Schistosomiasis is a neglected tropical disease (NTD) caused by helminthes from the Schistosoma genus. This NTD can cause systemic symptoms induced by the deposition of parasite eggs in the host liver, promoting severe complications. Functional studies to increase knowledge about parasite biology are required for the identification of new drug targets, because the treatment is solely based on praziquantel administration, a drug in which the mechanism of action is still unknown. Protein kinases are important for cellular adaptation and maintenance of many organisms homeostasis and, thus, are considered good drug targets for many pathologies. Accordingly, those proteins are also important for Schistosoma mansoni, as the parasite relies on specific environmental signals to develop into its different stages. However, the specific roles of protein kinases in S. mansoni biology are not well understood. This work aims at investigating the tyrosine-protein kinase FES (Feline Sarcoma) functions in the maintenance of S. mansoni life cycle, especially in the establishment of mammalian and invertebrate hosts' infection. In this regard, the verification of Smfes expression among S. mansoni stages showed that Smfes is more expressed in infective free-living stages: miracidia and cercariae. Schistosomula exposed to SmFES-dsRNA in vitro presented a reduction in movement and size and increased mortality. Mice infected with Smfes-knockeddown schistosomula exhibited a striking reduction in the area of liver granuloma and an increased rate of immature eggs in the intestine. Female adult worms recovered from mice presented a reduced size and changes in the ovary and vitellarium; and males exhibited damage in the gynecophoral canal. Subsequently, miracidia hatched from eggs exposed to SmFES-dsRNA presented changes in its capability to infect and to sense the snail mucus. In addition, the SmFES RNAi effect was stable from miracidia to cercariae. The establishment of infection with those cercariae reproduced the same alterations observed for the knocked-down schistosomula infection. Our findings show that SmFES tyrosine kinase (1) is important in schistosomula development and survival;(2) has a role in adult worms pairing and, consequently, female maturation; (3) might be essential for egg antigen expression, thus responsible for inducing granuloma formation

IntroductionThe human blood fluke parasite Schistosoma mansoni relies on diverse mechanisms to adapt to its diverse environments and hosts. Epigenetic mechanisms play a central role in gene expression regulation, culminating in such adaptations. Protein arginine methyltransferases (PRMTs) promote posttranslational modifications, modulating the function of histones and non-histone targets. The coactivator-associated arginine methyltransferase 1 (CARM1/PRMT4) is one of the S. mansoni proteins with the PRMT core domain.MethodsWe carried out in silico analyses to verify the expression of SmPRMTs in public datasets from different infection stages, single-sex versus mixed-worms, and cell types. The SmCARM1 function was evaluated by RNA interference. Gene expression levels were assessed, and phenotypic alterations were analyzed in vitro, in vivo, and ex vivo.ResultsThe scRNAseq data showed that SmPRMTs expression is not enriched in any cell cluster in adult worms or schistosomula, except for Smcarm1 expression which is enriched in clusters of ambiguous cells and Smprmt1 in NDF+ neurons and stem/germinal cells from schistosomula. Smprmt1 is also enriched in S1 and late female germ cells from adult worms. After dsRNA exposure in vitro, we observed a Smcarm1 knockdown in schistosomula and adult worms, 83 and 69%, respectively. Smcarm1-knockdown resulted in reduced oviposition and no significant changes in the schistosomula or adult worm phenotypes. In vivo analysis after murine infection with Smcarm1 knocked-down schistosomula, showed no significant change in the number of worms recovered from mice, however, a significant reduction in the number of eggs recovered was detected. The ex vivo worms presented a significant decrease in the ovary area with a lower degree of cell differentiation, vitelline glands cell disorganization, and a decrease in the testicular lobe area. The worm tegument presented a lower number of tubercles, and the ventral sucker of the parasites presented a damaged tegument and points of detachment from the parasite body.DiscussionThis work brings the first functional characterization of SmCARM1 shedding light on its roles in S. mansoni biology and its potential as a drug target. Additional studies are necessary to investigate whether the reported effects of Smcarm1 knockdown are a consequence of the SmCARM1-mediated methylation of histone tails involved in DNA packaging or other non-histone proteins.

and Mourão MM ( ) Corrigendum: Schistosoma mansoni coactivator associated arginine methyltransferase (SmCARM ) e ect on parasite reproduction.

O artigo teve como objetivo descrever e analisar o piloto de implantação do caderno de laboratório eletrônico em um laboratório de pesquisa de uma instituição pública de saúde considerando a viabilidade e os impactos dessa iniciativa. Tratou-se de um estudo de caso descritivo. Utilizou-se como referência para realização do projeto piloto, o Manual Práticas de Qualidade na Pesquisa Biomédica Básica, requisitos de integridade de dados baseado nos princípios ALCOA, ou seja, que os dados sejam, acurados, legíveis, contemporâneos, originais e atribuíveis, além de completos, consistentes, duradouros e disponíveis. Além dos requisitos citados, foram consideradas para a seleção do Caderno de Laboratório Eletrônico, as características mais relevantes para a instituição. Este trabalho possibilitou ao laboratório manter o atendimento aos requisitos das normas de Sistema de Gestão da Qualidade implementadas no laboratório, mas principalmente com maior efetividade, ao possibilitar a substituição do caderno de laboratório físico pelo eletrônico. Foi escolhido o que melhor atendia as necessidades institucionais, software open source, que permitia armazenamento dos dados na rede institucional, apresentava flexibilidade, facilidade de pesquisa, colaboração, segurança e flexibilidade. Os pesquisadores, técnicos e estudantes do grupo piloto consideraram que o impacto do uso do Caderno de Laboratório Eletrônico é muito positivo para a instituição, tanto para facilitar o registro das informações dos projetos, quanto o compartilhamento de informação e o acompanhamento pelos orientadores, além da maior facilidade na elaboração de relatórios, tese, dissertações e artigos.