Cell Cytoskeleton Dynamics: Mechano-Sensing Properties

`The actin cytoskeleton network is the dominant structure of eukaryotic cells. It is highlydynamic and plays a central role in a wide range of mechanical and biological functions.Cytoskeleton is composed mainly of actin filaments (F-actin) resulting from the self-assemblyof monomeric actin (G-actin) and cross-linked by actin cross-linking proteins (ACPs) whosenature and concentration determine the morphological and rheological properties of thenetwork. These actin filaments are reversibly coupled to membrane proteins (critical to theresponse of cells to external stress) and in conjunction with motor proteins from the myosinfamily, are able to generate contractile force during cell migration. Knowledge of actincytoskeleton and its rheological properties is therefore indispensable for understanding theunderlying mechanics and various biological processes of cells. Here, we present a 3-DBrownian dynamics (BD) computational model in which actin monomers polymerize andbecome cross-linked by two types of ACPs, forming either parallel filament bundles ororthogonal networks. Also, the active and dynamic behaviour of motors is included. In thissimulation, actin monomers, filaments, ACPs, and motors experience thermal motion andinteract with each other with binding probabilities and defined potentials. Displacements aregoverned by the Langevin equation, and positions of all elements are updated using the Eulerintegration scheme.In this first part of the work, the mechano-sensing properties of active networks are investigatedby evaluating stress and strain rate in response to different substrate stiffness

Giant and reversible inverse barocaloric effects near room temperature in ferromagnetic MnCoGeB0.03

Hydrostatic pressure represents an inexpensive and practical method of driving caloric effects in brittle magnetocaloric materials, which display first-order magnetostructural phase transitions whose large latent heats are traditionally accessed using applied magnetic fields. Here, moderate changes of hydrostatic pressure are used to drive giant and reversible inverse barocaloric effects near room temperature in the notoriously brittle magnetocaloric material MnCoGeB0.03. The barocaloric effects compare favorably with those observed in barocaloric materials that are magnetic. The inevitable fragmentation provides a large surface for heat exchange with pressure-transmitting media, permitting good access to barocaloric effects in cooling devices.Peer ReviewedPostprint (author's final draft

L’intégration du développement durable au sein des manifestations, à travers des guides de «bonnes pratiques»

Ce travail a pour but d’analyser la façon dont le développement durable est appliqué dans le monde de l’événementiel. Pour ce faire, la première partie de ce travail amène une définition du développement durable et présente un état des lieux actuel de son application au 21ème siècle. Dans un deuxième temps, 19 guides de bonnes pratiques indiquant comment organiser une manifestation durable, provenant de Suisse, d’Angleterre, du Canada ou encore d’Espagne, ont été analysés. Toutes les pratiques exposées à travers ces guides ont été répertoriées afin d’être analysées part des indicateurs durables. De cette première analyse, les pratiques ayant obtenus le plus de points sont reprises dans ce travail, commentées et présentées de façon à ce que toute personne puisse comprendre pourquoi une pratique est durable

Mesoporous Bioactive Glasses Equipped with Stimuli-Responsive Molecular Gates for Controlled Delivery of Levofloxacin against Bacteria

[EN] An increase of bone diseases incidence has boosted the study of ceramic biomaterials as potential osteo-inductive scaffolds. In particular, mesoporous bioactive glasses have demonstrated to possess a broad application in the bone regeneration field, due their osteo-regenerative capability and their ability to release drugs from the mesoporous structure. These special features have been studied as an option to fight against bone infection, which is one of the most common problems regarding bone regeneration therapies. In this work, a mesoporous bioglass functionalized with polyamines and capped with adenosine triphosphate (ATP) as the molecular gate was developed for the controlled release of the antibiotic levofloxacin. Phosphate bonds of ATP were hydrolyzed in the presence of acid phosphatase (APase), the concentration of which is significantly increased in bone infection due to the activation of bone resorption processes. The solid was characterized and tested successfully against bacteria. The final gated solid induced bacterial death only in the presence of acid phosphatase. Additionally, it was demonstrated that the solid is not toxic against human cells. The double function of the prepared material as a drug delivery system and bone regeneration enhancer confirms the possible development of a new approach in the tissue engineering field, in which controlled release of therapeutic agents can be finely tuned and, at the same time, osteoinduction is favored.The authors thank the Spanish Government for projects MAT2015-64139-C04-01-R, MAT2015-64831-R and MAT2016-75611-R (AEI/FEDER, UE). Generalitat Valenciana (project PROMETEOII/2014/047) and CIBER-BBN (project SPRING) are also acknowledged for their support. M.V.R. acknowledges funding from the European Research Council (Advanced Grant VERDI; ERC-2015-AdG Proposal 694160). L.P. thanks Universitat Politecnica de Valencia for her FPI grant. N.G.C. and A.G. thank to Ministerio de Ciencia e Innovacion and Ministerio de Educacion, Cultura y Deporte for their predoctoral fellowships. The authors also thank the Electron Microscopy Service at the UPV for their support.Polo, L.; Gómez-Cerezo, N.; García-Fernández, A.; Aznar, E.; Vivancos, J.; Arcos, D.; Vallet, M.... (2018). Mesoporous Bioactive Glasses Equipped with Stimuli-Responsive Molecular Gates for Controlled Delivery of Levofloxacin against Bacteria. Chemistry - A European Journal. 24(71):18944-18951. https://doi.org/10.1002/chem.201803301S18944189512471Li, J., & Wang, H.-L. (2008). Common Implant-Related Advanced Bone Grafting Complications: Classification, Etiology, and Management. Implant Dentistry, 17(4), 389-401. doi:10.1097/id.0b013e31818c4992Herford, A. S., & Dean, J. S. (2011). Complications in Bone Grafting. Oral and Maxillofacial Surgery Clinics of North America, 23(3), 433-442. doi:10.1016/j.coms.2011.04.004Arciola, C. 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Biomaterials. Science, 208(4446), 826-831. doi:10.1126/science.6246576Argyo, C., Weiss, V., Bräuchle, C., & Bein, T. (2013). Multifunctional Mesoporous Silica Nanoparticles as a Universal Platform for Drug Delivery. Chemistry of Materials, 26(1), 435-451. doi:10.1021/cm402592tYan, X. X., Deng, H. X., Huang, X. H., Lu, G. Q., Qiao, S. Z., Zhao, D. Y., & Yu, C. Z. (2005). Mesoporous bioactive glasses. I. Synthesis and structural characterization. Journal of Non-Crystalline Solids, 351(40-42), 3209-3217. doi:10.1016/j.jnoncrysol.2005.08.024Yan, X., Yu, C., Zhou, X., Tang, J., & Zhao, D. (2004). Highly Ordered Mesoporous Bioactive Glasses with Superior In Vitro Bone-Forming Bioactivities. Angewandte Chemie International Edition, 43(44), 5980-5984. doi:10.1002/anie.200460598Yan, X., Yu, C., Zhou, X., Tang, J., & Zhao, D. (2004). Highly Ordered Mesoporous Bioactive Glasses with Superior In Vitro Bone-Forming Bioactivities. 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Acta Materialia, 61(3), 890-911. doi:10.1016/j.actamat.2012.10.039Zhu, Y., & Kaskel, S. (2009). Comparison of the in vitro bioactivity and drug release property of mesoporous bioactive glasses (MBGs) and bioactive glasses (BGs) scaffolds. Microporous and Mesoporous Materials, 118(1-3), 176-182. doi:10.1016/j.micromeso.2008.08.046Lembo, D., Donalisio, M., Civra, A., Argenziano, M., & Cavalli, R. (2017). Nanomedicine formulations for the delivery of antiviral drugs: a promising solution for the treatment of viral infections. Expert Opinion on Drug Delivery, 15(1), 93-114. doi:10.1080/17425247.2017.1360863Chen, W., Ouyang, J., Liu, H., Chen, M., Zeng, K., Sheng, J., … Guo, S. (2016). Black Phosphorus Nanosheet-Based Drug Delivery System for Synergistic Photodynamic/Photothermal/Chemotherapy of Cancer. Advanced Materials, 29(5), 1603864. doi:10.1002/adma.201603864Li, B. L., Setyawati, M. I., Chen, L., Xie, J., Ariga, K., Lim, C.-T., … Leong, D. T. (2017). 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Triggered release in lipid bilayer-capped mesoporous silica nanoparticles containing SPION using an alternating magnetic field. Chemical Communications, 48(45), 5647. doi:10.1039/c2cc31563gKim, H.-J., Matsuda, H., Zhou, H., & Honma, I. (2006). Ultrasound-Triggered Smart Drug Release from a Poly(dimethylsiloxane)– Mesoporous Silica Composite. Advanced Materials, 18(23), 3083-3088. doi:10.1002/adma.200600387Tan, L., Yang, M.-Y., Wu, H.-X., Tang, Z.-W., Xiao, J.-Y., Liu, C.-J., & Zhuo, R.-X. (2015). Glucose- and pH-Responsive Nanogated Ensemble Based on Polymeric Network Capped Mesoporous Silica. ACS Applied Materials & Interfaces, 7(11), 6310-6316. doi:10.1021/acsami.5b00631Zhang, Z., Balogh, D., Wang, F., Tel-Vered, R., Levy, N., Sung, S. Y., … Willner, I. (2013). Light-induced and redox-triggered uptake and release of substrates to and from mesoporous SiO2 nanoparticles. 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Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery

"This is the peer reviewed version of the following article: Oroval, Mar, Paula Díez, Elena Aznar, Carmen Coll, María Dolores Marcos, Félix Sancenón, Reynaldo Villalonga, and Ramón Martínez-Máñez. 2016. Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery. Chemistry - A European Journal 23 (6). Wiley: 1353 60. doi:10.1002/chem.201604104, which has been published in final form at https://doi.org/10.1002/chem.201604104. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] We describe herein the preparation of glucose-sensitive capped mesoporous silica nanoparticles for insulin delivery. The new material consists of an expanded-pore nanometric silica support grafted with 1-propyl-1-H-benzimidazole groups, loaded with fluorescein isothiocyanate-labeled insulin (FITC-Ins) and capped by the formation of inclusion complexes between cyclodextrin-modified glucose oxidase (CD-GOx) and the benzimidazole groups grafted on the mesoporous support. Insulin delivery from the gated material in simulated blood plasma was assessed upon addition of glucose. Glucose is transformed by GOx into gluconic acid, which promoted the dethreading of the benzimidazole-CD-GOx inclusion complexes, allowing cargo release. Small quantities of this support would be needed to release the amount of insulin necessary to decrease diabetic blood glucose concentrations to regular levels.The authors thank the Spanish Government (projects CTQ2011-24355, MAT2015-64139-C4-1-R, CTQ2014-58989-P, and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. M.O. thanks the Universitat Politecnica de Valencia for her FPI grant. P.D. thanks the Ministerio de Economia y Competitividad for her FPI grant (BES-2012-054066). C.C. thanks the Generalitat Valenciana for her postdoctoral contract VALi+D.Oroval, M.; Díez, P.; Aznar, E.; Coll Merino, MC.; Marcos Martínez, MD.; Sancenón Galarza, F.; Villalonga, R.... (2017). Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery. Chemistry - A European Journal. 23(6):1353-1360. https://doi.org/10.1002/chem.201604104S13531360236Nicole, L., Laberty-Robert, C., Rozes, L., & Sanchez, C. (2014). Hybrid materials science: a promised land for the integrative design of multifunctional materials. Nanoscale, 6(12), 6267-6292. doi:10.1039/c4nr01788aBeltrán-Osuna, Á. A., & Perilla, J. E. (2015). Colloidal and spherical mesoporous silica particles: synthesis and new technologies for delivery applications. Journal of Sol-Gel Science and Technology, 77(2), 480-496. doi:10.1007/s10971-015-3874-2Trewyn, B. G., Slowing, I. I., Giri, S., Chen, H.-T., & Lin, V. S.-Y. (2007). Synthesis and Functionalization of a Mesoporous Silica Nanoparticle Based on the Sol–Gel Process and Applications in Controlled Release. Accounts of Chemical Research, 40(9), 846-853. doi:10.1021/ar600032uVallet-Regí, M., & Balas, F. (2008). Silica Materials for Medical Applications. The Open Biomedical Engineering Journal, 2(1), 1-9. doi:10.2174/1874120700802010001Sancenón, F., Pascual, L., Oroval, M., Aznar, E., & Martínez-Máñez, R. (2015). Gated Silica Mesoporous Materials in Sensing Applications. ChemistryOpen, 4(4), 418-437. doi:10.1002/open.201500053Aznar, E., Oroval, M., Pascual, L., Murguía, J. R., Martínez-Máñez, R., & Sancenón, F. (2016). Gated Materials for On-Command Release of Guest Molecules. Chemical Reviews, 116(2), 561-718. doi:10.1021/acs.chemrev.5b00456Aznar, E., Martínez-Máñez, R., & Sancenón, F. 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AHP choice in cocoa post-harvest technology for small-scale farmers

OPEN ACCESS JOURNAL: Articles are distributed under the terms of the Creative Commons Attribution-Non Commercial (by-nc) Spain 3.0 Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Ensuring that the post-harvest process yields good quality cocoa is a relevant research question. However, the literature currently lacks detailed studies of producers criteria for post-harvest technology selection. There is therefore a need for research that examines technology choice based on several criteria. This is the aim of our paper. We defined a cocoa post-harvest technology selection model to assist small producers in Ecuador. To do so, we employed the Analytical Hierarchy Process (AHP) to assess the following criteria: quality, processing cost and technology adoption capability. By considering only quality, we first performed a preliminary assessment of nine post-harvest technologies yielded by all possible combinations of fermentation and drying methods. Under the criterion quality , results show that no post-harvest technology is preferable to another. This implies that quality differences between producers do not derive from technology choice but rather from the rigour with which producers perform fermentation and drying processes. After adding the criteria processing cost and technology adoption capability , we performed the analysis again. This multi-criteria approach offered a better way to approximate small farmers real needs when selecting technology for cocoa post-harvest. Although quality was the highest-valued criterion, high scores attributed to some technologies in the other two criteria offset scores for quality. Thus, processing cost and technology adoption also emerged as relevant factors for small holders.The authors wish to thank the Ministry of Economy and Competitiveness (MINECO, Spain) and the European Regional Development Fund in the framework of the Agriinnova project "Organizational forms of innovation in agri-food sector and its effects on economic outcomes and innovation performance" (AGL2012-39793-C03-02) for their financial support. The authors also express their gratitude to the Escuela Superior Politecnica Agropecuaria de Manabi "Manuel Felix Lopez" for their support in the preparation of the experimental fieldwork.Vera Montenegro, L.; Baviera Puig, MA.; García Alvarez-Coque, JM. (2014). AHP choice in cocoa post-harvest technology for small-scale farmers. Spanish Journal of Agricultural Research. 12(3):542-552. https://doi.org/10.5424/sjar/2014123-5467S542552123Abdulai, A., Owusu, V., & Bakang, J.-E. A. (2011). 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Factors influencing farmers’ adoption of modern rice technologies and good management practices in the Philippines. Agricultural Systems, 110, 41-53. doi:10.1016/j.agsy.2012.03.010Mossu G, 1992. Drying in cocoa. The tropical agriculturist. McMiller Press, London, UK.Nielsen, D. S., Teniola, O. D., Ban-Koffi, L., Owusu, M., Andersson, T. S., & Holzapfel, W. H. (2007). The microbiology of Ghanaian cocoa fermentations analysed using culture-dependent and culture-independent methods. International Journal of Food Microbiology, 114(2), 168-186. doi:10.1016/j.ijfoodmicro.2006.09.010Ning H, Shao F, Sun X, Shan J, 2011. AHP-based evaluation on plant landscape of Huagangguanyu Park in Hangzhou. Hortic Sci 23: 717-724.Oracz, J., & Nebesny, E. (2014). Influence of roasting conditions on the biogenic amine content in cocoa beans of different Theobroma cacao cultivars. Food Research International, 55, 1-10. doi:10.1016/j.foodres.2013.10.032Papalexandratou, Z., Camu, N., Falony, G., & De Vuyst, L. 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Highly selective and sensitive detection of glutathione using mesoporous silica nanoparticles capped with disulfide-containing oligo(ethylene glycol) chains

[EN] Mesoporous silica nanoparticles loaded with safranin O and capped with disulfide-containing oligo(ethylene glycol) chains were used for the selective and sensitive fluorimetric detection of glutathione.Financial support from the Spanish Government (Project MAT2012-38429-C04-01) and the Generalitat Valencia (Project PROMETEOII/2014/047) is gratefully acknowledged. S. E. is grateful to the Generalitat Valenciana for his Santiago Grisolia fellow. Also, C. G. is grateful to the Spanish Ministry of Science and Innovation for the grant.El Sayed Shehata Nasr, S.; Giménez Morales, C.; Aznar Gimeno, E.; Martínez Mañez, R.; Sancenón Galarza, F.; Licchelli, M. (2015). Highly selective and sensitive detection of glutathione using mesoporous silica nanoparticles capped with disulfide-containing oligo(ethylene glycol) chains. Organic and Biomolecular Chemistry. 13(4):1017-1021. https://doi.org/10.1039/C4OB02083AS1017102113

Metformin attenuates the effect of Staphylococcus aureus on airway tight junctions by increasing PKCζ-mediated phosphorylation of occludin.

Airway epithelial tight junction (TJ) proteins form a resistive barrier to the external environment, however, during respiratory bacterial infection TJs become disrupted compromising barrier function. This promotes glucose flux/accumulation into the lumen which acts as a nutrient source for bacterial growth. Metformin used for the treatment of diabetes increases transepithelial resistance (TEER) and partially prevents the effect of bacteria but the mechanisms of action are unclear. We investigated the effect of metformin and Staphylococcus aureus on TJ proteins, zonula occludins (ZO)-1 and occludin in human airway epithelial cells (H441). We also explored the role of AMP-activated protein kinase (AMPK) and PKCζ in metformin-induced effects. Pretreatment with metformin prevented the S. aureus-induced changes in ZO-1 and occludin. Metformin also promoted increased abundance of full length over smaller cleaved occludin proteins. The nonspecific PKC inhibitor staurosporine reduced TEER but did not prevent the effect of metformin indicating that the pathway may involve atypical PKC isoforms. Investigation of TJ reassembly after calcium depletion showed that metformin increased TEER more rapidly and promoted the abundance and localization of occludin at the TJ. These effects were inhibited by the AMPK inhibitor, compound C and the PKCζ pseudosubstrate inhibitor (PSI). Metformin increased phosphorylation of occludin and acetyl-coA-carboxylase but only the former was prevented by PSI. This study demonstrates that metformin improves TJ barrier function by promoting the abundance and assembly of full length occludin at the TJ and that this process involves phosphorylation of the protein via an AMPK-PKCζ pathway

Transient Brewster angle reflectometry of spiropyran monolayers

Brewster angle reflectometry has been developed as a tool for determining the absorbance and refractive index changes in molecular monolayers containing spiropyran. The method is sensitive to changes in both the real and imaginary parts of the refractive index in the monolayers. It was used to monitor the conversion of spiropyran to merocyanine and the reversal of this reaction when the molecules were immobilised on quartz using silane coupling. An analytical solution of Fresnel formula allowed the transient reflectometry data to be converted into transient absorption information. Absorbances of transients as low as ~10-6 were possible using the current apparatus with a single laser pulse transient measurement. It was found that spiropyran photoconverted to merocyanine with an efficiency of ~0.1. The photochemical reversion of converted merocyanine to spiropyran occurred with efficiencies of 0.03–0.2 and this was probably site dependent. It was found that the thermal conversion from merocyanine to spiropyran was slow and even after 10 min there was no significant thermal reversion. This measurement was possible because the real part of the refractive index of the monolayer could be monitored with time using an off-resonance probe at a wavelength where the merocyanine did not absorb light meaning that the probe did not photobleach the sample. Thus our method also provides a non-intrusive method for probing changes in molecules in thin films

Enzyme-Controlled Nanodevice for Acetylcholine-Triggered Cargo Delivery Based on Janus Au-Mesoporous Silica Nanoparticles

"This is the peer reviewed version of the following article: Llopis-Lorente, Antoni, Paula Díez, Cristina de la Torre, Alfredo Sánchez, Félix Sancenón, Elena Aznar, María D. Marcos, Paloma Martínez-Ruíz, Ramón Martínez-Máñez, and Reynaldo Villalonga. 2017. Enzyme-Controlled Nanodevice for Acetylcholine-Triggered Cargo Delivery Based on Janus Au-Mesoporous Silica Nanoparticles. Chemistry - A European Journal 23 (18). Wiley: 4276 81. doi:10.1002/chem.201700603, which has been published in final form at https://doi.org/10.1002/chem.201700603. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] This work reports a new gated nanodevice for acetylcholine-triggered cargo delivery. We prepared and characterized Janus Au-mesoporous silica nanoparticles functionalized with acetylcholinesterase on the Au face and with supramolecular b-cyclodextrin: benzimidazole inclusion complexes as caps on the mesoporous silica face. The nanodevice is able to selectively deliver the cargo in the presence of acetylcholine via enzyme-mediated acetylcholine hydrolysis, locally lowering the pH and opening the supramolecular gate. Given the key role played by ACh and its relation with Parkinson's disease and other nervous system diseases, we believe that these findings could help design new therapeutic strategies.A.L.L. is grateful to "La Caixa" Banking Foundation for his PhD fellowship. The authors are gratitude to the Spanish Government (MINECO Projects MAT2012-38429-C04-01, MAT2015-64139-C4-1, CTQ2014-58989-P and CTQ2015-71936-REDT) and the Generalitat Valencia (Project PROMETEOII/2014/047) for support. The Comunidad de Madrid (S2013/MIT-3029, Programme NANOAVANSENS) is also gratefully acknowledged.Llopis-Lorente, A.; Díez, P.; De La Torre-Paredes, C.; Sanchez, A.; Sancenón Galarza, F.; Aznar, E.; Marcos Martínez, MD.... (2017). 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