RESUMO
Schistosomiasis is a neglected tropical disease caused by parasitic flatworms. Current treatment relies on just one partially effective drug, praziquantel (PZQ). Schistosoma mansoni Venus Kinase Receptors 1 and 2 (SmVKR1 and SmVKR2) are important for parasite growth and egg production, and are potential targets for combating schistosomiasis. VKRs consist of an extracellular Venus Flytrap Module (VFTM) linked via a transmembrane helix to a kinase domain. Here, we initiated a drug discovery effort to inhibit the activity of the SmVKR2 kinase domain (SmVKR2KD) by screening the GSK published kinase inhibitor set 2 (PKIS2). We identified several inhibitors, of which four were able to inhibit its enzymatic activity and induced phenotypic changes in ex vivo S. mansoni. Our crystal structure of the SmVKR2KD displays an active-like state that sheds light on the activation process of VKRs. Our data provide a basis for the further exploration of SmVKR2 as a possible drug target.
RESUMO
To expedite the discovery of novel molluscicides in the laboratory, this study aimed to evaluate the performance of a new molluscicidal assay. This assay is based on Oncomelania hupensis quadrasi snails and is called miniaturized plate test or mpt. To perform this assay, a 12-well plate, 3 snails per well, and 24-h exposure period were used. The performance of mpt was evaluated using niclosamide and Ardisia plant extract (tagpo extract) as test substances while WHO's guidelines for a conventional plate test (cpt) served as standard. One cpt and four mpt independent trials were performed for niclosamide and tagpo extract. Probit analysis of dose-response data was run in R to generate lethal concentrations (LC50 and LC90), while lethal ratio test was performed to detect significant difference between paired LC50s (or LC90s). Using niclosamide, the calculated LC50 values were 0.104, 0.127, 0.136, 0.139, and 0.140 g/m2 for cpt, mpt 1, mpt 2, mpt 3, and mpt 4, respectively, while the LC90 values were 0.266, 0.268, 0.244, 0.251, and 0.261 g/m2, using the same sequence, respectively. For tagpo extract, the LC50 values were 1.467, 1.547, 1.659, 1.797, and 1.659 g/m2, for cpt, mpt 1, mpt 2, mpt 3, and mpt 4, respectively, and the LC90s were 2.188, 2.195, 2.501, 2.358, and 2.501 g/m2, respectively. The lethal ratio test revealed that a significant difference exists between the LC50s of cpt and mpt 1 when using niclosamide with a lethal ratio and confidence limits of 0.820 (0.663, 0.977, p < 0.05) and another significant difference between LC50s of mpt 1 and mpt 3 using tagpo extract with computed lethal ratio and confidence limits of 0.861 (0.782, 0.939, p < 0.05). Taken together, the results point out that mpt generates accurate and reproducible lethal concentration values. Hence, mpt may be used as an alternative method to screen molluscicides that are active against schistosome snail vectors.
RESUMO
El trabajo tiene por finalidad discutir aspectos asociados a la inclusión digital en Brasil y Colombia, los retos educativos que se plantean y, especialmente, los procesos de innovación educativa mediada por tecnologías digitales de información y comunicación (TDIC). Las reflexiones sobre el tema se basan en el trabajo conducido en el marco de una investigación empírica sobre la influencia del nivel socioeconómico y las experiencias de aprendizaje mediadas por las tecnologías digitales en estudiantes universitarios brasileños y colombianos. Desde una perspectiva socioconstructivista y situada del aprendizaje, el trabajo parte de tres convicciones. La primera considera que las TDIC son importantes artefactos socioculturales mediadores de las prácticas sociales, configurando una nueva ecología del aprendizaje. La segunda refiere al hecho de que, en la sociedad de la información (SI), las condiciones de acceso y uso de las TDIC no se dan igualmente para todos, sino que deben analizarse teniendo en cuenta la influencia del poder económico de los diferentes países y el nivel socioeconómico de las personas. La tercera, es que las diversas experiencias de acceso y uso de las TDIC por las personas repercuten sobre las oportunidades educativas, restringiéndolas o ampliándolas y llevando a la construcción de diferentes rutas de aprendizaje. En este sentido, desde los aspectos de la inclusión digital en Brasil y Colombia, se discuten los retos que se plantean a la educación, especialmente a los procesos de innovación educativa.
This paper aims to discuss the aspects of digital inclusion in Brazil and Colombia, and the challenges to education and, especially, the processes of educational innovation mediated by digital information and communication technologies (DICT). The reflections about of subject are based on the work conducted in the mark of a larger empiric research on influence of socioeconomic level and learning experiences of Brazilian and Colombian undergraduates DICT-mediated. From a situated and sociocultural approach, this paper is based on three convictions. First considers that the DICT are important sociocultural artefacts that mediate the social practices, configuring a new ecology of learning. Second refers to the fact that, in information society, the conditions of access and use of the DITC are not equally for all, taking into account the influence of the economic power of different countries and socioeconomic levels of the people. Third conviction is that the different people experiences of access and use of DICT reverberate on the educational opportunities, restricting or expanding them and leading to the construction of different learning trajectories. In this sense, from the aspects of digital inclusion in Brazil and Colombia, the challenges that are posed to education are analyzed, especially the processes of educational innovation.
