Metabolic Factors and Their Influence on the Clinical Course and Response to HCV Treatment

Nowadays, direct-acting antivirals (DAA) have been used for hepatitis C virus (HCV) treatment leading to cure in 90–95% of non-cirrhotic patients depending on genotype, treatment experience, and regimen used. It was observed rates of antiviral response above 90% in compensated cirrhotic patients that should be treated for long time and/or ribavirin may be required. Metabolic syndrome, obesity, and insulin resistance are increasing worldwide and further contribute to hepatic steatosis and have long been recognized as a cause of lipid deposition in the liver. These factors affect the rate of antiviral response to interferon-based therapy, but it seems not impact DAA treatment. The effect of HCV eradication on hepatic steatosis and progression to fibrosis, cirrhosis, and hepatocellular carcinoma warrants further study in the era of direct-acting antivirals. Other factors that could be related to increase liver damage are vitamin D and associated polymorphisms. Patients with low concentration of total vitamin D [25(OH)D] presented high degree of fibrosis and high values of total cholesterol and triglycerides. In this chapter, we review the challenges and metabolic pathology associated with HCV infection and, discuss the influence of some metabolic factors which can cause liver damage

Curcumin-loaded lipid and polymeric nanocapsules stabilized by nonionic surfactants: An In Vitro and In Vivo antitumor activity on B16-F10 melanoma and macrophage uptake comparative study

Curcumin is a polyphenol obtained from the plant Curcuma longa (called turmeric) that displays several pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial and antitumoral activity, but clinical use has been limited by its poor solubility in water and, consequently, minimal systemic bioavailability. We have therefore formulated the drug into nanocarrier systems in an attempt to improve its therapeutic properties. This study evaluates the effect of intraperitoneally administered nanocapsules containing curcumin on subcutaneous melanoma in mice inoculated with B16-F10 cells, and on the cytotoxicity activity against B16-F10 cells in vitro. Phagocytic uptake of formulations was also evaluated upon incubation with macrophage J774 cells by fluorescence microscopy. Lipid and polymeric nanocapsules were prepared by the phase inversion and nanoprecipitation methods, respectively. The uptake of the lipid nanocapsules prepared using Solutol HS15 was significantly reduced in J774 cells. Curcumin, as free drug or as drug-loaded nanocapsules, was administrated at a dose of 6 mg/kg twice a week for 21 days. Free drug and curcuminloaded nanocapsules significantly reduced tumor volume (P < 0.05 vs. control), but no difference was found in the antitumor activity displayed by lipid and polymeric nanocapsules. This assumption was supported by the in vitro study, in which free curcumin as well as loaded into nanocapsules caused significant reduction of cell viability in a concentration- and time-dependent manner.Fil: Mazzarino, Letícia. Universidade Federal de Santa Catarina; BrasilFil: Silva, Luís F. C.. Universidade Federal de Santa Catarina; BrasilFil: Curta, Juliana C.. Universidade Federal de Santa Catarina; BrasilFil: Licínio, Marley A.. Universidade Federal de Santa Catarina; BrasilFil: Costa, Aline. Universidade Federal de Santa Catarina; BrasilFil: Pacheco, Letícia K.. Universidade Federal de Santa Catarina; BrasilFil: Siqueira, Jarbas M.. Universidade Federal de Santa Catarina; BrasilFil: Martinetti Montanari, Jorge Anibal. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Romero, Eder. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Assreuy, Jamil. Universidade Federal de Santa Catarina; BrasilFil: Santos Silva, Maria C.. Universidade Federal de Santa Catarina; BrasilFil: Lemos Senna, Elenara. Universidade Federal de Santa Catarina; Brasi

Estudo de Arquétipos aplicado ao jogo Say Bye to the Villains

O crescimento do mercado de jogos de tabuleiro (board games) resulta no surgimento de mais opções para os jogadores, contudo nem sempre os jogos apresentam uma narrativa capaz de cativar a atenção de seus jogadores. Uma história desinteressante pode ter como consequência uma baixa imersão ou até a total perda do interesse do jogador pelo artefato. Em decorrência disso, procurou-se fazer um estudo a respeito de narrativa e em seguida aplicar teorias dentro de um caso, ao jogo 1Say Bye to the Villains, a partir de experimentações e do desenvolvimento de novos personagens e mecânicas afim de enriquecer a narrativa do jogo e a experiência do jogador

Estudo de Arquétipos aplicado ao jogo Say Bye to the Villains

O crescimento do mercado de jogos de tabuleiro (board games) resulta no surgimento de mais opções para os jogadores, contudo nem sempre os jogos apresentam uma narrativa capaz de cativar a atenção de seus jogadores. Uma história desinteressante pode ter como consequência uma baixa imersão ou até a total perda do interesse do jogador pelo artefato. Em decorrência disso, procurou-se fazer um estudo a respeito de narrativa e em seguida aplicar teorias dentro de um caso, ao jogo 1Say Bye to the Villains, a partir de experimentações e do desenvolvimento de novos personagens e mecânicas afim de enriquecer a narrativa do jogo e a experiência do jogador

Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay

We thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center Tübingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC‐2017‐CoG‐771709 (to MGP), by national funds through FCT– Fundação para a Ciência e a Tecnologia, PTDC/BIA‐MIC/6982/2020 (to HV); PTDC/BIA‐PLA/3432/2012 (to SRF); FCT through MOSTMICRO‐ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and FCT fellowship SFRH/BD/147052/2019 (to BMS); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska‐Curie grant agreement No 839596 (to SS) and by the European Molecular Biology Organization through award ALTF 673‐2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com .A computer-aided drug design (CADD) approach was developed for a focused chemical library comprising a series of sixteen thiazolo[5,4-c]isoquinoline derivatives. Little is known about this group of heteroaromatic compounds, both from the point of view of their synthesis and their biological properties. First, our CADD approach included target prediction by Mondrian conformal prediction with the ChEMBL database. The acetylcholinesterase (AChE) was identified as having a high probability of thiazolo[5,4-c]isoquinolines being active against it. Secondly, the molecular docking predictions revealed four promising thiazoloisoquinolines (2, 7, 13 and 14) according to their prominent ligand-protein energy scores and relevant binding affinities with the AChE pocket residues. The subsequent in vitro evaluation of promising hits and related ones revealed a set of novel AChE inhibitors. Therefore, the findings reported herein may provide a new strategy for discovering novel AChE inhibitors.publishersversionpublishe

SIMBA: a web tool for managing bacterial genome assembly generated by Ion PGM sequencing technology

Background The evolution of Next-Generation Sequencing (NGS) has considerably reduced the cost per sequenced-base, allowing a significant rise of sequencing projects, mainly in prokaryotes. However, the range of available NGS platforms requires different strategies and software to correctly assemble genomes. Different strategies are necessary to properly complete an assembly project, in addition to the installation or modification of various software. This requires users to have significant expertise in these software and command line scripting experience on Unix platforms, besides possessing the basic expertise on methodologies and techniques for genome assembly. These difficulties often delay the complete genome assembly projects. Results In order to overcome this, we developed SIMBA (SImple Manager for Bacterial Assemblies), a freely available web tool that integrates several component tools for assembling and finishing bacterial genomes. SIMBA provides a friendly and intuitive user interface so bioinformaticians, even with low computational expertise, can work under a centralized administrative control system of assemblies managed by the assembly center head. SIMBA guides the users to execute assembly process through simple and interactive pages. SIMBA workflow was divided in three modules: (i) projects: allows a general vision of genome sequencing projects, in addition to data quality analysis and data format conversions; (ii) assemblies: allows de novo assemblies with the software Mira, Minia, Newbler and SPAdes, also assembly quality validations using QUAST software; and (iii) curation: presents methods to finishing assemblies through tools for scaffolding contigs and close gaps. We also presented a case study that validated the efficacy of SIMBA to manage bacterial assemblies projects sequenced using Ion Torrent PGM. Conclusion Besides to be a web tool for genome assembly, SIMBA is a complete genome assemblies project management system, which can be useful for managing of several projects in laboratories. SIMBA source code is available to download and install in local webservers at http://ufmg-simba.sourceforge.net

“A CIDADE DUVIDARÁ DO CASO” LITERATURA, REGIONALISMO E PATRIARCALISMO NO CONTO “A VINGANÇA DA PEROBA”, DE MONTEIRO LOBATO

The paper aims to discuss social thought in brazilian regionalist literature of the 20th, through a historical reflection carried out both by scholars of the subject and reflected and problematized by writers, as occurs with Monteiro Lobato in his book Urupês (1918), more specifically in the short story “A vingança da peroba”. The writer, a representative of pre-modernist realism, critically portrayed the reality of the interior of São Paulo and rural decadence by representing, in his collection of short stories, brazilian patriarchalism and the dynamics of interior life. Thus, the regional aspects ”“ scenery, characters, culture and language ”“ observed in accordance with the patriarchal family organization of the “caipira”, will be examined in the short story in question.O artigo tem por objetivo discorrer sobre o pensamento social na literatura regionalista brasileira do século XX, por intermédio de uma reflexão histórica realizada tanto por estudiosos do assunto, quanto refletida e problematizada por escritores, como ocorre com Monteiro Lobato em seu livro Urupês (1918), mais especificamente no conto “A vingança da peroba”. O referido autor, representante do realismo pré- modernista, abordou criticamente a realidade do interior paulista e a decadência rural, ao figurar, em sua coletânea de contos, o patriarcalismo brasileiro e a dinâmica da vida interiorana. Assim, aspectos regionais ”“ cenário, personagens, cultura, linguagem, etc. ”“ observados em consonância com a organização familiar patriarcal do caipira, serão examinados no referido conto

APRESENTAÇÃO DO DOSSIÊ TEMÁTICO: “EDUCAÇÃO EM CIÊNCIAS PARA NOVOS TEMPOS: PERSPECTIVAS E DEBATES CONTEMPORÂNEOS”

Apresentação do Dossi

Molecular systematics of the genus Artibeus (Chiroptera

a b s t r a c t A molecular phylogeny of the genus Artibeus using 19 of the 20 recognized species, many with samples from a broad geographic range, is presented. The analysis shows a clear distinction between the two subgenera (or genera), the &apos;large&apos; Artibeus and the &apos;small&apos; Dermanura, in both mitochondrial and nuclear genes. The placement and status of A. concolor remains inconclusive and is presented as the third subgenus Koopmania. The phylogenies and divergence time estimates show a marked influence of the Andes in the formation of the subgenera and the main lineages inside each subgenus. Nuclear genes showed a highly incomplete lineage sorting among species inside subgenera Artibeus and Dermanura. Indeed, shared alleles were also found between Artibeus and Koopmania, which are presumed to have split apart during the Miocene, showing that great care should be taken in using these markers. Cytochrome-b gene divergences and monophyly analyses suggest that A. lituratus and A. intermedius are indeed conspecifics. These analyses also suggested the existence of at least four &apos;new&apos; species revealing a significant cryptic diversity inside the genus