Transcriptogram analysis reveals relationship between viral titer and gene sets responses during corona-virus infection

To understand the difference between benign and severe outcomes after Coronavirus infection, we urgently need ways to clarify and quantify the time course of tissue and immune responses. Here we reanalyze 72-hour time-series microarrays generated in 2013 by Sims and collaborators for SARS-CoV- 1 in vitro infection of a human lung epithelial cell line. Transcriptograms, a Bioinformatics tool to analyze genome-wide gene expression data, allow us to define an appropriate context-dependent threshold for mechanistic relevance of gene differential expression. Without knowing in advance which genes are relevant, classical analyses detect every gene with statistically-significant differential expression, leaving us with too many genes and hypotheses to be useful. Using a Transcriptogram-based top-down approach, we identified three major, differentiallyexpressed gene sets comprising 219 mainly immuneresponse- related genes. We identified timescales for alterations in mitochondrial activity, signaling and transcription regulation of the innate and adaptive immune systems and their relationship to viral titer. The methods can be applied to RNA data sets for SARS-CoV-2 to investigate the origin of differential responses in different tissue types, or due to immune or preexisting conditions or to compare cell culture, organoid culture, animal models and human-derived samples

Estudo comparativo entre as normas ISO 21931:2010, NBR 15575 e os requisitos das certificações AQUA e LEED

The construction sector is responsible for generating large environmental impacts in order to minimize these impacts, environmental standards and seals for the construction were created. This article presents a comparative study between the preliminary requirements of ISO 21931: 2010 Sustainable Building, the requirements of AQUA-HQE stamps, LEED and the Performance Standard NBR 15575: 2013. For this, a literature search was conducted to carry out a comparative analysis of the requirements of each of them in order to know those common to all of them. As a result of this work was identified that the standard of performance, the AQUA seal and LEED are well aligned with the sustainability criteria, comfort and health of the user, and has the ISO 21931 standard has some of these items as options.A construção civil é um setor responsável pela geração de grandes impactos ambientais, visando minimizar esses impactos, foram criadas normas e selos ambientais para a construção. Este artigo apresenta um estudo preliminar comparativo entre os requisitos da Norma ISO 21931:2010 de Construção Sustentável, os requisitos dos selos AQUA-HQE, o LEED e a Norma de Desempenho NBR 15575:2013. Para tanto, foi realizado uma pesquisa bibliográfica para realizar uma análise comparativa dos requisitos de cada uma delas, tendo em vista conhecer aqueles comuns a todas elas. Como resultado deste trabalho foi identificado que a norma de desempenho, o selo AQUA e o LEED estão bem alinhados com os critérios de sustentabilidade, conforto e saúde do usuário, e já a norma ISO 21931 possui alguns desses itens como opcionais

Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells

Lead poisoning effects are wide and include nervous system impairment, peculiarly during development, leading to neural damage. Lead interaction with calcium and zinc-containing metalloproteins broadly affects cellular metabolism since these proteins are related to intracellular ion balance, activation of signaling transduction cascades, and gene expression regulation. In spite of lead being recognized as a neurotoxin, there are gaps in knowledge about the global effect of lead in modulating the transcription of entire cellular systems in neural cells. In order to investigate the effects of lead poisoning in a systemic perspective, we applied the transcriptogram methodology in an RNA-seq dataset of human embryonic-derived neural progenitor cells (ES-NP cells) treated with 30 µM lead acetate for 26 days. We observed early downregulation of several cellular systems involved with cell differentiation, such as cytoskeleton organization, RNA, and protein biosynthesis. The downregulated cellular systems presented big and tightly connected networks. For long treatment times (12 to 26 days), it was possible to observe a massive impairment in cell transcription profile. Taking the enriched terms together, we observed interference in all layers of gene expression regulation, from chromatin remodeling to vesicle transport. Considering that ES-NP cells are progenitor cells that can originate other neural cell types, our results suggest that lead-induced gene expression disturbance might impair cells’ ability to differentiate, therefore influencing ES-NP cells’ fate

Identification of strain-specific B-cell epitopes in Trypanosoma cruzi using genome-scale epitope prediction and high-throughput immunoscreening with peptide arrays

BACKGROUND: The factors influencing variation in the clinical forms of Chagas disease have not been elucidated; however, it is likely that the genetics of both the host and the parasite are involved. Several studies have attempted to correlate the T. cruzi strains involved in infection with the clinical forms of the disease by using hemoculture and/or PCR-based genotyping of parasites from infected human tissues. However, both techniques have limitations that hamper the analysis of large numbers of samples. The goal of this work was to identify conserved and polymorphic linear B-cell epitopes of T. cruzi that could be used for serodiagnosis and serotyping of Chagas disease using ELISA. METHODOLOGY: By performing B-cell epitope prediction on proteins derived from pair of alleles of the hybrid CL Brener genome, we have identified conserved and polymorphic epitopes in the two CL Brener haplotypes. The rationale underlying this strategy is that, because CL Brener is a recent hybrid between the TcII and TcIII DTUs (discrete typing units), it is likely that polymorphic epitopes in pairs of alleles could also be polymorphic in the parental genotypes. We excluded sequences that are also present in the Leishmania major, L. infantum, L. braziliensis and T. brucei genomes to minimize the chance of cross-reactivity. A peptide array containing 150 peptides was covalently linked to a cellulose membrane, and the reactivity of the peptides was tested using sera from C57BL/6 mice chronically infected with the Colombiana (TcI) and CL Brener (TcVI) clones and Y (TcII) strain. FINDINGS AND CONCLUSIONS: A total of 36 peptides were considered reactive, and the cross-reactivity among the strains is in agreement with the evolutionary origin of the different T. cruzi DTUs. Four peptides were tested against a panel of chagasic patients using ELISA. A conserved peptide showed 95.8% sensitivity, 88.5% specificity, and 92.7% accuracy for the identification of T. cruzi in patients infected with different strains of the parasite. Therefore, this peptide, in association with other T. cruzi antigens, may improve Chagas disease serodiagnosis. Together, three polymorphic epitopes were able to discriminate between the three parasite strains used in this study and are thus potential targets for Chagas disease serotyping

Seguridad de los profesionales de enfermería y del paciente ante la pandemia de COVID-19 en unidades críticas

Objetivo: evaluar la seguridad de los profesionales de enfermería y la cultura de seguridad del paciente durante su actuación profesional en el cuidado de pacientes sospechosos o con COVID-19. Método: estudio transversal realizado con 90 profesionales de unidades críticas de dos hospitales universitarios. Se utilizó un instrumento de caracterización sociodemográfica y de condiciones de salud, además de los constructos “Seguridad del profesional y del paciente” y Hospital Survey on Patient Safety Culture. Se realizaron análisis univariados entre el diagnóstico de COVID-19 y las características de los profesionales y se aplicó la correlación de Kendell entre los constructos. Resultados: el diagnóstico de COVID-19 mostró diferencia estadísticamente significativa entre los profesionales que actuaron por más de seis años en la unidad (p=0,020) y los ítems del constructo “Seguridad del profesional y del paciente” referentes a dudas sobre cómo retirar el Equipo de Protección Personal (p=0,013) y flujo seguro (p=0,021). Las dimensiones 2 (p=0,003), 3 (p=0,009), 4 (p=0,013), 6 (p<0,001) y 9 (p=0,024) del Hospital Survey on Patient Safety Culture se asociaron a la realización de formación. Conclusión: mayor tiempo de experiencia profesional de enfermería se asoció con la no infección por COVID-19. La percepción de la cultura de seguridad del paciente se relacionó con la realización de entrenamiento.Objective: to evaluate nursing professionals and patient safety culture during the professional performance in the care of suspected or infected patients with COVID-19. Method: a cross-sectional study carried out with 90 professionals from critical care units of two teaching hospitals. An instrument for sociodemographic characterization and health conditions was used, in addition to the constructs “Nursing professional and patient safety” and the Hospital Survey on Patient Safety Culture. Univariate analyzes were performed between the diagnosis of COVID-19 and the characteristics of Nursing professionals, applying Kendell’s correlation between the constructs. Results: the COVID-19 diagnosis presented a significant statistical difference between nursing professionals that worked for more than six years at the critical care unit (p=0.020) and the items of the construct “Nursing professional and patient safety” regarding the doubts about how to remove the personal protective equipment (p=0.013) and safety flow (p=0,021). The dimensions 2 (p=0.003), 3 (p=0.009), 4 (p=0.013), 6 (p<0.001), and 9 (p=0.024) of the Hospital Survey on Patient Safety Culture were associated with the accomplishment of training. Conclusion: a higher professional nursing experience time was associated with non-infection by COVID-19. The perception of the safety culture of the patient was related to the accomplishment of training.Objetivo: avaliar a segurança dos profissionais de enfermagem e a cultura de segurança do paciente durante a atuação profissional no atendimento de pacientes suspeitos ou com COVID-19. Método: estudo transversal realizado com 90 profissionais de unidades críticas de dois hospitais-escola. Foi utilizado um instrumento para caracterização sociodemográfica e condições de saúde, além dos constructos “Segurança do profissional e do paciente” e Hospital Survey on Patient Safety Culture. Foram realizadas análises univariadas entre o diagnóstico de COVID-19 e as características dos profissionais, aplicando-se a correlação de Kendell entre os constructos. Resultados: o diagnóstico de COVID-19 apresentou diferença estatisticamente significativa entre os profissionais que trabalhavam há mais de seis anos na unidade (p=0,020) e os itens do constructo “Segurança do profissional e do paciente” referentes às dúvidas sobre como retirar o equipamento de proteção individual (p=0,013) e fluxo seguro (p=0,021). As dimensões 2 (p=0,003), 3 (p=0,009), 4 (p=0,013), 6 (p<0,001) e 9 (p=0,024) do Hospital Survey on Patient Safety Culture foram associadas à realização de treinamentos. Conclusão: maior tempo de experiência profissional do profissional de enfermagem esteve associado a não infecção por COVID-19. A percepção de cultura de segurança do paciente esteve relacionada à realização de treinamentos

Cartografia e diplomacia: usos geopolíticos da informação toponímica (1750-1850)

O artigo explora dimensões geopolíticas da toponímia, registradas em documentos cartográficos, desde as reformas empreendidas pelo consulado pombalino em meados do século XVIII, até às primeiras décadas do século XIX, em meio ao processo de afirmação do Estado imperial pós-colonial.This paper explores the geopolitical dimensions of toponymy as registered in cartographic documents dating from the reforms pushed through by the consulate of Marquis of Pombal in the mid 18th century to the early decades of the 19th century, as the post-colonial imperial State established itself

Encapsulation into Stealth Liposomes Enhances the Antitumor Action of Recombinant Cratylia mollis Lectin Expressed in Escherichia coli

This study evaluated the in vivo antitumor potential of new recombinant lectin from seeds of Cratylia mollis (rCramoll) expressed in Escherichia coli, free or encapsulated in stealth liposomes, using mice transplanted with sarcoma 180. rCramoll-loaded stealth liposomes (rCramoll-lipo) were formulated by hydration of the lipid film followed by cycles of freezing and thawing, and about 60% of rCramoll was encapsulated. This novel preparation showed particle size, polydispersity index, and pH suitable for the evaluation of antitumor activity in vivo. Tumor growth inhibition rates were 68% for rCramoll and 80% for rCramoll-lipo. Histopathological analysis of the experimental groups showed that both free and encapsulated lectin caused no changes in the kidneys of animals. Hematological analysis revealed that treatment with rCramoll-lipo significantly increased leukocyte concentration when compared with the untreated and pCramoll group. In conclusion, the encapsulation of rCramoll in stealth liposomes improves its antitumor activity without substantial toxicity; this approach was more successful than the previous results reported for pCramoll loaded into conventional liposomes. At this point, a crucial difference between the antitumor action of free and encapsulated rCramoll was found along with their effects on immune cells. Further investigations are required to elucidate the mechanism(s) of the antitumor effect induced by rCramoll