Opening up the DNA methylome of dementia

Dementia is a complex clinical condition characterized by several cognitive impairments that interfere with patient independence in executing everyday tasks. Various neurodegenerative disorders have dementia in common among their clinical manifestations. In addition, these diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies and frontotemporal dementia, share molecular alterations at the neuropathological level. In recent years, the field of neuroepigenetics has expanded massively and it is now clear that epigenetic processes, such as DNA methylation, are mechanisms involved in both normal and pathological brain function. Despite the persistent methodological and conceptual caveats, it has been reported that several genes fundamental to the development of neurodegenerative disorders are deregulated by aberrant methylation patterns of their promoters, and even common epigenetic signatures for some dementia-associated pathologies have been identified. Therefore, understanding the epigenetic mechanisms that are altered in dementia, especially those associated with the initial phases, will allow us not only to understand the etiopathology of dementia and its progression but also to design effective therapies to reduce this global public health problem. This review provides an in-depth summary of our current knowledge about DNA methylation in dementia, focusing exclusively on the analyses performed in human brain

La pensée transmédiale: une étude des actions appliquées à la pensée critique dans le domaine de la littératie transmédia

The generation of so-called digital natives assumes the paradox of having a series of competences for which they have not been trained: those related to transmedia and digital communication. Their context and their surroundings make them prone to an everyday and effective use of nwe technologies, but not necessarily reflective, mature and appropriate. This article presents an analysis on the crossing of competences related to Transmedia Communication and those that have to do with Critical Thinking. Its fusion is what we have called Transmedial Thinking. To this aim, a case study has been taken as a reference, the Guidance Project by the Pompeu Fabra University, in Barcelona. Through it, a series of university and secondary school students develop Transmedia and Critical Thinking skills that enable their personal and social empowerment

Epigenetic mechanisms during ageing and neurogenesis as novel therapeutic avenues in human brain disorders

Ageing is the main risk factor for human neurological disorders. Among the diverse molecular pathways that govern ageing, epigenetics can guide age-associated decline in part by regulating gene expression and also through the modulation of genomic instability and high-order chromatin architecture. Epigenetic mechanisms are involved in the regulation of neural differentiation as well as in functional processes related to memory consolidation, learning or cognition during healthy lifespan. On the other side of the coin, many neurodegenerative diseases are associated with epigenetic dysregulation. The reversible nature of epigenetic factors and, especially, their role as mediators between the genome and the environment make them exciting candidates as therapeutic targets. Rather than providing a broad description of the pathways epigenetically deregulated in human neurological disorders, in this review, we have focused on the potential use of epigenetic enzymes as druggable targets to ameliorate neural decline during normal ageing and especially in neurological disorders. We will firstly discuss recent progress that supports a key role of epigenetic regulation during healthy ageing with an emphasis on the role of epigenetic regulation in adult neurogenesis. Then, we will focus on epigenetic alterations associated with ageing-related human disorders of the central nervous system. We will discuss examples in the context of psychiatric disorders, including schizophrenia and posttraumatic stress disorders, and also dementia or Alzheimer's disease as the most frequent neurodegenerative disease. Finally, methodological limitations and future perspectives are discussed.EU Joint Programme-Neurodegenerative Disease Research (JPND; EPI-AD Consortium)RecerCaixa Foundation, Federación Española de Enfermedades Raras (FEDER)Federación Española de Enfermedades Neuromusculares (ASEM)Fundación Isabel GemioAsociación Española Contra el Cáncer (AECC)Ministerio de Sanidad, Servicios Sociales e Igualda

Epigenetic mechanisms during ageing and neurogenesis as novel therapeutic avenues in human brain disorders

Ageing is the main risk factor for human neurological disorders. Among the diverse molecular pathways that govern ageing, epigenetics can guide age-associated decline in part by regulating gene expression and also through the modulation of genomic instability and high-order chromatin architecture. Epigenetic mechanisms are involved in the regulation of neural differentiation as well as in functional processes related to memory consolidation, learning or cognition during healthy lifespan. On the other side of the coin, many neurodegenerative diseases are associated with epigenetic dysregulation. The reversible nature of epigenetic factors and, especially, their role as mediators between the genome and the environment make them exciting candidates as therapeutic targets. Rather than providing a broad description of the pathways epigenetically deregulated in human neurological disorders, in this review, we have focused on the potential use of epigenetic enzymes as druggable targets to ameliorate neural decline during normal ageing and especially in neurological disorders. We will firstly discuss recent progress that supports a key role of epigenetic regulation during healthy ageing with an emphasis on the role of epigenetic regulation in adult neurogenesis. Then, we will focus on epigenetic alterations associated with ageing-related human disorders of the central nervous system. We will discuss examples in the context of psychiatric disorders, including schizophrenia and posttraumatic stress disorders, and also dementia or Alzheimer's disease as the most frequent neurodegenerative disease. Finally, methodological limitations and future perspectives are discussed

O audiovisual como ferramenta de empoderamento na pesquisa com jovens Estudos de caso: projetos HEBE e ActiFem

A presente comunicação expõe dois projetos de pesquisa, (ebe e Actidem, nos quais a metodologia participativa foi aplicada e, especiicamente, o audiovisual como ferramenta de empoderamento no trabalho com jovens. A aplicação da pedagogia audiovisual signiicou, em ambos os casos, uma breve formação técnica com o objetivo de ajudar os e as participantes a descobrir diferentes formas expressivas e questionar de que forma é possível gerar narrativas audiovisuais mais próximas da nossa maneira única de ver o mundo. Nos dois projetos, o audiovisual é apresentado como uma ferramenta empoderadora, tanto no nível individual, quanto possibilitando a autorrelexão, o pensamento crítico e a expressão de seu próprio crescimento pessoal, bem como na construção da identidade coletiva e de uma cidadania mais crítica, comprometida e participativa

Directing neuronal cell fate in vitro: achievements and challenges

Human pluripotent stem cell (PSC) technology and direct somatic cell reprogramming have opened up a promising new avenue in the field of neuroscience. These recent advances allow researchers to obtain virtually any cell type found in the human brain, making it possible to produce and study functional neurons in laboratory conditions for both scientific and medical purposes. Although distinct approaches have shown to be successful in directing neuronal cell fate in vitro, their refinement and optimization, as well as the search for alternative approaches, remains necessary to help realize the full potential of the eventually derived neuronal populations. Furthermore, we are currently limited in the number of neuronal subtypes whose induction is fully established, and different cultivation protocols for each subtype exist, making it challenging to increase the reproducibility and decrease the variances that are observed between different protocols. In this review, we summarize the progress that has been made in generating various neuronal subtypes from PSCs and somatic cells, with special emphasis on chemically defined systems, transcription factor-mediated reprogramming and epigenetic-based approaches. We also discuss the efforts that are being made to increase the efficiency of current protocols and address the potential for the use of these cells in disease modelling, drug discovery and regenerative medicine

Propuesta de anteproyecto arquitectónico de hogar para adultos mayores en el municipio de Diriamba, Carazo.

Presenta un anteproyecto arquitectónico de un hogar para adultos mayores, ante la necesidad de contar con un sitio especializado para la atención y cuidado adecuado de adultos de la tercera edad, en el municipio de Diriamba

THE INTERACTIVE DOCUMENTARY AS A CREATIVE AND ARTISTIC EXPERIENCE FOR YOUTH EMPOWERMENT: THE HEBE WEBDOC AS A CASE OF STUDY

Las posibilidades de interacción que ofrecen las nuevas tecnologías abren posibilidades inéditas tanto para la investigación del empoderamiento juvenil en el seno de la academia, como para el el diseño e implementación de metodologías participativas que favorezcan los procesos de empoderamiento de los jóvenes en la sociedad. El webdoc HEBE [www.hebewebdoc.com] que describimos en este artículo se presenta como un caso pionero en el terreno del empoderamiento juvenil por el hecho de aunar en una única plataforma interactiva relatos de empoderamiento concebidos como piezas audiovisuales, reflexiones sobre el proceso de creación a través de distintos focus group y, finalmente, la posibilidad de compartir digitalmente estos materiales audiovisuales para hacerlos dialogar con la ciudadanía. En la primera parte del artículo se detallan y analizan los tres factores principales que están en la base del webdoc HEBE: la evolución de las metodologías participativas de empoderamiento basadas en la creación audiovisual, la utilización de nuevos soportes transmediáticos que permiten la participación colectiva y, por último, la consolidación de una pedagogía del cine como vía de aprendizaje de una experiencia vital y emocional. En la segunda parte se detallan las fases del proceso de construcción del webdoc HEBE, profundizando en los aspectos más relevantes y exponiendo sus cualidades como herramienta de ciencia ciudadana. También se explica la metodología pedagógica aplicada en el taller de creación y el diseño de la página de navegación del webdoc que implica la construcción de narrativas que permitan al usuario reflexionar sobre los procesos, espacios y momentos de empoderamiento juvenil. Finalmente, en la tercera parte, se presentan los primeros resultados derivados de la finalización del diseño del webdoc como plataforma, a partir del análisis de las piezas resultantes, realizadas por los participantes del taller de pedagogía audiovisual. The interaction potential offered by new technologies open up unprecedented possibilities both for the investigation of youth empowerment within academia, and for the design and implementation of participatory methodologies that foster young people’s empowerment processes in society. The HEBE webdoc [www.hebewebdoc.com] described in this paper is presented as a pioneering case in the field of youth empowerment, as it combines within a single interactive platform: empowering stories in the form of audiovisual segments; reflections on the creative process as shown in various focus groups; and, finally, digital sharing in order to enable a dialogue between the materials and citizens. The first section provides details of and analyzes the three main factors on which the HEBE webdoc is based: the evolution of empowerment participatory methodologies based on audiovisual creation; the use of new transmedia formats that allow collective participation; and the establishment of a film pedagogy as a way to learn from an emotional life experience. The second section describes the stages of the HEBE webdoc building process, by detailing the most important aspects and revealing its qualities as a tool for citizen science. It also explains the pedagogical methodology applied in the workshop where it was created, and the webdoc site’s navigation layout, which involves the construction of narratives that enable the user to reflect on processes, spaces and youth empowerment moments. To conclude, the third section contains the initial results from the completed webdoc’s platform design, based on an analysis of the pieces resulting from the audiovisual education workshop, carried out by the participants

Flowability of granular materials with industrial applications: an experimental approach

Designing bulk material handling equipment requires a thorough understanding of the mechanical behaviour of powders and grains. Experimental characterization of granular materials is introduced focusing on flowability. A new prototype is presented which performs granular column collapse tests. The device consists of a channel whose design accounts for test inspection using visualization techniques and load measurements. A reservoir is attached where packing state of the granular material can be adjusted before run-off to simulate actual handling conditions by fluidisation and deaeration of the pile. Bulk materials on the market, with a wide range of particle sizes, can be tested with the prototype and the results used for classification in terms of flowability to improve industrial equipment selection processes.Postprint (published version