69 research outputs found

    O tema da busca pessoal nos Bildungsromane femininos contemporâneos Rubyfruit Jungle, Hotel du Lac e A Complicated Kindness

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    O objetivo deste artigo é tecer alguns comentários sobre o tema da busca pessoal nos Bildungsromane femininos contemporâneos Rubyfruit Jungle (1973), da norte-americana Rita Mae Brown, Hotel du Lac (1984), da inglesa Anita Brookner, e A Complicated Kindness (2004), de Miriam Toews. O processo de aprendizagem e de transformação em confronto com a realidade das protagonistas mostra que há uma contradição entre a posição conquistada pelas mulheres na sociedade contemporânea e a sua respectiva representação. Por isso, o tema da busca gira em torno dos anseios de identidade, realização pessoal e profissional, e liberdade de autoexpressão, denunciando que o poder de escolha e a tomada de decisão ainda sofrem forte influência das relações de gênero desiguais

    Tecniche di modellazione di reattori di disinfezione con agenti chimici: dall’IDDF alla CFD

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    Il processo di disinfezione ricopre un ruolo fondamentale negli impianti di potabilizzazione e depurazione. Un importante strumento di supporto alla progettazione e all’ottimizzazione di questa fase è la modellazione del processo, basata su un approccio convenzionale, come l’Integrated Disinfection Design Framework (IDDF), o su un approccio avanzato, come la fluidodinamica computazionale (Computational Fluid Dynamics, CFD). Nel presente lavoro, le due tecniche modellistiche, IDDF e CFD, sono state applicate per la modellazione a scala pilota di un reattore di contatto aperto a setti, confrontando le loro prestazioni nella descrizione del processo di disinfezione e svolgendo un’analisi di sensitività sui principali parametri operativi e cinetici. Una prima parte del lavoro si è concentrata sulla corretta applicazione delle due tecniche modellistiche, utilizzando i dati sperimentali disponibili per scopi di calibrazione, mentre nella seconda parte le due tecniche modellistiche sono state confrontate. Entrambi gli approcci sono risultati strumenti efficaci nel caso si disponga di dati sperimentali affidabili, indispensabili per la messa a punto e la corretta applicazione dei modelli. La scelta dell’approccio più idoneo non è univoca, ma dipende fondamentalmente dell’obiettivo del lavoro e dalle risorse computazionali disponibili. Per quanto un approccio semplificato come l’IDDF abbia dimostrato di essere uno strumento efficace per la stima dei fenomeni coinvolti nei processi di decadimento dell’ipoclorito di sodio, inattivazione batterica e formazione di sottoprodotti, questo tralascia qualsiasi informazione circa gli effetti locali, a differenza della CFD che ha invece evidenziato come la loro identificazione sia indispensabile per determinare e quantificare possibili fonti di non idealità

    DOF-binding sites additively contribute to guard cell-specificity of AtMYB60 promoter

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    <p>Abstract</p> <p>Background</p> <p>We previously demonstrated that the <it>Arabidopsis thaliana </it>AtMYB60 protein is an R2R3MYB transcription factor required for stomatal opening. <it>AtMYB60 </it>is specifically expressed in guard cells and down-regulated at the transcriptional levels by the phytohormone ABA.</p> <p>Results</p> <p>To investigate the molecular mechanisms governing <it>AtMYB60 </it>expression, its promoter was dissected through deletion and mutagenesis analyses. By studying different versions of <it>AtMYB60 </it>promoter::GUS reporter fusions in transgenic plants we were able to demonstrate a modular organization for the <it>AtMYB60 </it>promoter. Particularly we defined: a minimal promoter sufficient to confer guard cell-specific activity to the reporter gene; the distinct roles of different DOF-binding sites organised in a cluster in the minimal promoter in determining guard cell-specific expression; the promoter regions responsible for the enhancement of activity in guard cells; a promoter region responsible for the negative transcriptional regulation by ABA. Moreover from the analysis of single and multiple mutants we could rule out the involvement of a group of DOF proteins, known as CDFs, already characterised for their involvement in flowering time, in the regulation of <it>AtMYB60 </it>expression.</p> <p>Conclusions</p> <p>These findings shed light on the regulation of gene expression in guard cells and provide new promoter modules as useful tools for manipulating gene expression in guard cells, both for physiological studies and future biotechnological applications.</p

    Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development.

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    BACKGROUND & AIMS Fatty liver disease, including non-alcoholic fatty liver (NAFLD) and steatohepatitis (NASH), has been associated with increased intestinal barrier permeability and translocation of bacteria or bacterial products into the blood circulation. In this study, we aimed to unravel the role of both intestinal barrier integrity and microbiota in NAFLD/NASH development. METHODS C57BL/6J mice were fed with high-fat diet (HFD) or methionine-choline-deficient diet for 1 week or longer to recapitulate aspects of NASH (steatosis, inflammation, insulin resistance). Genetic and pharmacological strategies were then used to modulate intestinal barrier integrity. RESULTS We show that disruption of the intestinal epithelial barrier and gut vascular barrier (GVB) are early events in NASH pathogenesis. Mice fed HFD for only 1 week undergo a diet-induced dysbiosis that drives GVB damage and bacterial translocation into the liver. Fecal microbiota transplantation from HFD-fed mice into specific pathogen-free recipients induces GVB damage and epididymal adipose tissue enlargement. GVB disruption depends on interference with the WNT/β-catenin signaling pathway, as shown by genetic intervention driving β-catenin activation only in endothelial cells, preventing GVB disruption and NASH development. The bile acid analogue and farnesoid X receptor agonist obeticholic acid (OCA) drives β-catenin activation in endothelial cells. Accordingly, pharmacologic intervention with OCA protects against GVB disruption, both as a preventive and therapeutic agent. Importantly, we found upregulation of the GVB leakage marker in the colon of patients with NASH. CONCLUSIONS We have identified a new player in NASH development, the GVB, whose damage leads to bacteria or bacterial product translocation into the blood circulation. Treatment aimed at restoring β-catenin activation in endothelial cells, such as administration of OCA, protects against GVB damage and NASH development. LAY SUMMARY The incidence of fatty liver disease is reaching epidemic levels in the USA, with more than 30% of adults having NAFLD (non-alcoholic fatty liver disease), which can progress to more severe non-alcoholic steatohepatitis (NASH). Herein, we show that disruption of the intestinal epithelial barrier and gut vascular barrier are early events in the development of NASH. We show that the drug obeticholic acid protects against barrier disruption and thereby prevents the development of NASH, providing further evidence for its use in the prevention or treatment of NASH

    Tdp-25 Routing to Autophagy and Proteasome Ameliorates its Aggregation in Amyotrophic Lateral Sclerosis Target Cells

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    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motoneurons, while non-neuronal cells may contribute to disease onset and progression. Most ALS cases are characterized by the mislocalization and aggregation of the TAR DNA binding protein 43 (TDP-43) in affected cells. TDP-43 aggregates contain C-terminal TDP-43 fragments of 35 kDa (TDP-35) and 25 kDa (TDP-25) and have been mainly studied in motoneurons, while little is currently known about their rate of accumulation and clearance in myoblasts. Here, we performed a comparative study in immortalized motoneuronal like (NSC34; i-motoneurons) cells and stabilized myoblasts (C2C12; s-myoblasts) to evaluate if these two cell types differentially accumulate and clear TDP forms. The most aggregating specie in i-motoneurons is the TDP-25 fragment, mainly constituted by the \u201cprion-like\u201d domain of TDP-43. To a lower extent, TDP-25 also aggregates in s-myoblasts. In both cell types, all TDP species are cleared by proteasome, but TDP-25 impairs autophagy. Interestingly, the routing of TDP-25 fragment to proteasome, by overexpressing BAG1, or to autophagy, by overexpressing HSPB8 or BAG3 decreased its accumulation in both cell types. These results demonstrate that promoting the chaperone-assisted clearance of ALS-linked proteins is beneficial not only in motoneurons but also in myoblasts

    US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

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    This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

    Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

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    Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

    Consciência literária e posicionamento político no processo de composição de The Voyage Out, de Virginia Woolf

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    In this article, a discussion about the implications and developments in the relation between Literature and Politics is proposed in order to demystify generalized critical opinions in literary studies. To do this, articulations between theory and practice are made, based on Virginia Woolf’s composition process of her first novel, pointing out the author’s artistic ability and political consciousness.Neste artigo, propomos uma discussão sobre as implicações e desdobramentos da relação entre Literatura e Política, com o intuito de desmistificar certas posições críticas generalizadas no âmbito dos estudos literários. Para isso, fazemos algumas articulações entre teoria e aspectos do processo de composição do primeiro romance de Virginia Woolf, destacando a habilidade literária e a consciência política da autora
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