Reposicionamiento de fármacos en enfermedades mitocondriales

Mitochondrial diseases (MD) are a group of genetic disorders characterized by defects in the oxidative phosphorylation system (OXPHOS) or other metabolic disorders involving mitochondria. Currently there is no treatment for the majority of these diseases, so drug repositioning is an interesting and promising way to discover new therapies. In the present work a methodology has been developed, using Machine Learning (ML) techniques, which allows the prioritization of drugs with potential effects in MD. Through a ML/ML tandem use of two models, one for searching drugs with chemical and structural properties similar to the drugs currently used in MD, and another model for the prediction of new mitochondrial drug-target interactions, a total of 68 drugs (not present in the original set of drugs for model training) were prioritized. After a review of the 68 prioritized drugs, research studies have been found about seven drugs (D-Cysteine, Malic Acid, L-Glutamine, Folic acid, Beta-Alanine, Glycine and Beta-Amino Isobutyrate) that supports their potential beneficial effect on mitochondrial function and one work has been found about one prioritized drug (D-Serine) in which a possible detrimental effect on mitochondrial activity is described. Overall we concluded that the set of 68 prioritized drugs could contain new drugs with a potential beneficial effect for the treatment of MD.Las enfermedades mitocondriales (EM) son un conjunto de enfermedades de base genética caracterizadas por defectos en el sistema de fosforilación oxidativa (OXPHOS) u otros trastornos metabólicos en los que participan las mitocondrias. Actualmente no existe tratamiento para la inmensa mayoría de estas enfermedades, por lo que el reposicionamiento de fármacos es una estrategia interesante y prometedora para el descubrimiento de nuevas terapias. En el presente trabajo se ha desarrollado una metodología, mediante el uso de técnicas de Machine Learning (ML), que permite la priorización de fármacos con posibles efectos beneficiosos en el ámbito de las EM. Mediante el uso secuencial de dos modelos, uno para la búsqueda de fármacos con propiedades físico-químicas y estructurales similares a las de los fármacos que se usan actualmente en EM, y otro modelo para la predicción de nuevas interacciones fármaco-diana mitocondrial se han priorizado un total de 68 fármacos (no presentes en el set de fármacos con los que se entrenaron los modelos). Tras una revisión bibliográfica sobre los 68 fármacos priorizados se han encontrado trabajos sobre 7 fármacos del set que apoyan su posible efecto beneficioso en función mitocondrial (D-Cisteina, Ácido Málico, L-Glutamina, Ácido Fólico, Beta-Alanina, Glicina y Beta-Amino Isobutirato). Sólo se ha hallado una referencia sobre uno de los fármacos priorizados en el que se describe un posible efecto perjudicial sobre la actividad mitocondrial (D-Serina). Finalmente concluimos que el conjunto de 68 fármacos priorizados podría contener nuevos fármacos con un efecto potencialmente beneficioso en EM.Les malalties mitocondrials (EM) són un conjunt de malalties de base genètica caracteritzades per defectes en el sistema de fosforilació oxidativa (OXPHOS) o altres trastorns metabòlics en els quals participen els mitocondris. Actualment no existeix tractament per a la immensa majoria d'aquestes malalties, per la qual cosa el reposicionament de fàrmacs és una estratègia interessant i prometedora per al descobriment de noves teràpies. En el present treball s'ha desenvolupat una metodologia, mitjançant l'ús de tècniques de Machine Learning (ML), que permet la priorització de fàrmacs amb possibles efectes beneficiosos en l'àmbit de les EM. Mitjançant l'ús seqüencial de dos models, un per a la cerca de fàrmacs amb propietats físic-químiques i estructurals similars a les dels fàrmacs que s'usen actualment en EM, i un altre model per a la predicció de noves interaccionis fàrmac-diana mitocondrial s'han prioritzat un total de 68 fàrmacs (no presents en el set de fàrmacs amb els quals es van entrenar els models). Després d'una revisió bibliogràfica sobre els 68 fàrmacs prioritzats s'han trobat treballs sobre 7 fàrmacs del set que donen suport al seu possible efecte beneficiós en funció mitocondrial (D-Cisteina, Àcid Màlic, L-Glutamina, Àcid Fòlic, Beta-Alanina, Glicina i Beta-Amino Isobutirato). Només s'ha trobat una referència sobre un dels fàrmacs prioritzats en el qual es descriu un possible efecte perjudicial sobre l'activitat mitocondrial (D-Serina). Finalment concloem que el conjunt de 68 fàrmacs prioritzats podria contenir nous fàrmacs amb un efecte potencialment beneficiós en EM

Aditivacion de resinas epoxi mediante complejos poliméricos homo y heterometálicos con 1,3,5-triaza-7-fosfaadamantanofosfina (PTA) y 3,7-dimetil-1,3,7-triaza-5-phosphabiciclo[3.3.1]nonane (dmoPTA)

Publication number: ES2627009 A1 (26.07.2017) Also published as: ES2627009 B2 (22.01.2018) Application number: P201600099 (26.01.2016)La presente invención se relaciona con el uso de polímeros homo y heterometálicos con el ligando 1,3,5-triaza-7-fosfaadamantanofosfina (PTA) y 3,7-dimetil-1,3,7-triaza-5-phosphabiciclo[3.3.1]nonane) (dmoPTA), como aditivos de resinas epoxídicas. Estos aditivos previa disolución o suspensión mejoran y modifican las propiedades de las resinas confiriéndoles nuevas propiedades como color, conductividad eléctrica y magnética, resistencia térmica y al fuego, flexibilidad, distinto tiempo de curado, entre otras propiedades.Universidad de Almerí

Casual Learn: A Smart Application to Learn History of Art

Producción CientíficaSmart Learning promises the connection between formal and informal learning, but how to offer informal learning tasks related to formal learning is still a challenge. This demonstration paper presents CasualLearn, a smart learning application that bridges formal and informal learning to learn History of Art in the Spanish region of Castile and Leon. CasualLearn uses a dataset of 16,221 contextualized informal learning tasks that were semi-automatically created exploiting Open Data from the Web. CasualLearn offers these tasks to students based on their context: their geolocation, the activity they do and the topics covered in their formal education. A demo application is currently available for Android devices.Junta de Castilla y León (Project VA257P18)Ministerio de Ciencia, Innovación y Universidades (Project TIN2017-85179-C3-2-R)European Commission (Project grant 588438-EPP-1-2017-1-EL-EPPKA2-KA

The evolution of the subcontinental mantle beneath the Central Iberian Zone: Geochemical tracking of its mafic magmatism from the Neoproterozoic to the Cenozoic

Continental lithosphere is modified over eons in response to large-scale tectonic processes, such as rifting and collisions. The lithospheric mantle beneath central Iberia was affected by multiple Neoproterozoic to Cenozoic events including two orogenic cycles. However, the details of this evolution, and the relationship of the Iberian lithosphere to that beneath central Europe remains poorly constrained. We have compiled a trace element and isotope (Sr-Nd-Pb) data set (n = 230) regarding the main ten mafic magmatic episodes that intruded the central-western Iberia basement during a 575 Ma age range. In this long period, two orogenic events with accompanying mafic calc-alkaline magmatism (Cadomian and Variscan cycles) were followed by eight intraplate, alkaline or tholeiitic, magmatic inputs. The two orogenic episodes have subordinate mafic intrusions associated to a more voluminous felsic magmatism, which highlights both the major intracrustal recycling promoted and the significant crustal thickening accompanying these convergence tectonic events. Nevertheless, only minor crustal subduction signatures within deep mantle are observed in mafic magmas or mantle xenoliths after those two orogenic cycles, and the existence of an old (pre-Neoproterozoic) enriched subcontinental mantle beneath central Iberia is suggested. Mantle-derived magmas from central European basement terranes (Bohemian to Armorican-French Massif Central massifs) show a marked contrast of geochemical tracers during the same long time record. They show more juvenile and depleted mantle sources during the pre-Variscan times indicating their farther distance to continental Gondwana than the studied central Iberian terrane. Thus, the change in Nd isotopes and model ages associated with the Variscan orogeny is more abrupt in central European terranes. This collisional event was followed by the arrival of broadly similar mafic magmas in both southwestern and central European terranes, implying substantial crust-mantle interaction across a wide geographical area. The post-Variscan mafic magmatism, mainly from Cretaceous time, suggests a lithospheric mantle rejuvenation by widespread asthenospheric upwelling throughout these western circum-Mediterranean areas. However, the presence of minor episodes of intraplate K-rich alkaline magmatism involving enriched lithospheric mantle sources in the southernmost Mediterranean Europe marks a contrast, suggesting a complex lithospheric/asthenospheric mantle flow regime in these areas during post-collisional convergence between Africa and Eurasia

Orchestrating ubiquitous learning situations about Cultural Heritage with Casual Learn mobile application

Producción CientíficaCultural Heritage learners can highly benefit from ubiquitous learning approaches that connect in-classroom activities with active on-site learning opportunities. However, teachers face the problem that the current landscape of technological support for learning Cultural Heritage mostly consists of mobile applications for informal contexts, completely decoupled from curricular activities. This paper presents the results of an exploratory-sequential mixed-methods study that focuses on the feasibility, for non-technical expert teachers, of repurposing an existing mobile application in formal Cultural Heritage ubiquitous learning situations. Such feasibility is explored from the perspective of the orchestration metaphor. More specifically, we used the “5+3 aspects orchestration framework” to understand the orchestration challenges of four ubiquitous learning situations about Cultural Heritage carried out in two secondary schools. These situations involved five teachers and 139 students who used a mobile application called Casual Learn for several weeks. The results of the study suggest that, after a brief training, teachers can design, enact, and orchestrate ubiquitous learning situations that involve both in-classroom and out-classroom activities. The teachers were able to transfer to the students most of the orchestration load of out-classroom activities. The results also showed that the flow of learning artifacts and information between in- and out-classroom activities is a critical issue that needs to be addressed by developers of ubiquitous learning technological solutions.Junta de Castilla y Leon - Fondo Europeo de Desarrollo Regional (project VA257P18)Agencia Estatal de Investigación - Fondo Europeo de Desarrollo Regional (project TIN2017-85179-C3-2-R

Multiscale modelling for fusion and fission materials: the M4F project

The M4F project brings together the fusion and fission materials communities working on the prediction of radiation damage production and evolution and its effects on the mechanical behaviour of irradiated ferritic/martensitic (F/M) steels. It is a multidisciplinary project in which several different experimental and computational materials science tools are integrated to understand and model the complex phenomena associated with the formation and evolution of irradiation induced defects and their effects on the macroscopic behaviour of the target materials. In particular the project focuses on two specific aspects: (1) To develop physical understanding and predictive models of the origin and consequences of localised deformation under irradiation in F/M steels; (2) To develop good practices and possibly advance towards the definition of protocols for the use of ion irradiation as a tool to evaluate radiation effects on materials. Nineteen modelling codes across different scales are being used and developed and an experimental validation programme based on the examination of materials irradiated with neutrons and ions is being carried out. The project enters now its 4th year and is close to delivering high-quality results. This paper overviews the work performed so far within the project, highlighting its impact for fission and fusion materials science.This work has received funding from the Euratom research and training programme 2014-2018 under grant agreement No. 755039 (M4F project)