Recognition-based memory through familiarity assessment in severe Alzheimer’s disease

peer reviewe

Etude de couplage de procédés pour l élimination des COV en atmosphère confinée

L air confiné dans nos lieux de vie contient de nombreux polluants très faiblement concentrés. L amélioration de la qualité de l air intérieur passe donc par son traitement à l aide d un couplage de procédés. Cette thèse porte sur l étude du couplage de la biofiltration par un compost de déchets verts et de l adsorption sur charbon actif. L efficacité du procédé comportant une étape de biofiltration puis une étape d adsorption, pour traiter un effluent micropollué en toluène et présentant des pics de concentration pendant quelques heures par jour, a été évaluée expérimentalement. A ces niveaux de concentration, l efficacité du biofiltre est très forte, mais sensible aux variations brutales de charge massique en polluant. L étape d adsorption qui suit permet de maintenir l efficacité globale de traitement. Une expérience complémentaire sur le traitement d un effluent micropollué par biofiltration a montré le développement de microorganismes sur le milieu. La quantité d ammonium et la teneur en eau sont deux paramètres susceptibles d affecter les performances et la durée de vie du milieu, et doivent donc être contrôlés. L étude expérimentale de l adsorption du toluène sur le charbon actif, dans des conditions de très faibles concentrations, comme rencontrées dans l air intérieur, a conduit à la détermination du coefficient de Henry et des paramètres cinétiques d adsorption et de désorption du modèle de Thomas. La modélisation a mis en évidence que, pour ces faibles concentrations, le phénomène de désorption semble beaucoup plus lent et qu un modèle d équilibre pour la courbe de percée n est pas adapté : la cinétique globale d adsorption doit être prise en compte.The confined air in work and living places contains many pollutants at very low concentrations. So, the improvement of indoor air quality requires its treatment. This thesis deals with the study of a process coupling biofiltration by a green waste compost and adsorption onto activated carbon. The effectiveness of a process implementing a biofiltration stage followed by an adsorption stage, fed with a toluene micropolluted effluent, exhibiting peaks of concentration during a few hours every day, has been experimentally evaluated. At those levels of concentration, it appears that the removal efficiency of the biofilter is very high, but sensitive to brutal changes in pollutant mass loading. But the following adsorption stage contributes to maintain a high global treatment efficiency. An additional experiment implementing the treatment of a micropolluted effluent by several biofiltration columns has shown the development of microorganisms on compost. The amount of ammonium and the moisture content are two parameters liable to reduce the performances and the lifetime of the medium, and so have to be controlled. The experimental study of the adsorption of toluene onto activated carbon, at very low concentrations, as encountered indoor, leads to the determination of the Henry coefficient and the adsorption and desorption kinetic parameters of Thomas model. The modelling underlines that at those low concentrations, the desorption phenomenon seems to be slower than at high concentrations, and that an equilibrium model cannot fit the experimental breakthrough curve data : the global kinetic has to be taken into account.PAU-BU Sciences (644452103) / SudocSudocFranceF

Approches génotoxiques et transcriptomiques In Vitro pour la détermination de seuils de produits induisants des lésions oxydatives à l'ADN

Dans le contexte de l évaluation du risque, l existence d un mécanisme à seuil pour les produits générant un stress oxydant. Les espèces réactives de l oxygène peuvent induire des lésions oxydatives à l ADN en débordant les systèmes de défense cellulaires. Nous avons travaillé in vitro sur la lignée lymphoblastoïde humaine TK6 avec 3 agents oxydants (bromate de potassium, bléomycine, peroxyde d hydrogène). Le 1er objectif (approche génotoxique) a été d étudier les relations dose-effet afin de rechercher l existence de seuils. Différents NOELs ont été déterminés. Le 2nd objectif (approche transcriptomique) a été d identifier les mécanismes d action. Les principales voies de signalisation varient avec les doses et sont cohérentes avec la réponse aux dommages à l ADN et au stress cellulaire. L ensemble de ce travail montre donc la nécessité d une analyse globale combinant les techniques de toxicologie génétique traditionnelles et de toxicologie génomique.In the context of risk assessment, the existence of a thresholded-mechanism is suspected for some genotoxins inducing oxidative stress. Reactive oxygen species can generate oxidative DNA damage when cellular defence systems become overloaded. We worked in vitro on the human lymphoblastoid TK6 cell line with 3 oxidizing agents (potassium bromate, bleomycin, hydrogen peroxide). The 1st objective (genotoxic approach) was to investigate the dose-effect relationships to assess the existence of thresholds. Various NOELs were determined. The 2nd objective (transcriptomic approach) was to identify the mechanisms of action. The main signaling pathways depend on the dose and reflect the cellular response to DNA damage and cellular stress. Overall, this work shows the usefulness of a global analysis with the combination of standard genotoxicity assays and gene expression profiling technology.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Porous Maltodextrin-Based Nanoparticles: A Safe Delivery System for Nasal Vaccines

Vaccination faces limitations, and delivery systems additionally appear to have potential as tools to trigger protective immune responses against diseases. The nanoparticles studied are cationic maltodextrin-based nanoparticles with an anionic phospholipid core (NPL); they are a promising antigen delivery system, and their efficacy as drug vectors against complex diseases such as toxoplasmosis has already been demonstrated. Cationic compounds are generally described as toxic; therefore, it is of interest to evaluate the behavior of these NPL in vitro and in vivo. Here, we studied the in vitro toxicity (cytotoxicity and ROS induction in intestinal and airway epithelial cell lines) and the in vivo tolerability and genotoxicity of these nanoparticles administered by the nasal route to a rodent model. In vitro, these NPL were not cytotoxic and did not induce any ROS production. In vivo, even at very large doses (1000 times the expected human dose), no adverse effect and no genotoxicity were observed in lungs, stomach, colon, or liver. This study shows that these NPL can be safely used

Vectorization by nanoparticles decreases the overall toxicity of airborne pollutants.

Atmospheric pollution is mainly composed of volatile pollutants and particulate matter that strongly interact. However, their specific roles in the induction of cellular toxicity, in particular the impact of the vectorization of atmospheric pollutants by ultrafine particles, remains to be fully elucidated. For this purpose, non-toxic poly-lactic co-glycolic acid (PLGA) nanoparticles were synthesized and three pollutants (benzo(a)pyrene, naphthalene and di-ethyl-hexyl-phthalate) were adsorbed on the surface of the nanoparticles in order to evaluate the toxicity (cytotoxicity, genotoxicity and ROS induction) of these complexes to a human airway epithelial cell line. The adsorption of the pollutants onto the nanoparticles was confirmed by HPLC analysis. Interestingly, the cytotoxicity assays (MTT, LDH and CellTox Green) clearly demonstrated that the vectorization by nanoparticles decreases the toxicity of the adsorbed pollutants. Genotoxicity was assessed by the micronucleus test and the comet assay and showed no increase in primary DNA damage or in chromosomal aberrations of nanoparticle vectorized pollutants. Neither cytotoxicity nor genotoxicity was correlated with ROS induction. To conclude, our results indicate that the vectorization of pollutants by nanoparticles does not potentiate the toxicity of the pollutants studied and that, on the contrary, adsorption onto nanoparticles could protect cells against pollutants' toxicity

Les silex fossilifères (invertébrés marins et plantes terrestres) du Crétacé supérieur de Claix (Charente)

International audienceFossiliferous flint accumulations have been discovered in surface deposits at Claix, in Charente (SW France). These silicifications come both from alterites or limestones with flints, and from Palaeolithic or Neolithic habitats. A first part of the flints, beige or brown, is rich in bryozoans, pectinids and oysters Ceratostreon pliciferum Dujardin. Strongly alterated (oxydized, whitened) and scattered on large agricultural surfaces (fields, vines), they constitute relict nodules probably resulting from the secondary silicification of local shelly limestones of the Late Coniacian series during Palaeogene climatic weathering. Other silicified blocks (sandstones and flints) are devoid of oysters but very rich in plant fossils (angiosperms, conifers, and ferns). They have been observed both in sub-primary position, extracted from their alterites or limestones by plowings, and in archaeological context within Palaeolithic or Neolithic habitats. Their dating is difficult because a variable diachronism can exist between these different flints with plants, more or less anthropized. The presence of spatangoid echinoids, such as “Periaster” conicus d’Orbigny or “P.” oblongus d’Orbigny in the flints bearing plants argues for a Late Turonian dating. However, the geological synthesis of the regional Cretaceous series reveals occurrences of lignitic clay or marls both in the uppermost Turonian of Dordogne and in the lowermost Coniacian of Charente. Thus, the flints with plants of Claix could come not only from in situ or relict primary silicifications of uppermost Turonian deposits but from secondary silicifications of lowermost Coniacian deposits too (Palaeogene neoformation). The flora of the Claix flints is compared to the ones of Cretaceous flints from Archingeay-Les Nouillers (Charente-Maritime) and Torsac (Charente) and from the Late Cretaceous lignitic clay of Charente, Charente-Maritime and Dordogne.Des accumulations de silex particulièrement fossilifères ont été découvertes en gisements de surface sur la commune de Claix, en Charente (SO France). Ces silicifications proviennent, d’une part, d’altérites ou de calcaires à silex, d’autre part, de stations paléolithiques et néolithiques. Une partie de ces silex, de teinte beige à brune, est riche en bryozoaires, pectinidés et huîtres Ceratostreon pliciferum Dujardin. À la fois très altérés (oxydés, fortement patinés) et dispersés sur de vastes surfaces agricoles (champs, vignes), ils constituent des nodules relictes résultant vraisemblablement de la silicification secondaire des calcaires lumachelliques du Coniacien supérieur local lors de processus d’altérations paléogènes. D’autres blocs siliceux (quartzite, grès et silex) sont dépourvus d’huîtres mais très riches en restes végétaux (angiospermes, conifères et fougères). Ils ont été observés à la fois en position sub-primaire, arrachés par les labours de leur gangue carbonatée ou altéritique, et en contexte archéologique au sein de sites paléo- ou néolithiques. Leur datation est complexe car un diachronisme plus ou moins important peut exister entre ces différents silex à plantes anthropisés. La présence d’oursins spatangues de type « Periaster » conicus d’Orbigny ou « P. » oblongus d’Orbigny en association avec des plantes dans certains nodules siliceux est un argument en faveur d’une datation Turonien supérieur. Cependant, la synthèse géologique de la série crétacée régionale révèle l’existence d’argiles ou marnes ligniteuses tant dans le Turonien terminal en Dordogne que dans le Coniacien basal en Charente. Les silex à plantes de Claix pourraient donc provenir non seulement de silicifications primaires in situ ou relictes de faciès turoniens sommitaux mais aussi de silicifications secondaires de faciès coniaciens basaux (néoformations paléogènes). Leur flore est comparée à celles des silex crétacés à plantes d’Archingeay-Les Nouillers (Charente-Maritime) et Torsac (Charente) et celles des argiles ligniteuses du Crétacé supérieur de Charente, de Charente-Maritime et de Dordogne

Influence of the surface charge of PLGA nanoparticles on their in vitro genotoxicity, cytotoxicity, ROS production and endocytosis

International audienceWith the ongoing commercialization of nanotechnology products, human exposure to nanoparticles (NPs) is set to increase dramatically and an evaluation of their potential adverse effects is essential. Surface charge, among other physico-chemicals parameters, is a key criterion that should be considered when using a definition for nanomaterials in a regulatory context. It has recently been recognized as an important factor in determining the toxicity of NPs; however, a complete understanding of the mechanisms involved is still lacking. In this context, the aim of the present study was to investigate the influence of the surface charge modification of NPs on in vitro toxicity assays. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles bearing different surface charges, positive(+), neutral(n) or negative(-), were synthesized. In vitro genotoxicity assays (micronucleus and comet assays) coupled with an assessment of cytotoxicity, were performed in different cell lines (L5178Y mouse lymphoma cells, TK6 human B-lymphoblastoid cells and 16HBE14o- human bronchial epithelial cells). Reactive oxygen species (ROS) production and endocytosis studies were also performed. Our results showed that PLGA(+) NPs were cytotoxic. They are endocytosed by the clathrin pathway and induced ROS in the three cell lines. They led to chromosomal aberrations without primary DNA damage in 16HBE14o- cells, suggesting that aneuploidy may be considered as an important biomarker when assessing the genotoxic potential of NPs. Moreover, 16HBE14o- cells seem to be more suitable for the in vitro screening of inhaled NPs than the regulatory L5178Y and TK6 cells

When amnesic patients learn new melodies: a comparative analysis between Alzheimer’s Disease and Korsakoff’s Syndrome

peer reviewe

Altered intrinsic connectivity of the auditory cortex in congenital amusia

International audienceCongenital amusia, a neurodevelopmental disorder of music perception and production, has been associated with abnormal anatomical and functional connectivity in a right frontotemporal pathway. To investigate whether spontaneous connectivity in brain networks involving the auditory cortex is altered in the amusic brain, we ran a seed-based connectivity analysis, contrasting at-rest functional MRI data of amusic and matched control participants. Our results reveal reduced frontotemporal connectivity in amusia during resting state, as well as an overconnectivity between the auditory cortex and the default mode network (DMN). The findings suggest that the auditory cortex is intrinsically more engaged toward internal processes and less available to external stimuli in amusics compared with controls. Beyond amusia, our findings provide new evidence for the link between cognitive deficits in pathology and abnormalities in the connectivity between sensory areas and the DMN at rest