European Systemic Credit Risk Transmission Using Dynamic Bayesian Networks.

The analysis of systemic credit risk is one of the most important concerns within the financial system. Its complexity lies in adequately measuring how the transmission of systemic default spreads through assets or financial markets. The transmission structure of systemic credit risk across several European sectoral CDS is studied by dynamic Bayesian networks. The new approach allows for a more advanced analysis of systemic risk transmission, including long-term and more complex relationships. The modelling reveals as relevant only relationships between the original series and one- and twolagged series. Network structure learning displays a robust and stationary underlying risk transmission structure, pointing to a consolidated transmission mechanism of systemic credit risk between CDSs. Between 5% and 40% of sectoral CDS series variances are explained by the network relationships. The modelling allows us to ascertain which relationships between the CDS series show positive (amplifier) and negative (reducer) effects of systemic risk transmission

Nanotechnology in the Development of Novel Functional Foods or their Package. An Overview Based in Patent Analysis

[EN] In recent years nanotechnology has become a significant component in food industry. It is present in all food chain steps, from the design of new ingredients or additives, to the most modern systems of food quality methods or packaging, demonstrating the great potential of this new technology in a sector as traditional as food. However, while interest by industry in nanotechnology increases, the rejection by consumers, concerned about the potential risk, does too. The aim of this review is to evaluate the development of food nanotechnology by means of a patent analysis, highlighting current applications of nanotechnology along the whole food chain and contextualizing this evolution in the social scene.Financial support from the Spanish Government (project MAT2009-14564-C04-01 and AGL2010-20539) and the Generalitat Valencia (project PROMETEO/2009/016) are gratefully acknowledged. E.P. thanks the Ministerio de Educación for a fellowshipPérez-Esteve, É.; Bernardos Bau, A.; Martínez-Máñez, R.; Barat Baviera, JM. (2013). Nanotechnology in the Development of Novel Functional Foods or their Package. An Overview Based in Patent Analysis. Recent Patents on Food, Nutrition and Agriculture. 5(1):35-43. https://doi.org/10.2174/2212798411305010006S35435

Gothic stonework in the region of maestrazgo. Virtual models of vaulted systems for three octogonal chapels

Entre los siglos XIII y XV, la comarca histórica del Maestrazgo, vivió un momento de gran expansión económica que se vió reflejado en el auge de la arquitectura gótica, y de forma destacada en las poblaciones de Morella y Sant Mateu por su situación estratégica entre los reinos de Valencia y Aragón. Estas dos poblaciones albergan algunas de las más relevantes construcciones de esta época de las que, sin embargo, no existe información suficiente sobre su historia y procesos constructivos. Para cubrir este vacío se propone el estudio de tres casos concretos de un mismo tipo de capilla ochavada (1) que, según las fuentes bibliográficas consultadas, podrían haber sido realizadas por el mismo maestro cantero, Domènech Prunyonosa. El objetivo consiste en determinar las propuestas de los modelos teóricos utilizados a partir de un levantamiento topográfico y fotogramétrico de cada uno delos casos seleccionados lo suficientemente preciso para poder definir el despiece exacto de los nervios y plementerías que configuran sus correspondientes sistemas abovedados

Mesoporous Silica-Based Supports for the Controlled and Targeted Release of Bioactive Molecules in the Gastrointestinal Tract

JFS Special Issue: 75 Years of Advancing Food Science, and Preparing for the Next 75Mesoporous silica particles (MSPs) have attracted increasing interest as supports in the design of controlled delivery materials. Besides their excellent properties as loading supports (that is, large surface area and pore volume), the modification of their external surface with molecular/supramolecular ensembles allows the design of gated MSPs. Delivery systems based on gated MSPs show zero delivery until an adequate stimulus is present and triggers gate opening and the cargo is released. Encapsulation of bioactive molecules in gated MSPs may improve biological stability, facilitate component handling, mask unpleasant sensorial properties, and modulate the bioaccessibility of target molecules along the gastrointestinal tract. These properties make gated MSPs excellent candidates for encapsulating bioactive molecules and their subsequent utilization in the formulation of functional foods. This text highlights the most significant endogenous triggering stimuli that might be applied to design these site-specific delivery systems, as well as the strategies to develop them. Given the novelty of using MSPs in the food sector, the benefits and current potential limitations of employing MSPs in human food have been identified and discussed.Authors gratefully acknowledge the financial support from the Ministerio de Economia y Competitividad (Projects AGL2012-39597-C02-01, AGL2012-39597-C02-02, and MAT2012-38429-C04-01) and the Generalitat Valenciana (project PROME-TEO/2009/016). E.P. and M.R. are grateful to the Ministerio de Ciencia e Innovacion for their grants (AP2008-00620, AP2010-4369).Pérez-Esteve, É.; Ruiz Rico, M.; Martínez-Máñez, R.; Barat Baviera, JM. (2015). Mesoporous Silica-Based Supports for the Controlled and Targeted Release of Bioactive Molecules in the Gastrointestinal Tract. Journal of Food Science. 80(11):E2504-E2516. doi:10.1111/1750-3841.13095SE2504E2516801

Copper(II) complexes of quinoline polyazamacrocyclic scorpiand-type ligands: X-ray, equilibrium and kinetic studies

The formation of Cu(II) complexes with two isomeric quinoline-containing scorpiand-type ligands has been studied. The ligands have a tetraazapyridinophane core appended with an ethylamino tail including 2-quinoline (L1) or 4-quinoline (L2) functionalities. Potentiometric studies indicate the formation of stable CuL2+ species with both ligands, the L1 complex being 3–4 log units more stable than the L2 complex. The crystal structure of [Cu(L1)](ClO4)2·H2O shows that the coordination geometry around the Cu2+ ions is distorted octahedral with significant axial elongation; the four Cu–N distances in the equatorial plane vary from 1.976 to 2.183 Å, while the axial distances are of 2.276 and 2.309 Å. The lower stability of the CuL22+ complex and its capability of forming protonated and hydroxo complexes suggest a penta-dentate coordination of the ligand, in agreement with the type of substitution at the quinoline ring. Kinetic studies on complex formation can be interpreted by considering that initial coordination of L1 and L2 takes place through the nitrogen atom in the quinoline ring. This is followed by coordination of the remaining nitrogen atoms, in a process that is faster in the L1 complex probably because substitution at the quinoline ring facilitates the reorganization. Kinetic studies on complex decomposition provide clear evidence on the occurrence of the molecular motion typical of scorpiands in the case of the L2 complex, for which decomposition starts with a very fast process (sub-millisecond timescale) that involves a shift in the absorption band from 643 to 690 nm

Protection of folic acid through encapsulation in mesoporous silica particles included in fruit juices

[EN] Folic acid (FA) is a synthetic vitamin commonly used for food fortification. However, its vulnerability to processing and storage implies loss of efficiency, which would induce over-fortification by processors to obtain a minimum dose upon consumption. Recent studies have indicated potential adverse effects of FA overdoses, and FA protection during processing and storage could lead to more accurate fortification. In addition, sustained vitamin release after consumption would help improve its metabolism. The objective of this work was to study controlled FA delivery and stability in fruit juices to reduce potential over-fortification risks by using gated mesoporous silica particles (MSPs). The obtained results indicated that FA encapsulation in MSPs significantly improved its stability and contributed to controlled release after consumption by modifying vitamin bioaccessibility. These results confirmed the suitability of MSPs as support for controlled release and protection of bioactive molecules in food matrices in different food production and storage stages.Authors gratefully acknowledge the financial support from the Ministerio de Economia y Competitividad and FEDER-EU (Projects AGL2012-39597-C02-01, AGL2015-70235-C2-1-R, AGL2015-70235-C2-2-R and MAT2015-64139-C4-1-R (MINECO/FEDER)) and the Generalitat Valenciana (Project PROMETEOII/2014/047). M.R.R. is grateful to the Ministerio de Ciencia e Innovacion for her grant (AP2010-4369). The authors also thank the Electron Microscopy Service at the UPV for support.Ruiz Rico, M.; Pérez-Esteve, É.; Lerma-García, MJ.; Marcos Martínez, MD.; Martínez-Máñez, R.; Barat Baviera, JM. (2017). Protection of folic acid through encapsulation in mesoporous silica particles included in fruit juices. Food Chemistry. 218:471-478. https://doi.org/10.1016/j.foodchem.2016.09.097S47147821

Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic

[EN] The induction of senescence produces a stable cell cycle arrest in cancer cells, thereby inhibiting tumor growth; however, the incomplete immune cell-mediated clearance of senescent cells may favor tumor relapse, limiting the long-term anti-tumorigenic effect of such drugs. A combination of senescence induction and the elimination of senescent cells may, therefore, represent an efficient means to inhibit tumor relapse. In this study, we explored the antitumor efficacy of a combinatory senogenic and targeted senolytic therapy in an immunocompetent orthotopic mouse model of the aggressive triple negative breast cancer subtype. Following palbociclib-induced senogenesis and senolysis by treatment with nano-encapsulated senolytic agent navitoclax, we observed inhibited tumor growth, reduced metastases, and a reduction in the systemic toxicity of navitoclax. We believe that this combination treatment approach may have relevance to other senescence-inducing chemotherapeutic drugs and additional tumor types. Significance: While the application of senescence inducers represents a successful treatment strategy in breast cancer patients, some patients still relapse, perhaps due to the subsequent accumulation of senescent cells in the body that can promote tumor recurrence. We now demonstrate that a combination treatment of a senescence inducer and a senolytic nanoparticle selectively eliminates senescent cells, delays tumor growth, and reduces metastases in a mouse model of aggressive breast cancer. Collectively, our results support targeted senolysis as a new therapeutic opportunity to improve outcomes in breast cancer patients.The M.O. laboratory members thank the financial support from the Spanish Government (project SAF2017-84689-R (MINECO/AEI/FEDER, EU)) and the Generalitat Valenciana (project PROMETEO/2019/065). The R.M. laboratory members thank the financial support from the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/FEDER, EU) and the Generalitat Valenciana (project PROMETEO 2018/024). Both I.G. and B.L-T. are grateful to the Generalitat Valenciana and the Spanish Ministry of Economy, respectively, for their Ph.D. grants. I.G. would like to thank I. Borreda and J. Forteza and the Instituto Valenciano de Patologia for their special collaboration and F. Sancenon for his appreciated helpGaliana, I.; Lozano-Torres, B.; Sancho, M.; Alfonso-Navarro, M.; Bernardos Bau, A.; Bisbal, V.; Serrano, M.... (2020). Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic. Journal of Controlled Release. 323:624-634. https://doi.org/10.1016/j.jconrel.2020.04.045S624634323Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018). Hallmarks of Cellular Senescence. 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Cellular senescence and cancer chemotherapy resistance. Drug Resistance Updates, 15(1-2), 123-131. doi:10.1016/j.drup.2012.01.002Wieland, E., Rodriguez-Vita, J., Liebler, S. S., Mogler, C., Moll, I., Herberich, S. E., … Fischer, A. (2017). Endothelial Notch1 Activity Facilitates Metastasis. Cancer Cell, 31(3), 355-367. doi:10.1016/j.ccell.2017.01.007Milanovic, M., Fan, D. N. Y., Belenki, D., Däbritz, J. H. M., Zhao, Z., Yu, Y., … Schmitt, C. A. (2017). Senescence-associated reprogramming promotes cancer stemness. Nature, 553(7686), 96-100. doi:10.1038/nature25167Parrinello, S., Coppe, J.-P., Krtolica, A., & Campisi, J. (2005). Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. Journal of Cell Science, 118(3), 485-496. doi:10.1242/jcs.01635Kirkland, J. L., Tchkonia, T., Zhu, Y., Niedernhofer, L. J., & Robbins, P. D. (2017). The Clinical Potential of Senolytic Drugs. Journal of the American Geriatrics Society, 65(10), 2297-2301. doi:10.1111/jgs.14969Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017). Senescent cells: an emerging target for diseases of ageing. Nature Reviews Drug Discovery, 16(10), 718-735. doi:10.1038/nrd.2017.116Lozano-Torres, B., Estepa-Fernández, A., Rovira, M., Orzáez, M., Serrano, M., Martínez-Máñez, R., & Sancenón, F. (2019). The chemistry of senescence. Nature Reviews Chemistry, 3(7), 426-441. doi:10.1038/s41570-019-0108-0Zhu, Y., Tchkonia, T., Fuhrmann‐Stroissnigg, H., Dai, H. M., Ling, Y. Y., Stout, M. B., … Kirkland, J. L. (2016). Identification of a novel senolytic agent, navitoclax, targeting the Bcl‐2 family of anti‐apoptotic factors. Aging Cell, 15(3), 428-435. doi:10.1111/acel.12445Baar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., … de Keizer, P. L. J. (2017). Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell, 169(1), 132-147.e16. doi:10.1016/j.cell.2017.02.031Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … Kirkland, J. L. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell, 14(4), 644-658. doi:10.1111/acel.12344Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., … Zhou, D. (2015). Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nature Medicine, 22(1), 78-83. doi:10.1038/nm.4010Kile, B. T. (2014). The role of apoptosis in megakaryocytes and platelets. British Journal of Haematology, 165(2), 217-226. doi:10.1111/bjh.12757Aznar, 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.5b00456Llopis-Lorente, A., Lozano-Torres, B., Bernardos, A., Martínez-Máñez, R., & Sancenón, F. (2017). Mesoporous silica materials for controlled delivery based on enzymes. Journal of Materials Chemistry B, 5(17), 3069-3083. doi:10.1039/c7tb00348jSu, Y.-L., & Hu, S.-H. (2018). Functional Nanoparticles for Tumor Penetration of Therapeutics. Pharmaceutics, 10(4), 193. doi:10.3390/pharmaceutics10040193Giménez, C., de la Torre, C., Gorbe, M., Aznar, E., Sancenón, F., Murguía, J. R., … Amorós, P. (2015). Gated Mesoporous Silica Nanoparticles for the Controlled Delivery of Drugs in Cancer Cells. Langmuir, 31(12), 3753-3762. doi:10.1021/acs.langmuir.5b00139Agostini, A., Mondragón, L., Bernardos, A., Martínez-Máñez, R., Marcos, M. D., Sancenón, F., … Murguía, J. R. (2012). Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles. 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Senescence in premalignant tumours. Nature, 436(7051), 642-642. doi:10.1038/436642aBaker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., … van Deursen, J. M. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 479(7372), 232-236. doi:10.1038/nature10600Jaskelioff, M., Muller, F. L., Paik, J.-H., Thomas, E., Jiang, S., Adams, A. C., … DePinho, R. A. (2010). Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature, 469(7328), 102-106. doi:10.1038/nature09603Lehmann, M., Korfei, M., Mutze, K., Klee, S., Skronska-Wasek, W., Alsafadi, H. N., … Königshoff, M. (2017). Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosisex vivo. European Respiratory Journal, 50(2), 1602367. doi:10.1183/13993003.02367-2016Schafer, M. J., White, T. A., Iijima, K., Haak, A. J., Ligresti, G., Atkinson, E. J., … LeBrasseur, N. K. (2017). 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New Oleic Acid-Capped Mesoporous Silica Particles as Surfactant-Responsive Delivery Systems

[EN] A new delivery microdevice, based on hydrophobic oleic acid¿capped mesoporous silica particles and able to payload release in the presence of surfactants, has been developed. The oleic acid functionalization confers to the system a high hydrophobic character, which avoids cargo release unless surfactant molecules are present. The performance of this oleic¿acid capped microdevice in the presence of different surfactants is presented and its zero¿release operation in the absence of surfactants is demonstrated.The authors want to thank the Spanish Government (projects MAT2015-64139-C4-1-R, AGL2015-70235-C2-1-R and AGL2015-70235-C2-2-R (MINECO/FEDER)) and RTI2018-100910-B-C41, RTI2018-101599-B-C22 and RTI2018-101599-B-C21 (MCUI/AEI/FEDER, UE)) and Generalitat Valenciana (project PROMETEO/2018/024) for support. E.P.-R. thanks the Generalitat Valenciana for her predoctoral fellowship. A.B. wants to acknowledge the Spanish Government for the financial support Juan de la Cierva Incorporación IJCI-2014-21534. The authors also thank the Electron Microscopy Service at the UPV for support.Poyatos-Racionero, E.; Pérez-Esteve, É.; Marcos Martínez, MD.; Barat Baviera, JM.; Martínez-Máñez, R.; Aznar, E.; Bernardos Bau, A. (2019). New Oleic Acid-Capped Mesoporous Silica Particles as Surfactant-Responsive Delivery Systems. ChemistryOpen. 8(8):1052-1056. https://doi.org/10.1002/open.201900092S1052105688HARRISON, K. (2007). Introduction to polymeric drug delivery systems. Biomedical Polymers, 33-56. doi:10.1533/9781845693640.33Bourganis, V., Karamanidou, T., Kammona, O., & Kiparissides, C. (2017). Polyelectrolyte complexes as prospective carriers for the oral delivery of protein therapeutics. European Journal of Pharmaceutics and Biopharmaceutics, 111, 44-60. doi:10.1016/j.ejpb.2016.11.005El-Safty, S. A., Shenashen, M. A., & Ismail, A. A. (2012). 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Eugenol and thymol immobilised on mesoporous silica-based material as an innovative antifungal system: Application in strawberry jam

[EN] Essential oils and their main compounds have been studied in-depth for their antifungal properties against a wide variety of microorganisms. However, the strong odour emitted by them, even at low concentrations, makes their incorporation into food matrices difficult. Immobilisation of antimicrobial compounds on solid surfaces could be a strategy to reduce their odour impact. The antifungal effectiveness of eugenol and thymol bioactive agents, free and immobilised on mesoporous silica microparticles (MCM-41 family), and their impact on the final aroma and fungal decay of strawberry jam, were evaluated herein. Free eugenol and thymol exhibited good antifungal properties against the fungi strains tested, and thymol proved more effective. The antifungal activity of immobilised eugenol and thymol displayed greater antifungal activity for immobilised eugenol. The jams prepared with immobilised eugenol on MCM-41 microparticles exhibited no mould and yeast development during the studied storage time. The sensory evaluation confirmed that eugenol and thymol immobilisation reduced their typical strong impact on strawberry jam flavour. This work demonstrates the promising use of immobilised eugenol on mesoporous silica microparticles to control strawberry jam decay. (C) 2017 Elsevier Ltd. All rights reserved.Authors gratefully acknowledge the financial support from MINECO-Spanish Government and FEDER-EU (Projects AGL2012-39597-C02-01, AGL2015-70235-C2-1-R and MAT2015-64139-C4-1) and the Generalitat Valencia (Project PROMETEOII/2014/047). Furthermore, author Susana Ribes is grateful to the Universitat Politecnica de Valencia (UPV) for her FPI grant.Ribes-Llop, S.; Pérez-Esteve, É.; Ruiz Rico, M.; Fuentes López, A.; Talens Oliag, P.; Martínez-Máñez, R.; Barat Baviera, JM. (2017). Eugenol and thymol immobilised on mesoporous silica-based material as an innovative antifungal system: Application in strawberry jam. Food Control. 81:181-188. https://doi.org/10.1016/j.foodcont.2017.06.006S1811888

Enhanced antimicrobial activity of essential oil components immobilized on silica particles

[EN] The antimicrobial activity of essential oils components (EOCs) is well-known. However, their high volatility and powerful aroma limit their application in the formulation of a wide range of food products. In this context, the antimicrobial activity of carvacrol, eugenol, thymol and vanillin grafted onto the surface of three silica supports with different morphologies, textural properties and chemical reactivities (fumed silica, amorphous silica and MCM-41) was evaluated herein. Materials characterization revealed a good immobilization yield and all the devices showed a micro-scale particle size. Sensory evaluation revealed that sensory perception of EOCs decreases after covalent immobilization. Moreover, immobilization greatly enhanced the antimicrobial activity of the essential oil components against Listeria innocua and Escherichia coli compared to free components. The incorporation of EOCs immobilized on silica particles into pasteurized milk inoculated with L. innocua demonstrated their effectiveness not only for in vitro conditions, but also in a real food system.Authors gratefully acknowledge the financial support from the Ministerio de Economia, Industria y Competitividad and FEDER funds (Projects AGL2015-70235-C2-1-R, AGL2015-70235-C2-2-R and MAT2015-64139-C4-1-R (MINECO/FEDER)) and the Generalitat Valenciana (Project PROMETEOII/2014/047). M.R.R. is grateful to the Ministerio de Education, Cultura y Deporte for her grant (AP2010-4369). The authors also thank the Electron Microscopy Service at the UPV for support.Ruiz Rico, M.; Pérez-Esteve, É.; Bernardos Bau, A.; Sancenón Galarza, F.; Martínez-Máñez, R.; Marcos Martínez, MD.; Barat Baviera, JM. (2017). Enhanced antimicrobial activity of essential oil components immobilized on silica particles. Food Chemistry. 233:228-236. https://doi.org/10.1016/j.foodchem.2017.04.118S22823623