Rosmarinic acid, a new snake venom phospholipase A(2) inhibitor from Cordia verbenacea (Boraginaceae): antiserum action potentiation and molecular interaction

Many plants are used in traditional medicine as active agents against various effects induced by snakebite. The methanolic extract from Cordia verbenacea (Cv) significantly inhibited paw edema induced by Bothrops jararacussu snake venom and by its main basic phospholipase A(2) homologs, namely bothropstoxins I and II (BthTXs). The active component was isolated by chromatography on Sephadex LH-20 and by RP-HPLC on a C18 column and identified as rosmarinic acid (Cv-RA). Rosmarinic acid is an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid [2-O-cafeoil-3-(3,4-di-hydroxy-phenyl)-R-lactic acid]. This is the first report of RA in the species C. verbenacea ('baleeira', 'whaler') and of its anti-inflammatory and antimyotoxic properties against snake venoms and isolated toxins. RA inhibited the edema and myotoxic activity induced by the basic PLA(2)s BthTX-I and BthTX-II. It was, however, less efficient to inhibit the PLA(2) activity of BthTX-II and, still less, the PLA(2) and edema-inducing activities of the acidic isoform BthA-1-PLA(2), from the same venom, showing therefore a higher inhibitory activity upon basic PLA(2)s. RA also inhibited most of the myotoxic and partially the edema-inducing effects of both basic PLA(2)s, thus reinforcing the idea of dissociation between the catalytic and pharmacological domains. The pure compound potentiated the ability of the commercial equine polyvalent antivenom in neutralizing lethal and myotoxic effects of the crude venom and of isolated PLA(2)s in experimental models. CD data presented here suggest that, after binding, no significant conformation changes occur either in the Cv-RA or in the target PLA(2). A possible model for the interaction of rosmarinic acid with Lys49-PLA(2) BthTX-I is proposed. (c) 2005 Elsevier Ltd. All rights reserved.

Elucidation of carbohydrate molecular interaction mechanism of recombinant and native ArtinM

The quartz crystal microbalance (QCM) technique has been applied for monitoring the biorecognition of ArtinM lectins at low horseradish peroxidase glycoprotein (HRP) concentrations, using a simple kinetic model based on Langmuir isotherm in previous work.18 The latter approach was consistent with the data at dilute conditions but it fails to explain the small differences existing in the jArtinM and rArtinM due to ligand binding concentration limit. Here we extend this analysis to differentiate sugar-binding event of recombinant (rArtinM) and native (jArtinM) ArtinM lectins beyond dilute conditions. Equivalently, functionalized quartz crystal microbalance with dissipation monitoring (QCM-D) was used as real-time label-free technique but structural-dependent kinetic features of the interaction were detailed by using combined analysis of mass and dissipation factor variation. The stated kinetic model not only was able to predict the diluted conditions but also allowed to differentiate ArtinM avidities. For instance, it was found that rArtinM avidity is higher than jArtinM avidity whereas their conformational flexibility is lower. Additionally, it was possible to monitor the hydration shell of the binding complex with ArtinM lectins under dynamic conditions. Such information is key in understanding and differentiating protein binding avidity, biological functionality, and kinetics. © 2013 American Chemical Society.

Studies on the interaction between humic substances and conducting polymers for sensor application

The interaction between humic substances and poly(o-ethoxyaniline) (POEA), a conducting polymer, was investigated for both solution and self-assembled films. The results have shown that the humic substances induce a doping of POEA by protonation, as indicated by UV-Vis and Raman spectroscopies. The atomic force microscopy (AFM) studies on the self-assembled films have shown that the average roughness of the polymer film has increased after exposing it to humic substances (fulvic and humic acids), consistent with the interaction between POEA and humic substances. However, this change in morphology is reversible by washing the films with water in agreement with the electrical data allowing using this system in sensor applications. Here, the sensor formed by an array of different sensing units was able to detect and distinguish humic substances in aqueous solution, as shown by multivariate analysis (principal component analysis). The motivation to detect humic substance comes due to its importance in terms of quality control of water or soil. ©2005 Sociedade Brasileira de Química.

Quercetin reduces Staphylococcus aureus interaction with neutrophils

Flavonoids, including quercetin, have been reported to modulate the ability of Staphylococcus aureus to adhere to host tissue without exhibiting direct antibacterial activity. In the present study, we evaluated the interaction of S. aureus pretreated with 40 μg/mL of quercetin with neutrophils to assay oxidative burst stimulation, using luminol-amplified chemiluminescence. S. aureus pre-incubated with subinhibitory concentration of quercetin induced significantly less light emission by neutrophils than did untreated bacteria. The results of the present study demonstrate that quercetin decreases S. aureus uptake by neutrophils.

Non-inclusion complexes between riboflavin and cyclodextrins

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

Synthesis, Infrared Spectroscopy and Crystal Structure Determination of a New Decavanadate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Spectroscopic and electrochemical characterization of polyaniline and a ruthenium complex, mer-[RuCl3(dppb)(py)], in the form of Langmuir-Blodgett films

Langmuir monolayers and Langmuir-Blodgett (LB) films have been produced from polyaniline and a biphosphinic ruthenium complex, referred to as Rupy. Strong, repulsive interaction between the two components led to a nonlinear change in area per molecule and surface potential with the concentration of Rupy in the mixed film. Molecular interaction was also denoted in the spectroscopic and electrochemical properties of the Y-type LB transferred films. The Raman spectra of mixed PANI-Rupy films indicated that the degree of oxidation of PANI increased linearly with the concentration of Ropy. With PANI being increasingly oxidized by presence of Rupy, the electroactivity of the mixed films decreased with the amount of Rupy, to become undetectable when the mixed LB film is 501 mol in Rupy. The presence of Rupy caused the electrical properties of the mixed LB films to be less sensitive to environmental changes. The electrical capacitance of a mixed film changed only by 15% when the sample was taken from vacuum to air, whereas the change was 215% for a pure PANI LB film.

Structure of tick anticoagulant peptide at 1.6 Å resolution complexed with bovine pancreatic trypsin inhibitor

The structure of tick anticoagulant peptide (TAP) has been determined by X-ray crystallography at t.6 Å resolution complexed with bovine pancreatic trypsin inhibitor (BPTI). The TAP-BPTI crystals are tetragonal, a = b = 46.87, c = 50.35 Å, space group P41, four complexes per unit cell. The TAP molecules are highly dipolar and form an intermolecular helical array along the c-axis with a diameter of about 45 Å. Individual TAP units interact in a head-to-tail fashion, the positive end of one molecule associating with the distal negative end of another, and vice versa. The BPTI molecules have a uniformly distributed positively charged surface that interacts extensively through 14 hydrogen bonds and two hydrogen bonded salt bridges with the helical groove around the helical TAP chains. Comparing the structure of TAP in TAP-BPTI with TAP bound to factor Xa(Xa) suggests a massive reorganization in the N-terminal tetrapeptide and the first disulfide loop of TAP (CyS5(T)- Cys 15(T)) upon binding to Xa. The Tyr1(T)OH atom of TAP moves 14.2 Å to interact with Asp189 of the S1 specificity site, Arg3(T)CZ moves 5.0 Å with the guanidinium group forming a cation-π-electron complex in the S4 subsite of Xa, while Lys7(T)NZ differs in position by 10.6 Å in TAP-BPTI and TAP-Xa, all of which indicates a different pre-Xa-bound conformation for the N- terminal of TAP in its native state. In contrast to TAP, the BPTI structure of TAP-BPTI is practically the same as all those of previously determined structures of BPTI, only arginine and lysine side-chain conformations showing significant differences.

Biophysical Characterization of Interactions Involving Importin-α during Nuclear Import

Proteins containing the classical nuclear localization sequences (NLSs) are imported into the nucleus by the importin-α/β heterodimer. Importin-α contains the NLS binding site, whereas importin-β mediates the translocation through the nuclear pore. We characterized the interactions involving importin-α during nuclear import using a combination of biophysical techniques (biosensor, crystallography, sedimentation equilibrium, electrophoresis, and circular dichroism). Importin-α is shown to exist in a monomeric autoinhibited state (association with NLSs undetectable by biosensor). Association with importin-β (stoichiometry, 1:1; K D = 1.1 × 10 -8 M) increases the affinity for NLSs; the importin-α/β complex binds representative monopartite NLS (simian virus 40 large T-antigen) and bipartite NLS (nucleoplasmin) with affinities (K D = 3.5 × 10 -8 M and 4.8 × 10 -8 M, respectively) comparable with those of a truncated importin-α lacking the autoinhibitory domain (T-antigen NLS, K D = 1.7 × 10 -8 M; nucleoplasmin NLS, K D = 1.4 × 10 -8 M). The autoinhibitory domain (as a separate peptide) binds the truncated importin-α, and the crystal structure of the complex resembles the structure of full-length importin-α. Our results support the model of regulation of nuclear import mediated by the intrasteric autoregulatory sequence of importin-α and provide a quantitative description of the binding and regulatory steps during nuclear import.

New CP violation in neutrino oscillations

Measurements of CP-violating observables in neutrino oscillation experiments have been studied in the literature as a way to determine the CP-violating phase in the mixing matrix for leptons. Here we show that such observables also probe new neutrino interactions in the production or detection processes. Genuine CP violation and fake CP violation due to matter effects are sensitive to the imaginary and real parts of new couplings. The dependence of the CP asymmetry on the source-detector distance is different from the standard one and, in particular, enhanced at short distances. We estimate that future neutrino factories will be able to probe in this way new interactions that are up to four orders of magnitude weaker than the weak interactions. We discuss the possible implications for models of new physics. ©2001 The American Physical Society.

Magnetic behavior of poly(3-methylthiophene): Metamagnetism and room-temperature weak ferromagnetism

A weak ferromagnetic phase is shown in pressed pellets of partially doped poly(3-methylthiophene) (P3MT) in the whole range from 1.8 to 300 K in magnetic measurements. Thermoremanence data have been used to estimate the suppression of this phase to be around 815 K. We also show that instead of the classical antiferromagnetism for the first-order interaction that gives weak ferromagnetism as a second-order effect, metamagnetic behavior is observed. X-band electron spin resonance (ESR) measurements and magnetization measurements allowed us to estimate that 8.1% of the total number of spins contributes to the weak ferromagnetism at room temperature. The doping level obtained from the ESR data is in good agreement with that estimated from electron dispersive spectroscopy measurements.

A simplified spectrophotometric method for routine analysis of saccharin in commercial noncaloric sweeteners

A simple, rapid, and sensitive spectrophotometric method for routine analysis of saccharin in commercial noncaloric sweeteners is proposed. This method is based on the reaction of saccharin with tetrachloro-p-benzoquinone (p-chloranil) accelerated by hydrogen peroxide and conducted in an ethanol:acetone (4:1) medium, producing a violet-red compound (γ max = 550 nm). Beer's law is obeyed in a concentration range of 2.05 × 10 -4 to 3.00 × 10 -3 M with an excellent correlation coefficient (r = 0.9998). The detection limit was 1.55 × 10 -5 M, and the effect of interferences on the spectrophotometric measurements was evaluated. The proposed procedure was applied successfully to the determination of saccharin in noncaloric sweeteners. Recoveries were within 99.2-104.3% with standard deviations ranging from to 0.5-1.6%. Results of the proposed method compare very favorably with those given by the high-performance liquid chromatography method recommended by the Food and Drug Administration.

Mapping deformed hyperbolic potentials into nondeformed ones

In this work we introduce a mapping between the so-called deformed hyperbolic potentials, which are presenting a continuous interest in the last few years, and the corresponding nondeformed ones. As a consequence, we conclude that these deformed potentials do not pertain to a new class of exactly solvable potentials, but to the same one of the corresponding nondeformed ones. Notwithstanding, we can reinterpret this type of deformation as a kind of symmetry of the nondeformed potentials. © 2005 Elsevier B.V. All rights reserved.

Biomolecular information, brain activity and cognitive functions

Molecular neurobiology has provided an explanation of mechanisms supporting mental functions as learning, memory, emotion and consciousness. However, an explanatory gap remains between two levels of description: molecular mechanisms determining cellular and tissue functions, and cognitive functions. In this paper we review molecular and cellular mechanisms that determine brain activity, and then hypothetize about their relation with cognition and consciousness. The brain is conceived of as a dynamic system that exchanges information with the whole body and the environment. Three explanatory hypotheses are presented, stating that: a) brain tissue function is coordinated by macromolecules controlling ion movements, b) structured (amplitude, frequency and phase-modulated) local field potentials generated by organized ionic movement embody cognitive information patterns, and c) conscious episodes are constructed by a large-scale mechanism that uses oscillatory synchrony to integrate local field patterns. © by São Paulo State University.