Blockade of the Interaction of Calcineurin with FOXO in Astrocytes Protects Against Amyloid-βInduced Neuronal Death

Astrocytes actively participate in neuro-inflammatory processes associated to Alzheimer’s disease (AD), and other brain pathologies. We recently showed that an astrocyte-specific intracellular signaling pathway involving an interaction of the phosphatase calcineurin with the transcription factor FOXO3 is a major driver in AD associated pathological inflammation, suggesting a potential new druggable target for this devastating disease. We have now developed decoy molecules to interfere with calcineurin/FOXO3 interactions, and tested them in astrocytes and neuronal co-cultures exposed to amyloid-β (Aβ) toxicity. We observed that interference of calcineurin/FOXO3 interactions exerts a protective action against A-induced neuronal death and favors the production of a set of growth factors that we hypothesize form part of a cytoprotective pathway to resolve inflammation. Furthermore, interference of the A-induced interaction of calcineurin with FOXO3 by decoy compounds significantly decreased amyloid-β protein precursor (AβPP) synthesis, reduced the AβPP amyloidogenic pathway, resulting in lower Alevels, and blocked the expression of pro-inflammatory cytokines TNFα and IL-6 in astrocytes. Collectively, these data indicate that interrupting pro-inflammatory calcineurin/FOXO3 interactions in astrocytes triggered by Aβ accumulation in brain may constitute an effective new therapeutic approach in AD. Future studies with intranasal delivery, or brain barrier permeable decoy compounds, are warranted

Tuning the properties of ionic liquids by mixing with organic solvents: The case of 1-butyl-3-methylimidazolium glutamate with alkanols

Binary liquid mixtures of 1-butyl-3-methylimidazolium glutamate acid ([bmim][glu]) with alkanols (1-propanol, isobutanol and 1,2-propanediol) are studied in the full composition range as a function of temperature using a combined experimental and computational chemistry approach. Experimental thermophysical information as well as derived excess and mixing properties allowed to characterize these complex liquid mixtures in terms of deviation from ideality as well their relationships with the developed intermolecular forces and changes with the type of considered alkanols. Theoretical studies using quantum chemistry and classical molecular dynamics simulations provided nanoscopic characterization on the studied fluids, with particular attention to the extension and nature of hydrogen bonding and its effects on molecular arrangements and mixed fluids’ properties. The reported study provides a micro and macroscopic characterization of the considered aminoacid-based ionic liquid mixtures, thus contributing to the knowledge of sustainable ionic liquid systems mixed with organic solvents for fine tuning properties and developing task specific applications.Shiraz University of Technology and Ministerio de Ciencia, Innovación y Universidades (Spain, project RTI2018-101987-B-I00)

Insights on biodiesel blends with alkanol solvents

Thermophysical properties of mixtures of fatty acid esters with alkanols were measured in the whole composition range as a function of temperature for understanding features of biodiesel blends. Excess and mixing properties calculated from experimental measurements allowed to quantify and analyze the intermolecular forces in the considered systems. Likewise, molecular modelling studies using quantum chemistry and classical molecular dynamics simulations led to a detailed characterization of these systems at the nanoscopic level. The nature of hydrogen bonding in these liquid mixtures was particularly analyzed from macroscopic properties and theoretical modelling results. The reported experimental and computational study allowed to infer the relationships between the intermolecular forces and additional microscopic features and the mixtures macroscopic properties, which are relevant for the development and characterization of biodiesels. The non-ideality behavior of the studied systems shows relevant changes in hydrogen bonding structuring upon mixing, with the fatty acid esters largely disrupting the alcohols self-association, although ester – alcohol hydrogen bonding is developed, this type of interactions is remarkably weaker than those for alcohols. Therefore, the studied biodiesel blends macroscopic properties may be tuned and controlled through the amount of alcohols in the mixtures and rooted on its effect on hydrogen bonding.Shiraz University of Technology (Iran), Junta de Castilla y León (Spain, project BU094G18) and Ministerio de Ciencia, Innovación y Universidades (Spain, project RTI2018-101987-B-I00) for supporting this project. We also acknowledge SCAYLE (Supercomputación Castilla y León, Spain) for providing supercomputing facilities

Glutathione biosynthesis in Arabidopsis trichome cells

In Arabidopsis thaliana, trichome cells are specialized unicellular structures with uncertain functions. Based on earlier observations that one of the genes involved in cysteine biosynthesis (Atcys-3A) is highly expressed in trichomes, we have extended our studies in trichome cells to determine their capacity for glutathione (GSH) biosynthesis. First, we have analyzed by in situ hybridization the tissue-specific expression of the genes Atcys-3A and sat5, which encode O-acetylserine(thio)lyase (OASTL) and serine acetyltransferase (SAT), respectively, as well as gsh1 and gsh2, which encode γ-glutamylcysteine synthetase and glutathione synthetase, respectively. The four genes are highly expressed in leaf trichomes of Arabidopsis, and their mRNA accumulate to high levels. Second, we have directly measured cytoplasmic GSH concentration in intact cells by laser-scanning microscopy after labeling with monochlorobimane as a GSH-specific probe. From these measurements, cytosolic GSH concentrations of 238 ± 25, 80 ± 2, and 144 ± 19 μM were estimated for trichome, basement, and epidermal cells, respectively. Taking into account the volume of the cells measured using stereological techniques, the trichomes have a total GSH content more than 300-fold higher than the basement and epidermal cells. Third, after NaCl treatment, GSH biosynthesis is markedly decreased in trichomes. Atcys-3A, sat5, gsh1, and gsh2 mRNA levels show a decrease in transcript abundance, and [GSH](cyt) is reduced to 47 ± 5 μM. These results suggest the important physiological significance of trichome cells related to GSH biosynthesis and their possible role as a sink during detoxification processes.Dirección General de Investigación Científica y Técnica PB96-1367Junta de Andalucía CVI011

Student mentoring program at the Faculty of Pharmacy, University of Seville (2006/07 - present): SWOT analysis carried out by mentor students

El “Programa de Alumnos Tutores” (LCC, Facultad de Farmacia US) se viene realizando ininterrumpidamente desde 2006/07 hasta la actualidad. Propósito: tutela de alumnos de nuevo ingreso por parte de alumnos de cursos superiores (AATT) bajo la supervisión de Profesores Tutores. Pretende generar una actitud responsable en los AATT y favorecerles el desarrollo de habilidades sociales. El objetivo de este trabajo es recoger las opiniones de los AATT (algunos comenzaron en ediciones anteriores y continúan desinteresadamente). Se aborda mediante un análisis DAFO. Conclusión: se han detectado factores estratégicos críticos, para una vez identificados, usarlos y apoyar en ellos la marcha del “Programa de Alumnos Tutores”, consolidando las fortalezas, minimizando las debilidades, aprovechando las ventajas de las oportunidades, y eliminando o reduciendo las amenazas.The "Student Mentor Program" (Faculty of Pharmacy, US) has been running since 2006/07 – to present. Purpose: to mentor new students by senior students (Mentor Students) under the supervision of mentor professors. It aims to generate a responsible attitude in students and tutors to encourage the development of social skills. Objective: To collect the views of mentor students (some started in previous years and continue to selflessly), through a SWOT analysis. Conclusion: it has been found critical strategic factors. It intends to use these factors for strengthening the "Student Mentor Program"

Propagation characteristics of Cartesian Parabolic-Gaussian beams

We study the propagating and shaping characteristics of the novel one-dimensional Cartesian Parabolic-Gaussian beams. The transverse profile is described by the parabolic cylinder functions and are apodized by a Gaussian envelope. Their physical properties are studied in detail by finding the 2n -order intensity moments of the beam. Propagation through complex ABCD optical systems, normalization factor, beam width, the quality M 2 factor and its kurtosis parameter are derived. We discuss its behavior for different beam parameters and the relation between them. The Cartesian Parabolic-Gaussian beams carry finite power and form a biorthogonal set of solutions of the paraxial wave equation in Cartesian coordinates

Overweight and obesity prevention in Mexico: An intersectionality-based policy analysis

Excess weight (i.e., overweight and obesity) is higher among less educated groups, women, ethnic minorities, and in urban areas. Consistent with the intersectionality perspective, excess weight is more frequent in those who experience disadvantages in more than one area of inequity, e.g., women from a low social position. However, greater attention is paid to individual lifestyle factors, recommending behavioural lifestyle shifts rather than addressing social structural and intermediary determinants. Most public policies and interventions have focused on individual lifestyle components, despite evidence revealed that these interventions have a minimal impact and that it is necessary to move the field forward interventions on the contextual social determinants. Mexico is a unique scenario to analyze public policies and interventions to prevent excess weight from an intersectional perspective, given its concomitants features of high prevalence of excess weight (the second highest country in the world, with more than 75% of the adult population with overweight, including 36.1% of obesity), and high degree of social and gender inequality. Previous evidence in Mexico showed that interventions at the individual-level had little impact to prevent excess weight in lower social position groups. On the other hand, population-based strategies, such as the tax on sugar-sweetened beverages, appeared to be beneficial for all population groups, but especially for those at the bottom of the social hierarchy. Intersectionality has emerged as a highly regarded equity-informed tool for analyzing public policy. The Intersectionality-based Policy Analysis (IBPA) framework developed by Hankivsky (2014, https://pubmed.ncbi.nlm.nih.gov/25492385/) could contribute to identify and address multidimensional inequities and could lead to more effective and responsive policy decisions. The objective of this study is to analyze current nationally adult excess weight prevention public policies and interventions in Mexico, from an intersectionality perspective. Governmental websites, academic papers in English or Spanish, international and non-governmental organizations were searched for current strategies at the national level to prevent excess weight. Particular attention was paid to the current policies, interventions and actions to prevent adult obesity considered by the Global Obesity Observatory (https://data.worldobesity.org/). A total of 7 public policies and interventions were selected to develop a documental analysis (content analysis). First, the PROGRESS Plus framework was used to systematize the social axis of inequality mentioned in the public policy and intervention documents. PROGRESS is an acronym that aims to represent 8 dimensions of inequalities: place of residence, race/ethnicity, occupation, gender/sex, religion, education, socioeconomic status and social capital. Second, the selected documents were e analyzed through the IBPA framework. The questions of the IBPA framework have been adapted to the aims of this study, based on Kakar et al. (2021, https://www.sciencedirect.com/science/article/abs/pii/S0967070X20309276) research applying the IBPA framework for documental analysis. The selected documents were analyzed in order to disentangle to what extent they mention axes of social inequality, whether intersectionality is considered in framing the problem and or the potential solutions.Fil: Tumas, Natalia. Universitat Pompeu Fabra; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad. Universidad Nacional de Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad; ArgentinaFil: Benach, Joan. Universitat Pompeu Fabra; EspañaFil: Carreño, Paula. Universidad Nacional de Córdoba. Facultad de Medicina. Escuela de Nutrición; ArgentinaFil: de la Vega Avila Tulian, Candela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Getova, Simona. Universitat Pompeu Fabra; EspañaFil: Gutiérrez-Zamora Navarro, Mariana. Universitat Pompeu Fabra; EspañaFil: Pericàs, Juan M.. Vall Dhebron University Hospital; EspañaEuropean Consortium for Political Research General ConferenceInnsbruckAustriaUniversity of Innsbruc

Dynamic reflective color pixels based on molybdenum oxide

Active materials which show phase transitions, usually known as Phase Change Materials (PCM), have paved the way to a new generation of reconfigurable plasmonic platforms. Tunable color devices have experienced a great development in the recent years. In particular, reflective color filters can take advantage from sunlight to select and reflect a specific resonant wavelength in the visible spectrum range. Reflective displays are usually structural color filters based on asymmetric Fabry-Perot cavities (AFPCs). For a fixed geometry, most of AFPCs filters generate static color, limiting their potential as tunable color devices. Dynamic color is achieved by introducing an active layer whose optical properties can be modulated by an external stimuli. In this paper, we propose AFPCs based on molybdenum oxide (MoOx, 2<x<3) to achieve switchable on/off color reflective pixels. On and off states of the pixels are controlled through the stoichiometry of the MoOx layer.This work has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement (No 899598 – PHEMTRONICS)

Blockade of the Interaction of Calcineurin with FOXO in Astrocytes Protects Against Amyloid-beta-Induced Neuronal Death

Astrocytes actively participate in neuro-inflammatory processes associated to Alzheimer's disease (AD), and other brain pathologies. We recently showed that an astrocyte-specific intracellular signaling pathway involving an interaction of the phosphatase calcineurin with the transcription factor FOXO3 is a major driver in AD-associated pathological inflammation, suggesting a potential new druggable target for this devastating disease. We have now developed decoy molecules to interfere with calcineurin/FOXO3 interactions, and tested them in astrocytes and neuronal co-cultures exposed to amyloid-beta (A beta) toxicity. We observed that interference of calcineurin/FOXO3 interactions exerts a protective action against A beta-induced neuronal death and favors the production of a set of growth factors that we hypothesize form part of a cytoprotective pathway to resolve inflammation. Furthermore, interference of the A beta-induced interaction of calcineurin with FOXO3 by decoy compounds significantly decreased amyloid-beta protein precursor (A beta PP) synthesis, reduced the A beta PP amyloidogenic pathway, resulting in lower A beta levels, and blocked the expression of pro-inflammatory cytokines TNF alpha and IL-6 in astrocytes. Collectively, these data indicate that interrupting pro-inflammatory calcineurin/FOXO3 interactions in astrocytes triggered by A beta accumulation in brain may constitute an effective new therapeutic approach in AD. Future studies with intranasal delivery, or brain barrier permeable decoy compounds, are warranted.Peer ReviewedPostprint (author's final draft

Nuevo templo augusteo en la Colonia Augusta Firma Astigi

Romula nº 6 (2007), p. 75-114En el presente trabajo se presentan, aún de modo preliminar, las estructuras públicas de cronología romana documentadas en al Plaza de España de Écija, correspondientes a un edificio de culto cuya construcción se llevó a cabo coincidiendo con la fundación de la nueva colonia Augusta Firma Astigi, en época augustea. El estudio se completa con interesantes datos epigráficos que corroboran el carácter cultual del área, enmarcada en el ámbito forense de la ciudad.In this paper are presented preliminary results concerning the public structures from the Roman period documented in the Plaza de España of Écija (Seville), belonging to a cult building constructed in the first years after the foundation of the colonia Augusta Firma Astigi, in the augustan era. The study is completed with relevant epigraphic data that confirm the interpretation of the place as a cult complex included in the forum area of the Roman city.Versión del edito