Analysis of cellular responses of macrophages to zinc ions and zinc oxide nanoparticles: a combined targeted and proteomic approach

Two different zinc oxide nanoparticles, as well as zinc ions, are used to study the cellular responses of the RAW 264 macrophage cell line. A proteomic screen is used to provide a wide view of the molecular effects of zinc, and the most prominent results are cross-validated by targeted studies. Furthermore, the alteration of important macrophage functions (e.g. phagocytosis) by zinc is also investigated. The intracellular dissolution/uptake of zinc is also studied to further characterize zinc toxicity. Zinc oxide nanoparticles dissolve readily in the cells, leading to high intracellular zinc concentrations, mostly as protein-bound zinc. The proteomic screen reveals a rather weak response in the oxidative stress response pathway, but a strong response both in the central metabolism and in the proteasomal protein degradation pathway. Targeted experiments confirm that carbohydrate catabolism and proteasome are critical determinants of sensitivity to zinc, which also induces DNA damage. Conversely, glutathione levels and phagocytosis appear unaffected at moderately toxic zinc concentrations

Molecular responses of mouse macrophages to copper and copper oxide nanoparticles inferred from proteomic analyses

The molecular responses of macrophages to copper-based nanoparticles have been investigated via a combination of proteomic and biochemical approaches, using the RAW264.7 cell line as a model. Both metallic copper and copper oxide nanoparticles have been tested, with copper ion and zirconium oxide nanoparticles used as controls. Proteomic analysis highlighted changes in proteins implicated in oxidative stress responses (superoxide dismutases and peroxiredoxins), glutathione biosynthesis, the actomyosin cytoskeleton, and mitochondrial proteins (especially oxidative phosphorylation complex subunits). Validation studies employing functional analyses showed that the increases in glutathione biosynthesis and in mitochondrial complexes observed in the proteomic screen were critical to cell survival upon stress with copper-based nanoparticles; pharmacological inhibition of these two pathways enhanced cell vulnerability to copper-based nanoparticles, but not to copper ions. Furthermore, functional analyses using primary macrophages derived from bone marrow showed a decrease in reduced glutathione levels, a decrease in the mitochondrial transmembrane potential, and inhibition of phagocytosis and of lipopolysaccharide-induced nitric oxide production. However, only a fraction of these effects could be obtained with copper ions. In conclusion, this study showed that macrophage functions are significantly altered by copper-based nanoparticles. Also highlighted are the cellular pathways modulated by cells for survival and the exemplified cross-toxicities that can occur between copper-based nanoparticles and pharmacological agents

Sensing of Dietary Lipids by Enterocytes: A New Role for SR-BI/CLA-1

BACKGROUND: The intestine is responsible for absorbing dietary lipids and delivering them to the organism as triglyceride-rich lipoproteins (TRL). It is important to determine how this process is regulated in enterocytes, the absorptive cells of the intestine, as prolonged postprandial hypertriglyceridemia is a known risk factor for atherosclerosis. During the postprandial period, dietary lipids, mostly triglycerides (TG) hydrolyzed by pancreatic enzymes, are combined with bile products and reach the apical membrane of enterocytes as postprandial micelles (PPM). Our aim was to determine whether these micelles induce, in enterocytes, specific early cell signaling events that could control the processes leading to TRL secretion. METHODOLOGY/PRINCIPAL FINDINGS: The effects of supplying PPM to the apex of Caco-2/TC7 enterocytes were analyzed. Micelles devoid of TG hydrolysis products, like those present in the intestinal lumen in the interprandial period, were used as controls. The apical delivery of PPM specifically induced a number of cellular events that are not induced by interprandial micelles. These early events included the trafficking of apolipoprotein B, a structural component of TRL, from apical towards secretory domains, and the rapid, dose-dependent activation of ERK and p38MAPK. PPM supply induced the scavenger receptor SR-BI/CLA-1 to cluster at the apical brush border membrane and to move from non-raft to raft domains. Competition, inhibition or knockdown of SR-BI/CLA-1 impaired the PPM-dependent apoB trafficking and ERK activation. CONCLUSIONS/SIGNIFICANCE: These results are the first evidence that enterocytes specifically sense postprandial dietary lipid-containing micelles. SR-BI/CLA-1 is involved in this process and could be a target for further study with a view to modifying intestinal TRL secretion early in the control pathway

Rire en classe : le cas d’un enseignant en situation inédite

Cette recherche s’intéresse à la mise en œuvre de l’humour dans un contexte spécifique : une salle de cours informatique où un enseignant enseigne l’utilisation d’un logiciel alors que ce dernier n’est pas adapté à l’un des étudiants du groupe qui est déficient visuel. L’enseignant n’est pas préparé à cette situation et doit alors improviser. L’observation directe de cette séance de cours nous permettra de mettre en exergue les fonctions du rire et de l’humour dans cette situation. Nous verrons comment l’enseignant y a recours pour dépasser son embarras et instaurer/conserver une atmosphère de travail agréable.This research focuses on using humor in a specific context: a classroom where a teacher teaches the use of software so that it is not suitable for one of the students who is visually impaired. The teacher is not prepared for this situation and must improvise. Direct observation during this session will highlight the functions of laugh and humor in this situation. We’ll see how teacher uses them to overcome his embarrassment and establish / maintain a pleasant working atmosphere

Computer-mediated learning : the case of visually impaired students

Cette recherche porte sur les apprentissages médiés par les TICE chez les étudiants déficients visuels. La particularité de ces apprentissages réside dans la nécessité d’utiliser des outils informatiques adaptés afin de pallier le manque de vision. La dernière décennie s’inscrit dans un contexte où le cadre législatif en faveur des personnes en situation de handicap se met en place en parallèle d’une expansion du numérique. Nous prenons appui sur un corpus audio et audiovisuel issu d’expérience d’apprentissage in situ et d’entretiens semi-qualitatifs. Grâce à un système d’analyse pluridisciplinaire (analyse de contenu, analyse du discours, sociocognitivisme) notre étude vise, d’une part, à analyser quels sont les freins humains et techniques subsistant dans l’apprentissage de ces étudiants. D’autre part, nous nous intéressons aux stratégies d’adaptation mises en oeuvre par les étudiants mais aussi par les acteurs de la vie universitaire afin de pallier la déficience visuelle. Enfin, en explorant les différentes modalités sensorielles, nous nous attachons à apporter des pistes de réflexion et des préconisations visant à améliorer les conditions d’apprentissage.This research deals with learning and ICT with visually impaired students. This learning particularity needs to use appropriate tools to supply the lack of vision. During the last decade, the legislative framework for people with disabilities has been set up in parallel with an expansion of digital technology. We have based our work on audio and audiovisual data with in situ learning experience and semi-qualitative interviews. Using a system of multidisciplinary analysis (content analysis, discourse analysis, sociocognitivism), our study analyze first what are the human and technical obstacles remaining in the learning of these students. Second, we focus on strategies used by students but also by those involved in university environment to compensate a visual impaired. Finally, exploring the different sensory modalities, we strive to provide reflection and recommendations for improving these learning conditions

L’étudiant déficient visuel dans l’enseignement supérieur : ses rapports à l’institution, ses relations avec les enseignants et ses pairs

This research is interested in students with visual disabilities inclusion since the law « 2005» about equal opportunity. More specifically, we are interested in their relationship with the institution, theirs peers and theirs teachers. The results indicate that even if this law, by the creation of disabled student services office, facilitates the relationship with the institution, the social handicap representations can influence the relationships between the persons. These representations, impregnated by stereotypes, can constitute a difficulty in their inclusion with their non-disabled peers as well as a feeling of faintness in their relationship with their teachers. Therefore, communication difficulties can lead to impeding request for adaptation required to access to the educational resources

La pédagogie différenciée : un processus coopératif entre enseignant et étudiant déficient visuel ?

Cette recherche s'intéresse à la mise en œuvre d'une pédagogie différenciée dans le cadre d'un cursus de licence sur les nouvelles technologies de l’information et de la communication suivi par un étudiant non-voyant. Comment les enseignants qui ne sont pas informés des adaptations nécessaires à ce profil étudiant font-ils face à cette situation inédite ? Nous avons mis en place une méthodologie d'observation participante en tant que tuteur pédagogique auprès d'un étudiant non-voyant afin de recueillir des données nous permettant d'analyser les stratégies adaptatives des enseignants. Les premiers résultats nous permettent d'envisager la coopération enseignant/étudiant non-voyant comme principal facteur de réussite d'une pédagogie différenciée