Pré-implantation de l’Accompagnementcitoyen personnalisé d’intégration communautaire (APIC) : Adaptabilité, collaboration et financement, les déterminants d’une implantation réussie

Cette étude visait à identifier les facilitateurs, les obstacles et la faisabilité d’implanter un Accompagnement-citoyen personnalisé d’intégration communautaire (APIC) pour des aînés en perte d’autonomie et vivant dans la communauté. L’APIC est un suivi hebdomadaire de trois heures réalisé par un accompagnateur non professionnel formé et supervisé qui vise à optimiser la réalisation d’activités sociales et de loisirs de personnes ayant des incapacités. Une recherche-action a permis de réaliser des entretiens semi-dirigés auprès de 16 participants de la communauté. Les principaux facilitateurs de l’implantation sont l’adaptabilité de l’APIC et son appui scientifique, la reconnaissance d’un besoin, l’expertise et la collaboration. La présence de leaders ouverts à la nouveauté et d’individus offrant du soutien est favorable. Le financement de l’implantation, associé à un contexte économique défavorable, est un obstacle. La majorité des participants perçoivent qu’il serait faisable d’implanter l’APIC en l’intégrant à des structures bénévoles déjà existantes. Ces connaissances permettront d’optimiser l’implantation de l’APIC ou d’interventions similaires dans la communauté.Abstract : This study aimed to identify the facilitators and barriers to as well as the feasibility of Implementing Personalized Citizen Assistance for social participation (IPCA) in older adults with disabilities living in the community. The IPCA is a threehour, weekly follow-up achieved by trained and supervised non-professional assistants that aims to increase engagement in social and leisure activities of people living with disabilities. An action research study was conducted with 16 people from the community. The adaptability of the IPCA, the presence of scientific evidence, the acknowledgement of a need for such an intervention, as well as expertise and collaboration, were the main facilitators in implementation of the IPCA. Meanwhile, funding, associated with an unfavorable political and economic context, was a barrier. Overall, the majority of the participants perceived that the IPCA could be offered in the community by volunteers. This new knowledge will facilitate the implementation of IPCA or other similar interventions

Selective localization of Mfn2 near PINK1 enables its preferential ubiquitination by Parkin on mitochondria

Mutations in Parkin and PINK1 cause early-onset familial Parkinson's disease. Parkin is a RING-In-Between-RING E3 ligase that transfers ubiquitin from an E2 enzyme to a substrate in two steps: (i) thioester intermediate formation on Parkin and (ii) acyl transfer to a substrate lysine. The process is triggered by PINK1, which phosphorylates ubiquitin on damaged mitochondria, which in turn recruits and activates Parkin. This leads to the ubiquitination of outer mitochondrial membrane proteins and clearance of the organelle. While the targets of Parkin on mitochondria are known, the factors determining substrate selectivity remain unclear. To investigate this, we examined how Parkin catalyses ubiquitin transfer to substrates. We found that His433 in the RING2 domain contributes to the catalysis of acyl transfer. In cells, the mutation of His433 impairs mitophagy. In vitro ubiquitination assays with isolated mitochondria show that Mfn2 is a kinetically preferred substrate. Using proximity-ligation assays, we show that Mfn2 specifically co-localizes with PINK1 and phospho-ubiquitin (pUb) in U2OS cells upon mitochondrial depolarization. We propose a model whereby ubiquitination of Mfn2 is efficient by virtue of its localization near PINK1, which leads to the recruitment and activation of Parkin via pUb at these sites

A scientific resilience observatory for the Pacific islands and coasts: some results

International audienc

A scientific resilience observatory for the Pacific islands and coasts: some results

International audienc

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants