Lipid nanoparticles for cyclosporine a administration: Development, characterization, and in vitro evaluation of their immunosuppression activity

Cyclosporine A (CsA) is an immunosuppressant commonly used in transplantation for prevention of organ rejection as well as in the treatment of several autoimmune disorders. Although commercial formulations are available, they have some stability, bioavailability, and toxicity related problems. Some of these issues are associated with the drug or excipients and others with the dosage forms. With the aim of overcoming these drawbacks, lipid nanoparticles (LN) have been proposed as an alternative, since excipients are biocompatible and also a large amount of surfactants and organic solvents can be avoided. CsA was successfully incorporated into LN using the method of hot homogenization followed by ultrasonication. Three different formulations were optimized for CsA oral administration, using different surfactants: Tween® 80, phosphatidylcholine, taurocholate and Pluronic® F127 (either alone or mixtures). Freshly prepared Precirol nanoparticles showed mean sizes with a narrow size distribution ranging from 121 to 202 nm, and after freeze-drying were between 163 and 270 nm, depending on the stabilizer used. Surface charge was negative in all LN developed. High CsA entrapment efficiency of approximately 100% was achieved. Transmission electron microscopy was used to study the morphology of the optimized LN. Also, the crystallinity of the nanoparticles was studied by X-ray powder diffraction and differential scanning calorimetry. The presence of the drug in LN surfaces was confirmed by X-ray photoelectron spectroscopy. The CsA LN developed preserved their physicochemical properties for 3 months when stored at 4°C. Moreover, when the stabilizer system was composed of two surfactants, the LN formulations were also stable at room temperature. Finally, the new CsA formulations showed in vitro dose-dependent immunosuppressive effects caused by the inhibition of IL-2 levels secreted from stimulated Jurkat cells. The findings obtained in this paper suggest that new lipid nanosystems are a good alternative to produce physicochemically stable CsA formulations for oral administration

Poblamiento y Sociedad en el valle medio del Ebro durante la Antigüedad Tardía. Asentamientos rurales y cristianización entre los siglos IV y VIII.

Estudio de la evolución de los asentamientos rurales del valle medio del Ebro durante la Antigüedad Tardía (siglos IV-VIII) y de sus condicionantes sociales, con especial atención al proceso de implantación y difusión del cristianismo en estos territorios.<br /

The CORDEX Flagship Pilot Study in southeastern South America: a comparative study of statistical and dynamical downscaling models in simulating daily extreme precipitation events

The aim of this work is to present preliminary results of the statistical and dynamical simulations carried out within the framework of the Flagship Pilot Study in southeastern South America (FPS-SESA) endorsed by the Coordinated Regional Climate Downscaling Experiments (CORDEX) program. The FPS-SESA initiative seeks to promote inter-institutional collaboration and further networking with focus on extreme rainfall events. The main scientific aim is to study multi-scale processes and interactions most conducive to extreme precipitation events through both statistical and dynamical downscaling techniques, including convection-permitting simulations. To this end, a targeted experiment was designed considering the season October 2009 to March 2010, a period with a record number of extreme precipitation events within SESA. Also, three individual extreme events within that season were chosen as case studies for analyzing specific regional processes and sensitivity to resolutions. Four dynamical and four statistical downscaling models (RCM and ESD respectively) from different institutions contributed to the experiment. In this work, an analysis of the capability of the set of the FPS-SESA downscaling methods in simulating daily precipitation during the selected warm season is presented together with an integrated assessment of multiple sources of observations and available CORDEX Regional Climate Model simulations. Comparisons among all simulations reveal that there is no single model that performs best in all aspects evaluated. The ability in reproducing the different features of daily precipitation depends on the model. However, the evaluation of the sequence of precipitation events, their intensity and timing suggests that FPS-SESA simulations based on both RCM and ESD yield promising results. Most models capture the extreme events selected, although with a considerable spread in accumulated values and the location of heavy precipitation.Thanks to CORDEX for endorsing the FPS-SESA. This work was supported by the University of Buenos Aires 2018- 20020170100117BA grant; JMG, MLB, SAS, RPR funding from the Spanish Research Council (CSIC) I-COOP+ Program “reference COOPB20374”. JMG, JF and AL-G acknowledge support from the Spanish R&D Program through projects MULTI-SDM (CGL2015-66583-R) and INSIGNIA (CGL2016-79210-R), co-funded by the European Regional Development Fund (ERDF/FEDER). AL-G acknowledges support from the Spanish R&D Program through the predoctoral contract BES-2016-078158. Universidad de Cantabria simulations have been carried out on the Altamira Supercomputer at the Instituto de Física de Cantabria (IFCA-CSIC), member of the Spanish Supercomputing Network. MB acknowledges support from the Simons Associateship of the Abdus Salam International Centre for Theoretical Physics. RH acknowledges support from the project LTT17007 funded by the Ministry of Education, Youth, and Sports of the Czech Republic

Global pressures, specific responses: effects of nutrient enrichment in streams from different biomes

Fil: Artigas, Joan. Clermont Université. Université Blaise Pascal. Laboratoire Microorganismes: Génome et Environnement; FranceFil: García-Berthou, Emili. Institute of Aquatic Ecology. University of Girona. Girona; SpainFil: Bauer, Delia Elena. Instituto de Limnología Dr. Raúl A. Ringuelet (ILPLA). Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Castro, Maria I.. Department of Biology. National University of Colombia. Bogotá DC; ColombiaFil: Cochero, Joaquín. Instituto de Limnología Dr. Raúl A. Ringuelet (ILPLA). Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Colautti, Darío César. Instituto de Limnología Dr. Raúl A. Ringuelet (ILPLA). Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Cortelezzi, Agustina. Instituto de Limnología Dr. Raúl A. Ringuelet (ILPLA). Facultad de Ciencias Naturales y Museo. Universidad Nacional de La PlataFil: Donato, John C.. Department of Biology. National University of Colombia. Bogotá DC; ColombiaFil: Elosegi, Arturo. Faculty of Science and Technology. The University of the Basque Country. Bilbao; SpainFil: Feijoó, Claudia S.. INEDES. Department of Basic Sciences. National University of Luján. Luján; ArgentinaFil: Giorgi, Adonis. INEDES. Department of Basic Sciences. National University of Luján. Luján; ArgentinaFil: Gómez, Nora. Institute of Aquatic Ecology. University of Girona. Girona; SpainFil: Leggieri, Leonardo. Institute of Aquatic Ecology. University of Girona. Girona; SpainFil: Muñoz, Isabel. Department of Ecology. University of Barcelona. Barcelona; SpainFil: Rodrigues Capítulo, Alberto. Instituto de Limnología Dr. Raúl A. Ringuelet (ILPLA). Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Romaní, Anna M.. Institute of Aquatic Ecology. University of Girona. Girona; SpainFil: Sabater, Sergi. Catalan Institute for Water Research (ICRA). Scientific and Technological Park of the University of Girona. Girona; Spai

Global pressures, specific responses: effects of nutrient enrichment in streams from different biomes

We assessed the effects of nutrient enrichment on three stream ecosystems running through distinct biomes (Mediterranean, Pampean and Andean). We increased the concentrations of N and P in the stream water 1.6–4-fold following a before–after control–impact paired series (BACIPS) design in each stream, and evaluated changes in the biomass of bacteria, primary producers, invertebrates and fish in the enriched (E) versus control (C) reaches after nutrient addition through a predictive-BACIPS approach. The treatment produced variable biomass responses (2–77% of explained variance) among biological communities and streams. The greatest biomass response was observed for algae in the Andean stream (77% of the variance), although fish also showed important biomass responses (about 9–48%). The strongest biomass response to enrichment (77% in all biological compartments) was found in the Andean stream. The magnitude and seasonality of biomass responses to enrichment were highly site specific, often depending on the basal nutrient concentration and on windows of ecological opportunity (periods when environmental constraints other than nutrients do not limit biomass growth). The Pampean stream, with high basal nutrient concentrations, showed a weak response to enrichment (except for invertebrates), whereas the greater responses of Andean stream communities were presumably favored by wider windows of ecological opportunity in comparison to those from the Mediterranean stream. Despite variation among sites, enrichment globally stimulated the algal-based food webs (algae and invertebrate grazers) but not the detritus-based food webs (bacteria and invertebrate shredders). This study shows that nutrient enrichment tends to globally enhance the biomass of stream biological assemblages, but that its magnitude and extent within the food web are complex and are strongly determined by environmental factors and ecosystem structure.Instituto de Limnología "Dr. Raúl A. Ringuelet

Global CO2 emissions from dry inland waters share common drivers across ecosystems

Many inland waters exhibit complete or partial desiccation, or have vanished due to global change, exposing sediments to the atmosphere. Yet, data on carbon dioxide (CO2) emissions from these sediments are too scarce to upscale emissions for global estimates or to understand their fundamental drivers. Here, we present the results of a global survey covering 196 dry inland waters across diverse ecosystem types and climate zones. We show that their CO2 emissions share fundamental drivers and constitute a substantial fraction of the carbon cycled by inland waters. CO2 emissions were consistent across ecosystem types and climate zones, with local characteristics explaining much of the variability. Accounting for such emissions increases global estimates of carbon emissions from inland waters by 6% (~0.12 Pg C y−1). Our results indicate that emissions from dry inland waters represent a significant and likely increasing component of the inland waters carbon cycle

Mujeres y cultura en la Argentina del siglo XIX

Este libro es el resultado de buscar y rebuscar, acuciadas en un primer momento por una natural curiosidad hacia el siglo XIX, en el baúl de nuestras abuelas o incluso bisabuelas. Y nos encontramos no sólo con el pasado sino con nuestro pasado, rico, complejo, sorprendente en su infinita variedad de hallazgos. Experimentamos un sentimiento de ternura por esas mujeres y de profunda solidaridad ante el esfuerzo que realizaron, muchas veces en condiciones inhóspitas, incomprendidas por sus contemporáneos, varones y mujeres. No sólo mujeres con nombre propio sino mujeres generalmente anónimas forman una parte esencial de la historia no contada, oculta(da) en el polvo acumulado durante el transcurso de los años. Nuestra tarea, nuestra pasión es desenvolverla, descubrirla, deconstruirla. Un acto compartido entre muchas mujeres y algunos varones. En mayor o menor grado, cada artículo en Mujeres y cultura en la Argentina del siglo XIXcontribuye a este fin y también al de la construcción –la re-construcción- de la historia de mujeres en la Argentina. Hay todavía mucho por revolver en esos arcones. Sabemos que hay nombres escondidos todavía en publicaciones que debemos encontrar. Nombres de mujeres, sus labores, que han sido muy poco investigadas o que sencillamente desconocemos. Se trata de hacer visible una producción ignorada y una tradición desdibujada