Pharmacological Approaches to Antitrypanosomal Chemotherapy

There is an urgent need for new drugs for the chemotherapy of human African trypanosomiasis, Chagas disease and leishmaniasis. Progress has been made in the identification and characterization of novel drug targets for rational chemotherapy and inhibitors of trypanosomatid glycosomal enzymes, trypanothione reductase, ornithine decarboxylase, S-adenosylmethionine decarboxylase, cysteine proteases and of the purine and sterol biosynthetic pathways. However, less attention has been paid to the pharmacological aspects of drug design or to the use of drug delivery systems in the chemotherapy of African trypanosomiasis and Chagas disease. A review of research on pharmacology and drug delivery systems shows that there are new opportunities for improving the chemotherapy of these diseases.

The population structure of Trypanosoma cruzi: expanded analysis of 54 strains using eight polymorphic CA-repeat microsatellites

Recently we cloned and sequenced the first eight Trypanosoma cruzi polymorphic microsatellite loci and studied 31 clones and strains to obtain valuable information about the population structure of the parasite. We have now studied 23 further strains, increasing from 11 to 31 the number of strains obtained from patients with chronic Chagas disease. This expanded set of 54 strains and clones analyzed with the eight microsatellites markers confirmed the previously observed diploidy, clonal population organization and very high polymorphism of T. cruzi. Moreover, this new study disclosed two new features of the population genetic structure of T. cruzi. The first was the discovery that, similarly to what we had previously shown for strains isolated from insect vectors, mammals and humans with acute disease, isolates from patients in the chronic phase of Chagas disease could also be multiclonal, albeit at a reduced proportion. Second, when we used parsimony to display the genetic relationship among the clonal lineages in an unrooted Wagner network we observed, like before, a good correlation of the tree topography with the classification in three clusters on the basis of single locus analysis of the ribosomal RNA genes. However, a significant new finding was that now the strains belonging to cluster 2 split in two distant sub-clusters. This observation suggests that the evolutionary history of T. cruzi may be more complex than we previously thought.

Inteins in pathogenic fungi: a phylogenetic tool and perspectives for therapeutic applications

Inteins or "internal proteins" are coding sequences that are transcribed and translated with flanking sequences (exteins). After translation, the inteins are excised by an autocatalytic process and the host protein assumes its normal conformation and develops its expected function. These parasitic genetic elements have been found in important, conserved proteins in all three domains of life. Most of the eukaryotic inteins are present in the fungi kingdom and the PRP8 intein is one of the most widespread inteins, occurring in important pathogens such as Cryptococcus neoformans (varieties grubii and neoformans), Cryptococcus gattii, Histoplasma capsulatum and Paracoccidioides brasiliensis. The knowledge of conserved and non-conserved domains in inteins have opened up new opportunities for the study of population variability in pathogenic fungi, including their phylogenetic relationships and recognition or diagnoses of species. Furthermore, inteins in pathogenic fungi should also be considered a promising therapeutic drug target, since once the autocatalytic splicing is inhibited, the host protein, which is typically vital, will not be able to perform its normal function and the fungal cell will not survive or reproduce.

Decomposição de precursores metalorgânicos: uma técnica química de obtenção de filmes finos

This review focus the more relevant foundations and applications of the Metallo-Organic Decomposition (MOD) technique, mainly within the last decade. The technique has grown significantly, mainly due to the good results concerning the preparation of multicomponent oxide systems with composition, structural and morphologic control, in a relatively simple way. This opened new opportunities to obtain materials with well-defined electrical and optical properties.

Designing and manufacturing of a soybean harvest residue picker

ABSTRACT Soy harvest matches seasons with shortage of dry matter supply for ruminant feeding in most Brazilian soy-growing areas. Agricultural machinery-producing companies must have market perception, observing new opportunities and developing equipment to meet costumers’ needs. This paper aims to design, build, and test a device to collect soybean crop residues from the combine cleaning mechanism, consisting mainly of vegetable straw (chaff), and the other plant parts (stems) remain being deposited onto the ground. For equipment designing, we made use of the architectural design methodology proposed in the reference model for the agricultural machinery development process. The equipment was designed and built following the proposed methodology, then installed and put into operation in a John Deere 1165 combine. After initial testing and few adjustments, the device showed satisfactory chaff-collecting performance. The equipment consists of a screw conveyor assembled transversely to the combine and a centrifugal fan assembled on the side. The collected chaff is dumped into a trailer towed by tractor.

A teoria da perspectiva e as mudanças de preferência no mainstream: um prospecto Lakatoseano

The theory of the perspective and the changes of preference in the mainstream: a Lakatosean prospect. For many decades over the 20th Century, the mainstream of economics adopted a normative and axiomatic theory of individual behavior in which maximizing procedures were carried out by rationally unbounded agents. This status has been challenged on many grounds and alternative views from fields like psychology have found a way into the core of economics research frontier. Prospect theory, developed by psychologists Daniel Kahneman and Amos Tversky since the 1970s, has provided a more empirical, inductive and descriptive theory of decision making. It has made significant inroads into mainstream microeconomics, shaking the habits of some of its practitioners. This paper first takes stock of its main developments and then uses a Lakatosian framework to draw out its negative and positive heuristics. In what follows, its heuristics are compared to those of traditional rational decision-making theories. The differences between them are highlighted, pointing to changes in the mainstream of the profession and to new opportunities for research.

Domestic and peridomestic transmission of American cutaneous leishmaniasis: changing epidemiological patterns present new control opportunities

Predictions that deforestation would reduce American cutaneous leishmaniasis incidence have proved incorrect. Presentations at a recent international workshop, instead, demonstrated frequent domestication of transmission throughout Latin America. While posing new threats, this process also increases the effectiveness of vector control in and around houses. New approaches for sand fly control and effective targeting of resources are reviewed.

The new culture of electronic publishing

Local conditions in the past often limited opportunities for scholarly exchange. But now these limits are gone and the global workplace has replaced them. It is important to react to these changes. Every academic department must now adopt new methods and rethink processes. Another is the intense national and international debate about open access to scholarly knowledge. The Open Access Initiative shows that a change is taking place in the communication process. This change is also important for service departments within research institutions. Libraries, computer centers and related units have to ask themselves how to react appropriately to the new conditions. What services must be changed or redeveloped, and in what quality and quantity should they be offered? This article focuses on changes in the scholarly publication process. It describes both technological changes and the changes needed in people's attitudes.