Modulation of CYP1A1 by PKC Inhibitors and TPA Pre-Treatments in MH1C1 Rat Hepatoma Cells Exposed to 3 -Methylcholanthrene

Cytochrome P4501A1 (CYP1A1), an enzyme known to metabolize polycyclic aromatic hydrocarbons, is regulated by the aryl hydrocarbon receptor (AhR). The involvement of protein kinase C (PKC) in the regulation of AhR signal transduction pathway, has been widely studied but the role of specific PKC isoform(s) involved in this process it is not well clarified. To study which PKC isoform(s) is implicated in the regulation of CYP1A1, in the poorly tumorigenic MH1C1 rat hepatoma cells, we examined the effects of some PKC pharmacological inhibitors, Calphostin C (CAL), Staurosporine (STA) and H7, and of 12-0-tetradecanoyl phorbol 13-acetate (TPA), a PKC activator, on basal and 3- methylcholanthrene (MC)-induced CYP1A1 protein expression and mediated ethoxyresorufin O-deethylation (EROD) activity. In parallel, the activities of PKC-α, -βI, -δ and -ε isoforms, the most expressed in MH1C1 cells, were monitored. After pre-treatment with CAL, STA and H7, the MC-induced CYP1A1 protein and EROD activity were rapidly reduced with temporal profile similar to the profile of the activity of α and β1 PKC isoforms. Moreover, TPA pre-treatment induced a biphasic effect on EROD activity, and a decline of PKC -βI and -α, in first instance, and -δ and -ε activities later on. These findings clearly show that, in MH1C1 cells, PKC is involved in CYP1A1 regulation and that α and βI classic PKC isoforms play an active role in modulating this process.

David Hume and contractualism

David Hume belonged to the consecuencialist philosophical tendency, in which is included utilitarianism. This tendency was opposed to the normativism philosophy, in which is enrolled contractualism. This article analyzes the critique made by David Hume, from the utilitarianism perspective, against contractualism. The major philosophers of contractualism are Thomas Hobbes, John Locke and Jean Jacques Rousseau. Hume implemented three arguments in opposition to them: 1) historic: the social contract does not have any practical testing. Therefore it could not be presented as the foundation of the state; 2) philosophical: it is not the duty, but the interest that moves men to seek the formation of the political authority; 3) social: in the consciousness of the people, there is no trace of the social contract.Utilitarianism was one of the philosophical tendencies that finished the theoretical hegemony that contractualism had during the XVII and the XVIII centuries. Nonetheless from the historical and social point of view, the liberalization movements in many parts of the world, at that time, were inspired by contractualism. It means that from the theoretical point of view, utilitarianism, certainly, stressed the empirical origins of the state but not the rational justification of the political Authority. Hume was unable to understand the normative force that contractualism owns, which inspires human action.

Surveillance in Nineteen Eighty-Four : The Dismantling of Privacy in Oceania

The purpose of this essay is to analyze how certain elements of panopticism manage to dismantle the notion of privacy in George Orwell’s novel Nineteen Eighty-Four. By reading the text through a lens of panopticism, a theory introduced by Jeremy Bentham, I give examples on how the surveillance methods used by the Party share similarities with the system of surveillance within a Panoptic prison, but also in what ways that they differ. In the end, it is obvious that the society of Oceania cannot be considered to be a complete Panopticon, although several elements of panopticism are present within the text and that they dismantle the aspect of privacy in the novel. 

How can geographical information systems and spatial analysis inform a response to prescription opioid misuse? a discussion in the context of existing literature

Computed Tomography Perfusion Can Guide Endovascular Therapy in Bilateral Carotid Artery Dissection

Carotid artery dissection (CAD) is a major cause of stroke in those under age 45, accounting for around 20% of ischaemic events[1,2]. In the absence of known connective tissue disorders, most dissections are traumatic[2]. First-line management is comprised of antiplatelet or anticoagulation therapy, but many traumatic dissections progress despite this and carry the risk of long-term complications from embolism or stenosis[3]. We report a case of traumatic bilateral carotid dissection leading to progressive neurological symptoms and hypoperfusion on computed tomography perfusion (CTP), despite escalation in anticoagulation, which led to emergency carotid stenting.

New Foods, New Consumers: Innovation in Food Product Development

BACKGROUND: Today, new lifestyles, higher incomes and consumer awareness are creating consumer demand for a year-round supply of high-quality, diverse and innovative food products. However, when it comes to innovation, the food sector is less changeable when compared to other sectors, such as high technology. Still, in the past decades much and important developments have been achieved in several areas related to foods and the food industry. METHODS: A systematic review of scientific literature was conducted on Science Direct. The topics investigated were: aspects related to innovation in food development (such as the transfer of innovation, open innovation, collaborative innovation and consumer perception and its role in the developing process); the innovation in the food industry (particularly regarding the processing technologies and packaging, which are two prominent areas of innovation in this sector nowadays); the innovation in the cooking sector (particularly in regards to the molecular gastronomy and science based cooking). RESULTS: A total of 146 articles were included in the review and the aspects focused allowed confirming that innovation has been recognized as a key driver of economic growth. Within the framework of ‘open innovation’, a number of key issues related to the acquisition of external knowledge in food technology must be taken into consideration. Food product development is highly dependent on the consumer perception and acceptance, and hence it is of utmost importance to include the consumer in the development process to minimize failure probabilities. The sectors of the food industry where important developments and innovation are registered include the processing technologies and the packaging systems, where the latest progresses have produced very significant outcomes. CONCLUSION: The present work allowed verifying the latest improvements and trend towards food product development from two perspectives, the product itself and the industrial processing. This sector is undoubtedly a major key for the success and competitiveness nowadays in the food industry.

EVOLUÇÃO ESTRUTURAL DE BRACATINGAIS DA REGIÃO METROPOLITANA DE CURITIBA, PARANÁ, BRASIL

O objetivo deste trabalho foi estudar a evolução estrutural de espécies arbóreas em bracatingais, ao longo de vinte anos. A bracatinga ( Mimosa scabrella Benth.) é a espécie pioneira, de vida curta, que caracteriza os bracatingais. Sob as bracatingas forma-se um sub-bosque com outras espécies arbóreas, que vai assumindo o lugar da bracatinga com o passar dos anos e que é tratado como se fosse lenha da própria bracatinga, quando a área é cortada a cada 7 anos e a regeneração da bracatinga é novamente induzida com o uso do fogo. O processo de sucessão em bracatingais ainda não foi estudado e é útil identificar a idade em que as demais espécies passam a dominar o bracatingal. Trabalhou-se com 320 parcelas, distribuídas em bracatingais com idades variando de 3 a 20 anos, medidas entre 1998 e 2011. Foram medidos os DAP (diâmetro a altura do peito) e altura total de todas as espécies com DAP ≥ 5 cm. Observou-se que, aos 11 anos, o conjunto das espécies supera a bracatinga em número de indivíduos e aos 19 anos as espécies arbóreas já apresentam uma distribuição diamétrica semelhante ao de uma floresta em fase mais avançada. De forma geral observou-se que, após os 10 anos de idade, um bracatingal já começa a tomar forma de um capoeirão.

Improvement of Virtual Screening Predictions using Computational Intelligence Methods

Virtual Screening (VS) methods can considerably aid clinical research, predicting how ligands interact with drug targets. However, the accuracy of most VS methods is constrained by limitations in the scoring function that describes biomolecular interactions, and even nowadays these uncertainties are not completely understood. In order to improve accuracy of scoring functions used in most VS methods we propose a hybrid novel approach where neural networks (NNET) and support vector machines (SVM) methods are trained with databases of known active (drugs) and inactive compounds, this information being exploited afterwards to improve VS predictions.

Direct determination of Cu, Cd, Ni and Pb in aquatic humic substances by graphite furnace atomic absorption spectrometry

A method has been developed for the direct determination of Cu, Cd, Ni and Pb in aquatic humic substances (AHS) by graphite furnace atomic absorption spectrometry. AHS were isolated from water samples rich in organic matter, collected in the Brazilian Ecological Parks. All analytical curves presented good linear correlation coefficient. The limits of detection and quantification were in the ranges 2.5-16.7 mu g g(-1) and 8.5-50.0 mu g g(-1), respectively. The accuracy was determined using recovery tests, and for all analytes recovery percentages ranged from 93 - 98 %, with a relative standard deviation less than 4 %. The results indicated that the proposed method is a suitable alternative for the direct determination of metals in AHS.

A Staggered Decameric Assembly of Human C-Reactive Protein Stabilized by Zinc Ions Revealed by X-ray Crystallography

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A Catalytically Inactive Lys49 PLA2 Isoform from Bothrops jararacussu venom that Stimulates Insulin Secretion in Pancreatic Beta Cells

A new secretory phospholipase A2 (sPLA2) isoform from Bothrops jararacussu venom (BjVIII) has been characterized by causing platelet aggregation, an absent activity in BthTx-I, Prtx-I and PrTx-II sPLA2s. According to our results, BjVIII also enhances insulin release by the pancreatic beta cells. The complete amino acid sequence of the new isoform was determined by Edman degradation and de novo peptide sequencing. These analyses showed a G35K amino acid modification for BjVIII in comparison with BthTx-I, PrTx-I and Prtx-II, a structural difference that has been related to the conflicting biological activities among BjVIII and other Lys49 sPLA2s. The whole set of evidences collected in this work indicates that, besides the C-terminal region and B-wing of PLA2, the calcium binding loop in BjVIII should be considered as an important region, involved in the pharmacological effects of Lys49-sPLA2 isoforms from the Bothrops genus.

Bioactive compounds of citrus as health promoters

Citrus are a group of fruit species, quite heterogeneous in many aspects, including chemical composition of the fruit. Since ancient times, some citrus fruits were used to prevent and cure human diseases. In the recent decades, it has been demonstrated that fruits can actually help prevent and cure some diseases and above all, they are essential in a balanced diet. Citrus fruits, as one of the groups of fruit species, with greater importance in the world, have been studied for their effects on human health. Some species of citrus were referred as potential antioxidant based therapy for heart disease, cancer and inflammation. Fruit peels and seeds have also high antioxidant activity. The health benefits of citrus fruit have mainly been attributed to the high level of bioactive compounds, such as phenols (e.g., flavanone glycosides, hydroxycinnamic acids), carotenoids and vitamin C. These compounds are present in the fruit pulp and hence in the juice. But some bioactive compounds can be found in parts of the fruit which usually are not used for human food. The content of bioactive compounds depends on the species and cultivar, but also depends on the production system followed in the orchard. Citrus fruits, their derivatives and their by-products (peel, pulp and oil) are reach in different bioactive compounds and its maturity, postharvest and agroindustry processes influence their composition and concentration. The aim of this chapter was to review the main bioactive compounds of the different components of citrus and their relationship to health.

Bioactive Phenols in Small Fruits and Berries

Bioactive compounds are extra nutritional constituents occurring naturally in plant foods in small amounts, however in quantities enough to produce bioactive effects. Among bioactive compounds the phenolic compounds are a very large set of molecules, which include several groups such as for example flavonoids, phenolic acids or tannins. Small fruits and berries include a wide diversity of fruits, like grapes, strawberries, blackberries, blueberries, raspberries, cherries, hardi kiwi, gooseberries, cranberries, currants (black, white, red), physalis, crowberries, açaí, elderberries, dates or goji berries, and these frequently have been reported as having particularly high concentrations of phenolic compounds with antioxidant activity. Hence, the objective of this chapter is to review the literature about the type and contents of different phenolic compounds present in small fruits and berries, as well as their bioactive properties, including antioxidant capacity. All the fruits and berries investigated in this chapter were particularly rich in bioactive compounds, including phenolic compounds that provide the fruits with high antioxidant properties. The most relevant health promoting effects include anti-cancer, anti-inflamatory, neuro protective, cardio protective or anti-diabetes, thus indicating that these foods are a valuable resource to prevent and treat diseases.

A century of trends in adult human height

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.