49 results on '"Causse S"'
Search Results
2. Inhibition of colon cancer growth by docosahexaenoic acid involves autocrine production of TNFα
- Author
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Fluckiger, A, Dumont, A, Derangère, V, Rébé, C, de Rosny, C, Causse, S, Thomas, C, Apetoh, L, Hichami, A, Ghiringhelli, F, and Rialland, M
- Published
- 2016
- Full Text
- View/download PDF
3. Establishment of embryogenic cell suspension cultures of garlic (Allium sativum L.), plant regeneration and biochemical analyses
- Author
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Fereol, L., Chovelon, V., Causse, S., Triaire, D., Arnault, I., Auger, J., and Kahane, R.
- Published
- 2005
- Full Text
- View/download PDF
4. A new image of plantain diversity assessed by SSR, AFLP and MSAP markers
- Author
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Noyer, J. L., Causse, S., Tomekpe, K., Bouet, A., and Baurens, F. C.
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- 2005
- Full Text
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5. Evidence of a somatic embryogenesis process for plant regeneration in garlic (Allium sativum L.)
- Author
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Fereol, L., Chovelon, V., Causse, S., Michaux-Ferriere, N., and Kahane, R.
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- 2002
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6. Gene expression is a circular system: S03.2-2
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Choder, M., Haimovich, G., Medina, D., Millán-Zambrano, G., Bregman, A., Halel-Sharvit, L., Eldad, N., Causse, S., Barkai, O., Darzacq, X., Chávez, S., and Pérez-Ortín, J. E.
- Published
- 2012
7. Amylose cutanée dyschromique : une cause d’hyperpigmentation précoce
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Marniquet, M., primary, Aubert, H., additional, Barbarot, S., additional, Agard, C., additional, Causse, S., additional, and Cassagnau, E., additional
- Published
- 2019
- Full Text
- View/download PDF
8. Hsp110 Sustains Myd88-Dependent Nfkb Signaling in Activated B Cell Diffuse Large B Cell Lymphoma
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Boudesco , C., Causse , S., Hamman , A., Verhoeyen , E., Martin , L., Jardin , F., Fest , T., Wolz , O., Weber , A., Garrido , C., Jego , G., Université de Bourgogne (UB), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupe d'étude des proliférations lymphoïdes (GPL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Tübingen, Université de Bourgogne ( UB ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre International de Recherche en Infectiologie ( CIRI ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and université de Bourgogne, LNC
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[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,[ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology - Abstract
IF 7.702; International audience
- Published
- 2017
9. Synergies and divergence between LCA human toxicity assessment and Risk Assessment approaches
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Cornelus, M., Rosenbaum, R.K., Causse, S., Grammont, Vincent, Troise, Adrien, Garcia, J., Osset, P., Civs, Gestionnaire, EVEA MONTPELLIER FRA, Partenaires IRSTEA, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut National de l'Environnement Industriel et des Risques (INERIS), and SCORE LCA VILLEURBANNE FRA
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[SDV.TOX] Life Sciences [q-bio]/Toxicology ,[SDE]Environmental Sciences ,[SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health - Abstract
1. Introduction Beyond the assessment of toxic effects and risks within the framework of European regulations, such as REACh and CLP, other assessment methods for sanitary risks exist but differ from one country to another. Methodologies are different but always based on the founding principles of dose-response relationships and exposure scenarios describing the source-to-target vector. The complementarity of Life Cycle Assessment (LCA) and Chemical Risk Assessment (RA) may yield a more accurate and exhaustive approach to assess human toxicity. 2. Materials and methods 2.1. Panorama of methods assessing human toxicity Various approaches to assess human toxicity risks exist and allow to supply toxicity data. The classifications, such as those established by the European Union, allow to identify hazards of substances. Risk and hazard based approaches typically apply (reasonable) worst-case assumptions for modelling and data selection. In contrast, LCA toxicity assessment methods apply the concept of best-estimates. Another important difference is that RA is site-specific whereas LCA is site-generic. A number of relevant methods for human toxicity assessment within the LCA and RA frameworks have been analysed in order to allow for a mapping of the methods. The results and the divergences identified between the methods are presented in a condensed way. 2.2. Complementarities The methods have been analysed according to many criteria. This talk will underline the similarities and differences as well as the advantages and the associated drawbacks linked to each method. To support this analysis, a comparison based on a case study applying both LCA and RA methods was performed for the human toxicity assessment of a paraben-free cosmetic formula. A detergent was also analysed with different methods. Throughout the study, independent scientific experts have been associated to assure a peer-review of this study. 3. Results and discussion Propositions for the correct interpretation of results as well as their limitations and research needs were identified. Methodological issues will be discussed. Moreover, guidelines and recommendations for human toxicity assessment will be proposed, detailing which method serves which purpose, where they overlap and where they complement one another. This study invites experts to work together to find solutions to the current issues in human toxicity assessment.
- Published
- 2016
10. HSP110 promotes colorectal cancer growth through STAT3 activation
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Berthenet, K, primary, Bokhari, A'dem, additional, Lagrange, A, additional, Marcion, G, additional, Boudesco, C, additional, Causse, S, additional, De Thonel, A, additional, Svrcek, M, additional, Goloudina, A R, additional, Dumont, S, additional, Hammann, A, additional, Biard, D S, additional, Demidov, O N, additional, Seigneuric, R, additional, Duval, A, additional, Collura, A, additional, Jego, G, additional, and Garrido, C, additional
- Published
- 2016
- Full Text
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11. Hépatite induite par l’infliximab lors du traitement d’une maladie de Crohn vulvaire
- Author
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Caussé, S., Bouquin, R., Wylomanski, S., Flamant, M., Joubert, M., Dréno, B., and Quéreux, G.
- Published
- 2013
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- View/download PDF
12. Observance des biothérapies chez les patients atteints de psoriasis
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Vildy, S., primary, Anthoine, E., additional, Causse, S., additional, Aubert, H., additional, Bernier, C., additional, Maillard, H., additional, Body, S., additional, Poiraud, C., additional, Stalder, J.-F., additional, and Barbarot, S., additional
- Published
- 2015
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13. Molecular diversity of Rice grassy stunt virus in Vietnam
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Ta, H. A., Nguyen, D. P., Causse, S., Nguyen, T. D., Ngo, V. V., and Hébrard, Eugénie
- Abstract
Rice grassy stunt virus (RGSV, Tenuivirus) recently emerged on rice in Vietnam, causing high yield losses during 2006-2009. The genetic diversity of RGSV is poorly documented. In this study, the two genes encoded by each ambisense segment RNA3 and RNA5 of RGSV isolates from six provinces of South Vietnam were sequenced. P3 and Pc3 (RNA3) have unknown function, P5 (RNA5) encodes the putative silencing suppressor, and Pc5 (RNA5) encodes the nucleocapsid protein (N). The sequences of 17 Vietnamese isolates were compared with reference isolates from North and South Philippines. The average nucleotide diversity among the isolates was low. We confirmed a higher variability of RNA3 than RNA5 and Pc3 than P3. No relationships between the genetic diversity and the geographic distribution of RGSV isolates could be ascertained, likely because of the long-distance migration of the insect vector. This data will contribute to a better understanding on the RGSV epidemiology in South Vietnam, a prerequisite for further management of the disease and rice breeding for resistance.
- Published
- 2013
14. Développement et optimisation des méthodes de bioindication pour les plans d'eau - Indices ichtyofaune lacustre
- Author
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Causse, S., Gevrey, Muriel, Argillier, Christine, Hydrobiologie (UR HYAX), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), National hors Recherche (partenariat avec la sphère publique (sans AO)), irstea, and Onema
- Subjects
[SDE]Environmental Sciences ,ALPES - Abstract
L’application d’un protocole standard d’échantillonnage de l’ichtyofaune en plans d’eau a permis la constitution de bases de données nationales et européennes homogènes. Ces bases de données ont été utilisées pour sélectionner des métriques à même de rendre compte d’une altération de la qualité des milieux. Le travail de sélection de métriques a été conduit en parallèle sur les lacs naturels situés hors du secteur alpin, les lacs naturel des alpes et les retenues françaises. La méthode choisie est dite « site spécifique » et les conditions de référence ont été approchées par modélisation. Un indice constitué de 3 métriques (2 métriques d’abondance et une métrique de composition) a été proposé pour rendre compte de l’eutrophisation des plans d’eau hors secteur alpin. Deux métriques rentrent dans la composition de l’indice ichtyofaune permettant d’évaluer l’état des plans d’eau des Alpes. Pour les retenues, le travail de sélection des métriques n’est pas achevé. Les limites de ces méthodes qui n’ont pas fait l’objet d’une intercalibration, sont présentées.
- Published
- 2012
15. Development and optimisation of bioindicators for lakes - Fish lake indices
- Author
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Causse, S., Gevrey, Muriel, Argillier, Christine, Hydrobiologie (UR HYAX), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), National hors Recherche (partenariat avec la sphère publique (sans AO)), irstea, and Onema
- Subjects
[SDE]Environmental Sciences ,ALPES - Abstract
L’application d’un protocole standard d’échantillonnage de l’ichtyofaune en plans d’eau a permis la constitution de bases de données nationales et européennes homogènes. Ces bases de données ont été utilisées pour sélectionner des métriques à même de rendre compte d’une altération de la qualité des milieux. Le travail de sélection de métriques a été conduit en parallèle sur les lacs naturels situés hors du secteur alpin, les lacs naturel des alpes et les retenues françaises. La méthode choisie est dite « site spécifique » et les conditions de référence ont été approchées par modélisation. Un indice constitué de 3 métriques (2 métriques d’abondance et une métrique de composition) a été proposé pour rendre compte de l’eutrophisation des plans d’eau hors secteur alpin. Deux métriques rentrent dans la composition de l’indice ichtyofaune permettant d’évaluer l’état des plans d’eau des Alpes. Pour les retenues, le travail de sélection des métriques n’est pas achevé. Les limites de ces méthodes qui n’ont pas fait l’objet d’une intercalibration, sont présentées.
- Published
- 2012
16. Syndrome pied-main-bouche et orchite à Coxsackie virus A6
- Author
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Munch, M.C.M., primary, Aubert, H., additional, Bernier, C., additional, Causse, S., additional, and Stalder, J.-F., additional
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- 2014
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17. La petite protéine de choc thermique αB-crystallin a un rôle clé dans la fibrogenèse pulmonaire par son action sur la SMAD4
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Bellaye, P.-S., primary, Wettstein, G., additional, Burgy, O., additional, Besnard, V., additional, Joannes, A., additional, Colas, J., additional, Causse, S., additional, Marchal-Somme, J., additional, Crestani, B., additional, Garrido, C., additional, Camus, P., additional, and Bonniaud, P., additional
- Published
- 2014
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18. Implication de la plèvre et des cellules mésothéliales lors de la fibrose pulmonaire induite par la bléomycine administrée par voie générale
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Burgy, O., primary, Bellaye, P.-S., additional, Wettstein, G., additional, Colas, J., additional, Causse, S., additional, Garrido, C., additional, Camus, P., additional, and Bonniaud, P., additional
- Published
- 2014
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19. Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells
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Derangère, V, primary, Chevriaux, A, additional, Courtaut, F, additional, Bruchard, M, additional, Berger, H, additional, Chalmin, F, additional, Causse, S Z, additional, Limagne, E, additional, Végran, F, additional, Ladoire, S, additional, Simon, B, additional, Boireau, W, additional, Hichami, A, additional, Apetoh, L, additional, Mignot, G, additional, Ghiringhelli, F, additional, and Rébé, C, additional
- Published
- 2014
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20. La protoporphyrie érythropoïétique : enquête nationale et influence de l’exposition solaire
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Causse, S., primary, Dutartre, H., additional, Deybach, J.-C., additional, Nguyen, J.-M., additional, Raffray, E., additional, Pithon, M., additional, Stalder, J.-F., additional, and Barbarot, S., additional
- Published
- 2013
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21. Une acrocyanose unilatérale sévère révélant une pathomimie
- Author
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Durant, C., primary, Graveleau, J., additional, Causse, S., additional, Barrier, J., additional, and Connault, J., additional
- Published
- 2013
- Full Text
- View/download PDF
22. Réponse spectaculaire d’une maladie de Crohn vulvaire à l’infliximab
- Author
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Quereux, G., primary, Bouquin, R., additional, Causse, S., additional, Peuvrel, L., additional, Brocard, A., additional, Wylomanski, S., additional, and Dréno, B., additional
- Published
- 2011
- Full Text
- View/download PDF
23. Un hémangiome infantile résistant au propranolol
- Author
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Causse, S., primary, Aubert, H., additional, Stadler, J.-F., additional, and Barbarot, S., additional
- Published
- 2011
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- View/download PDF
24. EMBRYOGENIC CELL SUSPENSION CULTURES OF GARLIC (ALLIUM SATIVUM L.) AS METHOD FOR MASS PROPAGATION AND POTENTIAL MATERIAL FOR GENETIC IMPROVEMENT
- Author
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Fereol, L., primary, Chovelon, V., additional, Causse, S., additional, Kalumvueziko, M.L., additional, and Kahane, R., additional
- Published
- 2005
- Full Text
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25. Population genetics of Glossina palpalis palpalis from central African sleeping sickness foci
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Solano Philippe, Causse Sandrine, De Meeûs Thierry, Ravel Sophie, Simo Gustave, Melachio Trésor, Lutumba Pascal, Asonganyi Tazoacha, and Njiokou Flobert
- Subjects
Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Glossina palpalis palpalis (Diptera: Glossinidae) is widespread in west Africa, and is the main vector of sleeping sickness in Cameroon as well as in the Bas Congo Province of the Democratic Republic of Congo. However, little is known on the structure of its populations. We investigated G. p. palpalis population genetic structure in five sleeping sickness foci (four in Cameroon, one in Democratic Republic of Congo) using eight microsatellite DNA markers. Results A strong isolation by distance explains most of the population structure observed in our sampling sites of Cameroon and DRC. The populations here are composed of panmictic subpopulations occupying fairly wide zones with a very strong isolation by distance. Effective population sizes are probably between 20 and 300 individuals and if we assume densities between 120 and 2000 individuals per km2, dispersal distance between reproducing adults and their parents extends between 60 and 300 meters. Conclusions This first investigation of population genetic structure of G. p. palpalis in Central Africa has evidenced random mating subpopulations over fairly large areas and is thus at variance with that found in West African populations of G. p. palpalis. This study brings new information on the isolation by distance at a macrogeographic scale which in turn brings useful information on how to organise regional tsetse control. Future investigations should be directed at temporal sampling to have more accurate measures of demographic parameters in order to help vector control decision.
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- 2011
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26. Genome-wide association studies reveal novel loci controlling tuber flesh color and oxidative browning in Dioscorea alata.
- Author
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Dossa K, Morel A, Houngbo ME, Mota AZ, Malédon E, Irep JL, Diman JL, Mournet P, Causse S, Van KN, Cornet D, and Chair H
- Subjects
- Color, Polymorphism, Single Nucleotide, Dioscorea genetics, Dioscorea chemistry, Dioscorea metabolism, Dioscorea growth & development, Genome-Wide Association Study, Plant Tubers metabolism, Plant Tubers chemistry, Plant Tubers genetics, Plant Tubers growth & development, Genotype, Quantitative Trait Loci, Phenotype, Pigmentation genetics
- Abstract
Background: Consumers' preferences for food crops are guided by quality attributes. This study aimed at deciphering the genetic basis of quality traits, especially tuber flesh color (FC) and oxidative browning (OB) in Dioscorea alata, based on the genome-wide association studies (GWAS) approach. The D. alata panel was planted at two locations in Guadeloupe. At harvest, the FC was scored visually as white, cream, or purple on longitudinally sliced mature tubers. The OB was scored visually as the presence or absence of browning after 15 min of exposure of the sliced samples to ambient air., Results: Phenotypic characterization for FC and OB of a diverse panel of D. alata genotypes highlighted significant variation within the panel and across two locations. The genotypes within the panel displayed a weak structure and could be classified into three subpopulations. GWAS identified 14 and 4 significant associations for tuber FC and OB, respectively, with phenotypic variance, explained values ranging from 7.18% to 18.04%. Allele segregation analysis at the significantly associated loci highlighted the favorable alleles for the desired traits, i.e., white FC and no OB. A total of 24 putative candidate genes were identified around the significant signals. A comparative analysis with previously reported quantitative trait loci indicated that numerous genomic regions control these traits in D. alata., Conclusion: Our study provides important insights into the genetic control of tuber FC and OB in D. alata. The major and stable loci can be further utilized to improve selection in breeding programs for developing new cultivars with enhanced tuber quality. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)
- Published
- 2024
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27. cIAP1/TRAF2 interplay promotes tumor growth through the activation of STAT3.
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Dumétier B, Zadoroznyj A, Berthelet J, Causse S, Allègre J, Bourgeois P, Cattin F, Racoeur C, Paul C, Garrido C, and Dubrez L
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- Humans, Animals, Mice, TNF Receptor-Associated Factor 2 genetics, TNF Receptor-Associated Factor 2 metabolism, Mice, Nude, Fibroblasts metabolism, Inhibitor of Apoptosis Proteins metabolism, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, NF-kappa B metabolism, Neoplasms
- Abstract
Cellular inhibitor of apoptosis-1 (cIAP1) is a signaling regulator with oncogenic properties. It is involved in the regulation of signaling pathways controlling inflammation, cell survival, proliferation, differentiation and motility. It is recruited into membrane-receptor-associated signaling complexes thanks to the molecular adaptor TRAF2. However, the cIAP1/TRAF2 complex exists, independently of receptor engagement, in several subcellular compartments. The present work strengthens the importance of TRAF2 in the oncogenic properties of cIAP1. cIAPs-deficient mouse embryonic fibroblasts (MEFs) were transformed using the HRas-V12 oncogene. Re-expression of cIAP1 enhanced tumor growth in a nude mice xenograft model, and promoted lung tumor nodes formation. Deletion or mutation of the TRAF2-binding site completely abolished the oncogenic properties of cIAP1. Further, cIAP1 mediated the clustering of TRAF2, which was sufficient to stimulate tumor growth. Our TRAF2 interactome analysis showed that cIAP1 was critical for TRAF2 to bind to its protein partners. Thus, cIAP1 and TRAF2 would be two essential subunits of a signaling complex promoting a pro-tumoral signal. cIAP1/TRAF2 promoted the activation of the canonical NF-κB and ERK1/2 signaling pathways. NF-κB-dependent production of IL-6 triggered the activation of the JAK/STAT3 axis in an autocrine manner. Inhibition or downregulation of STAT3 specifically compromised the growth of cIAP1-restored MEFs but not that of MEFs expressing a cIAP1-mutant and treating mice with the STAT3 inhibitor niclosamide completely abrogated cIAP1/TRAF2-mediated tumor growth. Altogether, we demonstrate that cIAP1/TRAF2 binding is essential to promote tumor growth via the activation of the JAK/STAT3 signaling pathway., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2023
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28. Heat shock proteins and exosomes in cancer theranostics.
- Author
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Regimbeau M, Abrey J, Vautrot V, Causse S, Gobbo J, and Garrido C
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- Humans, Heat-Shock Proteins metabolism, Precision Medicine, Molecular Chaperones metabolism, Biomarkers metabolism, Exosomes metabolism, Neoplasms diagnosis, Neoplasms therapy, Neoplasms etiology
- Abstract
Heat shock proteins (HSPs) are a superfamily of molecular chaperones that were discovered through their ability to be induced by different stresses including heat shock. Other than their function as chaperones in proteins homeostasis, HSPs have been shown to inhibit different forms of cell death and to participate in cell proliferation and differentiation processes. Because cancer cells have to rewire their metabolism, they require a high amount of these stress-inducible chaperones for their survival. Therefore, HSPs are unusually abundant in cancer cells where they have oncogene-like functions. In cancer, HSPs have been involved in the regulation of apoptosis, immune responses, angiogenesis, metastasis and treatment resistance. Recently, HSPs have been shown to be secreted through exosomes by cancer cells. These tumor-derived exosomes can be used as circulating markers: HSP-exosomes have been reported as biomarkers of cancer dissemination, response to therapy and/or patient outcome. A new range of functions, mostly in modulation of anticancer immune responses, have been described for these extracellular HSPs. In this review, we will describe those recently reported functions of HSP-exosomes that makes them both targets for anticancer therapeutics and biomarkers for the monitoring of the disease. We will also discuss their emerging interest in cancer vaccines., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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29. Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors.
- Author
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Kieu TL, Pierre L, Derangère V, Perrey S, Truntzer C, Jalil A, Causse S, Groetz E, Dumont A, Guyard L, Arnould L, de Barros JP, Apetoh L, Rébé C, Limagne E, Jourdan T, Demizieux L, Masson D, Thomas C, Ghiringhelli F, and Rialland M
- Subjects
- Animals, Cell Line, Tumor, Down-Regulation genetics, Epithelial-Mesenchymal Transition, Female, Humans, Lipids, Mice, Neoplasm Metastasis, Receptors, Transforming Growth Factor beta metabolism, Transforming Growth Factor beta metabolism, Breast Neoplasms pathology, Fatty Acid Elongases metabolism, Lung Neoplasms genetics, Lung Neoplasms metabolism
- Abstract
Metastatic breast cancer cannot be cured, and alteration of fatty acid metabolism contributes to tumor progression and metastasis. Here, we were interested in the elongation of very long-chain fatty acids protein 5 (Elovl5) in breast cancer. We observed that breast cancer tumors had a lower expression of Elovl5 than normal breast tissues. Furthermore, low expression of Elovl5 is associated with a worse prognosis in ER
+ breast cancer patients. In accordance with this finding, decrease of Elovl5 expression was more pronounced in ER+ breast tumors from patients with metastases in lymph nodes. Although downregulation of Elovl5 expression limited breast cancer cell proliferation and cancer progression, suppression of Elovl5 promoted EMT, cell invasion and lung metastases in murine breast cancer models. The loss of Elovl5 expression induced upregulation of TGF-β receptors mediated by a lipid-droplet accumulation-dependent Smad2 acetylation. As expected, inhibition of TGF-β receptors restored proliferation and dampened invasion in low Elovl5 expressing cancer cells. Interestingly, the abolition of lipid-droplet formation by inhibition of diacylglycerol acyltransferase activity reversed induction of TGF-β receptors, cell invasion, and lung metastasis triggered by Elovl5 knockdown. Altogether, we showed that Elovl5 is involved in metastasis through lipid droplets-regulated TGF-β receptor expression and is a predictive biomarker of metastatic ER+ breast cancer., (© 2022. The Author(s).)- Published
- 2022
- Full Text
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30. Endoplasmic Reticulum Chaperones in Viral Infection: Therapeutic Perspectives.
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Kohli E, Causse S, Baverel V, Dubrez L, Borges-Bonan N, Demidov O, and Garrido C
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- Calnexin metabolism, Endoplasmic Reticulum metabolism, Humans, Molecular Chaperones metabolism, Endoplasmic Reticulum Chaperone BiP, Virus Diseases
- Abstract
Viruses are intracellular parasites that subvert the functions of their host cells to accomplish their infection cycle. The endoplasmic reticulum (ER)-residing chaperone proteins are central for the achievement of different steps of the viral cycle, from entry and replication to assembly and exit. The most abundant ER chaperones are GRP78 (78-kDa glucose-regulated protein), GRP94 (94-kDa glucose-regulated protein), the carbohydrate or lectin-like chaperones calnexin (CNX) and calreticulin (CRT), the protein disulfide isomerases (PDIs), and the DNAJ chaperones. This review will focus on the pleiotropic roles of ER chaperones during viral infection. We will cover their essential role in the folding and quality control of viral proteins, notably viral glycoproteins which play a major role in host cell infection. We will also describe how viruses co-opt ER chaperones at various steps of their infectious cycle but also in order to evade immune responses and avoid apoptosis. Finally, we will discuss the different molecules targeting these chaperones and the perspectives in the development of broad-spectrum antiviral drugs.
- Published
- 2021
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31. Tumor-Derived Exosomes: Hidden Players in PD-1/PD-L1 Resistance.
- Author
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Vautrot V, Bentayeb H, Causse S, Garrido C, and Gobbo J
- Abstract
Recently, immunotherapy has garnered increasing importance in cancer therapy, leading to substantial improvements in patient care and survival. By blocking the immune checkpoints-protein regulators of the immune system-immunotherapy prevents immune tolerance toward tumors and reactivates the immune system, prompting it to fight cancer cell growth and diffusion. A widespread strategy for this is the blockade of the interaction between PD-L1 and PD-1. However, while patients generally respond well to immunotherapy, a certain proportion of patients present tumors that resist these treatments. This portion can be very high in some cancers and hinders cancer curability. For this reason, current efforts are focusing on combining PD-1/PD-L1 immunotherapy with the targeting of other immune checkpoints to counter resistance and achieve better results. Exosomes, small vesicles secreted by almost any cell, including tumor cells, have proven to be key actors in this resistance. The exosomes released by tumor cells spread the immune-suppressive properties of the tumor throughout the tumor microenvironment and participate in establishing metastatic niches. In this review, we will describe immune checkpoints and immune modulators whose presence in tumor-derived exosomes (TEXs) has been established. We will focus on the most promising proteins under scrutiny for use in combination with PD-1 blockade therapy in a clinical setting, such as PD-L1, CTLA-4, TIM-3, CD73/39, LAG-3, and TIGIT. We will explore the immunosuppressive impact of these exosomal proteins on a variety of immune cells. Finally, we will discuss how they can change the game in immunotherapy and guide therapeutic decisions, as well as the current limits of this approach. Depending on the viewpoint, these exosomal proteins may either provide key missing information on tumor growth and resistance mechanisms or they may be the next big challenge to overcome in improving cancer treatment.
- Published
- 2021
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32. Genome-wide genotyping elucidates the geographical diversification and dispersal of the polyploid and clonally propagated yam (Dioscorea alata).
- Author
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Sharif BM, Burgarella C, Cormier F, Mournet P, Causse S, Van KN, Kaoh J, Rajaonah MT, Lakshan SR, Waki J, Bhattacharjee R, Badara G, Pachakkil B, Arnau G, and Chaïr H
- Subjects
- Biological Evolution, Genotype, Humans, Microsatellite Repeats, Polyploidy, Dioscorea genetics
- Abstract
Background and Aims: Inferring the diffusion history of many human-dispersed species is still not straightforward due to unresolved past human migrations. The centre of diversification and routes of migration of the autopolyploid and clonally propagated greater yam, Dioscorea alata, one of the oldest edible tubers, remain unclear. Here, we address yam demographic and dispersal history using a worldwide sample., Methods: We characterized genome-wide patterns of genetic variation using genotyping by sequencing 643 greater yam accessions spanning four continents. First, we disentangled the polyploid and clonal components of yam diversity using allele frequency distribution and identity by descent approaches. We then addressed yam geographical origin and diffusion history with a model-based coalescent inferential approach., Key Results: Diploid genotypes were more frequent than triploids and tetraploids worldwide. Genetic diversity was generally low and clonality appeared to be a main factor of diversification. The most likely evolutionary scenario supported an early divergence of mainland Southeast Asian and Pacific gene pools with continuous migration between them. The genetic make-up of triploids and tetraploids suggests that they have originated from these two regions before westward yam migration. The Indian Peninsula gene pool gave origin to the African gene pool, which was later introduced to the Caribbean region., Conclusions: Our results are congruent with the hypothesis of independent domestication origins of the two main Asian and Pacific gene pools. The low genetic diversity and high clonality observed suggest a strong domestication bottleneck followed by thousands of years of widespread vegetative propagation and polyploidization. Both processes reduced the extent of diversity available for breeding, and this is likely to threaten future adaptation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Annals of Botany Company.)
- Published
- 2020
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33. Fonio millet genome unlocks African orphan crop diversity for agriculture in a changing climate.
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Abrouk M, Ahmed HI, Cubry P, Šimoníková D, Cauet S, Pailles Y, Bettgenhaeuser J, Gapa L, Scarcelli N, Couderc M, Zekraoui L, Kathiresan N, Čížková J, Hřibová E, Doležel J, Arribat S, Bergès H, Wieringa JJ, Gueye M, Kane NA, Leclerc C, Causse S, Vancoppenolle S, Billot C, Wicker T, Vigouroux Y, Barnaud A, and Krattinger SG
- Subjects
- Africa, Agriculture methods, Climate Change, Digitaria classification, Domestication, Edible Grain classification, Evolution, Molecular, Genetic Variation, Genome, Plant, Molecular Sequence Annotation, Selection, Genetic, Species Specificity, Digitaria genetics, Edible Grain genetics
- Abstract
Sustainable food production in the context of climate change necessitates diversification of agriculture and a more efficient utilization of plant genetic resources. Fonio millet (Digitaria exilis) is an orphan African cereal crop with a great potential for dryland agriculture. Here, we establish high-quality genomic resources to facilitate fonio improvement through molecular breeding. These include a chromosome-scale reference assembly and deep re-sequencing of 183 cultivated and wild Digitaria accessions, enabling insights into genetic diversity, population structure, and domestication. Fonio diversity is shaped by climatic, geographic, and ethnolinguistic factors. Two genes associated with seed size and shattering showed signatures of selection. Most known domestication genes from other cereal models however have not experienced strong selection in fonio, providing direct targets to rapidly improve this crop for agriculture in hot and dry environments.
- Published
- 2020
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34. XPO1 regulates erythroid differentiation and is a new target for the treatment of β-thalassemia.
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Guillem F, Dussiot M, Colin E, Suriyun T, Arlet JB, Goudin N, Marcion G, Seigneuric R, Causse S, Gonin P, Gastou M, Deloger M, Rossignol J, Lamarque M, Choucair ZB, Gautier EF, Ducamp S, Vandekerckhove J, Moura IC, Maciel TT, Garrido C, An X, Mayeux P, Mohandas N, Courtois G, and Hermine O
- Subjects
- Cell Differentiation, Erythroblasts, Erythropoiesis, Humans, Exportin 1 Protein, Karyopherins genetics, Receptors, Cytoplasmic and Nuclear genetics, beta-Thalassemia drug therapy, beta-Thalassemia genetics
- Abstract
β-thalassemia major (β-TM) is an inherited hemoglobinopathy caused by a quantitative defect in the synthesis of β-globin chains of hemoglobin, leading to the accumulation of free a-globin chains that aggregate and cause ineffective erythropoiesis. We have previously demonstrated that terminal erythroid maturation requires a transient activation of caspase-3 and that the chaperone Heat Shock Protein 70 (HSP70) accumulates in the nucleus to protect GATA-1 transcription factor from caspase-3 cleavage. This nuclear accumulation of HSP70 is inhibited in human β-TM erythroblasts due to HSP70 sequestration in the cytoplasm by free a-globin chains, resulting in maturation arrest and apoptosis. Likewise, terminal maturation can be restored by transduction of a nuclear-targeted HSP70 mutant. Here we demonstrate that in normal erythroid progenitors, HSP70 localization is regulated by the exportin-1 (XPO1), and that treatment of β-thalassemic erythroblasts with an XPO1 inhibitor increased the amount of nuclear HSP70, rescued GATA-1 expression and improved terminal differentiation, thus representing a new therapeutic option to ameliorate ineffective erythropoiesis of β-TM.
- Published
- 2020
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35. Heat-shock proteins: chaperoning DNA repair.
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Dubrez L, Causse S, Borges Bonan N, Dumétier B, and Garrido C
- Subjects
- Animals, Apoptosis genetics, Cell Survival, Congenital Abnormalities pathology, DNA Damage, Genomic Instability, Humans, Neoplasms pathology, Neurodegenerative Diseases pathology, Protein Folding, Signal Transduction genetics, Congenital Abnormalities genetics, DNA Repair, Heat-Shock Proteins metabolism, Neoplasms genetics, Neurodegenerative Diseases genetics
- Abstract
Cells are repeatedly exposed to environmental or endogenous stresses that can alter normal cell behavior and increase cell vulnerability. In order to ensure tissue integrity and function, cells cope with cellular injuries by adapting their metabolism, protecting essential intracellular constituents, inhibiting cell death signaling pathways and activating those devoted to damage repair. The molecular chaperones of the heat-shock protein (HSP) family are critical effectors of this adaptive response. They protect intracellular proteins from misfolding or aggregation, inhibit cell death signaling cascades and preserve the intracellular signaling pathways that are essential for cell survival. Most HSPs are rapidly overexpressed in response to cellular injuries including genotoxic stress. DNA damage can dramatically alter cell behavior and contribute to a number of diseases including developmental defects, neurodegenerative disorders, and cancer. Thus, the ability of cells to repair DNA damage is essential for preserving cell integrity. DNA damage activates a coordinated response that includes detecting DNA lesions before their transmission to daughter cells, blocking cell cycle progression and DNA replication and repairing the damage. Although the role of HSPs in proteins homeostasis and cell death, especially apoptosis has been widely reported, much less is known about their function in DNA repair. This review aims to present the role of HSPs in DNA repair signaling pathways.
- Published
- 2020
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36. Yam genomics supports West Africa as a major cradle of crop domestication.
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Scarcelli N, Cubry P, Akakpo R, Thuillet AC, Obidiegwu J, Baco MN, Otoo E, Sonké B, Dansi A, Djedatin G, Mariac C, Couderc M, Causse S, Alix K, Chaïr H, François O, and Vigouroux Y
- Subjects
- Africa, Western, Agriculture, Base Sequence, Evolution, Molecular, Forests, Genome, Plant, Models, Statistical, Oryza genetics, Pennisetum genetics, Plant Leaves genetics, Polymorphism, Single Nucleotide genetics, Rivers, Whole Genome Sequencing, Crops, Agricultural genetics, Dioscorea genetics, Domestication, Genomics methods
- Abstract
While there has been progress in our understanding of the origin and history of agriculture in sub-Saharan Africa, a unified perspective is still lacking on where and how major crops were domesticated in the region. Here, we investigated the domestication of African yam ( Dioscorea rotundata ), a key crop in early African agriculture. Using whole-genome resequencing and statistical models, we show that cultivated yam was domesticated from a forest species. We infer that the expansion of African yam agriculture started in the Niger River basin. This result, alongside with the origins of African rice and pearl millet, supports the hypothesis that the vicinity of the Niger River was a major cradle of African agriculture.
- Published
- 2019
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37. Development of a cost-effective single nucleotide polymorphism genotyping array for management of greater yam germplasm collections.
- Author
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Cormier F, Mournet P, Causse S, Arnau G, Maledon E, Gomez RM, Pavis C, and Chair H
- Abstract
Using genome-wide single nucleotide polymorphism (SNP) discovery in greater yam ( Discorea alata L.), 4,593 good quality SNPs were identified in 40 accessions. One hundred ninety six of these SNPs were selected to represent the overall dataset and used to design a competitive allele specific PCR array (KASPar). This array was validated on 141 accessions from the Tropical Plants Biological Resources Centre (CRB-PT) and CIRAD collections that encompass worldwide D. alata diversity. Overall, 129 SNPs were successfully converted as cost-effective genotyping tools. The results showed that the ploidy levels of accessions could be accurately estimated using this array. The rate of redundant accessions within the collections was high in agreement with the low genetic diversity of D. alata and its diversification by somatic clone selection. The overall diversity resulting from these 129 polymorphic SNPs was consistent with the findings of previously published studies. This KASPar array will be useful in collection management, ploidy level inference, while complementing accurate agro-morphological descriptions., Competing Interests: The authors declare that they have no conflict of interest.
- Published
- 2019
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38. HSP27 is a partner of JAK2-STAT5 and a potential therapeutic target in myelofibrosis.
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Sevin M, Kubovcakova L, Pernet N, Causse S, Vitte F, Villeval JL, Lacout C, Cordonnier M, Rodrigues-Lima F, Chanteloup G, Mosca M, Chrétien ML, Bastie JN, Audia S, Sagot P, Ramla S, Martin L, Gleave M, Mezger V, Skoda R, Plo I, Garrido C, Girodon F, and de Thonel A
- Subjects
- Animals, Bone Marrow Cells immunology, Bone Marrow Cells pathology, Bone Marrow Transplantation, Cell Line, Tumor, Disease Models, Animal, Female, HEK293 Cells, HSP27 Heat-Shock Proteins immunology, Humans, Janus Kinase 2 immunology, K562 Cells, Leukocytes drug effects, Leukocytes immunology, Leukocytes pathology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Molecular Targeted Therapy, Mutation, Primary Myelofibrosis immunology, Primary Myelofibrosis pathology, STAT5 Transcription Factor immunology, Thrombopoietin genetics, Thrombopoietin immunology, Transduction, Genetic, Whole-Body Irradiation, HSP27 Heat-Shock Proteins genetics, Janus Kinase 2 genetics, Oligonucleotides pharmacology, Primary Myelofibrosis drug therapy, Primary Myelofibrosis genetics, STAT5 Transcription Factor genetics
- Abstract
Heat shock protein 27 (HSP27/HSPB1) is a stress-inducible chaperone that facilitates cancer development by its proliferative and anti-apoptotic functions. The OGX-427 antisense oligonucleotide against HSP27 has been reported to be beneficial against idiopathic pulmonary fibrosis. Here we show that OGX-427 is effective in two murine models of thrombopoietin- and JAKV617F-induced myelofibrosis. OGX-427 limits disease progression and is associated with a reduction in spleen weight, in megakaryocyte expansion and, for the JAKV617F model, in fibrosis. HSP27 regulates the proliferation of JAK2V617F-positive cells and interacts directly with JAK2/STAT5. We also show that its expression is increased in both CD34
+ circulating progenitors and in the serum of patients with JAK2-dependent myeloproliferative neoplasms with fibrosis. Our data suggest that HSP27 plays a key role in the pathophysiology of myelofibrosis and represents a new potential therapeutic target for patients with myeloproliferative neoplasms.- Published
- 2018
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39. N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.
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Dufour F, Rattier T, Shirley S, Picarda G, Constantinescu AA, Morlé A, Zakaria AB, Marcion G, Causse S, Szegezdi E, Zajonc DM, Seigneuric R, Guichard G, Gharbi T, Picaud F, Herlem G, Garrido C, Schneider P, Benedict CA, and Micheau O
- Subjects
- Amino Acid Sequence, Animals, Cell Line, Cytomegalovirus metabolism, Glycosylation, HCT116 Cells, Humans, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Mice, Mutagenesis, Site-Directed, Nanoparticles chemistry, Receptors, TNF-Related Apoptosis-Inducing Ligand deficiency, Receptors, TNF-Related Apoptosis-Inducing Ligand genetics, Sequence Alignment, Tunicamycin toxicity, Viral Proteins genetics, Viral Proteins metabolism, Apoptosis drug effects, Receptors, TNF-Related Apoptosis-Inducing Ligand metabolism, TNF-Related Apoptosis-Inducing Ligand toxicity
- Abstract
APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2. We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans. Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts. Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity. Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies. The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141. Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition.
- Published
- 2017
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40. Pleural inhibition of the caspase-1/IL-1β pathway diminishes profibrotic lung toxicity of bleomycin.
- Author
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Burgy O, Bellaye PS, Causse S, Beltramo G, Wettstein G, Boutanquoi PM, Goirand F, Garrido C, and Bonniaud P
- Subjects
- Animals, Cell Line, Cytoprotection, Disease Models, Animal, Humans, Idiopathic Pulmonary Fibrosis chemically induced, Idiopathic Pulmonary Fibrosis enzymology, Idiopathic Pulmonary Fibrosis pathology, Interleukin-1beta metabolism, Lung enzymology, Lung pathology, Mice, Inbred C57BL, Nigericin pharmacology, Pleura enzymology, Pleura pathology, Time Factors, Transforming Growth Factor beta1 metabolism, Anti-Inflammatory Agents pharmacology, Bleomycin, Caspase 1 metabolism, Caspase Inhibitors pharmacology, Idiopathic Pulmonary Fibrosis prevention & control, Interleukin 1 Receptor Antagonist Protein pharmacology, Interleukin-1beta antagonists & inhibitors, Lung drug effects, Pleura drug effects, Signal Transduction drug effects
- Abstract
Background: Idiopathic and toxic pulmonary fibrosis are severe diseases starting classically in the subpleural area of the lung. It has recently been suggested that pleural mesothelial cells acquire a myofibroblast phenotype under fibrotic conditions induced by TGF-β1 or bleomycin. The importance and role of inflammation in fibrogenesis are still controversial. In this work, we explored the role of IL-1β/caspase-1 signaling in bleomycin lung toxicity and in pleural mesothelial cell transformation., Methods: C57BL/6 mice were intravenously injected with either bleomycin or nigericin or NaCl as control. In vitro, the Met5A cell line was used as a model of human pleural mesothelial cells., Results: Intravenous injections of bleomycin induced lung fibrosis with histologically-proven peripheral distribution, collagen accumulation in the pleural and subpleural area, and overexpression of markers of myofibroblast transformation of pleural cells which migrated into the lung. These events were associated with an inflammatory process with an increase in neutrophil recruitment in pleural lavage fluid and increased caspase-1 activity. TGF-β1 was also overexpressed in pleural lavage fluid and was produced by pleural cells following intravenous bleomycin. In this model, local pleural inhibition of IL-1β with the IL-1β inhibitor anakinra diminished TGF-β1 and collagen accumulation. In vitro, caspase-1 inhibition interfered with Met5A cell transformation into the myofibroblast-like phenotype induced by bleomycin or TGF-β1. Moreover, nigericin, a caspase-1 activator, triggered transformation of Met5A cells and its intra-pleural delivery induced fibrogenesis in mice., Conclusions: We demonstrated, after intravenous bleomycin injection in mice, the role of the pleura and highlighted the key role of IL-1β/caspase-1 axis in this fibrogenesis process.
- Published
- 2016
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41. Extracellular HSP110 skews macrophage polarization in colorectal cancer.
- Author
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Berthenet K, Boudesco C, Collura A, Svrcek M, Richaud S, Hammann A, Causse S, Yousfi N, Wanherdrick K, Duplomb L, Duval A, Garrido C, and Jego G
- Abstract
HSP110 is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps the cells to survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently showed that colorectal cancer (CRC) patients with microsatellite instability (MSI) had an improved response to chemotherapy because they harbor an HSP110 inactivating mutation (HSP110DE9). In this work, we have used patients' biopsies and human CRC cells grown in vitro and in vivo (xenografts) to demonstrate that (1) HSP110 is secreted by CRC cells and that the amount of this extracellular HSP110 is strongly decreased by the expression of the mutant HSP110DE9, (2) Supernatants from CRC cells overexpressing HSP110 or purified recombinant human HSP110 (LPS-free) affect macrophage differentiation/polarization by favoring a pro-tumor, anti-inflammatory profile, (3) Conversely, inhibition of HSP110 (expression of siRNA, HSP110DE9 or immunodepletion) induced the formation of macrophages with a cytotoxic, pro-inflammatory profile. (4) Finally, this effect of extracellular HSP110 on macrophages seems to implicate TLR4. These results together with the fact that colorectal tumor biopsies with HSP110 high were infiltrated with macrophages with a pro-tumoral profile while those with HSP110 low were infiltrated with macrophages with a cytotoxic profile, suggest that the effect of extracellular HSP110 function on macrophages may also contribute to the poor outcomes associated with HSP110 expression.
- Published
- 2016
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42. Heat shock proteins in fibrosis and wound healing: good or evil?
- Author
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Bellaye PS, Burgy O, Causse S, Garrido C, and Bonniaud P
- Subjects
- Apoptosis drug effects, Apoptosis physiology, Cell Physiological Phenomena drug effects, Collagen metabolism, Endomyocardial Fibrosis physiopathology, HSP110 Heat-Shock Proteins metabolism, HSP47 Heat-Shock Proteins antagonists & inhibitors, HSP70 Heat-Shock Proteins metabolism, HSP90 Heat-Shock Proteins antagonists & inhibitors, Heat-Shock Proteins, Small metabolism, Humans, Pulmonary Fibrosis physiopathology, Transforming Growth Factor beta1 metabolism, Cell Physiological Phenomena physiology, Fibrosis physiopathology, Heat-Shock Proteins metabolism, Neoplasms physiopathology, Wound Healing physiology
- Abstract
Heat shock proteins (HSPs) are key regulators of cell homeostasis, and their cytoprotective role has been largely investigated in the last few decades. However, an increasing amount of evidence highlights their deleterious effects on several human pathologies, including cancer, in which they promote tumor cell survival, proliferation and drug resistance. Therefore, HSPs have recently been suggested as therapeutic targets for improving human disease outcomes. Fibrotic diseases and cancer share several properties; both pathologies are characterized by genetic alterations, uncontrolled cell proliferation, altered cell interactions and communication and tissue invasion. The discovery of new HSP inhibitors that have been shown to be efficacious against certain types of cancers has given rise to a new field of research that investigates the activity of these compounds in other incurable human diseases such as fibrotic disorders. The aim of this review is to discuss new findings regarding the involvement of HSPs in the pathogenesis of organ fibrosis and to note recent discoveries that indicate that HSPs could be important therapeutic targets to improve the current dismal outcome of fibrotic diseases., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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43. The small heat-shock protein αB-crystallin is essential for the nuclear localization of Smad4: impact on pulmonary fibrosis.
- Author
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Bellaye PS, Wettstein G, Burgy O, Besnard V, Joannes A, Colas J, Causse S, Marchal-Somme J, Fabre A, Crestani B, Kolb M, Gauldie J, Camus P, Garrido C, and Bonniaud P
- Subjects
- Active Transport, Cell Nucleus, Animals, Bleomycin, Cell Nucleus pathology, Cells, Cultured, Collagen metabolism, Disease Models, Animal, Epithelial Cells metabolism, Female, Fibroblasts metabolism, Humans, Idiopathic Pulmonary Fibrosis chemically induced, Idiopathic Pulmonary Fibrosis genetics, Idiopathic Pulmonary Fibrosis pathology, Idiopathic Pulmonary Fibrosis prevention & control, Interleukin-1beta genetics, Interleukin-1beta metabolism, Lung pathology, Mice, Mice, 129 Strain, Mice, Knockout, RNA Interference, Rats, Sprague-Dawley, Transcription Factors metabolism, Transfection, Transforming Growth Factor beta1 genetics, Transforming Growth Factor beta1 metabolism, Ubiquitin-Protein Ligases metabolism, Ubiquitination, alpha-Crystallin B Chain genetics, Cell Nucleus metabolism, Idiopathic Pulmonary Fibrosis metabolism, Lung metabolism, Smad4 Protein metabolism, alpha-Crystallin B Chain metabolism
- Abstract
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by the proliferation of myofibroblasts and the accumulation of extracellular matrix (ECM) in the lungs. TGF-β1 is the major profibrotic cytokine involved in IPF and is responsible for myofibroblast proliferation and differentiation and ECM synthesis. αB-crystallin is constitutively expressed in the lungs and is inducible by stress, acts as a chaperone and is known to play a role in cell cytoskeleton architecture homeostasis. The role of αB-crystallin in fibrogenesis remains unknown. The principal signalling pathway involved in this process is the Smad-dependent pathway. We demonstrate here that αB-crystallin is strongly expressed in fibrotic lung tissue from IPF patients and in vivo rodent models of pulmonary fibrosis. We also show that αB-crystallin-deficient mice are protected from bleomycin-induced fibrosis. Similar protection from fibrosis was observed in αB-crystallin KO mice after transient adenoviral-mediated over-expression of IL-1β or TGF-β1. We show in vitro in primary epithelial cells and fibroblasts that αB-crystallin increases the nuclear localization of Smad4, thereby enhancing the TGF-β1-Smad pathway and the consequent activation of TGF-β1 downstream genes. αB-crystallin over-expression disrupts Smad4 mono-ubiquitination by interacting with its E3-ubiquitin ligase, TIF1γ, thus limiting its nuclear export. Conversely, in the absence of αB-crystallin, TIF1γ can freely interact with Smad4. Consequently, Smad4 mono-ubiquitination and nuclear export are favoured and thus TGF-β1-Smad4 pro-fibrotic activity is inhibited. This study demonstrates that αB-crystallin may be a key target for the development of specific drugs in the treatment of IPF or other fibrotic diseases., (Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
- Published
- 2014
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44. Ustekinumab therapy for severe interstitial granulomatous dermatitis with arthritis.
- Author
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Leloup P, Aubert H, Causse S, Le Goff B, and Barbarot S
- Subjects
- Dermatitis complications, Dermatitis drug therapy, Dermatitis pathology, Granuloma complications, Granuloma pathology, Humans, Male, Middle Aged, Skin Diseases complications, Skin Diseases pathology, Ustekinumab, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Arthritis, Rheumatoid complications, Granuloma drug therapy, Skin Diseases drug therapy
- Published
- 2013
- Full Text
- View/download PDF
45. Molecular diversity of Rice grassy stunt virus in Vietnam.
- Author
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Ta HA, Nguyen DP, Causse S, Nguyen TD, Ngo VV, and Hébrard E
- Subjects
- Molecular Sequence Data, Nucleocapsid Proteins genetics, Phylogeny, Tenuivirus classification, Vietnam, Genetic Variation, Oryza virology, Plant Diseases virology, Tenuivirus genetics, Tenuivirus isolation & purification
- Abstract
Rice grassy stunt virus (RGSV, Tenuivirus) recently emerged on rice in Vietnam, causing high yield losses during 2006-2009. The genetic diversity of RGSV is poorly documented. In this study, the two genes encoded by each ambisense segment RNA3 and RNA5 of RGSV isolates from six provinces of South Vietnam were sequenced. P3 and Pc3 (RNA3) have unknown function, P5 (RNA5) encodes the putative silencing suppressor, and Pc5 (RNA5) encodes the nucleocapsid protein (N). The sequences of 17 Vietnamese isolates were compared with reference isolates from North and South Philippines. The average nucleotide diversity among the isolates was low. We confirmed a higher variability of RNA3 than RNA5 and Pc3 than P3. No relationships between the genetic diversity and the geographic distribution of RGSV isolates could be ascertained, likely because of the long-distance migration of the insect vector. This data will contribute to a better understanding on the RGSV epidemiology in South Vietnam, a prerequisite for further management of the disease and rice breeding for resistance.
- Published
- 2013
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46. Cryptic diversity within the major trypanosomiasis vector Glossina fuscipes revealed by molecular markers.
- Author
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Dyer NA, Ravel S, Choi KS, Darby AC, Causse S, Kapitano B, Hall MJ, Steen K, Lutumba P, Madinga J, Torr SJ, Okedi LM, Lehane MJ, and Donnelly MJ
- Subjects
- Animals, Cluster Analysis, DNA, Mitochondrial chemistry, DNA, Mitochondrial genetics, DNA, Ribosomal Spacer chemistry, DNA, Ribosomal Spacer genetics, Ethiopia, Humans, Microsatellite Repeats, Molecular Sequence Data, Phylogeography, Sequence Analysis, DNA, Tanzania, Insect Vectors, Tsetse Flies classification, Tsetse Flies genetics
- Abstract
Background: The tsetse fly Glossina fuscipes s.l. is responsible for the transmission of approximately 90% of cases of human African trypanosomiasis (HAT) or sleeping sickness. Three G. fuscipes subspecies have been described, primarily based upon subtle differences in the morphology of their genitalia. Here we describe a study conducted across the range of this important vector to determine whether molecular evidence generated from nuclear DNA (microsatellites and gene sequence information), mitochondrial DNA and symbiont DNA support the existence of these taxa as discrete taxonomic units., Principal Findings: The nuclear ribosomal Internal transcribed spacer 1 (ITS1) provided support for the three subspecies. However nuclear and mitochondrial sequence data did not support the monophyly of the morphological subspecies G. f. fuscipes or G. f. quanzensis. Instead, the most strongly supported monophyletic group was comprised of flies sampled from Ethiopia. Maternally inherited loci (mtDNA and symbiont) also suggested monophyly of a group from Lake Victoria basin and Tanzania, but this group was not supported by nuclear loci, suggesting different histories of these markers. Microsatellite data confirmed strong structuring across the range of G. fuscipes s.l., and was useful for deriving the interrelationship of closely related populations., Conclusion/significance: We propose that the morphological classification alone is not used to classify populations of G. fuscipes for control purposes. The Ethiopian population, which is scheduled to be the target of a sterile insect release (SIT) programme, was notably discrete. From a programmatic perspective this may be both positive, given that it may reflect limited migration into the area or negative if the high levels of differentiation are also reflected in reproductive isolation between this population and the flies to be used in the release programme.
- Published
- 2011
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47. Population genetics of Glossina palpalis palpalis from central African sleeping sickness foci.
- Author
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Melachio TT, Simo G, Ravel S, De Meeûs T, Causse S, Solano P, Lutumba P, Asonganyi T, and Njiokou F
- Subjects
- Animals, Cameroon, Cluster Analysis, Democratic Republic of the Congo, Female, Male, Microsatellite Repeats, Trypanosomiasis, African transmission, Disease Vectors, Genetic Variation, Phylogeography, Tsetse Flies classification, Tsetse Flies genetics
- Abstract
Background: Glossina palpalis palpalis (Diptera: Glossinidae) is widespread in west Africa, and is the main vector of sleeping sickness in Cameroon as well as in the Bas Congo Province of the Democratic Republic of Congo. However, little is known on the structure of its populations. We investigated G. p. palpalis population genetic structure in five sleeping sickness foci (four in Cameroon, one in Democratic Republic of Congo) using eight microsatellite DNA markers., Results: A strong isolation by distance explains most of the population structure observed in our sampling sites of Cameroon and DRC. The populations here are composed of panmictic subpopulations occupying fairly wide zones with a very strong isolation by distance. Effective population sizes are probably between 20 and 300 individuals and if we assume densities between 120 and 2000 individuals per km2, dispersal distance between reproducing adults and their parents extends between 60 and 300 meters., Conclusions: This first investigation of population genetic structure of G. p. palpalis in Central Africa has evidenced random mating subpopulations over fairly large areas and is thus at variance with that found in West African populations of G. p. palpalis. This study brings new information on the isolation by distance at a macrogeographic scale which in turn brings useful information on how to organise regional tsetse control. Future investigations should be directed at temporal sampling to have more accurate measures of demographic parameters in order to help vector control decision.
- Published
- 2011
- Full Text
- View/download PDF
48. Contrasting population structures of two vectors of African trypanosomoses in Burkina Faso: consequences for control.
- Author
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Koné N, Bouyer J, Ravel S, Vreysen MJ, Domagni KT, Causse S, Solano P, and de Meeûs T
- Subjects
- Animals, Burkina Faso epidemiology, Female, Insect Control methods, Male, Microsatellite Repeats, Trypanosomiasis, African prevention & control, Trypanosomiasis, African transmission, Tsetse Flies genetics, Disease Vectors, Trypanosomiasis, African veterinary, Tsetse Flies classification, Tsetse Flies growth & development
- Abstract
Background: African animal trypanosomosis is a major obstacle to the development of more efficient and sustainable livestock production systems in West Africa. Riverine tsetse species such as Glossina palpalis gambiensis Vanderplank and Glossina tachinoides Westwood are the major vectors. A wide variety of control tactics is available to manage these vectors, but their removal will in most cases only be sustainable if the control effort is targeting an entire tsetse population within a circumscribed area., Methodology/principal Findings: In the present study, genetic variation at microsatellite DNA loci was used to examine the population structure of G. p. gambiensis and G. tachinoides inhabiting four adjacent river basins in Burkina Faso, i.e. the Mouhoun, the Comoé, the Niger and the Sissili River Basins. Isolation by distance was significant for both species across river basins, and dispersal of G. tachinoides was ∼3 times higher than that of G. p. gambiensis. Thus, the data presented indicate that no strong barriers to gene flow exists between riverine tsetse populations in adjacent river basins, especially so for G. tachinoides., Conclusions/significance: Therefore, potential re-invasion of flies from adjacent river basins will have to be prevented by establishing buffer zones between the Mouhoun and the other river basin(s), in the framework of the PATTEC (Pan African Tsetse and Trypanosomosis Eradication Campaign) eradication project that is presently targeting the northern part of the Mouhoun River Basin. We argue that these genetic analyses should always be part of the baseline data collection before any tsetse control project is initiated.
- Published
- 2011
- Full Text
- View/download PDF
49. Short exposure to the DNA intercalator DRAQ5 dislocates the transcription machinery and induces cell death.
- Author
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Richard E, Causse S, Spriet C, Fourré N, Trinel D, Darzacq X, Vandenbunder B, and Heliot L
- Subjects
- Base Sequence, Cell Line, Tumor, DNA Primers, Humans, Polymerase Chain Reaction, RNA Polymerase II metabolism, Anthraquinones pharmacology, Cell Death drug effects, DNA drug effects, Intercalating Agents pharmacology, Transcription, Genetic drug effects
- Abstract
The fluorescent probe DRAQ5 which rapidly permeates cells and binds to DNA is potentially useful for functional studies of molecular dynamics and interactions in living nuclei. Within minutes after the incubation of human osteosarcoma U2OS cells with 5μm DRAQ5, the distributions of RNA polymerase II and some of its associated regulatory proteins HEXIM and cyclin T1 in the nucleus are severely impaired, and transcription is inhibited. Furthermore, 30min exposure to DRAQ5 induces death of U2OS cells 24h later. Incubation with Hoechst 33342 under similar conditions does not induce these effects. These results emphasize the importance of carefully examining the functional consequences of labeling DNA with intercalating fluorescent dyes before use., (© 2010 The Authors. Photochemistry and Photobiology © 2010 The American Society of Photobiology.)
- Published
- 2011
- Full Text
- View/download PDF
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