99 research outputs found

    Um periférico no centro: uma leitura da cidade de Recife na obra de Miró

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    Este artigo aborda a relação entre a cidade de Recife e suas representações em um recorte da produção poética do escritor Miró, compilada no livro Miró até Agora, editado pela Fundarpe. Tendo como referência o cotidiano social do autor, pretende-se destacar sua apreensão individual a respeito da realidade coletiva, que recria a cidade por meio de sua leitura poética. No presente artigo, propomos observar a cidade de Recife por meio de dinâmicas cotidianas e processos que afetam o homem como sujeito social, dentro do espaço urbano

    Testes de comportamento de fuga para avaliar os efeitos da aplicação de chorume de bovino e lodo de indústria láctea no solo

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    The application of organic wastes to agricultural soils is not risk-free and can affect soil invertebrates. Ecotoxicological tests based on the behavioral avoidance of earthworms and springtails were performed to evaluate effects of different fertilization strategies on soil quality and habitat function for soil organisms. These tests were performed in soils treated with: i) slurry and chemical fertilizers, according to the conventional fertilization management of the region, ii) conventional fertilization + sludge and iii) unfertilized reference soil. Both fertilization strategies contributed to soil acidity mitigation and caused no increase in soil heavy metal content. Avoidance test results showed no negative effects of these strategies on soil organisms, compared with the reference soil. However, results of the two fertilization managements differed: Springtails did not avoid soils fertilized with dairy sludge in any of the tested combinations. Earthworms avoided soils treated with sludge as of May 2004 (DS1), when compared with conventional fertilization. Possibly, the behavioral avoidance of earthworms is more sensitive to soil properties (other than texture, organic matter and heavy metal content) than springtailsA aplicação de resíduos orgânicos em solos agrícolas não está isenta de riscos e pode afetar os invertebrados do solo. Foram realizados testes ecotoxicológicos de comportamento de fuga usando minhocas e colêmbolos para avaliar os efeitos de diferentes estratégias de fertilização na qualidade do solo e na sua função de habitat. Esses testes foram realizados em solos que receberam: chorume e fertilizantes químicos – a estratégia de fertilização convencional na região; lodo adicionado à estratégia convencional; e solo-referência, não fertilizado. Ambas as estratégias de fertilização contribuíram para mitigar a acidez do solo e não contribuíram para aumento do teor em metais pesados do solo. Os resultados dos testes de fuga não mostraram efeitos negativos dessas estratégias nos organismos do solo, quando se comparam com os do solo-referência. Contudo, quando as duas estratégias de fertilização foram comparadas entre si, obtiveram-se resultados diferentes. Os colêmbolos não evitaram os solos fertilizados com lodo em nenhuma das combinações testadas. No entanto, as minhocas evitaram os solos que receberam lodo desde maio de 2004 (DS1). Possivelmente, o comportamento de fuga das minhocas é mais sensível às características do solo (que não a textura, a matéria orgânica e o teor de metais pesados) do que o dos colêmbolos.This study was supported by Fundação para a Ciência e a Tecnologia (Portugal), through a PhD grant to Mariana Matos-Moreira (SFRH/BD18486/ 2004) and to Júlia Niemeyer (SFRH/BD/28796/2006)S

    Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example

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    This article belongs to the Special Issue New Insights into Lysosomal Storage Disorders and Other Rare Genetic Diseases.Over recent decades, the many functions of RNA have become more evident. This molecule has been recognized not only as a carrier of genetic information, but also as a specific and essential regulator of gene expression. Different RNA species have been identified and novel and exciting roles have been unveiled. Quite remarkably, this explosion of novel RNA classes has increased the possibility for new therapeutic strategies that tap into RNA biology. Most of these drugs use nucleic acid analogues and take advantage of complementary base pairing to either mimic or antagonize the function of RNAs. Among the most successful RNA-based drugs are those that act at the pre-mRNA level to modulate or correct aberrant splicing patterns, which are caused by specific pathogenic variants. This approach is particularly tempting for monogenic disorders with associated splicing defects, especially when they are highly frequent among affected patients worldwide or within a specific population. With more than 600 mutations that cause disease affecting the pre-mRNA splicing process, we consider lysosomal storage diseases (LSDs) to be perfect candidates for this type of approach. Here, we introduce the overall rationale and general mechanisms of splicing modulation approaches and highlight the currently marketed formulations, which have been developed for non-lysosomal genetic disorders. We also extensively reviewed the existing preclinical studies on the potential of this sort of therapeutic strategy to recover aberrant splicing and increase enzyme activity in our diseases of interest: the LSDs. Special attention was paid to a particular subgroup of LSDs: the mucopolysaccharidoses (MPSs). By doing this, we hoped to unveil the unique therapeutic potential of the use of this sort of approach for LSDs as a whole.This research was partially funded by the FCT (FCT/PTDC/BBB-BMD/6301/2014 and EXPL/BTM-SAL/0659/2021), the Portuguese Society for Metabolic Disorders (Sociedade Portuguesa de Doenças Metabólicas, SPDM—Bolsa SPDM de apoio à investigação Dr Aguinaldo Cabral 2018 (2019DGH1629/SPDM2018I&D) and 2019 (2020DGH1834)), the Sanfilippo Children’s Foundation (SCF Incubator Grant 2019: 2019DGH1656/SCF2019I&D) and the MPS Society (2019DGH1642).info:eu-repo/semantics/publishedVersio

    Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses

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    (This article belongs to the Special Issue Molecular Mechanisms in Lysosomal Storage Diseases: From Pathogenesis to Therapeutic Strategies 2.0)ReviewDespite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders; the neurological symptoms are currently incurable, even in the cases where a disease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every patient-derived cell recapitulates relevant disease features. For the neuronopathic forms of MPSs, for example, this is particularly evident because of the obvious inability to access live neurons. This scenario changed significantly with the advent of induced pluripotent stem cell (iPSC) technologies. From then on, a series of differentiation protocols to generate neurons from iPSC was developed and extensively used for disease modeling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPSs and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analyses. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also hypothesize on a tempting alternative to establish MPS patient-derived neuronal cells in a much more expedite way, by taking advantage of the existence of a population of multipotent stem cells in human dental pulp to establish mixed neuronal and glial cultures.Funding: This work was partially supported by the Portuguese Society for Metabolic Disorders, SPDM (Bolsa SPDM de apoio à investigação Dr. Aguinaldo Cabral 2018; 2019DGH1629/SPDM2018I&D), Sanfilippo Children’s Foundation (2019DGH1656/SCF2019I&D), and Fundação para a Ciência e a Tecnologia, FCT: EXPL/BTM-SAL/0659/2021; UIDB/00211/2020—Centro de Estudos de Ciência Animal/Center for the Study of Animal Science; LA/P/0059/2020—Laboratório Associado para Ciência Animal e Veterinária/Associate Laboratory for Animal and Veterinary Sciences.info:eu-repo/semantics/publishedVersio
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