Translocating the blood-brain barrier using electrostatics

Copyright © 2012 Ribeiro,Domingues, Freire,Santos and Castanho. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.Mammalian cell membranes regulate homeostasis, protein activity, and cell signaling. The charge at the membrane surface has been correlated with these key events. Although mammalian cells are known to be slightly anionic, quantitative information on the membrane charge and the importance of electrostatic interactions in pharmacokinetics and pharmacodynamics remain elusive. Recently, we reported for the first time that brain endothelial cells (EC) are more negatively charged than human umbilical cord cells, using zeta-potential measurements by dynamic light scattering. Here, we hypothesize that anionicity is a key feature of the blood-brain barrier (BBB) and contributes to select which compounds cross into the brain. For the sake of comparison, we also studied the membrane surface charge of blood components—red blood cells (RBC), platelets, and peripheral blood mononuclear cells (PBMC).To further quantitatively correlate the negative zeta-potential values with membrane charge density, model membranes with different percentages of anionic lipids were also evaluated. From all the cells tested, brain cell membranes are the most anionic and those having their lipids mostly exposed, which explains why lipophilic cationic compounds are more prone to cross the blood-brain barrier.Fundação para a Ciência e Tecnologia — Ministério da Educação e Ciência (FCT-MEC, Portugal) is acknowledged for funding (including fellowships SFRH/BD/42158/2007 to Marta M.B. Ribeiro, SFRH/BD/41750/2007 to Marco M. Domingues and SFRH/BD/70423/2010 to João M. Freire) and project PTDC/QUI-BIQ/119509/2010. Marie Curie Industry-Academia Partnerships and Pathways (European Commission) is also acknowledged for funding (FP7-PEOPLE-2007-3-1-IAPP, Project 230654)

Lipoxidation and cancer immunity

Lipoxidation is a well-known reaction between electrophilic carbonyl species, formed during oxidation of lipids, and specific proteins that, in most cases, causes an alteration in proteins function. This can occur under physiological conditions but, in many cases, it has been associated to pathological process, including cancer. Lipoxidation may have an effect in cancer development through their effects in tumour cells, as well as through the alteration of immune components and the consequent modulation of the immune response. The formation of protein adducts affects different proteins in cancer, triggering different mechanism, such as proliferation, cell differentiation and apoptosis, among others, altering cancer progression. The divergent results obtained documented that the formation of lipoxidation adducts can have either anti-carcinogenic or pro-carcinogenic effects, depending on the cell type affected and the specific adduct formed. Moreover, lipoxidation adducts may alter the immune response, consequently causing either positive or negative alterations in cancer progression. Therefore, in this review, we summarize the effects of lipoxidation adducts in cancer cells and immune components and their consequences in the evolution of different types of cancer.publishe

Alterações bioquímicas em larvas de Danio rerio por exposição à mistura de herbicidas.

Resumo: A cana-de-açúcar é o carro-chefe da agricultura paulista e o Brasil é líder mundial na produção do etanol em larga escala, um combustível renovável que contribui para a redução da emissão de gases de efeito estufa, por evitar a queima de combustíveis fósseis. A alta produtividade desta cultura necessita, entretanto, do uso intensivo de defensivos agrícolas, que podem contaminar mananciais próximos às áreas de cultivo ou mesmo serem transportados afetando ecossistemas distantes. O uso simultâneo de diferentes herbicidas é comum nas lavouras, mas sua interação e o impacto sobre espécies não-alvo não são bem conhecidos. O objetivo deste trabalho foi avaliar o efeito da mistura de herbicidas ametrina e diuron, usada na lavoura canavieira, sobre o desenvolvimento embrionário e a atividade de biomarcadores de larvas de Danio rerio, um cipriníedo tropical amplamente utilizado em ensaios ecotoxicológicos

An open and parallel multiresolution framework using block-based adaptive grids

A numerical approach for solving evolutionary partial differential equations in two and three space dimensions on block-based adaptive grids is presented. The numerical discretization is based on high-order, central finite-differences and explicit time integration. Grid refinement and coarsening are triggered by multiresolution analysis, i.e. thresholding of wavelet coefficients, which allow controlling the precision of the adaptive approximation of the solution with respect to uniform grid computations. The implementation of the scheme is fully parallel using MPI with a hybrid data structure. Load balancing relies on space filling curves techniques. Validation tests for 2D advection equations allow to assess the precision and performance of the developed code. Computations of the compressible Navier-Stokes equations for a temporally developing 2D mixing layer illustrate the properties of the code for nonlinear multi-scale problems. The code is open source

Antony and Cleopatra

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Study of Metal/Polymer Interface of Parts Produced by a Hybrid Additive Manufacturing Approach

Acknowledgments This research work was supported by the Portuguese Foundation for Science and Technology (FCT) and Centro2020 through the Project reference: UID/Multi/04044/2013, PAMI - ROTEIRO/0328/2013 (Nº 022158) and Portuguese National Innovation Agency (ANI) through the Project reference POCI-01-0247-FEDER-017963, NEXT.parts – Next Generation of Advanced Hybrid Parts (co-promotion nº 17963).The additive manufacturing of multimaterial parts, e.g. metal/plastic, with functional gradients represents for current market demands a great potential of applications [1]. Metal Polymer parts combine the good mechanical properties of the metals with the low weight characteristics, good impact strength, good vibration and sound absorption of the polymers. Nevertheless, the coupling between metal and polymers is a great challenge since the processing factors for each one of them are very different. In addition, a system that makes the hybrid processing - metal/polymer - using only one operation is unknown [2, 3]. To overcome this drawback, a hybrid additive manufacturing system based on the additive technologies of SLM and SL was recently developed by the authors. The SLM and SL techniques joined enabling the production of a photopolymerization of the polymer in the voids of a 3D metal mesh previously produced by SLM [4]. The purpose of this work is the study on the metal/polymer interface of hybrid parts manufactured from the hybrid additive manufacturing system [5]. For this, a core of tool steel (H13) and two different types of photopolymers: one elastomeric (BR3D-DL-Flex) and another one rigid (BR3D-DL-Hard) are considered. A set of six samples for each one of metal core/polymer combination was manufactured and submitted to tensile tests.info:eu-repo/semantics/publishedVersio

Doses de nitrogênio em cobertura e formas de ureia no desempenho agronômico de genótipos de trigo.

O objetivo foi avaliar o efeito de doses de adubação nitrogenada em cobertura, provenientes de diferentes formas de ureia, em genótipos de trigo em sistema de semeadura direta. Os três genótipos avaliados foram: cultivares BRS 208 e BRS Pardela e linhagem IWT 04008, em Londrina-PR, totalizando três experimentos. O delineamento experimental utilizado foi de blocos casualizados em esquema fatorial 3 x 4, com quatro repetições, avaliando-se três formas de ureia em cobertura (ureia convencional, ureia com inibidor de urease e ureia protegida) com quatro doses de nitrogênio (N) (0, 40, 80 e 120 kg ha-1) aplicadas 20 dias após a emergência. Os dados obtidos nos experimentos foram analisados conjuntamente para avaliar o efeito de genótipo. As cultivares BRS 208 e BRS Pardela são mais produtivas do que a linhagem IWT 04008. O incremento das doses de N aumenta o ciclo até o espigamento e até a maturação, a massa seca da folha bandeira, o número de espigas m-2, o teor de nitrogênio do grão a porcentagem de acamamento, porém reduz a massa de mil grãos, o rendimento e o peso do hectolitro. Com a ocorrência de chuva logo após a aplicação, as formas de ureia em cobertura não interferem nas características agronômicas do trigo