Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe

\u3cem\u3eRPGRIP1\u3c/em\u3e and Cone-Rod Dystrophy in Dogs

Cone–rod dystrophies (crd) represent a group of progressive inherited blinding diseases characterized by primary dysfunction and loss of cone photoreceptors accompanying or preceding rod death. Recessive crd type 1 was described in dogs associated with an RPGRIP1 exon 2 mutation, but with lack of complete concordance between genotype and phenotype. This review highlights role of the RPGRIP1, a component of complex protein networks, and its function in the primary cilium, and discusses the potential mechanisms of genotype–phenotype discordance observed in dogs with the RPGRIP1 mutation

Exposition au rayonnement cosmique : surveillance du personnel de l’Armée de l’air navigant sur E-3F

Cette étude de poste repose, dans un premier temps, sur l’analyse d’une expérimentation consacrée aux mesures des débits d’équivalent de dose ambiante à bord des aéronefs de type E-3F. Ces résultats partiels sont complétés dans un second temps par une campagne de mesures de l’exposition individuelle à l’aide de dosimètres passifs et opérationnels gamma et neutrons. Les équipages de l’Armée de l’air navigant à bord des E-3F sont susceptibles de recevoir annuellement, à partir du niveau 300 et de 200 heures de vol, une dose efficace supérieure à 1 mSv. Il est donc impératif d’organiser une surveillance radiologique et médicale spécifique des équipages correspondant à ces critères de vol

Physico-chemical and mechanical degradation of polyamide 11 induced by hydrolysis and thermal ageing

International audienceThis paper deals with the effect of both temperature and water activity on polyamide 11 physico-chemical and mechanical properties. The purpose of this work is to describe the ductile-brittle transition of polyamides during ageing in a wet environment using a mechanical behavior model. For that it is necessary to make physico-chemical analyzes (DSC, FTIR, GPC, viscosity) and mechanical tests (uniaxial tensile test and DMTA). These characterizations were carried out on safe and samples aged until 60 days under hydrothermal conditions in acid water, and under purely thermal conditions in a neutral environment. Changes in mechanical properties with ageing were observed in the polymer and were correlated to morphological changes deduced from the physicochemical characterizations. An increase of the second yield stress related to the recrystallization and a decrease of the strain at break due to the decrease of the molecular weight were observed during ageing

Exposure to actinides: report on Ca-DTPA injections in CEA-AREVA centres

Ca-DTPA was used for the medical treatment of plutonium and americium contaminations in the CEA and AREVA plants from 1970 to 2003. This report is a survey of the administered injections of Ca-DTPA as a chelating molecule. This report will be part of the registration process for Ca-DTPA by intravenous administration, submitted by the Pharmacie Centrale des Armées. Out of 1158 injections administered to 469 persons, 548 events of possible or confirmed contaminations were reported. These employees were followed by occupational physicians according to the current regulations. The first part of the report is a summary of the most recent findings. Due to its short biological period and its limited action in the blood, Ca-DTPA does not chelate with plutonium and americium as soon as these elements are deposited in the target organs. This justifies an early treatment, even in cases of suspected contamination, followed by additional injections, if necessary. The second part presents data concerning these 1158 injections (contamination routes, posology, adverse effects, ...). These incidents took place at work, were most often minor, and did not require follow-up treatment. A study concerning the efficacy of the product was conducted on a group of people having received 5 or more injections. These results were compared with the efficacy theoretically estimated. Posologies and therapeutic recommendations were proposed based on these observations. Additional studies are needed to confirm these findings. This document is the first summary in this field. It is the result of the collaboration of the occupational medical departments, the laboratories of the CEA and the AREVA and a working group CEA-AREVA-SPRA

RPGRIP1 and Cone–Rod Dystrophy in Dogs

Cone-rod dystrophies (crd) represent a group of progressive inherited blinding diseases characterized by primary dysfunction and loss of cone photoreceptors accompanying or preceding rod death. Recessive crd type 1 was described in dogs associated with an RPGRIP1 exon 2 mutation, but with lack of complete concordance between genotype and phenotype. This review highlights role of the RPGRIP1, a component of complex protein networks, and its function in the primary cilium, and discusses the potential mechanisms of genotype-phenotype discordance observed in dogs with the RPGRIP1 mutation.8 page(s