Apolipoprotein E genotype is related to nitric oxide production in platelets

The presence of the, 4 allele of apolipoprotein E (APOE) is considered a risk factor for sporadic Alzheimer`s disease (AD). Our recent data demonstrated that the systemic modulation of oxidative stress in platelets and erythrocytes is disrupted in aging and AD. In this study, the relationship between APOE genotype and oxidative stress markers, both in AD patients and controls, was evaluated. The AD group showed an increase in the content of thiobarbituric acid-reactive substances (TBARS) and in the activities of nitric oxide synthase (NOS) and Na, K-ATPase, when compared to controls. Both groups had a similar cGMP content and superoxide dismutase activity. APOE epsilon 4 allele carriers showed higher NOS activity than non-carriers. These results suggest a possible influence of APOE genotype on nitric oxide (NO) production that might enhance the effects of age-related specific factor(s) associated with neurodegenerative disorders. Copyright (C) 2008 John Wiley & Sons, Ltd.

Interaction with calmodulin is important for the secretion of thimet oligopeptidase following stimulation

Thimet oligopeptidase (EC 3.4.24.15; EP24.15) was originally described as a neuropeptide-metabolizing enzyme, highly expressed in the brain, kidneys and neuroendocrine tissue. EP24.15 lacks a typical signal peptide sequence for entry into the secretory pathway and is secreted by cells via an unconventional and unknown mechanism. In this study, we identified a novel calcium-dependent interaction between EP24.15 and calmodulin, which is important for the stimulated, but not constitutive, secretion of EP24.15. We demonstrated that, in vitro, EP24.15 and calmodulin physically interact only in the presence of Ca(2+), with an estimated K(d) value of 0.52 mu m. Confocal microscopy confirmed that EP24.15 colocalizes with calmodulin in the cytosol of resting HEK293 cells. This colocalization markedly increases when cells are treated with either the calcium ionophore A23187 or the protein kinase A activator forskolin. Overexpression of calmodulin in HEK293 cells is sufficient to greatly increase the A23187-stimulated secretion of EP24.15, which can be inhibited by the calmodulin inhibitor calmidazolium. The specific inhibition of protein kinase A with KT5720 reduces the A23187-stimulated secretion of EP24.15 and inhibits the synergistic effects of forskolin with A23187. Treatment with calmidazolium and KT5720 nearly abolishes the stimulatory effects of A23187 on EP24.15 secretion. Together, these data suggest that the interaction between EP24.15 and calmodulin is regulated within cells and is important for the stimulated secretion of EP24.15 from HEK293 cells.

Shiga toxin-producing Escherichia coli and atypical enteropathogenic Escherichia coli strains isolated from healthy sheep of different populations in Sao Paulo, Brazil

Aims: Sheep are important carriers of Shiga toxin-producing Escherichia coli (STEC) in several countries. However, there are a few reports about ovine STEC in American continent. Methods and Results: About 86 E. coli strains previously isolated from 172 healthy sheep from different farms were studied. PCR was used for detection of stx(1), stx(2), eae, ehxA and saa genes and for the identification of intimin subtypes. Restriction fragment length polymorphism (RFLP)-PCR was performed to investigate the variants of stx(1) and stx(2), and the flagellar antigen (fliC) genes in nonmotile isolates. Five isolates were eae(+) and stx(-), and belonged to serotypes O128:H2/beta-intimin (2), O145:H2/gamma, O153:H7/beta and O178:H7/epsilon. Eighty-one STEC isolates were recovered, and the stx genotypes identified were stx(1c)stx(2d-O118) (46.9%), stx(1c) (27.2%), stx(2d-O118) (23.4%), and stx(1c)stx(2dOX3a) (2.5%). Pulsed-field gel electrophoresis (PFGE) revealed 27 profiles among 53 STEC and atypical enteropathogenic Escherichia coli (EPEC) isolates. Conclusions: This study demonstrated that healthy sheep in Sao Paulo, Brazil, can be carriers of potential human pathogenic STEC and atypical EPEC. Significance and Impact of the Study: As some of the STEC serotypes presently found have been involved with haemolytic uraemic syndrome (HUS) in other countries, the important role of sheep as sources of STEC infection in our settings should not be disregarded.

Sialic Acid Residues Are Essential for the Anaphylactic Activity of Murine IgG1 Antibodies

Glycosylation of the Ab molecule is essential for maintaining the functional structure of Fc region and consequently for Ab-mediated effector functions, such as binding to cells or complement system activation. Alterations in the composition of the sugar moiety can dramatically influence Ab activity; however, it is not completely clear how differences in the N-linked oligosaccharide structure impact the biological function of Abs. We have described that murine IgG1 Abs can be separated according to their ability to elicit in vivo anaphylaxis in a fraction of anaphylactic and other of non-anaphylactic molecules. Furthermore, we showed that the N-linked oligosaccharide chain is essential for the structural conformation of the anaphylactic IgG1, the binding to Fc gamma RIII on mast cells, and, consequently, for the ability to mediate anaphylactic reactions. In this study, we evaluated the contribution of individual sugar residues to this biological function. Differences in the glycan composition were observed when we analyzed oligosaccharide chains from anaphylactic or non-anaphylactic IgG1, mainly the presence of more sialic acid and fucose residues in anaphylactic molecules. Interestingly, the enzymatic removal of terminal sialic acid residues in anaphylactic IgG1 resulted in loss of the ability to trigger mast cell degranulation and in vivo anaphylactic reaction, similarly to the deglycosylated IgG1 Ab. In contrast, fucose removal did not affect the anaphylactic function. Therefore, we demonstrated that the ability of murine IgG1 Abs to mediate anaphylaxis is directly dependent on the amount of sialic acid residues associated to the oligosaccharide chain attached to the Fc region of these molecules. The Journal of Immunology, 2008, 181: 8308-8314.

A non-autonomous strongly damped wave equation: Existence and continuity of the pullback attractor

In this paper we consider the strongly damped wave equation with time-dependent terms u(tt) - Delta u - gamma(t)Delta u(t) + beta(epsilon)(t)u(t) = f(u), in a bounded domain Omega subset of R(n), under some restrictions on beta(epsilon)(t), gamma(t) and growth restrictions on the nonlinear term f. The function beta(epsilon)(t) depends on a parameter epsilon, beta(epsilon)(t) -> 0. We will prove, under suitable assumptions, local and global well-posedness (using the uniform sectorial operators theory), the existence and regularity of pullback attractors {A(epsilon)(t) : t is an element of R}, uniform bounds for these pullback attractors, characterization of these pullback attractors and their upper and lower semicontinuity at epsilon = 0. (C) 2010 Elsevier Ltd. All rights reserved.

MULTIPLICITY OF POSITIVE SOLUTIONS FOR A CLASS OF NONLINEAR SCHRODINGER EQUATIONS

This paper proves the multiplicity of positive solutions for the following class of quasilinear problems: {-epsilon(p)Delta(p)u+(lambda A(x) + 1)vertical bar u vertical bar(p-2)u = f(u), R(N) u(x)>0 in R(N), where Delta(p) is the p-Laplacian operator, N > p >= 2, lambda and epsilon are positive parameters, A is a nonnegative continuous function and f is a continuous function with subcritical growth. Here, we use variational methods to get multiplicity of positive solutions involving the Lusternick-Schnirelman category of intA(-1)(0) for all sufficiently large lambda and small epsilon.

C(k)-solvability near the characteristic set for a class of planar complex vector fields of infinite type

This paper deals with semi-global C(k)-solvability of complex vector fields of the form L = partial derivative/partial derivative t + x(r) (a(x) + ib(x))partial derivative/partial derivative x, r >= 1, defined on Omega(epsilon) = (-epsilon, epsilon) x S(1), epsilon > 0, where a and b are C(infinity) real-valued functions in (-epsilon, epsilon). It is shown that the interplay between the order of vanishing of the functions a and b at x = 0 influences the C(k)-solvability at Sigma = {0} x S(1). When r = 1, it is permitted that the functions a and b of L depend on the x and t variables, that is, L = partial derivative/partial derivative t + x(a(x, t) + ib(x, t))partial derivative/partial derivative x, where (x, t) is an element of Omega(epsilon).

Foliations and polynomial diffeomorphisms of R(3)

Let Y = (f, g, h): R(3) -> R(3) be a C(2) map and let Spec(Y) denote the set of eigenvalues of the derivative DY(p), when p varies in R(3). We begin proving that if, for some epsilon > 0, Spec(Y) boolean AND (-epsilon, epsilon) = empty set, then the foliation F(k), with k is an element of {f, g, h}, made up by the level surfaces {k = constant}, consists just of planes. As a consequence, we prove a bijectivity result related to the three-dimensional case of Jelonek`s Jacobian Conjecture for polynomial maps of R(n).

Nonexistence of global solutions for a class of complex vector fields on two-torus

The goal of this paper is study the global solvability of a class of complex vector fields of the special form L = partial derivative/partial derivative t + (a + ib)(x)partial derivative/partial derivative x, a, b epsilon C(infinity) (S(1) ; R), defined on two-torus T(2) congruent to R(2)/2 pi Z(2). The kernel of transpose operator L is described and the solvability near the characteristic set is also studied. (c) 2008 Elsevier Inc. All rights reserved.

Gevrey solvability near the characteristic set for a class of planar complex vector fields of infinite type

We study the Gevrey solvability of a class of complex vector fields, defined on Omega(epsilon) = (-epsilon, epsilon) x S(1), given by L = partial derivative/partial derivative t + (a(x) + ib(x))partial derivative/partial derivative x, b not equivalent to 0, near the characteristic set Sigma = {0} x S(1). We show that the interplay between the order of vanishing of the functions a and b at x = 0 plays a role in the Gevrey solvability. (C) 2008 Elsevier Inc. All rights reserved.

UNIVERSAL COVERING OF DRIFTLESS CONTROL SYSTEMS

Let M be a finite-dimensional manifold and Sigma be a driftless control system on M of full rank. We prove that for a given initial state x epsilon M, the covering space Gamma(Sigma, x) for a monotonic homotopy of trajectories of Sigma which is recently constructed in [1] coincides with the simply connected universal covering manifold of M and that the terminal projection epsilon(x) : Gamma(Sigma, x) -> M given by epsilon(x) ([alpha]) = alpha(1) is a covering mapping.

Regularity of solutions on the global attractor for a semilinear damped wave equation

We consider attractors A(eta), eta epsilon [0, 1], corresponding to a singularly perturbed damped wave equation u(tt) + 2 eta A(1/2)u(t) + au(t) + Au = f (u) in H-0(1)(Omega) x L-2 (Omega), where Omega is a bounded smooth domain in R-3. For dissipative nonlinearity f epsilon C-2(R, R) satisfying vertical bar f ``(s)vertical bar <= c(1 + vertical bar s vertical bar) with some c > 0, we prove that the family of attractors {A(eta), eta >= 0} is upper semicontinuous at eta = 0 in H1+s (Omega) x H-s (Omega) for any s epsilon (0, 1). For dissipative f epsilon C-3 (R, R) satisfying lim(vertical bar s vertical bar) (->) (infinity) f ``(s)/s = 0 we prove that the attractor A(0) for the damped wave equation u(tt) + au(t) + Au = f (u) (case eta = 0) is bounded in H-4(Omega) x H-3(Omega) and thus is compact in the Holder spaces C2+mu ((Omega) over bar) x C1+mu((Omega) over bar) for every mu epsilon (0, 1/2). As a consequence of the uniform bounds we obtain that the family of attractors {A(eta), eta epsilon [0, 1]} is upper and lower semicontinuous in C2+mu ((Omega) over bar) x C1+mu ((Omega) over bar) for every mu epsilon (0, 1/2). (c) 2007 Elsevier Inc. All rights reserved.

The doodle of a finitely determined map germ from R(2) to R(3)

Let f : U subset of R(2) -> R(3) be a representative of a finitely determined map germ f : (R(2), 0) -> (R(3), 0). Consider the curve obtained as the intersection of the image of the mapping f with a sufficiently small sphere s(epsilon)(2) centered at the origin in R(3), call this curve the associated doodle of the map germ f. For a large class of map germs the associated doodle has many transversal self-intersections. The topological classification of such map germs is considered from the point of view of the associated doodles. (C) 2009 Elsevier Inc. All rights reserved.

Numerical solution of the PTT constitutive equation for unsteady three-dimensional free surface flows

This work deals with the development of a numerical technique for simulating three-dimensional viscoelastic free surface flows using the PTT (Phan-Thien-Tanner) nonlinear constitutive equation. In particular, we are interested in flows possessing moving free surfaces. The equations describing the numerical technique are solved by the finite difference method on a staggered grid. The fluid is modelled by a Marker-and-Cell type method and an accurate representation of the fluid surface is employed. The full free surface stress conditions are considered. The PTT equation is solved by a high order method, which requires the calculation of the extra-stress tensor on the mesh contours. To validate the numerical technique developed in this work flow predictions for fully developed pipe flow are compared with an analytic solution from the literature. Then, results of complex free surface flows using the FIT equation such as the transient extrudate swell problem and a jet flowing onto a rigid plate are presented. An investigation of the effects of the parameters epsilon and xi on the extrudate swell and jet buckling problems is reported. (C) 2010 Elsevier B.V. All rights reserved.

Photoproduction of J/psi and of high mass e(+)e(-) in ultra-peripheral Au plus Au collisions at root s(NN)=200 GeV

We present the first measurement of photoproduction of J/psi and of two-photon production of high-mass e(+)e(-) pairs in electromagnetic (or ultra-peripheral) nucleus-nucleus interactions, using Au + Au data at root s(NN) = 200 GeV. The events are tagged with forward neutrons emitted following Coulomb excitation of one or both Au* nuclei. The event sample consists of 28 events with m(e+e-) > 2 GeV/c(2) with zero like-sign background. The measured cross sections at midrapidity of d sigma/dy (J/psi + Xn, y = 0) = 76 +/- 33 (stat) +/- 11 (syst) pb and d(2)sigma /dm dy (e(+) e(-) + Xn, y = 0) = 86 +/- 23(stat) +/- 16(syst) mu b/ (GeV/c(2)) for m(e+e-) epsilon vertical bar 2.0, 2.8 vertical bar GeV/c(2) have been compared and found to be consistent with models for photoproduction of J/psi and QED based calculations of two-photon production of e(+)e(-) pairs. (C) 2009 Elsevier B.V. All rights reserved.