Mechanism of Calcium Incorporation Inside Sol–Gel Silicate Bioactive Glass and the Advantage of Using Ca(OH)2 over Other Calcium Sources

Calcium is an essential component of osteogenesis and is often required for imparting significant bioactivity to synthetic bone substitutes and, in particular, silicate-based materials. However, the mechanism of calcium incorporation inside sol–gel silicates is poorly understood. In this work, we shed light on the determinant parameters for incorporation of calcium into acid–base-catalyzed sol–gel silicates at ambient temperature: increasing the pH above the isoelectric point of silicic acid and the nature of the calcium counterion in the calcium precursor are found to be the key. Based on our proposed reaction sequence, we were able to compare calcium precursors and select an ideal candidate compound for the synthesis of bioactive glasses (BG) and organic–inorganic hybrids at ambient temperature. Reproducible syntheses and gel times of SiO2–CaO BG were obtained using calcium hydroxide (CH), and we demonstrate its usability in the synthesis of promising BG–polycaprolactone hybrid scaffolds. BG and hybrids prepared with CH were able to form nanocrystalline nonstoichiometric apatite in simulated body fluid. The increased reliability of low-temperature syntheses associated with the use of a stable and inexpensive alkaline-earth precursor are major steps toward the translation of calcium silicate hybrids or other alkaline-earth silicates from bench to clinic

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Utilisation de petits ARN interférents pour le traitement de la maladie de Huntington

La maladie de Huntington (MH) est une maladie neurodégénérative autosomale dominante fatale causée par une expansion de triplets CAG dans le gène codant la huntingtine (htt). Actuellement, il n existe aucun traitement curatif pour cette pathologie. Des études récentes montrent que la technique d ARN interférence (ARNi) est prometteuse pour traiter des maladies autosomales dominantes dont la MH. Dans ce projet, nous avons développé les outils permettant d étudier la faisabilité et l efficacité de deux approches : l inactivation non allèle-spécifique des 2 allèles de la htt ou une inactivation allèle-spécifique de la forme mutée, chez des modèles rongeurs de la MH. La stratégie non allèle-spécifique s est montrée très efficace à long terme, même lorsque le traitement est initié après l apparition des symptômes. La dégradation de la forme sauvage provoque des modifications transcriptomiques dans des voies de signalisation associées à des fonctions connues de la htt. Ces changements d expression n altèrent pas l efficacité du traitement et ne sont pas associés à des effets délétères. Les effets à long terme d une dégradation partielle de la htt sauvage restent cependant à déterminer. En parallèle, nous avons développé une approche ciblant la htt mutée tout en préservant l expression de la forme sauvage, en tirant parti de la présence de SNP (polymorphisme nucléotidique simple) sur le gène de la htt. Cette approche a conduit à l inactivation efficace et sélective de la htt mutée, prévenant ainsi l apparition de la neuropathologie MH pour la majorité des SNP ciblés. L ensemble de ces résultats confirme la faisabilité et l efficacité de la stratégie ARNi pour traiter la MH.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Synaptojanin 1 Mutation in Parkinson's Disease Brings Further Insight into the Neuropathological Mechanisms

International audienceSynaptojanin 1 (SYNJ1) is a phosphoinositide phosphatase highly expressed in nerve terminals. Its two phosphatase domains dephosphorylate phosphoinositides present in membranes , while its proline-rich domain directs protein-protein interactions with synaptic components , leading to efficient recycling of synaptic vesicles in neurons. Triplication of SYNJ1 in Down ' s syndrome is responsible for higher level of phosphoinositides , enlarged endosomes , and learning deficits. SYNJ1 downregulation in Alzheimer ' s disease models is protective towards amyloid-beta peptide (Aí µí»½) toxicity. One missense mutation in one of SYNJ1 functional domains was recently incriminated in an autosomal recessive form of early-onset Parkinson ' s disease (PD). In the third decade of life , these patients develop progressive Parkinsonism with bradykinesia , dystonia , and variable atypical symptoms such as cognitive decline , seizures , and eyelid apraxia. The identification of this new gene , together with the fact that most of the known PD proteins play a role in synaptic vesicle recycling and lipid metabolism , points out that synaptic maintenance is a key player in PD pathological mechanisms. Studying PD genes as a network regulating synaptic activity could bring insight into understanding the neuropathological processes of PD and help identify new genes at fault in this devastating disorder

Dynamics of leaf mass per unit leaf area and root mass per unit root volume of young maize plants: implications for growth models

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Relation between Mechanical Hardening and Nitrogen Profile of PBII Nitrided Titanium Alloy

International audienceSurface treatments of Ti-6Al-4V alloys are of utmost importance for biomedical applications since they allow for tribological gain. Here, Ti-6Al-4V disks have been PBII nitrided at either 500, 600, 700 and 800 °C. A set of techniques (XRD, SEM-EDS, EBSD and GDOES) was used to characterize the surface microstructural and chemical changes. Nanoindentation was used to assess the induced changes in terms of mechanical properties. Two types of nitrided domains are revealed. Starting from the surface, a nitride bilayer composed of δ-TiN/ϵ-Ti2N with enhanced surface resistance is supported by an α-Ti(N) solid solution formed at depth. Hardness values peak at 12-14 GPa at the surface, which is almost twice as large as the bulk value (about 7 GPa). For the moderate temperatures used here, a deep (10-15 µm) and strong hardness (14 GPa) enhancement together with a smooth gradient can be achieved

Dendroécologie du hêtre en forêt de Soignes : Les cernes des arbres nous renseignent sur les changements récents et futurs

La dendroécologie combine la dendrochronologie et l’écologie forestière. Elle a permis d’analyser les cernes des hêtres de la forêt de Soignes et de comparer les tendances dans le contexte plus large des hêtraies de Belgique. Depuis la fin des années ‘70, le hêtre devient de plus en plus sensible au climat, surtout en Soignes. L’augmentation de la fréquence et de l’intensité des sécheresses printanières et des canicules ont affecté négativement la croissance annuelle des hêtres. Les prévisions climatiques pour le 21e siècle présage une rapide aggravation. Les risques encourus par l’essence aboutissent à de nouvelles réflexions sur la gestion de la hêtraie de Soignes. Pour les peuplements existants : une sylviculture dynamique avec des éclaircies fortes et fréquentes afin de limiter la concurrence pour les ressources et favoriser la croissance individuelle des arbres. Pour la régénération des vieilles hêtraies : les remplacer par d’autres essences plus tolérantes ou favoriser le mélange et confiner le hêtre aux surfaces limitées des stations les plus fraîches. Un risque mesuré pourrait être pris en regard du rôle patrimonial des hêtraies cathédrales en Soignes. Toutefois, ce faciès peut être obtenu avec d’autres essences.Accord cadre de recherche et vulgarisation forestière

Mediterranean long-term study shows correlation between Ostreopsis cf. ovata bloom timing and spring temperature

The 18th International Conference on Harmful Algae (ICHA), From ecosystems to socio-ecosystems, 21-26 October 2018, Nantes, France.-- 1 pageBenthic toxic dinoflagellate Ostreopsis cf. ovata events are responsible for ecological, sanitary and economic issues in different temperate areas and need better understanding. Every summer, from 2007 to 2017, Ostreopsis cf. ovata blooms have been monitored in Larvotto beach (Monaco, NW Mediterranean Sea), allowing for the achievement of one of the longest time series of Ostreopsis blooms worldwide. Five sites were sampled each year during the bloom period, from mid-June to end August, with collection of benthic cells. Blooms phenology (timing, length and maximum cell abundance) was highly variable across the study period. Variations of net growth rate estimated during the phases of bloom development were analyzed as a function of Sea Surface Temperature (SST). Surprisingly, the highest growth rates were not associated with the maximal temperature records (27.5°C) but were estimated when temperature ranged between 21°C and 25°C. Many authors suggested that global warming might have influenced Ostreopsis expansion from tropical areas to temperate waters, such as the Mediterranean Sea. Current results do not directly support this hypothesis, but suggest a more complex role of temperature in bloom dynamics than a simple facilitation factor for algal growth, at least in temperate areas. In order to characterize in more details the role of SST on O. cf. ovata bloom phenology, SST anomalies were calculated as differences between temperature values and the mean SST value over the 11 years of survey. A positive correlation (Spearman test, rs= 0.766, p < 0.01) was observed between positive anomalies of SST and the bloom precocity. This result indicates that blooms seem to occur earlier in the season when spring is warmer. The relation between SST and net growth rate as well as between SST anomalies and precocity of the blooms should be of great interest for modelers. Predicting the distribution and the phenology of Ostreopsis in European coastal waters is a crucial challenge, especially in a context of global warmingPeer Reviewe