519 research outputs found

    Dano moral e inexecução contratual

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    A presente monografia trata da responsabilidade civil por danos morais decorrente da quebra da relação jurídica contratual, tema ainda muito controverso no pensamento dos magistrados e doutrinadores. Objetiva uma sintonia que esclareça que a ofensa aos direitos de personalidade consagrados com a atual Carta Constitucional de 1988, desde que indo além da normalidade do dia-a-dia, podem dar ensejo à qualquer tipo de responsabilidade, seja ela contratual ou extracontratual, pois decorrem do princípio da boa-fé objetiva nas obrigações contratuais, que enseja o necessário dever de cuidado na maneira como se induz a aplicabilidade do pactuado, e na proteção da cláusula geral de tutela da dignidade da pessoa humana, que penaliza qualquer espécie de violação aos valores imateriais do homem

    Microbial community dynamics in soil depth profiles over 120,000 years of ecosystem development

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    Along a long-term ecosystem development gradient, soil nutrient contents and mineralogical properties change, therefore probably altering soil microbial communities. However, knowledge about the dynamics of soil microbial communities during long-term ecosystem development including progressive and retrogressive stages is limited, especially in mineral soils. Therefore, microbial abundances (quantitative PCR) and community composition (pyrosequencing) as well as their controlling soil properties were investigated in soil depth profiles along the 120,000 years old Franz Josef chronosequence (New Zealand). Additionally, in a microcosm incubation experiment the effects of particular soil properties, i.e., soil age, soil organic matter fraction (mineral-associated vs. particulate), O2 status, and carbon and phosphorus additions, on microbial abundances (quantitative PCR) and community patterns (T-RFLP) were analyzed. The archaeal to bacterial abundance ratio not only increased with soil depth but also with soil age along the chronosequence, coinciding with mineralogical changes and increasing phosphorus limitation. Results of the incubation experiment indicated that archaeal abundances were less impacted by the tested soil parameters compared to Bacteria suggesting that Archaea may better cope with mineral-induced substrate restrictions in subsoils and older soils. Instead, archaeal communities showed a soil age-related compositional shift with the Bathyarchaeota, that were frequently detected in nutrient-poor, low-energy environments, being dominant at the oldest site. However, bacterial communities remained stable with ongoing soil development. In contrast to the abundances, the archaeal compositional shift was associated with the mineralogical gradient. Our study revealed, that archaeal and bacterial communities in whole soil profiles are differently affected by long-term soil development with archaeal communities probably being better adapted to subsoil conditions, especially in nutrient-depleted old soils

    Reciprocal regulation of glycine-rich RNA-binding proteins via an interlocked feedback loop coupling alternative splicing to nonsense-mediated decay in Arabidopsis

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    The Arabidopsis RNA-binding protein AtGRP8 undergoes negative autoregulation at the post-transcriptional level. An elevated AtGRP8 protein level promotes the use of a cryptic 5′ splice site to generate an alternatively spliced transcript, as_AtGRP8, retaining the 5′ half of the intron with a premature termination codon. In mutants defective in nonsense-mediated decay (NMD) abundance of as_AtGRP8 but not its pre-mRNA is elevated, indicating that as_AtGRP8 is a direct NMD target, thus limiting the production of functional AtGRP8 protein. In addition to its own pre-mRNA, AtGRP8 negatively regulates the AtGRP7 transcript through promoting the formation of the equivalent alternatively spliced as_AtGRP7 transcript, leading to a decrease in AtGRP7 abundance. Recombinant AtGRP8 binds to its own and the AtGRP7 pre-mRNA, suggesting that this interaction is relevant for the splicing decision in vivo. AtGRP7 itself is part of a negative autoregulatory circuit that influences circadian oscillations of its own and the AtGRP8 transcript through alternative splicing linked to NMD. Thus, we identify an interlocked feedback loop through which two RNA-binding proteins autoregulate and reciprocally crossregulate by coupling unproductive splicing to NMD. A high degree of evolutionary sequence conservation in the introns retained in as_AtGRP8 or as_AtGRP7 points to an important function of these sequences

    Intervenciones psicológicas basadas en mindfulness y sus beneficios: estado actual de la cuestión

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    Las intervenciones basadas en mindfulness (IBM) se fundamentan en antiguas prácticas del budismo, actualizadas y adaptadas al contexto occidental. En la presente revisión se describirán las técnicas más usadas, para a continuación analizar los mecanismos de acción que el mindfulness (i.e., atención plena) parece activar como intervención psicológica. En la segunda parte se revisarán los estudios de tipo aplicado. Se comenzará analizando los ensayos clínicos y metaanálisis relativos a las intervenciones sobre problemas mentales. En un segundo momento se analizarán los estudios de eficacia y metaanálisis relativos a los problemas de salud física. En la parte final se tratan algunos temas importantes, como los posibles efectos adversos o los perfiles más adecuados a este tipo de intervención, y se revisan los temas que requieren de más investigación, como la eficacia comparada con otras técnicas de intervención ya validadas. La conclusión global en función de la investigación revisada es que las IBM son técnicas de gran versatilidad, ideales para contextos de atención primaria o similares y que logran sus mayores tasas de eficacia en pacientes con sintomatología de estrés, ansiedad o depresión

    Short-Term Treatment with Bisphenol-A Leads to Metabolic Abnormalities in Adult Male Mice

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    Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDC) used as the base compound in the manufacture of polycarbonate plastics. Although evidence points to consider exposure to BPA as a risk factor for insulin resistance, its actions on whole body metabolism and on insulin-sensitive tissues are still unclear. The aim of the present work was to study the effects of low doses of BPA in insulin-sensitive peripheral tissues and whole body metabolism in adult mice. Adult mice were treated with subcutaneous injection of 100 µg/kg BPA or vehicle for 8 days. Whole body energy homeostasis was assessed with in vivo indirect calorimetry. Insulin signaling assays were conducted by western blot analysis. Mice treated with BPA were insulin resistant and had increased glucose-stimulated insulin release. BPA-treated mice had decreased food intake, lower body temperature and locomotor activity compared to control. In skeletal muscle, insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit was impaired in BPA-treated mice. This impairment was associated with a reduced insulin-stimulated Akt phosphorylation in the Thr308 residue. Both skeletal muscle and liver displayed an upregulation of IRS-1 protein by BPA. The mitogen-activated protein kinase (MAPK) signaling pathway was also impaired in the skeletal muscle from BPA-treated mice. In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit

    Influence of Neonatal Hypothyroidism on Hepatic Gene Expression and Lipid Metabolism in Adulthood

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    Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology, but its specific influence in liver is less understood. Here, we studied how CH influences the liver gene expression program in adulthood. Pregnant rats were given the antithyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as reductions in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, the feed efficiency increased in CH, and this was accompanied by significant catch-up growth. On PND80, significant reductions in body mass, tail length, and circulating IGF-I levels remained in CH rats. Conversely, the mRNA levels of known GH target genes were significantly upregulated. The serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARα and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3 replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood

    Gut Microbiota Is a Key Modulator of Insulin Resistance in TLR 2 Knockout Mice

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    A genetic and pharmacological approach reveals novel insights into how changes in gut microbiota can subvert genetically predetermined phenotypes from lean to obese
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