Strand Analysis, a free online program for the computational identification of the best RNA interference (RNAi) targets based on Gibbs free energy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Identification and expression analysis of microRNAs and targets in the biofuel crop sugarcane

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Molecular models of protein targets from Mycobacterium tuberculosis

Structural characterization of enzymes that belong to microbial metabolic pathways is very important for structure-based drug design since some of these proteins may be present in the bacterial genome, but absent in humans. Thus, metabolic pathways became potential targets for drug design. The motivation of this work is the fact that Mycobacterium tuberculosis is the cause of the deaths of millions of people in the world, so that the structural characterization of protein targets to propose new drugs has become essential. DBMODELING is a relational database, created to highlight the importance of methods of molecular modeling applied to the Mycobacterium tuberculosis genome with the aim of proposing protein-ligand docking analysis. There are currently more than 300 models for proteins from Mycobacterium tuberculosis genome in the database. The database contains a detailed description of the reaction catalyzed by each enzyme and their atomic coordinates. Information about structures, a tool for animated gif image, a table with a specification of the metabolic pathway, modeled protein, inputs used in modeling, and analysis methods used in this project are available in the database for download. The search tool can be used for reseachers to find specific pathways or enzymes.

The use of biodiversity as source of new chemical entities against defined molecular targets for treatment of malaria, tuberculosis, and T-cell mediated diseases: a review

The modern approach to the development of new chemical entities against complex diseases, especially the neglected endemic diseases such as tuberculosis and malaria, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a defined target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, (iii) the development even in the initial stages of compounds with selective toxicity (the fundamental principle of chemotherapy), (iv) the evaluation of plant extracts as well as of pure substances. The current use of such technology, unfortunately, is concentrated in developed countries, especially in the big pharma. This fact contributes in a significant way to hamper the development of innovative new compounds to treat neglected diseases. The large biodiversity within the territory of Brazil puts the country in a strategic position to develop the rational and sustained exploration of new metabolites of therapeutic value. The extension of the country covers a wide range of climates, soil types, and altitudes, providing a unique set of selective pressures for the adaptation of plant life in these scenarios. Chemical diversity is also driven by these forces, in an attempt to best fit the plant communities to the particular abiotic stresses, fauna, and microbes that co-exist with them. Certain areas of vegetation (Amazonian Forest, Atlantic Forest, Araucaria Forest, Cerrado-Brazilian Savanna, and Caatinga) are rich in species and types of environments to be used to search for natural compounds active against tuberculosis, malaria, and chronic-degenerative diseases. The present review describes some strategies to search for natural compounds, whose choice can be based on ethnobotanical and chemotaxonomical studies, and screen for their ability to bind to immobilized drug targets and to inhibit their activities. Molecular cloning, gene knockout, protein expression and purification, N-terminal sequencing, and mass spectrometry are the methods of choice to provide homogeneous drug targets for immobilization by optimized chemical reactions. Plant extract preparations, fractionation of promising plant extracts, propagation protocols and definition of in planta studies to maximize product yield of plant species producing active compounds have to be performed to provide a continuing supply of bioactive materials. Chemical characterization of natural compounds, determination of mode of action by kinetics and other spectroscopic methods (MS, X-ray, NMR), as well as in vitro and in vivo biological assays, chemical derivatization, and structure-activity relationships have to be carried out to provide a thorough knowledge on which to base the search for natural compounds or their derivatives with biological activity.

Proteomic profiling of the molecular targets of interactions of the mastoparan peptide Protopolybia MP-III at the level of endosomal membranes from rat mast cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Perseveration in congenitally blind children: Effects of luminous and acoustic targets on a modified A-not-B task

The purpose of this study was to determine whether or not blind children perseverate during a modified Piagetian A-not-B reaching task, with conditions that employ luminous AB targets and acoustic AB targets. Ten congenitally blind children, ages 1-4 years, with residual vision for light, took part in this study. Behavioral and kinematic data were computed for participants' reaches, performed in six A trials and in two B trials, in both stimulus conditions. All of the children perseverated in the luminous condition, and none of them perseverated in the condition using acoustic targets. The children tilted their heads in the direction of the target as they reached towards it. However, this coupling action (head-reaching) occurred predominantly in the A trials in the acoustic condition. In the luminous condition, in contrast to the acoustic condition, the children took longer times to initiate the reaching movement. Also, in the luminous condition, the children explored the target surroundings, unlike the acoustic condition, in which they reached straight ahead. For these blind children, sound was more relevant to reaching than was the luminous stimulus. The luminous input caused perseveration in congenitally blind children in a similar way that has been reported in the literature for typically-developing, sighted infants, ages 8-12 months, performing A-not-B tasks with visual inputs. (C) 2012 Elsevier B.V. All rights reserved.

Uranium distribution and radon exhalation from Brazilian dimension stones

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Transfer coefficient measurements of uranium to the organs of Wistar rats, as a function of the uranium content in the food

Groups of animals (Wistar rats) were fed with rations doped with uranyl nitrate at concentrations ranging from 0.5 to 100 ppm. The uranium content in the ashes of the organs was measured by the neutron-fission track counting technique. The most striking result is that the transfer coefficients, as a function of the uranium concentration, exhibit a concave shape with a minimum around 20ppm-U for all organs. Explanations to interpret this finding are tentatively given. (C) 2001 Elsevier B.V. Ltd. All rights reserved.

Some constraints on the modeling using the uranium isotopes U-238 and U-234 for dating groundwaters from Guarany aquifer, South America

Groundwaters from the Guarany aquifer located at the South American continent and sampled at four wells with described geological sections in São Paulo State, Brazil, were chemically and isotopically analysed with two aims: to evaluate the quality of this important hydrological resource and to investigate the possibility of using the natural uranium isotopes U-234 and U-238 as a chronological tool, since the U-234/U-238 activity ratio and dissolved U content data in groundwater systems have generated models for dating purposes.

Uranium incorporation biokinetics in poultry bones as function of phytase doses

Neutron activation analysis has been used to study uranium incorporation in poultry bones as function of chow doped with : (a) uranium (20 ppm); (b) U-doped food (20 ppm) plus phytase (120 ppm) and (c) U-doped food (20 ppm) plus phytase (180 ppm). To investigate this situation experiments involving several groups of Cobb broilers was performed. Two animals per group were sacrificed weekly up to their adultness and uranium concentration in the tibia was measured. It was observed that the concentration of uranium (mug U/g bone) is decreasing all along the animal life spanning period of 14-42 days. This behavior suggests that the skeleton mass is growing faster than the corresponding accumulation of uranium. The administration of phytase seems not to alter this scenario.

Uranium in groundwaters from Botucatu-Piramboia aquifer, Brazil

Groundwater from 60 pumped tubular wells of the Botucatu-Piramboia aquifer system located at the Parana sedimentary basin in Brazil were chemically analysed with the aim of evaluating if the mechanisms related to the migration of uranium can generate concentrations greater than the maximum permissible limit in drinking water, as defined by the Brazilian national standards.

Uranium levels in the diet of São Paulo City residents

Natural levels of uranium in the diet of São Paulo City residents were studied, and radionuclide concentrations were measured by the fission track method on samples of typical adult food items. This information was used to evaluate the daily intake of uranium in individuals living in São Paulo City which is, according to our findings, around 0.97 mu g U/day. Using the ICRP Uranium-model, we estimated the uranium accumulation and committed doses in some tissues and organs, as function of time. We compared the output of the ICRP uranium biokinetic model, tailored for the conditions prevailing in São Paulo, with experimental data from other localities. Such comparison was possible by means of a simple method we developed, which allows normalization among experimental results from different regions where distinct values of chronic daily intake are observed. (c) 2006 Elsevier Ltd. All rights reserved.