Papers by Sabrina Vergnaud
<p>1B: Crystal structure of human muscle aldolase complexed with fructose 1,6-bisphosphate ... more <p>1B: Crystal structure of human muscle aldolase complexed with fructose 1,6-bisphosphate (isoenzyme A, PDB code 4ALD) superimposed with the tetrameric crystal structure of human brain aldolase (isoenzyme C, PDB code 1XFB), which is similar to the muscle isoenzyme. Chains A, B, C and D of isoenzyme C are shown in orange, light blue, light green and pink, respectively. Monomeric isoenzyme A is shown in grey and is superimposed on chain D of the tetrameric isoenzyme C. Fructose 1,6-bisphosphate co-crystallized with isoenzyme A is shown in yellow. The mutated residue described in this report (red arrow) and the mutated amino acids previously described are highlighted in the magnified structure. The structural and functional consequences of the mutations are described in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004711#pgen-1004711-t001" target="_blank">Table 1</a>. 1C: aldolase A, glucose-6-phosphate dehydrogenase (G6PD) and hexokinase activities in the erythrocytes of the parents, the healthy sibling and the 3 affected patients (*: patients 2, 3, 4). 1D: in vitro muscle study of anaerobic glycogenolysis and glycolysis (only patient 3); results of lactate production (µmol/g muscle in 30 minutes) after incubation with various substrates.</p
Http Www Theses Fr, 1999
La nadph oxydase est un complexe enzymatique multiproteique dont l'activite resulte de l'... more La nadph oxydase est un complexe enzymatique multiproteique dont l'activite resulte de l'assemblage au niveau d'un composant membranaire redox, le cytochrome b 5 5 8, et de facteurs proteiques solubles, p67phox, p47phox, p40phox et rac1/2. Elle catalyse le transfert d'electrons depuis le substrat nadph jusqu'a l'oxygene, conduisant a la production d'ions superoxyde o 2. Les mecanismes de l'assemblage du complexe oxydase et les modalites du transport d'electrons qui en resultent ne sont pas encore totalement elucides. Notre travail a consiste a etudier un modele de granulomatose septique caracterisee par l'absence du facteur cytosolique p67phox. Nous nous sommes attaches (1) a restaurer une activite oxydase dans les cellules modele utilisees (les lymphocytes b-ebv) par complementation avec la proteine manquante in vitro puis ex vivo et (2) a analyser les modalites de l'interaction des facteurs cytosoliques p67phox et p40phox. Les resultats montrent que dans les mecanismes d'assemblage des constituants de l'oxydase, le facteur cytosolique p67phox est limitant : dans la granulomatose septique cgdp67() le turnover de l'oxydase est de l'ordre de 10 a 20 s 1, apres complementation in vitro par le facteur p67phox recombinant il atteint une valeur (155 a 179 s 1) proche de celle des temoins (sujets sains). Mais l'activite oxydase restauree est complete seulement si les constituants de l'oxydase, incubes dans un milieu de reconstitution (systeme acellulaire heterologue), sont isoles de leur environnement tissulaire (membrane et cytosol) ce qui suggere la presence d'un facteur intervenant dans une regulation negative des mecanismes d'assemblage. Enfin le transfert des facteurs cytosoliques a la membrane implique la dissociation du complexe p67phox/p40phox dans le maintien de l'etat latent du complexe. La transfection ex vivo des lb-ebv mutants, a l'aide du vecteur pcep4, ne restaure pas d'activite oxydase alors que celle-ci est surexprimee dans les lb-ebv sains. Au contraire par transfection vectorialisee de exos-p67phox nous avons ete capables de complementer l'activite nadph oxydase de lb-ebv de cgdp67() d'environ 40% par rapport a l'activite temoin. Ces resultats demontrent que les mecanismes d'assemblage du complexe oxydase different in vivo de ce que l'on peut observer apres reconstitution in vitro.
Neuromuscular Diseases, 2015
Immuno-analyse & Biologie Spécialisée, 2008
Monsieur O. est suivi pour une « cytolyse hépatique chronique », découverte en 1996 au cours d'un... more Monsieur O. est suivi pour une « cytolyse hépatique chronique », découverte en 1996 au cours d'un bilan, montrant une forte augmentation des ASAT (n × 20), le reste du bilan est normal, les anticorps antinucléaires et la sérologie des hépatites B et C sont négatifs, enfin l'échographie et la biopsie hépatique montrent un aspect normal du parenchyme hépatique ! Entre 1996 et 2006, plusieurs bilans sont réalisés confirmant tous la forte augmentation des ASAT, les autres éléments du bilan restant normaux (l'ARN du VHC, les sérologies VIH et syphilis et le bilan d'auto-immunité complet sont tous négatifs). En novembre 2006, au centre hospitalier de Pau, le Dr Bonnefoy note la présence d'un examen clinique normal et le bilan confirme l'augmentation des ASAT à 580 UI/l avec des ALAT normales à 35 UI/l. Cette dissociation ASAT/ALAT fait évoquer l'hypothèse de la présence d'une macro-ASAT. Le prélèvement est adressé au CHU de Grenoble où le Dr Vergnaud met en évidence la macro-ASAT et identifie le complexe constitué d'une IgA liée à une ASAT de nature cytosolique. Conclusion : ce cas permet de rappeler l'existence rare de macro-ASAT, dont la mise en évidence peut éviter un certain nombre d'examens aussi inutiles que coûteux !
Pour evaluer les retentissements genetiques de l'association fotemustine (Muphoran) - dacarba... more Pour evaluer les retentissements genetiques de l'association fotemustine (Muphoran) - dacarbazine (Deticene) utilisee en clinique, la recidive ganglionnaire, d'un melanome achromique a ete transplantee, par voie sous cutanee, sur des souris athymiques âgees de six semaines. Le premier objectif de cette etude a ete la recherche de doses uniques ou fractionnees tolerees par l'animal par voie intra-peritoneale. Dans un second temps, la chimiosensibilite de l'association (fotemustine 20 mg/kg x 2; 6 et 10 jours apres la greffe - dacarbazine 20 mg/kg x 4; 14, 15, 16 et 17 jours apres la greffe) a ete etudiee, Au sacrifice des animaux (25 jours apres la greffe) une inhibition tumorale significative (temoins poids moyen tumoral : 13,07 ± 1 g - association 8 ± 1 g – 0,001<P<0,01) voisine de celle obtenue avec la fotemustine seule (8,41 ± 1 g – 0,001<P<0,01). Ce modele experimental semble donc peu repondre a la dacarbazine. L'analyse cytogenetique du melanome ...
P40phox associates with the neutrophil Triton X-100-insoluble cytoskeletal fraction and PMA-activ... more P40phox associates with the neutrophil Triton X-100-insoluble cytoskeletal fraction and PMA-activated membrane skeleton:
Clinica Chimica Acta, 2021
Background Lysosomal acid lipase deficiency (LALD, OMIM#278000) is a rare lysosomal disorder with... more Background Lysosomal acid lipase deficiency (LALD, OMIM#278000) is a rare lysosomal disorder with an autosomal recessive inheritance. The main clinical manifestations are related to a progressive accumulation of cholesteryl esters, triglycerides or both within the lysosome in different organs such as the liver, spleen, and cardiovascular system. A wide range of clinical severity is associated with LALD including a severe very rare antenatal/neonatal/infantile phenotype named Wolman disease and a late-onset form named cholesteryl ester storage disease (CESD). Methods This study aimed to investigate a cohort of at-risk patients (4174) presenting with clinical or biological signs consistent with LALD using the assessment of LAL activity on dried blood spots. Results LAL activity was lower than 0.05 nmol/punch/L (cut-off: 0.12) in 19 patients including 13 CESD and 6 Wolman. Molecular study has been conducted in 17 patients and succeeded in identifying 34 mutated alleles. Fourteen unique variants have been characterized, 7 of which are novel. Conclusion This study allowed to identify a series of patients and expanded the molecular spectrum knowledge of LALD. Besides, a new screening criteria grid based on the clinical/biological data from our study and the literature has been proposed in order to enhance the diagnosis rate in at risk populations.
Journal of Medical Genetics, 2021
IntroductionThis study aims to define the phenotypic and molecular spectrum of the two clinical f... more IntroductionThis study aims to define the phenotypic and molecular spectrum of the two clinical forms of β-galactosidase (β-GAL) deficiency, GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B, MPSIVB).MethodsClinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed.ResultsThe clinical presentations in patients with GM1-gangliosidosis are consistent with a phenotypic continuum ranging from a severe antenatal form with hydrops fetalis to an adult form with an extrapyramidal syndrome. Molecular studies evidenced 47 variants located throughout the sequence of the GLB1 gene, in all exons except 7, 11 and 12. Eighteen novel variants (15 substitutions and 3 deletions) were identified. Several variants were linked specifically to early-onset GM1-gangliosidosis, late-onset GM1-gangliosidosis or MPSIVB phenotypes. This integrative molecular and clinical stratification suggests a variant-driven patient assignmen...
Transplantation Proceedings, 2019
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Distributed under a Creative Commons Attribution-NonCommercial| 4.0 International License
Journal of Leukocyte Biology, 1999
NADPH oxidase is an O-generating enzyme found in phagocytes such as neutrophils. It is composed o... more NADPH oxidase is an O-generating enzyme found in phagocytes such as neutrophils. It is composed of a membrane-bound cytochrome b, the cytosolic proteins p67phox, p47phox, p40phox, and the G-protein p21rac. The system is dormant in resting cells but acquires catalytic activity on exposure to appropriate stimuli. Cytochrome b, p67phox, p47phox, and rac2 associate with the cytoskeleton and membrane skeleton of activated neutrophils. It is not known whether p40phox associates with the cytoskeleton. The purpose of this study was to analyze the subcellular distribution of p40phox. When resting neutrophils were lysed in Triton X-100 or octyl glucoside buffer and separated into detergent-soluble and detergent-insoluble fractions, p40phox and p67phox were mainly associated with the detergent-insoluble fraction (defined as the cytoskeleton), whereas p47phox was mainly found in the soluble fraction. Neutrophil activation by phorbol myristate acetate (PMA) induced p47phox translocation to the c...
European Journal of Biochemistry, 2000
Chronic granulomatous disease (CGD) is due to a functional defect of the O 2 2 generating NADPH o... more Chronic granulomatous disease (CGD) is due to a functional defect of the O 2 2 generating NADPH oxidase of phagocytes. Epstein±Barr-virus-immortalized B lymphocytes express all the constituents of oxidase with activity 100 times less than that of neutrophils. As in neutrophils, oxidase activity of Epstein±Barr-virus-immortalized B lymphocytes was shown to be defective in the different forms of CGD; these cells were used as a model for the complementation studies of two p67-phox-deficient CGD patients. Reconstitution of oxidase activity was performed in vitro by using a heterologous cell-free assay consisting of membrane-suspended or solubilized and purified cytochrome b 558 that was associated with cytosol or with the isolated cytosolicactivating factors (p67-phox, p47-phox, p40-phox) from healthy or CGD patients. In p67-phox-deficient CGD patients, two cytosolic factors are deficient or missing: p67-phox and p40-phox. Not more than 20% of oxidase activity was recovered by complementing the cytosol of p67-phox-deficient patients with recombinant p67-phox. On the contrary, a complete restoration of oxidase activity was observed when, instead of cytosol, the cytosolic factors were added in the cell-free assay after isolation in combination with cytochrome b 558 purified from neutrophil membrane. Moreover, the simultaneous addition of recombinant p67-phox and recombinant p40-phox reversed the previous complementation in a p40-phox dose-dependent process. These results suggest that in the reconstitution of oxidase activity, p67-phox is the limiting factor; the efficiency of complementation depends on the membrane tissue and the cytosolic environment. In vitro, the transition from the resting to the activated state of oxidase, which results from assembling, requires the dissociation of p40-phox from p67-phox for efficient oxidase activity. In the process, p40-phox could function as a negative regulatory factor and stabilize the resting state.
Arthritis Research & Therapy - ARTHRITIS RES THER, 2003
Heterogeneity and multifactoriality complicate diagnostics and our understanding of pathogenesis ... more Heterogeneity and multifactoriality complicate diagnostics and our understanding of pathogenesis of rheumatoid arthritis (RA). The only accepted serologic parameter (rheumatoid factor [RF]) is not disease specific, nor are any of several novel RA autoantibodies. We aimed at identifying profiles instead of individual autoreactivities allowing for unambiguous prediction of RA. Selected RA autoantigens were tested by ELISA (RF and anti-cyclic citrullinated peptide [anti-CCP]) or Western blot (heavy-chain-binding protein [BiP], heterogeneous ribonucleoprotein particle A2 [RA33/ hnRNP A2], calpastatin and calreticulin). Antibody reactivities were assayed from serum samples of 149 RA patients and 132 patients with other rheumatic diseases and from synovial fluids (SF) (58 RA, 65 non-RA). No single autoreactivity was sufficient for unambiguous prediction of RA. Frequencies of multiparameter profiles consisting of 3, 4, 5 and 6 autoreactivites were determined. Fifteen six-parameter serum profiles were exclusively expressed in RA patients, representing a cumulative sensitivity of 59%. Twelve SF profiles were exclusively expressed in 64% of RA patients. The self-learning classification algorithm CLASSIF1 was capable of accurately predicting RA when these profiles were present. Data profile analysis of RF/CCP/BiP/calpastatin/calreticulin/RA33 provided specific discrimination of 64% of RA. Most importantly, RA specific profiles were observed in 64% of patients with early disease (<12 months). For the first time, the accurate prediction of the class RA has been achieved by the use of multiparametric autoreactivity profiles. Because of early expression in disease, these profiles make it possible to start a disease-modifying therapy long before irreversible bone and joint destruction may develop. Additional RA-specific profiles are required to cover the entire group of RA patients. 2 Investigation of the reactivity patterns of antifilaggrin antibodies in sera and synovial fluids from patients with rheumatoid arthritis using citrullinated synthetic peptides
Prostaglandins & Other Lipid Mediators, 2005
We previously reported an activation of the 5-lipoxygenase pathway in aorta from streptozotocin-i... more We previously reported an activation of the 5-lipoxygenase pathway in aorta from streptozotocin-induced diabetic rats. The aim of this study was to investigate whether this activation was associated with an increased expression of 5-lipoxygenase, an increased cysteinyl leukotriene (CysLT) production in response to arachidonic acid or calcium ionophore A23187 and/or a hypersensitivity of the aorta to CysLTs in streptozotocin-induced diabetic rats. In aorta from diabetic and control rats, reverse transcriptase-PCR and western blot analysis with a specific 5-lipoxygenase antibody provided evidence for the presence of 5-lipoxygenase in aorta. However, the expression of 5-lipoxygenase was not significantly different between diabetic and control rats. Challenge by A23187 (10 microM) and arachidonic acid (10 microM and 0.1 mM) with or without A23187 (10 micromol/l) induced a significant increase of CysLT release (measured by enzyme immunoassay) that was in the same range in aorta from control and diabetic rats. In contrast, aortas from diabetic rats showed a greater sensitivity to LTC4 and LTD4 contractile effects. These data suggested that the activation of the 5-lipoxygenase pathway previously reported in streptozotocin-induced diabetic rats could be explained by an augmented sensitivity to CysLTs of the diabetic aorta.
Journal of Hypertension, 2002
Objectives We have previously reported that 5lipoxygenase-derived products, and particularly the ... more Objectives We have previously reported that 5lipoxygenase-derived products, and particularly the cysteinyl leukotrienes (CysLTs), were involved in angiotensin II (Ang II)-induced contractions in isolated aortas from spontaneously hypertensive rats. Design The aim of this study was to assess the role of CysLTs in the vascular response to Ang II in an Ang IIdependent model of hypertension, the (mRen-2)27 transgenic rats (TGs). Methods Intact aortic rings from TG and normotensive Sprague±Dawley rats (SDs) were suspended in organ chambers for isometric tension development in response to Ang II. In addition, the release of CysLTs in response to Ang II (0.3 ìmol/l) was measured by enzyme immunoassay. Results In isolated aortas from TG rats, pretreatment with the 5-lipoxygenase inhibitor (AA861, 10 ìmol/l) or the CysLT 1 receptor antagonist (MK571, 1 ìmol/l) signi®cantly (P < 0.05) reduced Ang II-induced contractions by 52 and 42%, respectively. In addition, Ang II induced a 2.6-fold increase in CysLT release (pg/mg dry weight tissue: 58.3 6 17.9 (Ang II, n 7) versus 22.5 6 5.9 (basal, n 7) P < 0.05), which was inhibited by the AT 1 receptor antagonist losartan (1 ìmol/l). In contrast, in aortas from SD rats, pretreatment with AA861 or MK571 did not alter Ang II-induced contraction and CysLT production remained unchanged after exposure to Ang II. Conclusion These data suggest that CysLTs are involved in the contractile responses to Ang II in isolated aortas from TG but not from SD rats.
Journal of Biological Chemistry, 2003
Phagocyte NADPH oxidase generates O 2. for defense mechanisms and cellular signaling. Myeloid-rel... more Phagocyte NADPH oxidase generates O 2. for defense mechanisms and cellular signaling. Myeloid-related proteins MRP8 and MRP14 of the S100 family are EF-hand calcium-binding proteins. MRP8 and MRP14 were coisolated from neutrophils on an anti-p47 phox matrix with oxidase cytosolic factors and identified by mass spectrometry. MRP8 and MRP14 are absent from Epstein-Barr virus-immortalized B lymphocytes, and, coincidentally, these cells display weak oxidase activity compared with neutrophils. MRP8/MRP14 that was purified from neutrophils enhanced oxidase turnover of B cells in vitro, suggesting that MRP8/MRP14 is involved in the activation process. This was confirmed ex vivo by cotransfection of Epstein-Barr virus-transformed B lymphocytes with genes encoding MRP8 and MRP14. In a semi-recombinant cell-free assay, recombinant MRP8/ MRP14 increased the affinity of p67 phox for cytochrome b 558 synergistically with p47 phox. Moreover, MRP8/ MRP14 initiated oxidase activation on its own, through a calcium-dependent specific interaction with cytochrome b 558 as shown by atomic force microscopy and a structure-function relationship investigation. The data suggest that the change of conformation in cytochrome b 558 , which initiates the electron transfer, can be mediated by effectors other than oxidase cytosolic factors p67 phox and p47 phox. Moreover, MRP8/MRP14 dimer behaves as a positive mediator of phagocyte NADPH oxidase regulation.
Biochemistry, 2000
NADPH oxidase activity depends on the assembly of the cytosolic activating factors, p67phox, p47-... more NADPH oxidase activity depends on the assembly of the cytosolic activating factors, p67phox, p47-phox, p40-phox, and Rac with cytochrome b 558. The transition from an inactive to an active oxidase complex induces the transfer of electrons from NADPH to oxygen through cytochrome b 558. The assembly of oxidase complex was studied in vitro after reconstitution in a heterologous cell-free assay by using true noncontact mode atomic force microscopy. Cytochrome b 558 was purified from neutrophils and Epstein-Barr virus-immortalized B lymphocytes and incorporated into liposomes. The effect of protein glycosylation on liposome size and oxidase activity was investigated. The liposomes containing the native hemoprotein purified from neutrophils had a diameter of 146 nm, whereas after deglycosylation, the diameter was reduced to 68 nm, although oxidase activity was similar in both cases. Native cytochrome b 558 was used after purification in reconstitution experiments to investigate the topography of NADPH oxidase once it was assembled. For the first time, atomic force microscopy illustrated conformational changes of cytochrome b 558 during the transition from the inactive to the active state of oxidase; height measurements allow the determination of a size of 4 nm for the assembled complex. In the processes that were studied, p67-phox displayed a critical function; it was shown to be involved in both assembly and activation of oxidase complex while p47-phox proceeded as a positive effector and increased the affinity of p67-phox with cytochrome b 558 , and p40-phox stabilizes the resting state. The results suggest that although an oligomeric structure of oxidase machinery has not been demonstrated, allosteric regulation mechanisms may be proposed.
Biochemical and Biophysical Research Communications, 2000
Pederson et al. Intracellular localization modulates targeting of ExoS, a type III cytotoxin, to ... more Pederson et al. Intracellular localization modulates targeting of ExoS, a type III cytotoxin, to eukaryotic signalling proteins, Molecu lar Microbiology (2002) 46 (5), 1381-1390.* Polack et al., "Protein Delivery by Pseudomonas Type III Secretion System: Ex Vivo Complementation of p67*-Deficient Chronic Granulomatous Disease." Biochemical and Biophysical Research Communications 275, pp. 854-858 (2000). Pederson et al., "Intracellular localization and processing of Pseudomonas aeruginos ExoS in eukaryotic cells." Molecular Microbiology 37(2), pp. 287-299 (2000). Pederson et al., "Intracellular localization modulates targeting of ExoS, a type III cytotoxin, to eukaryotic signaling proteins. Molecu lar Microbiology 46(5), pp. 1381-1390 (2002). Krall et al., "Intracellular targeting of two type III secreted cytokines." Abstracts of the General Meeting of the American Soci ety for Microbiology, 103, pp. 42-43 (2003). Cornelis et al., "The Yersinia Yop virulon: A bacterial system for subverting eukaryotic cells." Molecular Microbiology 23(5), pp. 861-867 (1997). Sory et al., "Identification of the YopE and YopH domains required for secretion and internalization into the cytosol of macrophages, using the cyaA gene fusion approach."
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1998
Ž. Like neutrophils, Epstein-Barr virus EBV-immortalized B lymphocytes express all constituents o... more Ž. Like neutrophils, Epstein-Barr virus EBV-immortalized B lymphocytes express all constituents of the NADPH oxidase complex necessary to generate superoxide anion O y. The NADPH oxidase activity in EBV-B lymphocytes is only 5% of 2 that measured in neutrophils upon PMA stimulation. Cytochrome b is the sole redox membrane component of NADPH 558 oxidase; it is the protein core around which cytosolic factors assemble in order to mediate oxidase activity. In the present study, we have compared the structural and functional properties of cytochrome b from EBV-B lymphocytes and 558 neutrophils. Cytochrome b from EBV-B lymphocyte plasma membrane, like that from neutrophils, is characterized by a 558 heterodimeric structure with a highly glycosylated b subunit, known as gp91-phox. While the amount of cytochrome b 558 Ž 10. recovered after purification from EBV-B lymphocytes ; 0.24 nmol from 10 cells was low compared to that recovered Ž. from neutrophils ; 10 nmol , the biochemical properties of purified cytochrome b from both EBV-B lymphocytes and 558 neutrophils were quite similar with respect to their differential spectra, redox potential, and FAD binding site. Once cytochrome b was extracted from the EBV-B lymphocyte membrane, it was able to mediate, in a reconstituted system of 558 O y production the same oxidase turnover as that found for cytochrome b extracted from neutrophils. A comparison 2 558 between membrane bound and soluble cytochrome b suggested that the weak oxidase activity measured in intact EBV-B 558 cells might be the result not only of the small amount of expressed cytochrome b , but also of a defect of the activation 558 process in lymphocyte membrane. q 1998 Elsevier Science B.V.
Toxicology in Vitro, 2013
Chalcones are naturally occurring compounds with diverse pharmacological activities. Chalcones de... more Chalcones are naturally occurring compounds with diverse pharmacological activities. Chalcones derive from the common structure: 1,3-diphenylpropenone. The present study aims to better understand the mechanistic pathways triggering chalcones anticancer effects and providing evidences that minor structural difference could lead to important difference in mechanistic effect. We selected two recently investigated chalcones (A and B) and investigated them on glioblastoma cell lines. It was found that chalcone A induced an apoptotic process (type I PCD), via the activation of caspase-3, -8 and -9. Chalcone A also increased CDK1/cyclin B ratios and decreased the mitochondrial transmembrane potential (ΔΨm). Chalcone B induced an autophagic cell death process (type II PCD), ROS-related but independent of both caspases and protein synthesis. Both chalcones increased Bax/Bcl2 ratios and decreased Ki67 and CD71 antigen expressions. The present investigation reveals that despite the close structure of chalcones A and B, significant differences in mechanism of effect were found.
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Papers by Sabrina Vergnaud