Efficiency of Antimicrobial Electrospun Thymol-Loaded Polycaprolactone Mats in Vivo

Due to the prevalence of antimicrobial resistant pathogens, natural products with long-term antimicrobial activities are considered as potential alternatives. In this work, polycaprolactone (PCL) electrospun fibers with mean diameters around 299 nm and loaded with 14.92 ± 1.31% w/w thymol (THY) were synthesized. The mats had appropriate elongation at break (74.4 ± 9.5%) and tensile strength (3.0 ± 0.5 MPa) to be potentially used as wound dressing materials. In vivo studies were performed using eight to ten week-old male SKH1 hairless mice. The infection progression was evaluated through a semiquantitative method and quantitative polymerase chain reaction. The analyses of post-mortem samples indicated that THY-loaded PCL fibers acted as inhibitors of Staphylococcus aureus ATCC 25923 strain growth being as efficient as chlorhexidine (CLXD). Histopathological and immunohistochemical studies showed that the PCL-THY-treated wounds were almost free of an inflammatory reaction. Therefore, wound dressings containing natural compounds can prevent infection and promote wound healing and prompt regeneration. Copyrigh

Structure-Guided Approach for the Development of MUC1-Glycopeptide-Based Cancer Vaccines with Predictable Responses

Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 956544. F.S.L., A.E.B., T.K.R., and S.T. are recipients of Sklodowska Curie ITN, DIRNANO, grant agreement No. 956544. F.C. thanks the Mizutani Foundation for Glycoscience (grant 220115). I.A.B. and A.A. thank the Asociación Española Contra el Cancer (AECC), sección La Rioja, for doctoral fellowship. We thank the ALBA (Barcelona, Spain) synchrotron beamline XALOC. We thank ARAID, the Agencia Estatal de Investigación (AEI, BFU2016-75633-P and PID2019-105451GB-I00 to R.H.-G., PID2021-127622OB-I00 and PDC2022-133725-C21 to F.C., PID2022-136735OB-I00 to A.M.), Universidad de La Rioja (REGI22/47 and REGI22/16), Gobierno de Aragón (E34_R17 and LMP58_18 to R.H.-G.) with FEDER (2014-2020) funds for “Building Europe from Aragón” for financial support, and the COST Action CA18103 INNOGLY: Innovation with Glycans new frontiers from synthesis to new biological targets. F.M. acknowledges Fundação para a Ciência e Tecnologia Portugal (FCT-Portugal) for 2020.00233.CEECIND and PTDC/BIA-MIB/31028/2017. A.S.G. thanks FCT-Portugal for PhD fellowships (SFRH/BD/140394/2018 and COVID/BD/152986/2023). F.M and A.S.G. thank UCIBIO project (UIDP/04378/2020 and UIDB/04378/2020), and Associate Laboratory Institute for Health and Bioeconomy - i4HB project (LA/P/0140/2020) and the National NMR Facility supported by FCT-Portugal (ROTEIRO/0031/2013-PINFRA/22161/2016, cofinanced by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). The authors thank Dr Vikki Cantrill for her help with the editing of this manuscript. Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 956544. F.S.L., A.E.B., T.K.R., and S.T. are recipients of Sklodowska Curie ITN, DIRNANO, grant agreement No. 956544. F.C. thanks the Mizutani Foundation for Glycoscience (grant 220115). I.A.B. and A.A. thank the Asociación Española Contra el Cancer (AECC), sección La Rioja, for doctoral fellowship. We thank the ALBA (Barcelona, Spain) synchrotron beamline XALOC. We thank ARAID, the Agencia Estatal de Investigación (AEI, BFU2016-75633-P and PID2019-105451GB-I00 to R.H.-G., PID2021-127622OB-I00 and PDC2022-133725-C21 to F.C., PID2022-136735OB-I00 to A.M.), Universidad de La Rioja (REGI22/47 and REGI22/16), Gobierno de Aragón (E34_R17 and LMP58_18 to R.H.-G.) with FEDER (2014–2020) funds for “Building Europe from Aragón” for financial support, and the COST Action CA18103 INNOGLY: Innovation with Glycans new frontiers from synthesis to new biological targets. F.M. acknowledges Fundação para a Ciência e Tecnologia Portugal (FCT-Portugal) for 2020.00233.CEECIND and PTDC/BIA-MIB/31028/2017. A.S.G. thanks FCT-Portugal for PhD fellowships (SFRH/BD/140394/2018 and COVID/BD/152986/2023). F.M and A.S.G. thank UCIBIO project (UIDP/04378/2020 and UIDB/04378/2020), and Associate Laboratory Institute for Health and Bioeconomy - i4HB project (LA/P/0140/2020) and the National NMR Facility supported by FCT-Portugal (ROTEIRO/0031/2013–PINFRA/22161/2016, cofinanced by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). The authors thank Dr Vikki Cantrill for her help with the editing of this manuscript. Publisher Copyright: © 2023 The Authors. Published by American Chemical SocietyMucin-1 (MUC1) glycopeptides are exceptional candidates for potential cancer vaccines. However, their autoantigenic nature often results in a weak immune response. To overcome this drawback, we carefully engineered synthetic antigens with precise chemical modifications. To be effective and stimulate an anti-MUC1 response, artificial antigens must mimic the conformational dynamics of natural antigens in solution and have an equivalent or higher binding affinity to anti-MUC1 antibodies than their natural counterparts. As a proof of concept, we have developed a glycopeptide that contains noncanonical amino acid (2S,3R)-3-hydroxynorvaline. The unnatural antigen fulfills these two properties and effectively mimics the threonine-derived antigen. On the one hand, conformational analysis in water shows that this surrogate explores a landscape similar to that of the natural variant. On the other hand, the presence of an additional methylene group in the side chain of this analog compared to the threonine residue enhances a CH/π interaction in the antigen/antibody complex. Despite an enthalpy-entropy balance, this synthetic glycopeptide has a binding affinity slightly higher than that of its natural counterpart. When conjugated with gold nanoparticles, the vaccine candidate stimulates the formation of specific anti-MUC1 IgG antibodies in mice and shows efficacy comparable to that of the natural derivative. The antibodies also exhibit cross-reactivity to selectively target, for example, human breast cancer cells. This investigation relied on numerous analytical (e.g., NMR spectroscopy and X-ray crystallography) and biophysical techniques and molecular dynamics simulations to characterize the antigen-antibody interactions. This workflow streamlines the synthetic process, saves time, and reduces the need for extensive, animal-intensive immunization procedures. These advances underscore the promise of structure-based rational design in the advance of cancer vaccine development.publishersversionpublishe

Structure-Guided Approach for the Development of MUC1-Glycopeptide-Based Cancer Vaccines with Predictable Responses

Mucin-1 (MUC1) glycopeptides are exceptional candidates for potential cancer vaccines. However, their autoantigenic nature often results in a weak immune response. To overcome this drawback, we carefully engineered synthetic antigens with precise chemical modifications. To be effective and stimulate an anti-MUC1 response, artificial antigens must mimic the conformational dynamics of natural antigens in solution and have an equivalent or higher binding affinity to anti-MUC1 antibodies than their natural counterparts. As a proof of concept, we have developed a glycopeptide that contains noncanonical amino acid (2S,3R)-3-hydroxynorvaline. The unnatural antigen fulfills these two properties and effectively mimics the threonine-derived antigen. On the one hand, conformational analysis in water shows that this surrogate explores a landscape similar to that of the natural variant. On the other hand, the presence of an additional methylene group in the side chain of this analog compared to the threonine residue enhances a CH/π interaction in the antigen/antibody complex. Despite an enthalpy–entropy balance, this synthetic glycopeptide has a binding affinity slightly higher than that of its natural counterpart. When conjugated with gold nanoparticles, the vaccine candidate stimulates the formation of specific anti-MUC1 IgG antibodies in mice and shows efficacy comparable to that of the natural derivative. The antibodies also exhibit cross-reactivity to selectively target, for example, human breast cancer cells. This investigation relied on numerous analytical (e.g., NMR spectroscopy and X-ray crystallography) and biophysical techniques and molecular dynamics simulations to characterize the antigen–antibody interactions. This workflow streamlines the synthetic process, saves time, and reduces the need for extensive, animal-intensive immunization procedures. These advances underscore the promise of structure-based rational design in the advance of cancer vaccine development

Structure-Guided Approach for the Development of MUC1-Glycopeptide-Based Cancer Vaccines with Predictable Responses

Mucin-1(MUC1)glycopeptidesareexceptionalcandidatesforpotentialcancervaccines.However,theirautoantigenicnatureoftenresultsinaweakimmuneresponse.Toovercomethisdrawback,wecarefullyengineeredsyntheticantigenswithprecisechemicalmodifications.Tobeeffectiveandstimulateananti-MUC1response,artificialantigensmustmimictheconforma-tionaldynamicsofnaturalantigensinsolutionandhaveanequivalentorhigherbindingaffinitytoanti-MUC1antibodiesthantheirnaturalcounterparts.Asa proofofconcept,wehavedevelopeda glycopeptidethatcontainsnoncanonicalaminoacid(2S,3R)-3-hydroxynorvaline.Theunnaturalantigenfulfillsthesetwopropertiesandeffectivelymimicsthethreonine-derivedantigen.Ontheonehand,conformationalanalysisinwatershowsthatthissurrogateexploresalandscapesimilartothatofthenaturalvariant.Ontheotherhand,thepresenceofanadditionalmethylenegroupinthesidechainofthisanalogcomparedtothethreonineresidueenhancesa CH/interactionintheantigen/antibodycomplex.Despiteanenthalpyentropybalance,thissyntheticglycopeptidehasabindingaffinityslightlyhigherthanthatofitsnaturalcounterpart.Whenconjugatedwithgoldnanoparticles,thevaccinecandidatestimulatestheformationofspecificanti-MUC1IgGantibodiesinmiceandshowsefficacycomparabletothatofthenaturalderivative.Theantibodiesalsoexhibitcross-reactivitytoselectivelytarget,forexample,humanbreastcancercells.Thisinvestigationreliedonnumerousanalytical(e.g.,NMRspectroscopyandX-raycrystallography)andbiophysicaltechniquesandmoleculardynamicssimulationstocharacterizetheantigenantibodyinteractions.Thisworkflowstreamlinesthesyntheticprocess,savestime,andreducestheneedforextensive,animal-intensiveimmunizationprocedures.Theseadvancesunderscorethepromiseofstructure-basedrationaldesignintheadvanceofcance

The European Solar Telescope

The European Solar Telescope (EST) is a project aimed at studying the magnetic connectivity of the solar atmosphere, from the deep photosphere to the upper chromosphere. Its design combines the knowledge and expertise gathered by the European solar physics community during the construction and operation of state-of-the-art solar telescopes operating in visible and near-infrared wavelengths: the Swedish 1m Solar Telescope, the German Vacuum Tower Telescope and GREGOR, the French Télescope Héliographique pour l'Étude du Magnétisme et des Instabilités Solaires, and the Dutch Open Telescope. With its 4.2 m primary mirror and an open configuration, EST will become the most powerful European ground-based facility to study the Sun in the coming decades in the visible and near-infrared bands. EST uses the most innovative technological advances: the first adaptive secondary mirror ever used in a solar telescope, a complex multi-conjugate adaptive optics with deformable mirrors that form part of the optical design in a natural way, a polarimetrically compensated telescope design that eliminates the complex temporal variation and wavelength dependence of the telescope Mueller matrix, and an instrument suite containing several (etalon-based) tunable imaging spectropolarimeters and several integral field unit spectropolarimeters. This publication summarises some fundamental science questions that can be addressed with the telescope, together with a complete description of its major subsystems

The European Solar Telescope

The European Solar Telescope (EST) is a project aimed at studying the magnetic connectivity of the solar atmosphere, from the deep photosphere to the upper chromosphere. Its design combines the knowledge and expertise gathered by the European solar physics community during the construction and operation of state-of-the-art solar telescopes operating in visible and near-infrared wavelengths: the Swedish 1m Solar Telescope, the German Vacuum Tower Telescope and GREGOR, the French Télescope Héliographique pour l’Étude du Magnétisme et des Instabilités Solaires, and the Dutch Open Telescope. With its 4.2 m primary mirror and an open configuration, EST will become the most powerful European ground-based facility to study the Sun in the coming decades in the visible and near-infrared bands. EST uses the most innovative technological advances: the first adaptive secondary mirror ever used in a solar telescope, a complex multi-conjugate adaptive optics with deformable mirrors that form part of the optical design in a natural way, a polarimetrically compensated telescope design that eliminates the complex temporal variation and wavelength dependence of the telescope Mueller matrix, and an instrument suite containing several (etalon-based) tunable imaging spectropolarimeters and several integral field unit spectropolarimeters. This publication summarises some fundamental science questions that can be addressed with the telescope, together with a complete description of its major subsystems

DESARROLLO DE UN MODELO PARA EL CÁLCULO DE CAUDALES DE DISEÑO Y CURVAS DE PROBABILIDAD DE FRECUENCIA DE CAUDALES EN BOMBEOS DIRECTOS

[EN] Description of a new model to calculate the probability density functions of flow and the design flow in pipes of irrigation networks in which the hydrant opening probability is not constant during the irrigation day. Clément formulation is adapted to the hypothesis of continuous irrigation and not allowed irrigation time period. These hypotheses cause a non equiprobable hydrant opening probability during the irrigation day. That behavior is quite common in direct pump pressurized irrigation networks and leads to high design flows compared to Clément formulation. Design flows calculated with three different models, proposed model, Clément formulation, and to RDDC, are compared in this paper.[ES] Se describe un nuevo modelo conceptual para el cálculo de curvas de densidad de probabilidad de caudales, y de los caudales de diseño, en redes de riego a la demanda en que no se cumple una de las principales hipótesis de la formulación de Clément: la igualdad de probabilidad de inicio de riego para todas las horas de la Jornada de Riego (JR). En este modelo, se adapta la formulación de Clément para condiciones en que existen horas no hábiles en la JR para el riego y además el riego se ejecuta de forma ininterrumpida. En tales casos no existe equiprobabilidad de apertura de hidrante a lo largo de la JR. Este comportamiento es habitual en el riego presurizado con sistemas con bombeo directo, e induce caudales de diseño sensiblemente superiores a los dados por la formulación tradicional. Se realiza, para un caso teórico, una comparación los caudales de diseño obtenidos mediante la formulación de Clément, mediante un procedimiento heurístico de simulación de múltiples escenarios (RDDC) y mediante la propuesta en este artículo.Faci, E.; Aliod, R.; Paño, J.; García Asín, S. (2015). DESARROLLO DE UN MODELO PARA EL CÁLCULO DE CAUDALES DE DISEÑO Y CURVAS DE PROBABILIDAD DE FRECUENCIA DE CAUDALES EN BOMBEOS DIRECTOS. En XXXIII CONGRESO NACIONAL DE RIEGOS. Valencia 16-18 junio de 2015. Editorial Universitat Politècnica de València. https://doi.org/10.4995/CNRiegos.2015.1513OC

Prospectiva en torno a las grandes dimensiones de los programas de Garantía Social.

El artículo se divide en cuatro apartados. En el primero, se presentan los antecedentes y el marco legal de los Programas de Garantía Social (PGS). En el segundo, se concretan los objetivos y modalidades de estos programas, las características del alumnado que los cursa y el perfil del profesorado que los imparte. El tercer apartado se centra en el contexto socio-educativo de la Comunidad de Castilla La Mancha y el estudio de los PGS que en ella se desarrollan. Además, se presentan las dimensiones de los cuestionarios elaborados para realizarlo. Por último, en el cuarto apartado, se exponen las conclusiones derivadas de su aplicación y análisis en el estudio de la implantación de los PGS en la Comunidad de Castilla La Mancha, y se hacen unas propuestas de optimizaciön que pueden generalizarse a otras comunidades autónomas

Prospectiva en torno a las grandes dimensiones de los programas de Garantía Social.

El artículo se divide en cuatro apartados. En el primero, se presentan los antecedentes y el marco legal de los Programas de Garantía Social (PGS). En el segundo, se concretan los objetivos y modalidades de estos programas, las características del alumnado que los cursa y el perfil del profesorado que los imparte. El tercer apartado se centra en el contexto socio-educativo de la Comunidad de Castilla La Mancha y el estudio de los PGS que en ella se desarrollan. Además, se presentan las dimensiones de los cuestionarios elaborados para realizarlo. Por último, en el cuarto apartado, se exponen las conclusiones derivadas de su aplicación y análisis en el estudio de la implantación de los PGS en la Comunidad de Castilla La Mancha, y se hacen unas propuestas de optimizaciön que pueden generalizarse a otras comunidades autónomas

Structural characterization of an unprecedented lectin-like antitumoral anti-MUC1 antibody.

The molecular basis of antibody 5E5, which recognizes the entire GalNAc unit as a primary epitope is disclosed. The antibody's contacts with the peptide are mostly limited to two residues, allowing it to show some degree of promiscuity. These findings open the door to the chemical design of peptide-mimetics for developing efficient anti-cancer vaccines and diagnostic tools