bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of plant genes regulated in resistant potato Solanum sparsipilum during the early stages of infection by Globodera pallida
Authors: Jolivet Katell , Grenier Eric , Bouchet Jean-Paul , Esquibet Magali , Kerlan Marie-Claire , Caromel Bernard , Mugniéry Didier , Lefebvre Véronique
Published: June 2007

Using a complementary (c)DNA-amplified fragment length polymorphism (AFLP) approach, we investigated differential gene expression linked to resistance mechanisms during the incompatible potato – Globodera pallida interaction. Expression was compared between a resistant and a susceptible potato clone, inoculated or not inoculated with G. pallida. These clones were issued from a cross between the resistant Solanum sparsipilum spl329.18 accession and the susceptible dihaploid S. tuberosum Caspar H3, and carried, respectively, resistant and susceptible alleles at the resistance quantitative trait loci (QTLs). Analysis was done on root fragments picked up at 4 time points, during a period of 6 days after infection, from penetration of the nematode in the root to degradation of the feeding site in resistant plants. A total of 2560 transcript-derived fragments (TDFs) were analyzed, resulting in the detection of 46 TDFs that were up- or downregulated. The number of TDFs that were up- or downregulated increased with time after inoculation. The majority of TDFs were upregulated at only 1 or 2 time points in response to infection. After isolation and sequencing of the TDFs of interest, a subset of 36 sequences were identified, among which 22 matched plant sequences and 2 matched nematode sequences. Some of the TDFs that matched plant genes showed clear homologies to genes involved in cell-cycle regulation, transcription regulation, resistance downstream signalling pathways, and defense mechanisms. Other sequences with homologies to plant genes of unknown function or without any significant similarity to known proteins were also found. Although not exhaustive, these results represent the most extensive list of genes with altered RNA levels after the incompatible G. pallida–potato interaction that has been published to date. The function of these genes could provide insight into resistance or plant defense mechanisms during incompatible potato-cyst nematode interactions.
A natural population of the butterfly Eurema hecabe with Wolbachia-induced female-biased sex ratio not by feminization
Authors: Narita Satoko , Nomura Masashi , Kageyama Daisuke
Published: June 2007

In butterflies, the adult sex ratio observed in the field is usually male-biased, although the sex ratio of their progeny is 1:1. This is due to the higher motility and larger behavioral range of males than females. As expected, the sex ratio of Eurema hecabe butterflies collected at 6 localities throughout Japan was male-biased. However, in Tsukuba, located in the central part of Japan, the sex ratio was found to be biased toward females. Their progeny reared in the laboratory also exhibited a female-biased sex ratio. A single strain of Wolbachia is considered to be the cause of the sex-ratio distortion, because antibiotic treatment reversed the sex ratio to 1:1, and only a single nucleotide sequence of wsp, a highly variable Wolbachia gene, was detected by molecular analysis. Cytogenetic analysis excluded the possibility of feminization as the underlying mechanism. In addition, when the wild-caught females that had already mated in nature were treated with antibiotics before oviposition, egg-hatch rates were extremely low, suggesting that the same Wolbachia strain also caused cytoplasmic incompatibility. Our findings suggest the possibility that a single strain of Wolbachia induces 2 distinct reproductive manipulations in the same host.
CAPS markers specific to Eb, Ee, and R genomes in the tribe Triticeae
Authors: Li X.-M. , Lee B.S. , Mammadov A.C. , Koo B.-C. , Mott I.W. , Wang R.R.-C.
Published: June 2007

Wild Triticeae grasses serve as important gene pools for forage and cereal crops. Understanding their genome compositions is pivotal for efficient use of this vast gene pool in germplasm-enhancement programs. Several cleaved amplified polymorphic sequence (CAPS) markers were developed to distinguish the Eb, Ee, and R genomes. With the aid of disomic addition lines of wheat, it was confirmed that all 7 chromosomes of Eb, Ee, and R genomes carry these genome-specific CAPS markers. Thus, the identified CAPS markers are useful in detecting and monitoring the chromosomes of these 3 genomes. This study also provides evidence suggesting that some Purdue and Chinese germplasm lines developed for barley yellow dwarf virus (BYDV) resistance are different from those developed in Australia. Furthermore, Thinopyrum intermedium and Thinopyrum ponticum were shown to have different genome constitutions. Sequence analyses of the 1272 bp sequences, containing Ty3/gypsy retrotransposons, from the Eb, Ee, and R genomes also shed light on the evolution of these 3 genomes.
GRANGER CAUSALITY BETWEEN MULTIPLE INTERDEPENDENT NEUROBIOLOGICAL TIME SERIES: BLOCKWISE VERSUS PAIRWISE METHODS
Authors: WANG XUE , CHEN YONGHONG , BRESSLER STEVEN L. , DING MINGZHOU
Published: June 2007

Granger causality is becoming an important tool for determining causal relations between neurobiological time series. For multivariate data, there is often the need to examine causal relations between two blocks of time series, where each block could represent a brain region of interest. Two alternative methods are available. In the pairwise method, bivariate autoregressive models are fit to all pairwise combinations involving one time series from the first block and one from the second. The total Granger causality between the two blocks is then derived by summing pairwise causality values from each of these models. This approach is intuitive but computationally cumbersome. Theoretically, a more concise method can be derived, which we term the blockwise Granger causality method. In this method, a single multivariate model is fit to all the time series, and the causality between the two blocks is then computed from this model. We compare these two methods by applying them to cortical local field potential recordings from monkeys performing a sensorimotor task. The obtained results demonstrate consistency between the two methods and point to the significance potential of utilizing Granger causality analysis in understanding coupled neural systems.
NOISE CONTROLLED SYNCHRONIZATION IN POTASSIUM COUPLED NEURAL MODELS
Authors: POSTNOV DMITRY E. , RYAZANOVA LUDMILA S. , ZHIRIN ROMAN A. , MOSEKILDE ERIK , SOSNOVTSEVA OLGA V.
Published: June 2007

The paper applies biologically plausible models to investigate how noise input to small ensembles of neurons, coupled via the extracellular potassium concentration, can influence their firing patterns. Using the noise intensity and the volume of the extracellular space as control parameters, we show that potassium induced depolarization underlies the formation of noise-induced patterns such as delayed firing and synchronization. These phenomena are associated with the appearance of new time scales in the distribution of interspike intervals that may be significant for the spatio-temporal oscillations in neuronal ensembles.
MAINTAINING SYNCHRONIZATION BY DECENTRALIZED FEEDBACK CONTROL IN TIME DELAY NEURAL NETWORKS WITH PARAMETER UNCERTAINTIES
Authors: CHEN MOU , JIANG CHANG-SHENG , WU QING-XIAN , CHEN WEN-HUA
Published: June 2007

A decentralized feedback control scheme is proposed to synchronize linearly coupled identical neural networks with time-varying delay and parameter uncertainties. Sufficient condition for synchronization is developed by carefully investigating the uncertain nonlinear synchronization error dynamics in this article. A procedure for designing a decentralized synchronization controller is proposed using linear matrix inequality (LMI) technique. The designed controller can drive the synchronization error to zero and overcome disruption caused by system uncertainty and external disturbance.
CONTROLLING SYNCHRONIZATION IN A NEURON-LEVEL POPULATION MODEL
Authors: CHAKRAVARTHY NIRANJAN , SABESAN SHIVKUMAR , IASEMIDIS LEON , TSAKALIS KOSTAS
Published: June 2007

We have studied coupled neural populations in an effort to understand basic mechanisms that maintain their normal synchronization level despite changes in the inter-population coupling levels. Towards this goal, we have incorporated coupling and internal feedback structures in a neuron-level population model from the literature. We study two forms of internal feedback — regulation of excitation, and compensation of excessive excitation with inhibition. We show that normal feedback actions quickly regulate/compensate an abnormally high coupling between the neural populations, whereas a pathology in these feedback actions can lead to abnormal synchronization and "seizure"-like high amplitude oscillations. We then develop an external control paradigm, termed feedback decoupling, as a robust synchronization control strategy. The external feedback decoupling controller acts to achieve the operational objective of maintaining normal-level synchronous behavior irrespective of the pathology in the internal feedback mechanisms. Results from such an analysis have an interesting physical interpretation and specific implications for the treatment of diseases such as epilepsy. The proposed remedy is consistent with a variety of recent observations in the human and animal epileptic brain, and with theories from nonlinear systems, adaptive systems, optimization, and neurophysiology.
QUANTUM NON-DEMOLITION BELL-STATE MEASUREMENT AND n-PARTY GHZ STATE PREPARATION IN QUANTUM DOT
Authors: GUO GUO-PING , ZHANG HUI , GUO GUANG-CAN
Published: June 2007

By exploiting the fermionic qubit parity measurement, we present a scheme to realize quantum non-demolition (QND) measurement of Bell states and generate n-party GHZ state in quantum dot. Compared with the original protocol, the required electron transfer before and after parity measurement can be nonadiabatic, which may speed up the operation speed and make the omitting of spin-orbit interaction more reasonable. This may help us to construct CNOT gate without highly precise control of coupling as the way of D. Gottesman and I. L. Chuang.
SCANNING ELECTRON MICROSCOPY OBSERVATION OF IN-DEVICE InAs/AlAs QUANTUM DOTS BY SELECTIVE ETCHING OF CAPPING LAYERS
Authors: SUN JIE , ZHOU DAYONG , LI RUOYUAN , ZHAO CHANG , YE XIAOLING , XU BO , CHEN YONGHAI , WANG ZHANGUO
Published: June 2007

Self-assembled InAs/AlAs quantum dots embedded in a resonant tunneling diode device structure are grown by molecular beam epitaxy. Through the selective etching in a C 6 H 8 O 7 · H 2 O-K 3 C 6 H 5 O 7 · H 2 O-H 2 O 2 buffer solution, 310 nm GaAs capping layers are removed and the InAs/AlAs quantum dots are observed by field-emission scanning electron microscopy. It is shown that as-fabricated quantum dots have a diameter of several tens of nanometers and a density of 1010 cm-2 order. The images taken by this means are comparable or slightly better than those of transmission electron microscopy. The undercut of the InAs/AlAs layer near the edges of mesas is detected and that verifies the reliability of the quantum dot images. The inhomogeneous oxidation of the upper AlAs barrier in H 2 O 2 is also observed. By comparing the morphologies of the mesa edge adjacent regions and the rest areas of the sample, it is concluded that the physicochemical reaction introduced in this letter is diffusion limited.
FACTORS THAT INFLUENCE PEAK POWER OF Q-SWITCHED FIBER LASER
Authors: SHANG LIANJU , NING JIPING , CAO ZHENZHONG , FAN GUOFANG , CHEN ZHIQIANG , HAN QUN , ZHANG HUAYONG
Published: June 2007

Q-switched fiber lasers are very attractive sources in many applications such as military affairs, surgical operation, laser machining, laser marking, nonlinear frequency conversion, range finding, remote sensing and optical time domain reflectometer. To improve the peak power of Q-switched fiber laser is what we pursue, and to know the factors that influence the peak power is what we should make clear first. In this paper, certain essential factors that influence the peak power are presented, with their theoretical basis clarified, which may be helpful to the design of the kindred Q-switched fiber lasers.
BAYESIAN NETWORKS VERSUS OTHER PROBABILISTIC MODELS FOR THE MULTIPLE DIAGNOSIS OF LARGE DEVICES
Authors: VÉRONIQUE DELCROIX , MOHAMED-AMINE MAALEJ , SYLVAIN PIECHOWIAK
Published: June 2007

Multiple diagnosis methods using Bayesian networks are rooted in numerous research projects about model-based diagnosis. Some of this research exploits probabilities to make a diagnosis. Many Bayesian network applications are used for medical diagnosis or for the diagnosis of technical problems in small or moderately large devices. This paper explains in detail the advantages of using Bayesian networks as graphic probabilistic models for diagnosing complex devices, and then compares such models with other probabilistic models that may or may not use Bayesian networks.
A LANGUAGE AND ENVIRONMENT FOR ANALYSIS OF DYNAMICS BY SIMULATION
Authors: BOSSE TIBOR , JONKER CATHOLIJN M. , VAN DER MEIJ LOURENS , TREUR JAN
Published: June 2007

This article presents the language and software environment LEADSTO that has been developed to model and simulate dynamic processes in terms of both qualitative and quantitative concepts. The LEADSTO language is a declarative order-sorted temporal language, extended with quantitative notions like integer and real. Dynamic processes can be modelled in LEADSTO by specifying the direct temporal dependencies between state properties in successive states. Based on the LEADSTO language, a software environment was developed that performs simulations of LEADSTO specifications, generates data-files containing traces of simulation for further analysis, and constructs visual representations of traces. The approach proved its worth in a number of research projects in different domains.
MULTI-ENGINE COLLABORATIVE BOOTSTRAPPING FOR WORD SENSE DISAMBIGUATION
Authors: DUAN JIANYONG , LU RUZHAN , LI XUENING
Published: June 2007

In this paper we propose a new word sense disambiguation method called Multi-engine Collaborative Bootstrapping (MCB) that combines different types of corpora and also uses two languages for bootstrapping. MCB uses the bilingual bootstrapping as its core algorithm that leading to incremental knowledge acquisition. The EM model is applied to train parameters in a base learner. The feature translation model is improved by semantic correlation estimation. In addition we use multi-engine selection to produce qualified starting seeds from parallel corpora and monolingual corpora. Those seeds that are generated through unsupervised machine learning approaches can also ensure bootstrapping effectiveness in contrast with manually selected seeds in spite of their different selection mechanisms. Experimental results prove the effectiveness of MCB. Some factors including feature space and starting seed number are concerned involved in our experiments because the EM algorithm is sensitive to starting values. Limitation of resources is also a concern.
A FAST ALGORITHM FOR BANDWIDTH MINIMIZATION
Authors: LIM ANDREW , RODRIGUES BRIAN , XIAO FEI
Published: June 2007

We propose a simple and direct node shifting method with hill climbing for the well-known matrix bandwidth minimization problem. Many heuristics have been developed for this NP-complete problem including the Cuthill-McKee (CM) and the Gibbs, Poole and Stockmeyer (GPS) algorithms. Recently, heuristics such as Simulated Annealing, Tabu Search and GRASP have been used, where Tabu Search and the GRASP with Path Relinking achieved significantly better solution quality than the CM and GPS algorithms. Experimentation shows that our method achieves the best solution quality when compared with these while being much faster than newly-developed algorithms.
ON GIRSANOV AND GENERALIZED FEYNMAN–KAC TRANSFORMATIONS FOR SYMMETRIC MARKOV PROCESSES
Authors: CHEN CHUAN-ZHONG , MA ZHI-MING , SUN WEI
Published: June 2007

Let X be a Markov process, which is assumed to be associated with a symmetric Dirichlet form [Formula: see text]. For [Formula: see text], the extended Dirichlet space, we have the classical Fukushima's decomposition: [Formula: see text], where [Formula: see text] is a quasi-continuous version of u, [Formula: see text] the martingale part and [Formula: see text] the zero energy part. In this paper, we investigate two important transformations for X, the Girsanov transform induced by [Formula: see text] and the generalized Feynman–Kac transform induced by [Formula: see text]. For the Girsanov transform, we present necessary and sufficient conditions for which to induce a positive supermartingale and hence to determine another Markov process [Formula: see text]. Moreover, we characterize the symmetric Dirichlet form associated with the Girsanov transformed process [Formula: see text]. For the generalized Feynman–Kac transform, we give a necessary and sufficient condition for the generalized Feynman–Kac semigroup to be strongly continuous.
EQUILIBRIUM KAWASAKI DYNAMICS OF CONTINUOUS PARTICLE SYSTEMS
Authors: KONDRATIEV YURI , LYTVYNOV EUGENE , RÖCKNER MICHAEL
Published: June 2007

We construct a new equilibrium dynamics of infinite particle systems in a Riemannian manifold X. This dynamics is an analog of the Kawasaki dynamics of lattice spin systems. The Kawasaki dynamics now is a process where interacting particles randomly hop over X. We establish conditions on the a priori explicitly given symmetrizing measure and the generator of this dynamics, under which a corresponding conservative Markov processes exists. We also outline two types of scaling limit of the equilibrium Kawasaki dynamics: one leading to an equilibrium Glauber dynamics in continuum (a birth-and-death process), and the other leading to a diffusion dynamics of interacting particles (in particular, the gradient stochastic dynamics).
REGULARITY OF SOLUTIONS TO LINEAR STOCHASTIC SCHRÖDINGER EQUATIONS
Authors: MORA CARLOS M. , REBOLLEDO ROLANDO
Published: June 2007

We develop linear stochastic Schrödinger equations driven by standard cylindrical Brownian motions (LSSs) that unravel quantum master equations in Lindblad form into quantum trajectories. More precisely, this paper establishes the existence and uniqueness of the smooth strong solution Xt to a LSS with regular initial condition. Moreover, we obtain that the mean value of the square norm of Xt is constant. We also treat the approximation of LSSs by ordinary stochastic differential equations. We apply our results to:

(i) models of quantum measurements of position and momentum; and

(ii) a system formed by fermions.
HEISENBERG–WEYL LIE ALGEBRA AND NATURAL EXPONENTIAL FAMILIES
Authors: MOHAMMED ZARAI
Published: June 2007

We present in this work a specific construction of raising and lowering operators for 2-orthogonal quasi-monomial polynomials associated with continuous and discrete natural exponential families. We use these operators in order to characterize the real class of cubic natural exponential families.
GRADED POLYNOMIAL IDENTITIES OF VERBALLY PRIME ALGEBRAS
Authors: DI VINCENZO ONOFRIO M. , NARDOZZA VINCENZO
Published: June 2007

Let F be a field and let E be the Grassmann algebra of an infinite dimensional F-vector space. For any p,q ∈ ℕ, the algebra Mp,q(E) can be turned into a ℤp+q × ℤ2-algebra by combining an elementary ℤp+q-grading with the natural ℤ2-grading on E. The tensor product Mp,q(E) ⊗ Mr,s(E) can be turned into a ℤ(p+q)(r+s) × ℤ2-algebra in a similar way. In this paper, we assume that F has characteristic zero and describe a system of generators for the graded polynomial identities of the algebras Mp,q(E) and Mp,q(E) ⊗ Mr,s(E) with respect to these new gradings. We show that this tensor product is graded PI-equivalent to Mpr+qs,ps+qr(E). This provides a new proof of the well known Kemer's PI-equivalence between these algebras. Then we classify all the graded algebras Mp,q(E) having no non-trivial monomial identities, and finally calculate how many non-isomorphic gradings of this new type are available for Mp,q(E).
ON THE CLASSIFICATION OF FINITE SANS-GROUPS
Authors: KORCHAGINA INNA
Published: June 2007

A finite SANS-group G is a group where NG(H) = CG(H) for every non-abelian subgroup H or G. In this paper, we provide a new proof and modify the statement for the structure theorem of the non-soluble SANS-groups.
AN AMALGAMATED DUPLICATION OF A RING ALONG AN IDEAL: THE BASIC PROPERTIES
Authors: D'ANNA MARCO , FONTANA MARCO
Published: June 2007

We introduce a new general construction, denoted by R ⋈ E, called the amalgamated duplication of a ring R along an R-module E, that we assume to be an ideal in some overring of R. (Note that, when E2 = 0, R ⋈ E coincides with the Nagata's idealization R ⋉ E.).

After discussing the main properties of the amalgamated duplication R ⋈ E in relation with pullback-type constructions, we restrict our investigation to the study of R ⋈ E when E is an ideal of R. Special attention is devoted to the ideal-theoretic properties of R ⋈ E and to the topological structure of its prime spectrum.
ARTINIAN MODULES OVER FC-HYPERCENTRAL GROUPS
Authors: KURDACHENKO L. A. , SEMKO N. N. , SUBBOTIN I. YA.
Published: June 2007

Artinian modules over a group ring DG, where G is an FC-hypercentral group and D is a Dedekind domain, are studied. In particular, the conditions under which an artinian DG-module is countably generated over D, and when the socular height of A is at most, have been obtained.
SIMPLE AND CATALYST-FREE SYNTHESIS OF SILICON OXIDE NANOWIRES AND NANOCOILS
Authors: CHEN XINQI , RUOFF RODNEY S.
Published: June 2007

In this paper, a simple method for synthesizing SiO x nanowires and nanocoils is presented. Si substrates with an oxide layer were placed in a tube furnace exposed to temperatures ranging from 900°C to 1200°C for a few hours under a mixture of flowing Ar and H2 gas maintained at ambient pressure. Nanowires were grown from the surface when the furnace temperature was above 1000°C and a high yield could be achieved at 1100°C. SiO x nanocoils have also been observed and the sample treated at 1000°C had the highest concentration of them. TEM images show that the nanowires and the nanocoils have an amorphous structure and analysis of EDX spectra (obtained in the TEM) shows that x varies from 1.2 to 2.0. The mechanism of growth is discussed.
Branched fibers in dystrophic mdx muscle are associated with a loss of force following lengthening contractions
Authors: Chan S. , Head S. I. , Morley J. W.
Published: June 2007

We demonstrated that the susceptibility of skeletal muscle to injury from lengthening contractions in the dystrophin-deficient mdx mouse is directly linked with the extent of fiber branching within the muscles and that both parameters increase as the mdx animal ages. We subjected isolated extensor digitorum longus muscles to a lengthening contraction protocol of 15% strain and measured the resulting drop in force production (force deficit). We also examined the morphology of individual muscle fibers. In mdx mice 1–2 mo of age, 17% of muscle fibers were branched, and the force deficit of 7% was not significantly different from that of age-matched littermate controls. In mdx mice 6–7 mo of age, 89% of muscle fibers were branched, and the force deficit of 58% was significantly higher than the 25% force deficit of age-matched littermate controls. These data demonstrated an association between the extent of branching and the greater vulnerability to contraction-induced injury in the older fast-twitch dystrophic muscle. Our findings demonstrate that fiber branching may play a role in the pathogenesis of muscular dystrophy in mdx mice, and this could affect the interpretation of previous studies involving lengthening contractions in this animal.
Linking mitochondrial function to diabetes mellitus: an animal's tale
Authors: Berdanier Carolyn D.
Published: June 2007

Diabetes mellitus is one of the most common genetic diseases that afflicts humans. It is not a single disease but a collection of diseases having in common an abnormal glucose-insulin relationship and a dysfunctional regulation of glucose homeostasis. Of interest is the diabetic state that results when the mitochondrial genome mutates. Epidemiological studies have shown this to occur in humans. Detailed metabolic studies that are impossible to conduct in humans have been carried out in the BHE/Cdb rat. This rat has a mutated mitochondrial ATPase 6 gene. Strategies to ameliorate the consequences of this mutation have been explored and some of the mechanisms for the transcription and translation of the mitochondrial gene product have been elucidated.
Effect of subcutaneous injections of PYY1-36 and PYY3-36 on appetite, ad libitum energy intake, and plasma free fatty acid concentration in obese males
Authors: Sloth Birgitte , Davidsen Louise , Holst Jens Juul , Flint Anne , Astrup Arne
Published: June 2007

Intraveneous (iv) PYY3-36 infusions have been reported to reduce energy intake (EI) in humans, whereas few studies exist on effects of PYY1-36. The aim of the present study was to examine effects of subcutaneous (sc) injections of PYY1-36 and PYY3-36 on appetite, ad libitum EI, plasma concentrations of PYY and free fatty acids (FFA) in obese males. Twenty-four males (BMI 27–40 kg/m2) were randomly assigned to two groups receiving sc injections of either PYY1-36 or PYY3-36 in a blinded, placebo-controlled, dose-escalating, cross-over study. Subjects were studied 5 days in succession, with escalating doses of PYY1-36 [saline, 50, 100, 150, and 200 pmol PYY1-36/kg lean body mass (LBM)], or PYY3-36 (saline, 25, 50, 75, and 100 pmol PYY3-36/kg LBM), respectively. PYY injections resulted in dose-dependent increases in plasma PYY levels but no effect on EI in either the PYY1-36 or the PYY3-36 group. However, increasing doses of PYY3-36, but not PYY1-36, resulted in increased ratings of satiety and decreased ratings of hunger, thirst, and prospective food consumption. Although not dose dependently, significant elevation of plasma FFA was seen after injection of PYY3-36, but not PYY1-36. Although sc administration of PYY was well tolerated, it remains to be determined whether high-dose PYY3-36 is sufficient in reducing EI in long-term trials, and if so, whether the reduction in EI occurs without nausea. PYY1-36 is unlikely to be important in regulating energy intake. The PYY3-36 administrations caused a non-dose-dependent mobilization of FFA, likely through a direct effect.
Oxidoreductase, morphogenesis, extracellular matrix, and calcium ion-binding gene expression in streptozotocin-induced diabetic rat heart
Authors: van Lunteren Erik , Moyer Michelle
Published: June 2007

Diabetes has far-ranging effects on cardiac structure and function. Previous gene expression studies of the heart in animal models of type 1 diabetes concur that there is altered expression of genes involved in lipid and protein metabolism, but they diverge with regard to expression changes involving many other functional groups of genes of mechanistic importance in diabetes-induced cardiac dysfunction. To obtain additional information about these controversial areas, genome-wide expression was assessed using microarrays in left ventricle from streptozotocin-diabetic and normal rats. There were 261 genes with statistically significant altered expression of at least ±1.5-fold, of which 124 were increased and 137 reduced by diabetes. Gene ontology assignment testing identified several statistical significantly overrepresented groups among genes with altered expression, which differed for increased compared with reduced expression. Relevant gene groups with increased expression by diabetes included lipid metabolism ( P < 0.001, n = 13 genes, fold change 1.5 to 14.6) and oxidoreductase activity ( P < 0.001, n = 17, fold change 1.5 to 4.6). Groups with reduced expression by diabetes included morphogenesis ( P < 0.00001, n = 28, fold change −1.5 to −5.1), extracellular matrix ( P < 0.02, n = 9, fold change −1.5 to −3.9), cell adhesion ( P < 0.05, n = 10, fold change −1.5 to −2.7), and calcium ion binding ( P < 0.01, n = 13, fold change −1.5 to −3.0). Array findings were verified by quantitative PCR for 36 genes. These data combined with previous findings strengthen the evidence for diabetes-induced cardiac gene expression changes involved in cell growth and development, oxidoreductase activity, and the extracellular matrix and also point out other gene groups not previously identified as being affected, such as those involved in calcium ion homeostasis.
Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion
Authors: Smeets Paul A. M. , Vidarsdottir Solrun , de Graaf Cees , Stafleu Annette , van Osch Matthias J. P. , Viergever Max A. , Pijl Hanno , van der Grond Jeroen
Published: June 2007

We previously showed that hypothalamic neuronal activity, as measured by the blood oxygen level-dependent (BOLD) functional MRI signal, declines in response to oral glucose intake. To further explore the mechanism driving changes in hypothalamic neuronal activity in response to an oral glucose load, we here compare hypothalamic BOLD signal changes subsequent to an oral vs. an intravenous (iv) glucose challenge in healthy humans. Seven healthy, normal-weight men received four interventions in random order after an overnight fast: 1) ingestion of glucose solution (75 g in 300 ml) or 2) water (300 ml), and 3) iv infusion of 40% glucose solution (0.5 g/kg body wt, maximum 35 g) or 4) infusion of saline (0.9% NaCl, equal volume). The BOLD signal was recorded as of 8 min prior to intervention (baseline) until 30 min after. Glucose infusion was associated with a modest and transient signal decline in the hypothalamus. In contrast, glucose ingestion was followed by a profound and persistent signal decrease despite the fact that plasma glucose levels were almost threefold lower than in response to iv administration. Accordingly, glucose ingestion tended to suppress hunger more than iv infusion ( P < 0.1). We infer that neural and endocrine signals emanating from the gastrointestinal tract are critical for the hypothalamic response to nutrient ingestion.
Pharmacological properties of the enhanced-affinity glucocorticoid fluticasone furoate in vitro and in an in vivo model of respiratory inflammatory disease
Authors: Salter Mark , Biggadike Keith , Matthews Joyce L. , West Michael R. , Haase Michael V. , Farrow Stuart N. , Uings Iain J. , Gray David W.
Published: June 2007

Fluticasone furoate (FF) is a novel enhanced-affinity glucocorticoid that has been developed as topical therapy for allergic rhinitis. The pharmacological properties of FF have been investigated using a number of in vitro experimental systems. FF demonstrated very potent glucocorticoid activity in several key pathways downstream of the glucocorticoid receptor (GR) as follows: the transrepression nuclear factor-κB (NF-κB) pathway, the transactivation glucocorticoid response element pathway, and inhibition of the proinflammatory cytokine tumor necrosis factor-α. Furthermore, FF showed the greatest potency compared with other glucocorticoids for preserving epithelial integrity and reducing epithelial permeability in response to protease- and mechanical-induced cell damage. FF showed a 30- to >330,000-fold selectivity for GR-mediated inhibition of NF-κB vs. the other steroid hormone receptors, substantially better than a number of other clinically used glucocorticoids. In studies examining the respiratory tissue binding properties of glucocorticoids, FF had the largest cellular accumulation and slowest rate of efflux compared with other clinically used glucocorticoids, consistent with greater tissue retention. The in vivo anti-inflammatory activity of FF was assessed in the Brown Norway rat ovalbumin-induced lung eosinophilial model of allergic lung inflammation. At a dose of only 30 μg, FF achieved almost total inhibition of eosinophil influx in the lung, an inhibition that was greater than that seen with the same dose of fluticasone propionate. In conclusion, the potent and selective pharmacological profile of FF described here could deliver an effective, safe, and sustained topical treatment of respiratory inflammatory diseases such as allergic rhinitis and asthma.
Centrally administered vasopressin cross-sensitizes rats to amphetamine and drinking hypertonic NaCl
Authors: McBride Shawna M. , Flynn Francis W.
Published: June 2007

Prior sodium restriction cross-sensitizes rats to the psychomotor effects of amphetamines and vice versa. Repeated central injections of vasopressin (VP) induce a psychomotor sensitization similar to amphetamine sensitization and repeated sodium deficiency. Thus brain VP signaling may be a common mechanism involved in mediating these two motivational systems. In experiment 1, we tested the hypothesis that rats previously sensitized to central VP would show enhanced psychomotor responses to amphetamine. Rats were administered saline, VP (50 ng), or amphetamine (1 mg/kg or 3 mg/kg) on days 1 and 2, and given saline or amphetamine on day 3. Amphetamine produced psychomotor arousal in all groups. However, amphetamine on day 3 elicited a significantly greater psychomotor response in rats that had prior injections of amphetamine or VP than in rats previously treated with saline. In experiment 2, the hypothesis that prior experience with central VP would cross-sensitize rats to drinking hypertonic sodium (NaCl) solutions was tested. Rats were administered VP (50 ng) or saline for 3 days. On the fourth day, nondeprived rats were given access to 0.3 M NaCl and water for 1 h. Control and saline-treated rats only drank 1 ml of 0.3 M NaCl, but rats previously exposed to central VP drank significantly more hypertonic saline (4 ml). These results show that prior experience with central VP cross-sensitizes rats to the psychomotor stimulant effects of amphetamine and the ingestion of concentrated NaCl solutions. This pattern of cross-sensitization links central VP signaling, amphetamine, and sodium deficiency, and therefore it may play a role in the cross-sensitization between sodium appetite and amphetamines.
Enhanced susceptibility to suicidal death of erythrocytes from transgenic mice overexpressing erythropoietin
Authors: Föller Michael , Kasinathan Ravi S. , Koka Saisudha , Huber Stephan M. , Schuler Beat , Vogel Johannes , Gassmann Max , Lang Florian
Published: June 2007

Eryptosis, a suicidal death of mature erythrocytes, is characterized by decrease of cell volume, cell membrane blebbing, and breakdown of cell membrane asymmetry with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include increased cytosolic Ca2+activity, which could result from activation of Ca2+-permeable cation channels. Ca2+triggers phosphatidylserine exposure and activates Ca2+-sensitive K+channels, leading to cellular K+loss and cell shrinkage. The cation channels and thus eryptosis are stimulated by Cl−removal and inhibited by erythropoietin. The present experiments explored eryptosis in transgenic mice overexpressing erythropoietin (tg6). Erythrocytes were drawn from tg6 mice and their wild-type littermates (WT). Phosphatidylserine exposure was estimated from annexin binding and cell volume from forward scatter in fluorescence-activated cell sorting (FACS) analysis. The percentage of annexin binding was significantly larger and forward scatter significantly smaller in tg6 than in WT erythrocytes. Transgenic erythrocytes were significantly more resistant to osmotic lysis than WT erythrocytes. Cl−removal and exposure to the Ca2+ionophore ionomycin (1 μM) increased annexin binding and decreased forward scatter, effects larger in tg6 than in WT erythrocytes. The K+ionophore valinomycin (10 nM) triggered eryptosis in both tg6 and WT erythrocytes and abrogated differences between genotypes. An increase of extracellular K+concentration to 125 mM blunted the difference between tg6 and WT erythrocytes. Fluo-3 fluorescence reflecting cytosolic Ca2+activity was larger in tg6 than in WT erythrocytes. In conclusion, circulating erythrocytes from tg6 mice are sensitized to triggers of eryptosis but more resistant to osmotic lysis, properties at least partially due to enhanced Ca2+entry and increased K+channel activity.
Control of extracellular cysteine/cystine redox state by HT-29 cells is independent of cellular glutathione
Authors: Anderson Corinna L. , Iyer Smita S. , Ziegler Thomas R. , Jones Dean P.
Published: June 2007

Human cell lines regulate the redox state (Eh) of the cysteine/cystine (Cys/CySS) couple in culture medium to approximately −80 mV, a value similar to the average Eh for Cys/CySS in human plasma. The mechanisms involved in regulation of extracellular Eh of Cys/CySS are not known, but GSH is released from tissues at rates proportional to tissue GSH concentration, and this released GSH could react with CySS to contribute to maintenance of this balance. The present study was undertaken to determine whether depletion of cellular GSH alters regulation of extracellular Cys/CySS Eh. Decrease of GSH in HT-29 cells by inhibiting synthesis with l-buthionine-[ S, R]-sulfoximine showed no effect on the rate of reduction of extracellular CySS to achieve a stable Eh for Cys/CySS in the culture medium. Limiting Cys and CySS in the culture medium also substantially decreased cellular GSH but resulted in no significant effect on extracellular Cys/CySS Eh. Addition of CySS to these cells showed that extracellular Cys/CySS Eh approached −80 mV at 4 h while cellular GSH and extracellular GSH/GSSG Eh recovered more slowly. Together, these results show that HT-29 cells have the capacity to regulate the extracellular Cys/CySS Eh by mechanisms that are independent of cellular GSH. The results suggest that transport systems for Cys and CySS and/or membranal oxidoreductases could be more important than cellular GSH in regulation of extracellular Cys/CySS Eh.
In vitro evidences for glucosensing capacity and mechanisms in hypothalamus, hindbrain, and Brockmann bodies of rainbow trout
Authors: Polakof Sergio , Míguez Jesús M. , Soengas José L.
Published: June 2007

We aimed to support in vitro the glucosensing capacity observed in vivo in rainbow trout hypothalamus, hindbrain, and Brockmann bodies (BB) and to obtain preliminary evidence of the mechanisms involved. The response of parameters involved in the glucosensing capacity [hexokinase, hexokinase IV (glucokinase), and pyruvate kinase activities and glucose and glycogen levels] was assessed in these tissues incubated for 1 h with 2, 4, or 8 mM d-glucose alone (control) or with specific agonists/inhibitors of the steps involved in glucosensing capacity in mammals. These agents were a competitor for glucose phosphorylation (15 mM mannose), sulfonylurea receptor-1 effectors (500 μM tolbutamide or diazoxide), glycolytic intermediates (15 mM glycerol, lactate, or pyruvate), and inhibitors of glucose transport (10 μM cytochalasin B), glycolysis [20 mM 2-deoxy-d-glucose (2-DG)], and L-type calcium channel (1 μM nifedipine). Control incubations of the three tissues displayed increased glucose and glycogen levels and glucokinase activities in response to increased medium glucose, thus supporting our previous in vivo studies. Furthermore, critical components of the glucosensing mammalian machinery are apparently functioning in the three tissues. The responses in brain regions to all substances tested (except 2-DG and nifedipine) were similar to those observed in mammals, suggesting a similar glucosensing machinery. In contrast, in BB, only the effects of 2-DG, lactate, pyruvate, diazoxide, and nifedipine were similar to those of mammalian β-cells, suggesting that some of the components of the piscine glucosensing model are different than those of mammals. Such differences may relate to the importance of amino acids rather than glucose signaling in the trout BB.
The effect of a low-protein diet in pregnancy on offspring renal calcium handling
Authors: Ashton Nick , Al-Wasil Saleh H. , Bond Helen , Berry Jacqueline L. , Denton John , Freemont Anthony J.
Published: June 2007

Low birth weight humans and rats exposed to a low-protein diet in utero have reduced bone mineral content. Renal calcium loss during the period of rapid skeletal growth is associated with bone loss. Because young rats exposed to low protein display altered renal function, we tested the hypothesis that renal calcium excretion is perturbed in this model. Pregnant Wistar rats were fed isocalorific diets containing either 18% (control) or 9% (low) protein throughout gestation. Using standard renal clearance techniques, Western blotting for renal calcium transport proteins, and assays for Na+-K+-ATPase activity and serum calcitropic hormones, we characterized calcium handling in 4-wk-old male offspring. Histomorphometric analyses of femurs revealed a reduction in trabecular bone mass in low-protein rats. Renal calcium (control vs. low protein: 10.4 ± 2.1 vs. 27.6 ± 4.5 nmol·min−1·100 g body wt−1; P < 0.01) and sodium excretion were increased, but glomerular filtration rate was reduced in low-protein animals. Total plasma calcium was reduced in low-protein rats ( P < 0.01), but ionized calcium, serum calcitropic hormone concentrations, and total body calcium did not differ. There was no significant change in plasma membrane Ca2+-ATPase pump, epithelial calcium channel, or calbindin-D28Kexpression in low-protein rat kidneys. However, Na+-K+-ATPase activity was 36% lower ( P < 0.05) in low-protein rats. These data suggest that the hypercalciuria of low-protein rats arises through a reduction in passive calcium reabsorption in the proximal tubule rather than active distal tubule uptake. This may contribute to the reduction in bone mass observed in this model.
Insulin causes renal dopamine D1 receptor desensitization via GRK2-mediated receptor phosphorylation involving phosphatidylinositol 3-kinase and protein kinase C
Authors: Banday Anees Ahmad , Fazili Fatima Rizwan , Lokhandwala Mustafa F.
Published: June 2007

The renal dopamine system plays an important role in sodium homeostasis and a defect in dopamine D1 receptor (D1R) function is present in hypertension, diabetes, and aging. Our previous studies in hyperinsulinemic animals and in renal cell cultures treated with insulin showed decrease in D1R number and defective coupling to G proteins; however, the exact mechanisms remained unknown. Therefore, we investigated insulin-mediated D1R desensitization and underlying molecular mechanism in opossum kidney (OK) cells. Chronic exposure (24 h) of OK cells to 10 nM insulin caused significant decrease in D1R number and agonist affinity. The D1R was hyperserine phosphorylated, uncoupled from G proteins and SKF38393 , a D1R agonist, failed to stimulate G proteins and inhibit Na-K-ATPase activity. Insulin increased protein kinase C (PKC) activity and caused G protein-coupled receptor kinase 2 (GRK2) translocation to the membranes. Tyrosine kinase inhibitor genistein and phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin blocked insulin-mediated PKC activation and GRK2 membranous translocation. In addition to genistein and wortmannin, GRK2 membranous tranlocation was also blocked by PKC inhibitor chelerythrine chloride and GRK2-specific siRNA. Genistein, wortmannin, chelerythrine chloride, and GRK2 siRNA abrogated D1R serine phosphorylation and normalized D1R expression and affinity in insulin-treated cells. Furthermore, these inhibitors and siRNA restored D1R G protein coupling and ability of SKF38393 to inhibit Na-K-ATPase activity. In conclusion, insulin-induced D1R desensitization involves PI3K, PKC, and GRK2. Insulin activates PI3K-PKC-GRK2 cascade, causing D1R serine phosphorylation, which leads to D1R downregulation and uncoupling from G proteins, and results in the failure of SKF38393 to stimulate G proteins and inhibit Na-K-ATPase activity.
Pore-forming epsilon toxin causes membrane permeabilization and rapid ATP depletion-mediated cell death in renal collecting duct cells
Authors: Chassin C. , Bens M. , de Barry J. , Courjaret R. , Bossu J. L. , Cluzeaud F. , Ben Mkaddem S. , Gibert M. , Poulain B. , Popoff M. R. , Vandewalle A.
Published: June 2007

Clostridium perfringens epsilon toxin (ET) is a potent pore-forming cytotoxin causing fatal enterotoxemia in livestock. ET accumulates in brain and kidney, particularly in the renal distal-collecting ducts. ET binds and oligomerizes in detergent-resistant membranes (DRMs) microdomains and causes cell death. However, the causal linkage between membrane permeabilization and cell death is not clear. Here, we show that ET binds and forms 220-kDa insoluble complexes in plasma membrane DRMs of renal mpkCCDcl4collecting duct cells. Phosphatidylinositol-specific phospholipase C did not impair binding or the formation of ET complexes, suggesting that the receptor for ET is not GPI anchored. ET induced a dose-dependent fall in the transepithelial resistance and potential in confluent cells grown on filters, transiently stimulated Na+absorption, and induced an inward ionic current and a sustained rise in [Ca2+]i. ET also induced rapid depletion of cellular ATP, and stimulated the AMP-activated protein kinase, a metabolic-sensing Ser/Thr kinase. ET also induced mitochondrial membrane permeabilization and mitochondrial-nuclear translocation of apoptosis-inducing factor, a potent caspase-independent cell death effector. Finally, ET induced cell necrosis characterized by a marked reduction in nucleus size without DNA fragmentation. DRM disruption by methyl-β-cyclodextrin impaired ET oligomerization, and significantly reduced the influx of Na+and [Ca2+]i, but did not impair ATP depletion and cell death caused by the toxin. These findings indicate that ET causes rapid necrosis of renal collecting duct cells and establish that ATP depletion-mediated cell death is not strictly correlated with the plasma membrane permeabilization and ion diffusion caused by the toxin.
Role of α/β and γ/δ T cells in renal ischemia-reperfusion injury
Authors: Hochegger Kathrin , Schätz Tobias , Eller Philipp , Tagwerker Andrea , Heininger Dorothea , Mayer Gert , Rosenkranz Alexander R.
Published: June 2007

T cells have been implicated in the pathogenesis of renal ischemia-reperfusion injury (IRI). To date existing data about the role of the T cell receptor (Tcr) are contradictory. We hypothesize that the Tcr plays a prominent role in the late phase of renal IRI. Therefore, renal IRI was induced in α/β, γ/δ T cell-deficient and wild-type mice by clamping renal pedicles for 30 min and reperfusing for 24, 48, 72, and 120 h. Serum creatinine increased equally in all three groups 24 h after ischemia but significantly improved in Tcr-deficient animals compared with wild-type controls after 72 h. A significant reduction in renal tubular injury and infiltration of CD4+ T-cells in both Tcr-deficient mice compared with wild-type controls was detected. Infiltration of α/β T cells into the kidney was reduced in γ/δ T cell-deficient mice until 72 h after ischemia. In contrast, γ/δ T cell infiltration was equal in wild-type and α/β T cell-deficient mice, suggesting an interaction between α/β and γ/δ T cells. Data from γ/δ T cell-deficient mice were confirmed by in vivo depletion of γ/δ T cells in C57BL/6 mice. Whereas α/β T cell-deficient mice were still protected after 120 h, γ/δ T cell-deficient mice showed a “delayed wild-type phenotype” with a dramatic increase in kidney-infiltrating α/β, Tcr-expressing CD4+ T-cells. This report provides further evidence that α/β T cells are major effector cells in renal IRI, whereas γ/δ T cells play a role as mediator cells in the first 72 h of renal IRI.