Injectable Magnetic-Responsive Short-Peptide Supramolecular Hydrogels: Ex Vivo and In Vivo Evaluation

This study was supported by project FIS2017-85954-R funded by MCIN/AEI/10.13039/501100011033/FEDER "Una manera de hacer Europa", Spain, grants FIS PI20/0317 and ICI19/00024 (BIOCLEFT) (MINECO, Instituto de Salud Carlos III, Spain, cofinanced by FEDER funds, European Union), grant PE-0395-2019 (Consejeri ' a de Salud y Familias, Junta de Andalucia ', Spain), and project PPJIB2020.07 (Universidad de Granada, Spain). M.C.M.-T. acknowledges grant PRE2018-083773 funded by MCIN/AEI/10.13039/501100011033 and FSE "El FSE invierte en tu futuro", Spain. C.G.-V. acknowledges grant FPU17/00491 funded by MCIN/AEI/10.13039/501100011033 and FSE "El FSE invierte en tu futuro", Spain. P.K., D.M., and J.-C.S. acknowledge the French Agence Nationale de la Recherche, Project Future Investments UCA JEDI no. ANR-15-IDEX-01 (project RheoGels) for financial support. Funding for open access charge: Universidad de Granada/CBUA.The inclusion of magnetic nanoparticles (MNP) in a hydrogel matrix to produce magnetic hydrogels has broadened the scope of these materials in biomedical research. Embedded MNP offer the possibility to modulate the physical properties of the hydrogel remotely and on demand by applying an external magnetic field. Moreover, they enable permanent changes in the mechanical properties of the hydrogel, as well as alterations in the micro- and macroporosity of its threedimensional (3D) structure, with the associated potential to induce anisotropy. In this work, the behavior of biocompatible and biodegradable hydrogels made with Fmoc-diphenylalanine (Fmoc-FF) (Fmoc = fluorenylmethoxycarbonyl) and Fmoc−arginine−glycine− aspartic acid (Fmoc-RGD) short peptides to which MNP were incorporated was studied in detail with physicochemical, mechanical, and biological methods. The resulting hybrid hydrogels showed enhance mechanical properties and withstood injection without phase disruption. In mice, the hydrogels showed faster and improved self-healing properties compared to their nonmagnetic counterparts. Thanks to these superior physical properties and stability during culture, they can be used as 3D scaffolds for cell growth. Additionally, magnetic short-peptide hydrogels showed good biocompatibility and the absence of toxicity, which together with their enhanced mechanical stability and excellent injectability make them ideal biomaterials for in vivo biomedical applications with minimally invasive surgery. This study presents a new approach to improving the physical and mechanical properties of supramolecular hydrogels by incorporating MNP, which confer structural reinforcement and stability, remote actuation by magnetic fields, and better injectability. Our approach is a potential catalyst for expanding the biomedical applications of supramolecular short-peptide hydrogels.Instituto de Salud Carlos III FIS PI20/0317 ICI19/00024European CommissionFSE "El FSE invierte en tu futuro", SpainFrench National Research Agency (ANR) ANR-15-IDEX-01Universidad de Granada/CBUAFIS2017-85954-R MCIN/AEI/10.13039/501100011033/FEDER PE-0395-2019 PPJIB2020.07 PRE2018-083773 MCIN/AEI/10.13039/501100011033 FPU17/0049

Database of pleistocene periglacial featuresin France: description of the online version

A database of Pleistocene periglacial features in France has been compiled from a review of academic literature and reports of rescue archaeology, the analysis of aerial photographs and new field surveys. Polygons, soil stripes, ice-wedge pseudomorphs, sand wedges and composite wedge pseudomorphs are included in the database together with their geographic coordinates, geological context, description and associated references. It is hoped that this database, which aim is to be integrated in broader studies, will stimulate further work on past permafrost reconstruction and will favour greater understanding of the climatic events that lead to the formation of the periglacial features. The database is available online on the AFEQ-CNF INQUA website (https://afeqeng.hypotheses.org/487). A folder that contains photographs and sketches of the features is also available on request.Une base de données des structures périglaciaires pléistocènes de France a été créée à partir d’une revue de la littérature scientifique, de rapports d’archéologie préventive, de l’analyse de photographies aériennes et de nouvelles prospections de terrain. Les polygones, les sols striés, les pseudomorphoses de coin de glace, les coins de sable et les pseudomorphoses de coin composite ont été répertoriés dans la base de données avec leurs coordonnées géographiques, le contexte géologique, leur description et les références bibliographiques associées. Nous espérons que cette base de données, dont le but est d’être intégrée dans des études plus larges, stimulera de prochains travaux sur la reconstitution du pergélisol pléistocène et favorisera une plus grande compréhension des événements climatiques qui ont conduit à la formation de ces structures périglaciaires. La base de données est disponible en ligne sur le site de l’AFEQ-CNF INQUA (https://afeqeng.hypotheses.org/487). Un dossier contenant les photographies et dessins des structures périglaciaires est également disponible sur demande

The Telomeric Protein TRF2 Regulates Angiogenesis by Binding and Activating the PDGFRβ Promoter

Telomeric repeat binding factor 2 (TRF2), which plays a central role in telomere capping, is frequently increased in human tumors. We reveal here that TRF2 is expressed in the vasculature of most human cancer types, where it colocalizes with the Wilms’ tumor suppressor WT1. We further show that TRF2 is a transcriptional target of WT1 and is required for proliferation, migration, and tube formation of endothelial cells. These angiogenic effects of TRF2 are uncoupled from its function in telomere capping. Instead, TRF2 binds and transactivates the promoter of the angiogenic tyrosine kinase platelet-derived growth factor receptor β (PDGFRβ). These findings reveal an unexpected role of TRF2 in neoangiogenesis and delineate a distinct function of TRF2 as a transcriptional regulator

Cancer-associated fibroblasts in renal cell carcinoma: implication in prognosis and resistance to anti-angiogenic therapy

International audienceObjectives: To investigate the role of cancer-associated fibroblasts (CAFs) in clear cell renal cell carcinoma (ccRCC) with respect to tumour aggressiveness, metastasis development, and resistance to anti-angiogenic therapy (vascular endothelial growth factor receptor-tyrosine kinase inhibitors [VEGFR-TKI]).Patients and methods: Our study involved tissue samples from three distinct and independent cohorts of patients with ccRCC. The presence of CAFs and tumour lymphangiogenesis was investigated, respectively, by transcriptional signatures and then correlated with tumour development and prognosis. The effect of these CAFs on tumour cell migration and VEGFR-TKI resistance was analysed on co-cultures of ccRCC cells with CAFs.Results: Results from our cohorts and from in silico investigations showed that VEGFR-TKI significantly increase the number of CAFs in tumours. In the same populations of patients with ccRCC, the proportion of intra-tumoral CAFs correlated to shorter disease-free and overall survival. The presence of CAFs was also correlated with lymphangiogenesis and lymph node metastasis. CAFs increased the migration and decreased the VEGFR-TKI-dependent cytotoxic effect of tumour cells.Conclusions: Our results show that VEGFR-TKI promote the development of CAFs, and CAFs favour tumour aggressiveness, metastatic dissemination, and resistance to treatment in ccRCC. CAFs could represent a new therapeutic target to fight resistance to treatment of ccRCC. Targeting CAF and immunotherapies combination are emerging as efficient treatments in many types of solid tumours. Our results highlight their relevance in ccRCC

Contact lenses and infectious keratitis: From a case-control study to a computation of the risk for wearers

Indexation en cours.International audiencePURPOSE: Contact lens (CL)-related microbial keratitis (MK) has major public health implications, with about 300 million wearers worldwide, and certain potentially modifiable risk factors. This study aimed to identify the risk factors of CL-related MK. METHODS: A multicenter case-control study was conducted between 2014 and 2017. Cases presenting with CL-related MK were submitted to an anonymous 52-item questionnaire, which was also completed by healthy controls. Univariate followed by multivariate logistic regression analysis was performed. Risk factors for CL-related MK were given as odds ratio (OR) with 95% confidence interval and P-value. RESULTS: The study included a total of 2267 patients (1198 cases and 1069 controls). The MK risk factors for the daily disposable lenses group were exceeding the lens renewal period (OR = 9.16, P = 0.008) and occasionally wearing CL when sleeping (OR = 15.83, P = 0.035). The most important risk factors in the nondaily disposable lenses group were lens cleaning solution distributed by eye care brands (OR = 3.50, P < 0.001) and failure to renew lens cases (OR = 3.39, P = 0.001). Statistically and clinically significant variables were used to establish the MK risk equation for CL wearers, allowing an individual calculation of the risk of MK under lenses. CONCLUSIONS: The MK risk equation is a valuable tool for educating patients about the risks associated with wearing CL. It allows the patient to be informed about their overall risk of infection while detailing the precipitating elements of the infectious risk with the aim of modifying risk behavior

Base de données des structures périglaciaires pléistocènes en France : description de la version accessible en ligne

International audienceA database of Pleistocene periglacial features in France has been compiled from a review of academic literature and reports of rescue archaeology, the analysis of aerial photographs and new field surveys. Polygons, soil stripes, ice-wedge pseudomorphs, sand wedges and composite wedge pseudomorphs are included in the database together with their geographic coordinates, geological context, description and associated references. It is hoped that this database, which aim is to be integrated in broader studies, will stimulate further work on past permafrost reconstruction and will favour greater understanding of the climatic events that lead to the formation of the periglacial features. The database is available online on the AFEQ-CNF INQUA website (https://afeqeng.hypotheses.org/487). A folder that contains photographs and sketches of the features is also available on request

Study of isospin diffusion from 40,48^{40,48}Ca+40,48+^{40,48}Ca experimental data at Fermi energies: direct comparisons with transport model calculations

This article presents an investigation of isospin equilibration in cross-bombarding $^{40,48}$Ca$+^{40,48}$Ca reactions at $35$ MeV/nucleon, by comparing experimental data with filtered transport model calculations. Isospin diffusion is studied using the evolution of the isospin transport ratio with centrality. The asymmetry parameter $\delta=(N-Z)/A$ of the quasiprojectile (QP) residue is used as isospin-sensitive observable, while a recent method for impact parameter reconstruction is used for centrality sorting.A benchmark of global observables is proposed to assess the relevance of the antisymmetrized molecular dynamics (AMD) model, coupled to GEMINI++, in the study of dissipative collisions. Our results demonstrate the importance of considering cluster formation to reproduce observables used for isospin transport and centrality studies.Within the AMD model, we prove the applicability of the impact parameter reconstruction method, enabling a direct comparison to the experimental data for the investigation of isospin diffusion.For both, we evidence a tendency to isospin equilibration with an impact parameter decreasing from $9$ to $3$ fm, while the full equilibration is not reached.A weak sensitivity to the stiffness of the equation of state employed in the model is also observed, with a better reproduction of the experimental trend for the neutron-rich reactions

Study of isospin diffusion from 40,48^{40,48}Ca+40,48+^{40,48}Ca experimental data at Fermi energies: direct comparisons with transport model calculations

This article presents an investigation of isospin equilibration in cross-bombarding $^{40,48}$Ca$+^{40,48}$Ca reactions at $35$ MeV/nucleon, by comparing experimental data with filtered transport model calculations. Isospin diffusion is studied using the evolution of the isospin transport ratio with centrality. The asymmetry parameter $\delta=(N-Z)/A$ of the quasiprojectile (QP) residue is used as isospin-sensitive observable, while a recent method for impact parameter reconstruction is used for centrality sorting.A benchmark of global observables is proposed to assess the relevance of the antisymmetrized molecular dynamics (AMD) model, coupled to GEMINI++, in the study of dissipative collisions. Our results demonstrate the importance of considering cluster formation to reproduce observables used for isospin transport and centrality studies.Within the AMD model, we prove the applicability of the impact parameter reconstruction method, enabling a direct comparison to the experimental data for the investigation of isospin diffusion.For both, we evidence a tendency to isospin equilibration with an impact parameter decreasing from $9$ to $3$ fm, while the full equilibration is not reached.A weak sensitivity to the stiffness of the equation of state employed in the model is also observed, with a better reproduction of the experimental trend for the neutron-rich reactions

Study of isospin diffusion from 40,48^{40,48}Ca+40,48+^{40,48}Ca experimental data at Fermi energies: direct comparisons with transport model calculations

This article presents an investigation of isospin equilibration in cross-bombarding $^{40,48}$Ca$+^{40,48}$Ca reactions at $35$ MeV/nucleon, by comparing experimental data with filtered transport model calculations. Isospin diffusion is studied using the evolution of the isospin transport ratio with centrality. The asymmetry parameter $\delta=(N-Z)/A$ of the quasiprojectile (QP) residue is used as isospin-sensitive observable, while a recent method for impact parameter reconstruction is used for centrality sorting.A benchmark of global observables is proposed to assess the relevance of the antisymmetrized molecular dynamics (AMD) model, coupled to GEMINI++, in the study of dissipative collisions. Our results demonstrate the importance of considering cluster formation to reproduce observables used for isospin transport and centrality studies.Within the AMD model, we prove the applicability of the impact parameter reconstruction method, enabling a direct comparison to the experimental data for the investigation of isospin diffusion.For both, we evidence a tendency to isospin equilibration with an impact parameter decreasing from $9$ to $3$ fm, while the full equilibration is not reached.A weak sensitivity to the stiffness of the equation of state employed in the model is also observed, with a better reproduction of the experimental trend for the neutron-rich reactions