Direct observation of oxidative stress on the cell wall of Saccharomyces cerevisiae strains with atomic force microscopy

We imaged pores on the surface of the cell wall of three different industrial strains of Saccharomyces cerevisiae using atomic force microscopy. The pores could be enlarged using 10 mM diamide, an SH residue oxidant that attacks surface proteins. We found that two strains showed signs of oxidative damage via changes in density and diameter of the surface pores. We found that the German strain was resistant to diamide induced oxidative damage, even when the concentration of the oxidant was increased to 50 mM. The normal pore size found on the cell walls of American strains had diameters of about 200nm. Under conditions of oxidative stress the diameters changed to 400nm.This method may prove to be a useful rapid screening process (45-60 min) to determine which strains are oxidative resistant, as well as being able to screen for groups of yeast that are sensitive to oxidative stress. This rapid screening tool may have direct applications in molecular biology (transference of the genes to inside of living cells) and biotechnology (biotransformations reactions to produce chiral synthons in organic chemistry.

Semipreparative enantioseparation of methamidophos by HPLC-UV and preliminary in vitro study of butyrylcholinesterase inhibition

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

Reduction of enantioselectivity in the kinetic disposition and metabolism of verapamil in rats exposed to toluene

Toluene and verapamil are subject to extensive oxidative metabolism mediated by CYP enzymes, and their interaction can be stereoselective. In the present study we investigated the influence of toluene inhalation on the enantioselective kinetic disposition of verapamil and its metabolite, norverapamil, in rats. Male Wistar rats (n = 6 per group) received a single dose of racemic verapamil (10 mg/kg) orally at the fifth day of nose-only toluene or air (control group) inhalation for 6 h/day (25, 50, and 100 ppm). Serial blood samples were collected from the tail up to 6 h after verapamil administration. The plasma concentrations of verapamil and norverapamil enantiomers were analyzed by LC-MS/MS by using a Chiralpak AD column. Toluene inhalation did not influence the kinetic disposition of verapamil or norverapamil enantiomers (p > 0.05, Kruskal-Wallis test) in rats. The pharmacokinetics of verapamil was enantioselective in the control group, with a higher plasma proportion of the S-verapamil (AUC 250.8 versus 120.4 ng.h.mL(-1); p <= 0.05, Wilcoxon test) and S-norverapamil (AUC 72.3 versus 52.3 ng.h.mL(-1); p <= 0.05, Wilcoxon test). Nose-only exposure to toluene at 25, 50, or 100 ppm resulted in a lack of enantioselectivity for both verapamil and norverapamil. The study demonstrates the importance of the application of enantioselective methods in studies on the interaction between solvents and chiral drugs.

Biochemical, histopathological and clinical evaluation of delayed effects caused by methamidophos isoforms and TOCP in hens: Ameliorative effects using control of calcium homeostasis

This work evaluated the potential of the isoforms of methamidophos to cause organophosphorus-induced delayed neuropathy (OPIDN) in hens. In addition to inhibition of neuropathy target esterase (NTE) and acetylcholinesterase (AChE), calpain activation, spinal cord lesions and clinical signs were assessed. The isoforms (+)-, (+/-)- and (-)-methamidophos were administered at 50 mg/kg orally; tri-ortho-cresyl phosphate (TOCP) was administered (500 mg/kg, po) as positive control for delayed neuropathy. The TOCP hens showed greater than 80% and approximately 20% inhibition of NTE and AChE in hen brain, respectively. Among the isoforms of methamidophos, only the (+)-methamidophos was capable of inhibiting NTE activity (approximately 60%) with statistically significant difference compared to the control group. Calpain activity in brain increased by 40% in TOCP hens compared to the control group when measured 24h after dosing and remained high (18% over control) 21 days after dosing. Hens that received (+)-methamidophos had calpain activity 12% greater than controls. The histopathological findings and clinical signs corroborated the biochemical results that indicated the potential of the (+)-methamidophos to be the isoform responsible for OPIDN induction. Protection against OPIDN was examined using a treatment of 2 doses of nimodipine (1 mg/kg, i.m.) and one dose of calcium gluconate (5 mg/kg, iv.). The treatment decreased the effect of OPIDN-inducing TOCP and (+)-methamidophos on calpain activity, spinal cord lesions and clinical signs. (C) 2012 Elsevier B.V. All rights reserved.

Comparative in vitro study of the inhibition of human and hen esterases by methamidophos enantiomers

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

Structural aspects of the fermion-boson mapping in two-dimensional gauge and anomalous gauge theories with massive fermions

Using a synthesis of the functional integral and operator approaches we discuss the fermion-buson mapping and the role played by the Bose field algebra in the Hilbert space of two-dimensional gauge and anomalous gauge field theories with massive fermions. In QED, with quartic self-interaction among massive fermions, the use of an auxiliary vector field introduces a redundant Bose field algebra that should not be considered as an element of the intrinsic algebraic structure defining the model. In anomalous chiral QED, with massive fermions the effect of the chiral anomaly leads to the appearance in the mass operator of a spurious Bose field combination. This phase factor carries no fermion selection rule and the expected absence of Theta-vacuum in the anomalous model is displayed from the operator solution. Even in the anomalous model with massive Fermi fields, the introduction of the Wess-Zumino field replicates the theory, changing neither its algebraic content nor its physical content. (C) 2002 Elsevier B.V. (USA).

Multiflavor soldering

In two dimensions the simple addition of two chiral bosons of opposite chiralities does not lead to a full massless scalar field. Similarly, in three dimensions the addition of two Maxwell-Chern-Simons fields of opposite helicities +/- 1 will not produce a parity invariant Maxwell-Proca theory. An interference term between the opposite chiralities (helicities) states is required in order to obtain the expected result. The so-called soldering procedure provides the missing interference Lagrangian in both 2D and 3D cases. In two dimensions such interference term allows to fuse two chiral fermionic determinants into, a non-chiral one. In a recent work we have generalized this procedure by allowing the appearance of an extra parameter which takes two possible values and leads to two different soldered Lagrangians. Here we apply this generalized soldering in a bosonic theory which has appeared in a partial bosonization of the 3D gauged Thirring model with N flavors. The multiplicity of flavors allow new types of solderings and help us to understand the connection between different perturbative approaches to bosonization in 3D. In particular, we obtain an interference term which takes us from a multiflavor Niaxwell-Chern-Simons theory to a pair of self-dual and anti-self-dual theories when we combine together both fermionic determinants of +1/2 and -1/2 helicity fermions. An important role is played by a set of pure non-interacting Chern-Simons fields which amount to a normalization factor in the fermionic determinants and act like spectators in the original theory but play an active role in the soldering procedure. Our results suggest that the generalized soldering could be used to provide dual theories in both 2D and 3D cases. (c) 2007 Elsevier B.V. All rights reserved.

Restrictions over two-dimensional gauge models with Thirring-like interaction

Some years ago, it was shown how fermion self-interacting terms of the Thirring-type impact the usual structure of massless two-dimensional gauge theories [1]. In that work only the cases of pure vector and pure chiral gauge couplings have been considered and the corresponding Thirring term was also pure vector and pure chiral respectively, such that the vector ( or chiral) Schwinger model should not lose its chirality structure due to the addition of the quartic interaction term. Here we extend this analysis to a generalized vector and axial coupling both for the gauge interaction and the quartic fermionic interactions. The idea is to perform quantization without losing the original structure of the gauge coupling. In order to do that we make use of an arbitrariness in the definition of the Thirring-like interaction.

New approaches in W gravities

We devote effort to studying some nonlinear actions, characteristic of W theories, in the framework of the soldering formalism. We disclose interesting new results concerning the embedding of the original chiral W particles in different metrical spaces in the final soldered action; i.e., the metric is modified by the soldering interference process. The results are presented in a weak field approximation for the W-N case when Ngreater than or equal to3 and also in an exact way for W-2. We promote a generalization of the interference phenomenon to W-N theories of different chiralities and show that the geometrical features introduced can yield a new understanding of the interference formalism in quantum field theories.

Monoamine oxidase inhibitory activities of indolylalkaloid toxins from the venom of the colonial spider Parawixia bistriata: Functional characterization of PwTX-I

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

Rapid configuration analysis of the solenopsins

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Theoretical study of omeprazole behavior: Racemization barrier and decomposition reaction

omeprazole is a substituted benzimidazole which suppresses gastric-acid secretion by means of H+, K+-ATPase inhibition. It is an optically active drug with the sulfur of the sulfoxide being the chiral center. This pro-drug can be easily converted into its respective sulfenamide at low pH. In this work, omeprazole has been studied in relation to racemization barrier and decomposition reaction. Quantum chemistry coupled to PCA chemometric method were used to find all minimum energy structures. Conformational analysis and calculation of racemization barriers were carried out by PM3 semiempirical method (Gaussian 98). The average racemization energy barrier for all minimum energy structures (43.56 kcal mol(-1)) can be related to the velocity constant in Eyring's equation. The enormous half-life time at 100 degrees C (9.04 x 10(4) years) indicates that the process cannot be observed in human time scale. on the other hand, the difference of free energy change (Delta(Delta G) = -266.78 kcal mol(-1)) for the decomposition reaction shows that the process is favorable to the sulfenamide formation. The highly negative Delta(Delta G) obtained for the decomposition reaction shows that this process is extremely exothermic. This result explains why omeprazole decomposes and does not racemize. (C) 2008 Wiley Periodicals, Inc.

Anomalous quartic gauge boson couplings at hadron colliders

We analyze the potential of the Fermilab Tevatron and CERN Large Hadron Collider (LHC) to study anomalous quartic vector-boson interactions gamma gamma ZZ and gammaW(+)W(-). Working in the framework of SU(2)(L) circle times U(1)(Y) chiral Lagrangians, we study the production of photon pairs accompanied by l(+) l(-), l(+/-) v, and jet pairs to impose bounds on these new couplings, taking into account the unitarity constraints. We compare our findings with the indirect limits coming from precision electroweak measurements as well as with presently available direct searches at CERN LEPII. We show that the Tevatron run II can provide limits on these quartic limits which are of the same order of magnitude as the existing bounds from LEPII searches. LHC will be able to tighten considerably the direct constraints on these possible new interactions, leading to more stringent limits than the presently available indirect ones.

Naturally light invisible axion in models with large local discrete symmetries

We show that by introducing appropriate local Z(N)(Ngreater than or equal to13) symmetries in electroweak models it is possible to implement an automatic Peccei-Quinn symmetry, at the same time keeping the axion protected against gravitational effects. Although we consider here only an extension of the standard model and a particular 3-3-1 model, the strategy can be used in any kind of electroweak model. An interesting feature of this 3-3-1 model is that if we add (i) right-handed neutrinos, (ii) the conservation of the total lepton number, and (iii) a Z(2) symmetry, the Z(13) and the chiral Peccei-Quinn U(1)P-Q symmetries are both accidental symmetries in the sense that they are not imposed on the Lagrangian but are just a consequence of the particle content of the model, its gauge invariance, renormalizability, and Lorentz invariance. In addition, this model has no domain wall problem.

SU(2,R)(q) symmetries of Non-Abelian Toda theories

The classical and quantum algebras of a class of conformal NA-Toda models are studied. It is shown that the SL(2,R)(q) Poisson brackets algebra generated by certain chiral and antichiral charges of the nonlocal currents and the global U(1) charge appears as an algebra of the symmetries of these models. (C) 1998 Elsevier B.V. B.V. All rights reserved.