Mutations in components of complement influence the outcome of Factor I-associated atypical hemolytic uremic syndrome

Genetic studies have shown that mutations of complement inhibitors such as membrane cofactor protein, Factors H, I, or B and C3 predispose patients to atypical hemolytic uremic syndrome (aHUS). Factor I is a circulating serine protease that inhibits complement by degrading C3b and up to now only a few mutations in the CFI gene have been characterized. In a large cohort of 202 patients with aHUS, we identified 23 patients carrying exonic mutations in CFI. Their overall clinical outcome was unfavorable, as half died or developed end-stage renal disease after their first syndrome episode. Eight patients with CFI mutations carried at least one additional known genetic risk factor for aHUS, such as a mutation in MCP, CFH, C3 or CFB; a compound heterozygous second mutation in CFI; or mutations in both the MCP and CFH genes. Five patients exhibited homozygous deletion of the Factor H-related protein 1 (CFHR-1) gene. Ten patients with aHUS had one mutation in their CFI gene (Factor I-aHUS), resulting in a quantitative or functional Factor I deficiency. Patients with a complete deletion of the CFHR-1 gene had a significantly higher risk of a bad prognosis compared with those with one Factor I mutation as their unique vulnerability feature. Our results emphasize the necessity of genetic screening for all susceptibility factors in patients with aHUS

Pronostic des transplantations rénales réalisées entre 2000 et 2008 chez les patients présentant un syndrome hémolytique et urémique primitif de l adulte associé aux mutations des facteurs H, I, MCP et C3 (l expérience française)

Le syndrome hémolytique et urémique (SHU) est défini par l association d une insuffisance rénale aiguë, d une thrombopénie et d une anémie hémolytique mécanique. Le SHU primitif est rare et évolue vers la dialyse définitive dans deux cas sur trois. Il est maintenant établi que le SHU primitif s associe à un défaut de régulation de la C3 convertase alterne, enzyme clé de la voie alterne du complément : plus de la moitié des patients présentent une mutation de protéines impliquées dans la régulation (facteur H, I, MCP) ou la formation (C3) de cette enzyme. Nous avons étudié l évolution de 56 greffes rénales réalisées entre 2000 et 2008 chez 51 adultes atteints de SHU primitif afin de mettre en évidence des facteurs de risque de récidive et de perte de greffon. Le taux de récidive s élève à 59%, en 12 mois dans 75% des cas. Il varie de 39% à 86% en fonction des mutations. Un antécédent familial de SHU primitif est un facteur de risque surajouté de récidive. Une immunosuppression sans anticalcineurines s associe à un risque accru de rejet sans modifier le risque de récidive. Le pronostic est sombre : deux tiers des récidives évoluent vers la perte du greffon, en 12 mois dans 72% des cas. L absence de mutation identifiée, une récidive survenant après le 3e mois et une créatininémie élevée lors de la récidive sont des facteurs de risque associés à survie rénale péjorative. Il est urgent que des études prospectives comparatives définissent la place d un traitement pré-emptif ou curatif par plasmathérapie, anticorps monoclonaux anti-C5 ou facteur H recombinant. Ce travail aidera à déterminer les patients qui pourront au mieux bénéficier de ces nouvelles thérapeutiques.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Use of matrix corrections in the calculation of surface composition of AgPd alloys in Auger electron spectroscopy

The surface segregation in binary alloys is often studied by Auger electron spectroscopy. However, the information obtained in the Auger spectra is representative of a region thicker than one monolayer. The Auger signal must be decomposed into the contributions of the different atomic layers. On the other hand, it is now well known that matrix correction factors must be used to relate the intensity of the Auger signal to the composition of the sample. As these two parameters are seldom put together in the treatment of Auger data, we tried to combine them for the study of the surface segregation in silver–palladium alloys. We calculated the matrix correction factors for AgPd alloys in the whole range of concentrations. The attenuation length corrections and the backscattering corrections were calculated on the basis of different models (Seah and Dench, Penn, Tanuma–Powell–Penn, Ichimura–Shimizu–Langeron, Reuter–Ichimura, etc.). The matrix corrections were compared to the Hall and Morabito approach and with previously published results. The matrix corrections were then introduced into a layer-by-layer model of interpretation of the Auger signal. While the surface composition calculated without matrix correction reveals silver enrichment relative to the bulk of the samples, the use of matrix corrections lead to an enrichment in silver that is strongly attenuated.FLWNAinfo:eu-repo/semantics/publishe

Piecing the barcoding puzzle of Palearctic water frogs ( Pelophylax ) sheds light on amphibian biogeography and global invasions

International audienceAbstract Palearctic water frogs (genus Pelophylax ) are an outstanding model in ecology and evolution, being widespread, speciose, either threatened or threatening to other species through biological invasions, and capable of siring hybrid offspring that escape the rules of sexual reproduction. Despite half a century of genetic research and hundreds of publications, the diversity, systematics and biogeography of Pelophylax still remain highly confusing, in no small part due to a lack of correspondence between studies. To provide a comprehensive overview, we gathered >13,000 sequences of barcoding genes from >1700 native and introduced localities and built multigene mitochondrial (~17 kb) and nuclear (~10 kb) phylogenies. We mapped all currently recognized taxa and their phylogeographic lineages (>40) to get a grasp on taxonomic issues, cyto‐nuclear discordances, the genetic makeup of hybridogenetic hybrids, and the origins of introduced populations. Competing hypotheses for the molecular calibration were evaluated through plausibility tests, implementing a new approach relying on predictions from the anuran speciation continuum. Based on our timetree, we propose a new biogeographic paradigm for the Palearctic since the Paleogene, notably by attributing a prominent role to the dynamics of the Paratethys, a vast paleo‐sea that extended over most of Europe. Furthermore, our results show that distinct marsh frog lineages from Eastern Europe, the Balkans, the Near East, and Central Asia ( P. ridibundus ssp.) are naturally capable of inducing hybridogenesis with pool frogs ( P. lessonae ). We identified 14 alien lineages (mostly of P. ridibundus ) over ~20 areas of invasions, especially in Western Europe, with genetic signatures disproportionally pointing to the Balkans and Anatolia as the regions of origins, in line with exporting records of the frog leg industry and the stocks of pet sellers. Pelophylax thus emerges as one of the most invasive amphibians worldwide, and deserves much higher conservation concern than currently given by the authorities fighting biological invasions

Renal Involvement in Cystic Fibrosis: Diseases Spectrum and Clinical Relevance

Background and objectives: Clinically relevant kidney involvement is uncommonly described in adult patients with cystic fibrosis (CF). We sought to report on a series of patients with CF and kidney biopsy–documented renal involvement