59 research outputs found
Mechanism of Calcium Incorporation Inside SolâGel 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 solâgel silicates is poorly understood. In this work, we shed light on the determinant parameters for incorporation of calcium into acidâbase-catalyzed solâgel 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 organicâinorganic hybrids at ambient temperature. Reproducible syntheses and gel times of SiO2âCaO BG were obtained using calcium hydroxide (CH), and we demonstrate its usability in the synthesis of promising BGâpolycaprolactone 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 neurodĂ©gĂ©nĂ©rative autosomale dominante fatale causĂ©e par une expansion de triplets CAG dans le gĂšne codant la huntingtine (htt). Actuellement, il n existe aucun traitement curatif pour cette pathologie. Des Ă©tudes rĂ©centes montrent que la technique d ARN interfĂ©rence (ARNi) est prometteuse pour traiter des maladies autosomales dominantes dont la MH. Dans ce projet, nous avons dĂ©veloppĂ© les outils permettant d Ă©tudier la faisabilitĂ© et l efficacitĂ© de deux approches : l inactivation non allĂšle-spĂ©cifique des 2 allĂšles de la htt ou une inactivation allĂšle-spĂ©cifique de la forme mutĂ©e, chez des modĂšles rongeurs de la MH. La stratĂ©gie non allĂšle-spĂ©cifique s est montrĂ©e trĂšs efficace Ă long terme, mĂȘme lorsque le traitement est initiĂ© aprĂšs l apparition des symptĂŽmes. La dĂ©gradation de la forme sauvage provoque des modifications transcriptomiques dans des voies de signalisation associĂ©es Ă des fonctions connues de la htt. Ces changements d expression n altĂšrent pas l efficacitĂ© du traitement et ne sont pas associĂ©s Ă des effets dĂ©lĂ©tĂšres. Les effets Ă long terme d une dĂ©gradation partielle de la htt sauvage restent cependant Ă dĂ©terminer. En parallĂšle, nous avons dĂ©veloppĂ© une approche ciblant la htt mutĂ©e tout en prĂ©servant l expression de la forme sauvage, en tirant parti de la prĂ©sence de SNP (polymorphisme nuclĂ©otidique simple) sur le gĂšne de la htt. Cette approche a conduit Ă l inactivation efficace et sĂ©lective de la htt mutĂ©e, prĂ©venant ainsi l apparition de la neuropathologie MH pour la majoritĂ© des SNP ciblĂ©s. L ensemble de ces rĂ©sultats confirme la faisabilitĂ© et l efficacitĂ© de la stratĂ©gie 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 (Aà ”Ă»œ) 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 Ύ-TiN/ϔ-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 ”m) and strong hardness (14 GPa) enhancement together with a smooth gradient can be achieved
DendroĂ©cologie du hĂȘtre en forĂȘt de Soignes : Les cernes des arbres nous renseignent sur les changements rĂ©cents et futurs
La dendroĂ©cologie combine la dendrochronologie et lâĂ©cologie forestiĂšre. Elle a permis dâanalyser les cernes des hĂȘtres de la forĂȘt de Soignes et de comparer les tendances dans le contexte plus large des hĂȘtraies de Belgique.
Depuis la fin des annĂ©es â70, le hĂȘtre devient de plus en plus sensible au climat, surtout en Soignes. Lâaugmentation de la frĂ©quence et de lâintensitĂ© des sĂ©cheresses printaniĂšres et des canicules ont affectĂ© nĂ©gativement la croissance annuelle des hĂȘtres. Les prĂ©visions climatiques pour le 21e siĂšcle prĂ©sage une rapide aggravation.
Les risques encourus par lâessence aboutissent Ă de nouvelles rĂ©flexions sur la gestion de la hĂȘtraie de Soignes. Pour les peuplements existants : une sylviculture dynamique avec des Ă©claircies fortes et frĂ©quentes afin de limiter la concurrence pour les ressources et favoriser la croissance individuelle des arbres. Pour la rĂ©gĂ©nĂ©ration des vieilles hĂȘtraies : les remplacer par dâautres essences plus tolĂ©rantes ou favoriser le mĂ©lange et confiner le hĂȘtre aux surfaces limitĂ©es des stations les plus fraĂźches. Un risque mesurĂ© pourrait ĂȘtre pris en regard du rĂŽle patrimonial des hĂȘtraies cathĂ©drales en Soignes. Toutefois, ce faciĂšs peut ĂȘtre obtenu avec dâautres essences.Accord cadre de recherche et vulgarisation forestiĂšre
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
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