Cell cycle arrest evidence, parasiticidal and bactericidal properties induced by L-amino acid oxidase from Bothrops atrox snake venom

The present article describes an L-amino acid oxidase from Bothrops atrox snake venom as with antiprotozoal activities in Trypanosoma cruzi and in different species of Leishmania (Leishmania braziliensis, Leishmania donovani and Leishmania major). Leishmanicidal effects were inhibited by catalase, suggesting that they are mediated by H(2)O(2) production. Leishmania spp. cause a spectrum of diseases, ranging from self-healing ulcers to disseminated and often fatal infections, depending on the species involved and the host`s immune response. BatroxLAAO also displays bactericidal activity against both Gram-positive and Gram-negative bacteria. The apoptosis induced by BatroxLAAO on HL-60 cell lines and PBMC cells was determined by morphological cell evaluation using a mix of fluorescent dyes. As revealed by flow cytometry analysis, suppression of cell proliferation with BatroxLAAO was accompanied by the significant accumulation of cells in the G0/G1 phase boundary in HL-60 cells. BatroxLAAO at 25 mu g/mL and 50 mu g/mL blocked G0-G1 transition, resulting in G0/G1 phase cell cycle arrest, thereby delaying the progression of cells through S and G2/M phase in HL-60 cells. This was shown by an accentuated decrease in the proportion of cells in S phase, and the almost absence of G2/M phase cell population. BatroxLAAO is an interesting enzyme that provides a better understanding of the ophidian envenomation mechanism, and has biotechnological potential as a model for therapeutic agents. (C) 2011 Elsevier Masson SAS. All rights reserved.

Snake Venom L-Amino Acid Oxidases: Some Consideration About their Functional Characterization

Snake Venom L-amino acid oxidases (LAAOs E.C. 1.4.3.2) are flavoenzymes broadly found in various snake venom compositions. LAAOs have become an attractive subject for molecular biology, biochemistry, physiology and medicine due to their actions on various cells and biological effects on platelets, apoptosis, hemorrhage and others. In this review we try to summarize some of these reports, with special emphasis on apoptosis, anti-protozoa, bactericidal and anti-viral activities.

Structural and functional properties of Bp-LAAO, a new L-amino acid oxidase isolated from Bothrops pauloensis snake venom

An L-amino acid oxidase (Bp-LAAO) from Bothrops pauloensis snake venom was highly purified using sequential chromatography steps on CM-Sepharose, Phenyl-Sepharose CL4B, Benzamidine Sepharose and C18 reverse-phase HPLC. Purified Bp-LAAO showed to be a homodimeric acidic glycoprotein with molecular weight around 65 kDa under reducing conditions in SDS-PAGE. The best substrates for Bp-LAAO were L-Met, L-Leu, L-Phe and L-Ile and the enzyme showed a strong reduction of its catalytic activity upon L-Met and L-Phe substrates at extreme temperatures. Bp-LAAO showed leishmanicidal, antitumoral and bactericidal activities dose dependently. Bp-LAAO induced platelet aggregation in platelet-rich plasma and this activity was inhibited by catalase. Bp-LAAC-cDNA of 1548 bp codified a mature protein with 516 amino acid residues corresponding to a theoretical isoelectric point and molecular weight of 6.3 and 58 kDa, respectively. Additionally, structural and phylogenetic studies identified residues under positive selection and their probable location in Elp-LAAO and other snake venom LAAOs (svLAAOs). Structural and functional investigations of these enzymes can contribute to the advancement of toxinology and to the elaboration of novel therapeutic agents. (C) 2009 Elsevier Masson SAS. All rights reserved.

Molecular cloning and biochemical characterization of a myotoxin inhibitor from Bothrops alternatus snake plasma

Phospholipases A(2) (PLA(2)s) are important components of Bothrops snake venoms, that can induce several effects on envenomations such as myotoxicity, inhibition or induction of platelet aggregation and edema. It is known that venomous and non-venomous snakes present PLA(2) inhibitory proteins (PLIs) in their blood plasma. An inhibitory protein that neutralizes the enzymatic and toxic activities of several PLA2s from Bothrops venoms was isolated from Bothrops alternatus snake plasma by affinity chromatography using the immobilized myotoxin BthTX-I on CNBr-activated Sepharose. Biochemical characterization of this inhibitory protein, denominated alpha BaltMIP, showed it to be a glycoprotein with Mr of similar to 24,000 for the monomeric subunit. CD spectra of the PLA(2)/inhibitor complexes are considerably different from those corresponding to the individual proteins and data deconvolution suggests that the complexes had a relative gain of helical structure elements in comparison to the individual protomers, which may indicate a more compact structure upon complexation. Theoretical and experimental structural studies performed in order to obtain insights into the structural features of aBaltMIP indicated that this molecule may potentially trimerize in solution, thus strengthening the hypothesis previously raised by other authors about snake PLIs oligomerization. (C) 2010 Elsevier Masson SAS. All rights reserved.

The effects of pH and ionic strength on topical delivery of a negatively charged porphyrin (TPPS(4))

Meso-tetra-[4-sulfonatophenyl]-porphyrin (TPPS(4)) is a charged porphyrin derivate used in photodynamic therapy (PDT) by parenteral administration. This study means to investigate potential enhancement for its topical delivery by determining the TPPS(4) dependence on the environmental characteristics and applying iontophoresis. In order to accomplish this task, cathodal and anodal iontophoresis as well as passive delivery of the drug were studied in vitro and in vivo in function of its concentration, pH and ionic strength. A reduction in drug concentration as well as the NaCl elimination from donor formulation at pH 2.0 increased TPPS(4) passive permeation through the skin in vitro. Iontophoresis improved TPPS(4) delivery across the skin when applied in solutions containing NaCl at pH 2.0, regardless electrode polarity. However, at pH 7.4, the amount of TPPS(4) permeated by iontophoresis was not different from that one permeated after passive experiments from a solution containing NaCl. Despite the fact that iontophoresis did not improve TPPS(4) transdermal delivery at this specific condition, in vivo experiments showed that 10 min of iontophoresis quickly and homogeneously delivered TPPS(4) to deeper skin layers when compared to passive administration, which is an important condition for topical treatment of skin tumors with PDT. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association.

Teacher strikes in Brazil and its representations: ""orderly disciplined class"" and ""education workers"" (Sao Paulo, 1963-1979)

This article analyses the teacher strikes that took place in the state of Sao Paulo ( Brazil). These strikes produced new representations of the profession and gave a particular visibility to its interest aggregation processes. These same strikes appeared as major incentives for the organisation of teachers in Brazil. The October 1963 strike - about six months before the military coup of 1964 - was the first to mobilise the whole of the teaching profession of the Sao Paulo state: primary and secondary education, public and private schools were all involved. The two other strikes, organised by teachers in the public schools in 1978 and 1979, took place under the dictatorship. As such, they had a particular significance in the process of recovering civil liberties in the final stages of the military regime in the 1980s. This article is based on an analysis of the front-page covering of these teacher strikes by the two major journals of the state, O Estado de S. Paulo and Folha de S. Paulo. With Chartier`s concept collective representations in mind, this approach allows us to grasp how large-circulation journals diffuse images of the profession and its organisational configurations. These press pictures are analysed by dint of the analytical frame Roland Barthes advanced in the 1960s, i.e. by reading their denoted, connoted and symbolic messages.

Determination of coalescence kernels for high-shear granulation using DEM simulations

Discrete element method (DEM) modeling is used in parallel with a model for coalescence of deformable surface wet granules. This produces a method capable of predicting both collision rates and coalescence efficiencies for use in derivation of an overall coalescence kernel. These coalescence kernels can then be used in computationally efficient meso-scale models such as population balance equation (PBE) models. A soft-sphere DEM model using periodic boundary conditions and a unique boxing scheme was utilized to simulate particle flow inside a high-shear mixer. Analysis of the simulation results provided collision frequency, aggregation frequency, kinetic energy, coalescence efficiency and compaction rates for the granulation process. This information can be used to bridge the gap in multi-scale modeling of granulation processes between the micro-scale DEM/coalescence modeling approach and a meso-scale PBE modeling approach.

Ladder operator for the one-dimensional Hubbard model

The one-dimensional Hubbard model is integrable in the sense that it has an infinite family of conserved currents. We explicitly construct a ladder operator which can be used to iteratively generate all of the conserved current operators. This construction is different from that used for Lorentz invariant systems such as the Heisenberg model. The Hubbard model is not Lorentz invariant, due to the separation of spin and charge excitations. The ladder operator is obtained by a very general formalism which is applicable to any model that can be derived from a solution of the Yang-Baxter equation.

Integrability of the Russian doll BCS model

We show that integrability of the BCS model extends beyond Richardson's model (where all Cooper pair scatterings have equal coupling) to that of the Russian doll BCS model for which the couplings have a particular phase dependence that breaks time-reversal symmetry. This model is shown to be integrable using the quantum inverse scattering method, and the exact solution is obtained by means of the algebraic Bethe ansatz. The inverse problem of expressing local operators in terms of the global operators of the monodromy matrix is solved. This result is used to find a determinant formulation of a correlation function for fluctuations in the Cooper pair occupation numbers. These results are used to undertake exact numerical analysis for small systems at half-filling.

Quantum mechanics as an approximation to classical mechanics in Hilbert space

Classical mechanics is formulated in complex Hilbert space with the introduction of a commutative product of operators, an antisymmetric bracket and a quasidensity operator that is not positive definite. These are analogues of the star product, the Moyal bracket, and the Wigner function in the phase space formulation of quantum mechanics. Quantum mechanics is then viewed as a limiting form of classical mechanics, as Planck's constant approaches zero, rather than the other way around. The forms of semiquantum approximations to classical mechanics, analogous to semiclassical approximations to quantum mechanics, are indicated.

Quantum symmetries and the Weyl–Wigner product of group representations

In the usual formulation of quantum mechanics, groups of automorphisms of quantum states have ray representations by unitary and antiunitary operators on complex Hilbert space, in accordance with Wigner's theorem. In the phase-space formulation, they have real, true unitary representations in the space of square-integrable functions on phase space. Each such phase-space representation is a Weyl–Wigner product of the corresponding Hilbert space representation with its contragredient, and these can be recovered by 'factorizing' the Weyl–Wigner product. However, not every real, unitary representation on phase space corresponds to a group of automorphisms, so not every such representation is in the form of a Weyl–Wigner product and can be factorized. The conditions under which this is possible are examined. Examples are presented.

A unified and complete construction of all finite dimensional irreducible representations of gl(2|2)

Representations of the non-semisimple superalgebra gl(2/2) in the standard basis are investigated by means of the vector coherent state method and boson-fermion realization. All finite-dimensional irreducible typical and atypical representations and lowest weight (indecomposable) Kac modules of gl(2/2) are constructed explicity through the explicit construction of all gl(2) circle plus gl(2) particle states (multiplets) in terms of boson and fermion creation operators in the super-Fock space. This gives a unified and complete treatment of finite-dimensional representations of gl(2/2) in explicit form, essential for the construction of primary fields of the corresponding current superalgebra at arbitrary level.

Superconducting Correlations in Metallic Nanoparticles: Exact Solution of the BCS Model by the Algebraic Bethe Ansatz

Superconducting pairing of electrons in nanoscale metallic particles with discrete energy levels and a fixed number of electrons is described by the reduced Bardeen, Cooper, and Schrieffer model Hamiltonian. We show that this model is integrable by the algebraic Bethe ansatz. The eigenstates, spectrum, conserved operators, integrals of motion, and norms of wave functions are obtained. Furthermore, the quantum inverse problem is solved, meaning that form factors and correlation functions can be explicitly evaluated. Closed form expressions are given for the form factors and correlation functions that describe superconducting pairing.

Fast evolution strategies

Evolution strategies are a class of general optimisation algorithms which are applicable to functions that are multimodal, nondifferentiable, or even discontinuous. Although recombination operators have been introduced into evolution strategies, the primary search operator is still mutation. Classical evolution strategies rely on Gaussian mutations. A new mutation operator based on the Cauchy distribution is proposed in this paper. It is shown empirically that the new evolution strategy based on Cauchy mutation outperforms the classical evolution strategy on most of the 23 benchmark problems tested in this paper. The paper also shows empirically that changing the order of mutating the objective variables and mutating the strategy parameters does not alter the previous conclusion significantly, and that Cauchy mutations with different scaling parameters still outperform the Gaussian mutation with self-adaptation. However, the advantage of Cauchy mutations disappears when recombination is used in evolution strategies. It is argued that the search step size plays an important role in determining evolution strategies' performance. The large step size of recombination plays a similar role as Cauchy mutation.

Matrix elements of U(2n) generators in a multishell spin-orbit basis. II. The two-shell nonzero shift ACCs and U(2n) generator MEs

This is the second in a series of articles whose ultimate goal is the evaluation of the matrix elements (MEs) of the U(2n) generators in a multishell spin-orbit basis. This extends the existing unitary group approach to spin-dependent configuration interaction (CI) and many-body perturbation theory calculations on molecules to systems where there is a natural partitioning of the electronic orbital space. As a necessary preliminary to obtaining the U(2n) generator MEs in a multishell spin-orbit basis, we must obtain a complete set of adjoint coupling coefficients for the two-shell composite Gelfand-Paldus basis. The zero-shift coefficients were obtained in the first article of the series. in this article, we evaluate the nonzero shift adjoint coupling coefficients for the two-shell composite Gelfand-Paldus basis. We then demonstrate that the one-shell versions of these coefficients may be obtained by taking the Gelfand-Tsetlin limit of the two-shell formulas. These coefficients,together with the zero-shift types, then enable us to write down formulas for the U(2n) generator matrix elements in a two-shell spin-orbit basis. Ultimately, the results of the series may be used to determine the many-electron density matrices for a partitioned system. (C) 1998 John Wiley & Sons, Inc.