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Infection of human placental cells by Brucella : Role of the multifunctional host protein CD98hc
No full textBrucellosis, an infectious disease caused by bacteria of the Brucella genus, is one of the major zoonosis around the globe. Initially an animal disease, the infection can be passed onto humans and increases the risk of obstetrical complications in pregnant infected women. During pregnancy, specialized placental cells called trophoblasts ensure the main functions of the placenta. Several of these functions involve the host protein CD98hc. This surface glycoprotein was shown by our group to be important during Brucella infection in different cell types. In this work, we studied the importance of CD98hc in Brucella infection of human trophoblasts and tried to decipher which specific function(s) of the protein was (were) hijacked by the bacteria. Knocking out the SLC3A2 gene (coding for CD98hc) turned out to be impossible, showing that this gene is essential in human trophoblasts. We could however obtain a cellular clone expressing a CD98hc protein with conformational and glycosylation changes in its C-terminal domain and that seems to be trapped in recycling endosomes. Nonetheless, such modifications were compatible with Brucella infection, giving clues about how bacteria could use CD98hc during infection. In another chapter of this work, we identified Gefitinib, an EGFR inhibitor used in the treatment of non-infectious diseases, as a promising drug to fight against brucellosis. This drug was shown to be effective in vitro against the 3 main zoonotic species of Brucella in human trophoblasts as well as murine macrophages. These findings provide new insights into the role of CD98hc in Brucella infection and new leads toward the development of improved brucellosis treatments.La brucellose, une maladie infectieuse causée par les bactéries du genre Brucella, est une des plus importantes zoonoses mondiales. Maladie animale, l’infection peut être transmise à l’Homme et augmente le risque de complications obstétricales chez la femme enceinte. Durant la grossesse, les cellules placentaires spécialisées appelées trophoblastes occupent les fonctions centrales au sein du placenta. Plusieurs de ces fonctions impliquent la protéine de l’hôte CD98hc. Cette glycoprotéine de surface a été démontrée par notre équipe comme étant importante pour l’infection de différents types cellulaires par Brucella. Dans cette étude, nous souhaitions évaluer l’importance de CD98hc dans l’infection par Brucella dans les trophoblastes humains et avons essayé de déterminer quelle(s) fonction(s) spécifique(s) de CD98hc étai(en)t détournées par la bactérie. Inactiver SLC3A2 (codant pour CD98hc) s’est révélé impossible, montrant le caractère essentiel de ce gène dans les trophoblastes humains. Nous avons cependant obtenu un clone cellulaire qui exprime une protéine avec des changements de conformation et de glycosylation dans son domaine C-ter et qui semble séquestrée dans les endosomes de recyclage. Toutes ces modifications sont cependant compatibles avec l’infection de ces cellules par Brucella, donnant ainsi des pistes sur la façon dont ces bactéries utilisent CD98hc au cours de l’infection. Dans un autre chapitre de ce travail, nous avons identifié le Géfitinib, un inhibiteur de l’EGFR utilisé dans le traitement de maladies non infectieuses, comme médicament prometteur pour lutter contre la brucellose. Le Géfitinib est en effet efficace in vitro contre les 3 principales espèces zoonotiques de Brucella dans les trophoblastes humains et les macrophages murins. Ces résultats fournissent de nouvelles perspectives quant au rôle de CD98hc dans l’infection par Brucella et de nouvelles pistes pour améliorer le traitement de la brucellose
Infection des cellules placentaires par Brucella : rôle de la protéine multifonctionnelle CD98hc
No full textLa brucellose, une maladie infectieuse causée par les bactéries du genre Brucella, est une des plus importantes zoonoses mondiales. Maladie animale, l’infection peut être transmise à l’Homme et augmente le risque de complications obstétricales chez la femme enceinte. Durant la grossesse, les cellules placentaires spécialisées appelées trophoblastes occupent les fonctions centrales au sein du placenta. Plusieurs de ces fonctions impliquent la protéine de l’hôte CD98hc. Cette glycoprotéine de surface a été démontrée par notre équipe comme étant importante pour l’infection de différents types cellulaires par Brucella. Dans cette étude, nous souhaitions évaluer l’importance de CD98hc dans l’infection par Brucella dans les trophoblastes humains et avons essayé de déterminer quelle(s) fonction(s) spécifique(s) de CD98hc étai(en)t détournées par la bactérie. Inactiver SLC3A2 (codant pour CD98hc) s’est révélé impossible, montrant le caractère essentiel de ce gène dans les trophoblastes humains. Nous avons cependant obtenu un clone cellulaire qui exprime une protéine avec des changements de conformation et de glycosylation dans son domaine C-ter et qui semble séquestrée dans les endosomes de recyclage. Toutes ces modifications sont cependant compatibles avec l’infection de ces cellules par Brucella, donnant ainsi des pistes sur la façon dont ces bactéries utilisent CD98hc au cours de l’infection. Dans un autre chapitre de ce travail, nous avons identifié le Géfitinib, un inhibiteur de l’EGFR utilisé dans le traitement de maladies non infectieuses, comme médicament prometteur pour lutter contre la brucellose. Le Géfitinib est en effet efficace in vitro contre les 3 principales espèces zoonotiques de Brucella dans les trophoblastes humains et les macrophages murins. Ces résultats fournissent de nouvelles perspectives quant au rôle de CD98hc dans l’infection par Brucella et de nouvelles pistes pour améliorer le traitement de la brucellose.Brucellosis, an infectious disease caused by bacteria of the Brucella genus, is one of the major zoonosis around the globe. Initially an animal disease, the infection can be passed onto humans and increases the risk of obstetrical complications in pregnant infected women. During pregnancy, specialized placental cells called trophoblasts ensure the main functions of the placenta. Several of these functions involve the host protein CD98hc. This surface glycoprotein was shown by our group to be important during Brucella infection in different cell types. In this work, we studied the importance of CD98hc in Brucella infection of human trophoblasts and tried to decipher which specific function(s) of the protein was (were) hijacked by the bacteria. Knocking out the SLC3A2 gene (coding for CD98hc) turned out to be impossible, showing that this gene is essential in human trophoblasts. We could however obtain a cellular clone expressing a CD98hc protein with conformational and glycosylation changes in its C-terminal domain and that seems to be trapped in recycling endosomes. Nonetheless, such modifications were compatible with Brucella infection, giving clues about how bacteria could use CD98hc during infection. In another chapter of this work, we identified Gefitinib, an EGFR inhibitor used in the treatment of non-infectious diseases, as a promising drug to fight against brucellosis. This drug was shown to be effective in vitro against the 3 main zoonotic species of Brucella in human trophoblasts as well as murine macrophages. These findings provide new insights into the role of CD98hc in Brucella infection and new leads toward the development of improved brucellosis treatments
Infection of human placental cells by Brucella : Role of the multifunctional host protein CD98hc
No full textBrucellosis, an infectious disease caused by bacteria of the Brucella genus, is one of the major zoonosis around the globe. Initially an animal disease, the infection can be passed onto humans and increases the risk of obstetrical complications in pregnant infected women. During pregnancy, specialized placental cells called trophoblasts ensure the main functions of the placenta. Several of these functions involve the host protein CD98hc. This surface glycoprotein was shown by our group to be important during Brucella infection in different cell types. In this work, we studied the importance of CD98hc in Brucella infection of human trophoblasts and tried to decipher which specific function(s) of the protein was (were) hijacked by the bacteria. Knocking out the SLC3A2 gene (coding for CD98hc) turned out to be impossible, showing that this gene is essential in human trophoblasts. We could however obtain a cellular clone expressing a CD98hc protein with conformational and glycosylation changes in its C-terminal domain and that seems to be trapped in recycling endosomes. Nonetheless, such modifications were compatible with Brucella infection, giving clues about how bacteria could use CD98hc during infection. In another chapter of this work, we identified Gefitinib, an EGFR inhibitor used in the treatment of non-infectious diseases, as a promising drug to fight against brucellosis. This drug was shown to be effective in vitro against the 3 main zoonotic species of Brucella in human trophoblasts as well as murine macrophages. These findings provide new insights into the role of CD98hc in Brucella infection and new leads toward the development of improved brucellosis treatments.La brucellose, une maladie infectieuse causée par les bactéries du genre Brucella, est une des plus importantes zoonoses mondiales. Maladie animale, l’infection peut être transmise à l’Homme et augmente le risque de complications obstétricales chez la femme enceinte. Durant la grossesse, les cellules placentaires spécialisées appelées trophoblastes occupent les fonctions centrales au sein du placenta. Plusieurs de ces fonctions impliquent la protéine de l’hôte CD98hc. Cette glycoprotéine de surface a été démontrée par notre équipe comme étant importante pour l’infection de différents types cellulaires par Brucella. Dans cette étude, nous souhaitions évaluer l’importance de CD98hc dans l’infection par Brucella dans les trophoblastes humains et avons essayé de déterminer quelle(s) fonction(s) spécifique(s) de CD98hc étai(en)t détournées par la bactérie. Inactiver SLC3A2 (codant pour CD98hc) s’est révélé impossible, montrant le caractère essentiel de ce gène dans les trophoblastes humains. Nous avons cependant obtenu un clone cellulaire qui exprime une protéine avec des changements de conformation et de glycosylation dans son domaine C-ter et qui semble séquestrée dans les endosomes de recyclage. Toutes ces modifications sont cependant compatibles avec l’infection de ces cellules par Brucella, donnant ainsi des pistes sur la façon dont ces bactéries utilisent CD98hc au cours de l’infection. Dans un autre chapitre de ce travail, nous avons identifié le Géfitinib, un inhibiteur de l’EGFR utilisé dans le traitement de maladies non infectieuses, comme médicament prometteur pour lutter contre la brucellose. Le Géfitinib est en effet efficace in vitro contre les 3 principales espèces zoonotiques de Brucella dans les trophoblastes humains et les macrophages murins. Ces résultats fournissent de nouvelles perspectives quant au rôle de CD98hc dans l’infection par Brucella et de nouvelles pistes pour améliorer le traitement de la brucellose
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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