COVID-19, a disease caused by SARS-CoV-2, was declared a pandemic in 2020 and created a global crisis in health systems, with more than 545 million confirmed cases and 6.33 million deaths. In this ...sense, this work aims to identify possible inhibitors of the SARS-CoV-2 RdRp enzyme using in silico approaches. RdRp is a crucial enzyme in the replication and assembly cycle of new viral particles and a critical pharmacological target in the treatment of COVID-19. We performed a virtual screening based on molecular docking from our in-house chemical library, which contains a diversity of 313 structures from different chemical classes. Nine compounds were selected since they showed important interactions with the active site from RdRp. Next, the ADME-Tox in silico predictions served as a filter and selected the three most promising compounds: a coumarin LMed-052, a hydantoin LMed-087, and a guanidine LMed-250. Molecular dynamics simulations revealed details such as changes in the positions of ligands and catalytic residues during the simulations compared to the complex from molecular docking studies. Binding free energy analysis was performed using the MMGBSA method, demonstrating that LMed-052 and LMed-087 have better affinities for the RdRp by energetic contributions to the stability of the complexes when compared to LMed-250. Furthermore, LMed-052 showed significant in vitro inhibition against MHV-3, decreasing 99% of viral titers. Finally, these findings are useful to guide structural modifications aiming to improve the potential of these compounds to act as inhibitors of SARS-CoV-2.
Communicated by Ramaswamy H. Sarma
O sorgo (Sorghum L. moench) é uma poaceae com características morfofisiológicas que conferem adaptaçãoàs condições de deficiência hídrica, o que a torna uma alternativa promissora para o Alto Sertão ...Sergipano.Uma maneira de selecionar materiais promissores de sorgo no melhoramento é analisar as correlações entreas variáveis morfológicas. Assim, objetivou-se utilizar a análise de trilha para seleção indireta de sorgoforrageiro com base nas características morfológicas na região do Alto Sertão Sergipano. O experimento foiconduzido na fazenda experimental da Embrapa Semiárido, em Nossa Senhora da Glória (SE), comdelineamento experimental em blocos casualizados e três repetições. Foram utilizados 16 tratamentos, sendo quatro testemunhas comerciais e 12 híbridos experimentais, total de 48 parcelas. As variáveis estudadas foram altura de planta, diâmetro do colmo, comprimento da panícula, estande final, peso do colmo, peso da folha, peso da panícula, peso da planta, matéria fresca, matéria seca, porcentagem de matéria seca e massa de forragem. Houve variabilidade entre os genótipos, e correlações fenotípicas fortes e positivas do peso da planta com peso do colmo, diâmetro do colmo e massa de forragem de 0,99, 0,92 e 0,78, respectivamente. A análise de trilha mostrou que o peso da planta apresentou maior correlação positiva (0,798) e alto efeito direto sobre a massa de forragem (0,949). Assim, recomenda-se a seleção indireta de sorgo com base na característica fenotípica maior massa de forragem, por meio do maior peso de planta.
Forage sorghum (Sorghum bicolor L.) has been grown in diverse climate variations, in warm and dry regions, or in regions with short drought periods. Thus, there is a need to select sorghum genotypes ...adapted to production systems under drought or rainy irregularities. This study evaluated the direct and indirect correlations among morphophysiological and productive characters of forage sorghum genotypes with Pearson’s correlation and path analysis. The experiment was designed under complete randomized blocks, with 25 treatments (genotypes) and three replicates. Analyzes of phenotypic correlation and the path analysis were done for plant height, panicle length, stem diameter, plant stand, green matter and dry matter yields, stem weight, plant weight, panicle weight, dry matter content, and forage mass. Plant weight presented the most significant direct effect on the forage mass (target variable), contributing to the increase in forage sorghum production. Therefore, heavier plants are more suitable to select forage sorghum genotypes indirectly, aiming to increase forage mass.
Multiple Sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) characterized by damage to the myelin sheaths of oligodendrocytes. Currently, there is no specific ...biomarker to identify the disease; however, a diagnostic criterion has been established based on patient's clinical, laboratory, and imaging characteristics, which assists in identifying this condition.
The primary method for diagnosing MS is the McDonald criteria, first described in 2001 and revised in the years 2005, 2012, and 2017. These criteria have been continuously reviewed to enhance specificity and sensitivity in the diagnosis of MS, thereby reducing errors in its differential diagnosis. An important differential diagnosis that shares overlapping features with MS, mainly the progressive forms, are leukodystrophies with demyelination as underlying pathology. Leukodystrophies comprise a rare group of genetically determined disorders that lead to either demyelination or hypomyelination of the central nervous system that can result neuroimaging changes as well as clinical findings similar to those observed in MS. Thus, systematic evaluation encompassing clinical presentation, neuroimaging findings, and laboratory metrics proves indispensable for a differential diagnosis.
As such, this study aimed to establish, clearly and objectively, the similarities and differences between MS and the main demyelinating leukodystrophies. The study analyzed the parameters of the McDonald criteria, including clinical, laboratory, and magnetic resonance imaging aspects, as found in patients with leukodystrophies through scoping literature review. The data were compared with the determinations of the revised 2017 McDonald criteria to facilitate the differential diagnosis of these diseases in clinical practice.
•Differential diagnosis that shares overlapping features with progressive MS are leukodystrophies with demyelination.•Leukodystrophies identified as sharing clinical, laboratory, and radiological features with progressive MS were ALD, KD, AD, MLD, and CTX.•Distinguishing features include the presence of inflammatory-related biomarkers, such as detection of OCBCSF and gadolinium enhancement evident in CNC MRI.
This study investigated the efficacy of aerobic exercise training (AET) in the prevention of dyslipidemia, insulin resistance (IR), and atherogenesis induced by severe low-sodium (LS) diet. LDL ...receptor knockout (LDLR KO) mice were fed a low-sodium (LS) (0.15% NaCl) or normal-sodium (NS; 1.27% NaCl) diet, submitted to AET in a treadmill, 5 times/week, 60 min/day, 15 m/min, for 90 days, or kept sedentary. Blood pressure (BP), plasma total cholesterol (TC) and triglyceride (TG) concentrations, lipoprotein profile, and insulin sensitivity were evaluated at the end of the AET protocol. Lipid infiltration, angiotensin II type 1 receptor (AT1), receptor for advanced glycation end products (RAGE), carboxymethyllysine (CML), and 4-hydroxynonenal (4-HNE) contents as well as gene expression were determined in the brachiocephalic trunk. BP and TC and gene expression were similar among groups. Compared to the NS diet, the LS diet increased vascular lipid infiltration, CML, RAGE, 4-HNE, plasma TG, LDL-cholesterol, and VLDL-TG. Conversely, the LS diet reduced vascular AT1 receptor, insulin sensitivity, HDL-cholesterol, and HDL-TG. AET prevented arterial lipid infiltration; increases in CML, RAGE, and 4-HNE contents; and reduced AT1 levels and improved LS-induced peripheral IR. The current study showed that AET counteracted the deleterious effects of chronic LS diet in an atherogenesis-prone model by ameliorating peripheral IR, lipid infiltration, CML, RAGE, 4-HNE, and AT1 receptor in the intima-media of the brachiocephalic trunk. These events occurred independently of the amelioration of plasma-lipid profile, which was negatively affected by the severe dietary-sodium restriction.
Zika virus (ZIKV) was first discovered in 1947 in Uganda but was not considered a public health threat until 2007 when it found to be the source of epidemic activity in Asia. Epidemic activity spread ...to Brazil in 2014 and continued to spread throughout the tropical and subtropical regions of the Americas. Despite ZIKV being zoonotic in origin, information about transmission, or even exposure of non-human vertebrates and mosquitoes to ZIKV in the Americas, is lacking. Accordingly, from February 2017 to March 2018, we sought evidence of sylvatic ZIKV transmission by sampling whole blood from approximately 2000 domestic and wild vertebrates of over 100 species in West-Central Brazil within the active human ZIKV transmission area. In addition, we collected over 24,300 mosquitoes of at least 17 genera and 62 species. We screened whole blood samples and mosquito pools for ZIKV RNA using pan-flavivirus primers in a real-time reverse-transcription polymerase chain reaction (RT-PCR) in a SYBR Green platform. Positives were confirmed using ZIKV-specific envelope gene real-time RT-PCR and nucleotide sequencing. Of the 2068 vertebrates tested, none were ZIKV positive. Of the 23,315 non-engorged mosquitoes consolidated into 1503 pools tested, 22 (1.5%) with full data available showed some degree of homology to insect-specific flaviviruses. To identify previous exposure to ZIKV, 1498 plasma samples representing 62 species of domestic and sylvatic vertebrates were tested for ZIKV-neutralizing antibodies by plaque reduction neutralization test (PRNT
). From these, 23 (1.5%) of seven species were seropositive for ZIKV and negative for dengue virus serotype 2, yellow fever virus, and West Nile virus, suggesting potential monotypic reaction for ZIKV. Results presented here suggest no active transmission of ZIKV in non-human vertebrate populations or in alternative vector candidates, but suggest that vertebrates around human populations have indeed been exposed to ZIKV in West-Central Brazil.
Escola de Games Junqueira, Morgana Schenkel; Ferreira, Tamara Cristina; Tonon, Guilherme Silva ...
Revista UFG,
04/2020, Letnik:
20
Journal Article
A Escola de Games trata-se de um projeto de extensão vinculado ao curso de Ciências da Computação da Universidade Federal de Goiás/Regional Jataí, cujas atividades estão sendo desenvolvidas desde ...2017 em escolas do município jataiense. Neste contexto, o trabalho apresenta um relato de experiência de três alunos da graduação, vinculados ao Programa de Bolsas de Extensão e Cultura no ano de 2017. O relato enfatiza a percepção do desenvolvimento do Pensamento Computacional, abordando aspectos do preparo dos graduandos em Ciências da Computação para a prática extensionista e relata as experiênciasdos universitários frente ao planejamento, desenvolvimento das atividades, estabelecimento de parâmetros de avaliação e registros, que versem sobre os desafios, oportunidades e aprendizados adquiridos no minicurso inaugural do projeto.
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