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Human African trypanosomiasis or sleeping sickness, caused by the protozoan parasite Trypanosoma brucei , is characterized by the manipulation of the host’s immune response to ensure parasite invasion and persistence. Uncovering key molecules that support parasite establishment is a prerequisite to interfere with this process. We identified Q586B2 as a T. brucei protein that induces IL-10 in myeloid cells, which promotes parasite infection invasiveness. Q586B2 is expressed during all T. brucei life stages and is conserved in all Trypanosomatidae. Deleting the Q586B2-encoding Tb927.6.4140 gene in T. brucei results in a decreased peak parasitemia and prolonged survival, without affecting parasite fitness in vitro, yet promoting short stumpy differentiation in vivo. Accordingly, neutralization of Q586B2 with newly generated nanobodies could hamper myeloid-derived IL-10 production and reduce parasitemia. In addition, immunization with Q586B2 delays mortality upon a challenge with various trypanosomes, including Trypanosoma cruzi . Collectively, we uncovered a conserved protein playing an important regulatory role in Trypanosomatid infection establishment. Sleeping sickness caused by African trypanosome parasites induces a chronic, and potentially lethal, infection in humans. Here, the authors uncover a conserved protein, Q586B2, playing an important regulatory role in Trypanosomatid infection establishment.

The availability of complete pathogen genomes has renewed interest in the development of diagnostics for infectious diseases. Synthetic peptide microarrays provide a rapid, high-throughput platform for immunological testing of potential B-cell epitopes. However, their current capacity prevent the experimental screening of complete \"peptidomes\". Therefore, computational approaches for prediction and/or prioritization of diagnostically relevant peptides are required. In this work we describe a computational method to assess a defined set of molecular properties for each potential diagnostic target in a reference genome. Properties such as sub-cellular localization or expression level were evaluated for the whole protein. At a higher resolution (short peptides), we assessed a set of local properties, such as repetitive motifs, disorder (structured vs natively unstructured regions), trans-membrane spans, genetic polymorphisms (conserved vs. divergent regions), predicted B-cell epitopes, and sequence similarity against human proteins and other potential cross-reacting species (e.g. other pathogens endemic in overlapping geographical locations). A scoring function based on these different features was developed, and used to rank all peptides from a large eukaryotic pathogen proteome. We applied this method to the identification of candidate diagnostic peptides in the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. We measured the performance of the method by analyzing the enrichment of validated antigens in the high-scoring top of the ranking. Based on this measure, our integrative method outperformed alternative prioritizations based on individual properties (such as B-cell epitope predictors alone). Using this method we ranked [Formula: see text]10 million 12-mer overlapping peptides derived from the complete T. cruzi proteome. Experimental screening of 190 high-scoring peptides allowed the identification of 37 novel epitopes with diagnostic potential, while none of the low scoring peptides showed significant reactivity. Many of the metrics employed are dependent on standard bioinformatic tools and data, so the method can be easily extended to other pathogen genomes.

Chagas heart disease is a major public concern since 30% of infected patients develop cardiac alterations. The relationship between Trypanosoma cruzi discrete typing units (DTUs) and the biological properties exhibited by the parasite population has yet to be elucidated. In this study, we analysed the expression of α-smooth muscle actin (α-SMA) and galectin-3 (Gal-3) associated with cardiac extracellular matrix (ECM) remodelling a murine chronic cardiomyopathy induced by Tc I genotypes. We found the induction of myocarditis was associated with the upregulation of Col I, α-SMA, Gal-3, IFN-γ and IL-13, as analysed by q-PCR. In myocardial areas of fibrosis, the intensity of myocarditis and significant ECM remodelling correlated with the presence of Col I-, Gal-3- and α-SMA-positive cells. These results are promising for the further efforts to evaluate the relevance of Gal-3 in Chagas heart disease, since this galectin was proposed as a prognosis marker in heart failure patients.

Galectins are animal lectins with high affinity for β-galactosides that drive the immune response through several mechanisms. In particular, the role of galectin-8 (Gal-8) in inflammation remains controversial. To analyze its role in a chronic inflammatory environment, we studied a murine model of infection. The parasite induces alterations that lead to the development of chronic cardiomyopathy and/or megaviscera in 30% of infected patients. The strong cardiac inflammation along with fibrosis leads to cardiomyopathy, the most relevant consequence of Chagas disease. By analyzing infected wild-type (iWT) and Gal-8-deficient (iGal-8KO) C57BL/6J mice at the chronic phase (4-5 months post-infection), we observed that the lack of Gal-8 favored a generalized increase in heart, skeletal muscle, and liver inflammation associated with extensive fibrosis, unrelated to tissue parasite loads. Remarkably, increased frequencies of neutrophils and macrophages were observed within cardiac iGal-8KO tissue by flow cytometry. It has been proposed that Gal-8, as well as other galectins, induces the surface expression of the inner molecule phosphatidylserine on activated neutrophils, which serves as an \"eat-me\" signal for macrophages, favoring viable neutrophil removal and tissue injury protection, a process known as preaparesis. We found that the increased neutrophil rates could be associated with the absence of Gal-8-dependent preaparesis, leading to a diminished neutrophil-clearing capability in macrophages. Thus, our results support that Gal-8 exerts an anti-inflammatory role in chronic infection.

This work presents the physicochemical characterization and activity of zirconia-supported silver catalysts for the oxidation of pollutants present in diesel engine exhaust (propane, propene, naphthalene and soot). A series of silver-supported catalysts AgxZ (x = 1, 5 and 10 wt.%, Z = zirconia) were prepared, which were studied by various characterization techniques. The results show that silver is mainly found under the form of small metal nanoparticles (<10 nm) dispersed over the support. The metallic phase coexists with the AgOx oxidic phases. Silver is introduced onto the zirconia, generating Ag–ZrO2 catalysts with high activity for the oxidation of propene and naphthalene. These catalysts also show some activity for soot combustion. Silver species can contribute with zirconia in the catalytic redox cycle, through a synergistic effect, providing sites that facilitate the migration and availability of oxygen, which is favored by the presence of structural defects. This is a novel application of the AgOx–Ag/ZrO2 system in the combustion reaction of propene and naphthalene. The results are highly promising, given that the T50 values found for both model molecules are quite low.

ZrO2 nH2O (hydrogel) impregnated with transition metals (Cu, Co, and Ni) was studied in this work as a precursor for the synthesis of CuO/ZrO2 (CuZ), CoOx/ZrO2 (CoZ), and NiO/ZrO2 (NiZ) catalysts, employed in the naphthalene oxidation reaction. Fresh and catalytically used materials were characterized by different physicochemical techniques, to compare the bulk and surface behavior, with particular attention to the effect of the supported metal species’ properties on the catalytic activity. Techniques such as X-ray diffraction (XRD), temperature programmed reduction (TPR), differential scanning calorimetry (DSC), Brunauer–Emmett–Teller (BET) surface area analyzer, diffuse reflectance spectroscopy (DRS UV–vis), and Raman spectroscopy, allow for establishing structural and textural aspects of the support, as well as the surface coordination and the accessibility of supported species. Results were in agreement with the CuZ > CoZ > NiZ sequence for the activity in naphthalene oxidation reaction. Electronic properties, ionic sizes, oxide phase deposition on the support surface, reducibility, metal–support interaction, and local site symmetry of metals seem to be decisive factors for the catalytic interaction with the gaseous phase.

Trypanosoma cruzi trans-sialidase consists of a C-terminal domain composed essentially of immunodominant amino acid repeat units (SAPA-repeats) and an amino region responsible for the enzymatic activity (catalytic domain). To investigate the possible function(s) of SAPA-repeats, recombinant trans-sialidases either containing or lacking the C-terminal region were tested in mice. The presence of SAPA-repeats in the intravenously injected protein has two consequences. First, they enhance the persistence of the trans-sialidase activity in blood. Second, SAPA-repeats promoted the production of antibodies directed to the catalytic domain that inhibit trans-sialidase activity. These results suggest that SAPA-repeats modulate the trans-sialidase activity in blood.

A test based on the inhibition by antibodies of the trans-sialidase was used to analyze infection by Trypanosoma cruzi, the agent of Chagas' disease. Sera collected during the longitudinal follow-up of benznidazole-treated acutely and congenitally infected patients became negative for T. cruzi as determined by tests presently used to assess cure; however, the sera remained positive for T. cruzi by the trans-sialidase inhibition assay (TIA) up to 14 years after treatment. Therefore, TIA is a highly sensitive marker for previous T. cruzi infection.

Objective To evaluate two debriefing strategies for the development of neonatal resuscitation skills in health professionals responsible for the critical newborn care in a high-complexity university Hospital. Results A simple blind randomized clinical trial was conducted. Twenty-four professionals (pediatricians, nurses, and respiratory therapists) were randomly assigned for two interventions; one group received oral debriefing and the other oral debriefing assisted by video. Three standardized clinical scenarios that were recorded on video were executed. A checklist was applied for the evaluation, administered by a reviewer blinded to the assignment of the type of debriefing . The two debriefing strategies increased the technical and behavioral neonatal resuscitation skills of the participants, without one being superior to the other. The coefficient of the difference in the compliance percentage between the two types of debriefing was − 3.6% (95% CI − 13.77% to 6.47%). When comparing the development of technical and behavioral skills among the professionals evaluated, no significant differences were found between the types of debriefing . The two debriefing strategies increase compliance percentages, reaching or approaching 100%. Trial Registration ClinicalTrials.gov NCT03606278. July 30, 2018. Retrospectively registered

Trypanosoma cruzi the agent of Chagas disease is a monophyletic but heterogeneous group conformed by several Discrete Typing Units (DTUs) named TcI to TcVI characterized by genetic markers. The trans-sialidase (TS) is a virulence factor involved in cell invasion and pathogenesis that is differentially expressed in aggressive and less virulent parasite stocks. Genes encoding TS-related proteins are included in a large family divided in several groups but only one of them contains TS genes. Two closely related genes differing in a T/C transition encode the enzymatically active TS (aTS) and a lectin-like TS (iTS). We quantified the aTS/iTS genes from TcII and TcVI aggressive and TcI low virulent strains and found variable aTS number (1-32) per haploid genome. In spite of being low TS enzyme-expressers, TcI strains carry 28-32 aTS gene copies. The intriguing absence of iTS genes in TcI strains together with the presence of aTS/iTS in TcII and TcVI strains (virulent) were observed. Moreover, after sequencing aTS/iTS from 38 isolates collected along the Americas encompassing all DTUs, the persistent absence of the iTS gene in TcI, TcIII and TcIV was found. In addition, the sequence clustering together with T/C transition analysis correlated to DTUs of T. cruzi. The consistence of TS results with both evolutionary genome models proposed for T. cruzi, namely the \"Two Hybridization\" and the \"Three Ancestor\" was discussed and reviewed to fit present findings. Parasite stocks to attempt genetic KO or to assay the involvement of iTS in parasite biology and virulence are finally available.