Lactic Acid Induces Aberrant Amyloid Precursor Protein Processing by Promoting Its Interaction with Endoplasmic Reticulum Chaperone Proteins

Lactic acid, a natural by-product of glycolysis, is produced at excess levels in response to impaired mitochondrial function, high-energy demand, and low oxygen availability. The enzyme involved in the production of β-amyloid peptide (Aβ) of Alzheimer's disease, BACE1, functions optimally at lower pH, which led us to investigate a potential role of lactic acid in the processing of amyloid precursor protein (APP).Lactic acid increased levels of Aβ40 and 42, as measured by ELISA, in culture medium of human neuroblastoma cells (SH-SY5Y), whereas it decreased APP metabolites, such as sAPPα. In cell lysates, APP levels were increased and APP was found to interact with ER-chaperones in a perinuclear region, as determined by co-immunoprecipitation and fluorescence microscopy studies. Lactic acid had only a very modest effect on cellular pH, did increase the levels of ER chaperones Grp78 and Grp94 and led to APP aggregate formation reminiscent of aggresomes.These findings suggest that sustained elevations in lactic acid levels could be a risk factor in amyloidogenesis related to Alzheimer's disease through enhanced APP interaction with ER chaperone proteins and aberrant APP processing leading to increased generation of amyloid peptides and APP aggregates

Experimental insight into redox transfer by iron- and sulfur-bearing serpentinite dehydration in subduction zones

International audienceDehydration of antigorite in subduction zones releases a large amount of aqueous fluid and volatile elements, which can potentially oxidize the mantle wedge. The redox capacity of three synthetic serpentinites with variable Fetotal, Fe3+ and S− contents is investigated using XANES spectroscopy at both, Fe and S K-edges. Experiments are performed between 450 and 900 °C, at 2 GPa and; conditions similar to those encountered in subduction zones.Redox reactions in the synthetic serpentinites, which involve Fe and S can be summarized as follows: 1) the reduction of (S−)-pyrite into (S2−)-pyrrhotite (∼450 °C), with ∼4.4 mg/g of the sulfur degassed most likely as H2S, 2) the consumption of magnetite that reacts with antigorite to form Fe-rich olivine (<500 °C), 3) the reduction of (Fe3+)-antigorite into (Fe2+)-antigorite (∼580 °C), occurring about 100 °C below the temperature of antigorite breakdown, 4) the main (Fe2+)-antigorite breakdown that forms olivine and enstatite (∼675 °C), and 5) the decomposition of minor amounts of (Fe2+/3+)-clinochlore (∼800 °C). The bulk Fe3+/Fetotal ratio is found to decrease with run temperature from ∼0.82–0.97 depending on the hydrous starting material, down to 0.1–0.2 in the high-temperature anhydrous assemblages.The evolution of mineral modes and Fe3+/Fetotal with temperature in our synthetic samples shows similar trends to what has been reported in serpentinite rocks collected, for example, along a metamorphic transect in the western Alps. We show that a large amount of O2-equivalent – up to 10 mol/kg of rock – can be generated at temperature around 450 °C due to the presence of oxides and sulfides such as magnetite and pyrite. Owing to the poor capacity of aqueous fluid to transfer redox conditions, we surmise that this O2-equivalent is “consumed” at the scale of the lithospheric-mantle top which is partially serpentinized and therefore bear strong redox gradients

DANTE Digital Pulse Processor for XRF and XAS experiments

DANTE is a new Digital Pulse Processor (DPP) developed for fluorescence detectors, like silicon drift detectors (SDDs) or High Purity Germanium detectors (HPGe), used in X-ray Fluorescence (XRF) and X-ray Absorption Spectroscopy (XAS) experiments at synchrotron facilities. Its main features are its optimal energy resolution and peak stability for detector count rate values up to 1-2 Mcps, and its enhanced rejection of pile-up events. In this paper, we present the first complete evaluation of DANTE performance in SOLEIL synchrotron facility. DANTE has been tested in laboratory with an X-ray generator source and in different experiments at LUCIA and PUMA beamlines at SOLEIL.Comment: Manuscript submitted to JINST, 22 pages, 20 figures. v02: Corrected version. v03: Referee comments include

Determination of Fe3+/ΣFe of olivine-hosted melt inclusions using Mössbauer and XANES spectroscopy

co-auteur étrangerInternational audienceIron speciation is linked to oxygen fugacity; hence the Fe3+/ΣFe ratio of glasses can reveal the oxygen fugacity of the system where they last equilibrated. Previous studies using X-ray Absorption Near Edge Structure (XANES) spectroscopy in silicate glasses and olivine-hosted melt inclusions have shown that arc basalts are more oxidized than mid-ocean ridge basalts (MORB) and oceanic island basalts (OIB). However, Cottrell et al. (2018) recently demonstrated that hydrous glasses can experience beam-induced oxidation during XANES analysis, leading to an overestimation of their Fe3+/ΣFe ratios. Here, we determined Fe3+/ΣFe ratios in olivine-hosted melt inclusions from various arc, MORB and OIB localities by Mössbauer and XANES spectroscopy. We carried out a careful evaluation of beam damage during XANES measurements that included detailed analysis of consecutive XANES spectra and collection of time series on hydrous basaltic and basanitic glasses using different radiation doses. Fe3+/ΣFe ratios obtained using both spectroscopy methods on the same sample set allowed us to confirm the oxidation state of those magmas and the reliability of our approach to avoid the effect of beam-induced oxidation during XANES analysis. Our results show that melt inclusions from MORBs, OIBs and arc basalts display mean Fe3+/ΣFe ratios of 0.10 ± 0.05 (2σ; n = 5), 0.13 ± 0.05 (2σ; n = 2) and 0.25 ± 0.15 (2σ; n = 19), respectively, while Mount Etna melt inclusions display a mean Fe3+/ΣFe ratio of 0.26 ± 0.05 (2σ; n = 7). These results confirm that arc magmas are more oxidized than those from hot spots and mid-ocean ridges

Imagerie X en biologie sur la ligne de lumière LUCIA

La fluorescence X est une technique permettant de déterminer la composition élémentaire d’un échantillon. En travaillant avec un faisceau de rayon X focalisé et en déplaçant l’échantillon par rapport au faisceau, des cartographies de fluorescence X peuvent être enregistrées. La ligne "LUCIA" (Ligne Utilisée pour la Caractérisation par Imagerie et Absorption [1], [2]) au synchrotron SOLEIL permet de réaliser ces d’expériences de micro-fluorescence (μXRF) dans le domaine des rayons X dits "tendres" (0.8-8 kev, informations au seuil K des éléments du Na au Fe et au seuil L du Ni au Ga ainsi qu'au seuil M des terres rares et des actinides). Afin d’enregistrer cartes élémentaires de µXRF, l’énergie des rayons X est sélectionnée en accord avec les éléments que l’on souhaite cartographier et le faisceau de rayons X, focalisé à 3 x 3 µm², est envoyé sur un échantillon hétérogènes placé sur une platine de translation x-z. Les informations obtenues permettent de déterminer la localisation des éléments, leur abondance relative, ainsi que les autres éléments auxquels ils sont éventuellement associés. La station de mesure est équipée d’un cryostat permettant de travailler aux températures de l’azote ou de l’hélium liquide. Ce dispositif est particulièrement intéressant pour les échantillons biologiques car il présente l’avantage d’éviter la détérioration de l’échantillon sous irradiation du faisceau de rayons X et de pouvoir analyser des coupes fines (15-30 µm) de tissus animaux ou végétaux préparées en cryo-microtomie sans aucun traitement chimique ni marquage préalable. Le mode d’acquisition en « FlyScan », récemment implémenté sur la ligne LUCIA, permet un gain de temps considérable par rapport au mode précédent d’acquisition en point par point. Il devient ainsi possible d’augmenter le nombre d’échantillons cartographiés pour obtenir des répétitions. Sur la ligne LUCIA, la cartographie µXRF peut être combinée à des expériences de micro-absorption X (µXAS) afin d’obtenir des informations sur l'environnement local des éléments analysés (état d’oxydation, coordinence, géométrie locale). Des points d'intérêt sont sélectionnés en fonction de la distribution des éléments obtenue sur une carte de µXRF préalablement enregistrée et un spectre XAS est collecté. Dans le domaine de la biologie, différents types d’application sont possibles comme la détermination de la distribution et de l’état d’oxydation des éléments métalliques dans des tissus ou cellules (nanoparticules, cations, complexes,…). L’analyse des éléments plus légers tels que le Cl, le S ou le P est particulièrement adaptée sur cette ligne. Deux exemples d’application en lien avec l’assimilation du P par les plantes sont présentés : le premier concerne des racines et nodules de légumineuses et le second des racines de pin mycorhizées. [1] Vantelon et al. 2016. The LUCIA beamline at SOLEIL. J. Synchrotron Radiat., 23, 635–640. [2] www.synchrotron-soleil.fr/Recherche/LignesLumiere/LUCIA

L’Université Technique du Moyen-Orient, Ankara

A nonintrusive diagnostics technique for flame soot based on near-infrared emission spectrometry présentée devan