Characterization of Erbium-Doped Nanoparticles in Transparent Glass Ceramic Optical Fibres

We report on using nanometric mass spectroscopy and molecular dynamics modelling to characterize the composition and structure of self-grown erbium-doped nanoparticles in transparent glass ceramic optical fibres fabricated by modified chemical vapour deposition without post-ceramming

Variation de la composition de nanoparticules de 1-10 nm obtenues par séparation de phase dans un verre de silice

National audienceLes verres contenant des nanoparticules ont de nombreuses applications industrielles, notamment grâce à leurs excellentes propriétés thermo-mécaniques [1]. Ils présentent aussi un intérêt pour les propriétés optiques. En effet, l'encapsulation d'ions luminescents (ions de terre rare par exemple) dans des nanoparticules entraînent de nouvelles propriétés de luminescence qui n'existeraient pas dans le verre hôte (bande d'émission élargie, efficacité quantique augmentée, etc) [2]. La préparation de tels verres repose sur des mécanismes de nucléation, croissance et de démixtion dont les premières étapes sont encore assez mal connues. Mais l'avènement de nouvelles techniques de caractérisation à l'échelle nanométrique permet d'améliorer notre compréhension de ces phénomènes. Par exemple, une évolution structurelle des nanoparticules à travers des phases cristallines métastables [3] ou une transformation d'un nucléus amorphe vers une nanoparticule cristalline [4] ont été observées. Des changements de composition ont aussi été rapportés pour des particules de taille 1-10 nm dans des alliages [5] et dans des métaux [6]. Dans cette présentation, nous nous intéressons à la composition de nanoparticules amorphes obtenues par séparation de phase dans un verre de silice. De telles études ont été rendues possibles grâce au développement récent de l'APT (Atom Probe Tomography) pour l'analyse des verres [7]. Nous étudions une fibre optique à base de silice préparée par le procédé MCVD (Modified Chemical Vapor Deposition). Les nanoparticules sont obtenues en incorporant du magnésium qui déclenche une séparation de phase grâce aux traitements thermiques inhérents au procédé MCVD [8]. La composition des nanoparticules dans le verre de silice dopée avec Mg, P, Ge et Er est étudiée dans la gamme 1-10 nm. Nous montrons la partition de Mg, P et Er dans ces nanoparticules ainsi qu'une modification de la composition en fonction de la taille des particules

Loss of the thyroid hormone-binding protein Crym renders striatal neurons more vulnerable to mutant huntingtin in Huntington's disease.

The mechanisms underlying preferential atrophy of the striatum in Huntington's disease (HD) are unknown. One hypothesis is that a set of gene products preferentially expressed in the striatum could determine the particular vulnerability of this brain region to mutant huntingtin (mHtt). Here, we studied the striatal protein µ-crystallin (Crym). Crym is the NADPH-dependent p38 cytosolic T3-binding protein (p38CTBP), a key regulator of thyroid hormone (TH) T3 (3,5,3'-triiodo-l-thyronine) transportation. It has been also recently identified as the enzyme that reduces the sulfur-containing cyclic ketimines, which are potential neurotransmitters. Here, we confirm the preferential expression of the Crym protein in the rodent and macaque striatum. Crym expression was found to be higher in the macaque caudate than in the putamen. Expression of Crym was reduced in the BACHD and Knock-in 140CAG mouse models of HD before onset of striatal atrophy. We show that overexpression of Crym in striatal medium-size spiny neurons using a lentiviral-based strategy in mice is neuroprotective against the neurotoxicity of an N-terminal fragment of mHtt in vivo. Thus, reduction of Crym expression in HD could render striatal neurons more susceptible to mHtt suggesting that Crym may be a key determinant of the vulnerability of the striatum. In addition our work points to Crym as a potential molecular link between striatal degeneration and the THs deregulation reported in HD patients

Erbium-doped transparent glass ceramic optical fibres: Characterization using mass spectroscopy and molecular dynamics modeling

Rare earth (RE) doped silica-based optical fibres with transparent glass ceramic (TGC) core were fabricated through the well-known modified chemical vapor deposition (MCVD) process without going through the commonly used stage of post-ceramming. The main characteristics of the RE-doped dielectric nanoparticles (DNP), their density and mean diameter in thefibres are dictated by various parameters. This paper reports on progresses in the fine characterization of the nanopaticles, particularly their dimensions and composition, using nanosclae mass spectroscpy and molecular dynamics modeling, and alteration of the spectroscopic properties of the erbium ions embedded within the phospho-silicate DNP. These results permit to get more insight into the complex process of the DNP self-nucleation and growth during the fibre fabrication process. This fabrication route could have important potentials in improving rare-earth-doped fibre amplifiers and laser sources

A role of mitochondrial complex II defects in genetic models of Huntington's disease expressing N-terminal fragments of mutant huntingtin.

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal expansion of a CAG repeat encoding a polyglutamine tract in the huntingtin (Htt) protein. The mutation leads to neuronal death through mechanisms which are still unknown. One hypothesis is that mitochondrial defects may play a key role. In support of this, the activity of mitochondrial complex II (C-II) is preferentially reduced in the striatum of HD patients. Here, we studied C-II expression in different genetic models of HD expressing N-terminal fragments of mutant Htt (mHtt). Western blot analysis showed that the expression of the 30 kDa Iron-Sulfur (Ip) subunit of C-II was significantly reduced in the striatum of the R6/1 transgenic mice, while the levels of the FAD containing catalytic 70 kDa subunit (Fp) were not significantly changed. Blue native gel analysis showed that the assembly of C-II in mitochondria was altered early in N171-82Q transgenic mice. Early loco-regional reduction in C-II activity and Ip protein expression was also demonstrated in a rat model of HD using intrastriatal injection of lentiviral vectors encoding mHtt. Infection of the rat striatum with a lentiviral vector coding the C-II Ip or Fp subunits induced a significant overexpression of these proteins that led to significant neuroprotection of striatal neurons against mHtt neurotoxicity. These results obtained in vivo support the hypothesis that structural and functional alterations of C-II induced by mHtt may play a critical role in the degeneration of striatal neurons in HD and that mitochondrial-targeted therapies may be useful in its treatment

Fiber Optic Dielectric Nanoparticles Characterization by Atom Probe Microscopy

International audienceThe engineered processing of dielectric nanoparticles (DNPs) in optical fibers via luminescent ion-doping of silica-based glass aims at providing an enhanced spectroscopic behavior compared to pure silica. These DNPs should positively impact applications in high power fiber lasers, light sources with new wavelengths and telecommunications. The prevalence of large phase immiscibility domains in silicate systems containing divalent metal oxides (Mg for instance) promotes the formation of DNPs through phase separation since heat treatments take place during the MCVD process. Even after 60 years of glass-ceramics research, lack of experimental data concerning early nucleation stages imposes variations in composition and heat treatments as processing steps [1]. Although classical nucleation theory was the first model proposed to explain those phenomena, growth rate mismatches remain wide. According to this capillary assumption-based model, nuclei and bulk share similar structure-composition relationship. Recent articles disprove assumption of structure, pointing toward DNPs structural changes [2] and transition from amorphous nuclei to crystalline DNPs [3]. Compositional changes for small particle sizes (~1-10 nm) have been measured in alloys with Anomalous Small Angle X-Ray Scattering (ASAXS) [4] and in steels with Atom Probe Tomography (APT) [5]. Recent developments in APT has allowed the extension of such studies to glass-ceramics [6], and in the current work, we report experimental data disproving the second capillary assumption at the early stage of nucleation-growth process. The atomic distribution map of Mg DNPs in silica-based glass doped with Mg, P, Ge and Er is reported in Figure 1 after APT analysis. In addition, quantitative assessment of Mg, P and Er content levels in DNPs smaller than 10nm in diameter (Figure 2) could refine the theories behind nucleation and growth mechanisms

The JAK/STAT3 Pathway Is a Common Inducer of Astrocyte Reactivity in Alzheimer's and Huntington's Diseases.

Astrocyte reactivity is a hallmark of neurodegenerative diseases (ND), but its effects on disease outcomes remain highly debated. Elucidation of the signaling cascades inducing reactivity in astrocytes during ND would help characterize the function of these cells and identify novel molecular targets to modulate disease progression. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway is associated with reactive astrocytes in models of acute injury, but it is unknown whether this pathway is directly responsible for astrocyte reactivity in progressive pathological conditions such as ND. In this study, we examined whether the JAK/STAT3 pathway promotes astrocyte reactivity in several animal models of ND. The JAK/STAT3 pathway was activated in reactive astrocytes in two transgenic mouse models of Alzheimer's disease and in a mouse and a nonhuman primate lentiviral vector-based model of Huntington's disease (HD). To determine whether this cascade was instrumental for astrocyte reactivity, we used a lentiviral vector that specifically targets astrocytes in vivo to overexpress the endogenous inhibitor of the JAK/STAT3 pathway [suppressor of cytokine signaling 3 (SOCS3)]. SOCS3 significantly inhibited this pathway in astrocytes, prevented astrocyte reactivity, and decreased microglial activation in models of both diseases. Inhibition of the JAK/STAT3 pathway within reactive astrocytes also increased the number of huntingtin aggregates, a neuropathological hallmark of HD, but did not influence neuronal death. Our data demonstrate that the JAK/STAT3 pathway is a common mediator of astrocyte reactivity that is highly conserved between disease states, species, and brain regions. This universal signaling cascade represents a potent target to study the role of reactive astrocytes in ND

Nakhlites and NanoSIMS via micro-CT characterisation

The nakhlite meteorites contain many mineral phases that precipitated from aqueous solutions and/or were produced by the aqueous alteration of primary igneous minerals. These minerals provide an important record of the history of water on the surface and subsurface of Mars. The isotopic composition of these minerals provides valuable information for reconstructing the physical and chemical environment during formation, as well as the likely geological setting in which fluids were present. In order to reconstruct fully the history of these samples it is essential to understand the multiple episodes of aqueous activity, the relationship between the various carbonate, clay and sulphate phases, and the intricate network of veins and fractures hosting the alteration mineral assemblages