Oral infectivity through carnivorism in murine model of Trypanosoma cruzi infection.

Introduction: Oral transmission of T. cruzi is probably the most frequent transmission mechanism in wild animals. This observation led to the hypothesis that consuming raw or undercooked meat from animals infected with T. cruzi may be responsible for transmitting the infection. Therefore, the general objective of this study was to investigate host-pathogen interactions between the parasite and gastric mucosa and the role of meat consumption from infected animals in the oral transmission of T. cruzi. Methods: Cell infectivity assays were performed on AGS cells in the presence or absence of mucin, and the roles of pepsin and acidic pH were determined. Moreover, groups of five female Balb/c mice were fed with muscle tissue obtained from mice in the acute phase of infection by the clone H510 C8C3hvir of T. cruzi, and the infection of the fed mice was monitored by a parasitemia curve. Similarly, we assessed the infective capacity of T. cruzi trypomastigotes and amastigotes by infecting groups of five mice Balb/c females, which were infected orally using a nasogastric probe, and the infection was monitored by a parasitemia curve. Finally, different trypomastigote and amastigote inoculums were used to determine their infective capacities. Adhesion assays of T. cruzi proteins to AGS stomach cells were performed, and the adhered proteins were detected by western blotting using monoclonal or polyclonal antibodies and by LC-MS/MS and bioinformatics analysis. Results: Trypomastigote migration in the presence of mucin was reduced by approximately 30%, whereas in the presence of mucin and pepsin at pH 3.5, only a small proportion of parasites were able to migrate (∼6%). Similarly, the ability of TCTs to infect AGS cells in the presence of mucin is reduced by approximately 20%. In all cases, 60-100% of the animals were fed meat from mice infected in the acute phase or infected with trypomastigotes or amastigotes developed high parasitemia, and 80% died around day 40 post-infection. The adhesion assay showed that cruzipain is a molecule of trypomastigotes and amastigotes that binds to AGS cells. LC-MS/MS and bioinformatics analysis, also confirmed that transialidase, cysteine proteinases, and gp63 may be involved in TCTs attachment or invasion of human stomach cells because they can potentially interact with different proteins in the human stomach mucosa. In addition, several human gastric mucins have cysteine protease cleavage sites. Discussion: Then, under our experimental conditions, consuming meat from infected animals in the acute phase allows the T. cruzi infection. Similarly, trypomastigotes and amastigotes could infect mice when administered orally, whereas cysteinyl proteinases and trans-sialidase appear to be relevant molecules in this infective process.

Untargeted Metabolomics Sheds Light on the Diversity of Major Classes of Secondary Metabolites in the Malpighiaceae Botanical Family.

Natural products produced by plants are one of the most investigated natural sources, which substantially contributed to the development of the natural products field. Even though these compounds are widely explored, the literature still lacks comprehensive investigations aiming to explore the evolution of secondary metabolites produced by plants, especially if classical methodologies are employed. The development of sensitive hyphenated techniques and computational tools for data processing has enabled the study of large datasets, being valuable assets for chemosystematic studies. Here, we describe a strategy for chemotaxonomic investigations using the Malpighiaceae botanical family as a model. Our workflow was based on MS/MS untargeted metabolomics, spectral searches, and recently described in silico classification tools, which were mapped into the latest molecular phylogeny accepted for this family. The metabolomic analysis revealed that different ionization modes and extraction protocols significantly impacted the chemical profiles, influencing the chemotaxonomic results. Spectral searches within public databases revealed several clades or genera-specific molecular families, being potential chemical markers for these taxa, while the in silico classification tools were able to expand the Malpighiaceae chemical space. The classes putatively annotated were used for ancestral character reconstructions, which recovered several classes of metabolites as homoplasies (i.e., non-exclusive) or synapomorphies (i.e., exclusive) for all sampled clades and genera. Our workflow combines several approaches to perform a comprehensive evolutionary chemical study. We expect it to be used on further chemotaxonomic investigations to expand chemical knowledge and reveal biological insights for compounds classes in different biological groups.

Transient medial prefrontal perturbation reduces false memory formation.

Knowledge extracted across previous experiences, or schemas, benefit encoding and retention of congruent information. However, they can also reduce specificity and augment memory for semantically related, but false information. A demonstration of the latter is given by the Deese-Roediger-McDermott (DRM) paradigm, where the studying of words that fit a common semantic schema are found to induce false memories for words that are congruent with the given schema, but were not studied. The medial prefrontal cortex (mPFC) has been ascribed the function of leveraging prior knowledge to influence encoding and retrieval, based on imaging and patient studies. Here, we used transcranial magnetic stimulation (TMS) to transiently perturb ongoing mPFC processing immediately before participants performed the DRM-task. We observed the predicted reduction in false recall of critical lures after mPFC perturbation, compared to two control groups, whereas veridical recall and recognition memory performance remained similar across groups. These data provide initial causal evidence for a role of the mPFC in biasing the assimilation of new memories and their consolidation as a function of prior knowledge.