Les mots étrangers de Vladimir Nabokov

Cette thèse démontre le caractère fondamental du multilinguisme de Nabokov dans son écriture en anglais : après avoir été un auteur prolifique en russe, l écrivain a opéré une transition linguistique et n a plus composé ses romans qu en langue anglaise. Cette dernière ne peut nullement être réduite à une langue seconde puisque Nabokov a su l écrire avant le russe et la parlait depuis l enfance. Il a par ailleurs bénéficié d une éducation polyglotte puisqu il maîtrisait parfaitement le français. Cette thèse étudie le style de Nabokov en soulignant sa créativité linguistique et en examinant le rôle fondateur que la traduction a joué dans le positionnement de ses différentes langues les unes par rapport aux autres. L identité bilingue de Nabokov a pour conséquence que son écriture est déviante, mais aussi défiante : elle est marquée d étrangeté (le caractère de ce qui est étrange) et d étrangéité (ce qui est étranger). Dans ses romans, la langue anglaise voit surgir en son sein des mots étrangers qui, typographiquement et sémantiquement, déstabilisent la lecture : le phénomène de l alternance codique (ou code-switching) est au cœur de cette thèse et interroge le rapport entre l auteur tyrannique (Couturier) et son lecteur. La langue anglaise elle-même perd de sa familiarité et devient étrangère : le bilinguisme de Nabokov lui confère un statut d étranger dans la langue, ce qui lui permet de voir la violence du langage (Lecercle) et de la faire apparaître, notamment grâce à des calembours et des néologismes. Nabokov est ce que Deleuze appelle un grand écrivain à l aide d une formule proustienne : ses livres sont écrits dans une sorte de langue étrangère .This thesis shows how central Nabokov s multilingualism was to his prose in English: after authoring several works in Russian, the writer changed languages and then only wrote his novels in English. It was not merely a second language for him because Nabokov could write English before Russian and he had spoken it since childhood. Besides, he enjoyed a polyglot education and was fluent in French. This thesis studies Nabokov s style in English by focusing on his linguistic creativity and by examining the founding role that translation played in how his several tongues were going to position themselves in relation to one another. Nabokov s bilingual identity means that his writing both challenges and deviates from the norm: it is dappled with strangeness and foreignness. In his novels, foreign words irrupt in the midst of the English prose and, typographically and semantically, they destabilize the reading experience: code-switching is at the heart of this thesis and questions the relation between the narrator s tyranny (Couturier) and his reader. English itself loses its familiarity and becomes a foreign language: Nabokov s bilingualism means he is like a foreigner in this tongue; therefore he reveals the violence of language (Lecercle) and puts it into play through puns and neologisms. Nabokov is what Deleuze calls, thanks to a Proustian expression, a great writer: his books are written in a kind of foreign language .NANTERRE-PARIS10-Bib. élec. (920509901) / SudocSudocFranceF

Suppression by thimerosal of ex-vivo CD4+ T cell response to influenza vaccine and induction of apoptosis in primary memory T cells.

International audienceThimerosal is a preservative used widely in vaccine formulations to prevent bacterial and fungal contamination in multidose vials of vaccine. Thimerosal was included in the multidose non-adjuvanted pandemic 2009 H1N1 vaccine Panenza. In the context of the analysis of the ex-vivo T cell responses directed against influenza vaccine, we discovered the in vitro toxicity Panenza, due to its content in thimerosal. Because thimerosal may skew the immune response to vaccines, we investigated in detail the ex-vivo effects of thimerosal on the fate and functions of T cells in response to TCR ligation. We report that ex-vivo exposure of quiescent or TCR-activated primary human T cells to thimerosal induced a dose-dependent apoptotic cell death associated with depolarization of mitochondrial membrane, generation of reactive oxygen species, cytochrome c release from the mitochondria and caspase-3 activation. Moreover, exposure to non-toxic concentrations of thimerosal induced cell cycle arrest in G0/G1 phase of TCR-activated T cells, and inhibition of the release of proinflammatory cytokines such as IFN gamma, IL-1 beta, TNF alpha, IL-2, as well as the chemokine MCP1. No shift towards Th2 or Th17 cells was detected. Overall these results underline the proapoptotic effect of thimerosal on primary human lymphocytes at concentrations 100 times less to those contained in the multidose vaccine, and they reveal the inhibitory effect of this preservative on T-cell proliferation and functions at nanomolar concentrations

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Toxicité et effets immunomodulateurs du Thimerosal sur les effecteurs de la réponse immunitaire antigrippale

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Les mots étrangers

Ce numéro de la Revue LISA aborde la problématique de l’empreinte et l’emprunt des mots ou des phrases en langue étrangère dans divers textes littéraires et documents de civilisation du monde anglophone du XVIIIème siècle à nos jours. Les articles réunis ici étudient comment l’irruption d’une langue dans une autre met en jeu des tensions de familiarité et d’altérité, soulevant des questions identitaires qu’il s’agisse de genre, de nationalité, ou de culture socio-religieuse. Ces études ont pour ambition de montrer comment l’entrecroisement des langues nourrit la création littéraire et contribue à la construction d’un cadre culturel historique, géographique et social. Elles analysent la question de l’étranger dans la langue, au double sens de l’intrus dans une culture d’une autre langue que la sienne d’une part, et d’autre part de l’aspect insolite de la langue étrangère qui trouble l’homogénéité d’un texte d’une autre langue. This issue of the Revue Lisa focuses on the use of foreign words and phrases in a variety of literary texts and civilisation documents in English from the period spanning the 18th century to the present. The articles presented here study how the intrusion of a foreign language in a text authored in English puts into play complex tensions of familiarity and otherness. That friction between languages also raises questions of identity related to gender and nationality, and the sense of belonging to a defined socio-religious community. The aim of these studies is to show how the interaction between English and other languages enriches literary creation and helps construct the historical, geographical and social framework of a particular culture. It addresses the issue of the foreigner using a language which is not his own, and that of the foreignness of the words of others which are woven into a text in another language

Dose-dependent Toxicity of Panenza on Memory T cells specific for influenza vaccine.

<p>A- PBMC from patients vaccinated with the seasonal flu vaccine (Mutagrip) and the pandemic 2009 H1N1 vaccine (Pandemrix) were collected 21 days after vaccine administration. Cells (5×10⁵ per well) were stimulated for 5 days with Mutagrip or the nonadjuvanted pandemic 2009 H1N1 Panenza vaccine at the indicated concentrations (vaccine concentration is expressed as the final concentration of HA). Cells were also stimulated with CMV or EBV peptides at 0.25 μg/ml, tetanus toxoid (TT) or tuberculin PPD at 5 μg/ml. Cultures were pulsed with 1 μCi per well of [3H] thymidine over the final 16 h of culture and cell proliferation expressed in cpm. All tests were done in triplicate and results show the mean values for three patients. The bars indicate the mean and standard deviation. Asterisks indicate significant <i>P-</i>values (p = 0.03) for comparison of cultures stimulated with Panenza at 0.02 to 0.5 μg/ml to cultures stimulated with 0.01 μg/ml of Panenza (ANOVA test). B- PBMC from Pandemrix vaccinated patients were incubated with soluble Panenza at indicated concentrations, or added to plates coated overnight at 4°C with indicated concentrations of Panenza. H3TdR (1μCi/well) was added at day 4 and T-cell proliferation was assessed at day 5. The bars indicate the mean and standard deviation. Asterisks indicate significant <i>P-</i>values (* <0.05, ** <0.01, ***<0.001) for comparison of cultures stimulated with coated Panenza to cultures stimulated with soluble Panenza. C- PBMC from a patient vaccinated with Mutagrip and then with Pandemrix were incubated overnight with culture medium, Mutagrip or Panenza at 0.25 μg/ml and the percentage of apoptotic cells was determined by flow cytometry combining 7-AAD staining with CD3 and CD4 membrane detection. Dot plots represent the co-expression of CD4 and 7-AAD on gated CD3⁺ T cells. D- PBMC from a patient vaccinated with Mutagrip and Panenza were incubated overnight with either vaccine at various concentrations and the percentage of apoptotic (7-AAD⁺) cells within indicated subsets was determined combining 7-AAD staining with CD19, CD3, CD8, CD4, CD56, CD16 or CD14. B cells were CD3⁻CD19⁺, T cells were CD3⁺CD8⁺ or CD3⁺ CD4⁺, NK cells were CD3⁻CD56⁺CD16⁺, monocytes were CD3⁻CD19⁻CD14⁺.</p

Thimerosal induces cytochrome c release and caspase-3 activation.

<p>A- Confocal analysis of PBMC incubated 16 hours either in the presence of thimerosal (0.9 or 3 μg/ml), or with staurosporine (1 μg/ml) as a positive control. Cells were processed for cytochrome c staining (green) and co-stained with DAPI (blue) to detect nuclei modifications. B-C Western blot analysis of active caspase-3 expression in PBMC incubated for 16 h in medium (unstimulated) (B) or stimulated with anti-CD3 mAbs (C). The impact of indicated concentrations of thimerosal or staurosporine on active caspase-3 expression is shown, together with the influence of the broad caspase inhibitor QVD and the anti-oxidant NAC.</p

Impact of thimerosal on cytokine and chemokine release upon TCR ligation.

<p>Pattern of cytokines and chemokines simultaneously quantified by multiplex bead assay arrays in supernatants from freshly isolated PBMC following 16-hour stimulation with anti-CD3/CD28 mAbs in the absence or presence of three different concentrations of thimerosal. The bars indicate the mean and standard deviation from experiments with three different donors. Asterisks indicate significant <i>P-</i>values (* <0.05, ANOVA test) for comparison with cultures without thimerosal.</p

Thimerosal inhibits T-cell proliferation and induces a G0/G1 cell cycle arrest.

<p>A- PBMC from a HD were labeled with CFSE and stimulated during 4 days with anti-CD3/CD28 mAbs in the presence or not of thimerosal. At the end of the culture, cells were co-stained with anti-CD4 mAbs and 7-AAD, and the rate of proliferation in CD4 T cells was determined (upper panel) combined with their priming for apoptosis (lower panel). B- The experiment of panel A was performed with 7 different HD and the bars indicate the mean and standard deviation. The left panel shows the percentage of total proliferating cells, the middle panel shows the proliferation of living cells and the right panel shows the proliferation of dying cells. Asterisks indicate significant <i>P-</i>values (* <0.05, ANOVA test) for comparison of cultures stimulated in the presence of thimerosal at 180 ng/ml to cultures stimulated in the absence of thimerosal. C: Cell cycle analysis of PBMC stimulated with anti-CD3/CD28 mAbs in the presence of thimerosal at three different concentrations. The pie charts show the repartition of cells in the various phases of the cell cycle. D- Curves show the mean values from 7 HD, demonstrating the accumulation of cells in G0/G1 phase and the disappearance of cells in the S phase after exposure to increasing concentrations of thimerosal. Asterisks indicate significant <i>P-</i>values (** <0.01, ***0.001) for comparison of the proportions of cells in G0/G1 or in S phase with or without thimerosal.</p

ROS induction by Thimerosal in TCR-activated T cells and anti-apoptotic effect of NAC.

<p>A- PBMC from a HD were stimulated overnight with anti-CD3 mAbs in the presence of thimerosal at 3 μg/ml, and NAC (2.5 μM) was added in half of the cultures. ROS production was detected with HE, ΔY_m was assessed using the DiOC₆(3) probe, and apoptosis was measured with 7-AAD. The dot plots show combined analysis of ΔY_m and apoptosis or ΔY_m and ROS production on gated CD4⁺ T cells, in a representative experiment out of three experiments performed with three different HD. B- PBMC from a HD were either unstimulated (left panel) or stimulated overnight with anti-CD3 mAbs in the presence or absence of thimerosal at 3 μg/ml (right panel). The anti-oxidant NAC (2.5 μM) was added in some cultures. The percentages of CD4⁺ and CD4⁻ T cells with a concomitant drop in ΔY_m and increased oxidizing ability (DIOC₆^high 7-AAD^neg) under the indicated culture conditions are shown. The bars indicate the mean and standard deviation from 3 experiments with three different donors. Asterisks indicate significant <i>P-</i>values (** <0.001, ***0.0001) for comparison of cultures stimulated with thimerosal and NAC to cultures stimulated with thimerosal only.</p