Immunologic changes in the peripheral blood transcriptome of individuals with early-stage chronic Chagas cardiomyopathy: a cross-sectional study.

Background: Chagas disease, caused by the protozoan parasite is a neglected disease that affects approximately 6 million individuals worldwide. Of those infected, 20-30% will go on to develop chronic Chagas cardiomyopathy (CCC), and many ultimately to advanced heart failure. The mechanisms by which this progression occurs are poorly understood.

Pathogenic signal peptide variants in the human genome.

Secreted and membrane proteins represent a third of all cellular proteins and contain N-terminal signal peptides that are required for protein targeting to endoplasmic reticulum (ER). Mutations in signal peptides affect protein targeting, translocation, processing, and stability, and are associated with human diseases. However, only a few of them have been identified or characterized.

Translational reprogramming as a driver of antimony-drug resistance in Leishmania.

Leishmania is a unicellular protozoan that has a limited transcriptional control and mostly uses post-transcriptional regulation of gene expression, although the molecular mechanisms of the process are still poorly understood. Treatments of leishmaniasis, pathologies associated with Leishmania infections, are limited due to drug resistance. Here, we report dramatic differences in mRNA translation in antimony drug-resistant and sensitive strains at the full translatome level.

Defective Human SRP Induces Protein Quality Control and Triggers Stress Response.

Regulation of Aberrant Protein Production (RAPP) is a protein quality control in mammalian cells. RAPP degrades mRNAs of nascent proteins not able to associate with their natural interacting partners during synthesis at the ribosome. However, little is known about the molecular mechanism of the pathway, its substrates, or its specificity.

Metabolite Biomarkers of Antimony Resistance.

parasites cause leishmaniasis, one of the most epidemiologically important neglected tropical diseases. exhibits a high ability of developing drug resistance, and drug resistance is one of the main threats to public health, as it is associated with increased incidence, mortality, and healthcare costs. The antimonial drug is the main historically implemented drug for leishmaniasis.

Drug-Induced Lipid Remodeling in Parasites.

parasites efficiently develop resistance against several types of drugs including antimonials, the primary antileishmanial drug historically implemented. The resistance to antimonials is considered to be a major risk factor for effective leishmaniasis treatment. To detect biomarkers/biopatterns for the differentiation of antimony-resistant strains, we employed untargeted global mass spectrometry to identify intracellular lipids present in antimony sensitive and resistant parasites before and after antimony exposure.

Regulation of Translation in the Protozoan Parasite .

Leishmaniasis represents a serious health problem worldwide and drug resistance is a growing concern. parasites use unusual mechanisms to control their gene expression. In contrast to many other species, they do not have transcriptional regulation.