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Elifsu Sabuncu

Journal articles

Sabuncu Elifsu, David Julie, Bernède-Bauduin Christian, Pépin Sophie, Leroy Michel, Boëlle Pierre-Yves, Watier Laurence, Guillemot Didier (2009)  Significant Reduction of Antibiotic Use in the Community after a Nationwide Campaign in France, 2002–2007   PLoS Med 6: 6. e1000084 June  
Abstract: Background Overuse of antibiotics is the main force driving the emergence and dissemination of bacterial resistance in the community. France consumes more antibiotics and has the highest rate of beta-lactam resistance in Streptococcus pneumoniae than any other European country. In 2001, the government initiated âKeep Antibiotics Workingâ; the program's main component was a campaign entitled âLes antibiotiques c'est pas automatiqueâ (âAntibiotics are not automaticâ) launched in 2002. We report the evaluation of this campaign by analyzing the evolution of outpatient antibiotic use in France 2000â2007, according to therapeutic class and geographic and age-group patterns. Methods and Findings This evaluation is based on 2000â2007 data, including 453,407,458 individual reimbursement data records and incidence of flu-like syndromes (FLSs). Data were obtained from the computerized French National Health Insurance database and provided by the French Sentinel Network. As compared to the preintervention period (2000â2002), the total number of antibiotic prescriptions per 100 inhabitants, adjusted for FLS frequency during the winter season, changed by â26.5% (95% confidence interval [CI] â33.5% to â19.6%) over 5 years. The decline occurred in all 22 regions of France and affected all antibiotic therapeutic classes except quinolones. The greatest decrease, â35.8% (95% CI â48.3% to â23.2%), was observed among young children aged 6â15 years. A significant change of â45% in the relationship between the incidence of flu-like syndromes and antibiotic prescriptions was observed. Conclusions The French national campaign was associated with a marked reduction of unnecessary antibiotic prescriptions, particularly in children. This study provides a useful method for assessing public-health strategies designed to reduce antibiotic use.
Notes: Related paper : Comment
Livio Riboli-Sasco, Elifsu Sabuncu (2008)  Initier aux approches interdisciplinaires dès le master : l’exemple du master 2 "Approches Interdisciplinaires du Vivant"   Natures Sciences Sociétés 16: Supp. 24-30 Sep  
Notes: Compte-rendu des Journées de lâAssociation Natures Sciences Sociétés Dialogues, Ãcole normale supérieure, Paris, 7 et 8 février 2007
Mohammed Moudjou, Julie Bernard, Elifsu Sabuncu, Christelle Langevin, Hubert Laude (2007)  Glycan chains modulate prion protein binding to immobilized metal ions.   Neurochem Int 50: 5. 689-695 Apr  
Abstract: PrP(c) is the normal isoform of the prion protein which can be converted into PrP(Sc), the pathology-associated conformer in prion diseases. It contains two N-linked glycan chains attached to the C-proximal globular domain. While the biological functions of PrP(c) are still unknown, its ability to bind Cu(2+) is well documented. The main Cu(2+)-binding sites are located in the N-proximal, unstructured region of the molecule. Here we report that PrP(c) glycans influence the capacity of PrP(c) from sheep brain or cultured Rov cells to bind IMAC columns loaded with Cu(2+) or Co(2+). Using different anti-PrP antibodies and PrP(c) glycosylation mutants, we show that the full length non-glycosylated form of PrP(c) has a higher binding efficiency for column-bound Cu(2+) and Co(2+) than the corresponding glycosylated form. Our findings raise the possibility that the accessibility of the PrP(c) metal ion-binding sites might be controlled by the glycan chains.
Elifsu Sabuncu, Sophie Paquet, Jérome Chapuis, Mohammed Moudjou, Thanh Lan Lai, Jacques Grassi, Udo Baron, Hubert Laude, Didier Vilette (2005)  Prion proteins from susceptible and resistant sheep exhibit some distinct cell biological features.   Biochem Biophys Res Commun 337: 3. 791-798 Nov  
Abstract: It is well established that natural polymorphisms in the coding sequence of the PrP protein can control the expression of prion disease. Studies with a cell model of sheep prion infection have shown that ovine PrP allele associated with resistance to sheep scrapie may confer resistance by impairing the multiplication of the infectious agent. To further explore the biochemical and cellular mechanisms underlying the genetic control of scrapie susceptibility, we established permissive cells expressing two different PrP variants. In this study, we show that PrP variants with opposite effects on prion multiplication exhibit distinct cell biological features. These findings indicate that cell biological properties of ovine PrP can vary with natural polymorphisms and raise the possibility that differential interactions of PrP variants with the cellular machinery may contribute to permissiveness or resistance to prion multiplication.
Sophie Paquet, Elifsu Sabuncu, Jean-Louis Delaunay, Hubert Laude, Didier Vilette (2004)  Prion infection of epithelial Rov cells is a polarized event.   J Virol 78: 13. 7148-7152 Jul  
Abstract: During prion infections, the cellular glycosylphosphatidylinositol-anchored glycoprotein PrP is converted into a conformational isoform. This abnormal conformer is thought to recruit and convert the normal cellular PrP into a likeness of itself and is proposed to be the infectious agent. We investigated the distribution of the PrP protein on the surface of Rov cells, an epithelial cell line highly permissive to prion multiplication, and we found that PrP is primarily expressed on the apical side. We further show that prion transmission to Rov cells is much more efficient if infectivity contacts the apical side, indicating that the apical and basolateral sides of Rov cells are not equally competent for prion infection and adding prions to the list of the conventional infectious agents (viruses and bacteria) that infect epithelial cells in a polarized manner. These data raise the possibility that apically expressed PrP may be involved in this polarized process of infection. This would add further support for a crucial role of PrP at the cell surface in prion infection of target cells.
Mohammed Moudjou, Eric Treguer, Human Rezaei, Elifsu Sabuncu, Erdmute Neuendorf, Martin H Groschup, Jeanne Grosclaude, Hubert Laude, Erdi Neuendorf (2004)  Glycan-controlled epitopes of prion protein include a major determinant of susceptibility to sheep scrapie.   J Virol 78: 17. 9270-9276 Sep  
Abstract: A key feature of prion encephalopathies is the accumulation of a misfolded form of the host glycoprotein PrP. Cell-free and cell culture studies have shown that the efficiency of conversion of PrP into the disease-associated form is influenced by its amino acid sequence and also by its carbohydrate moiety. Here, we characterize four novel glycoform-dependent monoclonal antibodies raised against prokaryotic recombinant sheep PrP. We demonstrate that these antibodies discriminate the PrP monoglycosylated species, since two of them recognize molecules that have the first Asn glycosylation site occupied (mono1) while the other two recognize molecules glycosylated at the second site (mono2). Remarkably, the recognition of PrP by the anti-mono2 antibodies was strongly influenced by the amino acid present at position 171, i.e., either Gln or Arg. This polymorphism is known to be the main determinant of susceptibility and resistance to scrapie in sheep. Altogether, our findings lead us to propose that each glycan chain controls the accessibility of PrP determinants located close upstream from their attachment site. The monoglycoform-assigned and the allotype-restricted antibodies described here, the first to date, should provide further opportunities to investigate the involvement of each glycan chain in PrP conversion in relation to prion strain diversity and the basis of the resistance conferred by the Arg-171 amino acid.
Elifsu Sabuncu, Stéphanie Petit, Annick Le Dur, Thanh Lan Lai, Jean-Luc Vilotte, Hubert Laude, Didier Vilette (2003)  PrP polymorphisms tightly control sheep prion replication in cultured cells.   J Virol 77: 4. 2696-2700 Feb  
Abstract: Prion diseases are fatal neurodegenerative disorders of animals and humans that are characterized by the conversion of the host-encoded prion protein (PrP) to an abnormal isoform. In several species, including humans, polymorphisms in the gene encoding the PrP protein tightly control susceptibility of individuals toward this disease. In the present study we show that Rov cells expressing an ovine PrP allele ((VRQ)PrP) associated with high susceptibility of sheep to scrapie were very sensitive to sheep prion transmission and replicated the agent to high titers. In contrast, we did not find any evidence of infection when Rov cells expressed similar levels of a PrP variant ((ARR)PrP) linked to resistance. Our data provide the first direct evidence that natural PrP polymorphisms may affect prion susceptibility by controlling prion replication at the cell level. The study of how PrP polymorphisms influence the genetic control of prion propagation in cultured Rov cells may help elucidate basic mechanisms of prion replication.

PhD theses



Antoine Blanchard, Hélène Monfeuillard, Elifsu Sabuncu (2009)  Mathias Théry, "La vie après la mort d'Henrietta Lacks", 2004, France, 23 min (ENSAD) ; Mathias Théry et Étienne Chaillou, "Cherche toujours", 2008, France, 52 min (Arte France / Les Films d'ici)   [Recensions]  
Abstract: Comment entrer dans lâintimité dâun chercheur ? Comment rendre compte de la vision du monde qui est la sienne ? Comment accéder à une authentique recherche en train de se faire ? à ces questions, le réalisateur Mathias Théry donne quelques éléments de réponse dans ses deux ï¬lms, La vie après la mort dâHenrietta Lacks (ci-après VAMHL) et Cherche toujours (CT). Le premier constitue son ï¬lm dâétudes à lâÃcole nationale supérieure des arts décoratifs. Le second est une commande du collectif « Sauvons la recherche », séduit par le travail effectué sur VAMHL, et a été coréalisé avec Ãtienne Chaillou.
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