Cisplatin-Membrane Interactions and Their Influence on Platinum Complexes Activity and Toxicity

Cisplatin and other platinum(II) analogs are widely used in clinical practice as anti-cancer drugs for a wide range of tumors. The primary mechanism by which they exert their action is through the formation of adducts with genomic DNA. However, multiple cellular targets by platinum(II) complexes have been described. In particular, the early events occurring at the plasma membrane (PM), i.e., platinum-membrane interactions seem to be involved in the uptake, cytotoxicity and cell-resistance to cisplatin. In fact, PM influences signaling events, and cisplatin-induced changes on membrane organization and fluidity were shown to activate apoptotic pathways. This review critically discusses the sequence of events caused by lipid membrane-platinum interactions, with emphasis on the mechanisms that lead to changes in the biophysical properties of the membranes (e.g., fluidity and permeability), and how these correlate with sensitivity and resistance phenotypes of cells to platinum(II) complexes

Formation of Ceramide/Sphingomyelin Gel Domains in the Presence of an Unsaturated Phospholipid: A Quantitative Multiprobe Approach

AbstractTo better understand how ceramide modulates the biophysical properties of the membrane, the interactions between palmitoyl-ceramide (PCer) and palmitoyl-sphingomyelin (PSM) were studied in the presence of the fluid phospholipid palmitoyl-oleoyl-phosphatidylcholine (POPC) in membrane model systems. The use of two fluorescent membrane probes distinctly sensitive to lipid phases allowed a thorough biophysical characterization of the ternary system. In these mixtures, PCer recruits POPC and PSM in the fluid phase to form extremely ordered and compact gel domains. Gel domain formation by low PCer mol fraction (up to 12mol %) is enhanced by physiological PSM levels (∼20–30mol % total lipid). For higher PSM content, a three-phase situation, consisting of fluid (POPC-rich)/gel (PSM-rich)/gel (PCer-rich) coexistence, is clearly shown. To determine the fraction of each phase a quantitative method was developed. This allowed establishing the complete ternary phase diagram, which helps to predict PCer-rich gel domain formation and explains its enhancement through PSM/PCer interactions

O LÚDICO NO PROCESSO PEDAGÓGICO DA EDUCAÇÃO INFANTIL: IMPORTANTE, PORÉM AUSENTE

This study observed and analyzed the presence of playful teaching practice on the educational action of teachers in the kindergarten school both from the public and private sectors in the city of São José do Rio Preto. By means of a bibliographical and empirical research, schools from four different parts of the city were evaluated and systematically observed. Later, a questionnaire was applied to the teachers. The main objective was to verify whether or not there were situations in which playful activities would be part of the teacher’s daily agenda, either as a planned activity or even used randomly, as well as the understanding of the teachers concerning this matter in the infantile education.Este estudio analisó la presencia del juguete en el hacer pedagógico de las maestras en guarderías de la red pública de la ciudad de São José do Rio Preto. Por medio de encuestas bibliográficas y empíricas, fueran abordadas escuelas distribuidas en los cuatro sectores de la ciudad en los cuales se realizó una observación sistematizada, y después la aplicación de una encuesta con los maestros. El objectivo primero fue verificar si en el cotidiano de las escuelas tenía o no situaciones de utilización de actividades lúdicas, planeamento de las actividades o empleo obligatorio, como también la comprensión de las mismas acerca de los juguetes infantiles.Este estudo observou e analisou a presença do lúdico no fazer educacional das professoras das escolas infantis das redes pública e particular da cidade de São José do Rio Preto. Por meio de pesquisas bibliográfica e empírica, foram abordadas escolas distribuídas nos quatro setores da cidade, nas quais se realizou, primeiramente, uma observação sistematizada e posteriormente a aplicação de um questionário junto às professoras. O principal objetivo foi verificar se no cotidiano escolar das unidades de ensino infantil envolvidas na pesquisa havia ou não situações de utilização de atividades lúdicas, planejamento das atividades ou seu uso aleatório, assim como a compreensão das professoras acerca do brincar na educação infantil. Os dados coletados foram tratados de modo comparativo entre os dois modelos de escolas compreendidas nos setores público e privado, o que possibilitou traçar um percurso do lúdico na educação infantil e no fazer pedagógico das professoras que, na época, atuavam nos distintos segmentos com a respectiva faixa etária

Fire Responses to the 2010 and 2015/2016 Amazonian Droughts

Extreme droughts in Amazonia cause anomalous increase in fire occurrence, disrupting the stability of environmental, social, and economic systems. Thus, understanding how droughts affect fire patterns in this region is essential for anticipating and planning actions for remediation of possible impacts. Focused on the Brazilian Amazon biome, we investigated fire responses to the 2010 and 2015/2016 Amazonian droughts using remote sensing data. Our results revealed that the 2015/2016 drought surpassed the 2010 drought in intensity and extent. During the 2010 drought, we found a maximum area of 846,800 km2 (24% of the Brazilian Amazon biome) with significant (p ≤ 0.05) rainfall decrease in the first trimester, while during the 2015/2016 the maximum area reached 1,702,800 km2 (47% of the Brazilian Amazon biome) in the last trimester of 2015. On the other hand, the 2010 drought had a maximum area of 840,400 km2 (23% of the Brazilian Amazon biome) with significant (p ≤ 0.05) land surface temperature increase in the first trimester, while during the 2015/2016 drought the maximum area was 2,188,800 km2 (61% of the Brazilian Amazon biome) in the last trimester of 2015. Unlike the 2010 drought, during the 2015/2016 drought, significant positive anomalies of active fire and CO2 emissions occurred mainly during the wet season, between October 2015 and March 2016. During the 2010 drought, positive active fire anomalies resulted from the simultaneous increase of burned forest, non-forest vegetation and productive lands. During the 2015/2016 drought, however, this increase was dominated by burned forests. The two analyzed droughts emitted together 0.47 Pg CO2, with 0.23 Pg CO2 in 2010, 0.15 Pg CO2 in 2015 and 0.09 Pg CO2 in 2016, which represented, respectively, 209%, 136%, 82% of annual Brazil’s national target for reducing carbon emissions from deforestation by 2017 (approximately 0.11 Pg CO2 year-1 from 2006 to 2017). Finally, we anticipate that the increase of fires during the droughts showed here may intensify and can become more frequent in Amazonia due to changes in climatic variability if no regulations on fire use are implemented

Large carbon sink potential of secondary forests in the Brazilian Amazon to mitigate climate change

Tropical secondary forests sequester carbon up to 20 times faster than old-growth forests. This rate does not capture spatial regrowth patterns due to environmental and disturbance drivers. Here we quantify the influence of such drivers on the rate and spatial patterns of regrowth in the Brazilian Amazon using satellite data. Carbon sequestration rates of young secondary forests (<20 years) in the west are ~60% higher (3.0 ± 1.0 Mg C ha−1 yr−1) compared to those in the east (1.3 ± 0.3 Mg C ha−1 yr−1). Disturbances reduce regrowth rates by 8–55%. The 2017 secondary forest carbon stock, of 294 Tg C, could be 8% higher by avoiding fires and repeated deforestation. Maintaining the 2017 secondary forest area has the potential to accumulate ~19.0 Tg C yr−1 until 2030, contributing ~5.5% to Brazil’s 2030 net emissions reduction target. Implementing legal mechanisms to protect and expand secondary forests whilst supporting old-growth conservation is, therefore, key to realising their potential as a nature-based climate solution

Toxicological and toxicogenetic effects of plants used in popular medicine and in cattle food

Toxicological and toxicogenetic effects of aqueous (tea) and hexanica fruit extract of Indigofera suffruticosa Mill, and hydroalcoholic root extract od Solanum agrarium Stendt. Were evaluated in Balb C male mice intraperitoneally exposed. A hepatotoxic effect was observed just for animals treated with aqueous fruit extract of I. suffruticosa. In relation to the toxicogenetic effect, just the group trreated with 12.5% of toxic dose of aqueous fruit extract of I. suffruticosa showed a statistically significant increase in the frequency of cells with chromosome aberrations (cytogenetic effect), although a slight increase was also observed for the highest dose (25% of LF50_ of hydroalcoholic root extract of S. agrarium. The results obtanied show that before S. agrarium is used as medicine and before the wide use of I. suffruticosa in cattle food, careful evaluation must be done

Practical computational toolkits for dendrimers and dendrons structure design

Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures. Herein we describe two novel graphical user interface (GUI) toolkits written in Python that provide an improved degree of automation for rapid assembly of dendrimers and generation of their 2D and 3D structures. Our first toolkit uses the RDkit library, SMILES nomenclature of monomers and SMARTS reaction nomenclature to generate SMILES and mol files of dendrimers without 3D coordinates. These files are used for simple graphical representations and storing their structures in databases. The second toolkit assembles complex topology dendrimers from monomers to construct 3D dendrimer structures to be used as starting points for simulation using existing and widely available software and force fields. Both tools were validated for ease-of-use to prototype dendrimer structure and the second toolkit was especially relevant for dendrimers of high complexity and size.Peer reviewe

Aplicação da biologia molecular no diagnóstico de doenças genéticas

With the advances of the so called Genomic Medicine, the molecular analysis of genetic diseases increased the needs of a full characterization of alterations shown by an individual and is becoming essential for a differential diagnosis in several cases. The purpose of the present paper is to describe the molecular diagnostic protocols used in the Molecular Genetics Laboratory of the Medical Genetics Service of the Hospital de Clínicas of Porto Alegre. Most of these protocols are aimed at the use of updated and specialized molecular biology techniques in Brazil. The objective is not only the characterization of the affected patient’s genotype, but also the improvement of genetic counseling through the use of more sensitive and trustable techniques and strategies for the detection of carriers and for prenatal diagnosis in future pregnancies.Com os avanços da chamada Medicina Genômica, a análise molecular de doenças genéticas vem sendo cada vez mais necessária para a completa caracterização das alterações apresentadas por um indivíduo ou até mesmo essencial para um diagnóstico diferencial em muitos casos. O objetivo deste artigo é descrever os protocolos de diagnóstico molecular utilizados no laboratório de genética molecular do Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, que visam, em sua maioria, a utilização de técnicas atualizadas e especializadas de biologia molecular no Brasil, para permitir não apenas a caracterização do genótipo dos pacientes afetados mas também para melhorar o aconselhamento genético através do uso de técnicas e estratégias mais sensíveis e mais confiáveis para a detecção de portadores e para o diagnóstico pré-natal em gestações futuras

Sinergismo de variáveis climáticas e incêndios florestais no estado do Acre

Este estudo visou compreender a influência das variáveis climáticas de precipitação e temperatura na ocorrência de incêndios florestais no Estado do Acre, Brasil. Nos últimos 40 anos, os incêndios têm se tornado mais frequentes, ocorrendo a cada 4 a 5 anos em diferentes partes da bacia Amazônica. A distribuição espacial e temporal dos incêndios florestais têm sido associadas às secas extremas ocasionadas pelo aumento anômalo da temperatura da superfície dos oceanos. Nas partes sul e sudoeste da Amazônia, onde está localizado o Estado do Acre, duas secas extremas recentes (2005 e 2010) têm sido associadas ao aquecimento da superfície da parte tropical do oceano Atlântico Norte. Neste estudo, selecionamos o número de dias consecutivos sem chuva (P↓) e o número de dias com temperatura máxima diária acima de 35°C (T↑35°C) para correlacionar com a área total anual acumulada de cicatrizes de incêndios florestais no município de Rio Branco, entre 1984 a 2018. Os dados climáticos foram coletados de estações pluviométricas na área de estudo. Os anos de secas extremas no Estado do Acre foram 2005, 2010 e 2016, somando 526.289 ha, que representa 98% dos incêndios mapeados. Estes anos coincidem com períodos &gt;40 dias consecutivos sem chuva e &gt;38 dias com temperatura máxima diárias acima de 35°C. Em 2016, houve o El Niño mais forte já registrado, havendo recorde do T↑35°C com 66 dias. Durante os anos de 2017 e 2018 observamos que o número de dias com T↑ 35°C e P↓ estiveram acima de 30 dias, contribuindo para ocorrência de 895 ha e 262 ha, respectivamente. O intervalo médio entre os grandes incêndios florestais entre 1984 a 2018 foi de 7,25 anos, sendo que nos 20 primeiros anos de monitoramento, houve um grande incêndio a cada década (1987 e 1998), e na última década, um grande e severo incêndio a cada 5 anos (2005, 2010 e 2016). O aumento na frequência de ocorrência de eventos climáticos extremos e incêndios florestais, é provável que estejam entrando em novo regime de fogo, um "novo normal" climático, aumentando chance de ocorrência de incêndios florestais no futuro no Estado do Acre