1,365 research outputs found

    OS LIMITES E AS POSSIBILIDADES NO TRATAMENTO DO DANO EXTRAPATRIMONIAL NA SEARA TRABALHISTA

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    O objeto do presente trabalho é fixar parâmetros que possam colaborar na identificação do dano extrapatrimonial na seara trabalhista, instituto jurídico que não deve ser confundido com o dano moral. Inicialmente, foi analisado o dano como pressuposto da responsabilidade civil, para, em seguida, apresentar a essência do dano extrapatrimonial. Ao fim, evidenciou-se a impossibilidade de criação de um microssistema quanto ao dano extrapatrimonial a partir um rol taxativo positivado pela Lei n.º 13.467/2017, o que desconsidera a unidade do sistema jurídico brasileiro

    Corticosterone alters materno-fetal glucose partitioning and insulin signalling in pregnant mice.

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    Glucocorticoids affect glucose metabolism in adults and fetuses, although their effects on materno-fetal glucose partitioning remain unknown. The present study measured maternal hepatic glucose handling and placental glucose transport together with insulin signalling in these tissues in mice drinking corticosterone either from day (D) 11 to D16 or D14 to D19 of pregnancy (term = D21). On the final day of administration, corticosterone-treated mice were hyperinsulinaemic (P 0.05). Insulin receptor and insulin-like growth factor type I receptor abundance did not differ with treatment in either tissue. Corticosterone upregulated the stress-inducible mechanistic target of rapamycin (mTOR) suppressor, Redd1, in liver (D16 and D19) and placenta (D19), in ad libitum fed animals (P < 0.05). Concomitantly, hepatic protein content and placental weight were reduced on D19 (P < 0.05), in association with altered abundance and/or phosphorylation of signalling proteins downstream of mTOR. Taken together, the data indicate that maternal glucocorticoid excess reduces fetal growth partially by altering placental glucose transport and mTOR signalling.The studies described in this manuscript were supported by a graduate studentship to ORV from the Centre for Trophoblast Research in Cambridge.This is the accepted manuscript of a paper published in The Journal of Physiology Volume 593, Issue 5, pages 1307–1321, 1 March 2015, DOI: 10.1113/jphysiol.2014.28717

    RNA Interference Is Responsible for Reduction of Transgene Expression after Sleeping Beauty Transposase Mediated Somatic Integration

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    Integrating non-viral vectors based on transposable elements are widely used for genetically engineering mammalian cells in functional genomics and therapeutic gene transfer. For the Sleeping Beauty (SB) transposase system it was demonstrated that convergent transcription driven by the SB transposase inverted repeats (IRs) in eukaryotic cells occurs after somatic integration. This could lead to formation of double-stranded RNAs potentially presenting targets for the RNA interference (RNAi) machinery and subsequently resulting into silencing of the transgene. Therefore, we aimed at investigating transgene expression upon transposition under RNA interference knockdown conditions. To establish RNAi knockdown cell lines we took advantage of the P19 protein, which is derived from the tomato bushy stunt virus. P19 binds and inhibits 21 nucleotides long, small-interfering RNAs and was shown to sufficiently suppress RNAi. We found that transgene expression upon SB mediated transposition was enhanced, resulting into a 3.2-fold increased amount of colony forming units (CFU) after transposition. In contrast, if the transgene cassette is insulated from the influence of chromosomal position effects by the chicken-derived cHS4 insulating sequences or when applying the Forg Prince transposon system, that displays only negligible transcriptional activity, similar numbers of CFUs were obtained. In summary, we provide evidence for the first time that after somatic integration transposon derived transgene expression is regulated by the endogenous RNAi machinery. In the future this finding will help to further improve the molecular design of the SB transposase vector system

    A Plant Extract of Ribes nigrum folium Possesses Anti-Influenza Virus Activity In Vitro and In Vivo by Preventing Virus Entry to Host Cells

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    Infections with influenza A viruses (IAV) are still amongst the major causes of highly contagious severe respiratory diseases not only bearing a devastating effect to human health, but also significantly impact the economy. Besides vaccination that represents the best option to protect from IAV infections, only two classes of anti-influenza drugs, inhibitors of the M2 ion channel and the neuraminidase, often causing resistant IAV variants have been approved. That is why the need for effective and amply available antivirals against IAV is of high priority. Here we introduce LADANIA067 from the leaves of the wild black currant (Ribes nigrum folium) as a potent compound against IAV infections in vitro and in vivo. LADANIA067 treatment resulted in a reduction of progeny virus titers in cell cultures infected with prototype avian and human influenza virus strains of different subtypes. At the effective dose of 100 µg/ml the extract did not exhibit apparent harming effects on cell viability, metabolism or proliferation. Further, viruses showed no tendency to develop resistance to LADANIA067 when compared to amantadine that resulted in the generation of resistant variants after only a few passages. On a molecular basis the protective effect of LADANIA067 appears to be mainly due to interference with virus internalisation. In the mouse infection model LADANIA067 treatment reduces progeny virus titers in the lung upon intranasal application. In conclusion, an extract from the leaves of the wild black currant might be a promising source for the development of new antiviral compounds to fight IAV infections

    Machine learning outperforms clinical experts in classification of hip fractures

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    Hip fractures are a major cause of morbidity and mortality in the elderly, and incur high health and social care costs. Given projected population ageing, the number of incident hip fractures is predicted to increase globally. As fracture classification strongly determines the chosen surgical treatment, differences in fracture classification influence patient outcomes and treatment costs. We aimed to create a machine learning method for identifying and classifying hip fractures, and to compare its performance to experienced human observers. We used 3659 hip radiographs, classified by at least two expert clinicians. The machine learning method was able to classify hip fractures with 19% greater accuracy than humans, achieving overall accuracy of 92%

    On the SigmaN cusp in the pp -> pK+Lambda reaction

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    Measurements of the pppK+Λpp \to pK^+\Lambda reaction at TpT_p = 2.28 GeV have been carried out at COSY-TOF. In addition to the Λp\Lambda p FSI and NN^* resonance excitation effects a pronounced narrow structure is observed in the Dalitz plot and in its projection on the pΛp\Lambda-invariant mass. The structure appears at the pppp \to NK+ΣK^+\Sigma threshold and is interpreted as Σ\SigmaN cusp effect. The observed width of 20 MeV/c2c^2 is substantially broader than anticipated from previous inclusive measurements. Angular distributions of this cusp structure are shown to be dissimilar to those in the residual pK+ΛpK^+\Lambda channel, but similar to those observed in the pK+Σ0pK^+\Sigma^0 channel
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