CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization

Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.5 mg/day for 3 days, as a 90-minute intravenous infusion) in 45 patients (15 per dose-cohort). Treatment was well tolerated, with only two Grade 3 treatment-related adverse events observed (hypersensitivity and diarrhea). The discharge rates by Days 8 and 15 were 56.8% and 81.8%, respectively, with data sustaining dose-effect. A mean 4.2 log10 viral load reduction was attained by Day 15. Improvement in inflammation markers was also noted in a seemingly dose-dependent manner. These results suggest that plitidepsin impacts the outcome of patients with COVID-19.This study has been funded by Pharmamar, S.A. (Madrid, Spain). This work was supported by grants from the Government of Spain (PIE_INTRAMURAL_ LINEA 1 - 202020E079; PIE_INTRAMURAL_CSIC-202020E043). The research of CBIG consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols pharmaceutical. We also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). N.I.U. has non-restrictive funding from PharmaMar to study the antiviral effect of Plitidepsin. N.J.K. was funded by grants from the National Institutes of Health (P50AI150476, U19AI135990, U19AI135972, R01AI143292, R01AI120694, and P01AI063302); by the Excellence in Research Award (ERA) from the Laboratory for Genomics Research (LGR), a collaboration between UCSF, UCB, and GSK (#133122P); by the Roddenberry Foundation, and gifts from QCRG philanthropic donors. This work was supported by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement #HR0011-19-2-0020. The views, opinions, and/or findings contained in this material are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. This research was partly funded by CRIP (Center for Research for Influenza Pathogenesis), a NIAID supported Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), by DARPA grant HR0011-19-2-0020, by supplements to NIAID grants U19AI142733, U19AI135972 and DoD grant W81XWH-20-1-0270, and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384)), and anonymous donors to AG-S. S.Y. received funding from a Swiss National Foundation (SNF) Early Postdoc Mobility fellowship (P2GEP3_184202).N

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.This work was supported by grants from the Government of Spain (PIE_INTRAMURAL_ LINEA 1 - 202020E079; PIE_INTRAMURAL_CSIC-202020E043). The research of CBIG consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols pharmaceutical. We also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). N Izquierdo-Useros has nonrestrictive funding from PharmaMar to study the antiviral effect of Plitidepsin. NJ Krogan was funded by grants from the National Institutes of Health (P50AI150476, U19AI135990, U19AI135972, R01AI143292, R01AI120694, and P01AI063302); by the Excellence in Research Award (ERA) from the Laboratory for Genomics Research (LGR), a collaboration between the University of California, San Francisco (UCSF), University of California, Berkley (UCB), and GlaxoSmithKline (GSK) (#133122P); by the Roddenberry Foundation, and gifts from QCRG philanthropic donors. This work was supported by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement #HR0011-19-2-0020. The views, opinions, and/or findings contained in this material are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. This research was partly funded by Center for Research for Influenza Pathogenesis and Transmission (CRIPT), a National Institute of Allergy and Infectious Diseases (NIAID) supported Center of Excellence for Influenza Research and Response (CEIRS, contract # 75N93021C00014), by DARPA grant HR0011-19-2-0020, by supplements to NIAID grants U19AI142733, U19AI135972, and DoD grant W81XWH-20-1-0270, and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384)), and anonymous donors to A García-Sastre. S Yildiz received funding from a Swiss National Foundation Early Postdoc Mobility fellowship (P2GEP3_184202).Peer reviewe

Spanish internal migration: is there anything new to say?

Abstract Spanish internal migration has long been resistant to traditional economic explanations. However, this paper examines the data for the period 1999–2006 after considerable changes in the Spanish economy. Moreover, it examines migration at the disaggregated level of Spanish provinces rather than regions, the usual unit of measurement. Using a spatial error model as well as a spatial autoregression model it finds the differentials in wages and unemployment between provinces to be significant explanatory variables. House prices are also important in accounting for the dynamics of internal migration. Les migrations internes en Espagne: qu'y a-t-il de nouveau? Les migrations internes en Espagne résistent, depuis toujours, à des explications économiques traditionnelles. Cependant, la présente communication examine les données relatives à la période 1999–2006, dans le sillage des changements considérables qui sont survenus dans l’économie espagnole. Elle se penche également sur la migration au niveau désagrégé de provinces espagnoles plutôt que de régions, unité de mesure traditionnelle. En utilisant un modèle d'erreur spatiale ainsi qu'un modèle à autorégression spatiale, elle en conclut que les différences sur le plan des salaires et du chômage entre les différentes provinces constituent des variables explicatives significatives. En outre, le prix de l'immobilier résidentiel joue également un rôle important dans l'examen de la dynamique des migrations internes. Migracin interior espaola: Queda algo nuevo por decir? La migración interior española lleva mucho tiempo resistiéndose a las explicaciones económicas tradicionales. No obstante, este artículo examina los datos de 1999–2006, después de considerables cambios en la economía española. Asimismo, examina la migración al nivel desagregado de provincias españolas, en lugar de regiones, que representa la unidad típica de medida. Utilizando un modelo de error espacial, así como un modelo de autorregresión espacial, se descubre que los diferenciales en salarios y empleo entre las provincias son importantes variables explicativas. Los precios de la vivienda también son importantes a la hora de comprender la dinámica de la migración interior.Internal migration, Spain, spatial error model, J61, O15, R23,

Effect of nanostructure on the supercapacitor performance of activated carbon xerogels obtained from hydrothermally carbonized glucose-graphene oxide hybrids

Activated carbon xerogels with a cellular morphology were obtained from hydrothermally carbonized glucose-graphene oxide (GO) hybrids and tested as supercapacitor electrodes. The effect of the chemical activation (using KOH) on the nanometer-scale morphology, local structure, porous texture and surface chemistry of the resulting carbon materials was investigated and correlated with their electrochemical behaviour. The electrochemical performance of the activated xerogels was studied in a three-electrode cell using 1 M H2SO4 as the electrolyte. The results underlined the relevant role played by the xerogel nanomorphology; more specifically, xerogels with cellular structures exhibiting well-connected, continuous and very thin (â 5-15 nm) carbon walls (prepared with lower amounts of activating agent) favored ionic diffusion and electronic conduction compared to materials with broken, thicker walls (obtained from higher amounts of activating agent). The effect of nanomorphology and local structure was also made apparent when the xerogels were used as actual supercapacitor electrodes. Particularly, a symmetric capacitor assembled from a carbon xerogel with very thin walls and relatively high graphitic character delivered a much higher specific capacitance than that of a commercial activated carbon (223 vs 153 F g-1 at 100 mA g-1) as well as a significantly improved retention of capacitance at high current densities

Anales de Edafología y Agrobiología Tomo 25 Número 11-12

Estudio de la composición mineral de gramíneas y leguminosas a lo largo del ciclo vegetativo, por J. M. Albareda y A. Martín.-- Estudio de concreciones ferruginosas de Mesones (Guadajajara), por J. Galván, J. García Vicente, J. J. Alonso y H. Carvajal.-- Estudio de la vermiculita de Estepona, por J. García Vicente y Mª C. Rodríguez.-- Los suelos de la provincia de Cáceres, por J. Forteza Bonnin, A. García Rodríguez, Mª Sánchez Camazano y Mª T. Martín Patiño.-- Los suelos de la provincia de Cáceres, por J. Forteza Bonnin, A. García Rodríguez, Mª Sánchez Camazano y Mª T. Martín Patiño. Diferenciación de los principales minerales sedimentarios mediante técnicas de tinción selectiva, por P. Arévalo Carretero.-- La humificación en Jos suelos de bosque de Quercus ile.r desarrollados sobre substrato calizo y silícico, por F. Velasco .-- Nutrición nitrogenada en el Bersim, por L. Jimeno y J. M. Lozano.-- Vanadio y la reducción de nitratos en las plantas, por L. Catalina.-- Vanadio y la reducción de nitratos en las plantas (II), por L. Catalina.-- Vanadio y la reducción de nitratos en las plantas (III), por L. Catalina.-- Acción nematicida de la urea contra Tylen.chulus semipenetrans Cobb., por A. Ortuño Martínez, J. Gómez Gómez y F. Cánovas Candel.-- Notas. Asociación Internacional de Ciencia del Suelo.—Consejeros.-- II Coloquio Europeo de Diagnóstico Foliar y Fertilización de los Cultivos.-- Simposio de Agroquímica.-- Cursillo Regional de Ciencias de la Naturaleza.-- Centros.-- VI Simposio Internacional de Química Agrícola.-- XVII Congreso Internacional de Horticultura.-- Congresos, reuniones internacionales y becas.-- Reunión del Comité Permanente de los Coloquios Europeos y Mediterráneos sobre el control de la alimentació. de plantas cultivadas.-- Coloquio de la dinámica de las biocenosis del suelo.-- Centro de Edafología y Biología Aplicada del Segura.-- IV Reunión del Grupo español de Sedimentología.-- Second Latin American Soil Biology Congress.--Biblografía.-- Sixth lnternational Congress for Electron Microscopy.-- Transmission electron microscopy of metals (Gareth Thomas).-- Electron microscopy of thin crystals (P. B. Hirsch, A. Howie, R. B. Nicholson, D. W. Pashley y M. J. Whelan)Peer reviewe

Anales de Edafología y Agrobiología Tomo 26 Número 7-8

Estudio de las relaciones entre los diferentes componentes minerales de gramíneas y leguminosas a lo largo del ciclo vegetativo, por J. M. Albareda y A . Martín.-- Complejos interlaminares de sorción, por Douglas M. C. Mac Ewan.-- Estudio físico-químico de unas biotitas, por Mª C. Rodríguez Pascual y J. García Vicente.-- Fraccionamiento de la materia orgánica del suelo con pirofosfato-sulfato sódico, por T. Carballas y F. Guitián.-- Influencia del sodio sobre la nutrición nitrogenada del tomate, por V. Hernando, L. Jimeno y C. Cadahia.-- El fósforo en la remolacha azucarera (Beta vulguris) por José M. Pozuelo y Albert Ulrich.-- Estudio por espectrografía de infrarrojo de las arcillas de algunos suelos de Andalucía occidental, por J. L. Pérez Rodríguez y F. Martín Martínez.-- Variación térmica de las propiedades ópticas de lepidolita y zinnwaldita, por J. Iñiguez, F. Arrese y Julio Rodríguez .-- Estudio de un suelo rojo mediterráneo en Almagro (Ciudad Real), por Trinidad Aleixandre.--Determinación de cinc en materiales vegetales por fotometría de llama por absorción atómica, por J. Ramírez-Muñoz.-- La morfología de los minerales detríticos en relación con sus propiedades estructurales, por J. Pérez Mateos y J. Galván García.-- Notas. S. E. el Jefe del Estado en el C. S. I. C.-- XXXVII Congreso Internacional de Química Industrial.-- Asociación de Investigadores para la mejora del cultivo de la remolacha azucarera.-- IV Reunión de la Comisión Rectora del Centro «La Mayora».-- VII Simposio Internacional de Agroquímica.-- Conferencias de Introducción a la Ciencia.-- Comité Inter-Institutos para el Estudio de Técnicas de Diagnóstico Foliar.-- XIII Reunión Bienal de la Real Sociedad Española de Física y Química.-- Sociedad Española de Ciencia del SueloPeer reviewe