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Background: Microglial cells are resident macrophages of the central nervous system. Genome‐wide association studies identified numerous Alzheimer's disease (AD) risk genes highly or exclusively expressed in microglia, supporting their role as major players in AD pathogenesis. We aim to describe the effect of microglia activation on synaptic connectivity and its potential modulation by AD risk genes. Method: We developed a microfluidic co‐culture device where fluidically isolated, mature neuronal synapses are brought in contact with microglia, enabling exclusive genetic and pharmacological interventions to neurons and microglia. We cultured cortical neurons from WT embryonic mice in pre‐ and postsynaptic chambers for 7 days, after which primary microglia from 10‐month‐old WT and APP (hAPPJ20, PDGFAPPSw,Ind) mice were added into the synapse chamber. Microglia morphology and synaptic connectivity near microglia were analyzed via immunocytochemistry and confocal microscopy. Result: Exposure to lipopolysaccharide (LPS) activated microglia as evidenced by increased surface area and circularity. Morphological changes were correlated with Interleukin‐1 concentration in the medium, indicative of an inflammatory response. We observed a higher reactivity to LPS in microglia from APP mice compared to WT mice, suggesting that genotype‐related differences in microglia reactivity could also be applicable to pathologically relevant stimuli, such as exposure to amyloid‐β oligomers. On‐going work is focused on the synapse pruning process via live‐cell recordings of fluorescent microglia and neurons expressing fluorescently‐tagged synaptic proteins. This model will be used to characterize the dynamic response of microglia to amyloid‐β and include microglia harvested from mice carrying mutations for microglia‐related AD risk genes. Conclusion: Our microfluidic co‐culture device enables specific modulation and high‐content analysis of microglial activity and synaptic connectivity in physiological and AD pathological conditions. [ABSTRACT FROM AUTHOR]

Background: FERMT2 has been identified as a genetic risk factor for AD. We have reported that the FERMT2 protein is a partner of APP and a loss of FERMT2 (kindlin‐2) function altered both axonal growth and long‐term potentiation in an APP‐dependent manner. In this study, we aimed to identify the molecular mechanisms leading to loss of FERMT2 function. Method: We aimed to identify proteases and other factors that regulate the cleavage of FERMT2 protein, which appears to be a mechanism that modulates its functions. The impact on FERMT2 cleavage and molecular interactions were analyzed by Co‐IP and WB. Consequences of these molecular interactions between FERMT2 and its partners on APP metabolism were then investigated using HEK‐APP cell lines. Result: We identified a caspase‐dependent cleavage of FERMT2 that could be a molecular mechanism involved in the regulation of cell adhesion processes by inhibiting the ability of FERMT2 to interact with its partners. Furthermore, these results suggest that c‐Src activity, already known to regulate FERMT2 pathway, may have an impact on APP metabolism through regulation of FERMT2 cleavage. Conclusion: Altogether, our data provide new mechanisms for understanding the involvement of the genetic risk factor FERMT2 in the pathophysiological processes of AD. [ABSTRACT FROM AUTHOR]

Adsorption phenomena and surface-derived reactions on interfaces are fundamentally important processes in environmental chemistry, energy, catalysis, or materials processing, and play a crucial role in the control of membrane performance. Adsorption of species at the surface of membrane materials has been a vast topic of investigation for decades, with both fundamental impact and direct spin-off in industry. In this minireview, the pivotal role of adsorption for both gas-phase and liquid-phase membrane separations is underlined with a focus on inorganic and composite membrane materials, their design strategies, transport mechanisms and associated performance. A particular attention is dedicated to fouling phenomena and emerging surface treatment methods. Finally the role of adsorption for membrane microstructure characterisation and defect detection is discussed. [ABSTRACT FROM AUTHOR]

The increase in the severity of hydrological droughts in the Mediterranean basin in relation to climate change leads to the need to better understand the origin of the water resource to improve its management. The defined study area, the Cevennes upper watershed of the Gardons, presents quite significant variations in terms of low water flows. This article questions these differences and proposes to explain these variances in flows not by a rainfall difference but by a variation in the contribution of the geological reservoirs present in the different watersheds.The study was conducted mainly during the summers of 2018 and 2019 where flows and geochemistry of surface water and groundwater were monitored in 9 watersheds. The use of mixing model in addition to this geochemical-hydrological coupling allows to quantify the contribution of the different formations and shows strong contrast between them. At low water, two formations, black micaschists and limestone, appear to be essential to sustain the flow: they would feed the streams studied to the extent of 41 and 17 % respectively, while they cover only 13 and 8 % of the considered area. The analysis of the contribution of the respective geological formations allows to explain the observed specific discharge of the rivers in the study area.This information of contribution in low water coupled with the flow allows to identify the most productive reservoirs and could help to prioritize the protection of these in view of the scarcity of the resource that will result from climate change.

The use of CRMP (Calcined Resin Microsphere Pelletization) process for AmBB (Americium Bearing Blankets) fabrication is today a key research axis in americium transmutation domain, where its very high activity requires minimization of powder dissemination. In this aim, the use of oxide microspheres as compaction precursors is a promising clean alternative to powder metallurgy. Understanding the different steps of densification during CRMP pellet sintering thus appears as fundamental to obtain final materials with the specific features required for AmBB. The densification curve recorded in dynamic conditions shows different sintering steps. A first decrease of shrinkage rate happens at low temperature, around 1100 K. This phenomenon is not normally observed in the sintering of conventional powders. Chemical and microstructural studies were performed on (U,Am)O 2 and also on (Ce,Gd)O 2 surrogate compound to highlight the causes of this low-temperature sintering step. Multiscale reorganization finally appears as the sole explanation, through the sintering of nanometric aggregate present in the green pellet and related to the morphology of the starting microspheres employed as pelletization precursors. [ABSTRACT FROM AUTHOR]

Mixed uranium-americium oxides are one of the materials envisaged for Americium Bearing Blankets dedicated to transmutation in fast neutron reactors. Conversion and fabrication processes are currently developed to make those materials in the form of dense and homogeneous oxide ceramic pellets or dense granulates incorporating uranium and americium. Their development points out the need of a simplified and optimized process which could lower hazards linked to dust generation of highly contaminating and irradiating compounds and facilitate material transfer in remote handling operations. This reason motivated the development of innovative “dustless” route such as the Weak Acid Resin route (WAR) which provides the oxide precursors in the form of sub-millimeter-sized microspheres with optimal flowability and limits dust generation during conversion and fabrication steps. This study is thus devoted to the synthesis of mixed uranium-americium oxide microspheres by the WAR process and to the characterization of such precursors. This work also deals with their application to the fabrication of dense or porous pellets and with their potential use as dense spherules to make Sphere-Pac fuel. [ABSTRACT FROM AUTHOR]

A mixture design method is developed to investigate the effects of R7T7 glass composition on the residual rate of alteration in di-ionized water at 50 °C. The 12 variables are SiO 2 , B 2 O 3 , Na 2 O, Al 2 O 3 , CaO, ZnO, NiO + CoO, Fe 2 O 3 , MoO 3 , ZrO 2 , FP remaining (Fission Products and actinides remaining) and platinoïds. The method is detailed in this paper and a following publication will deal with the results of its implementation. This experimental design involves 27 glass compositions (with 29 oxides in each glass composition) which are used as training data to estimate the composition effects and to build the predictive alteration models. Three additional glass compositions were formulated to validate the models and to compare the results with other studies. Leaching experiments were planned in residual regime conditions with a monthly monitoring of the pH and the concentrations in solution. Normalized mass loss and alteration rate are calculated and linear regressions were carried out to statistically treat the experimental data. [ABSTRACT FROM AUTHOR]

Background: Using genome‐wide association studies, BIN1 was identified as the most associated risk gene for Alzheimer's Disease (AD) after APOE. A 3bp insertion allele was shown to increase BIN1 expression in human brains and AD risk. BIN1 has more than 10 isoforms and the contribution of BIN1 and its isoforms to AD pathogenesis remains unclear. The aim of this work was to assess the neurotoxicity of BIN1 isoforms and understand the underlying mechanisms. Method: We generated Drosophila transgenic lines expressing brain, muscular and ubiquitous human BIN1 isoforms 1, 8 and 9 respectively. We analyzed BIN1 isoform neurotoxicity using cornea neutralization, immunofluorescence, electrophysiology and electron microscopy in the fly eye photoreceptor neurons. Result: We showed that adult eye‐specific expression of the brain BIN1 isoform 1 (BIN1‐1) resulted in an age‐dependent loss of photoreceptor neurons. Interestingly, the effect was specific of this isoform only. We tested truncated BIN1‐1 forms and showed that the BIN1‐1‐specific CLAP domain is necessary for the BIN1‐1 induced neurodegeneration. This domain is involved in endocytosis and vesicular trafficking. In addition, photoreceptor neuron degeneration was characterized by a strong accumulation of vesicles with endosomal markers suggesting a blockade of the endosome‐lysosome pathway. We further found that modulation of Rab5, Rab4 and Rab11, involved at the level of the early and recycling endosomes, abrogated photoreceptor degeneration, indicating that BIN1‐1 toxicity is due to the blockade of the endosome‐lysosome pathway likely at the level of early endosomes. Finally, as endosomes are involved in synaptic vesicles formation and postsynaptic receptor recycling, we tested the electrophysiological consequences of BIN1‐1 expression. Although not affected in young flies, we observed that expression of BIN1‐1 affected early photoreceptor neuron synaptic transmission. Conclusion: Altogether, these results show that an increase of the BIN1 isoform 1 impairs the endosome‐lysosome pathway, thereby affecting synaptic transmission and inducing neurodegeneration. Interestingly, enlarged endosomes have been shown to be one of the first cytopathological markers of the disease and synaptic transmission is affected early in AD pathogenesis. These results suggest that an increase in BIN1 isoform1 could contribute to early steps of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Objectives: Pigmented villonodular synovitis (PVNS) is a rare but disabling disease. The objective was to describe the clinical presentation and outcomes of PVNS according to its localization. Methods: Retrospective, systematic study of all cases of biopsy-proven PVNS followed in 1 tertiary-care center specialized in isotopic synoviorthesis. Cases were selected by keyword. Collected data included disease localization, therapeutic modalities, and outcomes. Results: A total of 122 cases (mean age 33.0 ± 13.1 years, 58% female, 89% diffuse form) of histologically confirmed PVNS were analyzed with a mean follow-up of 5.8 ± 4.3 years (707 patient-years total). The main localizations were the knee (75%) and ankle (16%). Clinical presentation included joint pain (80%) and joint effusion (79%) with hemarthrosis (75% of analyzed articular fluid). The mean delay before diagnosis was 2.9 ± 3.7 years. Magnetic resonance imaging was helpful for diagnosis in 83%. Surgical synovectomy was initially performed in 98% of cases and was often associated with isotopic synoviorthesis (knee: 57%; other localizations: 74%). In patients with a diffuse form treated at first line by surgery followed by isotopic synoviorthesis, the relapse rate was 30% (knee) and 9% (other localizations), respectively, with a mean delay before relapse of 2.6 ± 2.4 and 2.4 ± 0.9 years, respectively. Conclusions: PVNS occurs in young adults, mainly in the knee joint; joint pain and effusion with hemarthrosis are the most frequent signs. Relapse is frequent, in particular, for diffuse knee PVNS; the usefulness of isotopic synoviorthesis remains to be confirmed. [Copyright &y& Elsevier]