Estudos químicos, biológicos e ecotoxicológicos de Schinus terebinthifolia Raddi para o controle de Aedes aegypti

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2020.Aedes aegypti é o principal vetor transmissor de arboviroses como dengue, Zika e chikungunya. As estratégias de combate a este vetor são limitadas por resistência múltipla a inseticidas, impactos deletérios ao ambiente e toxicidade em organismos não-alvo. Na busca de alternativas para o combate do Ae. aegypti, o potencial de componentes da espécie de planta Schinus terebinthifolia foi estudado. Análises quimiométricas demonstraram que o perfil metabólico de amostras ativas é claramente diferente da composição metabólica de amostras inativas no mosquito. Adicionalmente, estas análises aceleraram o processo de purificação bioguiada, que resultou no isolamento do alquilresorcinol conhecido como bilobol, que demonstrou potente atividade larvicida em Ae. aegypti (CL50 7,67 mg/L em menos de 24 h). Para assegurar que o bilobol é um candidato viável como larvicida ecologicamente seguro, o processo de degradação e a toxicidade aguda deste alquilresorcinol em peixe-zebra, um organismo não-alvo, foram explorados. Um método de quantificação com parâmetros validados foi desenvolvido e utilizado para avaliar a degradação de bilobol em água ao longo de tempo. O teste Fish Embryo Toxicity (FET) foi aplicado para avaliar a toxicidade aguda de bilobol e seus produtos de degradação. Os resultados demonstraram que o bilobol degrada gradualmente com o passar do tempo e desaparece quase totalmente após 96 h, transformando-se em pequenas cadeias alifáticas. Quando submetido ao teste FET, bilobol apresentou CL50 6,00 mg/L em 96 horas pós-fertilização (hpf). Após 24 e 96 horas de degradação (hod), CL50 diminuiu para 18,88 e > 40 mg/L, respectivamente. Estes resultados indicaram que os produtos de degradação são menos tóxicos que o bilobol em sua forma fundamental. Portanto, foi possível concluir que o bilobol não apresenta toxicidade significativa para embriões de peixe-zebra, e nem mostra sinais de persistência no ambiente. Adicionalmente, o bilobol pode ser encontrado em grandes quantidades não só em S. terebinthifolia, mas também no resíduo industrial da castanha de caju. Sendo assim, o bilobol é uma alternativa de larvicida ecologicamente sustentável, já que não é persistente, tem indicação de baixa toxicidade em organismos não-alvo e representa uma forma de aproveitar enormes quantidade de material descartado pela indústria alimentícia.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).Aedes aegypti is the main transmitting vector of arboviruses such as chikungunya, Zika and dengue. The current vector control strategies are limited due to multiple insecticide resistance, deleterious impacts on the environment, and toxicity to non-target organisms. In the search of new alternatives for Ae. aegypti combat, the potential of components from the plant species Schinus terebinthifolia was studied. Chemometric analyses demonstrated that the metabolic profile of active samples clearly differentiated from the metabolic composition of inactive samples in Ae. aegypti. Furthermore, these analyses helped speed the bioguided purification process that resulted in isolation an alkylresorcinol known as bilobol. Bilobol demonstrated potent larvicidal activity against Ae. aegypti (LC50 7.67 mg/L in less than 24 h). To ensure that bilobol is a viable alternative as an eco-friendly larvicide, the degradation process and acute toxicity of this alkylresorcinol in zebrafish, a non-target organism, were explored. A quantification method with validated parameters was developed and used to evaluate bilobol degradation in water over time. The Fish Embryo Toxicity (FET) test was applied to evaluate the acute toxicity of bilobol along with its degradation derivates. Results demonstrated that bilobol gradually degrades over time and almost completely disappears after 96 h, turning into small aliphatic chains. When submitted to the FET test, bilobol presented LC50 6.00 mg/L at 96 hpf. After 24 and 96 h of degradation, LC50 dropped to 18.88 and > 40 mg/L, respectively. These results indicated that the degradation derivates are less toxic than bilobol in its fundamental form. Therefore, it was possible to conclude that bilobol does not present significant toxicity to zebrafish embryos nor does it show signs of persistence in the environment. Additionally, bilobol can be found in high quantities not only in S. terebinthifolia, but also in cashew nut industry waste. Thus, bilobol constitutes an alternative environmentally friendly larvicide since it is not persistent, has indications of low toxicity to non- target organisms and presents a way to seize massive quantities of material discarded by the food industry

Investigação da atividade de extratos de Schinus terebinthifolia em larvas de Aedes aegypti

Trabalho de Conclusão de Curso (graduação)—Universidade de Brasília, Faculdade de Ciências da Saúde, Departamento em Farmácia, 2017.Aedes aegypti é o principal vetor transmissor de arboviroses como dengue, Zika, chikungunya e febre amarela, doenças que tem sido motivo de grande preocupação em inúmeros países. Apesar dos avanços no desenvolvimento de vacinas, apenas a imunização contra febre amarela está disponível, tornando o combate ao vetor a principal arma no controle da transmissão de arboviroses. Além disso, a resistência aos inseticidas mais utilizados, assim como seus efeitos deletérios ao ambiente, fazem necessária a busca por agentes alternativos para auxiliar no controle do vetor. Sendo assim, o objetivo deste estudo foi investigar a atividade de extratos de Schinus terebinthifolia em larvas de Aedes aegypti. Essa pesquisa esta inserida dentro do Componente 1 do projeto ArboControl – pesquisa para o controle do vetor Aedes aegypti, no âmbito da investigação larvicida do Banco de Extratos de Plantas do Bioma Cerrado do Laboratório de Farmacognosia/FS/UnB. Foram testados 12 diferentes extratos de S. terebinthifolia, dos quais sete apresentaram mortalidade acumulada superior a 90% das larvas testadas. A atividade larvicida se concentrou nos extratos de baixa a média polaridade. Quatro destes extratos foram préfracionados em SPE-Diol, e as frações resultantes foram testadas em larvas do 3° estádio. As frações ativas foram analisadas por RMN 1H, e revelaram a presença predominante de ácidos graxos insaturados. Essa observação preliminar do perfil químico sugere possível atividade larvicida de ácidos graxos insaturados presentes em extratos de Schinus terebinthifolia. Estes extratos terão sua atividade investigada mais afundo e, com continuidade do fracionamento, objetivando a identificação e isolamento das substâncias larvicidas.Aedes aegypti is the main vector of arboviruses such as dengue, Zika, chikungunya and yellow fever, diseases that are cause of great concern worldwide. Despite advances in vaccine development, only immunization against yellow fever is currently available, making vector control the main weapon in controlling arboviruses transmission. In addition, resistance to the most frequently used insecticides, as well as their deleterious effects on the environment, make it necessary to search for alternative agents to aid in vector control. Thus, the purpose of this study was to investigate the activity of extracts of Schinus terebinthifolia in Aedes aegypti larvae. This research is part of Component 1 of the ArboControl project - search for control of the vector Aedes aegypti, in the scope of larvicidal investigation of the Bank of Plant Extracts of the Cerrado Biome from Laboratório de Farmacognosia/FS/UnB. Twelve different S. terebinthifolia extracts were tested, of which seven presented cumulative larvae mortality higher than 90%. The larvicidal activity was concentrated in the extracts of low to medium polarity. Four of these extracts were pre-fractionated in SPE-Diol. The most active fractions in this assay were subjected to 1H NMR analysis, which revealed predominant presence of unsaturated fatty acids in all samples. Therefore, it was possible to suggest that the larvicidal activity found in extracts of Schinus terebinthifolia is related to the presence of unsaturated fatty acids. All extracts will have their activity further investigated and fractionated in the follow-up of this project, aiming at the identification and isolation of larvicidal compounds

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Determination of the strong coupling constant αs from transverse energy–energy correlations in multijet events at s√=8 TeV using the ATLAS detector

Measurements of transverse energy–energy correlations and their associated asymmetries in multi-jet events using the ATLAS detector at the LHC are presented. The data used correspond to s√=8 TeV proton–proton collisions with an integrated luminosity of 20.2 fb−1 . The results are presented in bins of the scalar sum of the transverse momenta of the two leading jets, unfolded to the particle level and compared to the predictions from Monte Carlo simulations. A comparison with next-to-leading-order perturbative QCD is also performed, showing excellent agreement within the uncertainties. From this comparison, the value of the strong coupling constant is extracted for different energy regimes, thus testing the running of αs(μ) predicted in QCD up to scales over 1 TeV . A global fit to the transverse energy–energy correlation distributions yields αs(mZ)=0.1162±0.0011(exp.) +0.0084−0.0070(theo.) , while a global fit to the asymmetry distributions yields a value of αs(mZ)=0.1196±0.0013(exp.) +0.0075−0.0045(theo.)

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study

IntroductionSARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators.MethodsA sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array.ResultsIn the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester.Discussion and conclusionFrom an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women