Neurodegenerative disorders, including Tauopathies that involve tau protein, base their pathological mechanism on forming proteinaceous aggregates, which has a deleterious effect on cells triggering an inflammatory response. Moreover, tau inhibitors can exert their mechanism of action through noncovalent and covalent interactions. Thus, Michael’s addition appears as a feasible type of interaction involving an α, β unsaturated carbonyl moiety to avoid pathological confirmation and further cytotoxicity. Moreover, we isolated three compounds from Antarctic lichens Cladonia cariosa and Himantormia lugubris: protolichesterinic acid (1), fumarprotocetraric acid (2), and lichesterinic acid (3). The maleimide cysteine labeling assay showed that compounds 1, 2, and 3 inhibit at 50 µM, but compounds 2 and 3 are statistically significant. Based on its inhibition capacity, we decided to test compound 2 further. Thus, our results suggest that compound 2 remodel soluble oligomers and diminish β sheet content, as demonstrated through ThT experiments. Hence, we added externally treated oligomers with compound 2 to demonstrate that they are harmless in cell culture. First, the morphology of cells in the presence of aggregates does not suffer evident changes compared to the control. Additionally, the externally added aggregates do not provoke a substantial LDH release compared to the control, indicating that treated oligomers do not provoke membrane damage in cell culture compared with aggregates alone. Thus, in the present work, we demonstrated that Michael’s acceptors found in lichens could serve as a scaffold to explore different mechanisms of action to turn tau aggregates into harmless species.

En el presente artículo se realiza un análisis de las estrategias y metodologías de enseñanza utilizadas por algunas Instituciones de Educación Superior en Colombia, para continuar con el desarrollo de algunos programas de Ingeniería durante el aislamiento social, producto de la COVID-19. Para realizar el estudio se propone un diseño metodológico con enfoque mixto, estructurado en dos fases, donde se diseña, implementa y analiza el instrumento utilizado para la recolección de la información. Los resultados demuestran que hay correspondencia entre docentes y estudiantes, respecto a la duración de los encuentros síncronos, el uso de la pizarra digital, el manejo de software especializado, la capacitación continua, el desarrollo cuidadoso de secuencia didáctica y optimización de tiempos de trabajo. Con base en los resultados obtenidos, los docentes de Ingeniería podrían redireccionar las estrategias utilizadas en el desarrollo de sus cursos para continuar con ellos en tiempos de emergencia según su propio contexto.

This paper presents a combined approach<br />with two aims. The first is to analyze the<br />reported sequence of the enzyme ubiquitin<br />carboxyl-terminal hydrolase 14 of Giardia<br />intestinalis (UBP6) through computational<br />methods to find components related with<br />its hypothetical function. The second is<br />to determine if the protein-coding gene is<br />expressed in G. intestinalis and, if such is<br />the case, also determine its transcription<br />pattern along the life cycle of the parasite. It<br />was established that the protein belongs to<br />the family of Cys-dependent deubiquitinases<br />and more specifically to ubiquitin specific<br />proteases (USPs). Moreover, the catalytic<br />center with the complete triad as well as<br />typical features of the USP motif were also<br />identified. Since the computational findings<br />suggest that the enzyme could be functional,<br />reverse transcription coupled to PCR was<br />used as a first approach to establish if in fact<br />the coding gene is expressed in the parasite.<br />Interestingly, it was found not only that<br />the gene is expressed, but also that there<br />is a transcription variation along the life<br />cycle of the parasite. These two findings are<br />the starting point for further studies since<br />they tentatively suggest that this enzyme<br />could be involved in the protein turnover<br />that occurs during parasite encystation.<br />Although preliminary, this study is the first<br />report concerning the study of a specific<br />deubiquitinating enzyme in the parasite G.<br />intestinalis.