Specific Inhibition of the Redox Activity of Ape1/Ref-1 by E3330 Blocks Tnf-A-Induced Activation of Il-8 Production in Liver Cancer Cell Lines

APE1/Ref-1 is a main regulator of cellular response to oxidative stress via DNA-repair function and co-activating activity on the NF-κB transcription factor. APE1 is central in controlling the oxidative stress-based inflammatory processes through modulation of cytokines expression and its overexpression is responsible for the onset of chemoresistance in different tumors including hepatic cancer. We examined the functional role of APE1 overexpression during hepatic cell damage related to fatty acid accumulation and the role of the redox function of APE1 in the inflammatory process. HepG2 cells were stably transfected with functional and non-functional APE1 encoding plasmids and the protective effect of APE1 overexpression toward genotoxic compounds or FAs accumulation, was tested. JHH6 cells were stimulated with TNF-α in the presence or absence of E3330, an APE1 redox inhibitor. IL-8 promoter activity was assessed by a luciferase reporter assay, gene expression by Real-Time PCR and cytokines (IL-6, IL-8, IL-12) levels measured by ELISA. APE1 over-expression did not prevent cytotoxicity induced by lipid accumulation. E3330 treatment prevented the functional activation of NF-κB via the alteration of APE1 subcellular trafficking and reduced IL-6 and IL-8 expression induced by TNF-α and FAs accumulation through blockage of the redox-mediated activation of NF-κB. APE1 overexpression observed in hepatic cancer cells may reflect an adaptive response to cell damage and may be responsible for further cell resistance to chemotherapy and for the onset of inflammatory response. The efficacy of the inhibition of APE1 redox activity in blocking TNF-α and FAs induced inflammatory response opens new perspectives for treatment of inflammatory-based liver diseases

First observations of anthropogenic underwater noise in a large multi-use lake

Over the last fifty years, anthropogenic noise has increased dramatically in aquatic environments and is now recognised as a chronic form of pollution in coastal waters. However, this form of pollution has been largely neglected in inland water bodies. To date, very few studies have investigated the noise spectra in freshwater environments and at present no legislation exists to protect freshwater organisms from anthropogenic noise. The present study represents the first assessment of anthropogenic noise pollution in a large multi-use lake by characterising noise levels of the main ferry landings of the lake of Windermere, UK using Passive Acoustic Monitoring (PAM). During November 2014, acoustic samples (10 min long) were collected from such areas using a calibrated omni-directional hydrophone and their spectral content was analysed in 1/3 octave bands (dB re 1 µPa). Results indicate that the current noise levels in Windermere warrant further investigation as a potential threat to the fish community which occurs in this already delicate and pressured habitat. Based on results obtained, it is recommended that further studies focus on a wider geographical and temporal range in order to start to fill the knowledge and legislative gaps regarding anthropogenic noise monitoring in fresh waters

Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced neuronal cell death in the cerebellum of Ugt1 KO mice

Severe hyperbilirubinemia is toxic during central nervous system development. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced encephalopathy and eventually death by kernicterus. Despite extensive studies, the molecular and cellular mechanisms of bilirubin toxicity are still poorly defined. To fill this gap, we investigated the molecular processes underlying neuronal injury in a mouse model of severe neonatal jaundice, which develops hyperbilirubinemia as a consequence of a null mutation in the Ugt1 gene. These mutant mice show cerebellar abnormalities and hypoplasia, neuronal cell death and die shortly after birth because of bilirubin neurotoxicity. To identify protein changes associated with bilirubin-induced cell death, we performed proteomic analysis of cerebella from Ugt1 mutant and wild-type mice. Proteomic data pointed-out to oxidoreductase activities or antioxidant processes as important intracellular mechanisms altered during bilirubin-induced neurotoxicity. In particular, they revealed that down-representation of DJ-1, superoxide dismutase, peroxiredoxins 2 and 6 was associated with hyperbilirubinemia in the cerebellum of mutant mice. Interestingly, the reduction in protein levels seems to result from post-translational mechanisms because we did not detect significant quantitative differences in the corresponding mRNAs. We also observed an increase in neuro-specific enolase 2 both in the cerebellum and in the serum of mutant mice, supporting its potential use as a biomarker of bilirubin-induced neurological damage. In conclusion, our data show that different protective mechanisms fail to contrast oxidative burst in bilirubin-affected brain regions, ultimately leading to neurodegeneration. \ua9 2015 Macmillan Publishers Limited All rights reserved

Association between practice of physical activity, educational level and food intake profile of truck drivers

A demanda da sociedade moderna intensificou o trabalho ininterrupto em diversas profissões. Além disso, o modo de organização da sociedade, com atividades predominantemente mecanizadas, tem contribuído para a prevalência de hábitos de vida não saudáveis, como a inatividade física. Este estudo objetiva verificar se fatores ocupacionais, sociodemográficos, antropométricos e alimentares estão associados à prática de atividade física insuficiente e se há diferenças nessa associação entre motoristas de caminhão que trabalham de dia ou à noite. Participaram da pesquisa 470 motoristas de caminhão, que responderam a questionários de dados sociodemográficos, atividade física e frequência alimentar. Foi realizada uma regressão logística univariada para verificar a associação entre atividade física insuficiente e as demais variáveis. Além disso, a regressão logística múltipla foi testada para obter modelos que mostrem a associação de conjuntos de variáveis relacionados à atividade física insuficiente. Os resultados indicaram que a prática de atividade física está associada ao maior nível de escolaridade (OR = 1,84; IC = 1,22-2,76) e menor consumo de bebidas alcoólicas (OR = 1,59; IC = 1,04-2,45). Maior ingestão de cereais integrais (OR = 1,63; IC = 1,08-2,46) foi associada à prática regular de atividade física. Entre os trabalhadores noturnos, foi encontrada associação entre a prática regular de atividade física, maior consumo de cereais integrais (OR = 2,02; IC =1,13-3,60) e menor consumo de carboidratos simples (OR = 1,91; IC = 1,08-3,37).The modern society's demand has intensified uninterrupted work among several professional categories. Besides that, the society's organization, with activities that are predominantly mechanized, has contributed to unhealthy life habits, such as lack of physical activity. The study aims to verify the association of occupational, social-demographic, anthropometric and food intake data with insufficient practice of physical activities and if there are any differences in this association between day and night truck drivers. The 470 truck drivers who participated in this study answered social-demographic, physical activity and food frequency questionnaires. Univariate logistic regression analysis was used to verify the association between insufficient physical activity and the other variables. Additionally, multiple logistic regression was tested to obtain models that show the association between sets of variables related to insufficient physical activity. The results indicated that practice of physical activities is associated with high educational level (OR=1.84; CI = 1.22-2.76) and low alcohol consumption (OR = 1.59; CI = 1.04-2.45). High intake of whole grains (OR = 1.63; CI = 1.08-2.46) was associated with regular practice of physical activity. Among the night workers, we found the association between regular practice of physical activity, high consumption of whole grains (OR = 2.02; CI = 1.13-3.60) and low consumption of simple carbohydrates (OR = 1.91; CI = 1.08-3.37)

O ethos revolucionário da esquerda armada brasileira: o caso do Movimento Revolucionário 8 de Outubro.

Este artigo tem por objetivo analisar a constituição de um ethos revolucionário pelos militantes da esquerda armada brasileira, em específico, por intermédio da trajetória do Movimento Revolucionário 8 de Outubro. Através do conceito de geração proposto pelo historiador Jean-François Sirinelli, buscamos compreender como os militantes da esquerda armada, constituintes da geração de 1968, ao optarem pelo enfrentamento armado à ditadura civil-militar brasileira, construíram uma perspectiva revolucionária coletiva e individual, consolidando uma maneira específica de agir, baseada em valores éticos

Definition of innovative material scenarios through digitization processes

The ongoing synergy between the digitization of the building process and new paradigms related to the production of architectural constructions and building elements, pave the way for the definition of new scenarios that are worth investigating. The recurring question, indeed, is how the most advanced digital techniques for material production can have a tangible impact on architecture and its morphological languages.  In the field of building design, the chance to turn digital data into matter represents a key point to deal with, in order to demonstrate the possibility to transfer actual benefits from other sectors related to the construction industry

Da responsabilidade trabalhista do sócio sob o prisma da desconsideração da personalidade jurídica da empresa

O presente estudo tem por objetivo analisar o instituto da personalidade jurídica, bem assim a teoria maior e menor que tratam de sua desconsideração, identificando, à luz dos princípios que regem a seara juslaboralista e dos diplomas legais que versam a respeito da matéria, o modelo que deve ser observado nos processos trabalhistas. Outrossim, aborda a espécie de responsabilidade a ser imputada aos sócios das empresas em virtude de dívidas trabalhistas, o procedimento a ser observado para a concretização e o período de extensão desta responsabilidade, inclusive sob o enfoque o Novo Código de Processo Civil. Lei nº 103.105/2015This paper intents to analyze the institute of legal personality, as well as the bigger and smaller theories dealing with their disregard by identifying, in the light of the principles governing the labor laws and statutes that deal on the matter, the model that must be observed in labor claims. Furthermore, it addresses the kind of responsibility to be allocated to the partners of companies due to labor debts, the procedure to be followed for the implementation and the extension period this responsibility, even under the approach the New Code of Civil Procedure. Law Nº. 103.105/201