On the pathogenesis of Plasmodium vivax malaria: Perspectives from the Brazilian field

Life-threatening Plasmodium vivax malaria cases, while uncommon, have been reported since the early 20th century. Unfortunately, the pathogenesis of these severe vivax malaria cases is still poorly understood. In Brazil, the proportion of vivax malaria cases has been steadily increasing, as have the number of cases presenting serious clinical complications. The most frequent syndromes associated with severe vivax malaria in Brazil are severe anaemia and acute respiratory distress. Additionally, P. vivax infection may also result in complications associated with pregnancy. Here, we review the latest findings on severe vivax malaria in Brazil. We also discuss how the development of targeted field research infrastructure in Brazil is providing clinical and ex vivo experimental data that benefits local and international efforts to understand the pathogenesis of P. vivax. (C) 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Assignment of Putative Functions to Membrane "Hypothetical Proteins" from the Trypanosoma cruzi Genome

Protozoan parasites cause thousands of deaths each year in developing countries. The genome projects of these parasites opened a new era in the identification of therapeutic targets. However, the putative function could be predicted for fewer than half of the protein-coding genes. In this work, all Trypanosoma cruzi proteins containing predicted transmembrane spans were processed through an automated computational routine and further analyzed in order to assign the most probable function. The analysis consisted of dissecting the whole predicted protein in different regions. More than 5,000 sequences were processed, and the predicted biological functions were grouped into 19 categories according to the hits obtained after analysis. One focus of interest, due to the scarce information available on trypanosomatids, is the proteins involved in signal-transduction processes. In the present work, we identified 54 proteins belonging to this group, which were individually analyzed. The results show that by means of a simple pipeline it was possible to attribute probable functions to sequences annotated as coding for "hypothetical proteins.'' Also, we successfully identified the majority of candidates participating in the signal-transduction pathways in T. cruzi.

On the Evolution of Hexose Transporters in Kinetoplastid Potozoans

Glucose, an almost universally used energy and carbon source, is processed through several well-known metabolic pathways, primarily glycolysis. Glucose uptake is considered to be the first step in glycolysis. In kinetoplastids, a protozoan group that includes relevant human pathogens, the importance of glucose uptake in different phases of the life cycles is well established, and hexose transporters have been proposed as targets for therapeutic drugs. However, little is known about the evolutionary history of these hexose transporters. Hexose transporters contain an intracellular N- and C-termini, and 12 transmembrane spans connected by alternate intracellular and extracellular loops. In the present work we tested the hypothesis that the evolutionary rate of the transmembrane span is different from that of the whole sequence and that it is possible to define evolutionary units inside the sequence. The phylogeny of whole molecules was compared to that of their transmembrane spans and the loops connecting the transmembrane spans. We show that the evolutionary units in these proteins primarily consist of clustered rather than individual transmembrane spans. These analyses demonstrate that there are evolutionary constraints on the organization of these proteins; more specifically, the order of the transmembrane spans along the protein is highly conserved. Finally, we defined a signature sequence for the identification of kinetoplastid hexose transporters.

Expression analysis of stem cell-related genes reveal OCT4 as a predictor of poor clinical outcome in medulloblastoma

Aberrant expression of stem cell-related genes in tumors may confer more primitive and aggressive traits affecting clinical outcome. Here, we investigated expression and prognostic value of the neural stem cell marker CD133, as well as of the pluripotency genes LIN28 and OCT4 in 37 samples of pediatric medulloblastoma, the most common and challenging type of embryonal tumor. While most medulloblastoma samples expressed CD133 and LIN28, OCT4 expression was found to be more sporadic, with detectable levels occurring in 48% of tumors. Expression levels of OCT4, but not CD133 or LIN28, were significantly correlated with shorter survival (P <= 0.0001). Median survival time of patients with tumors hyperexpressing OCT4 and tumors displaying low/undetectable OCT4 expression were 6 and 153 months, respectively. More importantly, when patients were clinically stratified according to their risk of tumor recurrence, positive OCT4 expression in primary tumor specimens could discriminate patients classified as average risk but which further deceased within 5 years of diagnosis (median survival time of 28 months), a poor clinical outcome typical of high risk patients. Our findings reveal a previously unknown prognostic value for OCT4 expression status in medulloblastoma, which might be used as a further indicator of poor survival and aid postoperative treatment selection, with a particular potential benefit for clinically average risk patients.