bluuebunny/crossref_metadata_2025_split huggingface dataset:
La validité de la notion de « handicap linguistique » en question
Authors: Guérin Emmanuelle 
Published: February 2014

L’auteure analyse de façon critique la notion de « handicap linguistique » pour mettre en lumière les arguments sur lesquels elle se fonde. Il s’agit de montrer qu’elle n’a de valeur qu’en discours et ne renvoie en aucun cas à un déficit de compétences des élèves concernés. Elle s’interroge sur le rôle de l’école en particulier et de la société en général dans la persistance à stigmatiser et, d’une certaine manière, à contraindre à l’échec scolaire, certains individus. L’étude s’appuie sur des entretiens avec des enfants, des adolescents et des jeunes adultes, à priori concernés par le « handicap linguistique », pour montrer comment ils intègrent et participent malgré eux, malgré la réalité des pratiques langagières appréhendable, au maintien d’une telle catégorisation, bien qu’elle leur soit défavorable.
Prendre en compte les pratiques personnelles d'écriture numérique des élèves en lycée professionnel
Authors: Perret Cécile , Massart-Laluc Vincent 
Published: February 2014

Les inégalités persistent au sein de l’école qui, malgré les ambitions affichées, peine à réaliser sa mission d’émancipation et à rendre réelle l’égalité des chances, notamment en ce qui concerne les pratiques d’écriture numérique. La réflexion proposée s’appuie sur une enquête auprès d’élèves de lycée professionnel. L’objectif est de mieux saisir quelles sont leurs pratiques d’écriture numérique, afin de construire avec et à partir d’elles des contenus d’enseignements et une réflexion didactique propre à réduire la fracture d’usage. L’enquête met en lumière certains savoirs déjà-là sur lesquels peut s’appuyer le travail didactique du professeur de français : recherche lexicale, réécriture. L’article tente de situer sur un schéma les nouveaux types d’écrits à l’œuvre dans les pratiques numériques, par rapports aux discours scolaires plus traditionnels, et s’interroge sur les possibles transferts de compétences dans les activités et dispositifs scolaires déjà en vigueur et encore à développer.
Une lecture junguienne de la littérature médiévale
Authors: Hincapié Leonardo 
Published: February 2014

Les lectures psychanalytiques de la littérature ont fait bien du chemin tout au long du XXe siècle. La psychologie analytique, créée par Carl Gustav Jung, a une relation de base indispensable avec les notions de cette nouvelle science humaine, mais ses approches critiques de la littérature (et de l’art en général) ont été peu nombreuses. À partir des concepts fondateurs utilisés par Jung, notamment de son explication du fonctionnement des symboles et des mythes, on essaiera de comprendre quel nouveau regard sa théorie permet de porter sur l’œuvre littéraire médiévale.
Liminalité et performance : de l’anthropologie de Victor Turner aux Folies Tristan
Authors: Patera Teodoro 
Published: February 2014

Cet article propose un exemple d’approche anthropologique de la littérature, à travers l’utilisation des outils conceptuels de liminalité et performance empruntés à la théorie de Victor Turner et appliqués aux textes des Folies Tristan. La liminalité se présente comme le champ de la pure possibilité, elle est le trait qui signale une situation sociale prête à accueillir des retournements radicaux des structures présentes, où les composantes du système culturel avec ses symboles subissent une sorte de déconstruction-recomposition ludique opérée par les êtres liminaires, sujets qui refusent le principe d’identité, leur caractère primaire étant la métamorphose. Selon Turner, la performance est le moyen de réalisation de cette réécriture des codes culturels dans la zone grise de la liminalité : c’est à travers la mise en scène de son corps que l’être liminaire déstructure le système culturel et crée du nouveau à partir de ce qui est déjà connu. En analysant la manière dont ces catégories anthropologiques s’incarnent dans l’écriture des deux textes de la tradition tristanienne, cet article se propose d’éclaircir la logique dialogique que le personnage liminaire Tristan gère dans son rapport toujours conflictuel avec tous les personnages qui l’entourent et dans son édification d’un système alternatif au système actuel.
Industrialisation, désindustrialisation, ré-industrialisation en Europe
Authors: Raggi Pascal 
Published: February 2014

Au milieu des années 1960, avec environ 20 millions de tonnes produites par an, la France était le 4ème producteur européen d’acier derrière l’URSS, la RFA et le Royaume-Uni. Près des deux tiers de cette production étaient élaborés en Lorraine où 100 000 ouvriers et employés travaillaient dans les usines sidérurgiques. Moins d’une génération plus tard, la désindustrialisation, issue en grande partie par la crise économique des années 1970, conduit à un effondrement considérable des effectifs de la sidérurgie. Aujourd’hui, il n’y a plus que 8000 sidérurgistes dans la région. Mais, du milieu des années 1960 à l’aube du XXIe siècle, l’industrie sidérurgique régionale s’est aussi adaptée aux nouvelles conditions du marché mondial de l’acier. Cette adaptation est un élément d’un processus de ré-industrialisation. Pour la région Lorraine, la désindustrialisation – décrite comme une succession de licenciements massifs, de fermetures de sites et de destructions d’usines – et la ré- industrialisation – vue comme une adaptation à la mondialisation – peuvent être interprétées autant comme de profondes transformations sociales que comme des évolutions économiques.
La recherche et l’innovation, derniers remparts contre la désindustrialisation ?
Authors: Carbonell Mauve , Grinberg Ivan , Laparra Maurice 
Published: February 2014

La désindustrialisation touche depuis trente ans le secteur de l’aluminium en France. La plupart des usines françaises ont fermé et les enjeux économiques, devenus mondiaux, ont durablement transformé un secteur qui fut l'un des fleurons de l'industrie française. En 1959, le Laboratoire de recherches des fabrications (LRF), un centre de recherches sur l'électrolyse (de l’aluminium), à Saint-Jean-de-Maurienne, est créé à quelques mètres de l'usine productrice d'aluminium. Le LRF est l’unique laboratoire français et l’un des plus importants au monde dans son domaine. Seule de l'ancien modèle économique du XXe siècle, l'usine de Saint-Jean, démarrée en 1907, a survécu grâce à sa double fonction : production de métal et vitrine d'une technologie à succès. Cette longévité est-elle due à l'important centre de recherches auquel elle est reliée ? Est-ce son rôle d'usine-vitrine technologique qui lui a permis de résister ? Plus généralement, la recherche seule peut-elle permettre ou favoriser le maintien en France d'une activité industrielle que beaucoup voient condamnée ?
Involvement of Notch in Activation and Effector Functions of γδ T cells
Authors: Gogoi Dimpu , Dar Asif A. , Chiplunkar Shubhada V. 
Published: February 2014

Abstract
Notch signaling plays a pivotal role in cell fate decision and lineage commitment of lymphocytes. Although the role of Notch in CD4+ and CD8+ αβ T cells is well documented, there are no reports on how Notch signaling regulates effector functions of γδ T cells. γδ T cells are a minor fraction in the peripheral blood but are known to play a major role in defense against pathogens and tumors. In this study, we show that Notch receptors (mRNA and protein) are expressed in peripheral γδ T cells. Inhibition of Notch signaling by γ-secretase inhibitor inhibited the proliferation and IFN-γ secretion of γδ T cells in response to stimulation with phosphoantigens and anti-CD3 mAb. In the presence of γ-secretase inhibitor, the antitumor cytolytic ability of γδ T cells was inhibited with a decreased CD107a expression. Knockdown of Notch1 and Notch2 genes in γδ T cells using small interfering RNA inhibited their antitumor cytotoxic potential. Our study describes for the first time, to our knowledge, the role of Notch as an additional signal contributing to Ag-specific effector functions of γδ T cells.
Type I IFN Induces Binding of STAT1 to Bcl6: Divergent Roles of STAT Family Transcription Factors in the T Follicular Helper Cell Genetic Program
Authors: Nakayamada Shingo , Poholek Amanda C. , Lu Kristina T. , Takahashi Hayato , Kato Masanari , Iwata Shigeru , Hirahara Kiyoshi , Cannons Jennifer L. , Schwartzberg Pamela L. , Vahedi Golnaz , Sun Hong-wei , Kanno Yuka , O’Shea John J. 
Published: February 2014

Abstract
CD4+ T follicular helper cells (TFH) are critical for the formation and function of B cell responses to infection or immunization, but also play an important role in autoimmunity. The factors that contribute to the differentiation of this helper cell subset are incompletely understood, although several cytokines including IL-6, IL-21, and IL-12 can promote TFH cell formation. Yet, none of these factors, nor their downstream cognate STATs, have emerged as nonredundant, essential drivers of TFH cells. This suggests a model in which multiple factors can contribute to the phenotypic characteristics of TFH cells. Because type I IFNs are often generated in immune responses, we set out to investigate whether these factors are relevant to TFH cell differentiation. Type I IFNs promote Th1 responses, thus one possibility was these factors antagonized TFH-expressed genes. However, we show that type I IFNs (IFN-α/β) induced B cell lymphoma 6 (Bcl6) expression, the master regulator transcription factor for TFH cells, and CXCR5 and programmed cell death-1 (encoded by Pdcd1), key surface molecules expressed by TFH cells. In contrast, type I IFNs failed to induce IL-21, the signature cytokine for TFH cells. The induction of Bcl6 was regulated directly by STAT1, which bound to the Bcl6, Cxcr5, and Pdcd1 loci. These data suggest that type I IFNs (IFN-α/β) and STAT1 can contribute to some features of TFH cells but are inadequate in inducing complete programming of this subset.
Antigen-Dependent Integration of Opposing Proximal TCR-Signaling Cascades Determines the Functional Fate of T Lymphocytes
Authors: Wolchinsky Ron , Hod-Marco Moran , Oved Kfir , Shen-Orr Shai S. , Bendall Sean C. , Nolan Garry P. , Reiter Yoram 
Published: February 2014

Abstract
T cell anergy is a key tolerance mechanism to mitigate unwanted T cell activation against self by rendering lymphocytes functionally inactive following Ag encounter. Ag plays an important role in anergy induction where high supraoptimal doses lead to the unresponsive phenotype. How T cells “measure” Ag dose and how this determines functional output to a given antigenic dose remain unclear. Using multiparametric phospho-flow and mass cytometry, we measured the intracellular phosphorylation-dependent signaling events at a single-cell resolution and studied the phosphorylation levels of key proximal human TCR activation- and inhibition-signaling molecules. We show that the intracellular balance and signal integration between these opposing signaling cascades serve as the molecular switch gauging Ag dose. An Ag density of 100 peptide–MHC complexes/cell was found to be the transition point between dominant activation and inhibition cascades, whereas higher Ag doses induced an anergic functional state. Finally, the neutralization of key inhibitory molecules reversed T cell unresponsiveness and enabled maximal T cell functions, even in the presence of very high Ag doses. This mechanism permits T cells to make integrated “measurements” of Ag dose that determine subsequent functional outcomes.
Thiopalmitoylation of Altered Peptide Ligands Enhances Their Protective Effects in an Animal Model of Multiple Sclerosis
Authors: Cloake Nancy C. , Beaino Wissam , Trifilieff Elisabeth , Greer Judith M. 
Published: February 2014

AbstractPreviously, we have shown that conjugation of a palmitic chain via a thioester bond to a cysteine residue in weakly or nonencephalitogenic or neuritogenic peptides markedly enhances their ability to induce autoimmune disease in an MHC class II–restricted manner. From those studies, however, it was not clear whether thiopalmitoylation of the peptides was merely enhancing their disease-inducing potential or whether the lipid was itself playing a pathogenic role. To investigate this further, we have now tested the effects of thiopalmitoylation on MHC class II–restricted altered peptide ligands (APLs), which are normally protective in experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. We hypothesized that if thiopalmitoylation of a peptide merely enhances its innate potential, then thiopalmitoylated APLs (S-palmAPLs) should show enhanced protective effects. Alternatively, if thiopalmitoylation itself can make a peptide pathogenic, then S-palmAPLs should have decreased therapeutic potential. We synthesized APLs and corresponding S-palmAPLs and showed that the S-palmAPLs were much more effective than the nonconjugated APL at inhibiting the development of experimental autoimmune encephalomyelitis. This was due to several features of the S-palmAPL:S-palmAPL–primed cells show an enhanced ability to proliferate and produce the anti-inflammatory cytokine, IL-10, in vitro. Furthermore, the bioavailability of S-palmAPL was greatly enhanced, compared with the nonpalmitoylated APL, and S-palm APL was taken up more rapidly into dendritic cells and channeled into the MHC class II processing pathway. These results show that thiopalmitoylation of MHC class II–restricted peptides is a simple way to enhance their effects in vivo and could have wide therapeutic application.
IRF4 in Dendritic Cells Inhibits IL-12 Production and Controls Th1 Immune Responses against Leishmania major
Authors: Akbari Masoud , Honma Kiri , Kimura Daisuke , Miyakoda Mana , Kimura Kazumi , Matsuyama Toshifumi , Yui Katsuyuki 
Published: February 2014

Abstract
IRF4 is a transcription factor from the IRF factor family that plays pivotal roles in the differentiation and function of T and B lymphocytes. Although IRF4 is also expressed in dendritic cells (DCs) and macrophages, its roles in these cells in vivo are not clearly understood. In this study, conditional knockout mice that lack IRF4 in DCs or macrophages were generated and infected with Leishmania major. Mice lacking DC expression of IRF4 showed reduced footpad swelling compared with C57BL/6 mice, whereas those lacking IRF4 in macrophages did not. Mice with IRF4-deficient DCs also showed reduced parasite burden, and their CD4+ T cells produced higher levels of IFN-γ in response to L. major Ag. In the draining lymph nodes, the proportion of activated CD4+ T cells in these mice was similar to that in the control, but the proportion of IFN-γ–producing cells was increased, suggesting a Th1 bias in the immune response. Moreover, the numbers of migrating Langerhans cells and other migratory DCs in the draining lymph nodes were reduced both before and postinfection in mice with IRF4 defects in DCs, but higher levels of IL-12 were observed in IRF4-deficient DCs. These results imply that IRF4 expression in DCs inhibits their ability to produce IL-12 while promoting their migratory behavior, thus regulating CD4+ T cell responses against local infection with L. major.
GM-CSF–Responsive Monocyte-Derived Dendritic Cells Are Pivotal in Th17 Pathogenesis
Authors: Ko Hyun-Ja , Brady Jamie L. , Ryg-Cornejo Victoria , Hansen Diana S. , Vremec David , Shortman Ken , Zhan Yifan , Lew Andrew M. 
Published: February 2014

Abstract
Although multiple dendritic cell (DC) subsets have the potential to induce Th17 differentiation in vitro, the key DC that is critical in Th17 induction and Th17-mediated disease remains moot. In this study, we revealed that CCR2+ monocyte-derived DCs (moDCs), but not conventional DCs, were critical for in vivo Th17 induction and autoimmune inflammation. Functional comparison in vitro indicated that moDCs are the most potent type of Th17-inducing DCs compared with conventional DCs and plasmacytoid DCs. Furthermore, we demonstrated that the importance of GM-CSF in Th17 induction and Th17-mediated disease is its endowment of moDCs to induce Th17 differentiation in vivo, although it has little effect on moDC numbers. Our findings identify the in vivo cellular targets that can be selectively manipulated to ameliorate Th17-mediated inflammatory diseases, as well as the mechanism of GM-CSF antagonism in such diseases.
A Direct and Nonredundant Role for Thymic Stromal Lymphopoietin on Antiviral CD8 T Cell Responses in the Respiratory Mucosa
Authors: Shane Hillary L. , Klonowski Kimberly D. 
Published: February 2014

Abstract
Mucosally produced thymic stromal lymphopoietin (TSLP) regulates Th2 responses by signaling to dendritic cells and CD4 T cells. Activated CD8 T cells express the TSLP receptor (TSLPR), yet a direct role for TSLP in CD8 T cell immunity in the mucosa has not been described. Because TSLP shares signaling components with IL-7, a cytokine important for the development and survival of memory CD8 T cells in systemic infection models, we hypothesized that TSLP spatially and nonredundantly supports the development of these cells in the respiratory tract. In this study, we demonstrate that influenza infection induces the early expression of TSLP by lung epithelial cells with multiple consequences. The global loss of TSLP responsiveness in TSLPR−/− mice enhanced morbidity and delayed viral clearance. Using a competitive adoptive transfer system, we demonstrate that selective loss of TSLPR signaling on antiviral CD8 T cells decreases their accumulation specifically in the respiratory tract as early as day 8 after infection, primarily due to a proliferation deficiency. Importantly, the subsequent persistence of memory cells derived from this pool was also qualitatively and quantitatively affected. In this regard, the local support of antiviral CD8 T cells by TSLP is well suited to the mucosa, where responses must be tempered to prevent excessive inflammation. Taken together, these data suggest that TSLP uniquely participates in local immunity in the respiratory tract and modulation of TSLP levels may promote long-term CD8 T cell immunity in the mucosa when other prosurvival signals are limiting.
Inflammatory Cytokines Break Down Intrinsic Immunological Tolerance of Human Primary Keratinocytes to Cytosolic DNA
Authors: Chiliveru Srikanth , Rahbek Stine H. , Jensen Simon K. , Jørgensen Sofie E. , Nissen Sara K. , Christiansen Stig H. , Mogensen Trine H. , Jakobsen Martin R. , Iversen Lars , Johansen Claus , Paludan Søren R. 
Published: February 2014

Abstract
Keratinocytes are involved in protecting the body from infections and environmental challenges, but also in inflammatory conditions like psoriasis. DNA has emerged as a potent stimulator of innate immune responses, but there is largely no information of how keratinocytes respond to cytosolic DNA. In this study, we report that human keratinocytes are tolerant to cytoplasmic DNA. However, if treated with inflammatory cytokines, keratinocytes gained the capacity to respond to DNA through a mechanism antagonized by the antimicrobial peptide LL37, proposed to be involved in activation and regulation of skin inflammation. The DNA sensor IFN-inducible protein 16 (IFI16) colocalized with DNA and the signaling molecule stimulator of IFN genes (STING) in the cytoplasm only in cytokine-stimulated cells, correlating with recruitment of the essential kinase TANK-binding kinase 1. Moreover, IFI16 was essential for DNA-driven innate immune responses in keratinocytes. Finally, IFI16 was upregulated in psoriasis skin lesions and localized to the cytoplasm in a subpopulation of cells. Collectively, this work suggests that inflammatory environments in the skin can lead to breakdown of tolerance for DNA in keratinocytes, which could contribute to the development of inflammatory diseases.
IFN-γ–Producing and IL-17–Producing γδ T Cells Differentiate at Distinct Developmental Stages in Murine Fetal Thymus
Authors: Shibata Kensuke , Yamada Hisakata , Nakamura Masataka , Hatano Shinya , Katsuragi Yoshinori , Kominami Ryo , Yoshikai Yasunobu 
Published: February 2014

Abstract
γδ T cells develop at the double-negative (DN) 2 and DN3 stages and acquire functions to produce IL-17 and IFN-γ in fetal thymus. However, the relationship between differentiation stages and their functions was unclear. In this study, we found that, although IFN-γ–producing and IL-17–producing γδ T cells developed from DN2 cells, only IFN-γ–producing γδ T cells developed from DN3 cells, indicating the direct generation of IL-17–producing γδ T cells from the DN2 stage, not through the DN3 stage. Single-cell analysis revealed that DN2 cells contained heterogeneous γδ T cell precursors with or without an ability to develop IL-17 producers. Inactivation of B cell leukemia/lymphoma 11b, a zinc finger transcription factor responsible for transition from early to late stages of DN2 cells, completely abrogated the development of IL-17–producing γδ T cells, although a unique subset of IFN-γ–producing γδ T cells expressing a high level of promyelocytic leukemia zinc finger was able to develop. Thus, our results reveal that γδ T cells are functionally differentiated to IFN-γ and IL-17 producers at different developmental stages in fetal thymus.
Halofuginone-Induced Amino Acid Starvation Regulates Stat3-Dependent Th17 Effector Function and Reduces Established Autoimmune Inflammation
Authors: Carlson Thaddeus J. , Pellerin Alex , Djuretic Ivana M. , Trivigno Catherine , Koralov Sergei B. , Rao Anjana , Sundrud Mark S. 
Published: February 2014

Abstract
The IL-23 pathway is genetically linked to autoimmune disease in humans and is required for pathogenic Th17 cell function in mice. However, because IL-23R–expressing mature Th17 cells are rare and poorly defined in mice at steady-state, little is known about IL-23 signaling. In this study, we show that the endogenous CCR6+ memory T cell compartment present in peripheral lymphoid organs of unmanipulated mice expresses Il23r ex vivo, displays marked proinflammatory responses to IL-23 stimulation in vitro, and is capable of transferring experimental autoimmune encephalomyelitis. The prolyl-tRNA synthetase inhibitor halofuginone blocks IL-23–induced Stat3 phosphorylation and IL-23–dependent proinflammatory cytokine expression in endogenous CCR6+ Th17 cells via activation of the amino acid starvation response (AAR) pathway. In vivo, halofuginone shows therapeutic efficacy in experimental autoimmune encephalomyelitis, reducing both established disease progression and local Th17 cell effector function within the CNS. Mechanistically, AAR activation impairs Stat3 responses downstream of multiple cytokine receptors via selective, posttranscriptional suppression of Stat3 protein levels. Thus, our study reveals latent pathogenic functions of endogenous Th17 cells that are regulated by both IL-23 and AAR pathways and identifies a novel regulatory pathway targeting Stat3 that may underlie selective immune regulation by the AAR.