Conformational Isomerization Involving Conserved Proline Residues Modulates Oligomerization of the NS1 Interferon Response Inhibitor from the Syncytial Respiratory Virus

Interferon response suppression by the respiratory syncytial virus relies on two unique nonstructural proteins, NS1 and NS2, that interact with cellular partners through high-order complexes. We hypothesized that two conserved proline residues, P81 and P67, participate in the conformational change leading to oligomerization. We found that the molecular dynamics of NS1 show a highly mobile C-terminal helix, which becomes rigid upon in silico replacement of P81. A soluble oligomerization pathway into regular spherical structures at low ionic strengths competes with an aggregation pathway at high ionic strengths with an increase in temperature. P81A requires higher temperatures to oligomerize and has a small positive effect on aggregation, while P67A is largely prone to aggregation. Chemical denaturation shows a first transition, involving a high fluorescence and ellipticity change corresponding to both a conformational change and substantial effects on the environment of its single tryptophan, that is strongly destabilized by P67A but stabilized by P81A. The subsequent global cooperative unfolding corresponding to the main β-sheet core is not affected by the proline mutations. Thus, a clear link exists between the effect of P81 and P67 on the stability of the first transition and oligomerization/aggregation. Interestingly, both P67 and P81 are located far away in space and sequence from the C-terminal helix, indicating a marked global structural dynamics. This provides a mechanism for modulating the oligomerization of NS1 by unfolding of a weak helix that exposes hydrophobic surfaces, linked to the participation of NS1 in multiprotein complexes.Fil: Conci, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: de Oliveira, Guilherme A. P.. Universidade Federal do Rio de Janeiro; BrasilFil: Pagani, Talita Duarte. Universidade Federal do Rio de Janeiro; BrasilFil: Esperante, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Borkosky, Silvina Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Aran, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Alonso, Leonardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Mohana Borges, Ronaldo. Universidade Federal do Rio de Janeiro; BrasilFil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Aerobic Swim Training Restores Aortic Endothelial Function by Decreasing Superoxide Levels in Spontaneously Hypertensive Rats

OBJECTIVE: We aimed to determine whether aerobic training decreases superoxide levels, increases nitric oxide levels, and improves endothelium-dependent vasodilation in the aortas of spontaneously hypertensive rats. METHODS: Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were distributed into 2 groups: sedentary (SHRsd and WKYsd, n=10 each) and swimming-trained (SHRtr, n=10 and WKYtr, n=10, respectively). The trained group participated in training sessions 5 days/week for 1 h/day with an additional work load of 4% of the animal’s body weight. After a 10-week sedentary or aerobic training period, the rats were euthanized. The thoracic aortas were removed to evaluate the vasodilator response to acetylcholine (10-10 to 10-4 M) with or without preincubation with L-NG-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10-4 M) in vitro. The aortic tissue was also used to assess the levels of the endothelial nitric oxide synthase and nicotinamide adenine dinucleotide oxidase subunit isoforms 1 and 4 proteins, as well as the superoxide and nitrite contents. Blood pressure was measured using a computerized tail-cuff system. RESULTS: Aerobic training significantly increased the acetylcholine-induced maximum vasodilation observed in the SHRtr group compared with the SHRsd group (85.9±4.3 vs. 71.6±5.2%). Additionally, in the SHRtr group, superoxide levels were significantly decreased, nitric oxide bioavailability was improved, and the levels of the nicotinamide adenine dinucleotide oxidase subunit isoform 4 protein were decreased compared to the SHRsd group. Moreover, after training, the blood pressure of the SHRtr group decreased compared to the SHRsd group. Exercise training had no effect on the blood pressure of the WKYtr group. CONCLUSIONS: In SHR, aerobic swim training decreased vascular superoxide generation by nicotinamide adenine dinucleotide oxidase subunit isoform 4 and increased nitric oxide bioavailability, thereby improving endothelial function

Habitação popular e arquitetura Projeto Quinta Monroy de Alejandro Aravena em Brasília

Pesquisa de iniciação científica que investiga as possibilidades de mitigar as questõesreferentes ao déficit habitacional junto ao tema da habitação social. O estudo procurarelacionar, por meio comparativo, as soluções adotadas em dois modelos de fundamentaçãodos conceitos inerentes ao planejamento habitacional, participativo e deliberativo, e àsmedidas de mitigação das demandas habitacionais sociais. Com esse propósito a pesquisaverifica a possibilidade de implantar em Brasília o modelo de planejamento para a habitaçãosocial utilizado no Chile por ocasião do Projeto Quinta Monroy de Alejandro Aravena. Paratal investigação, são abordados os antecedentes históricos relacionados às duas regiões e osfundamentos relativos aos modelos de planejamento habitacional. A verificação quanto àviabilidade do processo foi realizada mediante o método comparativo no qual, apósdescrever as condições e realidades dos objetos de estudos, Projeto Quinta Monroy e BairroCrixá, avaliamos a possibilidade de implantação do modelo participativo em meio a históricobrasileiro de soluções ao déficit habitacional. O Projeto Quinta Monroy foi o trabalho peloqual, o arquiteto Alejandro Aravena, obteve qualificação superior nas questões deplanejamento habitacional e colaborou para seu reconhecimento com o prêmio Pritzker. Talprojeto traz a possibilidade de participação do usuário nas diversas etapas de concepção, deelaboração, de execução e de permanência na moradia. Como termo comparativo domodelo utilizado no Brasil e, especificamente em Brasília, foi escolhido o Bairro Crixá. Oprojeto e o planejamento habitacional para o Bairro Crixá, apesar de sua publicidade demodelo inovador, revela os mesmos processos de tratamento da questão habitacional noBrasil que remontam aos tradicionais conjuntos habitacionais implantados ao longo doséculo XX. Por fim, a pesquisa traça o paralelo entre os dois modelos de planejamento paraa habitação social, elencando os motivos que comprometem a implantação de projetosemelhante ao Quinta Monroy em Brasília e as providências necessárias para fazê-lo valer. Oprocesso comparativo das duas iniciativas resultou em algumas observações muitopertinentes. Em primeiro lugar, pode-se notar certa disparidade em se tratando da produçãode habitação social, sobretudo na comparação entre o histórico social e a implantação doscomplexos habitacionais, da Quinta Monroy e do Bairro Crixá, os dois países seguiramcaminhos muito divergentes

Habitação social: breve histórico da condição de moradia das famílias que vivem em áreas de parcelamento irregular no Distrito Federal

Pesquisa de iniciação científica que visa analisar as condições habitacionais de famílias emáreas de parcelamento irregular no Distrito Federal, através de uma pesquisa exploratóriapor meio da realização de um estudo de caso sobre uma dessas ocupações, sendo escolhidoo bairro Vila do Boa, em São Sebastião. Para melhor compreensão dos processos deocupação irregular na área de estudo, a fim de identificar sua dinâmica de surgimento ecrescimento, foi realizado um breve histórico das tipologias habitacionais em nível nacional,distrital e no próprio Vila do Boa. Nesse contexto, estabeleceu-se um paralelo entre aspropostas de resolução para os problemas habitacionais no país, destacando os programasde habitação social e a implementação de leis sobre habitação social, e a constância dashabitações efêmeras em ocupações irregulares. Assim, por meio do objeto de estudoselecionado, foi proposta uma análise tipológica e urbanística desta modalidade dehabitação social. Essa análise, realizada a partir da divisão da área de estudo em sete regiões,buscou estabelecer os diferentes estágios de ocupação, bem como os elementos decomposição das tipologias quanto ao seu nível de qualidade e acabamento construtivo emPrecários, Alternativos, Intermediários e Definitivos. Como considerações finais, pode-sedestacar em um primeiro momento, a notável carência de uma política pública adequada aosaspectos habitacionais desenvolvidos em áreas carentes e periféricas no DF, com arecorrente prática de distribuição de lotes e de regularização pós-ocupação, não garantindoqualidade de moradia à população, que recorre a autoconstrução sistematicamente. Emsequência, nota-se a preferência popular por tipologias efêmeras, sendo a autoconstruçãouma opção atrativa à população devido à grande oferta de terras desocupadas em áreas depreservação, aos altos preços de intervenções urbanísticas pelo governo, à falta de habitaçãosocial que atenda às necessidades de sua população alvo e a vantagem direta dos materiaisprecários que permitem uma rápida substituição, devido ao baixo investimento econômico,em casos de eventuais remoções pelo Governo

Antimicrobial activity of silver nanoparticles synthesized by the fungus Curvularia inaequalis

Silver nanoparticles have been widely reported in literature due to their vast industrial application in different areas. In this work, we explored a simple procedure for the biosynthesis of silver nanoparticles at room temperature from the action of Curvularia inaequalis as reduction agent. The degree of aggregation and size of biosynthesized particles were optimized from a factorial design involving combined variation of three different parameters of preparation. The resulting colloidal dispersion of silver nanoparticles presented strong antimicrobial activity against Escherichia coli and Klebsiella pneumoniae in an indication that C. inaequalis represents a new potential candidate for alternative biosynthesis of silver nanoparticles with antimicrobial activity.Keywords: Antimicrobial activity, fungi, silver nanoparticlesAfrican Journal of Biotechnology Vol. 12(20), pp. 2917-292

Dye aggregation and influence of pre-micelles on heterogeneous catalysis: a photophysical approach

Common cationic dyes used for laser and fluorescent probes present low solubility in water. In order to increase the dye concentration in aqueous solutions, anionic surfactant can be added. The strong interaction between anionic surfactant and cationic dye can affect drastically the dye absorption and fluorescence properties. Here we observed that the fluorescence of the species in aqueous solution is maximized at condition of complete micellization of surfactants at critical micelle concentration (CMC). In addition, combined measurements of absorption, emission and fluorescence lifetime provide fundamental information on the critical concentration of H-aggregates formation and monomer separation, induced by pre-micelles and homomicelles on different surfactant sodium dodecylsulphate (SDS) concentration. The experimental results show how to find precisely the critical concentration of H-aggregates by optical method in two different xanthene-derived molecules: rhodamine 6G and rhodamine B. The adequate transference of electron from excited dye to the conduction band of semiconductor (TiO2) promotes the creation of reactive species that provides the degradation of dye with advantage of use of irradiation in the visible region and strong photobleaching with direct exposure to the visible light irradiation in a scale of time of 10 min

Perceptual analysis of heterogeneous stakeholders on the impact of the Rio 2016 games in the territory of Lagoa Rodrigo de Freitas

Highlights: Development of partnership with local entities for integrated social actions; Actions and projects are developed as close as possible to the public audience; Participation in meetings and community councils; Establishment of constant dialog between social management and community leaders; Dialog with public entities; Work communication with all the impacts caused by the implementation of the megaproject, according to the affected area. Goal: Analyze, through a case study, what were the effects resulting from the Rio 2016 Olympic Games in the territory of Lagoa Rodrigo de Freitas, and how they were perceived by the stakeholders during and after the performance. Design / Methodology / Approach: On-site open and participant observation, semi-structured interviews, and on-site questionnaires and descriptive statistics Results: A series of consequences were triggered, affecting each of the different stakeholders in different ways. Limitations of the investigation: Megaprojects promote mutually positive and negative impacts concerning the local stakeholders and their multiple and different perceptions. Thus, results cannot be generalized. Practical implications: Fragmentation of the megaproject, heterogeneity, and perceptions of different stakeholders Originality / Value: Practices that are sensitive to the stakeholders’ engagement and impacts perceived

Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence

Introduction and objectives: The incidence of cholangiocarcinoma (CCA) has been increasing globally. Although a concomitant increase in the incidence of metabolic disorders might suggest a causal relationship, the data are scarce. We aimed to describe the prevalence of metabolic disorders in patients with CCA and report the clinical features and outcomes. Patients and Methods: Retrospective study including patients with CCA. Patients were divided into: (1) past history of diabetes or/and overweight/obesity (“metabolic disorder group”) and (2) without any of these features (“non-metabolic-disorder group”). A Cox regression model was used to determine the prognostic factors. Results: 122 patients were included. In total, 36 (29.5%) had overweight/obesity, 24 (19.7%) had diabetes, and 8 (6.6%) had both. A total of 29 (23.8%) patients had resectable disease and received upfront surgery. A total of 104 (85.2%) received chemotherapy for advanced/recurrent disease. The overall survival of the cohort was 14.3 months (95% CI: 10.1–17.3). ECOG-PS 0 (p < 0.0001), resectable disease (p = 0.018) and absence of vascular invasion (p = 0.048) were independently associated with better prognosis. The “metabolic disorder group” (n = 52) had a median survival of 15.5 months (95% CI 10.9–33.9) vs. 11.5 months (95% CI 8.4–16.5) in the “non-metabolic-disorder group” (n = 70) (HR: 1.10; 95% CI 0.62–1.94). Patients with resectable disease in the “metabolic group” had longer survival than patients in the “non-metabolic group” (43.4 months (95% CI 33.9-NR) vs. 21.8 months (95% CI 8.6–26.9); HR = 0.12, 95% CI 0.03–0.59). Conclusion: Metabolic disorders are frequent among CCA patients. Underlying metabolic comorbidities may be associated with prognosis in resectable CCA. There is a need to explore the mechanism that drives CCA carcinogenesis in a metabolic background