Long-term miR-669a therapy alleviates chronic dilated cardiomyopathy in dystrophic mice.

BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of chronic morbidity and mortality in muscular dystrophy (MD) patients. Current pharmacological treatments are not yet able to counteract chronic myocardial wastage, thus novel therapies are being intensely explored. MicroRNAs have been implicated as fine regulators of cardiomyopathic progression. Previously, miR-669a downregulation has been linked to the severe DCM progression displayed by Sgcb-null dystrophic mice. However, the impact of long-term overexpression of miR-669a on muscle structure and functionality of the dystrophic heart is yet unknown. METHODS AND RESULTS: Here, we demonstrate that intraventricular delivery of adeno-associated viral (AAV) vectors induces long-term (18 months) miR-669a overexpression and improves survival of Sgcb-null mice. Treated hearts display significant decrease in hypertrophic remodeling, fibrosis, and cardiomyocyte apoptosis. Moreover, miR-669a treatment increases sarcomere organization, reduces ventricular atrial natriuretic peptide (ANP) levels, and ameliorates gene/miRNA profile of DCM markers. Furthermore, long-term miR-669a overexpression significantly reduces adverse remodeling and enhances systolic fractional shortening of the left ventricle in treated dystrophic mice, without significant detrimental consequences on skeletal muscle wastage. CONCLUSIONS: Our findings provide the first evidence of long-term beneficial impact of AAV-mediated miRNA therapy in a transgenic model of severe, chronic MD-associated DCM.

Application extraterritoriale du droit international des droits de l'homme

Les obligations de l'Etat en matière de droits de l'homme s'étendent-elles au-delà de ses frontières? Le sujet prend une importance considérable actuellement: interventions militaires à l'étranger, opérations de paix, occupation militaire, centres de détention à l'étranger, mouvements séparatistes soutenus par un Etat étranger, éloignement des étrangers, entraide judiciaire et administrative internationale, exequatur de décisions étrangères violant les droits de l'homme... Ces thèmes, et d'autres, sont abordés dans l'ouvrage sous l'angle du Pacte ONU II, de la CEDH, et de la Convention et la Déclaration américaines dans une approche comparative et systématique. L'ouvrage analyse en détail la jurisprudence et la pratique internationales relatives à ces instruments. L'auteur est avocat au Barreau du Canton de Vaud (Lausanne) et titulaire d'un LL.M. de l'Université de Cambridge.

Urban image classification with semisupervised multiscale cluster kernels

This paper presents a semisupervised support vector machine (SVM) that integrates the information of both labeled and unlabeled pixels efficiently. Method's performance is illustrated in the relevant problem of very high resolution image classification of urban areas. The SVM is trained with the linear combination of two kernels: a base kernel working only with labeled examples is deformed by a likelihood kernel encoding similarities between labeled and unlabeled examples. Results obtained on very high resolution (VHR) multispectral and hyperspectral images show the relevance of the method in the context of urban image classification. Also, its simplicity and the few parameters involved make the method versatile and workable by unexperienced users.

La controverse avant le film : quelle politique pour Good Night, And Good Luck ?

This article aims to explain how newspapers commented on the movie Good Night, and Good Luck before its release. The media coverage anticipated George Clooney's film as a partisan attack launched against George W. Bush's policy since 9/11. Clooney advocates another reading: the historic confrontation between journalist Edward Murrow and Senator Joseph McCarty permits to reflect on the crucial role that the media play for democracy. Such reflection tries to prevent the dividing of the public sphere into antagonistic camps opposing "friends" to "foes," a division that undermines the possibility of a true pluralism. Our socio-semiotic analysis will focus on the critical work accomplished by the media, and on the way that work determines the collective meaning of a cultural object. Simultaneously, we will discuss the necessary conditions for pluralism in a public sphere.

Same Performance Changes after Live High-Train Low in Normobaric vs. Hypobaric Hypoxia.

PURPOSE: We investigated the changes in physiological and performance parameters after a Live High-Train Low (LHTL) altitude camp in normobaric (NH) or hypobaric hypoxia (HH) to reproduce the actual training practices of endurance athletes using a crossover-designed study. METHODS: Well-trained triathletes (n = 16) were split into two groups and completed two 18-day LTHL camps during which they trained at 1100-1200 m and lived at 2250 m (P i O2 = 111.9 ± 0.6 vs. 111.6 ± 0.6 mmHg) under NH (hypoxic chamber; FiO2 18.05 ± 0.03%) or HH (real altitude; barometric pressure 580.2 ± 2.9 mmHg) conditions. The subjects completed the NH and HH camps with a 1-year washout period. Measurements and protocol were identical for both phases of the crossover study. Oxygen saturation (S p O2) was constantly recorded nightly. P i O2 and training loads were matched daily. Blood samples and VO2max were measured before (Pre-) and 1 day after (Post-1) LHTL. A 3-km running-test was performed near sea level before and 1, 7, and 21 days after training camps. RESULTS: Total hypoxic exposure was lower for NH than for HH during LHTL (230 vs. 310 h; P < 0.001). Nocturnal S p O2 was higher in NH than in HH (92.4 ± 1.2 vs. 91.3 ± 1.0%, P < 0.001). VO2max increased to the same extent for NH and HH (4.9 ± 5.6 vs. 3.2 ± 5.1%). No difference was found in hematological parameters. The 3-km run time was significantly faster in both conditions 21 days after LHTL (4.5 ± 5.0 vs. 6.2 ± 6.4% for NH and HH), and no difference between conditions was found at any time. CONCLUSION: Increases in VO2max and performance enhancement were similar between NH and HH conditions.