Influenza and SARS-coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts.

The type II transmembrane serine proteases TMPRSS2 and HAT activate influenza viruses and the SARS-coronavirus (TMPRSS2) in cell culture and may play an important role in viral spread and pathogenesis in the infected host. However, it is at present largely unclear to what extent these proteases are expressed in viral target cells in human tissues. Here, we show that both HAT and TMPRSS2 are coexpressed with 2,6-linked sialic acids, the major receptor determinant of human influenza viruses, throughout the human respiratory tract. Similarly, coexpression of ACE2, the SARS-coronavirus receptor, and TMPRSS2 was frequently found in the upper and lower aerodigestive tract, with the exception of the vocal folds, epiglottis and trachea. Finally, activation of influenza virus was conserved between human, avian and porcine TMPRSS2, suggesting that this protease might activate influenza virus in reservoir-, intermediate- and human hosts. In sum, our results show that TMPRSS2 and HAT are expressed by important influenza and SARS-coronavirus target cells and could thus support viral spread in the human host

Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response

Aims: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. Material and Methods: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot® and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (−71T>C) gene polymorphisms were identified by TaqMan® Real-time PCR. Results: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3–8.0, p < 0.05). Conclusion: SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy

“Quem ensina também aprende” : a formação pela prática de professores primários na província do Paraná

Resumo Segundo a historiografia da educação brasileira, muitas foram as ações relacionadas aos modos de formar professores primários durante o período imperial. Desses estudos, a maioria se centra na formação de professores atrelada à instituição das escolas normais, entretanto, há uma parcela menor de trabalhos que se propõem a discutir outro aspecto da formação de professores ao longo do século XIX, mais especificamente, a forma como sujeitos que não frequentaram esse espaço institucional (a escola normal), constituíram-se docentes primários. O artigo que aqui se apresenta partilha dessa perspectiva, e volta o olhar para os modos de formação pela prática de professores primários no Paraná na segunda metade do século XIX, por compreender que esse tipo de formação marcou um período em que a instrução pública estava se consolidando em meio a ações, deliberações, dificuldades e tensões, na tentativa de melhorias de sua condição. A pesquisa valeu-se da consulta da legislação educacional do período e de documentos advindos dos sujeitos envolvidos com a instrução pública, naquele momento, disponíveis no acervo do Arquivo Público do Paraná. No cotejamento e análise das fontes, é possível afirmar, que a formação pela prática dos professores primários na província do Paraná se deu no decorrer do desenvolvimento do processo de constituição do magistério primário

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Investigating block programming tools in high school to support Education 4.0: A Systematic Mapping Study

In Education 4.0, a personalized learning process is expected, and that students are the protagonist. In this new education format, it is necessary to prepare students with the skills and competencies of the 21st-Century, such as teamwork, creativity, and autonomy. One of the ways to develop skills and competencies in students can be through block programming, which can be used with emerging technologies such as robotics and IoT and in an interdisciplinary way. Thus, block programming in High School is important because it is possible to work on aspects such as problem-solving, algorithmic thinking, among other skills (Perin et al., 2021), which are necessary in the contemporary world. Thus, our Systematic Mapping Study (SMS) aims to identify which block programming tools support of Education 4.0 in High School. Overall, 46 papers were selected, and data were extracted. Based on the results, a total of 24 identified block programming tools that can be used in high school collaboratively and playfully and with an interdisciplinary methodology. Moreover, it was possible to see that most studies address block programming with high school students, demonstrating a lack of studies that address block programming with teachers. This SMS contributed to identifying block programming tools, emerging technologies, audience (teacher or student), and learning spaces where block programming is being worked on

Expression pattern of influenza virus and SARS-coronavirus activating proteases and receptors in human tissues.

<p>Cell types expressing TMPRSS2, ACE2, HAT, 2,6-linked sialic acid are marked+, while those that do not express these molecules are marked−. “weakly” refers to a low level of staining.</p

Proteolytic activation of influenza virus hemagglutinin and SARS spike protein is conserved between TMPRSS2 of human, porcine, avian and murine origin.

<p>(A) Expression plasmids encoding the HA of the 1918 influenza virus and the indicated proteases or empty vector (pcDNA) were transiently cotransfected into 293T cells. The cells were then treated with PBS or trypsin, and HA cleavage was detected by Western blot analysis of cell lysates using a monoclonal antibody specific for HA. Detection of ß-actin served as loading control. (B) Lentiviral reporter viruses bearing 1918 HA and NA or the VSV-G glycoproteins were generated in 293T cells coexpressing the indicated proteases or empty vector (pcDNA), treated with PBS (black bars) or trypsin (white bars), and used for infection of 293T target cells. Viruses harboring no glycoprotein were generated in parallel as control. Luciferase activities in the cell lysates were determined at 72 h post infection. The results of a representative experiment performed in triplicates are shown. Error bars indicate standard deviation (SD). Comparable results were obtained in a separate experiment. (C) To detect SARS-S cleavage in cis, expression plasmids coding for SARS-S and the indicated proteases or empty vector (pcDNA) were transiently cotransfected into 293T cells, which were then treated with trypsin or PBS. Subsequently, S-protein cleavage was detected by Western blot analysis of cell lysates using a serum specific for the S1 subunit of SARS-S. SARS-S cleavage fragments produced by trypsin and TMPRSS2 are indicated by asterisks. Detection of ß-actin served as a loading control. (D) Effector 293T cells were cotransfected with a SARS-S expression plasmid and a plasmid encoding GAL4-VP16 and mixed with target cells cotransfected with a plasmid encoding a GAL4-VP16 responsive luciferase expression cassette and an ACE2 expression plasmid or protease expression plasmid or empty plasmid. The effector and target cells were mixed, treated with PBS (black bars) or trypsin (white bars) and the luciferase activities in cell lysates quantified at 48 h after cell mixing. The results of a representative experiment performed in triplicates are shown. Error bars indicate standard deviation (SD). Similar results were observed in two independent experiments.</p