Uso di cellule staminali embrionali per lo studio in vitro dei meccanismi molecolari di regionalizzazione della corteccia cerebrale

Durante lo sviluppo della corteccia gradienti di morfogeni attraversano il neuroepitelio suddividendolo in distinti domini funzionali. L'informazione contenuta in tali gradienti è successivamente tradotta nell'attivazione di specifiche costellazioni di geni nella progenie postmitotica. Una classe di morfogeni particolarmente importante nel patterning corticale è quella dei fattori FGF. Infatti l'espressione di FGF8 in posizione mediale anteriore nel telencefalo di topo in via di sviluppo è necessaria per la corretta specificazione delle strutture corticali più rostrali. Anche COUP-TF1, un gene essenziale per la specificazione dell'identità corticale caudale, è espresso nel neuroepitelio neocorticale con un gradiente caudo-rostrale complementare a quello di FGF8. Inoltre l'espressione di questi due fattori è mutualmente regolata; pertanto diminuendo l'espressione dell'uno, l'altro risponde espandendo il proprio dominio d'espressione. \\In questo lavoro abbiamo messo appunto un modello per lo studio in vitro del patterning corticale mediante utilizzo di neuroni ottenuti dal differenziamento di cellule staminali embrionali di topo. Abbiamo quindi utilizzato tale modello per caratterizzare il meccanismo di regolazione di COUP-TF1 da parte di FGF8. Abbiamo dimostrato come il trattamento tardivo con FGF8 determini una riduzione nell'espressione di COUP-TF1 senza alterare l'identità corticale dei neuroni generati. Inoltre tale repressione sembra essere mediata -almeno in parte- a livello post-trascrizionale, poiché l'overespressione della 3'UTR di COUP-TF1 scherma il trascritto endogeno dalla repressione traduzionale mediata da FGF8. Infine abbiamo identificato alcuni microRNA upregolati dal trattamento con FGF8 e possibili candidati come repressori traduzionali di COUP-TF1

The Protagonist\u27s Experience: Temporality, Narrative, and Harmonic Process in Brahms\u27s Solo Lieder

This dissertation explores musical and poetic temporality—expressions of the past, present, and future—in eighteen of Johannes Brahms’s solo Lieder. The selected songs illustrate that common tonal patterns in Brahms’s instrumental music, including tonal and modal ambiguities and associative harmonies, also suggest recurring narrative archetypes in his songs. Separate poetic and musical analyses use literary theory (narratology), as well as Schenkerian analysis and Schoenbergian conceptions of motivic development. Narratological interpretations of poetry by Daumer, Platen, Köstlin, Goethe, Groth, Schenkendorf, Hebbel, and others first demonstrate that a series of psychological transformations form a lyric poem’s “plot” or “temporal progression.” This subjective level of discourse communicates the poetic protagonist’s perceptions, desires, anxieties, and mental states or incidents. Each poem’s structural features (its tense, syntax, meter, and rhyme) also contribute to its expression of real and implied temporalities. Close readings of each song’s musical structure interpret harmonic processes such as cadentially realized keys, implied keys, and prolonged harmonies as actualizing latent poetic temporalities. These harmonic processes model the protagonist’s non-linear experience of time as memories, dreams, anticipations, and other perceptions distort the ongoing present. Comparisons between Brahms’s songs that share the keys of F minor, B minor, F# minor, and E major suggest that he engaged with his own compositional past through self-modeling. I explore possible intertextual connections between Brahms’s songs and songs by Josephine Lang, Franz Schubert, and Caspar Othmayr, as well as explore Brahms’s engagement with his own compositional past. My interpretation of the voice and piano as musical agents links each analysis to performance. By realizing conflicts and oppositions between these agents, a singer and pianist might enact the psychological transformations that the poem implies and that Brahms’s musical setting realizes

The 1922 Week of Modern Art and the nationalist element in the discourse on music in Brazil

O ensaio examina o discurso crítico sobre música que se estabeleceu no Brasil e a relação da intelectualidade com essa arte, evidenciando que parâmetros do nacional-modernismo sempre estiveram na base de ambos. Numa sequência histórica, parte-se da própria Semana de Arte Moderna (1922) e percorrem-se os seus desdobramentos, flagrando e interpretando, entre os diversos episódios e revisionismos conceituais ao longo dos anos, as oscilações de interesse crítico em relação às manifestações musicais eruditas e populares. A hipótese é de que, no cenário contemporâneo, tenha-se esgotado a força propulsora do argumento nacional-modernista, não mais capaz de bem articular as questões apresentadas pelas produções musicais da atualidade. The essay examines the critical discourse on music that was established in Brazil and the relationship of the intellectuality with this art, demonstrating that parameters of national-modernism were always at the base of both. In a historical sequence, it starts with the Week of Modern Art (1922) and follows its evolutions, highlighting and interpreting, among the various episodes and conceptual revisionisms over the years, the oscillations of critical interest in relation to classical and popular musical manifestations. The hypothesis is that, in the contemporary scenario, the propulsive force of the national-modernist argument has ended, since it is no longer capable of articulating the questions posed by today's musical productions.

Rediscutindo a relação entre música e linguagem a partir das análises de Paolo Virno

O texto analisa como algumas das novas concepções do fenômeno da linguagem, particularmente as do filósofo italiano Paolo Virno, podem alterar a maneira como ela é comparada com a música. Em vez de repropor um entendimento da linguagem nos moldes da tradição logocêntrica, ou seja, com o foco prioritariamente dirigido para o significado, o conteúdo e, portanto, o aspecto cognitivo, Paolo Virno aborda o sentido da linguagem como praxis, ressaltando seu aspecto performático e ritualístico

A relevância da gestão da qualidade em serviços nas microempresas

A qualidade se apresenta como fator importante na atividade das empresas, se mostrando como uma das melhores formas para alcançar o crescimento sustentável da organização. Considerando sua adoção como uma oportunidade de melhorar aspectos operacionais, minimizar os custos, eliminar falhas e satisfazer sua clientela, uma gestão de qualidade se torna indispensável à gestão organizacional. Através do levantamento bibliográfico pôde-se perceber que as micro e pequenas empresas possuem um papel de extrema importância no Brasil, sendo então necessário incentivá-las na meta de se manterem atuantes num mercado tão competitivo e que se cresce a cada dia. A gestão de qualidade quando bem aplicada, torna esse objetivo mais fácil e viável. Diante disso a presente pesquisa tem como objetivo principal pesquisar e compreender a Gestão da Qualidade e sua relevância para as mesmas, por meio de ações eficientes que garantam esse processo. Como metodologia, utilizou-se a pesquisa exploratória, bibliográfica. Este projeto propõe abordar a qualidade em serviços como fator relevante para a consolidação da Gestão da Qualidade nas organizações estudadas, sendo estas um fator relevante para o desenvolvimento e estruturação de qualquer empresa no mercado

The microRNA miR-21 Is a Mediator of FGF8 Action on Cortical COUP-TFI Translation

The morphogen FGF8 plays a pivotal role in neocortical area patterning through its inhibitory effect on COUP-TFI/Nr2f1 anterior expression, but its mechanism of action is poorly understood. We established an in vitro model of mouse embryonic stem cell corticogenesis in which COUP-TFI protein expression is inhibited by the activation of FGF8 in a time window corresponding to cortical area patterning. Interestingly, overexpression of the COUP-TFI 3′UTR reduces the inhibitory effect of FGF8 on COUP-TFI translation. FGF8 induces the expression of few miRNAs targeting COUP-TFI 3′UTR in silico. We found that the functional inhibition of miR-21 can effectively counteract the inhibitory effect of FGF8 in vitro and regulate COUP-TFI protein levels in vivo. Accordingly, miR-21 expression is complementary to COUP-TFI expression during corticogenesis. These data support a translational control of COUP-TFI gradient expression by FGF8 via miR-21 and contribute to our understanding of how regionalized expression is established during neocortical area mapping

Effect Of Priming On Seed Vigor Of Wheat (Triticum Aestivum L.)

Priming is a process that controls the process of hydration of seeds for the ongoing metabolic processes before germination. Research on priming was conducted at ICERI seed laboratory from May to September 2009 to evaluate the effect of different priming methods on wheat seed vigor. Physical properties and chemical composition of seed were evaluated before seeds were treated. The priming treatment were conducted by soaking 250 g of seed in 500 mL of solution for hydropriming and halopriming. Two seed lots of Nias and Dewata variety were subjected to heated and unheated distilled water for 12hours and subjected to KCl and CaCl2 at 10, 20, and 30 ppm and unprimed seed. The experiment were arranged in completely randomized design, replicated thrice. Vigor evaluation by observed seed germination, simultaneity growth, germination rate, seedling dry weight, electric conductivity of seed leakage and length of primary root. The results showed that highest germination, simultaneity growth, seedling dry weight, and length of primary root, were priming treatment with KCl 30 ppm and CaCl2 20 and 30 ppm. Priming with distilled water for 12 hours gave higher germination percentage and simultaneity growth

A cross-species spatiotemporal proteomic analysis identifies UBE3A-dependent signaling pathways and targets

Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of neuronal E3 ligase UBE3A. Restoring UBE3A levels is a potential disease-modifying therapy for AS and has recently entered clinical trials. There is paucity of data regarding the molecular changes downstream of UBE3A hampering elucidation of disease therapeutics and biomarkers. Notably, UBE3A plays an important role in the nucleus but its targets have yet to be elucidated. Using proteomics, we assessed changes during postnatal cortical development in an AS mouse model. Pathway analysis revealed dysregulation of proteasomal and tRNA synthetase pathways at all postnatal brain developmental stages, while synaptic proteins were altered in adults. We confirmed pathway alterations in an adult AS rat model across multiple brain regions and highlighted region-specific differences. UBE3A reinstatement in AS model mice resulted in near complete and partial rescue of the proteome alterations in adolescence and adults, respectively, supporting the notion that restoration of UBE3A expression provides a promising therapeutic option. We show that the nuclear enriched transketolase (TKT), one of the most abundantly altered proteins, is a novel direct UBE3A substrate and is elevated in the neuronal nucleus of rat brains and human iPSC-derived neurons. Taken together, our study provides a comprehensive map of UBE3A-driven proteome remodeling in AS across development and species, and corroborates an early UBE3A reinstatement as a viable therapeutic option. To support future disease and biomarker research, we present an accessible large-scale multi-species proteomic resource for the AS community (https://www.angelman-proteome-project.org/)

A eutherian-specific microRNA controls the translation of Satb2 in a model of cortical differentiation

Cerebral cortical development is controlled by key transcription factors that specify the neuronal identities in the different layers. The mechanisms controlling their expression in distinct cells are only partially known. We investigated the expression and stability of Tbr1, Bcl11b, Fezf2, Satb2, and Cux1 mRNAs in single developing mouse cortical cells. We observe that Satb2 mRNA appears much earlier than its protein and in a set of cells broader than expected, suggesting an initial inhibition of its translation, subsequently released during development. Mechanistically, Satb2 30UTR modulates protein translation of GFP reporters during mouse corticogenesis. We select miR541, a eutherian-specific miRNA, and miR-92a/b as the best candidates responsible for SATB2 inhibition, being strongly expressed in early and reduced in late progenitor cells. Their inactivation triggers robust and premature SATB2 translation in both mouse and human cortical cells. Our findings indicate RNA interference as a major mechanism in timing cortical cell identities