Article title: Analysis of the evolution in the idea of sustainability of future teachers after an intervention in the classroom

Hemos llevado a cabo una intervención con futuros maestros de Educación Primaria con la intención de trabajar el concepto de sostenibilidad. La secuencia desarrollada incluye la elaboración de un proyecto y una unidad didáctica por investigación escolar. A través de un portafolio los alumnos expresaron sus reflexiones sobre su idea de sostenibilidad. Para analizarlas se diseñó una tabla de niveles con indicadores. Más de la mitad del alumnado ha tenido una evolución significativa progresando desde ideas ligadas a aspectos físico-naturales exclusivamente, hacia un modelo emergente que incluye aspectos más sociales, complejos e interconectados.We have carried out an intervention with future teachers of Primary Education with the intention of working on the concept of sustainability. The sequence includes the elaboration of a project and a didactic unit by school research. Through a portfolio the students expressed their thoughts on their idea of sustainability. To analyze them, a table of levels with indicators was designed. More than half of the students have had a significant evolution progressing from ideas linked to natural physical aspects exclusively, towards an emerging model that includes more social, complex and interconnected aspects

Excited-states of a rhenium carbonyl diimine complex: solvation models, spin-orbit coupling, and vibrational sampling effects

Presentamos una investigación química cuántica de los estados excitados del complejo [Re (CO) 3 (Im) (Phen)] + (Im = imidazol; Phen = 1,10-fenantrolina) en solución que incluye acoplamientos de giro-órbita y muestreo vibracional. Para este objetivo, implementamos la mecánica cuántica / mecánica molecular (QM / MM) de incrustación electrostática en el conjunto de programas funcionales de densidad de Ámsterdam, adecuados para cálculos funcionales de densidad dependientes del tiempo que incluyen acoplamientos de órbita de espín. La nueva implementación se emplea para simular el espectro de absorción del complejo, que se compara con los resultados de la solvatación continua implícita y la inclusión de densidad congelada. Se utilizan simulaciones de dinámica molecular para muestrear las conformaciones del estado fundamental en la solución. Los resultados demuestran que cualquier estudio de los estados excitados de [Re (CO) 3 (Im) (Phen)] + en solución y su dinámica debe incluir un muestreo extenso de movimiento vibracional y acoplamientos de giro-órbita.We present a quantum-chemical investigation of the excited states of the complex [Re(CO)3(Im)(Phen)]+ (Im = imidazole; Phen = 1,10-phenanthroline) in solution including spin–orbit couplings and vibrational sampling. To this aim, we implemented electrostatic embedding quantum mechanics/molecular mechanics (QM/MM) in the Amsterdam Density Functional program suite, suitable for time-dependent density functional calculations including spin–orbit couplings. The new implementation is employed to simulate the absorption spectrum of the complex, which is compared to the results of implicit continuum solvation and frozen-density embedding. Molecular dynamics simulations are used to sample the ground state conformations in solution. The results demonstrate that any study of the excited states of [Re(CO)3(Im)(Phen)]+ in solution and their dynamics should include extensive sampling of vibrational motion and spin–orbit couplings.• Austrian Science Fund. Proyecto I2883, para Sebastian Mai, Aurora Muñoz-Losa, Letizia González Herrero • Agence Nationale de la Recherche (ANR). Proyecto ANR-15-CE29-0027, para Hugo Gattuso, Maria Fumanal, Antonio Monari, Chantal Daniel • Financial Reporting Council y Labex CSC. Proyecto ANR-10-LABX-0026_CSC, para Maria Fumanal, Chantal Daniel • Action CM1405 - COSTpeerReviewe

Photosynthetic Light-Harvesting Is Tuned by the Heterogeneous Polarizable Environment of the Protein

In photosynthesis, special antenna proteins that contain multiple light-absorbing molecules (chromophores) are able to capture sunlight and transfer the excitation energy to reaction centers with almost 100% quantum efficiencies. The critical role of the protein scaffold in holding the appropriate arrangement of the chromophores is well established and can be intuitively understood given the need to keep optimal dipole−dipole interactions between the energy-transferring chromophores, as described by Förster theory more than 60 years ago. However, the question whether the protein structure can also play an active role by tuning such dipole−dipole interactions has not been answered so far, its effect being rather crudely described by simple screening factors related to the refractive index properties of the system. Here, we present a combined quantum chemical/molecular mechanical approach to compute electronic couplings that accounts for the heterogeneous dielectric nature of the protein−solvent environment in atomic detail. We apply the method to study the effect of dielectric heterogeneity in the energy migration properties of the PE545 principal light-harvesting antenna of the cryptomonad Rhodomonas CS24. We find that dielectric heterogeneity can profoundly tune by a factor up to 4 the energy migration rates between chromophore sites compared to the average continuum dielectric view that has historically been assumed. Our results indicate that engineering of the local dielectric environment can potentially be used to optimize artificial light-harvesting antenna systems

Solvent effects on de-excitation channels in the p-coumaric acid methyl ester anion, an analogue of the photoactive yellow protein (PYP) chromophore

En un intento por arrojar luz sobre los efectos ambientales en los canales de desactivación del cromóforo PYP, se comparan los mecanismos de desactivación radiativa y no radiactiva del éster metílico del ácido p- cúmico aniónico (pCE - ) en la fase gaseosa y la solución acuosa en el CASPT2 // CASSCF / cc-pVDZ nivel y, cuando sea necesario, a nivel CASPT2 // CASPT2 / cc-pVDZ. Encontramos que el solvente produce modificaciones dramáticas en el perfil de energía libre del estado S1. Dos estructuras retorcidas que son mínimas en la fase gaseosa no pudieron ser localizadas en solución acuosa. Además, la estabilidad relativa de los mínimos y las intersecciones cónicas (IC) se revierte con respecto a los valores de la fase gaseosa, lo que afecta a las rutas de desactivación prevalentes. Como consecuencia de estos cambios, se abren tres canales de de-excitación competitivos en solución acuosa: la emisión de fluorescencia desde un mínimo planar en S1, la fotoisomerización trans - cis a través de un IC que implica la rotación del doble enlace de vinilo y el no desvitación radiativa, no reactiva, a través de la IC asociada a la rotación del enlace simple adyacente al grupo fenilo. En la fase gaseosa, los mínimos son las estructuras con menor energía, mientras que en solución la estructura CI β , caracterizada por una gran separación de cargas, se estabiliza fuertemente mediante interacciones con moléculas de agua y se convierte en la estructura con la energía más baja en S1. Estos hechos explican la baja señal de fluorescencia de pCE - en solución acuosa y la presencia de fotoisomerización trans - cis parcial en este sistema.In an attempt to shed light on the environmental effects on the deactivation channels of the PYP chromophore, radiative and non-radiative deactivation mechanisms of the anionic p-coumaric acid methyl ester (pCE−) in the gas phase and water solution are compared at the CASPT2//CASSCF/cc-pVDZ level and, when necessary, at the CASPT2//CASPT2/cc-pVDZ level. We find that the solvent produces dramatic modifications on the free energy profile of the S1 state. Two twisted structures that are minima in the gas phase could not be localized in aqueous solution. Furthermore, the relative stability of minima and conical intersections (CIs) is reverted with respect to the gas phase values, affecting the prevalent de-excitation paths. As a consequence of these changes, three competitive de-excitation channels are open in aqueous solution: the fluorescence emission from a planar minimum on S1, the trans–cis photoisomerization through a CI that involves the rotation of the vinyl double bond and the non-radiative, non-reactive, de-excitation through the CI associated with the rotation of the single bond adjacent to the phenyl group. In the gas phase, the minima are the structures with lower energy, while in solution the CIβ structure, characterized by a large charge separation, is strongly stabilized by interactions with water molecules and becomes the structure with the lowest energy on S1. These facts explain the low fluorescence signal of pCE− in aqueous solution and the presence of partial trans–cis photoisomerization in this system.Trabajo financiado por: Gobierno de Extremadura. Consejería de Economía, Comercio e Innovación. Proyecto GR15169peerReviewe

Optimización y caracterización del proceso de polimerización de "Dermatophagoides pteronyssinus" modificado químicamente con glutaraldehído

La inmunoterapia es el único tratamiento que puede alterar el curso natural de las enfermedades alérgicas. La eficacia de las vacunas inmunoterapéuticas está asociada a la capacidad de activar el sistema inmunológico responsable de la síntesis de anticuerpos IgG y la reducción a largo plazo de IgE, causante de las reacciones alérgicas inmediatas. Se han hecho mejoras en los extractos alergénicos de las vacunas para reducir los efectos secundarios ocasionados con la inmunoterapia como la modificación química de éstos, obteniendo un polimerizado de alto peso molecular. Se ha demostrado la capacidad que tienen reduciendo la alergenicidad y manteniendo su inmunogenicidad. Hemos realizado modificaciones con glutaraldehído a un extracto de Dermatophagoides pteronyssinus (ácaro del polvo), en dos condiciones de temperatura diferentes, 5ºC±3 y a temperatura ambiente, 20ºC±3. Se ha comparado la actividad inmunogénica que tienen cada uno de ellos y su alergenicidad con respecto al producto nativo sin modificar, confirmando que las muestras polimerizadas poseen una disminución de la fijación de IgE a sus correspondientes epitopos alergénicos, y mantienen su eficacia ya que favorecen la inducción de IgG en el sistema inmunológico, por tanto se consigue obtener vacunas más seguras que permiten un menor número de inyecciones en un periodo más corto de tiempo, disminuyendo así el riesgo de reacciones sistémicas al pacient

Energy Flow in the Cryptophyte PE545 Antenna Is Directed by Bilin Pigment Conformation

Structure-based calculations are combined with quantitative modeling of spectra and energy transfer dynamics to detemine the energy transfer scheme of the PE545 principal light-harvesting antenna of the cryptomonad Rhodomonas CS24. We use a recently developed quantum-mechanics/molecular mechanics (QM/MM) method that allows us to account for pigment-protein interactions at atomic detail in site energies, transition dipole moments, and electronic couplings. In addition, conformational flexibility of the pigment-protein complex is accounted for through molecular dynamics (MD) simulations. We find that conformational disorder largely smoothes the large energetic differences predicted from the crystal structure between the pseudosymmetric pairs PEB50/61C-PEB50/61D and PEB82C-PEB82D. Moreover, we find that, in contrast to chlorophyll-based photosynthetic complexes, pigment composition and conformation play a major role in defining the energy ladder in the PE545 complex, rather than specific pigment-protein interactions. This is explained by the remarkable conformational flexibility of the eight bilin pigments in PE545, characterized by a quasi-linear arrangement of four pyrrole units. The MD-QM/MM site energies allow us to reproduce the main features of the spectra, and minor adjustments of the energies of the three red-most pigments DBV19A, DBV19B, and PEB82D allow us to model the spectra of PE545 with a similar quality compared to our original model (model E from Novoderezhkin et al. Biophys. J.2010, 99, 344), which was extracted from the spectral and kinetic fit. Moreover, the fit of the transient absorption kinetics is even better in the new structure-based model. The largest difference between our previous and present results is that the MD-QM/MM calculations predict a much smaller gap between the PEB50/61C and PEB50/61D sites, in better accord with chemical intuition. We conclude that the current adjusted MD-QM/MM energies are more reliable in order to explore the spectral properties and energy transfer dynamics in the PE545 complex

Prácticas de campo colaborativas en el área de producción animal

Memoria ID-041. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2019-2020

Constraining the preservation of organic compounds in Mars analog nontronites after exposure to acid and alkaline fluids

The presence of organic matter in lacustrine mudstone sediments at Gale crater was revealed by the Mars Science Laboratory Curiosity rover, which also identified smectite clay minerals. Analogue experiments on phyllosilicates formed under low temperature aqueous conditons have illustrated that these are excellent reservoirs to host organic compounds against the harsh surface conditions of Mars. Here, we evaluate whether the capacity of smectites to preserve organic compounds can be influenced by a short exposure to different diagenetic fluids. We analyzed the stability of glycine embedded within nontronite samples previously exposed to either acidic or alkaline fluids (hereafter referred to as “treated nontronites”) under Mars-like surface conditions. Analyses performed using multiple techniques showed higher photodegradation of glycine in the acid-treated nontronite, triggered by decarboxylation and deamination processes. In constrast, our experiments showed that glycine molecules were preferably incorporated by ion exchange in the interlayer region of the alkali-treated nontronite, conferring them a better protection against the external conditions. Our results demonstrate that smectite previously exposed to fluids with different pH values influences how glycine is adsorbed into their interlayer regions, affecting their potential for preservation of organic compounds under contemporary Mars surface conditionsEuropean Commission | Ref. FP7 n. 307496European Commission | Ref. H2020 n. 818602Ministerio de Economía | Ref. MDM-2017-0737Ministerio de Economía | Ref. ESP2017-89053-C2-1-

Capecitabine and irinotecan with bevacizumab 2-weekly for metastatic colorectal cancer: the phase II AVAXIRI study

Background: The optimal sequence of chemotherapeutic agents is not firmly established for the treatment of metastatic colorectal cancer (mCRC). This phase II multi-centre study investigated the efficacy and tolerability of a standard capecitabine plus irinotecan (XELIRI) regimen with bevacizumab in previously untreated patients with mCRC. Methods: Patients received intravenous irinotecan 175 mg/m2 on day 1 and oral capecitabine 1000 mg/m2 (800 mg/m2 for patients >65 years of age) twice daily on days 2–8, followed by a 1-week rest, and bevacizumab 5 mg/kg as an intravenous infusion on day 1 every 2 weeks. Results: Seventy-seven patients were included in the intention-to-treat and safety populations. Progression-free survival at 9 months was 61%. The overall response and disease control rates were 51% and 84%, respectively. Median progression-free and overall survival times were 11.9 and 24.8 months, respectively. 48 patients (62%) had at least one grade 3/4 adverse event, the most common being asthenia, diarrhoea and neutropenia. Quality of life varied little over the study period with mean visual analogue scale general health scores ranging from 71 to 76 over cycles 1–11. Conclusion: Our study found irinotecan and capecitabine administered fortnightly with bevacizumab in patients with mCRC to be an effective and tolerable regimen. Trial registration: clinicaltrials.gov identifier NCT00875771. Trial registration date: 04/02/2009. Keywords: Irinotecan, Capecitabine, Bevacizumab, Metastatic colorectal cancer, Chemotherap

BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy

Glycolysis; Melanomas; Targeted therapyGlucólisis; Melanomas; Terapia dirigidaGlucòlisi; Melanomes; Teràpia dirigidaNRAS-mutated melanoma lacks a specific line of treatment. Metabolic reprogramming is considered a novel target to control cancer; however, NRAS-oncogene contribution to this cancer hallmark is mostly unknown. Here, we show that NRASQ61-mutated melanomas specific metabolic settings mediate cell sensitivity to sorafenib upon metabolic stress. Mechanistically, these cells are dependent on glucose metabolism, in which glucose deprivation promotes a switch from CRAF to BRAF signaling. This scenario contributes to cell survival and sustains glucose metabolism through BRAF-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2/3 (PFKFB2/PFKFB3). In turn, this favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop that couples glycolytic flux and the RAS signaling pathway. An in vivo treatment of NRASQ61 mutant melanomas, including patient-derived xenografts, with 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence for NRAS-oncogene contributions to metabolic rewiring and a proof-of-principle for the treatment of NRASQ61-mutated melanoma combining metabolic stress (glycolysis inhibitors) and previously approved drugs, such as sorafenib.This work was funded by Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, “A way to make Europe”/“Investing in your future”) PI14/0375-Fondos FEDER J.A.R., PI17/00043-Fondos FEDER; J.A.R., PI20/0384-Fondos FEDER; J.A.R., Euronanomed2-ISCIII (AC16/00019)-Fondos FEDER; J.A.R., Asociación Española Contra el Cancer (AECC-GCB15152978SOEN) (supported P.G.M., K.M.); J.A.R., Ramón Areces Foundation (supported K.M. and research); J.A.R. (PI17/00412)-Fondos FEDER; R.B., A.M., A.N.S. We thank A. Zorzano’s laboratory for technical assistance and performance of Seahorse technology