2011 Año de la Investigación en el Alzheimer

Every year on September 21, World Alzheimer’s Day is celebrated, the most common cause of neurodegenerative dementia in people over 65 years old. Alzheimer’s produces a progressive and total deterioration of cognitive functions (memory loss, language alteration, loss of sense of orientation, and executive functions), often accompanied by changes in personality and behavior, and which leads to a dramatic reduction in the individual’s ability to carry out daily life activitiesEl 21 de septiembre de cada año se celebra el Día Mundial de la enfermedad de Alzheimer, la causa más frecuente de demencia neurodegenerativa en las personas mayores de 65 años. El Alzheimer produce un deterioro progresivo y total de las funciones cognitivas (pérdida de memoria, alteración del lenguaje, pérdida del sentido de la orientación y de las funciones ejecutivas), frecuentemente acompañada de cambios en la persona- lidad y en el comportamiento, y que conlleva una dramática reducción de la capacidad del individuo para  llevar a cabo las actividades de su vida diaria

In vitro modeling of dysfunctional glial cells in neurodegenerative diseases using human pluripotent stem cells

Most neurodegenerative diseases are characterized by a complex and mostly still unresolved pathology. This fact, together with the lack of reliable models, have precluded the development of effective therapies counteracting the disease progression. In the past few years, several studies have evidenced that lack of proper functionality of glial cells (astrocytes, microglia and oligodendrocytes) has a key role in the pathology of several neurodegenerative conditions including Alzheimer´s disease, amyotrophic lateral sclerosis and multiple sclerosis among others. However, this glial dysfunction is poorly modelled by available animal models, and we hypothesize that patientderived cells can serve as a better platform where to study this glial dysfunction. In this sense, human pluripotent stem cells (hPSCs) has revolutionized the field allowing the generation of disease-relevant neural cell types that can be used for disease modelling, drug screening and, possibly, cell transplantation purposes. In the case of the generation of oligodendrocytes (OLs) from hPSCs, we have developed a fast and robust protocol to generate surface antigen O4-positive (O4+) and myelin basic protein-positive OLs from hPSCs in only 22 days, including from patients with multiple sclerosis or amyotrophic lateral sclerosis. The generated cells resemble primary human OLs at the transcriptome level and can myelinate neurons in vivo. Using in vitro OLneuron co-cultures, effective myelination of neurons can also be demonstrated. This platform is being translated as well to the generation of the other glial cell types, allowing the derivation of patient-specific glial cells where to model disease-specific dysfunction. This methodology can be used for elucidating pathogenic pathways associated with neurodegeneration and to identify therapeutic targets susceptible of drug modulation, contributing to the development of novel and effective drugs for these devastating disorders.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Supported by PI18/01557 (to AG) and P18/1556 (to JV) grants from ISCiii of Spain co-financed by FEDER funds from European Union, and PI-0276-2018 grant (to JAGL) from Consejeria de Salud of Junta de Andalucia. JAGL held a postdoctoral contract from the I Research Plan Propio of the University of Malaga. CV and KE were supported by IWT-SBO-150031-iPSCAF and the Thierry Lathran Foundation grant – ALS-OL, and KN by FWO1166518

Análisis del lenguaje audiovisual en el desarrollo de la historia de amor de la telenovela coreana playful kiss

El presente trabajo de investigación tuvo como objetivo analizar los elementos del lenguaje audiovisual que acompañan a la historia de amor de la telenovela Playful Kiss. Para ello se observó las escenas del primer capítulo empleando dos técnicas de recolección de datos: ficha de observación y entrevistas, los cuales fueron validados por el coeficiente de V de Aiken arrojando un resultado de 91%. La investigación es hermenéutica, con un enfoque cualitativo y un diseño de estudio de caso. En conclusión, los elementos del lenguaje audiovisual se presentan en la telenovela Playful Kiss de manera atractiva y ficticia. Esto se puede apreciar a través de las escenas de fantasía y acciones de los protagonistas

Implementación de un sistema de gestión en el programa Árboles para Lima ejecutado por SERPAR, en Lima Metropolitana

Universidad Nacional Agraria La Molina. Facultad de Agronomía. Departamento Académico de HorticulturaEl presente documento se basa en la experiencia de trabajo desarrollada en el programa “Árboles para Lima” dentro de la Subgerencia de Arborización y Servicios Externos del Servicio de Parques de Lima (SERPAR). En dicha área se promovió concientizar acerca del cuidado del medioambiente a la población a través de la realización de arborizaciones urbanas en forma sostenible en cooperación con las municipalidades distritales de Lima Metropolitana. Al respecto, se señala la importancia de la concientización de la población sobre el cuidado del medioambiente mediante: i) capacitaciones sobre arborización urbana a los operarios municipales de áreas verdes y a los vecinos interesados en arborizar sus comunidades, ii) plantaciones de árboles en zonas urbanas y iii) posteriores supervisiones programadas de las plantaciones. Se puede resaltar que, en menos de dos años de ejecución del programa “Árboles para Lima” se logró la plantación de más de 300 000 árboles para zonas urbanas dentro de 41 distritos de Lima Metropolitana (Servicio de Parques de Lima, 2021), que contaban con convenio vigente con SERPAR. Se utilizó como pauta para la ejecución del programa, el sistema de gestión que se desarrolla en este trabajo académico. De este modo, el presente trabajo académico se elaboró con el anhelo de convertirse en una guía sobre la implementación de un sistema de gestión en un programa de arborización urbana, desde el área administrativa hasta el área técnica agronómica, en Lima Metropolitana

Recovery of deformation substructure and coarsening of particles on annealing severely plastically deformedAl–Mg–Si alloy and analysis of strengthening mechanisms

An Al–Mg–Si alloy was annealed to various solutionized and aged states and was then severely plastically deformed by equal channel angular pressing (ECAP). These materials were subsequently annealed for a range of times and temperatures to induce precipitation, dislocation recovery, and grain growth, with changes of mechanical behavior followed by tensile testing. Precipitation of excess solute was seen to occur in all cases, independent of the initial heat treated state, but the particles present appear to play only a small role in stabilizing the deformation substructure, at least until significant particle and grain coarsening has occurred, when discontinuous grain coarsening can be provoked. The strength of materials is examined, and the respective contributions of loosely arranged dislocations, many grain boundaries, and dispersed particles are deduced. It is shown that dislocation strengthening is significant in as-deformed, as well as lightly annealed materials, with grain boundary strengthening providing the major contribution thereafterComunidad de Madrid (CAM) under Contract No. 07N/0087/2002Peer reviewe

Some practical issues on modeling transport

Apoyo financiado por la SIEAWe present a mathematical model, which is considered a strategic alliance of two or more companies that hire and subcontract respectively, a service charge. It is considered a cost function to consider amending the alliance, justifies the need for the alliance and observed decrease in costs to service users.SIEA UAEME

Bone marrow-derived mesenchymal stem cells transplantation produces a tissue recovery in hydrocephalic mice

In congenital hydrocephalus, cerebrospinal fluid accumulation is associated to ischemia/hypoxia, metabolic impairment, neuronal damage and astrocytic reaction, which cause significant mortality and life-long neurological complications. Currently, there are no effective therapies for congenital hydrocephalus. Bone marrow-derived mesenchymal stem cells (BM-MSC) are considered as a potential therapeutic tool for neurodegenerative diseases due to their ability for migrating and producing neuroprotector factors when they are transplanted. The aim of this research was to study the ability of BM-MSC to reach the degenerated regions and to detect their neuroprotector effects, using an animal model of congenital hydrocephalus, the hyh mouse. Fluorescent BM-MSC were analyzed by flow-cytometry and multilineage cell differentiation. BM-MSC were brain-ventricle injected into hyh mice. Wild-type and saline-injected hyh mice were used as controls. Inmunohistochemical, RT-PCR and High Resolution Magic Angle Spinning spectroscopy (HRMAS) analyses were carried out. After administration, integrated BM-MSC were identified inside the periventricular astrocyte reaction. They were detected producing glial-derived neuroprotector factor (GDNF), neural growth factor (NGF), and brain-derived neuroprotector factor (BDNF). Tissue recovery was detected with a reduction of apoptotic cells in the periventricular walls and of the levels of glutamate, glutamine, taurine, and creatine, all of them markers of tissue damage in hydrocephalus.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. ISCIII PI15/00619 y FEDE

Epothilone-d rescues cognition and attenuates alzheimer’s disease-like pathology in APP/PS1 mice

AIMS: Cognitive decline in Alzheimer's disease (AD) patients has been linked to synaptic damage and neuronal loss. Hyperphosphorylation of tau protein destabilizes microtubules leading to the accumulation of autophagy/vesicular material and the generation of dystrophic neurites, thus contributing to axonal/synaptic dysfunction. In this study, we analyzed the effect of a microtubule-stabilizing compound in the progression of the disease in the hippocampus of APP751SL/PS1M146L transgenic model. METHODS: APP/PS1 mice (3 month-old) were treated with a weekly intraperitoneal injection of 2 mg/kg epothilone-D (Epo-D) for 3 months. Vehicle-injected animals were used as controls. Mice were tested on the Morris water maze, Y-maze and object-recognition tasks for memory performance. Abeta, AT8, ubiquitin and synaptic markers levels were analyzed by Western-blots. Hippocampal plaque, synaptic and dystrophic loadings were quantified by image analysis after immunohistochemical stainings. RESULTS: Epo-D treated mice exhibited a significant improvement in the memory tests compared to controls. The rescue of cognitive deficits was associated to a significant reduction in the AD-like hippocampal pathology. Levels of Abeta, APP and ubiquitin were significantly reduced in treated animals. This was paralleled by a decrease in the amyloid burden, and more importantly, in the plaque-associated axonal dystrophy pathology. Finally, synaptic levels were significantly restored in treated animals compared to controls. CONCLUSION: Epo-D treatment promotes synaptic and spatial memory recovery, reduces the accumulation of extracellular Abeta and the associated neuritic pathology in the hippocampus of APP/PS1 model. Therefore, microtubule stabilizing drugs could be considered therapeutical candidates to slow down AD progression. Supported by FIS-PI12/01431 and PI15/00796 (AG),FIS-PI12/01439 and PI15/00957(JV)Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

SYSTEMIC ADMINISTRATION OF EPOTHYLONE-D RECUES MEMORY AND AMELIORATES ALZHEIMER’S DISEASE-LIKE PATHOLOGY IN APP/PS1 MICE

Aims Cognitive and memory decline in Alzheimer's disease (AD) patients is highly related to synaptic dysfunction and neuronal loss. Tau hyperphosphorylation destabilizes microtubules leading to axonal transport failure, accumulation of autophagy/vesicular material and the generation of dystrophic neurites, thus contributing to axonal/synaptic dysfunction. In this study, we analyzed the effect of a microtubule-stabilizing drug in the progression of the disease in an APP751SL/PS1M146L transgenic model. Method APP/PS1 mice (3 month-old) were weekly treated with 2 mg/kg intraperitoneal injections of Epothilone-D (Epo-D) for 3 months. Vehicle-injected animals were used as controls. For memory performance, animals were tested on the object-recognition tasks, Y-maze and Morris water maze. Levels of Abeta, ubiquitin, AT8 and synaptic markers were analyzed by Western-blot. Hippocampal plaque burden, dystrophic and synaptic loadings were quantified after immunostaining by image analysis. Results Epo-D treated mice showed a significant improvement in the performance of hippocampus-associated cognitive tests compared to controls. This memory recovery correlated with a significant reduction in the AD-like hippocampal pathology. Abeta, APP and ubiquitin levels were significantly reduced in treated animals, and a decrease in both the plaque loading and the axonal pathology was also found. Finally, synaptic levels were significantly preserved in treated animals in comparison with controls. Conclusion Epo-D treatment promotes synaptic and cognitive improvement, reduces the accumulation of extracellular Abeta and the associated neuritic pathology in the hippocampus of APP/PS1 model. Therefore, microtubule stabilizing drugs could be considered therapeutical candidates to slow down AD progression.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Supported by FIS-PI15/00796 (AG), FIS-PI15/00957(JV) and co-financed by FEDER funds from European Union

Matrix grain refinement in Al-TiAl composites by severe plastic deformation: influence of particle size and processing route

The microstructure and mechanical behaviour of Al-based composites reinforced with TiAl intermetallic particles has been examined in the as-extruded state and after processing by equal channel angular pressing (ECAP). The latter produces a grain size reduction in the aluminium matrix to values of 500 nm, using route A, and 750 nm, using route C. The ECAP produces up to a 75% increase in the yield stress of the composites, being more rapid when route A is used. The strengthening effect by ECAP is much larger than that obtained by increasing the volume fraction of reinforcement particles from 25 to 50% in these compositesThanks to the Spanish Ministry of Education and Science for financing this study under project number MAT2003-01540.Peer reviewe