversial since transient knock-down of BubR1 was found to prevent meiotic prophase arrest and chromosome segregation in a checkpoint independent manner. We employed a conditional knockout approach in mouse oocytes to dissect the meiotic roles of BubR1. We show that BubR1 is required for diverse meiotic functions, including persistent spindle assembly checkpoint activity, timing of meiosis I, and establishment of robust kinetochore-microtubule attachments in a meiosis specific manner, but not prophase I arrest. These data reveal that BubR1 plays a multi-faceted role in chromosome segregation during the first meiotic division and suggest that age-related loss of BubR1 is a key determinant of formation of aneuploid oocytes as women approach menopause. Using mouse oocytes, a second aspect of my thesis reveals that cyclin A2 promotes entry into meiosis, as well as an additional unexpected role, namely, its requirement for separase- dependent sister chromatid separation in meiosis II
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
Le paysage phosphoprotéomique entre la première et la deuxième division méiotique
No full textLa méiose est une division cellulaire spécialisée au cours de laquelle une seule phase S est suivie d'une succession de deux phases M qui se produisent sans phase S intermédiaire. Cela signifie que la période entre les deux divisions doit être étroitement régulée afin d'assurer le déclenchement et l'inhibition de processus biologiques spécifiques. La transition entre la première et la deuxième division méiotique est unique en ce sens qu'il est essentiel que certains événements tels que la duplication du centrosome et la ségrégation des chromosomes se reproduisent, tandis que la réplication de l'ADN doit être strictement inhibée pour assurer la poursuite correcte de la méiose. Le maître régulateur du cycle cellulaire est le complexe cycline-Cdk qui assure une progression de phase ordonnée à travers la phosphorylation de divers substrats. Une analyse globale du phosphoprotéome de la transition MI-MII a été réalisée dans un contexte de type sauvage et comparée au paysage de phosphoprotéome précédemment généré de la sortie mitotique pour déterminer en quoi la fin de la mitose est différente de la fin de la méiose I. Cela a révélé un inattendu, inversé schéma de phosphorylation sur les phosphosites Cdk complets et un comportement opposé des principaux motifs consensus de la kinase entre la transition MI-MII et la sortie de la mitose. Une deuxième analyse globale du phosphoprotéome a été réalisée après une diminution complète de l'activité de Cdk en métaphase I. Nous avons constaté qu'une baisse artificielle de l'activité de Cdk pendant la transition MI-MII récapitule une sortie de type mitotique dans la méiose I, avec le schéma des ondes séquentielles phosphomotives restaurées . Cela suggère que le cycle cellulaire méiotique a la plasticité nécessaire pour recréer le paysage de la mitose et pour ordonner la déphosphorylation du substrat de la même manière via l'activité de base de la kinase. Cependant, d'autres stratégies doivent être mises en place afin de permettre la régulation spécialisée de la transition MI-MII, telles que l'expression spécifique de la cycline et la présence d'autres régulateurs spécifiques à la méiose. Dans l'ensemble, nos résultats fournissent de nouvelles informations sur le paysage de la phosphorylation de la transition MI-MII et les mécanismes potentiels impliqués dans sa régulation.Meiosis is a specialized cell division during which a single S-phase is followed by a succession of two M-phases that occur without an intermediate S-phase. This means that the period between the two divisions has to be tightly regulated in order to ensure the onset and inhibition of specific biological processes. The transition between the first and second meiotic division is unique in that it is essential some events such as centrosome duplication and chromosome segregation reoccur, while DNA replication must be strictly inhibited to ensure the correct continuation of meiosis. The master regulator of the cell cycle is the cyclin-Cdk complex which ensures ordered phase progression through the phosphorylation of various substrates. A global phosphoproteome analysis of the MI-MII transition was performed in a wild type context and compared with the previously generated phosphoproteome landscape of mitotic exit to address how the end of mitosis is different from the end of meiosis I. This revealed an unexpected, reversed pattern of phosphorylation on full Cdk phosphosites, and an opposite behaviour of major kinase consensus motifs between the MI-MII transition and mitosis exit. A second global phosphoproteome analysis was performed after a complete decrease of Cdk activity in metaphase I. We found that an artificial drop in Cdk activity during MI-MII transition recapitulates a mitotic-like exit in meiosis I, with the pattern of phosphomotif sequential waves restored. This suggests that the meiotic cell cycle has the plasticity to recreate the mitosis landscape and to order substrate dephosphorylation in the same way through baseline kinase activity. However other strategies have to be put in place in order to allow the specialized regulation of the MI-MII transition, such as specific cyclin expression and presence of other meiosis-specific regulators. Altogether, our results provide new insights into the phosphorylation landscape of the MI-MII transition and the potential machineries involved in its regulation
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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