113 research outputs found
LA TERRA SIGILLATA ORIENTALE A E B DALLE INDAGINI PRESSO LA SPONDA EST DEL PORTO DI AQUILEIA: ANALISI CRONO-TIPOLOGICA, REPERTI E CONTESTI DI PROVENIENZA
No full textThis study examines the Eastern Sigillata ceramics from ex Fondo Sandrigo, located along the eastern bank of Aquileia’s river port. Excavations (2010–2024) have revealed a long occupation sequence (1st century BCE–7th century CE) and ten chronological phases documenting the site's transformation. Research results presented below aim to enrich the corpus of fine Eastern ceramics in Aquileia. The presence of Eastern Sigillata A and B, despite the competitive local and Italic sigillata production, highlights Aquileia's role in long-distance trade networks. The quantitative and typological analysis identifies 40 specimens, 65% belonging to Eastern Sigillata A and 35% to Eastern Sigillata B. These findings contribute to the understanding of patterns of ceramic circulation connecting the Eastern Mediterranean to northern Adriatic. The study enhances knowledge of Aquileia’s commercial dynamics through an integrated archaeological approach
New lysosomal acid lipase gene mutants explain the phenotype of Wolman disease and cholesteryl ester storage disease
No full textEvolutionarily Conserved Heterogeneous Nuclear Ribonucleoprotein (hnRNP) A/B Proteins Functionally Interact with Human and Drosophila TAR DNA-binding Protein 43 (TDP-43).
No full textHuman TDP-43 represents the main component of neuronal inclusions found in patients with neurodegenerative diseases, especially frontotemporal lobar degeneration and amyotrophic lateral sclerosis. In vitro and in vivo studies have shown that the TAR DNA-binding protein 43 (TDP-43) Drosophila ortholog (TBPH) can biochemically and functionally overlap the properties of the human factor. The recent direct implication of the human heterogeneous nuclear ribonucleoproteins (hnRNPs) A2B1 and A1, known TDP-43 partners, in the pathogenesis of multisystem proteinopathy and amyotrophic lateral sclerosis supports the hypothesis that the physical and functional interplay between TDP-43 and hnRNP A/B orthologs might play a crucial role in the pathogenesis of neurodegenerative diseases. To test this hypothesis and further validate the fly system as a useful model to study this type of diseases, we have now characterized human TDP-43 and Drosophila TBPH similarity in terms of protein-protein interaction pathways. In this work we show that TDP-43 and TBPH share the ability to associate in vitro with Hrp38/Hrb98DE/CG9983, the fruit fly ortholog of the human hnRNP A1/A2 factors. Interestingly, the protein regions of TDP-43 and Hrp38 responsible for reciprocal interactions are conserved through evolution. Functionally, experiments in HeLa cells demonstrate that TDP-43 is necessary for the inhibitory activity of Hrp38 on splicing. Finally, Drosophila in vivo studies show that Hrp38 deficiency produces locomotive defects and life span shortening in TDP-43 with and without animals. These results suggest that hnRNP protein levels can play a modulatory role on TDP-43 functions
Dual role of G-runs and hnRNP F in the regulation of a mutation-activated pseudoexon in the fibrinogen gamma-chain transcript.
No full textMost pathological pseudoexon inclusion events originate from single activating mutations, suggesting that many intronic sequences are on the verge of becoming exons. However, the precise mechanisms controlling pseudoexon definition are still largely unexplored. Here, we investigated the cis-acting elements and trans-acting regulatory factors contributing to the regulation of a previously described fibrinogen gamma-chain (FGG) pseudoexon, which is activated by a deep-intronic mutation (IVS6-320A>T). This pseudoexon contains several G-run elements, which may be bound by heterogeneous nuclear ribonucleoproteins (hnRNPs) F and H. To explore the effect of these proteins on FGG pseudoexon inclusion, both silencing and overexpression experiments were performed in eukaryotic cells. While hnRNP H did not significantly affect pseudoexon splicing, hnRNP F promoted pseudoexon inclusion, indicating that these two proteins have only partially redundant functions. To verify the binding of hnRNP F and the possible involvement of other trans-acting splicing modulators, pulldown experiments were performed on the region of the pseudoexon characterized by both a G-run and enrichment for exonic splicing enhancers. This 25-bp-long region strongly binds hnRNP F/H and weakly interacts with Serine/Arginine-rich protein 40, which however was demonstrated to be dispensable for FGG pseudoexon inclusion in overexpression experiments. Deletion analysis, besides confirming the splicing-promoting role of the G-run within this 25-bp region, demonstrated that two additional hnRNP F binding sites might instead function as silencer elements. Taken together, our results indicate a major role of hnRNP F in regulating FGG pseudoexon inclusion, and strengthen the notion that G-runs may function either as splicing enhancers or silencers of the same exon
A Construção curricular popular crítica no ensino de ciências naturais e suas implicações na prática docente
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Programa de Pós-Graduação em Educação Científica e Tecnológica, Florianópolis, 2010A presente pesquisa investiga o processo de Reorientação Curricular Popular Crítico no Ensino de Ciências, no município de Chapecó/SC, envolvendo as mudanças nas práticas pedagógicas dos professores, através da participação nesse processo. Para isso, explicita e contextualiza os pressupostos freireanos presentes nesse movimento de reorientação curricular na área de Ciências Naturais e busca identificar quais pressupostos freireanos foram incorporados pelos educadores no seu fazer pedagógico. A investigação configura-se como uma pesquisa qualitativa e os dados empíricos foram obtidos mediante a aplicação de instrumentos baseados em ilustrações e entrevista, assim como o estudo de documentos. O grupo investigado compõe-se de professores da área que atuam de 5ª a 8ª séries do ensino fundamental. Os referenciais teóricos de análise são os estudos de Paulo Freire sobre a Educação Libertadora e as categorias elencadas são: dialogicidade, inédito-viável e repensar na ação. A pesquisa revelou algumas dificuldades por parte dos professores em trabalhar, a partir das falas significativas, seja em perceber a contribuição da área, seja na seleção dos conteúdos programáticos. Mas, de modo geral, as análises realizadas revelaram mudanças nas práticas dos professores, sendo que alguns princípios foram incorporados pela maioria, na prática cotidiana. Dentre eles, destaco a valorização dos saberes dos alunos, a relação entre a realidade e o conhecimento científico, a necessidade da interdisciplinaridade e do trabalho coletivo na ação docente. Porém, a prática pedagógica, via Tema Gerador, não se encontra mais na rede municipal de ensino de Chapecó, pois algumas condições necessárias à sua continuidade não se encontram à disposição. São elas: abertura para a pesquisa com a comunidade, acompanhamento pedagógico com momentos de estudo e aprofundamento, apoio das direções escolares, coletivo de professores coeso e resistente. O que se observa são iniciativas isoladas, na forma e resistência, por alguns professores em continuar trabalhando dialogicamente com seus alunos
Evaluation of decontamination effects and sequential pre-osteoblast migration to titanium microimplants in an in vitro approach using scaffolds produced by additive manufacturing
No full textA peri-implantite é um desafio clínico atual, sendo que a complexidade desse cenário aumenta ao considerarmos que um mesmo protocolo de descontaminação pode levar a resultados diferentes dependendo das características da superfície do implante tratado. O objetivo deste estudo foi utilizar um novo modelo in vitro para avaliar a migração de pré-osteoblastos, o potencial de descontaminação do titânio, mudanças na rugosidade da superfície, alterações químicas e modificações na molhabilidade de microimplantes de titânio após o uso de diferentes protocolos de descontaminação. Para isto, foram utilizados no experimento 120 microimplantes de titânio lisos (L) e 120 rugosos (R). Para o grupo controle, foram selecionados aleatoriamente 15 microimplantes L e 15 R (L-C / R-C), enquanto que os demais foram incubados em cultura de Escherichia coli. Em seguida, os microimplantes contaminados foram tratados de acordo com 7 protocolos de descontaminação diferentes, sendo: submersão em EDTA gel a 24% (EDTA; n=15), submersão em clorexidina a 4% (CX; n=15), limpeza com gaze embebida em clorexidina a 4% (GCX; n=15), limpeza com gaze embebida em água ultrapura (GMQ; n= 15), raspagem com cureta metálica (RA; n=15), uso de escova de titânio (ETi; n=15) e implantoplastia (IP; n=15). As áreas contaminadas remanescentes foram avaliadas por imagens de microscopia eletrônica de varredura (MEV), a composição química foi determinada por espectroscopia por dispersão em energia (EDS), a molhabilidade pela técnica do menisco e a rugosidade superficial por meio de um perfilador óptico. Após, os microimplantes foram inseridos em arcabouço impresso tridimensionalmente e preenchido com uma cultura 3D de células pré-osteoblásticas (MC3T3-E1 subclone 14). A migração celular foi avaliada por ensaio de luminescência após 24, 72 e 120 h. Como resultado observou-se maior concentração de bactérias no grupo R-C do que no L-C (p0,05), mas os valores nos grupos L-IP e L-CX foram estatisticamente inferiores ao do grupo L-C (p0,05) e entre os grupos R-C, R-EDTA e R-GCX (p>0,05). Assim, pode-se concluir que todos os protocolos avaliados levaram a alguma mudança na rugosidade, molhabilidade e/ou deposição química superficial, sendo que os grupos GCX, RA, ETi e IP apresentaram o melhor potencial de descontaminação tanto em microimplantes L quanto em R. A migração celular, por sua vez, demonstrou melhor resultados com os protocolos EDTA, GCX, RA e ETi nos microimplantes L e EDTA e GCX nos R. A junção de ambos os resultados sugere uma indicação do uso dos protocolos GCX, RA e ETi em superfícies lisas e GCX nas rugosas.Peri-implantitis is a current clinical challenge and the complexity of this scenario increases considering that the same treatment can lead to different outcomes depending on the implant surface characteristics. The objective of this study was to use a new in-vitro model to assess titanium decontamination, surface roughness, chemical changes, wettability and preosteoblast migration after using different decontamination protocols. It was used 120 smooth (S) and 120 rough (R) titanium microimplants at the experiment. For the control group, 15 S and 15 R microimplants (R-C/S-C) were randomly selected, while the others were incubated in Escherichia coli culture. Then, 7 different decontamination protocols were used: 24% EDTA gel submersion (EDTA; n= 15), 4% chlorhexidine submersion (CHL; ; n= 15), surface cleaning with gauze soaked in 4% chlorhexidine (GCHL; n= 15), surface cleaning with gauze soaked in ultrapure water (GUW; n= 15), scaling with metallic curette (SC; n=15), titanium brush (TiB; n= 15) and implantoplasty (IP; n= 15). Remaining contaminated areas were assessed by scanning electron microscopy (SEM) images. The chemical composition was investigated by EDS, wettability by meniscus technique and roughness by an optical profiler. After, microimplants were inserted in a 3D-printed scaffold imbibed with a 3D-cell culture of preosteoblasts (MC3T3-E1 subclone 14). Cellular migration was assessed with luminescence assay after 24, 72 and 120h. As result, a higher bacteria concentration was observed in R-C than in S-C (p 0,05), but the values at groups S-IP and S-CHL were statistically inferior than S-C (p0.05), or between the groups R-C, R-EDTA and R-GCX (p>0.05). Thus, it can be concluded that all decontamination protocols resulted in changes in roughness, wettability and chemical composition, with GCHL, SC, TiB an IP presenting the best decontamination potential for both S and R microimplants. On the other hand, cell migration assay showed better results with the protocols EDTA, GCHL, SC and ETi for S microimplants, and EDTA and GCHL for the R. The junction of those results suggest an indication of the protocols GCX, SC and ETi for smooth surfaces and GCX for rough
Análise das viabilidades técnica e econômica entre a laje nervurada e a laje treliçada em uma estrutura de concreto armado
No full textNa construção civil as edificações estruturadas em concreto armado com o uso de lajes maciças aos poucos estão sendo substituídas por outros tipos de lajes, como é o caso das alternativas das lajes nervuradas e das lajes treliçadas, ênfase deste estudo. Diante disso, o estudo teve por objetivo principal comparar as viabilidades técnicas e econômicas entre os tipos de lajes nervuradas (Caso 1) e lajes treliçadas (Caso 2) em uma edificação de dois pavimentos de uso comercial de concreto armado. Para atender ao objetivo foram efetuados os dimensionamentos das estruturas propostas com laje nervurada e laje treliçada empregando-se o software estrutural Eberick. Com os resultados obtidos foi realizado um comparativo entre os modelos estruturais do Caso 1 e Caso 2 e foram analisadas as variáveis da distribuição das cargas verticais; os pesos do aço; os volumes de concreto; as áreas das formas; os deslocamentos das estruturas; e os custos dos materiais, no intuito de definir a melhor alternativa técnica e econômica para o projeto proposto. Os resultados indicaram que para a edificação de dois pavimentos de uso comercial de concreto armado avaliada neste estudo, a laje treliçada (Caso 2) apresenta melhor desempenho técnico e menor custo financeiro ao ser comparada com a utilização da laje nervurada (Caso 1), representando uma economia de R153.434,65. [resumo fornecido pelo autor
Optineurin Shapes Basal and LPS-Induced Transcriptomes in BV2 Microglia
No full textThe OPTN gene, which encodes the adaptor protein optineurin, is genetically linked to amyotrophic lateral sclerosis and frontotemporal dementia, diseases characterized by chronic microglial activation. Optineurin regulates inflammatory signaling, autophagy, and trafficking, but its role in microglia remains incompletely understood. Here, we used bulk RNA sequencing to profile CRISPR-Cas9-mediated optineurin knockout (KO) and wild-type BV2 microglia under basal conditions and upon LPS stimulation. At baseline, optineurin KO altered ~7% of the transcriptome, with a predominant downregulation of type I interferon and antiviral pathways, suggesting its role in maintaining basal immune readiness. LPS stimulation reprogrammed ~35% of genes in wild-type microglia, inducing immune effectors and suppressing cell cycle regulators, whereas in optineurin-deficient cells, the response was blunted with only ~16% of genes changing relative to the KO baseline. Furthermore, LPS-treated optineurin KO microglia notably diverged from LPS-treated wild-type cells, with ~26% differentially expressed genes (DEGs). This included impaired induction of inflammatory programs and persistence of cell cycle-associated transcripts. Most DEGs in LPS-treated KO cells were unique to this condition, highlighting optineurin-dependent pathways specific to inflammatory challenge. Overall, our study provides a systems-level framework for investigating optineurin in microglia and neurodegeneration, establishing it as a key regulator of the microglial transcriptome, with its loss reshaping innate immune and cell cycle programs
Projeto tecnologias sociais para a gestão da água? TSGA: contribuição para a gestão participativa da água.
No full textProjeto: 06.09.06.001
NMR assignments for the C-terminal domain of human TDP-43
No full text5 pages, 2 tablesTransactive response DNA-binding protein of 43 kDa (TDP-43) is a 414-residue protein whose aberrant aggregation is implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration (FTLD). Intriguingly, TDP-43 has also been shown to functionally oligomerize to carry out physiological functions. TDP-43 also exists in mixed condensates or granules with other proteins (e.g. neuronal or stress granules), and its large C-terminal domain (CTD, residues 267-414) seems responsible for TDP-43 both homo- and heterotypic interactions underlying such diverse functional and pathological aggregation events. A myriad of distinct triggers may drive TDP-43 oligomerization, including interaction partners or changes in pH or salinity. In this Assignment Note, we report the complete backbone and a wealth of side chain chemical shift assignments for the CTD of TDP-43 at pH 4. The assignments presented here provide a solid starting point to study the aggregation pathway of TDP-43 at pH values below those considered physiological but relevant in pathological settings, and to contrast the aggregation behaviour under distinct conditions and in the presence of interacting partners.This work has been funded by Grants CTQ2017-84371-P to D.P.-U. and SAF2016-76678-C2-2-R to D.V.L., from the Spanish MINECO; Grant MCB1412253 from the U. S. National Science Foundation to A.E.M; AriSLA (PathensTDP project) to E.B.; and Grant LCF/BQ/PR19/11700003 from La Caixa Foundation (ID 100010434) to M.M. NMR experiments were performed in the “Manuel Rico” NMR Laboratory (LMR) of the Spanish National Research Council (CSIC), a node of the Spanish Large-Scale National Facility (ICTS R-LRB).Peer reviewe
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