Le patrimoine culturel immatériel au seuil des sciences sociales

L’entrée en vigueur de la Convention sur la sauvegarde du patrimoine culturel immatériel (PCI) de 2003 a abouti, dès 2009, au dépôt des premières candidatures sur les listes de l’Unesco, alors même que le champ du PCI était encore peu connu des chercheurs et des acteurs du patrimoine. Après plusieurs années marquées par la prédominance des recherches ethnologiques sur ce nouveau patrimoine, le Centre culturel international de Cerisy-la-Salle (Normandie) accueillait du 24 au 29 septembre 2012 un colloque international rassemblant des chercheurs de plusieurs disciplines (ethnologues, anthropologues, économistes, juristes, historiens, géographes), des responsables de l’Unesco, des fonctionnaires de l’administration culturelle et des acteurs de terrain associatifs. Les participants y confrontaient pour la première fois des lectures contrastées de l’histoire du PCI, de la valeur politique de ce patrimoine et du rôle qu’y tient la participation des « communautés ». Nourrit de nombreuses études de cas empruntées au contexte international mais aussi au contexte territorial de la Normandie, ce colloque de Cerisy fut ainsi la première entreprise intellectuelle collective de grande ampleur consacrée au PCI où ont été énoncés les prémisses de recherches pluridisciplinaires promises aux développements que l’on constate aujourd’hui. Il a de ce fait constitué un tournant décisif dans les études patrimoniales liées à l’immatériel. Cet important volume réunit les actes de cette rencontre majeure qui a fait date dans l’histoire de la réflexion sur la mise en œuvre de la Convention Unesco

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

BACKGROUND Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS A total of 663 patients underwent randomization and were followed for a mean (+/- SD) of 5.3 +/- 2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P = 0.02). The number of serious adverse events did not differ significantly between the treatment groups (P = 0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation

Dynamique des actions nouvelles qualifications et émergence d'opérateurs collectifs multidimensionnels : contribution à une nouvelle approche du jeu des acteurs.

International audienc

Histidine-rich designer peptides of the LAH4 family promote cell delivery of a multitude of cargo

International audienc

Overcoming the Challenges Imposed by Humoral Immunity to AAV Vectors to Achieve Safe and Efficient Gene Transfer in Seropositive Patients

International audienceOne of the major goals of in vivo gene transfer is to achieve long-term expression of therapeutic transgenes in terminally differentiated cells. The extensive clinical experience and the recent approval of Luxturna ® (Spark Therapeutics, now Roche) and Zolgensma ® (AveXis, now Novartis) place vectors derived from adeno-associated viruses (AAV) among the best options for gene transfer in multiple tissues. Despite these successes, limitations remain to the application of this therapeutic modality in a wider population. AAV was originally identified as a promising virus to derive gene therapy vectors because, despite infecting humans, it was not associated with any evident disease. Thee large proportion of AAV infections in the human population is now revealing as a limitation because after exposure to wild-type AAV, anti-AAV antibodies develops and may neutralize the vectors derived from the virus. Injection of AAV in humans is generally well-tolerated although the immune system can activate after the recognition of AAV vectors capsid and genome. The formation of high-titer neutralizing antibodies to AAV after the first injection precludes vector re-administration. Thus, both pre-existing and post-treatment humoral responses to AAV vectors greatly limit a wider application of this gene transfer modality. Different methods were suggested to overcome this limitation. The extensive preclinical data available and the large clinical experience in the control of AAV vectors immunogenicity are key to clinical translation and to demonstrate the safety and efficacy of these methods and ultimately bring a curative treatment to patients

Determination of Anti-Adeno-Associated Virus Vector Neutralizing Antibody Titer with an In Vitro

Adeno-associated virus (AAV) vectors are a platform of choice for in vivo gene transfer applications. However, neutralizing antibodies (NAb) to AAV can be found in humans and some animal species as a result of exposure to the wild-type virus, and high-titer NAb develop following AAV vector administration. In some conditions, anti-AAV NAb can block transduction with AAV vectors even when present at low titers, thus requiring prescreening before vector administration. Here we describe an improved in vitro, cell-based assay for the determination of NAb titer in serum or plasma samples. The assay is easy to setup and sensitive and, depending on the purpose, can be validated to support clinical development of gene therapy products based on AAV vectors

Optimising histidine rich peptides for efficient DNA delivery in the presence of serum

International audienc

Low-dose liver targeted gene therapy for Pompe disease enhances therapeutic efficacy of ERT via immune tolerance induction

International audiencePompe disease results from acid α-glucosidase (GAA) deficiency and enzyme replacement therapy (ERT) with recombinant human (rh) GAA has clinical benefits, although its limitations include the short half-life of GAA and the formation of antibody responses. The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV) vector containing a liver-specific promoter. GAA knockout (KO) mice were administered either a weekly injection of rhGAA (20 mg/kg), or a single injection of AAV2/8-LSPhGAA (8x1011 vector genomes (vg)/kg). Both treatments significantly reduced glycogen content of the heart and diaphragm. While ERT triggered anti-GAA antibody formation, there was no detectable antibody response following AAV vector administration. The efficacy of 3 lower dosages of AAV2/8-LSPhGAA was evaluated in GAA-KO mice, either alone or in combination with ERT. The minimum effective dose (MED) identified was 8x1010 vg/kg to reduce glycogen content in the heart and diaphragm of GAA-KO mice. A 3-fold higher dose was required to suppress antibody responses to ERT. Efficacy from liver gene therapy was slightly greater in male mice than in females. Vector dose correlated inversely with anti-GAA antibody formation, while higher vector doses suppressed previously formed anti-GAA antibodies as late as 25 weeks after the start of ERT and achieved biochemical correction of glycogen accumulation. In conclusion, we identified the MED for effective AAV2/8-LSPhGAA-mediated tolerogenic gene therapy in Pompe disease mice

Investigation of DNA Condensing Properties of Amphiphilic Triblock Cationic Polymers by Atomic Force Microscopy

International audienceIntroduction of nucleic acids into cells is an important biotechnology research field which also holds great promise for therapeutic applications. One of the key steps in the gene delivery process is compaction of DNA into nanometric particles. The study of DNA condensing properties of three linear cationic triblock copolymers poly(ethylenimine-bpropylene glycol-b-ethylenimine), namely, LPEI50-PPG36-LPEI50, LPEI19-PPG36-LPEI19, and LPEI14-PPG68-LPEI14, indicates that proper DNA condensation is driven by both the charge and the size of the respective cationic hydrophilic linear polyethylenimine (LPEI) and neutral hydrophobic poly(propylene glycol) (PPG) parts. Atomic force microscopy was used to investigate the interactions of the triblock copolymers with plasmid DNA at the single molecule level and to enlighten the mechanism involved in DNA condensation