Sex ratio and dynamic behavior in populations of the exotic blowfly Chrysomya albiceps (Diptera, Calliphoridae)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

How C-terminal carboxyamidation alters the biological activity of peptides from the venom of the eumenine solitary wasp

Inflammatory peptides display different types of post-transcriptional modifications, such as C-terminal amidation, that alter their biological activity. Here we describe the structural and molecular dynamics features of the mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF-NH2), found in the venom of the solitary wasp, and of its carboxyl-free C-terminal form (EMP-AF-COO-) characterized by a reduced activity. Circular dichroism indicates that both peptides switch from a random coil conformation in water to a helical structure in TFE and SDS micelles. NMR data, in 30% TFE, reveal that the two peptides fold into an alpha-helix spanning most of their length, while they differ in terms of molecular rigidity. To understand the origins of the conformational flexibility observed in the case of EMP-AF-COO-, a 5 ns MD simulation was carried out for each peptide, in an explicit water/TFE environment. The results show that the two peptides differ in an H-bond between Leu14 NH2 and the backbone carbonyl of Ile11. The loss of that H-bond in EMP-AF-COO- leads to a significant modification of its structural dynamics. In fact, as evidenced by essential dynamics analysis, while EMP-AF-NH2 exists mainly as a rigid structure, EMP-AF-COO- presents two helical stretches that fluctuate in some sort of independent fashion. We conclude that the diverse biological activity of the two peptides is not simply due to the reduction of the net positive charge, as generally suggested, but also to a structural perturbation of the amphipathic alpha-helix that affects their ability to perturb the cell membrane.

Efeitos da informação comportamental na dinâmica intrínseca do controle postural

Esse estudo teve como objetivo examinar possíveis alterações na dinâmica intrínseca de crianças e adultos decorrentes de informações externas na realização de uma tarefa de manutenção da postura ereta. Participaram do estudo dez crianças de 8 anos de idade e dez adultos jovens de ambos os gêneros. Eles permaneceram na posição ereta dentro de uma sala móvel que foi movimentada continuamente para frente e para trás. Os participantes recebiam informação sobre o movimento da sala e eram solicitados a não oscilar ou a oscilar junto com o movimento da mesma. Os resultados mostraram que a manipulação da informação visual induziu oscilação corporal correspondente (dinâmica intrínseca) em crianças e adultos. Informação sobre o movimento da sala e solicitação de uma ação (informação comportamental) alteraram o relacionamento entre informação visual e oscilação corporal. Crianças apresentaram mais dificuldades em alterar a dinâmica intrínseca do que adultos, indicando que elas são mais dependentes da dinâmica intrínseca do que adultos. Esses resultados trazem implicações importantes para a situação de ensino-aprendizagem, pois indica que aprendizagem envolvendo crianças deve ser estruturada propiciando condições mais favoráveis para alterações na dinâmica intrínseca para que os objetivos da mesma sejam alcançados.

Correlation of temperature induced conformation change with optimum catalytic activity in the recombinant G/11 xylanase A from Bacillus subtilis strain 168 (1A1)

The 1.7 angstrom resolution crystal structure of recombinant family G/11 beta-1,4-xylanase (rXynA) from Bacillus subtilis 1A1 shows a jellyroll fold in which two curved P-sheets form the active-site and substrate-binding cleft. The onset of thermal denaturation of rXynA occurs at 328 K, in excellent agreement with the optimum catalytic temperature. Molecular dynamics simulations at temperatures of 298-328 K demonstrate that below the optimum temperature the thumb loop and palm domain adopt a closed conformation. However, at 328 K these two domains separate facilitating substrate access to the active-site pocket, thereby accounting for the optimum catalytic temperature of the rXynA. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Conformational features of cepacian: the exopolysaccharide produced by clinical strains of Burkholderia cepacia

Conformational energy calculations and molecular dynamics investigations, both in water and in dimethyl sulfoxide, were carried out on the exopolysaccharide cepacian produced by the majority of the clinical strains of Burkholderia cepacia, an opportunistic pathogen causing serious lung infection in patients affected by cystic fibrosis, the investigation was aimed at defining the structural and conformational features, which might be relevant for clarification of the structure-function relationships of the polymer. The molecular dynamics calculations were carried out by Ramachandran-type energy plots of the disaccharides that constitute the polymer repeating unit. The dynamics of an oligomer composed of three repeating units were investigated in water and in Me2SO, a non-aggregating solvent. Analysis of the time persistence of hydrogen bonds showed the presence of a large number of favourable interactions in water, which were less evident in Me2SO. The calculations on the cepacian chain indicated that polymer conformational features in water were affected by the lateral chains, but were also largely dictated by the presence of solvent. Moreover, the large number of intra-chain hydrogen bonds in water disappeared in Me2SO solution, increasing the average dimension of the polymer chains. (c) 2005 Elsevier Ltd. All rights reserved.

Interfacial surface charge and free accessibility to the PLA(2)-active site-like region are essential requirements for the activity of Lys49 PLA(2) homologues

Lys49 phospholipase A(2) homologues are highly myotoxic and cause extensive tissue damage but do not display hydrolytic activity towards natural phospholipids. The binding of heparin, heparin derivatives and polyanionic compounds such as suramin result in partial inhibition (up to 60%) of the myotoxic effects due to a change in the overall charge of the interfacial surface. In vivo experiments demonstrate that polyethylene glycol inhibits more than 90% of the myotoxic effects without exhibiting secondary toxic effects. The crystal structure of bothropstoxin-I complexed with polyethylene glycol reveals that this inhibition is due to steric hindrance of the access to the PLA(2)-active site-like region. These two inhibitory pathways indicate the roles of the overall surface charge and free accessibility to the PLA2-active site-like region in the functioning of Lys49 phospholipases A(2) homologues. Molecular dynamics simulations, small angle X-ray scattering and structural analysis indicate that the oligomeric states both in solution and in the crystalline states of Lys49 phospholipases A2 are principally mediated by hydrophobic contacts formed between the interfacial surfaces. These results provide the framework for the potential application of both clinically approved drugs for the treatment of Viperidae snakebites. (c) 2006 Elsevier Ltd. All rights reserved.

Structural studies of prephenate dehydratase from Mycobacterium tuberculosis H37Rv by SAXS, ultracentrifugation, and computational analysis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Study of the mechanism of action of anoplin, a helical antimicrobial decapeptide with ion channel-like activity, and the role of the amidated C-terminus

Anoplin, an antimicrobial, helical decapeptide from wasp venom, looses its biological activities by mere deamidation of its C-terminus. Secondary structure determination, by circular dichroism spectroscopy in amphipathic environments, and lytic activity in zwitterionic and anionic vesicles showed quite similar results for the amidated and the carboxylated forms of the peptide. The deamidation of the C-terminus introduced a negative charge at an all-positive charged peptide, causing a loss of amphipathicity, as indicated by molecular dynamics simulations in TFE/water mixtures and this subtle modification in a peptide's primary structure disturbed the interaction with bilayers and biological membranes. Although being poorly lytic, the amidated form, but not the carboxylated, presented ion channel-like activity on anionic bilayers with a well-defined conductance step; at approximately the same concentration it showed antimicrobial activity. The pores remain open at trans-negative potentials, preferentially conducting cations, and this situation is equivalent to the interaction of the peptide with bacterial membranes that also maintain a high negative potential inside. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.

Three- and Four-Nucleon Bound States in Three Dimensions, Without PW Decomposition

A brief review of a three-dimensional (3D) numerical method to solve few-nucleon bound and scattering states, without the standard partial-wave (PW) decomposition, is presented. The approach is applied to three-and four-nucleon bound states, by considering the solutions of the corresponding Faddeev-Yakubovsky (FY) integral equations in momentum space. Realistic spin-isospin dependent 3D and PW formalism are presented for the alpha particle and the triton binding energies, with numerical results given in both schemes for comparison.

3D calculation of Tucson-Melbourne 3NF effect in triton binding energy

As an application of the new realistic three-dimensional (3D) formalism reported recently for three-nucleon (3N) bound states, an attempt is made to study the effect of three-nucleon forces (3NFs) in triton binding energy in a non partial wave (PW) approach. The spin-isospin dependent 3N Faddeev integral equations with the inclusion of 3NFs, which are formulated as function of vector Jacobi momenta, specifically the magnitudes of the momenta and the angle between them, are solved with Bonn-B and Tucson-Melbourne NN and 3N forces in operator forms which can be incorporated in our 3D formalism. The comparison with numerical results in both, novel 3D and standard PW schemes, shows that non PW calculations avoid the very involved angular momentum algebra occurring for the permutations and transformations and it is more efficient and less cumbersome for considering the 3NF.

Alkyl Hydroxybenzoic Acid Derivatives that Inhibit HIV-1 Protease Dimerization

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Local order around rare earth ions during the devitrification of oxyfluoride glasses

Erbium L-3-edge extended x-ray absorption fine structure (EXAFS) measurements were performed on rare earth doped fluorosilicate and fluoroborate glasses and glass ceramics. The well known nucleating effects of erbium ions for the crystallization of cubic lead fluoride (based on x-ray diffraction measurements) and the fact that the rare earth ions are present in the crystalline phase (as indicated by Er3+ emission spectra) seem in contradiction with the present EXAFS analysis, which indicates a lack of medium range structural ordering around the Er3+ ions and suggests that the lead fluoride crystallization does not occur in the nearest neighbor distance of the rare earth ion. Molecular dynamics simulations of the devitrification process of a lead fluoride glass doped with Er3+ ions were performed, and results indicate that Er3+ ions lower the devitrification temperature of PbF2, in good agreement with the experimental results. The genuine role of Er3+ ions in the devitrification process of PbF2 has been investigated. Although Er3+ ions could indeed act as seeds for crystallization, as experiments suggest, molecular dynamics simulation results corroborate the experimental EXAFS observation that the devitrification does not occur at its nearest neighbor distance. (c) 2008 American Institute of Physics.

Clustering of rare earth in glasses, aluminum effect: experiments and modeling

Luminescent spectra of Eu3+-doped sol-gel glasses have been analyzed during the densification process and compared according to the presence or not of aluminum as a codoping ion. A transition temperature from hydrated to dehydroxyled environments has been found different for doped and codoped samples. However, only slight modifications have been displayed from luminescence measurements beyond this transition. To support the experimental analysis, molecular dynamics simulations have been performed to model the doped and codoped glass structures. Despite no evidence of rare earth clustering reduction due to aluminum has been found, the modeled structures have shown that the luminescent ions are mainly located in aluminum-rich domains. The synthesis of both experimental and numerical analyses has lead us to interpret the aluminum effect as responsible for differences in structure of the luminescent sites rather than for an effective dispersion of the rare earth ions. (C) 2004 Elsevier B.V. All rights reserved.

CRYSTALLINE FRAGMENTS IN GLASSES

The nature of tetrahedral molecular fragments is investigated in SiSe2 glasses using the molecular-dynamics method. The glass consists of both edge-sharing (ES) and corner-sharing tetrahedra. The ES tetrahedra are the building blocks of chain-like-molecular fragments. The two-edge-sharing tetrahedra are the nucleus, and corner-sharing configurations provide connecting hinges between fragments. Statistics of rings and fragments reveals that threefold and eightfold rings are most abundant, chainlike fragments that are typically 10-15 angstrom long occur mostly in eightfold rings, and the longest fragments occur in elevenfold rings.

Luminescence and non-radiative processes in lanthanide squarate hydrates

The luminescence properties of solid hydrated lanthanide squarates (Ln2(C4O4)3(H2O) x; x = 8 or 13;Ln3+ = Gd, La, Eu, Tb, Pr) are reported for temperatures down to 4.2K. The luminescence of the squarate group is observed for the Gd3+ and La3+ compounds at low temperatures (below 150K). The Pr3+ compound does not show any emission at all, not even at 4.2K. This is ascribed to the quenching of the Pr3+ emission by multiphonon relaxation and/or concentration quenching. The quantum efficiencies of the 5D0 emission of Eu3+ and of the 5D4 emission of Tb3+ in these squarate complexes are strikingly different. Whereas the Tb3+ emission shows a temperature independent quantum efficiency of 50% upon ligand excitation, the Eu3+ emission is strongly quenched, showing a temperature dependent quantum efficiency of 0.8% at 4.2K upon ligand excitation. This quenching is ascribed to the low energy position of the charge-transfer state of Eu3+ in these compounds.