High-throughput platforms for the screening of new therapeutic targets for neurodegenerative diseases

Despite the recent progress in the understanding of neurodegenerative disorders, a lack of solid fundamental knowledge on the etiology of many of the major neurodegenerative diseases has made it difficult to obtain effective therapies to treat these conditions. Scientists have been looking to carry out more-human-relevant studies, with strong statistical power, to overcome the limitations of preclinical animal models that have contributed to the failure of numerous therapeutics in clinical trials. Here, we identify currently existing platforms to mimic central nervous system tissues, healthy and diseased, mainly focusing on cell-based platforms and discussing their strengths and limitations in the context of the high-throughput screening of new therapeutic targets and drugs.This work had the financial support of Fundação para a Ciência e Tecnologia ( FCT ) through National Funds and, when applicable, co-financed by the FEDER through the PT2020 Partnership Agreement under the 4293 Unit I&D. D.N. Rocha acknowledges FCT for her PhD grant

IV Conferência Ibérica de Inovação na Educação com TIC (ieTIC 2016): livro de atas

Este livro contém todos os artigos apresentados na IV Conferência Ibérica de Inovação na Educação com TIC realizado no Instituto Politécnico de Bragança nos dias 6 e 7 de Maio de 201

II Encontro Internacional de Formação na Docência (INCTE): livro de resumos

O II Encontro Internacional de Formação na Docência apresenta os seguintes objetivos: problematizar, no quadro do processo de Bolonha, as estruturas curriculares da formação de educadores e professores; debater propostas didáticas inovadoras na formação para a docência; refletir sobre as práticas formativas nos diversos contextos; analisar o contributo da formação na dinamização das instituições; aprofundar a comunicação entre os diferentes intervenientes na formação numa perspetiva de educação para o desenvolvimento. O Encontro está estruturado em quatro grandes eixos temáticos: Currículo e formação de educadores e professores (CFEP) Este eixo temático integra as questões do currículo, da inovação curricular e as novas perspetivas curriculares, no âmbito da formação inicial ou continuada de educadores e professores, incluindo a discussão de modelos e processos curriculares de diferente natureza e de trabalhos ou propostas de formação de educadores e professores, nos diversos contextos. Didática e formação de educadores e professores (DFEP) Este eixo temático integra aspetos dos diferentes saberes disciplinares em contexto escolar, abarcando a reflexão sobre os contributos da didática na formação de educadores e professores para uma construção progressiva de formas de compreender e agir conscientemente em situações educativas. Práticas educativas e supervisão pedagógica (PESP) Este eixo temático integra o desenvolvimento de práticas de formação de educadores e professores nas escolas, compreendendo a problematização dos papéis a desempenhar pelos diversos intervenientes, numa perspetiva de trabalho colaborativo e da construção de uma identidade profissional consciente, empenhada e responsável. Formação docente e educação para o desenvolvimento (FDED) Este eixo temático integra aspetos formativos do ensino e da aprendizagem relacionados com a promoção de uma cidadania global responsável, abrangendo a discussão de projetos e práticas educativas potenciadoras de uma educação para o desenvolvimento

II Encontro Internacional de Formação na Docência (INCTE): livro de atas

Este livro contém os artigos do I Encontro Internacional de Formação na Docência (INCTE), realizado nos dias 5 e 6 de maio de 2017 no Instituto Politécnico de Bragança

V Conferência Ibérica de Inovação na Educação com TIC: ieTIC2019: livro de resumos

Os tempos actuais são estimulantes para quem tem de estudar e aprender. Pela primeira vez há a possibilidade de acesso livre ao conhecimento, à sua explicação e à sua partilha. Tal é possibilitado pelas Tecnologias de Informação e de Comunicação e assim continuará no futuro. Conhecê-las, aplicá-las no processo de ensino/aprendizagem, enquadrá-las no sistema de valores da sociedade aberta e da cidadania responsável, é uma necessidade de quem investiga, de quem ensina e de quem decide.O ieTIC, através dos seus quatro eixos temáticos, continua a permitir-nos a construir conhecimento sobre as TIC e a explorar novas avenidas de práticas pedagógicas que desafiam os papéis tradicionais de professor e de aluno. O ieTIC ajuda-nos a recordar que o século XXI não é igual ao que está para trás!info:eu-repo/semantics/publishedVersio

Study of the injection molding of a polarizing beam splitter

We describe the replication of a relief grating that behaves like a polarizing beam splitter by injection molding. Measurements of the grating master, nickel shim, and replica, performed by atomic force microscopy, allow establishing a limit for the injection molding technique (currently used in CD fabrication) to aspect ratios of approximately 0.15. Although this limit strongly reduces the diffraction efficiency of the elements as well as their polarizing properties, extinction ratios of approximately 10:1 were measured for the replicas in a large range of wavelengths. (c) 2006 Optical Society of America.45110010

V Conferência Ibérica de Inovação na Educação com TIC: ieTIC2019: atas da conferência

O Departamento de Tecnologia Educativa e Gestão de Informação da Escola Superior de Educação do Instituto Politécnico de Bragança e o Departamento de Didáctica, Organización y Métodos de Investigación da Universidad de Salamanca realizaram, nos dias 07 e 08 de fevereiro de 2019, a V edição da conferência Ibérica de Inovação na Educação com Tecnologias da Informação e Comunicação (ieTIC2019). A ieTIC2019 continua a ser um espaço de discussão de temáticas em diversas áreas relevantes no âmbito do planeamento, desenvolvimento e utilização de tecnologias educativas em prol da inovação educativa.El Departamento de Tecnología Educativa y Gestión de información de la Escuela Superior de Educación del Instituto Politécnico de Braganza y el Departamento de Didáctica, Organización y Métodos de Investigación de la Universidad de Salamanca realizaran, 07 e 08 de febrero del 2019, la V edición de la Conferencia Ibérica de Innovación en la Educación con Tecnologías de la Información y Comunicación (ieTIC2019). La ieTIC2019 sigue siendo un espacio de discusión de temáticas en diversas áreas relevantes en el marco de la planificación, desarrollo y utilización de tecnologías educativas en favor de la innovación educativa.The Department of Educational Technology and Information Management of the School of Education of the Polytechnic Institute of Bragança and the Department of Didactics, Organization and Research Methods of Salamanca University, held on February 7 and 8, 2019, the 5th Edition of the Iberian Conference on Innovation in Education with Information and Communication Technologies (ieTIC2019). ieTIC2019 is the right place for thematic debate in several relevant areas concerning the planning, development and use of educational technologies within the framework of educational innovation

Hydrogel-Assisted Antisense LNA Gapmer Delivery for In Situ Gene Silencing in Spinal Cord Injury

After spinal cord injury (SCI), nerve regeneration is severely hampered due to the establishment of a highly inhibitory microenvironment at the injury site, through the contribution of multiple factors. The potential of antisense oligonucleotides (AONs) to modify gene expression at different levels, allowing the regulation of cell survival and cell function, together with the availability of chemically modified nucleic acids with favorable biopharmaceutical properties, make AONs an attractive tool for novel SCI therapy developments. In this work, we explored the potential of locked nucleic acid (LNA)-modified AON gapmers in combination with a fibrin hydrogel bridging material to induce gene silencing in situ at a SCI lesion site. LNA gapmers were effectively developed against two promising gene targets aiming at enhancing axonal regeneration—RhoA and GSK3ß. The fibrin-matrix-assisted AON delivery system mediated potent RNA knockdown in vitro in a dorsal root ganglion explant culture system and in vivo at a SCI lesion site, achieving around 75% downregulation 5 days after hydrogel injection. Our results show that local implantation of a AON-gapmer-loaded hydrogel matrix mediated efficient gene silencing in the lesioned spinal cord and is an innovative platform that can potentially combine gene regulation with regenerative permissive substrates aiming at SCI therapeutics and nerve regeneration.This work was supported by Fundação para a Ciência e a Tecnologia ( FCT , Portugal) in the framework of the Harvard-Portugal Medical School Program ( HMSP-ICT/0020/2010 ); Project NORTE-01-0145-FEDER-000008 , supported by the Norte Portugal Regional Operational Programme (NORTE 2020) , under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) ; Fundo Europeu de Desenvolvimento Regional funds through COMPETE 2020 - Operational Program for Competitiveness and Internationalization (POCI) , Portugal 2020; by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” ( POCI-01-0145-FEDER-007274 ); Marie Curie Actions of the European Community’s 7th Framework Program ( PIEF-GA-2011-300485 to P.M.D.M.); Santa Casa da Misericordia de Lisboa – Prémio Neurociências Mello e Castro , and FCT fellowship SFRH/BPD/108738/2015 (to P.M.D.M). Funding for open access charge: Project NORTE-01-0145-FEDER-000012 , financed by Norte Portugal Regional Operational Programme (NORTE 2020) , under the PORTUGAL 2020 Partnership Agreement, through the ERDF . We would like to acknowledge the support from Paula Magalhães and Tânia Meireles from the i3S Cell Culture and Genotyping Core Facility in real-time PCR experiments

Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease

Parkinson’s disease’s etiology is unknown, although evidence suggests the involvement of oxidative modifications of intracellular components in disease pathobiology. Despite the known involvement of the extracellular matrix in physiology and disease, the influence of oxidative stress on the matrix has been neglected. The chemical modifications that might accumulate in matrix components due to their long half-live and the low amount of extracellular antioxidants could also contribute to the disease and explain ineffective cellular therapies. The enriched striatal extracellular matrix from a mouse model of Parkinson’s disease was characterized by Raman spectroscopy. We found a matrix fingerprint of increased oxalate content and oxidative modifications. To uncover the effects of these changes on brain cells, we morphologically characterized the primary microglia used to repopulate this matrix and further quantified the effects on cellular mechanical stress by an intracellular fluorescence resonance energy transfer (FRET)-mechanosensor using the U-2 OS cell line. Our data suggest changes in microglia survival and morphology, and a decrease in cytoskeletal tension in response to the modified matrix from both hemispheres of 6-hydroxydopamine (6-OHDA)-lesioned animals. Collectively, these data suggest that the extracellular matrix is modified, and underscore the need for its thorough investigation, which may reveal new ways to improve therapies or may even reveal new therapies.This research was funded by FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and Portuguese funds through FCT (ID/BIM/04293/2020), UnIC (UID/IC/00051/2019), iBiMED (UID/BIM/04501/2020 and POCI-01-0145-FEDER-007628), and LAQV/REQUIMTE (UIDB/50006/2020) research units as well as RV’s Fellowship Grant (IF/00286/2015). Ana Freitas acknowledges FCT for her PhD scholarship (SFRH/BD/111423/2015), Miguel Aroso is hired through the Scientific Employment Stimulus from FCT (CEECIND/03415/2017), and M.L. has an FCT RJEC Id 3762 contract.The authors thank Eduardo D Martín Montiel for his support, fruitful discussions, suggestions, and technical and scientific help. The authors also thank Sofia Lamas and all the i3S Animal facility personnel for their support with the animals throughout the study. Raman spectroscopy, together with wide field and confocal microscopy, were performed at the i3S Scientific Platform Bioimaging, member of the PPBI (Plataforma Portuguesa de Bioimagem, POCI-01-0145-FEDER-022122)