1,720,962 research outputs found
O-GlcNAcylation de la Thymidylate Synthase : un mécanisme de sensibilisation au 5-fluorouracile dans le cancer colorectal
No full textO-GlcNAcylation (O-N-acetylglucosaminylation) is a dynamic and reversible PTM (post-translational modification) controlled by a couple of unique antagonist enzymes : OGT (O-GlcNAc transferase) and OGA (O-GlcNAcase). O GlcNAcylation is considered as a nutritional sensor and regulates a plethora of fundamental cellular mechanisms. By targeting oncoproteins and tumor suppressors, dysregulation of O-GlcNAcylation is associated with carcinogenesis and tumor progression. However, its role in the anti-cancer therapy response has been poorly investigated. Recently, hyper O-GlcNAcylation has been shown to impact the response of some cancers to drugs such as tamoxifen, cisplatin, bortezomib and 5-FU (5-fluorouracil). 5-FU is the CRC (colorectal cancer) gold standard chemotherapy and TS (Thymidylate synthase) is its main target. Overexpression of TS is a biomarker of 5-FU resistance already used clinically. TS has been shown to be O-GlcNAcylated but the role of this PTM has not been elucidated. We therefore analyzed the « cross-talk » between O-GlcNAcylation and 5-FU response based on the hypothesis that O-GlcNAcylation impacts the sensitivity to 5-FU by regulating TS. In vivo mouse model of human CRC and colon non-cancerous and cancerous cells were used to analyze the effect of 5 FU on total O-GlcNAcylation and, reciprocally, the impact of O-GlcNAcylation on TS level/activity and 5-FU response. Our in vitro data corroborate our in vivo results and support that 5-FU decreases O-GlcNAcylation and, reciprocally, that O-GlcNAcylation increases TS level and sensitizes CRC to 5-FU. We deciphered the underlying molecular mechanism which highlights the role of O-GlcNAcylation towards TS stability and protection against proteasomal degradation. Two TS O-GlcNAcylated sites have been identified: at Thr251 within the dimerization interface and at Thr306 within the carboxy-terminal degron sequence known to control TS degradation. Together, our results propose a new therapeutic approach combining 5-FU-based therapy with an OGA inhibitor to improve the CRC drug responseLa O-GlcNAcylation (O-N-acétylglucosaminylation) est une MPT (modification post-traductionnelle) dynamique et réversible catalysée par un unique couple d’enzymes antagonistes : l’OGT (O-GlcNAc transférase) et l’OGA (O GlcNAcase). Elle est considérée comme un véritable senseur nutritionnel et régule un grand nombre de mécanismes cellulaires fondamentaux. En ciblant des oncoprotéines et des suppresseurs de tumeur, sa dérégulation est associée à la cancérogenèse et la progression tumorale. En revanche, son rôle dans la réponse aux thérapies anti-cancéreuses est très peu étudié. Il a été néanmoins montré récemment que l’hyper-O-GlcNAcylation impacte la réponse de certains cancers à des drogues telles que le tamoxifène, le cisplatine, le bortézomib et le 5-FU (5-fluorouracile). Le 5-FU est la chimiothérapie de référence du CCR (cancer colorectal) et la TS (Thymidylate Synthase) sa cible principale. La surexpression de la TS est un biomarqueur de résistance au 5-FU utilisé en clinique. La TS a été montrée comme étant O-GlcNAcylée mais le rôle de cette MPT n’a pas été élucidé. Il nous est donc paru intéressant d’analyser le « cross-talk » entre O-GlcNAcylation et réponse au 5-FU dans le CCR dans l’hypothèse que la O-GlcNAcylation pourrait impacter la sensibilité au 5-FU en régulant sa cible TS. Un modèle murin in vivo de CCR humains et des cellules coliques non cancéreuses et cancéreuses ont été utilisés pour analyser l’effet du 5-FU sur la O-GlcNAcylation globale des protéines et réciproquement l’impact de la O-GlcNAcylation sur le niveau et l’activité de la TS, et la réponse au 5-FU. Nos données in vitro corroborent nos résultats in vivo et soutiennent que le 5-FU diminue la O-GlcNAcylation globale et que, réciproquement, la O-GlcNAcylation augmente le niveau de TS et sensibilise le CCR au 5-FU. Nous avons déchiffré le mécanisme moléculaire sous-jacent mettant en lumière le rôle de la O-GlcNAcylation dans la stabilisation de la TS et sa protection contre la dégradation protéasomale. Deux sites de O-GlcNAcylation de la TS ont été identifiés : la Thr251 à l’interface de dimérisation de l’enzyme et la Thr306 dans la séquence dégron carboxy-terminale connue pour contrôler sa dégradation. Ensemble nos résultats proposent une nouvelle stratégie thérapeutique combinant le 5-FU à un inhibiteur de l’OGA afin d’améliorer la réponse du CCR à la chimiothérapie à base de 5-FU
O-GlcNAcylation of Thymidylate Synthase : a 5-fluorouracil sensitization mechanism in colorectal cancer
No full textLa O-GlcNAcylation (O-N-acétylglucosaminylation) est une MPT (modification post-traductionnelle) dynamique et réversible catalysée par un unique couple d’enzymes antagonistes : l’OGT (O-GlcNAc transférase) et l’OGA (O GlcNAcase). Elle est considérée comme un véritable senseur nutritionnel et régule un grand nombre de mécanismes cellulaires fondamentaux. En ciblant des oncoprotéines et des suppresseurs de tumeur, sa dérégulation est associée à la cancérogenèse et la progression tumorale. En revanche, son rôle dans la réponse aux thérapies anti-cancéreuses est très peu étudié. Il a été néanmoins montré récemment que l’hyper-O-GlcNAcylation impacte la réponse de certains cancers à des drogues telles que le tamoxifène, le cisplatine, le bortézomib et le 5-FU (5-fluorouracile). Le 5-FU est la chimiothérapie de référence du CCR (cancer colorectal) et la TS (Thymidylate Synthase) sa cible principale. La surexpression de la TS est un biomarqueur de résistance au 5-FU utilisé en clinique. La TS a été montrée comme étant O-GlcNAcylée mais le rôle de cette MPT n’a pas été élucidé. Il nous est donc paru intéressant d’analyser le « cross-talk » entre O-GlcNAcylation et réponse au 5-FU dans le CCR dans l’hypothèse que la O-GlcNAcylation pourrait impacter la sensibilité au 5-FU en régulant sa cible TS. Un modèle murin in vivo de CCR humains et des cellules coliques non cancéreuses et cancéreuses ont été utilisés pour analyser l’effet du 5-FU sur la O-GlcNAcylation globale des protéines et réciproquement l’impact de la O-GlcNAcylation sur le niveau et l’activité de la TS, et la réponse au 5-FU. Nos données in vitro corroborent nos résultats in vivo et soutiennent que le 5-FU diminue la O-GlcNAcylation globale et que, réciproquement, la O-GlcNAcylation augmente le niveau de TS et sensibilise le CCR au 5-FU. Nous avons déchiffré le mécanisme moléculaire sous-jacent mettant en lumière le rôle de la O-GlcNAcylation dans la stabilisation de la TS et sa protection contre la dégradation protéasomale. Deux sites de O-GlcNAcylation de la TS ont été identifiés : la Thr251 à l’interface de dimérisation de l’enzyme et la Thr306 dans la séquence dégron carboxy-terminale connue pour contrôler sa dégradation. Ensemble nos résultats proposent une nouvelle stratégie thérapeutique combinant le 5-FU à un inhibiteur de l’OGA afin d’améliorer la réponse du CCR à la chimiothérapie à base de 5-FU.O-GlcNAcylation (O-N-acetylglucosaminylation) is a dynamic and reversible PTM (post-translational modification) controlled by a couple of unique antagonist enzymes : OGT (O-GlcNAc transferase) and OGA (O-GlcNAcase). O GlcNAcylation is considered as a nutritional sensor and regulates a plethora of fundamental cellular mechanisms. By targeting oncoproteins and tumor suppressors, dysregulation of O-GlcNAcylation is associated with carcinogenesis and tumor progression. However, its role in the anti-cancer therapy response has been poorly investigated. Recently, hyper O-GlcNAcylation has been shown to impact the response of some cancers to drugs such as tamoxifen, cisplatin, bortezomib and 5-FU (5-fluorouracil). 5-FU is the CRC (colorectal cancer) gold standard chemotherapy and TS (Thymidylate synthase) is its main target. Overexpression of TS is a biomarker of 5-FU resistance already used clinically. TS has been shown to be O-GlcNAcylated but the role of this PTM has not been elucidated. We therefore analyzed the « cross-talk » between O-GlcNAcylation and 5-FU response based on the hypothesis that O-GlcNAcylation impacts the sensitivity to 5-FU by regulating TS. In vivo mouse model of human CRC and colon non-cancerous and cancerous cells were used to analyze the effect of 5 FU on total O-GlcNAcylation and, reciprocally, the impact of O-GlcNAcylation on TS level/activity and 5-FU response. Our in vitro data corroborate our in vivo results and support that 5-FU decreases O-GlcNAcylation and, reciprocally, that O-GlcNAcylation increases TS level and sensitizes CRC to 5-FU. We deciphered the underlying molecular mechanism which highlights the role of O-GlcNAcylation towards TS stability and protection against proteasomal degradation. Two TS O-GlcNAcylated sites have been identified: at Thr251 within the dimerization interface and at Thr306 within the carboxy-terminal degron sequence known to control TS degradation. Together, our results propose a new therapeutic approach combining 5-FU-based therapy with an OGA inhibitor to improve the CRC drug respons
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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