Piperamides and their derivatives as potential anti-trypanosomal agents

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

Bioprospection of yeasts as biocontrol agents against phytopathogenic molds

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Comercialização de caju in natura na região noroeste do estado de São Paulo

Para estimar e analisar os custos de comercialização e identificar locais e formas de comercialização do caju, foram realizadas, durante o ano de 2000/01, entrevistas com produtores, técnicos da extensão rural, agentes intermediários e pesquisadores de órgãos públicos. Também foram levantadas informações na Companhia de Entrepostos e Armazéns Gerais de São Paulo (CEAGESP). Os custos agregados pelo segmento da comercialização devem-se, em grande parte, às despesas com o transporte até os grandes centros atacadistas, e também à comissão definida pelo atacadista. Para o produtor da região Noroeste do Estado de São Paulo, o ideal seria direcionar sua produção para os meses de janeiro a junho, garantindo assim melhores preços e com isso resultados mais satisfatórios.

Resistance inducing agents on the biology and probing behaviour of the greenbug in wheat

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Reducing the gap between mobile and intelligent software agents

This paper presents an approach to integrate an artificial intelligence (AI) technique, concretely rule-based processing, into mobile agents. In particular, it focuses on the aspects of designing and implementing an appropriate inference engine of small size to reduce migration costs. The main goal is combine two lines of agent research, First, the engineering oriented approach on mobile agent architectures, and, second, the AI related approach on inference engines driven by rules expressed in a restricted subset of first-order predicate logic (FOPL). In addition to size reduction, the main functions of this type of engine were isolated, generalized and implemented as dynamic components, making possible not only their migration with the agent, but also their dynamic migration and loading on demand. A set of classes for representing and exchanging knowledge between rule-based systems was also proposed.

Crystallographic and pre-steady-state kinetics studies on binding of NADH to wild-type and isoniazid-resistant enoyl-ACP(CoA) reductase enzymes from Mycobacterium tuberculosis

An understanding of isoniazid (INH) drug resistance mechanism in Mycobacterium tuberculosis should provide significant insight for the development of newer anti-tubercular agents able to control INH-resistant tuberculosis (TB). The inhA-encoded 2-trans enoyl-acyl carrier protein reductase enzyme (InhA) has been shown through biochemical and genetic studies to be the primary target for INH. In agreement with these results, mutations in the inhA structural gene have been found in INH-resistant clinical isolates of M. tuberculosis, the causative agent of TB. In addition, the InhA mutants were shown to have higher dissociation constant values for NADH and lower values for the apparent first-order rate constant for INH inactivation as compared to wild-type InhA. Here, in trying to identify structural changes between wild-type and INH-resistant InhA enzymes, we have solved the crystal structures of wild-type and of S94A, I47T and I21V InhA proteins in complex with NADH to resolutions of, respectively, 2.3 angstrom, 2.2 angstrom, 2.0 angstrom, and 1.9 angstrom. The more prominent structural differences are located in, and appear to indirectly affect, the dinucleotide binding loop structure. Moreover, studies on pre-steady-state kinetics of NADH binding have been carried out. The results showed that the limiting rate constant values for NADH dissociation from the InhA-NADH binary complexes (k(off)) were eleven, five, and tenfold higher for, respectively, I21V, I47T and S94A INH-resistant mutants of InhA as compared to INH-sensitive wildtype InhA. Accordingly, these results are proposed to be able to account for the reduction in affinity for NADH for the INH-resistant InhA enzymes. (c) 2006 Elsevier Ltd. All rights reserved.

DETECTION OF INFECTIOUS-DISEASE AGENTS IN TISSUE BY IMMUNOCYTOCHEMISTRY

1. Immunocytochemical procedures have played an increasingly larger role in the identification of infectious disease agents in tissue sections owing to the increased availability and specificity of antibody reagents, the great sensitivity of the methods, and the relative facility with which the studies are performed.2. Immunocytochemical methods can be applied to routine formalin-fixed tissue for the detection of infectious agents such as viruses, bacteria, fungi, and protozoa among other microorganisms for diagnostic and research purposes.

Crystallographic studies on the binding of isonicotinyl-NAD adduct to wild-type and isoniazid resistant 2-trans-enoyl-ACP (CoA) reductase from Mycobacterium tuberculosis

The resumption of tuberculosis led to an increased need to understand the molecular mechanisms of drug action and drug resistance, which should provide significant insight into the development of newer compounds. Isoniazid (INH), the most prescribed drug to treat TB, inhibits an NADH-dependent enoyl-acyl carrier protein reductase (InhA) that provides precursors of mycolic acids, which are components of the mycobacterial cell wall. InhA is the major target of the mode of action of isoniazid. INH is a pro-drug that needs activation to form the inhibitory INH-NAD adduct. Missense mutations in the inhA structural gene have been identified in clinical isolates of Mycobacterium tuberculosis resistant to INH. To understand the mechanism of resistance to INH, we have solved the structure of two InhA mutants (121V and S94A), identified in INH-resistant clinical isolates, and compare them to INH-sensitive WT InhA structure in complex with the INH-NAD adduct. We also solved the structure of unliganded INH-resistant S94A protein, which is the first report on apo form of InhA. The salient features of these structures are discussed and should provide structural information to improve our understanding of the mechanism of action of, and resistance to, INH in M. tuberculosis. The unliganded structure of InhA allows identification of conformational changes upon ligand binding and should help structure-based drug design of more potent antimycobacterial agents. (c) 2007 Elsevier B.V. All rights reserved.