Targeting RyR Activity Boosts Antisense Exon 44 and 45 Skipping in Human DMD Skeletal or Cardiac Muscle Culture Models.

Systemic delivery of antisense oligonucleotides (AO) for DMD exon skipping has proven effective for reframing DMD mRNA, rescuing dystrophin expression, and slowing disease progression in animal models. In humans with Duchenne muscular dystrophy treated with AOs, low levels of dystrophin have been induced, and modest slowing of disease progression has been observed, highlighting the need for improved efficiency of human skipping drugs. Here, we demonstrate that dantrolene and Rycals S107 and ARM210 potentiate AO-mediated exon skipping of exon 44 or exon 45 in patient-derived myotube cultures with appropriate mutations. Further, dantrolene is shown to boost AO-mediated exon skipping in patient-derived, induced cardiomyocyte cultures. Our findings further validate the ryanodine receptors (RyR) as the likely target responsible for exon skip boosting and demonstrate potential applicability beyond exon 51 skipping. These data provide preclinical support of dantrolene trial as an adjuvant to AO-mediated exon-skipping therapy in humans and identify a novel Rycal, ARM210, for development as a potential exon-skipping booster. Further, they highlight the value of mutation-specific DMD culture models for basic discovery, preclinical drug screening and translation of personalized genetic medicines

Mise en évidence de la présence du virus de la Mosaique de l'igname (YMV) en Guyane

Des échantillons d'ignames Dioscorea trifida collectés en Guyane française présentent des symptômes de mosaïque en arêtes de poisson. On montre que ces plantes contiennent un potyvirus flexueux, produisant des inclusions cytoplasmiques de type pinwheels et transmis par pucerons sur le mode non persistant. L'isolat étudié est proche du Yam Mosaic Virus décrit en Côte d'Ivoire, il réagit avec un antiserum anti-YMV- Côte d'Ivoire et sa protéine capside présente une mobilité électrophorétique identique, mais il produit des symptômes plus marqués sur Nicotiana benthamiana et présente une mobilité électrophorétique différente de celle d'isolats provenant de Guadeloupe (FWI); Des précautions doivent être prises pour éviter tout échange international de matériel infecté. ----- Yam plants, Dioscorea trifida, collected in French Guyana showed chromatic fish -bone symptoms on their leaves. The plants were found infected by a potyvirus with flexuous rods, produccing pinwheels in infected cytoplasm, transmitted mechanically and buy aphids in a non persisten manner. The virus reacted with an antiserum prepared against the Ivory Coast isolate of Yam Mosaic Virus an their coat proteins presented the same electrophoretic mobility. Differences in electrophoretic mobility were found with a yam potyvirus collected in Guadeloupe (FWI); the guyana isolate produced also a more severe vein-banding on Nicotiane benthammiana leaves than the other Yam isolates. Precautions must be taken in order to avoid any international exchange of infected material

TROP 03 - Le paludisme en Guyane Française, deux populations : l'une liée à l'activité d'orpaillage et celle des peuples autochtones

National audienceLe paludisme en Guyane Française, deux populations : l'une liée à l'activité d'orpaillage et celle des peuples autochtone

Potentialité d'invasion, en Méditerranée occidentale, par des potyvirus proches du Papaya ringspot virus (PRSV)

Supplément 1National audienc

Technical feasibility assessment of a PEM fuel cell refrigerator system

PEM Fuel Cells (PEMFCs), fueled by hydrogen, are electrochemical devices that convert hydrogen to useful power and two by-products: heat and water. They cover an important part of power applications namely in the transportation area, and in other practical applications that are either stationary or portable. In particular, the domestic refrigerator is one of the daily and indispensable applications but with a high-energy demand due to the high running time cycles. This work is a technical assessment of the feasibility of building a coupled “PEM Fuel Cell – Refrigerator” system. Real technical data for the refrigerator are collected, processed and evaluated. The obtained results show reasonable flows consumption rates. In fact, the refrigerator requires a flow rate of 1.607 slpm of hydrogen and 8 slpm of air at a pressure of respectively 3 atm and 1 atm. The water is produced at a rate of 1.285 10−3 slpm. The annual amount of hydrogen consumed by the refrigerator is estimated to 28, 47 kg. The energy provided to the refrigerator is about 130 W and the energy needed by the air compressor is 28, 24 W. A technical solution is suggested at the end of this work to reduce the start and stop cycles of the fuel cell

Technical feasibility assessment of a PEM fuel cell refrigerator system

International audienc

Orpailleurs clandestins : prévalences des statuts VIH, VHB, VHC, VHD et syphilitique d’une population isolée et méconnue

International audienc