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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
Contribution of molecular modeling to the study of human disease : Application to ATP7B transporter and receptor 5HT2B
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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
Molecular modeling of Tubulin-Ligand complexes
No full textLes microtubules sont des polymères cylindriques de tubuline-αβ, membres du cytosquelette eucaryote. Ils possèdent une dynamique intrinsèque nécessaire à de nombreuses fonctions cellulaires telle que la mitose. L’hydrolyse du nucléotide GTP dans les polymères de tubuline-αβ ainsi que les interactions entre la tubuline et les protéines partenaires ou les molécules à visées pharmacologiques, jouent un rôle critique sur la dynamique des microtubules. Durant cette thèse, des approches de modélisation moléculaire ont été utilisées pour mieux appréhender les interactions tubuline-ligand à l’échelle atomique et contribuer au développement de nouvelles molécules actives. Des simulations de dynamiques moléculaires ont été réalisées pour étudier l’effet de différents nucléotides dans la tubuline-β sur la structure et la dynamique du protofilament de tubuline. Nous proposons un rôle du résidu αE254 dans la coordination du magnésium catalytique. Nous observons également des changements conformationnels aux interfaces latérales et un réarrangement de structure aux interfaces longitudinales qui peuvent affecter la stabilisation du microtubule. Des travaux menés au laboratoire ont montré que la colchicine et le carbendazime se fixent dans des poches voisines dans la sous-unité tubuline-β et inhibent la prolifération cellulaire. Nous avons proposé un site de fixation du carbendazime dans les complexes tubuline-colchicine à l’aide de l’amarrage moléculaire et de simulations de dynamiques moléculaires. Ces expériences ont mené au design de molécules hybrides composées des noyaux colchicine et carbendazime reliés par un linker. Une de ces molécules hybrides a été synthétisée et testée avec succès sur des lignées de cellules HeLa. Enfin, nous avons construit des peptides cycliques dérivées d’I19L, un peptide anti-microtubule identifié au laboratoire. Des simulations de dynamique moléculaire et des calculs d’énergie libre de liaisons ont permis d’évaluer ces peptides. Enfin, des mutations ont été proposées afin d’optimiser l’interaction entre le meilleur peptide et la tubuline.Microtubules are cylindrical polymers of αβ-tubulin heterodimers, members of the eukaryotic cytoskeleton. They possess an intrinsic dynamics which is necessary to any cellular functions such as the mitosis. It has long been recognized that GTP hydrolysis in αβ-tubulin polymers plays a critical role in this dynamics as well as the interactions between tubulin and the protein partners or the drugs. In this thesis, molecular modeling approaches are applied to three theoretical studies to gain insight at the atomic scale about tubulin-ligand interactions and to contribute to the development of new active compounds. Molecular dynamics simulations were used to study the effect of the different nucleotide states at β-tubulin on the protofilament structure and dynamics. We propose a role for residue αE254 in catalytic magnesium coordination. We also observe conformational changes and structure rearrangement at lateral and longitudinal interfaces that can affect the microtubule stabilization. Previous work carried out in the laboratory showed that colchicine and carbendazime bind neighboring pockets in the β-tubulin subunit and inhibit cell proliferation. We proposed a binding site of carbendazime on the tubulin-colchicine complex, using docking and molecular dynamics simulation, which lead to the design of hybrid molecules composed of both colchicines and carbendazime moieties attached with a linker. One of these hybrid molecules has been synthesized and successfully tested on HeLa cells. Finally, we designed four cyclic peptides based on I19L, an anti-microtubule peptide identified at the laboratory. Molecular dynamic simulations and binding free energy calculations were used to evaluate these peptides. Mutations were then proposed on the best peptide to increase its interactions with tubulin
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
Study of molecular mechanisms involved in the impairment of mitochondrial function in a rare genetic disease of aging : mandibuloacral dysplasia associated to MTX2
No full textLe Syndrome de Dysplasie Mandibulo-Acrale (MADaM) lié au gène mtx-2 est une maladie génétique rare qui induit un vieillissement prématuré, conduisant au décès des patients vers l'âge de 14 ans. Cette pathologie résulte d'une mutation autosomique dominante de novo du gène mtx-2, responsable de la synthèse de la protéine MTX-2 localisée sur la membrane externe des mitochondries. Les patients atteints du syndrome MADaM présentent diverses altérations cellulaires, notamment une résistance à l'apoptose induite par le TNF-alpha, une augmentation de la sénescence et de l'autophagie, ainsi qu'une diminution de la prolifération cellulaire. Le réseau mitochondrial est anormalement fragmenté, entraînant une réduction de la phosphorylation oxydative et, par conséquent, une diminution de la production d'ATP. La fragmentation du réseau mitochondrial est également observée sur la souche mtx-2 de Caenorhabditis elegans (C. elegans). Ma thèse a débuté par la validation de la pertinence de ce modèle pour étudier la physiopathologie du syndrome MADaM. J'ai entrepris une série de tests phénotypiques, morphologiques et structurels, comprenant l'évaluation de la durée de vie des vers et l'analyse de la cuticule par microscopie à force atomique (AFM) et de la microscopie électronique à balayage. Les observations phénotypiques ont révélé un vieillissement accéléré chez les nématodes mtx-2. Les analyses en microscopie électronique à balayage, confirmées par l'AFM, ont mis en évidence des altérations de la structure mitochondriale et un désordre marqué de la cuticule. En utilisant une première approche transcriptomique, j'ai identifié plusieurs voies de signalisation impliquées dans le vieillissement, notamment l'apoptose, la signalisation de l'insuline, mTOR, AMPK, le calcium et la voie Wnt. Les gènes du collagène, de l'actine et du cytosquelette ont également été fortement affectés, comme confirmé par qRT PCR, indiquant une perturbation du transport des mitochondries dans les cellules et une modification de la structure de la cuticule. De plus, les fonctions mitochondriales ont été sévèrement altérées, démontrant des perturbations des gènes liés à la mitophagie, ainsi qu'une régulation à la baisse des complexes de la chaîne respiratoire et du cycle de Krebs. Au cours de ma thèse, j'ai principalement axé mes recherches sur la mitochondrie et les manifestations du vieillissement cutané à travers l'étude de la cuticule du nématode. En utilisant les données des voies de signalisation identifiées, nous avons sélectionné des approches thérapeutiques potentielles, notamment avec les médicaments suivants : la rapamycine, le lonafarnib, la metformine, le vérapamil et le bleu de méthylène. Les résultats ont été significatifs pour le bleu de méthylène, molécule aux propriétés antioxydantes capable de piéger les radicaux libres. Nous avons découvert que le bleu de méthylène pouvait restaurer l'aspect morphologique des mitochondries observées en AFM, améliorant chez les nématodes la respiration basale et durée de vie. De plus, une autre approche transcriptomique après traitement au bleu de méthylène a montré une restauration des gènes du collagène, de la cuticule, et de ceux impliqués dans les principales fonctions mitochondriales. Le transcriptome des nématodes mtx-2 traités semble partager d'avantage de similitudes avec celui des nématodes au phénotype sauvage. En fin de compte, nos travaux ont confirmé que C. elegans représente un modèle d'une importance cruciale pour l'étude du gène mtx-2 et pour la réalisation d'études précliniques visant à trouver des solutions thérapeutiques pour le Syndrome MADaM. L'aboutissement de mon étude a été d'identifier un potentiel traitement : le bleu de méthylène.Mandibuloacral Dysplasia Syndrome (MADaM) linked to the mtx-2 gene is a rare genetic disease that induces premature ageing, leading to the death of patients around the age of 14. The disease results from an autosomal dominant de novo mutation in the mtx-2 gene, which is responsible for the synthesis of the MTX-2 protein located on the outer membrane of the mitochondria. Patients with MADaM syndrome display a variety of cellular alterations, including resistance to TNF-alpha-induced apoptosis, increased senescence and autophagy, and decreased cell proliferation. The mitochondrial network is abnormally fragmented, leading to reduced oxidative phosphorylation and, consequently, reduced ATP production. Fragmentation of the mitochondrial network is also observed in the mtx-2 strain of Caenorhabditis elegans (C. elegans). My thesis began by validating the relevance of this model for studying the pathophysiology of MADaM syndrome. I undertook a series of phenotypic, morphological and structural tests, including assessment of the lifespan of the worms and analysis of the cuticle by atomic force microscopy (AFM) and scanning electron microscopy. Phenotypic observations revealed accelerated ageing in mtx-2 nematodes. Scanning electron microscopy analyses, confirmed by AFM, revealed alterations in mitochondrial structure and a marked disorder of the cuticle. Using an initial transcriptomic approach, I identified several signaling pathways involved in ageing, including apoptosis, insulin signaling, mTOR, AMPK, calcium and the Wnt pathway. The collagen, actin and cytoskeleton genes were also strongly affected, as confirmed by qRT PCR, indicating a disruption of mitochondrial transport within cells and a change in cuticle structure. In addition, mitochondrial functions were severely altered, showing disruption of mitophagy-related genes, as well as down-regulation of respiratory chain complexes and the Krebs cycle. During my thesis, I mainly focused my research on mitochondria and the manifestations of skin ageing through the study of the nematode cuticle. Using data from the signaling pathways identified, we selected potential therapeutic approaches, in particular with the following drugs: rapamycin, lonafarnib, metformin, verapamil and methylene blue. The results were significant for methylene blue, a molecule with antioxidant properties capable of trapping free radicals. We discovered that methylene blue could restore the morphological appearance of mitochondria observed in AFM, improving basal respiration and lifespan in nematodes. In addition, another transcriptomic approach after treatment with methylene blue showed a restoration of the collagen and cuticle genes, as well as those involved in the main mitochondrial functions. The transcriptome of treated mtx-2 nematodes seems to share more similarities with that of nematodes with a wild-type phenotype. Ultimately, our work confirmed that C. elegans represents a crucially important model for studying the mtx-2 gene and for carrying out preclinical studies aimed at finding therapeutic solutions for MADaM syndrome. The outcome of my study was to identify a potential treatment: methylene blue
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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