Final report on deployment of consolidated platform and the overall architecture

This document is the final report about the activities of the Work Package 4 (WP4), aiming at provisioning a consistent e-infrastructure gradually integrating the existing isolated software solutions in the structural biology field into a single computing and data processing environment, based on the state of the art grid and cloud open source software tools and frameworks. This report follows the documents D4.3, MS14, D4.5 and MS15, respectively delivered at project month 15, 24, 26, 34, so that mostly the progress achieved until project month 36 not already described in the previous D4.5 ten months ago will be reported here, with references to MS15 when possible. The document starts with an updated description of the resources potentially available for the project from the EGI e-infrastructure, on top of which we built the consolidated West-Life platform. It then presents a detailed view of resource usage and their geographical distribution in the third and last year of the project, as obtained from the EGI Accounting Portal. The remaining of the document reports in details the final achievements about the three main aspects of the platform: the consolidated job management mechanism, the programmatic access to datasets and the unified security and accounting model

Estudio de los valores y su influencia en el comportamiento de los niños/as del centro de educación inicial Juan Francisco Cevallos de la ciudad de Cotacachi en el año lectivo 2012-2013

Determinar la incidencia en la práctica de los valores, en el comportamiento de los niños/as del Centro de Educación Inicial “Juan Francisco Cevallos” de la ciudad de Cotacachi, en el año lectivo 2012-2013.El presente informe final recoge las experiencias y hallazgos de la investigación sobre el tema: estudio de los valores y su influencia en el comportamiento de los niños/as del Centro de Educación Inicial ¿Juan Francisco Cevallos¿ de la ciudad de Cotacachi en el año lectivo 2012 2013, con una Guía Didáctica de Estrategias Metodológicas para desarrollar la práctica vivencial de valores, como propuesta de mejoramiento. El proceso de investigación seleccionó cuidadosamente su diseño, tipo y enfoque para enmarcarlo en la realidad contextual del problema y procurar obtener la información objetiva concreta y valiosa, relacionada con el tema y establecer las conclusiones como punto de partida para seleccionar una propuesta alternativa. Se seleccionó la metodología y las técnicas apropiadas, tales como descriptiva, propositiva y documental; se ubicó el lugar del estudio así como la población investigada que presentó el problema a tratar, siendo un tema de vital importancia para el desarrollo del ser ante la sociedad. Las encuestas permitieron describir el fenómeno social y llegar a la conclusión más importante del tema: se contó con la valiosa colaboración de los docentes y padres de familia, los mismos que señalan que una guía de estrategias metodológicas para fomentar la práctica de valores éticos y morales en los niños/as del Centro de Educación Inicial ¿Juan Francisco Cevallos¿ sería un buen aporte académico y práctico para la formación integral de los niños/as que conforman esta institución. Sobre esta información se procedió al diseño de una guía de estrategias metodológicas que permitan fomentar la práctica de valores en los niños/as del Centro de Educación Inicial ¿Juan Francisco Cevallos¿. La guía se basará en actividades de trabajo cooperativo, socialización y contará con recursos didácticos específicos apropiados para la edad de los niños y su centro de interés. Se añaden los impactos generados por la ejecución de este trabajo de investigación y la difusión con el personal docente responsable. El informe incluye además, las referencias bibliográficas consultadas y los anexos correspondientes

Surface functionalization of PLGA nanoparticles to increase transport across the BBB for Alzheimers disease

Alzheimers disease (AD) is a chronic neurodegenerative disorder that accounts for about 60% of all diagnosed cases of dementia worldwide. Although there are currently several drugs marketed for its treatment, none are capable of slowing down or stopping the progression of AD. The role of the blood-brain barrier (BBB) plays a key role in the design of a successful treatment for this neurodegenerative disease. Nanosized particles have been proposed as suitable drug delivery systems to overcome BBB with the purpose of increasing bioavailability of drugs in the brain. Biodegradable poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs) have been particularly regarded as promising drug delivery systems as they can be surface-tailored with functionalized molecules for site-specific targeting. In this review, a thorough discussion about the most recent functionalization strategies based on PLGA-NPs for AD and their mechanisms of action is provided, together with a description of AD pathogenesis and the role of the BBB in brain targeting.A.C. [Amanda Cano] acknowledges the support of the Spanish Ministry of Science, Innovation and Universities under the grant Juan de la Cierva (FJC2018-036012-I). Authors acknowledge the support of the Spanish Ministry of Economy and Competitiveness under the project SAF2017-84283-R; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED, CB06/05/0024) and Portuguese Science and Technology Foundation (FCT) for the strategic fund (UIDB/04469/2020).info:eu-repo/semantics/publishedVersio

Connectivity of coastal and neritic fish larvae to the deep waters

Four ichthyoplankton cruises and backward tracking experiments were conducted to study the connectivity of coastal and neritic fish larvae over the continental slope and to the oceanic deep-water region of the western Gulf of Mexico. Distribution patterns of larval abundance at oceanic stations showed higher abundance and the presence of larvae at oceanic stations during two cruises. Larval transport was simulated using outputs of a data assimilation model that represented the flow conditions during each cruise. Higher abundances of larvae of coastal and neritic species at oceanic stations agreed with offshore transport inferred from numerical experiments seeding particles over different spatial scales (stations vs. transects). Satellite images of surface chlorophyll were consistent with the circulation patterns indicated by the model, indicating filaments of shelf waters were transported toward the transects with higher larval abundances. Particle tracking experiments indicated that the northwestern shelf provinces of Perdido, Tamaulipas, and Texas were the main source of propagules to the oceanic region, while shelf provinces of northern Veracruz, Campeche, Yucatan, Louisiana, and Mississippi-Alabama contributed much less. The length and intensity of the shelf front limited ichthyoplankton cross-shelf exchange during some cruises, and mesoscale anticyclonic and cyclonic eddies advected larvae to the deep-water region during others. The agreement between the spatial distribution of fish larvae and the simulated larval transport confirm that circulation models are a valuable tool for examining potential dispersal pathways of neritic species, as long as similar spatial and temporal scales as the ones used in this study are considered.Fil: Cano Compaire, Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Consejo Nacional de Ciencia y Tecnología de México. Centro de Investigación Científica y de Educación Superior de Ensenada Baja California; MéxicoFil: Pérez Brunius, Paula. Consejo Nacional de Ciencia y Tecnología de México. Centro de Investigación Científica y de Educación Superior de Ensenada Baja California; MéxicoFil: Jiménez Rosenberg, Sylvia Patricia Adelheid. Instituto Politécnico Nacional. Centro Interdisciplinario de Ciencias Marinas; MéxicoFil: Rodríguez Outerelo, Javier. Consejo Nacional de Ciencia y Tecnología de México. Centro de Investigación Científica y de Educación Superior de Ensenada Baja California; MéxicoFil: Echeverri García, Laura del Pilar. Consejo Nacional de Ciencia y Tecnología de México. Centro de Investigación Científica y de Educación Superior de Ensenada Baja California; MéxicoFil: Herzka, Sharon Z.. Consejo Nacional de Ciencia y Tecnología de México. Centro de Investigación Científica y de Educación Superior de Ensenada Baja California; Méxic

Geological Characterization, Mapping and Sampling of the Tailing Pond From Cerro El Toro, Region La Libertad-Perú

The present article shows the working methodology of the project field Development and validation of a clean technology for the integral treatment of neutralization of effluents and metallurgical tailings in the use of calcareous agents 1 Geological Characterization 2 Delimitation of the area of environmental influence for legal exploitation 3 Mapping 4 Sampling 5 Calculation of the volume of tailings 6 Study of the environmental impact of legal exploitation relationships It should be noted each one of these activities are important as part of the methodology of work in field which one are developed in the tailing Cerro El Toro which has been divided the aforementioned relationship into 73 sampling points grouped according to the relationships Salinas 1 Salinas 2 Salinas 3 Montoro and Melva whose volume has been determined through the software AutoCAD Civil which has determined that tailings have the following volume Salinas 1 1917 5 m3 Salinas 2 20331 48 m3 Salinas 3 18375 m3 Montoro 668 56 m3 y Melva 27945 5 m3 whose volume allowed the obtention of a representative sample of the tailing for been studied of their Environmental Quality of tailing which gives through the geochemical characterization analysis with the purpose of determining the Real Impact of the pollution of tailing in the mining communities of Shiracmaca and Coigobamb

Molecular and in vivo studies of a glutamate-class prolyl-endopeptidase for coeliac disease therapy

The digestion of gluten generates toxic peptides, among which a highly immunogenic proline-rich 33-mer from wheat α-gliadin, that trigger coeliac disease. Neprosin from the pitcher plant is a reported prolyl endopeptidase. Here, we produce recombinant neprosin and its mutants, and find that full-length neprosin is a zymogen, which is self-activated at gastric pH by the release of an all-β pro-domain via a pH-switch mechanism featuring a lysine plug. The catalytic domain is an atypical 7+8-stranded β-sandwich with an extended active-site cleft containing an unprecedented pair of catalytic glutamates. Neprosin efficiently degrades both gliadin and the 33-mer in vitro under gastric conditions and is reversibly inactivated at pH > 5. Moreover, co-administration of gliadin and the neprosin zymogen at the ratio 500:1 reduces the abundance of the 33-mer in the small intestine of mice by up to 90%. Neprosin therefore founds a family of eukaryotic glutamate endopeptidases that fulfils requisites for a therapeutic glutenase.This study was supported in part by grants from Spanish and Catalan public and private bodies (grant/fellowship references PID2019-107725RG-I00 to F.X.G.-R., A.R.B., U.E. and T.G.; BES-2016-076877 to S.R.M., BES-2015-074583 to L.A.M., Beatriu de Pinós 2018BP00163 to U.E., 2017SGR3 and Fundació La Marató de TV3 201815 to F.X.G.-R., U.E., A.R.B. and T.G.)

Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue

Omomyc; Mass spectrometry; Protein therapeuticsOmomyc; Espectrometría de masas; Terapéutica de proteínasOmomyc; Espectrometria de masses; Terapèutica de proteïnesMYC is an oncoprotein causally involved in the majority of human cancers and a most wanted target for cancer treatment. Omomyc is the best-characterized MYC dominant negative to date. In the last years, it has been developed into a therapeutic miniprotein for solid tumor treatment and recently reached clinical stage. However, since the in vivo stability of therapeutic proteins, especially within the tumor vicinity, can be affected by proteolytic degradation, the perception of Omomyc as a valid therapeutic agent has been often questioned. In this study, we used a mass spectrometry approach to evaluate the stability of Omomyc in tumor biopsies from murine xenografts following its intravenous administration. Our data strongly support that the integrity of the functional domains of Omomyc (DNA binding and dimerization region) remains preserved in the tumor tissue for at least 72 hours following administration and that the protein shows superior pharmacokinetics in the tumor compartment compared with blood serum.This research has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 872212 and from the Ministerio de Ciencia e Innovacion under grant no. RTC2019-007067-1

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia – Departamentos de Cauca, Nariño, Quindío y Valle del Cauca

Presentamos un análisis crítico de algunos impactos psicosociales generados por la violencia en diferentes regiones de Colombia debido al conflicto armado el cual dio inicio desde mayo de 1964 y aunque ha tenido 5 fases diferentes cada una de ellas registra el horror y dolor que vivieron las víctimas dejando heridas que, aunque quizá hayan sanado, sus cicatrices son imborrables. Con la firma del acuerdo de paz llevado a cabo en diciembre del año 2016 entre el Gobierno Nacional y las FARC-EP se pretendía cimentar bases para consolidar una paz sostenible como una apuesta integral para las transformaciones que el país necesitaba, en la actualidad se mantienen activos varios grupos armados que no se sometieron al proceso, se está a la espera que los actores respeten la autonomía e independencia de la Jurisdicción en espacial para la Paz y así se pueda llevar a cabo esta labor y las victimas afectadas puedan ser reparadas por los daños generados. Este documento cuenta con análisis de relatos de violencia y esperanza realizados por el grupo de estudio, inicialmente se toma el relato de “Ana Ligia” una mujer desplazada con secuelas del conflicto que determinan impactos psicosociales y psicológicos que generan padecimientos como descontrol emocional, trastorno de estrés postraumático TEPT e insomnio, resaltando que frente a todas las situaciones de horror que vivió, en la protagonista se reconoce un posicionamiento subjetivo de empoderamiento a través de la poesía donde da valor a su habilidad, transformando su historia de dolor y desarraigo en una historia de vida enriquecida. Para el caso de “Peñas Coloradas” una comunidad que ha sufrido los impactos del conflicto de diversas maneras y en repetidas ocasiones, se estudia el caso generando preguntas orientadoras y determinadas estrategias en el abordaje psicosocial para trabajar con esta comunidad que a pesar de sus afectaciones tiene mucha capacidad de resiliencia. Para concluir el presente trabajo se deja evidencia del informe analítico de la foto voz, donde se realiza una investigación participativa comunitaria, y a través de la fotografía se plasma una realidad comunitaria en diferentes contextos de violencia y la actuación de sus integrantes.We present a critical analysis about some psycho-social impacts generated by the violence in different regions of Colombia due to the armed conflict which started from May of 1964 and even it has had 5 different stages, each one of them register the horror and pain that lived the victims, leaving wounds that maybe had healed but their scars are no erasable. With the signature is the Peace agreement put through in December of 2016 between the National Government and the FARC-EP; It was pretended to bade the basis for consolidating a sustainable peace as an integral bet for the transformations the country needed. Currently are maintained activated several armed groups that didn't submit to the process. Is in standby the wait that the actors respect the autonomy and independence of the Special Jurisdiction for Peace and thus can be carried out this Labour and the affected victims can be repaired about the generated damages. This document counts with the analysis of violence narrations and hope, done by the study group; initially is taken the "Ana Ligia'' telling, a displaced woman with consequences of the conflict that determine psycho-social and psychological impacts that generate sufferings like emotional lack of control, post-traumatic stress transformation PTST and insomnia, bringing out that in front of all the situations of horror that she lived. Is recognized in the protagonist a subjective positioning of empowerment through the poetry where she gives value to her ability, transforming her painful and rootlessness story to an enriched life one. In the "Peñas Coloradas" case, a community that has suffered the conflict impacts by diverse manners and repeatedly; The case is studied generating orienting questions and determining strategies on the psycho-social undertake for working with this community that despite its affectations is capable of being resilient. To conclude the present work, evidence is left about the analytical report of the photo-voice, where is done a participative communal research and through the photography is given form to a communal reality in different contexts of violence and the action of the community members

Correlations between the NMR Lipoprotein Profile, APOE Genotype, and Cholesterol Efflux Capacity of Fasting Plasma from Cognitively Healthy Elderly Adults

Cholesterol efflux capacity (CEC) is of interest given its potential relationship with several important clinical conditions including Alzheimer's disease. The inactivation of the APOE locus in mouse models supports the idea that it is involved in determining the CEC. With that in mind, we examine the impact of the plasma metabolome profile and the APOE genotype on the CEC in cognitively healthy elderly subjects. The study subjects were 144 unrelated healthy individuals. The plasma CEC was determined by exposing cultured mouse macrophages treated with BODIPY-cholesterol to human plasma. The metabolome profile was determined using NMR techniques. Multiple regression was performed to identify the most important predictors of CEC, as well as the NMR features most strongly associated with the APOE genotype. Plasma 3-hydroxybutyrate was the variable most strongly correlated with the CEC (r = 0.365; p = 7.3 × 10-6). Male sex was associated with a stronger CEC (r = -0.326, p = 6.8 × 10-5). Most of the NMR particles associated with the CEC did not correlate with the APOE genotype. The NMR metabolomics results confirmed the APOE genotype to have a huge effect on the concentration of plasma lipoprotein particles as well as those of other molecules including omega-3 fatty acids. In conclusion, the CEC of human plasma was associated with ketone body concentration, sex, and (to a lesser extent) the other features of the plasma lipoprotein profile. The APOE genotype exerted only a weak effect on the CEC via the modulation of the lipoprotein profile. The APOE locus was associated with omega-3 fatty acid levels independent of the plasma cholesterol level.Peer reviewe

Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver

The deficiency of CITRIN, the liver mitochondrial aspartate–glutamate carrier (AGC), is the cause of four human clinical phenotypes, neonatal intrahepatic cholestasis caused by CITRIN deficiency (NICCD), silent period, failure to thrive and dyslipidemia caused by CITRIN deficiency (FTTDCD), and citrullinemia type II (CTLN2). Clinical symptoms can be traced back to disruption of the malate-aspartate shuttle due to the lack of citrin. A potential therapy for this condition is the expression of aralar, the AGC present in brain, to replace citrin. To explore this possibility we have first verified that the NADH/NAD+ ratio increases in hepatocytes from citrin(−/−) mice, and then found that exogenous aralar expression reversed the increase in NADH/NAD+ observed in these cells. Liver mitochondria from citrin (−/−) mice expressing liver specific transgenic aralar had a small (~ 4–6 nmoles x mg prot−1 x min−1) but consistent increase in malate aspartate shuttle (MAS) activity over that of citrin(−/−) mice. These results support the functional replacement between AGCs in the liver. To explore the significance of AGC replacement in human therapy we studied the relative levels of citrin and aralar in mouse and human liver through absolute quantification proteomics. We report that mouse liver has relatively high aralar levels (citrin/aralar molar ratio of 7.8), whereas human liver is virtually devoid of aralar (CITRIN/ARALAR ratio of 397). This large difference in endogenous aralar levels partly explains the high residual MAS activity in liver of citrin(−/−) mice and why they fail to recapitulate the human disease, but supports the benefit of increasing aralar expression to improve the redox balance capacity of human liver, as an effective therapy for CITRIN deficienc