109 research outputs found

    Caractérisations structurales et tribologiques de couches d'oxydes de titane créées par faisceau Laser

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    Des couches incolores et jaunes ont été obtenues par un traitement laser Nd/YAG impulsionnel à la surface d'un substrat en titane. Les évolutions de la structure ont été étudiées à la suite de test de fretting à l'aide d'analyses Raman. Ces analyses Raman montrent que les évolutions engendrées par les frottements sont différentes entre ces couches incolores et jaunes même si leurs comportements tribologiques et leurs morphologies sont proches

    IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells

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    Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al

    Multiple innovations underpinned branching form diversification in mosses

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    International audienceBroad-scale evolutionary comparisons have shown that branching forms arose by convergencein vascular plants and bryophytes, but the trajectory of branching form diversificationin bryophytes is unclear. Mosses are the most species-rich bryophyte lineage andtwo sub-groups are circumscribed by alternative reproductive organ placements. In one,reproductive organs form apically, terminating growth of the primary shoot (gametophore)axis. In the other, reproductive organs develop on very short lateral branches. Aswitch from apical to lateral reproductive organ development is proposed to have primedbranching form diversification. Moss gametophores have modular development and each module develops from a singleapical cell. Here we define the architectures of 175 mosses by the number of module classes,branching patterns and the pattern in which similar modules repeat. Using ancestral characterstate reconstruction we identify two stages of architectural diversification. During a first stage there were sequential changes in the module repetition pattern, reproductiveorgan position, branching pattern and the number of module classes. During a secondstage, vegetative changes occurred independently of reproductive fate. The results pinpoint the nature of developmental change priming branching form diversificationin mosses and provide a framework for mechanistic studies of architectural diversificatio

    Dysregulated Recruitment of the Histone Methyltransferase EZH2 to the Class II Transactivator (CIITA) Promoter IV in Breast Cancer Cells

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    One mechanism frequently utilized by tumor cells to escape immune system recognition and elimination is suppression of cell surface expression of Major Histocompatibility Class II (MHC II) molecules. Expression of MHC II is regulated primarily at the level of transcription by the Class II Transactivator, CIITA, and decreased CIITA expression is observed in multiple tumor types. We investigate here contributions of epigenetic modifications to transcriptional silencing of CIITA in variants of the human breast cancer cell line MDA MB 435. Significant increases in histone H3 lysine 27 trimethylation upon IFN-γ stimulation correlate with reductions in transcription factor recruitment to the interferon-γ inducible CIITA promoter, CIITApIV, and with significantly increased CIITApIV occupancy by the histone methyltransferase enhancer of zeste homolog 2 (EZH2). Most compelling is evidence that decreased expression of EZH2 in MDA MB 435 variants results in significant increases in CIITA and HLA-DRA mRNA expression, even in the absence of interferon-γ stimulation, as well as increased cell surface expression of MHC II. Together, these data add mechanistic insight to prior observations of increased EZH2 expression and decreased CIITA expression in multiple tumor types
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