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Therapeutic efficacy of in-vivo IL-12 plasmid delivery using microbubble-assisted ultrasound in a B16F10 mouse melanoma model: A proof of concept
No full textInternational audienceIn-vivo targeted delivery of immunostimulatory molecules for melanoma treatment is a promising strategy to overcome complexity, toxicity, and cost associated with current immunotherapies. Among these molecules, interleukine-12 (IL-12) is a potent immunostimulatory cytokine that plays a major role in antitumoral immune response. However, systemic administration of IL-12 induces severe side effects, highlighting the need for efficient and safe in-vivo delivery modalities. Microbubble-assisted ultrasound (MB-assisted US) is an emerging non-invasive and targeted method for therapeutic molecule delivery. This study aimed to evaluate its efficacy for intratumoral (i.t.) delivery of a plasmid encoding IL-12 (pIL-12) in a mouse melanoma model. In-vitro, delivery of 5 or 10 g of pIL-12 into melanoma cell suspensions using MB-assisted US increased IL-12 concentration to 1429 ± 125 and 2352 ± 125 pg/mL, respectively, whereas pIL-12 treatment alone did not elicit IL-12 secretion. Similarly, acoustically mediated delivery of 10 or 50 g of pIL-12 into melanoma spheroids significantly increased IL-12 concentration - 131 ± 7 and 250 ± 60 pg/mL respectively - compared to pIL-12 alone (0 pg/mL for 10 g and 7.5 ± 7.5 pg/mL for 50 g). In-vivo, acoustically mediated pIL-12 delivery increased serum mIL-12 concentration by 5-fold compared with i.t. pIL-12 injection alone, promoting NK cell recruitment and activation within the tumor microenvironment. By day 15, this strategy reduced tumor volume by 2.5-fold relative to i.t. pIL-12 alone and improved mouse health status. These findings confirm that MB-assisted US is a relevant modality for in-vivo delivery of immunostimulatory molecules in melanoma therapy
Plasma jet and plasma treated aerosol induced permeation of reconstructed human epidermis
No full textInternational audienceAs plasma-treated liquids have many applications in plasma medicine, their cutaneous effects for cosmetic purposes are also considered as an alternative way to treat skin without the electric hazards and limitations correlated with the use of a direct plasma. Our previous work on human skin explants showed increased transdermal diffusion of cosmetic ingredients (caffeine, hyaluronic acid) after direct plasma treatment. Despite this proven efficacy, these protocols still face limitations dealing with toxicity, small treatment areas and uneven surface coverage. To overcome these limitations and broaden the scope of non-thermal-plasma-based technology for skin care, this study presents for the first time the development and assessment of a plasma aerosol device to nebulize plasma-treated liquids on skin model
"La mujer habitada" en la trayectoria de Gioconda Belli: entre feminismo y sandinismo
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Cholesterol Remodeling by CH25h Rewires IFITM3 Trafficking and Secretion Without Enhancing Antiviral Restriction
No full textInternational audienceType I interferon induces multiple protein effectors to inhibit viral replication. Among these, the interferon-induced transmembrane protein (IFITM3) and the cholesterol-25-hydroxylase (CH25h) converge on the inhibition of viral entry by altering the behavior of membranes. Here, we dissect the functional and mechanistic relationship between these two membrane-acting effectors using HIV-1 and vesicular stomatitis virus (VSV) as models. We show that IFITM3 and CH25h restrict viral entry with similar efficiency, but act in a largely redundant manner during infection. Their redundancy is consistent across infection systems, cell types, and entry assays, indicating that both factors converge on a shared biophysical block to membrane fusion. Unexpectedly, we uncover a second layer of interplay in which the CH25h-25HC axis remodels IFITM3 trafficking. Exposure to 25-hydroxycholesterol drives IFITM3 from endolysosomal compartments to the plasma membrane, impairs its internalization into early endosomes, and increases its secretion in exosomal vesicles. These effects occur independently of direct antiviral activity and reveal that CH25h regulates IFITM3 cellular dynamics. Together, our study identifies a previously unrecognized cross-regulatory circuit between two IFN-induced antiviral pathways, highlighting how lipid remodeling by CH25h, and potentially by other cellular factors, can contribute to control the behavior of IFITM3. Importance Type I interferons induce numerous antiviral factors that frequently target the same vulnerable steps of viral infection, but how these factors influence one another is not well understood. IFITM3 and the CH25h are two potent, broad-acting inhibitors of viral membrane fusion. Here, we show that although their antiviral activities are largely redundant against HIV-1 and VSV, CH25h profoundly alters the biology of IFITM3. The product of the enzymatic activity of CH25h, the oxysterol 25HC, redistributes IFITM3 from endosomal compartments to the plasma membrane and enhances its release in exosomal vesicles— effects independent of direct antiviral activity. These findings reveal an unexpected layer of cross-regulation between lipid-modifying enzymes and membrane-embedded restriction factors. More broadly, they highlight how interferon-driven lipid remodeling can reshape the trafficking and secretion of antiviral proteins, expanding the functional landscape of innate immunity beyond viral entry inhibition
PRIMA HTR
No full textPRIMA HTR Model — Italian Early Modern Manuscripts (late 16th–18th c.)The PRIMA HTR model was developed within the framework of the ERC project PRIMA — Manuscripts in the Age of Print, hosted at the Centre d’Études Supérieures de la Renaissance (CESR – UMR 7323), Université de Tours, with the support of the LIFAT computer science laboratory (Université de Tours), which provided the high-performance computing infrastructure used for model training.The model is designed to support large-scale transcription and analysis of Italian manuscript heritage from the late sixteenth to the eighteenth century, with a particular focus on literary, satirical and poetic texts. We invite scholars and institutions working on early modern Italian manuscripts to use this model and, whenever possible, to publish the resulting transcriptions in open repositories, in order to contribute to the continuous improvement of both the model and the associated training datasets.Training data and methodologyThe model is the result of fine-tuning on a heterogeneous corpus of Italian handwritten sources from the late sixteenth to the eighteenth century, including poetic, satirical, narrative and documentary texts, on top of a base model trained on a wide range of Latin-script handwritten documents. In order to increase the diversity of writing styles, the training corpus also incorporates a selection of early modern printed calligraphy manuals, used to introduce additional stylistic variation in letterforms and writing practices.Its performance was further optimized through the injection of synthetic training data generated from the manuscript material under study, in order to improve robustness to scribal variation and layout heterogeneity.The complete data augmentation workflow is documented in the project Gitlab repository: https://scm.univ-tours.fr/cesr/prima/data_augmentationSource collectionsA representative portion of the training corpus is derived from digitized manuscripts preserved in the following institutions (non-exhaustive list):- Biblioteca Nazionale Centrale di Firenze - Biblioteca Marucelliana, Firenze- Biblioteca dell’Archiginnasio, Bologna- Fondo Joppi, Udine- Biblioteca Bertoliana, Vicenza - Biblioteca Angelica, Roma- Biblioteca Nazionale Centrale di Roma - Bibliothèque universitaire Droit-Lettres, Université Grenoble AlpesThe authors gratefully acknowledge these institutions for making their collections available for scholarly research.Transcription and normalizationNormalization and transcription practices strictly follow the PRIMA transcription guidelines deposited in the Gitlab: https://scm.univ-tours.fr/cesr/prima/htrFundingThe PRIMA project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme, Grant agreement No. 101142242.Funded by the European Union. Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them
Dictionary and society: Contrastive study of Chinese, English and French (meta)lexicographic traditions
No full textInternational audienceThe dictionary, as a cultural and social object, has garnered increasing attention for its significance as a distinct subject of study. These essential works capture various facets of political, cultural, economic, and social life, reflecting ongoing progress (Gouws 2020; Pruvost 2021; Yong & Peng 2022, etc.). This intersection between dictionaries and society is referred to as sociolexicography (Busse 2002) and is defined as ‘the study of how social processes influence the content and structure of dictionaries’. This line of inquiry also falls under metalexicography (Zgusta 1971; Quemada 1968; Pruvost 2021; Gouws 2020; De Schryver 2023, etc.).While scholars from both Western and Eastern traditions have explored the history of dictionaries in their respective countries, few studies adopt a contrastive perspective. This paper offers a diachronic analysis of traditional dictionaries in three different languages: English (Indo-European family), French (inflectional and derivational type), and Chinese (Sino-Tibetan family, isolating or analytic structure), and their traditional metalexicographic cultures. We trace the evolution of these dictionaries through three distinct periods: prior to their inception (pre-16th century), the era of early dictionaries (16th-19th centuries), and the advent of modern dictionaries (20th century onward). This comparison highlights the significant relationship between dictionaries and the societies in which they were created
Symposium "Diversité des évolutions des Masters FLE/S en France, entre choix, contrainte et anticipations. Témoignages réflexifs, historicisations, mises en perspectives"
No full textInternational audienceCe symposium inscrit dans l’axe « Évolutions institutionnelles et transformations curriculaires dans l’enseignement de la didactique du FLE » avait pour objectif de proposer des témoignages réflexifs historicisants et contrastés sur les évolutions de différents masters FLE/S en France depuis le passage des maitrises aux masters (Castellotti & Huver 2012). Il s’agissait, à travers ces témoignages, de mettre en perspective les choix que nous avons opérés dans nos formations respectives à la lumière des questions suivantes :-Quelles évolutions de nos politiques de formation : quels éléments de permanence et quelles diversifications depuis la création du / des Masters (au niveau des mentions, parcours, articulation à l’option FLE de licence, etc.) ; influences des contraintes institutionnelles : évolution des dénominations des Master, politiques nationales et locales d’allocation des moyens, enjeux de visibilité et de positionnement dans le paysage des formations (Masters FLE et au-delà), enjeux d’internationalisation ;-Quelles évolutions de nos contenus et / ou de nos modalités d’enseignement : en lien avec la question des enjeux contemporains dans un contexte globalisé ;-Quelles articulations recherche – formation – intervention
Dire l'aidance dans le cas de la maladie d'Alzheimer : du dit, du suggéré à l’impensé,
No full textInternational audience« Je ne suis pas son aidante, je suis sa femme ». Malgré une visibilité grandissante de l’aidance dans l’espace public se dire « aidant » reste compliqué. Le mot véhicule des représentations sociales empreintes de valeurs contradictoires. Dans le contexte de la maladie d’Alzheimer, il s’inscrit en plus dans un impensé culturel : celui de vivre avec une maladie qui efface progressivement l’histoire sur laquelle s’est construit le lien affectif et pourtant d’accepter le rôle d’aidant en vertu de ce lien. Le choix d’aborder l’aidance par les discours, par une analyse des mots et formulations langagières, permet de comprendre comment ces discours (re)construisent une identité dans et à travers l’aidance. Nous identifions ainsi des pratiques plus ou moins opérationnelles, des savoirs progressivement construits, mais aussi des résistances – matérielles ou subjectives – auxquelles les aidants se heurtent pour assumer les tâches nécessaires, sans négliger les sources de satisfaction ou d’insatisfaction qu’ils trouvent dans la relation d’aide. L’ouvrage, inscrit en sciences du langage, apporte un point de vue complémentaire à celui des sciences humaines et sociales sur un maillon essentiel de la chaine de soin mais encore mal connu et reconnu
