Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Prominence of the Instability of a Stabilizing Agent in the Changes in Physical State of a Hybrid Nanomaterial

International audienceShaping ability of hybrid nanomaterials is a key point for their further use in devices. It is therefore crucial to control it. To this end, it is necessary that the macroscopic properties of the material remain constant over time. Here, we evidence by multinuclear Magic‐Angle Spinning Nuclear Magnetic Resonance spectroscopic study including 17O isotope exchange that for a ZnO‐alkylamine hybrid material, the partial carbonation of amine into ammonium carbamate molecules is behind the conversion from highly viscous liquid to a powdery solid when exposed to air. This carbonation induces modification and reorganization of the organic shell around the nanocrystals and affects significantly the macroscopic properties of the material such as it physical state, its solubility and colloidal stability. This study, straightforwardly extendable, highlights that the nature of the functional chemical group allowing connecting the stabilizing agent (SA) to the surface of the nanoparticles is of tremendous importance especially if the SA is reactive with molecules present in the environment

Nanocrystal-ligand interactions deciphered: the influence of HSAB and pK(a) in the case of luminescent ZnO

International audienceDespite all the efforts made by the scientific community to rationalize the interaction of organic molecules with nanocrystals (Ncs), we are still at the level of the empirical recipe when the material behavior in solution is concerned. In an effort to address this issue, the analysis of the luminescence measurements of ZnO Ncs in the presence of various organic substrates using a Langmuir adsorption model was carried out to determine for the first time the affinity constants and the number of binding sites as well as to rank the interaction strengths of these substrates with regard to ZnO Ncs. The results were confirmed by NMR spectroscopic studies, which, besides, provided a deep understanding of the substrate-ZnO Nc interactions. Analysis of the results using pK(a) and HSAB theory demonstrates that the interaction of a given substrate can be determined by its pK(a)versus the pK(a) of the organic molecules present at the surface of pristine Ncs and that the hard or soft character of the substrates can govern the emission intensity of the ZnO Ncs

Self-Assembly of ZnO Nanoparticles - An NMR Spectroscopic Study

International audienceThe role of ligands (i.e. hexadecylamine, dodecylamine, or octylamine associated with oleic acid) on the formation of ZnO nanoparticle superlattice structures (NSSs) was investigated by NMR spectroscopy in C7D8. This full study demonstrates that ion‐paired ammonium carboxylates play a crucial role in NSS formation. Using different NMR spectroscopic experiments, such as 1H NMR, pulsed field gradient spin‐echo (PGSE) NMR, and NOESY, we evidenced that the introduction of long‐alkyl‐chain carboxylic acid molecules into a colloidal solution of ZnO nanoparticles (NPs) stabilized by amine ligands leads to rearrangement of the amines on the surface of the NPs with the formation of ammonium carboxylate. This NMR spectroscopic study evidences the dependence of the nature of the ligands adsorbed on the NP surface on the colloid concentration. At high concentration, several ligand shells with a lot of ion‐paired ammonium carboxylate and inclusion of amine are observed. At low concentration, the ion‐paired ammonium carboxylate shells are replaced by amine shells. This NMR spectroscopic study suggests that the driving force of NSS formation is the presence of ion‐paired ammonium carboxylate shells around the nanoparticle

Estrogen receptor of primary breast cancers: Evidence for intracellular proteolysis

SCOPUS: ar.jinfo:eu-repo/semantics/publishe