Crystal structure of garciniaphenone and evidences on the relationship between keto-enol tautomerism and configuration

Garciniaphenone (=rel-(1R,5R,7R)-3-benzoyl-4-hydroxy-8,8-dimethyl-1,7-bis(3-methylbut-2-en-1-yl)bicyclo[3.3.1]non-3-ene-2,9-dione; 1). a novel natural product, was isolated from a hexane extract of Garcinia brasiliensis fruits. The crystal structure of 1 as well as the selected geometrical and Configurational features were compared with those of known related polyprenylated benzophenones. Garciniaphenone is the first representative of polyprenylated benzophenones without a prenyl substituent at C(5). Notably, the absence of a 5-prenyl substituent has an impact on the molecular geometry. The tautomeric form of 1 in the solid state was readily established by a residual-electronic-density map generated by means of a difference Fourier analysis, and there is an entirely delocalized six-membered chelate ring encompassing the keto-enol moiety. The configuration at C(7) was used to rationalize the nature of the keto-enol tautomeric form within 1. The intermolecular array in the network is maintained by nonclassical intermolecular H-bonds.

Resilience of protein-protein interaction networks as determined by their large-scale topological features

The relationship between the structure and function of biological networks constitutes a fundamental issue in systems biology. Particularly, the structure of protein-protein interaction networks is related to important biological functions. In this work, we investigated how such a resilience is determined by the large scale features of the respective networks. Four species are taken into account, namely yeast Saccharomyces cerevisiae, worm Caenorhabditis elegans, fly Drosophila melanogaster and Homo sapiens. We adopted two entropy-related measurements (degree entropy and dynamic entropy) in order to quantify the overall degree of robustness of these networks. We verified that while they exhibit similar structural variations under random node removal, they differ significantly when subjected to intentional attacks (hub removal). As a matter of fact, more complex species tended to exhibit more robust networks. More specifically, we quantified how six important measurements of the networks topology (namely clustering coefficient, average degree of neighbors, average shortest path length, diameter, assortativity coefficient, and slope of the power law degree distribution) correlated with the two entropy measurements. Our results revealed that the fraction of hubs and the average neighbor degree contribute significantly for the resilience of networks. In addition, the topological analysis of the removed hubs indicated that the presence of alternative paths between the proteins connected to hubs tend to reinforce resilience. The performed analysis helps to understand how resilience is underlain in networks and can be applied to the development of protein network models.

Structure and Calcium-Binding Activity of LipL32, the Major Surface Antigen of Pathogenic Leptospira sp.

Leptospixosis, a spirochaetal zoonotic disease caused by Leptospira, has been recognized as an important emerging infectious disease. LipL32 is the major exposed outer membrane protein found exclusively in pathogenic leptospires, where it accounts for up to 75% of the total outer membrane proteins. It is highly immunogenic, and recent studies have implicated LipL32 as an extracellular matrix binding protein, interacting with collagens, fibronectin, and laminin. In order to better understand the biological role and the structural requirements for the function of this important lipoprotein, we have determined the 2.25-angstrom-resolution structure of recombinant LipL32 protein corresponding to residues 21-272 of the wild-type protein (LipL32(21-272)). The LipL32(21-272) monomer is made of a jelly-roll fold core from which several peripheral secondary structures protrude. LipL32(21-272) is structurally similar to several other jelly-roll proteins, some of which bind calcium ions and extracellular matrix proteins. Indeed, spectroscopic data (circular dichroism, intrinsic tryptophan fluorescence, and extrinsic 1-amino-2-naphthol-4-sulfonic acid fluorescence) confirmed the calcium-binding properties of LipL32(21-272). Ca(2+) binding resulted in a significant increase in the thermal stability of the protein, and binding was specific for Ca(2+) as no structural or stability perturbations were observed for Mg(2+), Zn(2+), or Cu(2+). Careful examination of the crystal lographic structure suggests the locations of putative regions that could mediate Ca(2+) binding as well as binding to other interacting host proteins, such as collagens, fibronectin, and lamixidn. (C) 2009 Elsevier Ltd. All rights reserved.

Structure, Dynamics, and RNA Interaction Analysis of the Human SBDS Protein

Shwachman-Bodian-Diamond syndrome is an autosomal recessive genetic syndrome with pleiotropic phenotypes, including pancreatic deficiencies, bone marrow dysfunctions with increased risk of myelodysplasia or leukemia, and skeletal abnormalities. This syndrome has been associated with mutations in the SBDS gene, which encodes a conserved protein showing orthologs in Archaea and eukaryotes. The Shwachman-Bodian-Diamond syndrome pleiotropic phenotypes may be an indication of different cell type requirements for a fully functional SBDS protein. RNA-binding activity has been predicted for archaeal and yeast SBDS orthologs, with the latter also being implicated in ribosome biogenesis. However, full-length SBDS orthologs function in a species-specific manner, indicating that the knowledge obtained from model systems may be of limited use in understanding major unresolved issues regarding SBDS function, namely, the effect of mutations in human SBDS on its biochemical function and the specificity of RNA interaction. We determined the solution structure and backbone dynamics of the human SBDS protein and describe its RNA binding site using NMR spectroscopy. Similarly to the crystal structures of Archaea, the overall structure of human SBDS comprises three well-folded domains. However, significant conformational exchange was observed in NMR dynamics experiments for the flexible linker between the N-terminal domain and the central domain, and these experiments also reflect the relative motions of the domains. RNA titrations monitored by heteronuclear correlation experiments and chemical shift mapping analysis identified a classic RNA binding site at the N-terminal FYSH (fungal, Yhr087wp, Shwachman) domain that concentrates most of the mutations described for the human SBDS. (C) 2010 Elsevier Ltd. All rights reserved.

Electronic structure and spectra of a new molecular species: SI. A theoretical contribution

A high level theoretical approach is used to characterize for the first time a manifold of doublet and quartet A + S and Omega states correlating with the first two dissociation channels of an as yet experimentally unknown molecular species, SI, sulfur monoidide. A set of spectroscopic constants is determined, including vibrationally averaged spin-orbit coupling constants, vibrationally averaged dipole moments, and dissociation energies. The transition dipole moment function for the spin-forbidden transition a (4)Sigma -X (2)Pi, and the associated radiative lifetimes were also evaluated. Two possibilities to detect transitions experimentally and to derive spectroscopic constants are suggested. (C) 2011 Elsevier B. V. All rights reserved.

The Molecular Chaperone Hsp70 Family Members Function by a Bidirectional Heterotrophic Allosteric Mechanism

The Hsp70 family is one of the most important and conserved molecular chaperone families. It is well documented that Hsp70 family members assist many cellular processes involving protein quality control, as follows: protein folding, transport through membranes, protein degradation, escape from aggregation, intracellular signaling, among several others. The Hsp70 proteins act as a cellular pivot capable of receiving and distributing substrates among the other molecular chaperone families. Despite the high identity of the Hsp70 proteins, there are several homologue Hsp70 members that do not have the same role in the cell, which allow them to develop and participate in such large number of activities. The Hsp70 proteins are composed of two main domains: one that binds ATP and hydrolyses it to ADP and another which directly interacts with substrates. These domains present bidirectional heterotrophic allosteric regulation allowing a fine regulated cycle of substrate binding and release. The general mechanism of the Hsp70s cycle is under the control of ATP hydrolysis that modulates the low (ATP-bound state) and high (ADP-bound state) affinity states of Hsp70 for substrates. An important feature of the Hsp70s cycle is that they have several co-chaperones that modulate their cycle and that can also interact and select substrates. Here, we review some known details of the bidirectional heterotrophic allosteric mechanism and other important features for Hsp70s regulating cycle and function.

Evaluation of Postpolymerization as a Function of the Storage Time of Triethylene Glycol Dimethacrylate/2,2-Bis[4-(2-Hydroxy-3-Methacryloxy-Prop-1-Oxy)-Phenyl]-propane Bisphenyl-alpha-Glycidyl Ether Dimethacrylate Copolymers Used in Dental Resins by Differential Scanning Calorimetry and Dynamic Mechanical Analysis

The aim of this work was to evaluate the effect of the storage time on the thermal properties of triethylene glycol dimethacrylate/2,2-bis[4-(2-hydroxy-3-methacryloxy-prop-1-oxy)-phenyl]propane bisphenyl-alpha-glycidyl ether dimethacrylate (TB) copolymers used in formulations of dental resins after photopolymerization. The TB copolymers were prepared by photopolymerization with an Ultrablue IS light-emitting diode, stored in the dark for 160 days at 37 degrees C, and characterized with differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and Fourier transform infrared spectroscopy with attenuated total reflection. DSC curves indicated the presence of an exothermic peak, confirming that the reaction was not completed during the photopolymerization process. This exothermic peak became smaller as a function of the storage time and was shifted at higher temperatures. In DMA studies, a plot of the loss tangent versus the temperature initially showed the presence of two well-defined peaks. The presence of both peaks confirmed the presence of residual monomers that were not converted during the photopolymerization process. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 112: 679-684, 2009

Pressure Perturbation Calorimetry and Guest-Host Chemistry of NDMG and N-MAP with p-Sulfonatocalix[6]arene

The aim of this project is to provide an explanation for recently obtained binding constants for two similar guest molecules, NDMG and N-MAP, with a p-sulfonatocalix[6]arene host in ammonium acetate buffer. This work was done primarily using pressure perturbation calorimetry, which is a technique that determines the coefficient of thermal expansion, α, which is in turn related to the solute molecule's effect on the order of the surrounding water molecules. A series of experiments were designed to test the effects of suspected confounding variables on the validity of PPC data. PPC was then used to study NDMG and N-MAP in ammonium acetate buffer. NDMG exhibited a minimum in α as function of temperature, while N-MAP did not. This difference was theorized to be due to the formation of an intramolecular hydrogen bond in monocationic NDMG that would lower the heat capacity of the molecule and better distribute the molecule's charge. Computational work and nuclear magnetic resonance spectroscopy confirmed that monocationic, ring-closed NDMG has less concentrated charge and more constrained motion than monocationic, ring-open NDMG. This evidence supports the theory that monocationic NDMG forms an intramolecular hydrogen bond and that this may be responsible for the minimum in α. This difference may explain the differences in binding constants between NDMG and N-MAP.

Macroeconomic policy and poverty in Brazil

O Brasil é um país onde os 50% mais pobres se apropriam aproximadamente de 10% da renda agregada, e os 10% mais ricos detêm quase 50% deste mesmo. O colorário desse alto grau de desigualdade é que se uma pessoa está somente preocupada em maximizar o nível de GPD, a função de bem–estar social implícita adotada devota parte do seu peso ao bem-estar de 10% da população. Em outras palavras, a concentração brasileira de renda cria uma anomalia dentro da perspectiva de agente representativo implícito na análise macroeconômica aonde as pessoas valem aquilo que ganham. A análise da pobreza inverte esse peso estrutural da população, estipulando zero de peso para o segmento não pobre da sociedade e atribuindo pesos aos indivíduos que aumentam com suas necessidades insatisfeitas. Esse projeto estuda as conexões entre a evolução macroeconômica Brasileira recente e da pobreza. A análise é dividida em duas partes: A primeira parte descreve a evolução da pobreza brasileira e seus principais determinantes macroeconômicos durante os últimos 15 anos. A segunda parte tira proveito das mudanças da pobreza e desigualdades medidas durante o período 1993-96 para estudar seus principais determinantes macroeconômicos. Dado a maior importância do Plano Real, uma especial atenção foi dada a análise dos impactos da desinflação no nível e na distribuição de renda e a possível sinergia entre essas duas dimensões de determinação da pobreza. A terceira parte do projeto decompõe as mudanças dos diversos índices de pobreza através dos diferentes grupos dado pelas características dos chefes de família (i.e.; sexo, anos de estudo, raça, classe trabalhadora, setores de atividades, região, densidade populacional). Depois essa decomposição é avançada um passo desatrelando as mudanças nessa diferentes células de pobreza em termos de suas respectivas mudanças em termos de desigualdade da renda per capita. Esse perfil de pobreza ajuda a mapear as diferentes fontes de mudança da pobreza na análise histórica e fornece consistência interna para os exercícios de análises contra-factuais.

Análise teórico-metodológica das monografias do curso de turismo da UFMA que abordam o assunto da gestão de negócios turísticos no período de 2001 a 2005.

Este trabalho tem por finalidade analisar as características teóricas e metodológicas das monografias defendidas no curso de turismo da Universidade Federal do Maranhão – UFMA, que tratam de assuntos voltados para a temática em Gestão de Negócios turísticos no período de 2001/2005. Trabalham-se as principais definições e conceitos relacionados à pesquisa, mostrando ser a pesquisa um ato não isolado, processual e sistematizado. Apresenta a importância e as funções da pesquisa afirmando que a mesma vem conquistando um certo espaço na vida acadêmica por melhorar as práticas educativas bem como contribuindo para melhoria de vida dos cidadãos, quando unida à tecnologia, além de apresentar a importância dos métodos de investigação nos vários níveis e fases. Aborda sobre a pesquisa nas diversas concepções na universidade de forma contextualizada. Aborda sobre a função social da pesquisa estimulando a divulgação científica, vinculando esta responsabilidade como débito social do pesquisador para com a comunidade científica. A pesquisa configura-se como um método descritivo - exploratório analisado segundo três matrizes: paradigmática, tipológica e o mapa conceitual que serviram como critério orientador, onde as monografias foram metodicamente analisadas em sua estrutura no nível teórico, apresentando as principais temáticas trabalhadas, as críticas e as propostas, bem como os autores mais citados e os tipos de documento mais pesquisados. No nível técnico são analisados a característica das pesquisas, as técnicas, instrumentos e procedimentos utilizados na coleta e analise dos dados. No nível epistemológico foram observados os critérios de validação, as concepções de causalidade e de ciência, e os pressupostos lógico – gnosiológicos. Os dados obtidos, analisados a luz do referencial teórico apontam para necessidade de um maior rigor científico e espírito crítico por parte dos pesquisadores.

KittyCat: a cognitive model of structure-form discovery

Cognition is a core subject to understand how humans think and behave. In that sense, it is clear that Cognition is a great ally to Management, as the later deals with people and is very interested in how they behave, think, and make decisions. However, even though Cognition shows great promise as a field, there are still many topics to be explored and learned in this fairly new area. Kemp & Tenembaum (2008) tried to a model graph-structure problem in which, given a dataset, the best underlying structure and form would emerge from said dataset by using bayesian probabilistic inferences. This work is very interesting because it addresses a key cognition problem: learning. According to the authors, analogous insights and discoveries, understanding the relationships of elements and how they are organized, play a very important part in cognitive development. That is, this are very basic phenomena that allow learning. Human beings minds do not function as computer that uses bayesian probabilistic inferences. People seem to think differently. Thus, we present a cognitively inspired method, KittyCat, based on FARG computer models (like Copycat and Numbo), to solve the proposed problem of discovery the underlying structural-form of a dataset.

Transfer function-noise modeling and spatial interpolation to evaluate the risk of extreme (shallow) water-table levels in the Brazilian Cerrados

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Burrows with Chimneys of the Fiddler Crab Uca thayeri: Construction, Occurrence, and Function

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

Crystal structure of Bn IV in complex with myristic acid: A Lys49 myotoxic phospholipase A(2) from Bothrops neuwiedi venom

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Parametric correlation functions to model the structure of permanent environmental (co)variances in milk yield random regression models

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