Theoretical study on the molecular mechanism for the reaction of VO2+ with C2H4

The complex reaction between VO2+ ((1)A(1)/(3)A) and C2H4 (Ag-1(g)/(3)A(1)) to yield VO+ ((1)Delta/(3)Sigma) and CH3CHO ('A'/(3)A) has been studied by means of B3LYP/6-31G* and B3LYP/6-311G(2d,p) calculations. The structures of all reactants, products, intermediates, and transition structures of this reaction have been optimized and characterized at the fundamental singlet and first excited triplet electronic states. Crossing points are localized, and possible spin inversion processes are discussed by means of the intrinsic reaction coordinate approach. Relevant stationary points along the most favorable reaction pathways have been studied at the CCSD/6-311G(2d,p)//B3LYP/6-311G(2d,p) calculation level. The theoretical results allow the development of thermodynamic and kinetic arguments about the reaction pathways of the title process. In the singlet state, the first step is the barrierless obtention of a reactant complex associated with the formation of a V-C bond, while in the triplet state a three-membered ring addition complex with the V bonded to the two C atoms is obtained. Similar behavior is found in the exit channels: the product complexes can be formed from isolated products without barriers. The reactant and product complexes are the most stable stationary points in the singlet and triplet electronic states. From the singlet state reactant complex, two reaction pathways are posssible to reach the triplet state product complex. (i) A mechanism in which a hydrogen transfer process is the first and rate limiting step and the second step is an oxygen transfer between vanadium and carbon atoms with a concomitant change in the spin state. The crossing point between singlet and triplet spin states is not kinetically relevant because it takes place at a later stage occurring in the exit channel. (ii) A mechanism in which the first stage renders a four-membered ring between vanadyl cation and the ethylene fragment and an oxygencarbon bond is formed; on going from this minimum to the second transition structure, associated with a carbon-vanadium bond breaking process, the crossing point between singlet and triplet spin states is reached. The final step is the hydrogen transfer between both carbon atoms to yield the product complex. In this case the spin change opens a lower barrier pathway. The transition structures with larger values of relative energies for both reactive channels of VO2+ ((1)A(1)) + C2H4 (Ag-1) --> VO+ ((3)Sigma) + CH3CHO ((1)A') present similar energies, and the two reaction pathways can be considered as competitive.

Molecular assay optimized by Taguchi experimental design method for venous thromboembolism investigation

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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)

Paleodistributions and Comparative Molecular Phylogeography of Leafcutter Ants (Atta spp.) Provide New Insight into the Origins of Amazonian Diversity

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Molecular models of NS3 protease variants of the Hepatitis C virus

Background: Hepatitis C virus (HCV) currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed.Results: the atomic coordinates of crystallographic structure 1CU1 and 1DY9 were used as starting model for modeling of the NS3 protease variant structures. The NS3 protease variant structures are composed of six subdomains, which occur in sequence along the polypeptide chain. The protease domain exhibits the dual beta-barrel fold that is common among members of the chymotrypsin serine protease family. The helicase domain contains two structurally related beta-alpha-beta subdomains and a third subdomain of seven helices and three short beta strands. The latter domain is usually referred to as the helicase alpha-helical subdomain. The rmsd value of bond lengths and bond angles, the average G-factor and Verify 3D values are presented for NS3 protease variant structures.Conclusions: This project increases the certainty that homology modeling is an useful tool in structural biology and that it can be very valuable in annotating genome sequence information and contributing to structural and functional genomics from virus. The structural models will be used to guide future efforts in the structure-based drug design of a new generation of NS3 protease variants inhibitors. All models in the database are publicly accessible via our interactive website, providing us with large amount of structural models for use in protein-ligand docking analysis.

A física no contexto da biologia molecular

Nas últimas décadas tem havido uma crescente abordagem física no estudo de moléculas e sistemas macromoleculares de interesse biológico. Essa abordagem inclui tanto aspectos experimentais quanto teóricos. de fato, há um vasto campo a ser explorado pela física nessa área. Discutimos neste texto as características gerais e formação básica do profissional interessado em ter como objeto o estudo de sistemas biomoleculares, tanto em nível de graduação como na pós-graduação. Nessa linha de pensamento, assuntos como a formação básica e os fundamentos biológicos e físicos são discutidos.

A systematic approach to identify STRE-binding proteins of the gsn glycogen synthase gene promoter in Neurospora crassa

The gene encoding glycogen synthase in Neurospora crassa (gsn) is transcriptionally down-regulated when mycelium is exposed to a heat shock from 30 to 45 degrees C. The gsn promoter has one stress response element (STRE) motif that is specifically bound by heat shock activated nuclear proteins. In this work, we used biochemical approaches together with mass spectrometric analysis to identify the proteins that bind to the STRE motif and could participate in the gsn transcription regulation during heat shock. Crude nuclear extract of heat-shocked mycelium was prepared and fractionated by affinity chromatography. The fractions exhibiting DNA-binding activity were identified by electrophoretic mobility shift assay (EMSA) using as probe a DNA fragment containing the STRE motif DNA-protein binding activity was confirmed by Southwestern analysis. The molecular mass (MM) of proteins was estimated by fractionating the crude nuclear extract by SDS-PAGE followed by EMSA analysis of the proteins corresponding to different MM intervals. Binding activity was detected at the 30-50 MM kDa interval. Fractionation of the crude nuclear proteins by IEF followed by EMSA analysis led to the identification of two active fractions belonging to the pIs intervals 3.54-4.08 and 6.77-7.31. The proteins comprising the MM and pI intervals previously identified were excised from a 2-DE gel, and subjected to mass spectrometric analysis (MALDI-TOF/TOF) after tryptic digestion. The proteins were identified by search against the MIPS and MIT N. crassa databases and five promising candidates were identified. Their structural characteristics and putative roles in the gsn transcription regulation are discussed.

Electrochemical capacitance spectroscopy and capacitive relaxation of the changeover process in iron hexacyanoferrate molecular compound

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

Molecular phylogeny, morphology and their implications for the taxonomy of Eriocaulaceae

Eriocaulaceae é uma família pantropical com dez gêneros e cerca de 1.400 espécies, com centro de diversidade no Novo Mundo, especialmente no Brasil. A última revisão da família foi publicada há mais de 100 anos, e até recentemente, as relações genéricas e infra-genéricas ainda eram pouco resolvidas. Entretanto, tem havido nos últimos 30 anos, um grande esforço por parte de pesquisadores brasileiros para preencher as lacunas existentes, utilizando caracteres morfológicos e anatômicos, complementados por dados adicionais de diferentes fontes, como palinologia, química, embriologia, genética de populações, citologia e, mais recentemente, estudos de filogenia molecular. Tal conjunto de dados tem levado a uma re-avaliação do relacionamento filogenético dentro da familia. Neste trabalho são apresentados novos dados para as regiões de ITS e trnL-F, analisadas separadamente e em combinação, usando máxima parcimônia e inferência Bayesiana. Os dados obtidos confirmam resultados já publicados, e mostram que muitos caracteres tradicionalmente usados para diferenciação e circunscrição dos gêneros dentro da família são homoplásicos. Uma nova descrição e chave genérica para a família, utilizando caracteres de várias fontes são apresentadas, refletindo a taxonomia atual das Eriocaulaceae.

PR gene families of citrus: their organ specific-biotic and abiotic inducible expression profiles based on ESTs approach

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Surface pressure-area isotherms for Langmuir monolayers and a docking molecular orientation of perylene tetracarboxylic derivatives on a water surface

The surface pressure-molecular area (pi-A) isotherms for Langmuir monolayers of four perylenetetracarboxylic (PTCD) derivatives, measured with varying subphase temperatures and compression speeds, are reported. The behavior of these PTCD derivatives at the water-air interface is modeled using the rigid docking method. This approach is the first attempt to model the molecular orientation of PTCD on the water surface to be compared with experimental Langmuir isotherms. Through this methodology, it would be possible to anticipate aggregation and determine if favorable spatial orientations of perylenes are generated on the water surface. The pi-A isotherm experiments show that these molecules can support high surface pressures, indicating strong packing on the water surface and that the isotherms are compression speed independent but temperature dependent. The molecular orientation and stacking was further examined in Langmuir-Blodgett (LB) monolayers deposited onto glass and glass coated with Ag island films using UV-visible absorption and surface-enhanced fluorescence (SEF) measurements.

The Brazilian pediatric myelodysplastic cooperative group strategies: are they relevant to improve educational approach and correct diagnosis?

Brazil is a wide country with huge contrasts. Its peculiarities can highlight environmental factors that could influence the frequencies of different cancers. The standard treatment and results achieved from several different areas of the country may not be found in others. The establishment of a national cooperative group has the potential to improve outcomes. The The Brazilian Cooperative Group on Pediatric Patients with Myelodysplastic Syndrome (BCG-MDS-PED) was first organized in January 1997 as a working group of hematologists, pediatric oncologists, pediatric-hematologists, molecular biologists and other professionals in order to study pediatric (age < 18 years) MDS. Six distinct subcommittees constituted with members from several universities: cytology, histopathology, clinical, cytogenetics, molecular biology and epidemiology. The goals of the BCG-MDS-PED were: (i) to offer support for diagnosis and orientation for treatment; (ii) educational Support for the colleagues all over the country and (iii) research on pathogenesis and new approaches for pediatric MDS patients. There are socio-economical differences among the five regions of the country. The BCG-MDS-PED believes that it is absolutely necessary to Study the clinical, cellular, molecular and epidemiological aspects of MDS, taking in account these peculiar differences among populations and regions. Since 1997, 114 pediatric cases were referred to the BCG-MDS-PED from 21 centres. Seven Brazilian states have sent cases to the group, 31 patients were referred from universities, 73 patients from pediatric oncology units (foundations) and 10 patients came from private clinics. Some of these patients have been followed up and/or treated by the physician who referred them to the BCG-MDS-PED for confirmation of the initial diagnosis. The majority of these physicians have required orientation on diagnostic and treatment issues, as well as to complete cytogenetic and molecular studies. From these 114 patients, 64 patients were confirmed as MDS. We believe that, the more numerous the MDS-studied cases, the more experienced will be the referee group on clinical and laboratory features on childhood MDS in Brazil. (C) 2002 Published by Elsevier B.V. Ltd.

Jahn-Teller effect on the structure of the Sm-doped PbTiO3: A theoretical approach

Samarium doped PbTiO3 (PT:Sm) and pure PbTiO3 (PT) powders were obtained by polymeric precursor method. These powders were characterized by X-ray diffraction (XRD) and theoretical calculations using the CRYSTAL98 program. The effect of the samarium atom is taken into account only indirectly. The experimental models were compared with the cubic (ideal) and tetragonal theoretical models. The structure deformations existent in the experimental compounds were analyzed from the tiny structural differences that lead to perturbations in the crystal orbital splittings. This paper proposes an efficient alternative methodology for defining structural distortions. (c) 2007 Elsevier B.V. All rights reserved.

Nonadiabatic calculations of the oscillator strengths for the helium atom in the hyperspherical adiabatic approach

Energies and wavefunctions are calculated for the bound states of the helium atom in the hyperspherical adiabatic approach by the full inclusion of nonadiabatic couplings. We show that the use of appropriate asymptotic radial boundary conditions not only allows the efficient calculation of energies accurate up to a few ppm for the ground state but also gives increasingly precise results for high-lying excited states with a unique set of equations. The accuracy of the wavefunctions is demonstrated by the calculation of oscillator strengths in the length form for transitions between stares ii S-1(e) and (n + 1) P-1(0) up to n = 29, in agreement with variational calculations.