NIELSEN COINCIDENCE THEORY OF FIBRE-PRESERVING MAPS AND DOLD`S FIXED POINT INDEX

Let M -> B, N -> B be fibrations and f(1), f(2): M -> N be a pair of fibre-preserving maps. Using normal bordism techniques we define an invariant which is an obstruction to deforming the pair f(1), f(2) over B to a coincidence free pair of maps. In the special case where the two fibrations axe the same and one of the maps is the identity, a weak version of our omega-invariant turns out to equal Dold`s fixed point index of fibre-preserving maps. The concepts of Reidemeister classes and Nielsen coincidence classes over B are developed. As an illustration we compute e.g. the minimal number of coincidence components for all homotopy classes of maps between S(1)-bundles over S(1) as well as their Nielsen and Reidemeister numbers.

Structure and Mode of Action of Microplusin, a Copper II-chelating Antimicrobial Peptide from the Cattle Tick Rhipicephalus (Boophilus) microplus

Microplusin, a Rhipicephalus (Boophilus) microplus antimicrobial peptide (AMP) is the first fully characterized member of a new family of cysteine-rich AMPs with histidine-rich regions at the N and C termini. In the tick, microplusin belongs to the arsenal of innate defense molecules active against bacteria and fungi. Here we describe the NMR solution structure of microplusin and demonstrate that the protein binds copper II and iron II. Structured as a single alpha-helical globular domain, microplusin consists of five alpha-helices: alpha 1 (residues Gly-9 to Arg-21), alpha 2 (residues Glu-27 to Asn-40), alpha 3 (residues Arg-44 to Thr-54), alpha 4 (residues Leu-57 to Tyr-64), and alpha 5 (residues Asn-67 to Cys-80). The N and C termini are disordered. This structure is unlike any other AMP structures described to date. We also used NMR spectroscopy to map the copper binding region on microplusin. Finally, using the Gram-positive bacteria Micrococcus luteus as a model, we studied of mode of action of microplusin. Microplusin has a bacteriostatic effect and does not permeabilize the bacterial membrane. Because microplusin binds metals, we tested whether this was related to its antimicrobial activity. We found that the bacteriostatic effect of microplusin was fully reversed by supplementation of culture media with copper II but not iron II. We also demonstrated that microplusin affects M. luteus respiration, a copper-dependent process. Thus, we conclude that the antibacterial effect of microplusin is due to its ability to bind and sequester copper II.

Selectivity in the mechanism of action of antimicrobial mastoparan peptide Polybia-MP1

Many potent antimicrobial peptides also present hemolytic activity, an undesired collateral effect for the therapeutic application. Unlike other mastoparan peptides, Polybia-MP1 (IDWKKLLDAAKQIL), obtained from the venom of the social wasp Polybia paulista, is highly selective of bacterial cells. The study of its mechanism of action demonstrated that it permeates vesicles at a greater rate of leakage on the anionic over the zwitterionic, impaired by the presence of cholesterol or cardiolipin; its lytic activity is characterized by a threshold peptide to lipid molar ratio that depends on the phospholipid composition of the vesicles. At these particular threshold concentrations, the apparent average pore number is distinctive between anionic and zwitterionic vesicles, suggesting that pores are similarly formed depending on the ionic character of the bilayer. To prospect the molecular reasons for the strengthened selectivity in Polybia-MP1 and its absence in Mastoparan-X, MD simulations were carried out. Both peptides presented amphipathic alpha-helical structures, as previously observed in Circular Dichroism spectra, with important differences in the extension and stability of the helix; their backbone solvation analysis also indicate a different profile, suggesting that the selectivity of Polybia-MP1 is a consequence of the distribution of the charged and polar residues along the peptide helix, and on how the solvent molecules orient themselves according to these electrostatic interactions. We suggest that the lack of hemolytic activity of Polybia-MP1 is due to the presence and position of Asp residues that enable the equilibrium of electrostatic interactions and favor the preference for the more hydrophilic environment.

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.

Contributions to the theory of magnetorotational instability and waves in a rotating plasma

The one-fluid magnetohydrodynamic (MHD) theory of magnetorotational instability (MRI) in an ideal plasma is presented. The theory predicts the possibility of MRI for arbitrary 0, where 0 is the ratio of the plasma pressure to the magnetic field pressure. The kinetic theory of MRI in a collisionless plasma is developed. It is demonstrated that as in the ideal MHD, MRI can occur in such a plasma for arbitrary P. The mechanism of MRI is discussed; it is shown that the instability appears because of a perturbed parallel electric field. The electrodynamic description of MRI is formulated under the assumption that the dispersion relation is expressed in terms of the permittivity tensor; general properties of this tensor are analyzed. It is shown to be separated into the nonrotational and rotational parts. With this in mind, the first step for incorporation of MRI into the general theory of plasma instabilities is taken. The rotation effects on Alfven waves are considered.

Disruption of Saccharomyces cerevisiae by Plantaricin 149 and investigation of its mechanism of action with biomembrane model systems

The action of a synthetic antimicrobial peptide analog of Plantaricin 149 (Pln149a) against Saccharomyces cerevisiae and its interaction with biomembrane model systems were investigated. Pln149a was shown to inhibit S. cerevisiae growth by more than 80% in YPD medium, causing morphological changes in the yeast wall and remaining active and resistant to the yeast proteases even after 24 h of incubation. Different membrane model systems and carbohydrates were employed to better describe the Pln149a interaction with cellular components using circular dichroism and fluorescence spectroscopies, adsorption kinetics and surface elasticity in Langmuir monolayers. These assays showed that Pln149a does not interact with either mono/polysaccharides or zwitterionic LUVs, but is strongly adsorbed to and incorporated into negatively charged surfaces, causing a conformational change in its secondary structure from random-coil to helix upon adsorption. From the concurrent analysis of Pln149a adsorption kinetics and dilatational surface elasticity data, we determined that 2.5 mu M is the critical concentration at which Pln149a will disrupt a negative DPPG monolayer. Furthermore, Pln149a exhibited a carpet-like mechanism of action, in which the peptide initially binds to the membrane, covering its surface and acquiring a helical structure that remains associated to the negatively charged phospholipids. After this electrostatic interaction, another peptide region causes a strain in the membrane, promoting its disruption. (C) 2009 Elsevier B.V. All rights reserved.

A new nitrosyl ruthenium complex: Synthesis, chemical characterization, in vitro and in vivo antitumor activities and probable mechanism of action

This study describes the synthesis of a new ruthenium nitrosyl complex with the formula [RuCl(2)NO(BPA)] [BPA = (2-hydroxybenzyl)(2-methylpyridyl)amine ion], which was synthesized and characterized by spectroscopy, cyclic voltammetry, X-ray crystallography, and theoretical calculation data. The biological studies of this complex included in vitro cytotoxic assays, which revealed its activity against two different tumor cell lines (HeLa and Tm5), with efficacy comparable to that of cisplatin, a metal-based drug that is administered in clinical treatment. The in vivo studies showed that [RuCl2NO(BPA)] is effective in reducing tumor mass. Also, our results suggest that the mechanism of action of [RuCl(2)NO(BPA)] includes binding to DNA, causing fragmentation of this biological molecule, which leads to apoptosis. (C) 2011 Elsevier Masson SAS. All rights reserved.

ALGEBRAIC AND GEOMETRIC THEORY OF THE TOPOLOGICAL RING OF COLOMBEAU GENERALIZED FUNCTIONS

We continue the investigation of the algebraic and topological structure of the algebra of Colombeau generalized functions with the aim of building up the algebraic basis for the theory of these functions. This was started in a previous work of Aragona and Juriaans, where the algebraic and topological structure of the Colombeau generalized numbers were studied. Here, among other important things, we determine completely the minimal primes of (K) over bar and introduce several invariants of the ideals of 9(Q). The main tools we use are the algebraic results obtained by Aragona and Juriaans and the theory of differential calculus on generalized manifolds developed by Aragona and co-workers. The main achievement of the differential calculus is that all classical objects, such as distributions, become Cl-functions. Our purpose is to build an independent and intrinsic theory for Colombeau generalized functions and place them in a wider context.

Lie algebra methods for the applications to the statistical theory of turbulence

Approximate Lie symmetries of the Navier-Stokes equations are used for the applications to scaling phenomenon arising in turbulence. In particular, we show that the Lie symmetries of the Euler equations are inherited by the Navier-Stokes equations in the form of approximate symmetries that allows to involve the Reynolds number dependence into scaling laws. Moreover, the optimal systems of all finite-dimensional Lie subalgebras of the approximate symmetry transformations of the Navier-Stokes are constructed. We show how the scaling groups obtained can be used to introduce the Reynolds number dependence into scaling laws explicitly for stationary parallel turbulent shear flows. This is demonstrated in the framework of a new approach to derive scaling laws based on symmetry analysis [11]-[13].

Molecular modeling and UV-vis spectroscopic studies on the mechanism of action of reversed chloroquine (RCQ)

Reversed chloroquine (RCQ) is a multiple ligand compound active against chloroquine-sensitive and resistant falciparum malaria. It is composed by a 4-aminoquinoline moiety (like that present in chloroquine (CQ)) joined to imipramine (IMP), a modulating agent that also showed intrinsic antiplasmodial activity against Brazilian Plasmodium falciparum isolates resistant to CQ. Molecular modeling and ultraviolet-visible spectroscopy (UV-vis) studies strongly suggest that the interaction between RCQ and heme is predominant through the quinoline moiety in a mechanism of action similar to that observed for CQ. (C) 2010 Elsevier Ltd. All rights reserved.

Investigating the Nature of Noble Gas-Copper Bonds by the Quantum Theory of Atoms in Molecules

We investigated noble gas copper bonds in linear complexes represented by the NgCuX general formula in which Ng and X stand for a noble gas (neon, argon, krypton, or xenon) and a halogen (fluorine, chlorine or bromine), respectively, by coupled cluster methods and modified cc-pVQZ basis sets. The quantum theory of atoms in molecules (QTAIM) shows a linear relation between the dissociation energy or noble gas-copper bonds and the amount of electronic charge transferred mainly from the noble gas to copper during complexation. Large changes in the QTAIM quadrupole moments of copper and noble gases resulting from this bonding and a comparison between NgCuX and NgNaCl systems indicate that these noble gas-copper bonds should be better interpreted as predominantly covalent. Finally, QTAIM atomic dipoles of noble gases in NgNaCl systems agree satisfactorily with atomic dipoles given by a simple model for these NgNa van der Waals bonds.