bluuebunny/crossref_metadata_2025 huggingface dataset:
ENHANCEMENT OF SUBTHRESHOLD SENSORY NERVE ACTION POTENTIALS DURING MUSCLE TENSION MEDIATED NOISE
Authors: CHIOU-TAN FAYE Y. , MAGEE KEVIN N. , ROBINSON LAWRENCE R. , NELSON MAUREEN R. , TUEL STEPHEN S. , KROUSKOP THOMAS A. , MOSS FRANK
Published: October 2004

In certain nonlinear systems, of which neurons are an example, the addition of random fluctuations, or “noise”, can enhance the detectability or transmission efficiency of a weakly applied signal. This counterintuitive statistical process, called stochastic resonance, —first advanced as a possible explanation for the observed periodic recurrences of the Earth’s ice ages [Benzi et al., 1981; Nicolis, 1993] —has by now been well established in a variety of physical systems [Wiesenfeld & Moss, 1995]. Recently it has been observed in the sensory nervous systems of two different arthropods [Douglass et al., 1994; Levin & Miller, 1996; Pei et al., preprint] and may be deeply linked to the evolution of all sensory systems. We report here the results of an experiment—the first in a human modality—designed to study the possibility of SR in the median nerve. Moreover, two additional features of this work are unique: first, our study makes use of the internal noise (as opposed to previous protocols wherein the noise was introduced externally) and second, we study the transmission of an aggregate stimulus through a bundle of individual neurons which are thought to be connected in parallel, a subject of recent theoretical [Collins et al., 1995] and experimental [Bezrukov & Vodynoy, 1995] interest. In our experiment, near subthreshold electrical stimuli were applied periodically to the median nerve, and responses were detected and signal averaged by electromyography. The internal noise intensity was mediated by muscle tension. The results are consistent with the hypothesis that internally generated electrical noise can enhance the signal transmission efficiency in this modality.
PERIODIC ORBITS AND INVARIANT SURFACES OF 4D NONLINEAR MAPPINGS
Authors: VRAHATIS M.N. , BOUNTIS T.C. , KOLLMANN M.
Published: October 2004

The accurate computation of periodic orbits and the knowledge of their stability properties are very important for studying the behavior of many physically interesting dynamical systems. In this paper, we describe first an efficient numerical method for computing periodic orbits of 4D mappings of any period and to any desired accuracy. This method always converges rapidly to a periodic orbit independently of the initial guess, which is very useful when the mapping has many periodic orbits close to each other, as in the case of conservative maps. We illustrate this method on a 4D symplectic mapping, by computing some of its periodic orbits and determining their particular arrangement in the 4D space, according to their stability characteristics. We then obtain periodic orbits associated with sequences of (rational) winding numbers converging on a pair of irrationals and discuss the possible existence of an analogue of Greene’s criterion for 4D symplectic mappings.
PLANE FOLIATION OF TWO-DIMENSIONAL NONINVERTIBLE MAPS
Authors: CHRISTIAN MIRA , JEAN-PIERRE CARCASSES , GILLES MILLÉRIOUX , LAURA GARDINI
Published: October 2004

The plane foliation consists in associating a sheet with each determination of the inverse map. Such sheets join by pairs at curves called “critical curves”, locus of points having two coincident rank-one preimages. The knowledge of the foliation, i.e., the sheets organization, is of first importance for understanding the properties of noninvertible maps, in particular those of chaotic attractors, basins, and their bifurcations.
LINEAR SUPERPOSITION OF CHAOTIC AND ORDERLY VIBRATIONS ON TWO SERIALLY CONNECTED STRINGS WITH A VAN DER POL JOINT
Authors: CHEN GOONG , ZHOU JIANXIN , HSU SZE-BI
Published: October 2004

Two identical vibrating strings are serially coupled end-to-end with nonlinear joints that behave like a Van der Pol oscillator. This coupled PDE system has an infinite dimensional center manifold of orderly periodic solutions of vibration for which the nonlinearity at the joint is not excited. Based upon the authors’ study of chaotic vibration on a single vibrating string in [Chen et al., 1995], we analyze the special structure of the nonlinear reflection operator by decoupling. The decoupled operator has a linear part which is idempotent, and this linear part does not interact with the iterates of the nonlinear part. Using this, we show that chaotic vibrations and orderly periodic vibrations coexist and satisfy a certain rule of linear superposition, namely, if u is a linear periodic solution and if U is a general nonlinear solution, then U+Cu is also a solution for any constant C. Numerical simulations and computer graphics are also included to illustrate the superposition effect.
A METHOD FOR THE SYNCHRONIZATION OF HYPERCHAOTIC CIRCUITS
Authors: BRUCOLI MICHELE , CARNIMEO LEONARDA , GRASSI GIUSEPPE
Published: October 2004

In this paper the Carroll–Pecora concept of chaotic system synchronization is extended to the synchronization of hyperchaotic circuits. A circuit exhibiting a hyperchaotic behavior is duplicated to generate two cascaded response subsystems, properly driven by synchronizing signals. Conditions for achieving synchronization are illustrated in detail. The proposed method is applied to two identical unidirectionally coupled hyperchaotic Chua’s circuits.
ANALYSIS OF THE BEHAVIOR OF A RANDOM NONLINEAR DELAY DISCRETE EQUATION
Authors: CABRERA JUAN L. , DE LA RUBIA F. JAVIER
Published: October 2004

The stability problem for a class of nonlinear delay discrete equations under parametric noise perturbations is considered. The effect of the delay on the asymptotic behavior of the system is studied, and a power law dependency between an optimal noise correlation time for the escape from the physically meaningful region and the memory strength is numerically deduced. The influence of multiple delays is also analyzed.
CHARACTERIZATION AND DYNAMICS OF PATTERN FORMATION IN CELLULAR NEURAL NETWORKS
Authors: CROUNSE K.R. , CHUA L.O. , THIRAN P. , SETTI G.
Published: October 2004

We study some properties of pattern formation arising in large arrays of locally coupled first-order nonlinear dynamical systems, namely Cellular Neural Networks (CNNs).

We will present exact results to analyze spatial patterns for symmetric coupling and to analyze spatio-temporal patterns for anti-symmetric coupling in one-dimensional lattices, which will then be completed by approximative results based on a spatial and/or temporal frequency approach. We will discuss the validity of these approximations, which bring a lot of insight.

This spectral approach becomes very convenient for the two-dimensional lattice, as exact results get more complicated to establish. In this second part, we will only consider a symmetric coupling between cells. We will show what kinds of motifs can be found in the patterns generated by 3×3 templates. Then, we will discuss the dynamics of pattern formation starting from initial conditions which are a small random noise added to the unstable equilibrium: this can generally be well predicted by the spatial frequency approach. We will also study whether a defect in a pure pattern can propagate or not through the whole lattice, starting from initial conditions being a localized perturbation of a stable pattern: this phenomenon is no longer correctly predicted by the spatial frequency approach. We also show that patterns such as spirals and targets can be formed by “seed” initial conditions — localized, non-random perturbations of an unstable equilibrium. Finally, the effects on the patterns formed of a bias term in the dynamics are demonstrated.
DISCRETE ROTATING WAVE SOLUTIONS FOR SYSTEM OF GLOBALLY COUPLED JOSEPHSON JUNCTIONS
Authors: HUANG Y.S. , ARONSON D.G.
Published: October 2004

For a general system of Josephsons junctions, when the number of junctions is sufficiently large, there exist discrete rotating wave solutions as long as either the resistance of the load is not zero or the capacitance of the load is not infinity. Here, we show that these discrete rotating wave solutions, together with all their derivatives, converge to a certain wave form exponentially fast when the number of junctions in the array tends to infinity. Moreover, when the number of junctions is sufficiently large the discrete rotating wave solution is unique up to a time shift and permutation.
CLASS IV BEHAVIOR IN CELLULAR AUTOMATA MODELS OF PHYSICAL SYSTEMS
Authors: MARKUS MARIO , KUSCH INGO , RIBEIRO ANTÓNIO , ALMEIDA PEDRO
Published: October 2004

Wolfram’s cellular automata [1986] can be classified according to their asymptotic behavior: class I (homogeneous), class II (periodic), class III (chaotic) and class IV (“undecidable”, i.e. erratically changing between periodicity and chaos). While these automata are purely number-theoretical and suffer from ill-defined parametrization, we present here examples of automata describing actual physical systems and governed by well-defined control parameters: resting states between earthquakes, pigmentation on the shells of molluscs, and two-dimensional reaction–diffusion systems. We find that the dynamics of these three systems can be classified analogously to Wolfram’s automata. Moreover, we find agreement between class IV simulations and real shell patterns, indicating that these shells indeed present evidence for class IV behavior in nature. In addition, we performed an intuitively appealing quantification by averaging the fluctuations of the borders of error-propagation patterns.
WAVE PROPAGATION, PATTERN FORMATION AND MEMORY EFFECTS IN LARGE ARRAYS OF INTERCONNECTED CHAOTIC CIRCUITS
Authors: OGORZAŁEK MACIEJ J. , GALIAS ZBIGNIEW , DABROWSKI ANDRZEJ , DABROWSKI WLADYSŁAW
Published: October 2004

We investigate complex dynamic phenomena in arrays composed of interacting chaotic circuits. Such arrays can be thought of as a model of nonlinear phenomena in spatially extended (high-dimensional or infinite-dimensional) systems and active media with potential applications in brain function modelling and signal processing. In this paper we consider a particular structure of the network in which there exist locally double diffusive interactions between the cells. Such a double interaction can be considered as a paradigm and means for understanding very complex interactions existing in real systems where neighboring cells can communicate in various ways. We consider two basic cases where separate cells without coupling exhibit two different types of chaotic behavior. Depending on the connection structure, initial conditions imposed in the cells the array exhibits various kinds of spatially ordered chaotic waves. Patterns of behavior depending on the excitation of the array and the connection structure are studied in some detail. We present results of simulations showing cooperative phenomena. Depending on the connection structure between the cells and their initial states the array can show spatially ordered patterns of behavior. Such orderly spatial patterns resulting in arrays of chaotic elements are referred to as self-organization. We observed travelling target waves and chaotic wavefronts behaving like autowaves. This kind of autowave-like behavior in arrays of chaotic elements is to our knowledge described for the first time.
PRACTICAL SYNCHRONIZATION OF CHAOS VIA NONLINEAR FEEDBACK SCHEME
Authors: SEKIETA M. , KAPITANIAK T.
Published: October 2004

We discussed the problem of synchronization of two slightly different chaotic systems and address the problem of the effect of parameter differences on the synchronization. The concept of practical synchronization which is equivalent to the consideration of a tolerance in the synchronization condition was introduced. We showed that small differences of system parameters can significantly destroy the synchronization regime of linearly coupled chaotic systems.
STOCHASTIC RESONANCE IN NONLINEAR TRANSMISSION OF SPIKE SIGNALS: AN EXACT MODEL AND AN APPLICATION TO THE NEURON
Authors: CHAPEAU-BLONDEAU FRANÇOIS , GODIVIER XAVIER
Published: October 2004

Nonlinear transmission of trains of pulses enhanced by noise addition through stochastic resonance is studied. First, an exact model is presented which describes stochastic resonance in the transmission of a periodic train of pulses by a threshold system in the presence of arbitrarily distributed white noise. Second, a simulation demonstrates a novel possibility of stochastic resonance in the neuron, in the nonlinear transmission of spike trains assisted by noise. Third, it is shown that the exact model can provide a satisfactory approximation of stochastic resonance in the neuron, as the reported effect is mainly sensitive to correlations at a dominant time scale formed by the coherent period, and to the overall input signal amplitude relative to the threshold of the nonlinearity. The present results enlarge the scope of the effect of noise-enhanced transmission of signals through stochastic resonance, and also of the possible mechanisms for neural information processing.
A METHOD FOR ENCODING MESSAGES BY TIME TARGETING OF THE TRAJECTORIES OF CHAOTIC SYSTEMS
Authors: GLIGOROSKI D. , DIMOVSKI D. , KOCAREV L. , URUMOV V. , CHUA L.O.
Published: October 2004

We suggest a method for encoding messages by chaotic dynamical systems. The main idea is that by targeting the trajectories of some chaotic dynamical system with time constraint, someone can send a information to the remote recipient. The concept is based on setting receptors in the phase space of the dynamical system, and then targeting the trajectory between them. We considered the time of arriving from one receptor to another as a carrier of information obtained by searching in the table of values for arriving times.
SYNCHRONIZATION STABILITY ANALYSIS OF THE CHAOTIC RÖSSLER SYSTEM
Authors: XIE QINGXIAN , CHEN GUANRONG
Published: October 2004

In this paper we show, both analytically and experimentally, that the Rössler system synchronization is either asymptotically stable or orbitally stable within a wide range of the system key parameters. In the meantime, we provide some simple sufficient conditions for synchronization stabilities of the Rössler system in a general situation. Our computer simulation shows that the type of stability of the synchronization is very sensitive to the initial values of the two (drive and response) Rössler systems, especially for higher-periodic synchronizing trajectories, which is believed to be a fundamental characteristic of chaotic synchronization that preserves the extreme sensitivity to initial conditions of chaotic systems.
ON AUTOMATED DERIVATION OF AMPLITUDE EQUATIONS IN NONLINEAR BIFURCATION PROBLEMS
Authors: PISMEN LEONID M. , RUBINSTEIN BORIS Y. , VELARDE MANUEL G.
Published: October 2004

Examples of computer-assisted derivation of amplitude equations valid in the vicinity of a bifurcation point are presented. Bifurcation of wave trains is studied for the dissipation-modified KdV equation. The methodology using Mathematica programming language is outlined, stressing its potential to tackle a wide class of problems in nonlinear science.
ERROR GROWTH DYNAMICS IN SPATIALLY EXTENDED SYSTEMS
Authors: VANNITSEM S. , NICOLIS C.
Published: October 2004

A class of spatially extended systems allowing for tuning the degree of attractor non-uniformity, the strength and the range of the spatial coupling is investigated with emphasis on the dynamics of the evolution of small initial errors. Depending on the values of these parameters and on the properties of the initial error field various patterns of growth are found ranging from subexponential to superexponential ones. The mechanisms of error transfer between different spatial scales is analyzed and the respective role of the Lyapunov vectors and singular vectors for short time behavior is clarified.
COARSE-GRAINING INVARIANT ORBITS OF ONE-DIMENSIONAL ℤp-LINEAR CELLULAR AUTOMATA
Authors: BARBÉ ANDRÉ M.
Published: October 2004

This paper studies the properties of state-time evolution patterns of one-dimensional linear cellular automata over the field ℤp (p prime) which are invariant under certain coarse-graining operations.

A procedure is developed for finding all solutions to this invariance problem. The resulting patterns display a complexity which may range from periodic over self-similar, quasi-periodic, quasi-randomlike towards randomlike. Conditions for the existence of periodic solutions are derived.
PERIODICALLY FORCED HYDROCARBON OXIDATION REACTION IN A CSTR
Authors: SIDHU H. S. , FORBES L. K. , GRAY B. F.
Published: October 2004

In this paper we examine in detail the effects of forcing the thermokinetic or the chain-thermal model of hydrocarbon oxidation (proposed by B. F. Gray and C. H. Yang) in a Continuously Stirred Tank Reactor (CSTR). Here, the reaction has been subjected to periodic modulation of the input and output flows of chemicals. This investigation has uncovered rich non-linear dynamical characteristics including primary resonances, super and sub-harmonic resonances, quasi-periodic solutions and chaotic oscillations. These regions of chaos are normally interrupted by windows of periodic behaviour. The transitions to chaos were mainly found to be of three types: Feigenbaum period-doubling cascade, Ruelle-Takens-Newhouse approach through quasi-periodicity, and intermittency. The presence of these chaotic solutions was confirmed by computing the Lyapunov exponents. The results presented here are of potential benefit to industrial practice, since they show great increases in product selectivity when appropriate operating conditions are chosen in this forcing strategy.
MODELING NEURONS BY SIMPLE MAPS
Authors: KINOUCHI OSAME , TRAGTENBERG MARCELO H. R.
Published: October 2004

We introduce a simple generalization of graded response formal neurons which presents very complex behavior. Phase diagrams in full parameter space are given, showing regions with fixed points, periodic, quasiperiodic and chaotic behavior. These diagrams also represent the possible time series learnable by the simplest feed-forward network, a two input single-layer perceptron. This simple formal neuron (‘dynamical perceptron’) behaves as an excitable ele ment with characteristics very similar to those appearing in more complicated neuron models like FitzHugh-Nagumo and Hodgkin-Huxley systems: natural threshold for action potentials, dampened subthreshold oscillations, rebound response, repetitive firing under constant input, nerve blocking effect etc. We also introduce an ‘adaptive dynamical perceptron’ as a simple model of a bursting neuron of Rose-Hindmarsh type. We show that networks of such elements are interesting models which lie at the interface of neural networks, coupled map lattices, excitable media and self-organized criticality studies.
STATISTICAL LAWS FOR COMPUTATIONAL COLLAPSE OF DISCRETIZED CHAOTIC MAPPINGS
Authors: DIAMOND PHIL , POKROVSKII ALEXEI
Published: October 2004

When a dynamical system is realized on a computer, the computation is of a discretization, where finite machine arithmetic replaces continuum state space. For chaotic dynamical systems, the discretizations often have collapsing effects to a fixed point or to short cycles. Statistical properties of this phenomenon can be modeled by random mappings with an absorbing center. The model gives results which are very much in line with computational experiments and there appears to be a type of universality summarised by an Arcsine Law. The effects are discussed with special reference to the family of mappings fl(x)=1−|1−2x|l,x∈[0, 1], 1<l≤2. Computer experiments show close agreement with predictions of the model.
WAVELET ANALYSIS OF A NONLINEAR OSCILLATOR TRANSIENT DURING SYNCHRONIZATION
Authors: FRANCO H.
Published: October 2004

A forced nonlinear oscillator can exhibit complex transient spectra even in the absence of chaotic phenomena. Series of evenly spaced lines appear in spectrograms of the numerically computed oscillations. They can be explained by means of a simple model describing the dynamics of the energy exchange between the external oscillating force and the nonlinear system. The resulting amplitude and phase modulations are shown to produce the spectral line structures. Frequencies incommensurable with other present frequencies can be generated by the nonlinear system.
Transcriptional regulation of murineSlc22a1(Oct1) by peroxisome proliferator agonist receptor-α and -γ
Authors: Nie Wenxian , Sweetser Seth , Rinella Mary , Green Richard M.
Published: October 2004

The transport and metabolism of organic cationic endobiotics, nutrients, and drugs are essential hepatic functions. Slc22A1 is the basolateral liver transporter mediating the uptake of organic cations; however, little is known about the regulation of this transport protein. Peroxisome proliferator agonist receptor (PPAR)-α and -γ agonists are commonly used agents that regulate many hepatocellular transport functions. Thus the purpose of this study was to examine the effects of PPAR agonists on the hepatic regulation and function of Slc22a1. Mice and H35 cells were administered PPAR-α and -γ agonists, and the effect on Slc22a1 gene expression was measured. We subsequently cloned the Slc22a1 promoter and employed chimeric constructs to assay Slc22a1 gene transcription. The effects of PPAR-agonist treatment on organic cation uptake was also assayed. Slc22a1 expression was increased by PPAR-α and -γ agonist treatment in both murine livers and H35 cells. Gene expression in H35 cells was further increased following transfection with expression vectors of PPAR transcription factors and PPAR agonist treatment. We cloned the promoter region of Slc22a1 and identified a PPAR-response element, and transfections with chimeric Slc22a1; promoter-reporter gene constructs demonstrate that the increased gene expression was transcriptionally regulated. Functional assays confirmed that cells treated with PPAR agonists displayed significant increases in organic cation uptake. PPAR-α and -γ agonists transcriptionally increase Slc22a1 gene expression, and the increased Slc22a1 expression results in enhanced cellular organic cation uptake. These studies may have implication for the uptake of organic cationic drugs and for lipid metabolism.
Ecabet sodium inhibitsHelicobacter pylorilipopolysaccharide-induced activation of NADPH oxidase 1 or apoptosis of guinea pig gastric mucosal cells
Authors: Kusumoto Kenji , Kawahara Tsukasa , Kuwano Yuki , Teshima-Kondo Shigetada , Morita Kyoko , Kishi Kyoichi , Rokutan Kazuhito
Published: October 2004

Helicobacter pylori LPS activates a homolog of gp91phox, NADPH oxidase 1 (Nox1), in guinea pig gastric mucosal cells cultured in 10% FBS-containing medium. RT-PCR and Northern hybridization demonstrated that H. pylori LPS stimulated expression of Nox1 and a novel p47phoxhomolog (Noxo1) mRNAs with a peak at 4 h, followed by upregulation of superoxide anion (O2−) generation. Pretreatment with 10 mg/ml of a nonabsorbable antigastric ulcer drug, ecabet sodium (ecabet), completely blocked these two mRNA expressions and the upregulation of O2−production. Under low (0.1%)-FBS conditions, H. pylori LPS predominantly caused apoptosis of the cells. Ecabet completely blocked the LPS-triggered phosphorylation of transforming growth factor-β-activated kinase 1 (TAK1) and TAK1-binding protein 1, activation of caspase 8, loss of mitochondrial membrane potential, release of cytochrome c, activation of caspase 3, and appearance of apoptotic cells. In contrast, ecabet had no effect on ethanol- or etoposide-initiated apoptosis. The ecabet-pretreated cells exhibited the responsiveness to H. pylori LPS, similarly as untreated control cells did, when ecabet was removed by washing before the addition of H. pylori LPS. Incubation of H. pylori LPS with ecabet eliminated the toxic effects of the LPS, and nondenatured polyacrylamide gel electrophoresis indicated the formation of higher molecular mass complexes between H. pylori LPS and ecabet, suggesting that ecabet may interact with H. pylori LPS and block the activation of Toll-like receptor 4 (TLR4). Our results suggest that ecabet may suppress TLR4-mediated inflammation or accelerated apoptosis caused H. pylori infection.
IQGAPs are differentially expressed and regulated in polarized gastric epithelial cells
Authors: Chew Catherine S. , Okamoto Curtis T. , Chen Xunsheng , Qin Hai Yan
Published: October 2004

IQGAPs, GTPase-activating proteins with an IQ motif, are thought to regulate many actin cytoskeleton-based activities through interactions with Cdc42 and Rac. Recently, Cdc42 was implicated in regulation of gastric parietal cell HCl secretion, and IQGAP2 was immunolocalized with Cdc42 to F-actin-rich intracellular canalicular membranes of isolated gastric parietal cells in primary culture. Here we sought to define distribution and localization of IQGAP1 and IQGAP2 in major oxyntic (acid-secreting) gastric mucosal cell types and to determine whether secretory agonists modulate these proteins. Differential staining protocols were used to identify different cell populations (parietal, chief, surface/pit, and mucous neck cells) in semi-intact glands isolated from rabbit gastric mucosae and to characterize these same cells after dispersion and fractionation on isopycnic density gradients with simultaneous staining for F-actin, H+-K+-ATPase, and GSII lectin-binding sites. There was a pronounced increase in intracellular F-actin staining in dispersed chief cells, apparently from internalization of F-actin-rich apical membranes that normally abut the gland lumen. Therefore, other membrane-associated proteins might also be redistributed by disruption of cell-cell contacts. Western blot analyses were used to quantitate relative concentrations of IQGAPs in defined mucosal cell fractions, and gastric glands were used for in situ localizations. We detected uniform levels of IQGAP2 expression in oxyntic mucosal cells with predominant targeting to regions of cell-cell contact and nuclei of all cell types. IQGAP2 was not detected in parietal cell intracellular canaliculi. IQGAP1 expression was variable and targeted predominantly to the cortex of chief and mucous neck cells. Parietal cells expressed little or no IQGAP1 vs. other mucosal cell types. Phosphoprotein affinity chromatography, isoelectric focusing, and phosphorylation site analyses indicated that both IQGAP1 and IQGAP2 are phosphoproteins potentially regulated by [Ca2+]i/PKC and cAMP signaling pathways, respectively. Stimulation of glands with carbachol, which elevates [Ca2+]iand activates PKC, induced apparent translocation of IQGAP1, but not IQGAP2, to apical poles of chief (zymogen) and mucous neck cells. This response was mimicked by PMA but not by ionomycin or by elevation of [cAMP]iwith forskolin. Our observations support a novel, PKC-dependent role for IQGAP1 in regulated exocytosis and suggest that IQGAP2 may play a more general role in regulating cell-cell interactions and possibly migration within the gastric mucosa.
Induced microsomal PGE synthase-1 is involved in cyclooxygenase-2-dependent PGE2 production in gastric fibroblasts
Authors: Shinji Yoko , Tsukui Taku , Tatsuguchi Atsushi , Shinoki Kei , Kusunoki Masafumi , Suzuki Kenji , Hiratsuka Tetsuro , Wada Ken , Futagami Seiji , Miyake Kazumasa , Gudis Katya , Sakamoto Choitsu
Published: October 2004

We have previously shown that the cyclooxygenase (COX)-2/PGE2 pathway plays a key role in VEGF production in gastric fibroblasts. Recent studies have identified three PGE synthase (PGES) isozymes: cytosolic PGES (cPGES) and microsomal PGES (mPGES)-1 and -2, but little is known regarding the expression and roles of these enzymes in gastric fibroblasts. Thus we examined IL-1β-stimulated mPGES-1 and cPGES mRNA and protein expression in gastric fibroblasts by quantitative PCR and Western blot analysis, respectively, and studied both their relationship to COX-1 and -2 and their roles in PGE2 and VEGF production in vitro. IL-1β stimulated increases in both COX-2 and mPGES-1 mRNA and protein expression levels. However, COX-2 mRNA and protein expression were more rapidly induced than mPGES-1 mRNA and protein expression. Furthermore, MK-886, a nonselective mPGES-1 inhibitor, failed to inhibit IL-1β-induced PGE2 release at the 8-h time point, while totally inhibiting PGE2 at the later stage. However, MK-886 did inhibit IL-1β-stimulated PGES activity in vitro by 86.8%. N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide (NS-398), a selective COX-2 inhibitor, totally inhibited PGE2 production at both the 8-h and 24-h time points, suggesting that COX-2-dependent PGE2 generation does not depend on mPGES-1 activity at the early stage. In contrast, NS-398 did not inhibit VEGF production at 8 h, and only partially at 24 h, whereas MK-886 totally inhibited VEGF production at each time point. These results suggest that IL-1β-induced mPGES-1 protein expression preferentially coupled with COX-2 protein at late stages of PGE2 production and that IL-1β-stimulated VEGF production was totally dependent on membrane-associated proteins involved in eicosanoid and glutathione metabolism (MAPEG) superfamily proteins, which includes mPGES-1, but was partially dependent on the COX-2/PGE2 pathway.
Effects of increased intracellular cAMP on carbachol-stimulated zymogen activation, secretion, and injury in the pancreatic acinar cell
Authors: Chaudhuri A. , Kolodecik T. R. , Gorelick F. S.
Published: October 2004

A characteristic of acute pancreatitis is the premature activation and retention of enzymes within the pancreatic acinar cell. Because ligands linked to cAMP production may prevent some forms of pancreatitis, we evaluated the effects of increased intracellular cAMP in the rat pancreatic acinar cell. Specifically, this study examined the effects of the cholinergic agonist carbachol and agents that increase cAMP [secretin and 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP)] on zymogen activation (trypsin and chymotrypsin), enzyme secretion, and cellular injury in isolated pancreatic acini. Although cAMP agonists affected the responses to physiological concentrations of carbachol (1 μM), their most prominent effects were observed with supraphysiological concentrations (1 mM). When secretin was added to 1 mM carbachol, there was a slight increase in zymogen activation, but no change in the secretion of amylase or chymotrypsin. Furthermore, coaddition of secretin increased parameters of cell injury (trypan blue exclusion, lactic dehydrogenase release, and morphological markers) compared with carbachol (1 mM) alone. Although directly increasing cellular cAMP by 8-Br-cAMP caused much greater zymogen activation than carbachol (1 mM) alone or with secretin, 8-Br-cAMP cotreatment reduced all parameters of injury to the level of unstimulated acini. Furthermore, 8-Br-cAMP dramatically enhanced the secretion of amylase and chymotrypsin from the acinar cell. This study demonstrates that increasing acinar cell cAMP can overcome the inhibition of enzyme secretion caused by high concentrations of carbachol and eliminate acinar cell injury.
NF1 transcriptional factor(s) is required for basal promoter activation of the human intestinal NaPi-IIb cotransporter gene
Authors: Xu Hua , Uno Jennifer K. , Inouye Michael , Collins James F. , Ghishan Fayez K.
Published: October 2004

The human intestinal type IIb Na+-Picotransporter (hNaPi-IIb) gene promoter lacks a TATA box and has a high GC content in the 5′-flanking region. To understand the mechanism of hNaPi-IIb gene transcription, the current study was performed to characterize the minimal promoter region and transcriptional factor(s) necessary to activate gene expression in human intestinal cells (Caco-2). With the use of progressively shorter promoter constructs, a minimal promoter extending from bp −58 to +15 was identified and shown to direct high levels of hNaPi-IIb cotransporter expression in Caco-2 cells. Gel mobility shift assays (GMSAs) indicated that two regions could be bound by nuclear proteins from Caco-2 cells: region A at bp −26/−23 and region B at bp −44/−35. The introduction of mutations in region A abolished promoter activity, whereas mutations in region B had no effect. Deletion mutants of the same regions showed identical results. Furthermore, DNase I footprinting experiments confirmed the observation made by GMSAs. Additional studies, which used a specific nuclear factor 1 (NF1) antiserum, demonstrated that NF1 protein(s) binds to the minimal promoter at region A. These results indicated that the NF1 protein(s) is required to activate the basal transcription of hNaPi-IIb gene under normal growth conditions. This study has thus identified a new target gene in the small intestinal epithelium that is directly regulated by NF1 transcriptional factor(s).
Moderate maternal vitamin A deficiency alters myogenic regulatory protein expression and perinatal organ growth in the rat
Authors: Downie D. , Antipatis C. , Delday M. I. , Maltin C. A. , Sneddon A. A.
Published: October 2004

Vitamin A deficiency is one of the most common dietary deficiencies in the developing world and is a major health concern where it is associated with increased risk of fetal and infant mortality and morbidity. Early studies in the rat demonstrated that, in addition to respiratory problems, neonates showed evidence of mobility problems in response to moderate vitamin A deficiency. This study investigated whether moderate deficiency of this vitamin plays a role in regulating key skeletal muscle regulatory pathways during development. Thirty female rats were fed vitamin A-moderate (VAM) or vitamin A-sufficient diets from weaning and throughout pregnancy. Fetal and neonatal hindlimb and muscle samples were collected on days 13.5, 15.5, 17.5, and 19.5 of pregnancy and 1 day following birth. Mothers fed the VAM diet had reduced retinol concentrations at all time points studied ( P < 0.01), and neonates had reduced relative lung weights ( P < 0.01). Fetal weight and survival did not differ between groups but neonatal survival was lower in the VAM group where neonates had increased relative heart weights ( P < 0.05). Analysis of myogenic regulatory factor expression and calcineurin signaling in fetuses and neonates demonstrated decreased protein levels of myf5 [50% at 17.5 dg ( P < 0.05)], myogenin [70% at birth ( P < 0.001)], and myosin heavy chain fast [50% at birth ( P < 0.05)] in response to moderate vitamin A deficiency. Overall, these changes suggest that vitamin A status during pregnancy may have important implications for fetal muscle development and subsequent muscle function in the offspring.
Relationship between body size, Na+-K+-ATPase activity, and membrane lipid composition in mammal and bird kidney
Authors: Turner Nigel , Haga Kurt L. , Hulbert A. J. , Else Paul L.
Published: October 2004

We investigated the relationship between body size, Na+-K+-ATPase molecular activity, and membrane lipid composition in the kidney of five mammalian and eight avian species ranging from 30-g mice to 280-kg cattle and 13-g zebra finches to 35-kg emus, respectively. Na+-K+-ATPase activity was found to be higher in the smaller species of both groups. In small mammals, the higher Na+-K+-ATPase activity was primarily the result of an increase in the molecular activity (turnover rate) of individual enzymes, whereas in small birds the higher Na+-K+-ATPase activity was the result of an increased enzyme concentration. Phospholipids from both mammals and birds contained a relatively constant percentage of unsaturated fatty acids; however, phospholipids from the smaller species were generally more polyunsaturated, and a complementary significant allometric increase in monounsaturate content was observed in the larger species. In particular, the relative content of the highly polyunsaturated docosahexaenoic acid [22:6( n-3)] displayed the greatest variation with body mass, scaling with allometric exponents of −0.21 and −0.26 in the mammals and birds, respectively. This allometric variation in fatty acid composition was correlated with Na+-K+-ATPase molecular activity in mammals, whereas in birds molecular activity only correlated with membrane cholesterol content. These relationships are discussed with respect to the metabolic intensity of different-sized animals.
Transcriptional regulation of TNF-α production in neutropenia
Authors: Daley Jean M. , Ivanenko-Johnston Tetiana , Reichner Jonathan S. , Albina Jorge E.
Published: October 2004

Neutropenia has been shown to markedly increase plasma TNF-α concentration after LPS injection and to enhance LPS-induced mortality. Experiments reported here demonstrate that the 15-fold higher plasma TNF-α concentration elicited by LPS in neutropenic vs. nonneutropenic unanesthetized mice correlated with increased hepatic and splenic, but not pulmonary, TNF-α mRNA. Core 2 β-1,6- N-acetylglucosaminyltransferase-null and CD18-deficient mice also exhibited exaggerated plasma TNF-α responses to LPS injection. Findings suggest that extravasated neutrophils inhibit systemic TNF-α production and that they do so through organ-selective mechanisms involving CD18 integrin and selectin binding.
Effects of acupuncture on vasopressin-induced emesis in conscious dogs
Authors: Tatewaki Makoto , Strickland Carmen , Fukuda Hiroyuki , Tsuchida Daisuke , Hoshino Etsuo , Pappas Theodore N. , Takahashi Toku
Published: October 2004

Although acupuncture has a significant clinical benefit, the mechanism of acupuncture remains unclear. Vasopressin, a posterior pituitary hormone, is involved in nausea and vomiting in humans and dogs. To investigate the antiemetic effects of acupuncture on vasopressin-induced emesis, gastroduodenal motor activity and the frequency of retching and vomiting were simultaneously recorded in conscious dogs. In seven dogs, four force transducers were implanted on the serosal surfaces of the gastric body, antrum, pylorus, and duodenum. Gastroduodenal motility was continuously monitored throughout the experiment. Vasopressin was intravenously infused at a dose of 0.1 U·kg−1·min−1 for 20 min. Electroacupuncture (EA, 1–30 Hz) at pericardium-6 (PC6), bladder-21 (BL21), or stomach-36 (ST36) was performed before, during, and after the vasopressin infusion. To investigate whether the opioid pathway is involved in EA-induced antiemetic effects, naloxone (a central and peripheral opioid receptor antagonist) or naloxone methiodide (a peripheral opioid receptor antagonist) was administered before, during, and after EA and vasopressin infusion. Intravenous infusion of vasopressin induced retching and vomiting in all dogs tested. Retrograde peristaltic contractions occurred before the onset of retching and vomiting. EA (10 Hz) at PC6 significantly reduced the number of episodes of retching and vomiting. EA at PC6 also suppressed retrograde peristaltic contractions. In contrast, EA at BL21 or ST36 had no antiemetic effects. The antiemetic effect of EA was abolished by pretreatment with naloxone but not naloxone methiodide. It is suggested that the antiemetic effect of acupuncture is mediated via the central opioid pathway.
Effect of 3β-hydroxysteroid dehydrogenase inhibition by trilostane on blood pressure in the Dahl salt-sensitive rat
Authors: Gomez-Sanchez Elise P. , Samuel Jacqueline , Vergara Gaston , Ahmad Naveed
Published: October 2004

The brains of rats and humans express the enzymes required for the synthesis of aldosterone from cholesterol, including the 3β-steroid dehydrogenase that catalyzes the conversion of pregnenolone to progesterone in the pathway of adrenal steroid synthesis. Salt-induced hypertension in the Dahl inbred salt-sensitive (SS/jr) rat is associated with normal to low levels of circulating aldosterone, yet it is abrogated by the central infusion of mineralocorticoid receptor antagonists. To test the hypothesis that de novo synthesis of aldosterone in the brain has a pathophysiological role in the salt-induced hypertension of the SS rat, the 3β-steroid dehydrogenase antagonist trilostane was infused continuously intracerebroventricularly or subcutaneously in two different cohorts of Dahl SS/jr rats, one female, the other male, during and after the development of salt-induced hypertension. The doses of trilostane used had no effect on blood pressure when infused subcutaneously. Animals receiving vehicle intracerebroventricularly experienced a 30- to 45-mmHg increase in systolic blood pressure measured by tail cuff. The intracerebroventricular, but not subcutaneous, infusion of 0.3 μg/h trilostane effectively blocked the increase in systolic blood pressure and reversed the hypertension produced by drinking 0.9% saline. Trilostane was equally effective in female and male rats. Weight gain, serum aldosterone and corticosterone concentrations, and behavior assessed subjectively and by elevated plus maze were unchanged by the trilostane treatment. These studies suggest that the synthesis in the brain of a mineralocorticoid receptor agonist, probably aldosterone, is responsible in part for the salt-induced hypertension of the inbred Dahl SS/jr rat.
Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves
Authors: D'Andrea Michael R. , Saban Marcia R. , Gerard Norma P. , Wershil Barry K. , Saban Ricardo
Published: October 2004

A spatial association between mast cells and nerves has been described in both the gastrointestinal and genitourinary tracts. However, the factors that influence the anatomic relationship between mast cells and nerves have not been completely defined. It has been suggested that the high-affinity receptor for substance P [neurokinin-1 (NK1)] might modulate this interaction. We therefore assessed mast cell-nerve relationships in tissues isolated from wild-type and NK1receptor knockout (NK1−/−) mice. We now report that, in the complete absence of NK1receptor expression, there is a significant increase in the number of mast cells without a change in the anatomic relationship between mast cell and nerves in stomach and bladder tissues at the light microscopic level. We next determined whether transplanted mast cells would maintain their spatial distribution, number, and contact with nerve elements. For this purpose, mast cell-deficient KitW/KitW−vmice were reconstituted with wild-type or NK1−/−bone marrow. No differences in mast cell-nerve contact were observed. These results suggest that NK1receptor expression is important in the regulation of the number of mast cells but is not important in the interaction between mast cells and nerves. Furthermore, the interaction between mast cells and nerves is not mediated through NK1receptor expression on the mast cell. Further studies are needed to determine the molecular pathway involved in mast cell migration and interaction with nerve elements, but the model of reconstitution of KitW/KitW−vmice with mast cells derived from different genetically engineered mice is a useful approach to further explore these mechanisms.
Depression of cell metabolism and proliferation by membrane-permeable and -impermeable modulators: role for AMP-to-ATP ratio
Authors: Menze Michael A. , Clavenna Matthew J. , Hand Steven C.
Published: October 2004

The metabolic and developmental depression commonly observed during natural states of dormancy, such as diapause and quiescence, is typically accompanied by an increase in the intracellular ratio of AMP to ATP. We investigated the impact of artificially increasing the AMP-to-ATP ratio in mouse macrophages. Evidence is presented here that the P2X7receptor channel can be used as an effective means to load cells with membrane-impermeable compounds. Intracellular loading of adenosine-5′- O-thiomonophosphate (AMPS), a nonhydrolyzable analog of 5′-AMP and potent activator of AMP-activated protein kinase, significantly depresses metabolism and proliferation of macrophages. The intracellular effective AMP-to-ATP ratio obtained (the sum of AMPS plus endogenous 5′-AMP) was 0.073, well above that reported to activate AMP-activated protein kinase in vitro. Optimizing both the conditions under which the P2X7receptor channel is opened and the duration of opening facilitates high analog uptake and ∼98% survivorship. An advantage to AMPS is its minimal impact on other components of the nucleotide pool, most notably the unchanged concentration of ADP. An alternative way to shift the effective AMP-to-ATP ratio is by incubation with the membrane-permeable compound 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), which is phosphorylated intracellularly to form the 5′-AMP analog ZMP. Despite a rapid intracellular accumulation of AICAR, conversion to ZMP was slow and inefficient. Furthermore, AICAR incubation increased cellular ADP, and, although cell proliferation was depressed, the overall cellular energy flow was unchanged. The rapid action of AMPS avoids upregulation of compensatory metabolic pathways and may provide a viable approach for promoting cell stasis.
Restraint stress delays solid gastric emptying via a central CRF and peripheral sympathetic neuron in rats
Authors: Nakade Yukiomi , Tsuchida Daisuke , Fukuda Hiroyuki , Iwa Masahiro , Pappas Theodore N. , Takahashi Toku
Published: October 2004

Central corticotropin-releasing factor (CRF) delays gastric emptying through the autonomic nervous system. CRF plays an important role in mediating delayed gastric emptying induced by stress. However, it is not clear whether a sympathetic or parasympathetic pathway is involved in the mechanism of central CRF-induced inhibition of solid gastric emptying. The purpose of this study was to investigate whether 1) CRF inhibits solid gastric emptying via a peripheral sympathetic pathway and 2) stress-induced inhibition of solid gastric emptying is mediated via a central CRF and peripheral sympathetic pathways. Using male Sprague-Dawley rats, CRF was injected intracisternally with or without various adrenergic-blocking agents. To investigate whether central CRF-induced inhibition of solid gastric emptying is mediated via a peripheral sympathetic pathway, rats underwent celiac ganglionectomy 1 wk before the gastric emptying study. After solid meal ingestion (90 min), gastric emptying was calculated. To investigate the role of endogenous CRF in stress-induced delayed gastric emptying, a CRF type2receptor antagonist, astressin2-B, was intracisternally administered. Rats were subjected to a restraint stress immediately after the feeding. Intracisternal injection of CRF (0.1–1.0 μg) dose-dependently inhibited solid gastric emptying. The inhibitory effect of CRF on solid gastric emptying was significantly blocked by guanethidine, propranolol, and celiac ganglionectomy but not by phentolamine. Restraint stress significantly delayed solid gastric emptying, which was improved by astressin2-B, guanethidine, and celiac ganglionectomy. Our research suggests that restraint stress inhibits solid gastric emptying via a central CRF type2receptor and peripheral sympathetic neural pathway in rats.