bluuebunny/crossref_metadata_2025 huggingface dataset:
PERTURBATIVE SYMMETRIES ON NONCOMMUTATIVE SPACES
Authors: BLOHMANN CHRISTIAN
Published: February 2005

Perturbative deformations of symmetry structures on noncommutative spaces are studied in view of noncommutative quantum field theories. The rigidity of enveloping algebras of semisimple Lie algebras with respect to formal deformations is reviewed in the context of star products. It is shown that rigidity of symmetry algebras extends to rigidity of the action of the symmetry on the space. This implies that the noncommutative spaces considered can be realized as star products by particular ordering prescriptions which are compatible with the symmetry. These symmetry preserving ordering prescriptions are calculated for the quantum plane and four-dimensional quantum Euclidean space. The result can be used to construct invariant Lagrangians for quantum field theory on noncommutative spaces with a deformed symmetry.
INTERFERENCE OF OUTGOING ELECTROMAGNETIC WAVES GENERATED BY TWO POINT-LIKE SOURCES
Authors: YAREMKO YURIJ
Published: February 2005

An energy–momentum carried by electromagnetic field produced by two point-like charged particles is calculated. Integration region considered in the evaluation of the bound and emitted quantities produced by all points of world-lines up to the end points at which particles' trajectories puncture an observation hyperplane y0=t. Radiative part of the energy–momentum contains, apart from usual integrals of Larmor terms, also the sum of work done by Lorentz forces of point-like charges acting on one another. Therefore, the combination of wave motions (retarded Liénard–Wiechert solutions) leads to the interaction between the sources.
3-MANIFOLD INVARIANTS FROM COSETS
Authors: XU FENG
Published: February 2005

We construct unitary modular categories for a general class of coset conformal field theories based on our previous study of these theories in the algebraic quantum field theory framework using subfactor theory. We also consider the calculations of the corresponding 3-manifold invariants. It is shown that under certain index conditions the link invariants colored by the representations of coset factorize into the products of the the link invariants colored by the representations of the two groups in the coset. But the 3-manifold invariants do not behave so simply in general due to the nontrivial branching rules of the coset. Examples in the parafermion cosets and diagonal cosets show that 3-manifold invariants of the coset may be finer than the products of the 3-manifold invariants associated with the two groups in the coset, and these two invariants do not seem to be simply related in some cases, for an example, in the cases when there are issues of "fixed point resolutions". In the later case our framework provides a representation theory understanding of the underlying unitary modular categories which has not been obtained before.
COSMOLOGICAL TERM AND FUNDAMENTAL PHYSICS
Authors: ALDROVANDI R. , BELTRÁN ALMEIDA J. P. , PEREIRA J. G.
Published: February 2005

A nonvanishing cosmological term in Einstein's equations implies a nonvanishing spacetime curvature even in the absence of any kind of matter. It would, in consequence, affect many of the underlying kinematic tenets of physical theory. The usual commutative spacetime translations of the Poincaré group would be replaced by the mixed conformal translations of the de Sitter group, leading to obvious alterations in elementary concepts such as time, energy and momentum. Although negligible at small scales, such modifications may come to have important consequences both in the large and for the inflationary picture of the early Universe. A qualitative discussion is presented, which suggests deep changes in Hamiltonian, Quantum and Statistical Mechanics. In the primeval universe as described by the standard cosmological model, in particular, the equations of state of the matter sources could be quite different from those usually introduced.
EXPLORING FIFTH FORCE INTERACTIONS WITH 18TH CENTURY TECHNOLOGY
Authors: STEFFEN JASON H.
Published: February 2005

Many theories which unify gravity with the other known forces of nature predict the existence of an intermediate-range "fifth force" similar to gravity. Such a force could be manifest as a deviation from the gravitational inverse-square law. Currently, at distances near 10-1 m, the inverse-square law is known to be correct to about one part per thousand. I present the design of an experiment that will improve this limit by two orders of magnitude. This is accomplished by constructing a torsion pendulum and source mass apparatus that are particularly insensitive to Newtonian gravity and, simultaneously, maximally sensitive to violations of the same.
QUANTUM STABILIZATION OF A RELATIVISTIC DEGENERATE STAR BEYOND THE CHANDRASEKHAR MASS LIMIT
Authors: SILVERMAN M. P.
Published: February 2005

In contrast to the widely held belief that a degenerate star that has exhausted its nuclear fuel will, if sufficiently massive, unremittingly collapse to a singularity in space (unless the contraction is prevented by some unknown process of quantum gravity acting at the scale of the Planck length), I present a heuristic argument, based on known quantum processes, for the existence of stable equilibrium states of neutron stars and quark stars with macroscopic radii and masses unconstrained by the Chandrasekhar and Oppenheimer–Volkoff limits. The processes that stabilize the star against gravitational contraction involve strong magnetic coupling of the constituent fermions and fermionic pair production at the expense of gravitational potential energy.
VIRTUAL BLACK HOLES AND THE S-MATRIX
Authors: GRUMILLER D.
Published: February 2005

A brief review on virtual black holes is presented, with special emphasis on phenomenologically relevant issues like their influence on scattering or on the specific heat of (real) black holes. Regarding theoretical topics, the results important for (the avoidance of) information loss are summarized.

After recalling Hawking's Euclidean notion of virtual black holes and a Minkowskian notion which emerged in studies of 2D models, the importance of virtual black holes for scattering experiments is addressed. Among the key features is that virtual black holes tend to regularize divergences of quantum field theory and that a unitary S-matrix may be constructed. Also, the thermodynamical behavior of real evaporating black holes may be ameliorated by interactions with virtual black holes. Open experimental and theoretical challenges are mentioned briefly.
CONFLICT BETWEEN WATER SUPPLY AND ENVIRONMENTAL HEALTH RISK: A COMPUTATIONAL NEURAL NETWORK APPROACH
Authors: COPPOLA EMERY , SZIDAROVSZKY FERENC
Published: February 2005

A two-person conflict is analyzed, where a water company and a community are the players and water supply and health risk constitute the payoff functions. An aquifer's response to different pumping policies is estimated at points of interest by a computational neural network, which was trained using simulation data from MODFLOW, a large-scale complicated finite difference model. Using the weighting method, the Pareto frontier is first determined, and four particular resolution methodologies are applied. The numerical results are analyzed and compared.
THE FIRM AS A NEXUS OF STRATEGIES
Authors: DOW GREGORY K.
Published: February 2005

This paper replaces the standard view of the firm as a nexus of contracts with a repeated game framework where input contributions and side payments are self-enforced. General production technologies and flexible transfers among team members are allowed. When an incentive constraint binds, input demand and output supply are influenced by the discount factor, the probability of exogenous team dissolution, and the aggregate value of outside options. When this incentive constraint does not bind, the firm maximizes profit in the usual way. I discuss examples involving the Cobb-Douglas technology, firms with a single residual claimant, and partnerships.
ORIGINS OF THE GENETIC CODE: The Escaped Triplet Theory
Authors: Yarus Michael , Caporaso J. Gregory , Knight Rob
Published: February 2005

▪ Abstract  There is very significant evidence that cognate codons and/or anticodons are unexpectedly frequent in RNA-binding sites for seven of eight biological amino acids that have been tested. This suggests that a substantial fraction of the genetic code has a stereochemical basis, the triplets having escaped from their original function in amino acid–binding sites to become modern codons and anticodons. We explicitly show that this stereochemical basis is consistent with subsequent optimization of the code to minimize the effect of coding mistakes on protein structure. These data also strengthen the argument for invention of the genetic code in an RNA world and for the RNA world itself.
AN ABUNDANCE OF RNA REGULATORS
Authors: Storz Gisela , Altuvia Shoshy , Wassarman Karen M.
Published: February 2005

▪ Abstract  The importance of small, noncoding RNAs that act as regulators of transcription, of RNA modification or stability, and of mRNA translation is becoming increasingly apparent. Here we discuss current knowledge of regulatory RNA function and review how the RNAs have been identified in a variety of organisms. Many of the regulatory RNAs act through base-pairing interactions with target RNAs. The base-pairing RNAs can be grouped into two general classes: those that are encoded on the opposite strand of their target RNAs such that they contain perfect complementarity with their targets, and those that are encoded at separate locations on the chromosome and have imperfect base-pairing potential with their targets. Other regulatory RNAs act by modifying protein activity, in some cases by mimicking the structures of other RNA or DNA molecules.
STRUCTURE, FUNCTION, AND FORMATION OF BIOLOGICAL IRON-SULFUR CLUSTERS
Authors: Johnson Deborah C. , Dean Dennis R. , Smith Archer D. , Johnson Michael K.
Published: February 2005

▪ Abstract  Iron-sulfur [Fe-S] clusters are ubiquitous and evolutionary ancient prosthetic groups that are required to sustain fundamental life processes. Owing to their remarkable structural plasticity and versatile chemical/electronic features [Fe-S] clusters participate in electron transfer, substrate binding/activation, iron/sulfur storage, regulation of gene expression, and enzyme activity. Formation of intracellular [Fe-S] clusters does not occur spontaneously but requires a complex biosynthetic machinery. Three different types of [Fe-S] cluster biosynthetic systems have been discovered, and all of them are mechanistically unified by the requirement for a cysteine desulfurase and the participation of an [Fe-S] cluster scaffolding protein. Important mechanistic questions related to [Fe-S] cluster biosynthesis involve the molecular details of how [Fe-S] clusters are assembled on scaffold proteins, how [Fe-S] clusters are transferred from scaffolds to target proteins, how various accessory proteins participate in [Fe-S] protein maturation, and how the biosynthetic process is regulated.
SELENOPROTEIN P: An Extracellular Protein with Unique Physical Characteristics and a Role in Selenium Homeostasis
Authors: Burk Raymond F. , Hill Kristina E.
Published: February 2005

▪ Abstract  Selenoprotein P is an abundant extracellular glycoprotein that is rich in selenocysteine. It has two domains with respect to selenium content. The N-terminal domain of the rat protein contains one selenocysteine residue in a UxxC redox motif. This domain also has a pH-sensitive heparin-binding site and two histidine-rich amino acid stretches. The smaller C-terminal domain contains nine selenocysteine and ten cysteine residues. Four isoforms of selenoprotein P are present in rat plasma. They share the same N terminus and amino acid sequence. One isoform is full length and the three others terminate at the positions of the second, third, and seventh selenocysteine residues. Selenoprotein P turns over rapidly in rat plasma with the consequence that approximately 25% of the amount of whole-body selenium passes through it each day. Evidence supports functions of the protein in selenium homeostasis and oxidant defense. Selenoprotein P knockout mice have very low selenium concentrations in the brain, the testis, and the fetus, with severe pathophysiological consequences in each tissue. In addition, those mice waste moderate amounts of selenium in the urine. Selenoprotein P binds to endothelial cells in the rat, and plasma levels of the protein correlate with prevention of diquat-induced lipid peroxidation and hepatic endothelial cell injury. The mechanisms of these apparent functions remain speculative and much work on the mechanism of selenoprotein P function lies ahead. Measurement of selenoprotein P in human plasma has shown that it is depressed by selenium deficiency and by cirrhosis. Selenium supplementation of selenium-deficient human subjects showed that glutathione peroxidase activity was optimized before selenoprotein P concentration was optimized, indicating that plasma selenoprotein P is the better index of human selenium nutritional status.
DROSOPHILA NUTRIGENOMICS CAN PROVIDE CLUES TO HUMAN GENE-NUTRIENT INTERACTIONS
Authors: Ruden Douglas M. , De Luca Maria , Garfinkel Mark D. , Bynum Kerry L. , Lu Xiangyi
Published: February 2005

▪ Abstract  Nutrigenomics refers to the complex effects of the nutritional environment on the genome, epigenome, and proteome of an organism. The diverse tissue- and organ-specific effects of diet include gene expression patterns, organization of the chromatin, and protein post-translational modifications. Long-term effects of diet range from obesity and associated diseases such as diabetes and cardiovascular disease to increased or decreased longevity. Furthermore, the diet of the mother can potentially have long-term health impacts on the children, possibly through inherited diet-induced chromatin alterations. Drosophila is a unique and ideal model organism for conducting nutrigenomics research for numerous reasons. Drosophila, yeast, and Caenorhabditis elegans all have sophisticated genetics as well as sequenced genomes, and researchers working with all three organisms have made valuable discoveries in nutrigenomics. However, unlike yeast and C. elegans, Drosophila has adipose-like tissues and a lipid transport system, making it a closer model to humans. This review summarizes what has already been learned in Drosophila nutrigenomics (with an emphasis on lipids and sterols), critically evaluates the data, and discusses fruitful areas for future research.
Progression of vascular and neural dysfunction in sciatic nerves of Zucker diabetic fatty and Zucker rats
Authors: Oltman Christine L. , Coppey Lawrence J. , Gellett Jill S. , Davidson Eric P. , Lund Donald D. , Yorek Mark A.
Published: February 2005

We have examined the progression of vascular and neural deficits in Zucker rats, Zucker diabetic fatty (ZDF) diabetic rats, and age-matched lean ZDF rats from 8 to 40 wk of age. Both the ZDF diabetic and Zucker rats were glucose intolerant at 8 wk of age. The Zucker rats did not become hyperglycemic but were hyperinsulinemic through 32 wk of age. All ZDF diabetic rats became hyperglycemic by 8 wk of age. Through their life span, serum free fatty acids and triglycerides levels were significantly higher in Zucker and ZDF diabetic rats compared with age-matched lean ZDF rats. After 24 and 28 wk of age, endoneurial blood flow was significantly decreased in ZDF diabetic and Zucker rats. Motor nerve conduction velocity was significantly decreased after 12–14 wk of age in ZDF diabetic rats and at 32 wk of age in Zucker rats. ACh-mediated vascular relaxation of epineurial arterioles of the sciatic nerve was impaired after 8–10 wk of age in ZDF diabetic rats and after ∼16 wk of age in Zucker rats. In contrast, vascular relaxation mediated by calcitonin gene-related peptide was impaired significantly after 28 wk of age in ZDF diabetic rats but not impaired in Zucker rats up to 40 wk of age. Markers of oxidative stress were differentially elevated in ZDF diabetic rats and Zucker rats. These data indicate that vascular and neural dysfunction develops in both Zucker and ZDF diabetic rats but at different rates, which may be the result of hyperglycemia.
The scar neovasculature after myocardial infarction in rats
Authors: Wang Bin , Ansari Ramin , Sun Yao , Postlethwaite Arnold E. , Weber Karl T. , Kiani Mohammad F.
Published: February 2005

A series of novel techniques, adapted from the field of tumor biology, were developed to quantify vascular structure and function and to explore the role of ANG II receptor AT1 in cardiac remodeling after myocardial infarction (MI). We examined the scar neovasculature at 1–4 wk post-MI in Sprague-Dawley rats with a view toward its ability to deliver and exchange oxygen. CD31 and DiOC7( 3 ) staining was used to visualize anatomical vessels vs. those perfused. EF5/Cy3 immunohistochemical staining was used to quantify tissue hypoxia. We compared untreated controls with rats treated with losartan, an AT1 receptor antagonist. Our findings indicated that, at the infarct site, there was not only a 42–75% (1–4 wk post-MI) decrease in the number of anatomical vessels compared with controls but also a decrease in the fraction of perfused vessels from 70% in normal coronary vasculature to 48% at the infarct site. These changes were accompanied by progressive increases in diffusion distance and tissue hypoxia (100% increase in EF5/Cy3 staining at 4 wk post-MI). Losartan-treated rats exhibited a significantly less marked reduction in vascular perfusion and a significantly lesser extent of tissue hypoxia. Over the course of 4 wk post-MI, there is a reduction in coronary vasculature at the infarct site, the extent of which is attenuated by losartan. These findings implicate AT1 receptor upregulation, and perhaps angiotensin-related peptides, as being antiangiogenic.
Electrotonic influences on action potential duration dispersion in small hearts: a simulation study
Authors: Sampson Kevin J. , Henriquez Craig S.
Published: February 2005

Intrinsic spatial variations in repolarization currents in the heart can produce spatial gradients in action potential duration (APD) that serve as possible sites for conduction block and the initiation of reentrant activity. In well-coupled myocardium, however, electrotonic influences at the stimulus site and wavefront collision sites act to modulate any intrinsic heterogeneity in APD. These effects alter APD gradients over an extent larger than that suggested by the length constant associated with propagation and, thus, are hypothesized to play a greater role in smaller hearts used as experimental models of human disease. This study uses computer simulation to investigate how heart size, tissue properties, and the spatial assignment of cell types affect functional APD dispersion. Simulations were carried out using the murine ventricular myocyte model of Pandit et al. or the Luo-Rudy mammalian model in three-dimensional models of mouse and rabbit ventricular geometries. Results show that the spatial extent of the APD dispersion is related to the dynamic changes in transmembrane resistance during recovery. Also, because of the small dimensions of the mouse heart, electrotonic effects on APD primarily determine the functional dispersion of refractoriness, even in the presence of large intrinsic cellular heterogeneity and reduced coupling. APD dispersion, however, is found to increase significantly when the heart size increases to the size of a rabbit heart, unmasking intrinsic cell types.
Modulation of cardiac mast cell-mediated extracellular matrix degradation by estrogen
Authors: Chancey Amanda L. , Gardner Jason D. , Murray David B. , Brower Gregory L. , Janicki Joseph S.
Published: February 2005

There are fundamental differences between males and females with regard to susceptibility to heart disease. Although numerous animal models of heart failure have demonstrated that premenopausal females are afforded cardioprotection and, therefore, fare better in the face of cardiac disease than their male counterparts, many questions as to how this occurs still exist. Recently, we showed that 1) increased mast cell density is associated with adverse ventricular remodeling and 2) chemically induced mast cell degranulation using compound 48/80 resulted in remarkable changes in matrix metalloproteinase (MMP) activity, cardiac collagen structure, and cardiac diastolic function in normal male rats. With the known gender differences in cardiac disease in mind, we sought to examine the effects of chemically induced cardiac mast cell degranulation in isolated, blood-perfused hearts of intact female rats, ovariectomized female rats, and ovariectomized female rats treated with 17β-estradiol. In response to mast cell degranulation, no significant differences in cardiac function, MMP-2 activity, or collagen volume fraction were observed between intact female rats and ovariectomized female rats treated with estrogen. In the ovariectomized female group, a significant rightward shift in the left ventricular pressure-volume relation, accompanied by a marked 133% increase in active MMP-2 values over that in the intact female group, was noted after treatment with compound 48/80 ( P ≤ 0.05), along with a significant reduction in collagen volume fraction below control (0.46 ± 0.23 vs. 0.73 ± 0.13%, P ≤ 0.05). These findings indicate that estrogen's cardioprotective role can be partially mediated by its effects on cardiac mast cells, MMPs, and the extracellular matrix.
αvβ3- and α5β1-integrin blockade inhibits myogenic constriction of skeletal muscle resistance arterioles
Authors: Martinez-Lemus Luis A. , Crow Tracy , Davis Michael J. , Meininger Gerald A.
Published: February 2005

In isolated resistance arterioles with spontaneous tone, ligation of α4β1- and α5β1-integrins induces vasoconstriction whereas ligation of αvβ3-integrin induces vasodilation. However, whether integrins directly participate in myogenic constriction to pressure elevation is not known. To answer this question, isolated rat skeletal muscle arterioles were exposed to step increments in pressure in the absence or presence of peptides and function-blocking antibodies known to bind α4β1-, α5β1-, or αvβ3-integrins while vessel diameter was continually monitored. Myogenic constriction, as assessed by the ability of isolated arterioles to reduce their diameter in response to two consecutive increments in intraluminal pressure (90–110 and 110–130 cmH2O), was not affected by treatment with any of the control peptides (RAD, LEV), a control antibody (anti-rat major histocompatibility complex), an α4β1-integrin-binding peptide (LDV), or an anti-α4-integrin antibody. In contrast, α5β1-integrin blockade with either anti-α5- or anti-β1-integrin antibody caused a significant inhibition of myogenic constriction. Also, both RGD peptide and anti-β3-integrin antibody inhibited myogenic constriction. These results indicate that α5β1- and αvβ3-integrins are necessary for myogenic constriction and further suggest that integrins are part of the mechanosensory apparatus responsible for the ability of vascular smooth muscle cells to detect and/or respond to changes in intraluminal pressure.
A role for platelet-derived growth factor β-receptor in a newborn rat model of endothelin-mediated pulmonary vascular remodeling
Authors: Jankov Robert P. , Kantores Crystal , Belcastro Rosetta , Yi Soojin , Ridsdale Ross A. , Post Martin , Tanswell A. Keith
Published: February 2005

Newborn rats exposed to 60% O2for 14 days develop endothelin (ET)-1-dependent pulmonary hypertension with vascular remodeling, characterized by increased smooth muscle cell (SMC) proliferation and medial thickening of pulmonary resistance arteries. Using immunohistochemistry and Western blot analyses, we examined the effect of exposure to 60% O2on expression in the lung of receptors for the platelet-derived growth factors (PDGF), which are implicated in the pathogenesis of arterial smooth muscle hyperplasia. We observed a marked O2-induced upregulation of PDGF-α and -β receptors (PDGF-αR and -βR) on arterial smooth muscle. This led us to examine pulmonary vascular PDGF receptor expression in 60% O2-exposed rats given SB-217242, a combined ET receptor antagonist, which we found prevented the O2-induced upregulation of PDGF-βR, but not PDGF-αR, on arterial smooth muscle. PDGF-BB, a major PDGF-βR ligand, was found to be a potent in vitro inducer of hyperplasia and DNA synthesis in cultured pulmonary artery SMC from infant rats. A critical role for PDGF-βR ligands in arterial SMC proliferation was confirmed in vivo using a truncated soluble PDGF-βR intervention, which attenuated SMC proliferation induced by exposure to 60% O2. Collectively, these data are consistent with a major role for PDGF-βR-mediated SMC proliferation, acting downstream of increased ET-1 in a newborn rat model of 60% O2-induced pulmonary hypertension.
Difference in proangiogenic potential of systemic and pulmonary endothelium: role of CXCR2
Authors: Moldobaeva Aigul , Wagner Elizabeth M.
Published: February 2005

The systemic vasculature in and surrounding the lung is proangiogenic, whereas the pulmonary vasculature rarely participates in neovascularization. We studied the effects of the proangiogenic ELR+ CXC chemokine MIP-2 (macrophage inflammatory protein-2) on endothelial cell proliferation and chemotaxis. Mouse aortic, pulmonary arterial, and lung microvascular endothelial cells were isolated and subcultured. Proliferation ([3H]thymidine uptake) and migration (Transwell chemotaxis) were evaluated in each cell type at baseline and upon exposure to MIP-2 (1–100 ng/ml) without and with exposure to hypoxia (24 h)-reoxygenation. Baseline proliferation did not vary among cell types, and all cells showed increased proliferation after MIP-2. Aortic cell chemotaxis increased markedly upon exposure to MIP-2; however, neither pulmonary artery nor lung microvascular endothelial cells responded to this chemokine. Assessment of CXCR2, the G protein-coupled receptor through which MIP-2 signals, displayed no baseline difference in mRNA, protein, or cell surface expression among cell types. Exposure to hypoxia increased expression of CXCR2of aortic endothelial cells only. Additionally, aortic cells, compared with pulmonary cells, showed significantly greater protein and activity of cathepsin S, a proteolytic enzyme important for cell motility. Thus the combined effects of increased cathepsin S activity, providing increased motility and enhanced CXCR2expression after hypoxia, both contribute to the proangiogenic phenotype of systemic arterial endothelial cells.
Partial SP-B deficiency perturbs lung function and causes air space abnormalities
Authors: Nesslein Lori L. , Melton Kristin R. , Ikegami Machiko , Na Cheng-Lun , Wert Susan E. , Rice Ward R. , Whitsett Jeffrey A. , Weaver Timothy E.
Published: February 2005

Surfactant protein B (SP-B) is required for function of newborn and adult lung, and partial deficiency has been associated with susceptibility to lung injury. In the present study, transgenic mice were produced in which expression of SP-B in type II epithelial cells was conditionally regulated. Concentrations of SP-B were maintained at 60–70% of that normally present in control. Immunostaining for SP-B demonstrated cellular heterogeneity in expression of the protein. In subsets of type II cells in which SP-B staining was decreased, immunostaining for pro-SP-C was increased and lamellar body ultrastructure was disrupted, consistent with focal SP-B deficiency. Fluorescence-activated cell sorting analyses of freshly isolated type II cells identified a population of cells with low SP-B content and a smaller population with increased SP-B content, confirming nonuniform expression of the SP-B transgene. Focal air space enlargement, without cellular infiltration or inflammation, was observed. Pressure-volume curves indicated that maximal tidal volume was unchanged; however, hysteresis was modestly altered and residual volumes were significantly decreased in the SP-B-deficient mice. Chronic, nonuniform SP-B deficiency perturbed pulmonary function and caused air space enlargement.
Hepatic β-oxidation and carnitine palmitoyltransferase I in neonatal pigs after dietary treatments of clofibric acid, isoproterenol, and medium-chain triglycerides
Authors: Peffer Pasha Lyvers , Lin Xi , Odle Jack
Published: February 2005

A suckling piglet model was used to study nutritional and pharmacologic means of stimulating hepatic fatty acid β-oxidation. Newborn pigs were fed milk diets containing either long- or medium-chain triglycerides (LCT or MCT). The long-chain control diet was supplemented further with clofibric acid (0.5%) or isoproterenol (40 ppm), and growth was monitored for 10–12 days. Clofibrate increased rates of hepatic peroxisomal and mitochondrial β-oxidation of [1-14C]-palmitate by 60 and 186%, respectively. Furthermore, malonyl-CoA sensitive carnitine palmitoyltransferase (CPT I) activity increased 64% ( P < 0.05) in pigs receiving clofibrate. Increased CPT I activity was not congruent with changes in message, as elevated abundance of CPT I mRNA was not detected ( P = 0.16) when assessed by qRT-PCR. Neither rates of β-oxidation nor CPT activities were affected by dietary MCT or by isoproterenol treatment ( P > 0.1). Collectively, these findings indicate that clofibrate effectively induced hepatic CPT activity concomitant with increased fatty acid β-oxidation.
Sympathetic denervation does not prevent a reduction in fat pad size of rats or mice treated with peripherally administered leptin
Authors: Rooks Cherie R. , Penn Dawn M. , Kelso Emily , Bowers Robert R. , Bartness Timothy J. , Harris Ruth B. S.
Published: February 2005

Leptin increases sympathetic nervous system (SNS) activity in brown adipose tissue and renal nerves. Experiments described here tested whether SNS innervation is required for peripheral, physiological concentrations of leptin to reduce body fat. In experiment 1, one epididymal (EPI) fat pad was sympathectomized by local injection of 6-hydroxydopamine (6OHDA) in C57BL/6 mice that were then infused for 13 days with PBS or 10 μg leptin/day from an intraperitoneal miniosmotic pump. Surprisingly, EPI denervation increased total body fat of PBS-infused mice but leptin decreased the size of both injected and noninjected EPI pads in 6OHDA mice. Experiment 2 was identical except for the use of male Sprague-Dawley rats that were infused with 50 μg leptin/day. Leptin had little effect on EPI weight or norepinephrine (NE) content, but denervation of one EPI pad decreased the effect of leptin on intact EPI, inguinal and retroperitoneal (RP) fat and increased the size of the mesenteric fat pad. Experiment 3 included groups in which either one EPI or one RP pad was denervated. RP denervation reduced RP NE content but did not prevent a leptin-induced reduction in fat pad mass. Therefore, the SNS is not required for low doses of leptin to reduce body fat. EPI denervation significantly increased adipocyte number in contralateral EPI and RP fat pads and this was prevented by leptin. These changes in intact pads of rats with one denervated fat pad imply communication between fat depots and suggest that both leptin and the SNS regulate the size of individual depots.
Nuclear Factor κB Signaling in Atherogenesis
Authors: de Winther Menno P.J. , Kanters Edwin , Kraal Georg , Hofker Marten H.
Published: February 2005

Atherosclerosis is an inflammatory disease, characterized by the accumulation of macrophage-derived foam cells in the vessel wall and accompanied by the production of a wide range of chemokines, cytokines, and growth factors. These factors regulate the turnover and differentiation of immigrating and resident cells, eventually influencing plaque development. One of the key regulators of inflammation is the transcription factor nuclear factor κB (NF-κB), which, for a long time, has been regarded as a proatherogenic factor, mainly because of its regulation of many of the proinflammatory genes linked to atherosclerosis. NF-κB may play an important role in guarding the delicate balance of the atherosclerotic process as a direct regulator of proinflammatory and anti-inflammatory genes and as a regulator of cell survival and proliferation. Here we address recent literature on the function of NF-κB in inflammatory responses and its relation to atherosclerosis.
Magnetic Resonance Imaging During Untreated Ventricular Fibrillation Reveals Prompt Right Ventricular Overdistention Without Left Ventricular Volume Loss
Authors: Berg Robert A. , Sorrell Vincent L. , Kern Karl B. , Hilwig Ronald W. , Altbach Maria I. , Hayes Melinda M. , Bates Kathryn A. , Ewy Gordon A.
Published: February 2005

Background—

Most out-of-hospital ventricular fibrillation (VF) is prolonged (>5 minutes), and defibrillation from prolonged VF typically results in asystole or pulseless electrical activity. Recent visual epicardial observations in an open-chest, open-pericardium model of swine VF indicate that blood flows from the high-pressure arterial system to the lower-pressure venous system during untreated VF, thereby overdistending the right ventricle and apparently decreasing left ventricular size. Therefore, inadequate left ventricular stroke volume after defibrillation from prolonged VF has been postulated as a major contributor to the development of pulseless rhythms.

Methods and Results—

Ventricular dimensions were determined by MRI for 30 minutes of untreated VF in a closed-chest, closed-pericardium model in 6 swine. Within 1 minute of untreated VF, mean right ventricular volume increased by 29% but did not increase thereafter. During the first 5 minutes of untreated VF, mean left ventricular volume increased by 34%. Between 20 and 30 minutes of VF, stone heart occurred as manifested by dramatic thickening of the myocardium and concomitant substantial decreases in left ventricular volume.

Conclusions—

In this closed-chest swine model of VF, substantial right ventricular volume changes occurred early and did not result in smaller left ventricular volumes. The changes in ventricular volumes before the late development of stone heart do not explain why defibrillation from brief duration VF (<5 minutes) typically results in a pulsatile rhythm with return of spontaneous circulation, whereas defibrillation from prolonged VF (5 to 15 minutes) does not.
Trafficking of the Membrane Type-1 Matrix Metalloproteinase in Ischemia and Reperfusion
Authors: Deschamps Anne M. , Yarbrough William M. , Squires Christina E. , Allen Rebecca A. , McClister David M. , Dowdy Kathryn B. , McLean Julie E. , Mingoia Joseph T. , Sample Jeffrey A. , Mukherjee Rupak , Spinale Francis G.
Published: February 2005

Background—

The matrix metalloproteinases (MMPs) contribute to regional remodeling after prolonged periods of ischemia and reperfusion (I/R), but specific MMP types activated during this process remain poorly understood. A novel class, the membrane-type MMPs (MT-MMPs), has been identified in the myocardium, but activity of these MMP types has not been assessed in vivo, particularly during I/R.

Methods and Results—

Pigs (30 kg, n=8) were instrumented with microdialysis catheters to measure MT1-MMP activity in both ischemic and nonischemic (remote) myocardium. A validated MT1-MMP fluorogenic substrate was infused through the microdialysis system, and changes in fluorescence were reflective of MT1-MMP activity at steady state, during ischemia (90 minutes), and during reperfusion (120 minutes). At peak ischemia, MT1-MMP activity was increased by >40% in the ischemic region, with no change in the remote region, which persisted with reperfusion (
P
<0.05). After I/R, MT1-MMP abundance was increased by >50% (
P
<0.05). Differential centrifugation revealed that the endosomal fraction (which contains subcellular organelles) within the ischemic myocardium was associated with a >135% increase in MT1-MMP (
P
<0.05). Furthermore, in an isolated left ventricular myocyte model of I/R, hypoxia (simulated ischemia) induced a >70% increase in MT1-MMP abundance in myocytes, and confocal microscopy revealed MT1-MMP internalization during this time period and reemergence to the membrane with reperfusion.

Conclusions—

These unique results demonstrate that a specific MMP type, MT1-MMP, is increased in abundance and activity with I/R and is likely attributed, at least in part, to changes in intracellular trafficking.
Atherosclerotic Abdominal Aortic Aneurysm and the Interaction Between Autologous Human Plaque-Derived Vascular Smooth Muscle Cells, Type 1 NKT, and Helper T Cells
Authors: Chan Woon Ling , Pejnovic Nada , Hamilton Hamish , Liew Tze Vun , Popadic Dusan , Poggi Alessandro , Khan Shazia M.
Published: February 2005

Immune cell infiltration, vascular smooth muscle cell (VSMC) proliferation, and apoptosis are pathological hallmarks of atherosclerosis. The multifocal, chronic, and inflammatory nature of this disease of the cardiovascular system complicates targeted cellular therapy and emphasizes the need to understand the role and interaction of immune cells with VSMCs. We characterized the immune cell subsets present in human atherosclerotic tissue derived from atherosclerotic abdominal aortic aneurysm (AAA) and expanded them to study their interaction with autologous plaque-derived VSMCs in vitro. We show here that apart from T lymphocytes, plaque infiltrates consist of lots of NK cells and significant proportions of NKT cells that express T cell receptor (TCR) αβ, CD4, and the NK markers CD56 and CD161. The infiltrates are predominantly IFN-γ–producing Type 1 lymphoid cells. When cocultured, the T and NKT cells adhere to VSMCs. CD4
+
T cells enhance VSMC proliferation. VSMCs in turn enhance CD4
+
CD161
+
NKT but not CD4
+
or CD8
+
T cell proliferation. CD4
+
CD161
+
NKT cells inhibit VSMC proliferation by inducing apoptosis. Our results suggest that the interactions of Type 1 CD4
+
T and CD4
+
CD161
+
NKT cells with VSMCs may regulate VSMC proliferation and death respectively in atherosclerosis and the balance of these interactions could determine plaque stability.
Identification of Hypertension-Related Genes Through an Integrated Genomic-Transcriptomic Approach
Authors: Yagil Chana , Hubner Norbert , Monti Jan , Schulz Herbert , Sapojnikov Marina , Luft Friedrich C. , Ganten Detlev , Yagil Yoram
Published: February 2005

In search for the genetic basis of hypertension, we applied an integrated genomic-transcriptomic approach to identify genes involved in the pathogenesis of hypertension in the Sabra rat model of salt-susceptibility. In the genomic arm of the project, we previously detected in male rats two salt-susceptibility QTLs on chromosome 1,
SS1a
(
D1Mgh2-D1Mit11
; span 43.1 cM) and
SS1b
(
D1Mit11-D1Mit4
; span 18 cM). In the transcriptomic arm, we studied differential gene expression in kidneys of SBH/y and SBN/y rats that had been fed regular diet or salt-loaded. We used the Affymetrix Rat Genome RAE230 GeneChip and probed >30 000 transcripts. The research algorithm called for an initial genome-wide screen for differentially expressed transcripts between the study groups. This step was followed by cluster analysis based on 2×2 ANOVA to identify transcripts that were of relevance specifically to salt-sensitivity and hypertension and to salt-resistance. The two arms of the project were integrated by identifying those differentially expressed transcripts that showed an allele-specific hypertensive effect on salt-loading and that mapped within the defined boundaries of the salt-susceptibility QTLs on chromosome 1. The differentially expressed transcripts were confirmed by RT-PCR. Of the 2933 genes annotated to rat chromosome 1, 1102 genes were identified within the boundaries of the two blood pressure QTLs. The microarray identified 2470 transcripts that were differentially expressed between the study groups. Cluster analysis identified genome-wide 192 genes that were relevant to salt-susceptibility and/or hypertension, 19 of which mapped to chromosome 1. Eight of these genes mapped within the boundaries of QTLs
SS1a
and
SS1b
. RT-PCR confirmed 7 genes, leaving
TcTex1, Myadm, Lisch7, Axl-like, Fah, PRC1-like, and Serpinh1
. None of these genes has been implicated in hypertension before. These genes become henceforth targets for our continuing search for the genetic basis of hypertension.
Caveolin-1 Facilitates Mechanosensitive Protein Kinase B (Akt) Signaling In Vitro and In Vivo
Authors: Sedding Daniel G. , Hermsen Jennifer , Seay Ulrike , Eickelberg Oliver , Kummer Wolfgang , Schwencke Carsten , Strasser Ruth H. , Tillmanns Harald , Braun-Dullaeus Ruediger C.
Published: February 2005

Mechanotransduction represents an integral part of vascular homeostasis and contributes to vascular lesion formation. Previously, we demonstrated a mechanosensitive activation of phosphoinositide 3-kinase (PI3-K)/protein kinase B (Akt) resulting in p27
Kip1
transcriptional downregulation and cell cycle entry of vascular smooth muscle cells (VSMC). In this study, we further elucidated the signaling from outside-in toward PI3-K/Akt in vitro and in an in vivo model of elevated tensile force. When VSMC were subjected to cyclic stretch (0.5 Hz at 125% resting length), PI3-K, Akt, and Src kinases were found activated. Disrupting caveolar structures with β-cyclodextrin or transfection of VSMC with caveolin-1 antisense oligonucleotides (ODN) prevented PI3-K and Akt activation and cell cycle entry. Furthermore, PI3-K and Akt were resistant to activation when Src kinases were inhibited pharmacologically or by overexpression of a kinase-dead c-Src mutant. α
V
β
3
integrins were identified to colocalize with PI3-K/caveolin-1 complexes, and blockade of α
V
β
3
integrins prevented Akt activation. The central role of caveolin-1 in mechanotransduction was further examined in an in vivo model of elevated tensile force. Interposition of wild-type (WT) jugular veins into WT carotid arteries resulted in a rapid Akt activation within the veins that was almost abolished when veins of caveolin-1 knockout (KO) mice were used. Furthermore, late neointima formation within the KO veins was significantly reduced. Our study provides evidence that PI3-K/Akt is critically involved in mechanotransduction of VSMC in vitro and within the vasculature in vivo. Furthermore, caveolin-1 is essential for the integrin-mediated activation of PI3-K/Akt.
Sex Differences in Stroke Care and Outcomes
Authors: Kapral Moira K. , Fang Jiming , Hill Michael D. , Silver Frank , Richards Janice , Jaigobin Cheryl , Cheung Angela M.
Published: February 2005

Background—

Stroke is an important cause of death and disability in women as well as men. However, little is known about sex differences in stroke care and outcomes.

Methods—

The Registry of the Canadian Stroke Network (RCSN) captured data on patients with stroke seen at acute care hospitals across Canada. We used data from phase 1 (July 2001 to February 2002) and phase 2 (June to December 2002) of the RCSN to compare stroke presentation, management, and 6-month outcomes in women and men using multivariable regression techniques to adjust for age and other factors.

Results—

The study sample included 3323 patients, with 1527 women. Stroke symptoms at presentation were similar in women and men, except that women were more likely to present with headaches and were less likely to have brain stem or cerebellar symptoms. There were no sex differences in the use of neuroimaging, thrombolysis, antithrombotic therapy, or consultations. Women were less likely than men to receive care on an acute stroke unit, but this difference was no longer significant after adjustment for age and other factors. Women were more likely than men to be discharged to long-term care and had greater disability at 6 months. Mortality and quality of life at 6 months were similar in women and men.

Conclusions—

Among patients participating in the RCSN, there were no major sex differences in stroke presentation or management. Compared with men, women were more often institutionalized and had a slightly worse functional status at 6 months after stroke.
Is Heparin Treatment the Optimal Management for Cerebral Venous Thrombosis?
Authors: Röttger Carina , Madlener Katharina , Heil Matthias , Gerriets Tibo , Walberer Maureen , Wessels Tiemo , Bachmann Georg , Kaps Manfred , Stolz Erwin
Published: February 2005

Background—

Based on a newly developed model of reversible superior sagittal sinus (SSS) thrombosis in the rat, we investigated the effect of thrombolytic and anticoagulant treatment on recanalization, brain parenchymal changes, and motor deficits.

Methods—

Thrombosis of the SSS was induced by topical application of ferric chloride. Occlusion was confirmed by magnetic resonance angiography (MRA). Six hours after operation, single treatment with 10 mg recombinant tissue plasminogen activator (rtPA)/kg and 6 mg abciximab/kg or subcutaneous injection of 450 IU/kg enoxaparin twice daily was started, each group containing 10 rats. Follow-up MRI with T2- and diffusion-weighted images was performed on the first, second, and seventh postoperative day.

Results—

Control and enoxaparin-treated animals developed diffuse brain edema without infarction or intracerebral bleeding. This was indicated by an increase of T2 relaxation time and a decrease of the apparent diffusion coefficient in the parasagittal and lateral cortex. In these groups, the degree of recanalization after 7 days was comparable (48% versus 52%). Enoxaparin-treated animals showed significant amelioration of functional deficits. Clinical outcome was best in the abciximab-treated group, with a residual sinus occlusion of 36% after 1 week. Highest recanalization was achieved by lysis with rtPA (85%).

Conclusion—

Enoxaparin treatment in rats with cerebral venous thrombosis significantly influences clinical outcome. However, it has no effect on recanalization. GPIIb/IIIa antagonists and rtPA accelerate thrombolysis. They may represent an alternative in treatment of cerebral venous thrombosis.
NF-κB Activation Plays a Role in Superoxide-Mediated Cerebral Endothelial Dysfunction After Hypoxia/Reoxygenation
Authors: Xie Hui , Ray Patricio E. , Short Billie Lou
Published: February 2005

Background and Purpose—

Cerebral vascular injury occurs in response to hypoxia/reoxygenation (H/R). However, the cellular signaling pathways that regulate this event remain unclear. The present study was designed to determine whether reactive oxygen species (ROS) mediate endothelial dysfunction after H/R in cerebral resistance arteries and, if so, the relative contribution of ROS, NADPH oxidase, and a nuclear factor-κB (NF-κB) pathway.

Methods—

Arterial diameter and intraluminal pressure were simultaneously measured on rat posterior cerebral arteries (PCA). Superoxide was measured by 5-μmol/L lucigenin-enhanced chemiluminescence.

Results—

Hypoxia/reoxygenation selectively inhibited cerebral vasodilation to the endothelium-dependent agonist acetylcholine (Ach) (0.01 to 10 μmol/L) by ≈50%. Impaired vasodilation after H/R was reversed by 2,2,6,6-tetramethylpiperidine-
N
-oxyl (Tempo) (100 μmol/L), a cell-permeable superoxide dismutase mimetic, and partially by ebselen (10 μmol/L), a peroxynitrite scavenger. H/R-impaired vasodilation to Ach was also preserved by apocynin (1 mmol/L), a specific inhibitor for NADPH oxidase. Correspondingly, H/R significantly increased lucigenin-detectable superoxide, which was reduced by either Tempo or apocynin, but not by allopurinol (10 μmol/L), an inhibitor of xanthine oxidase. Finally, the NF-κB inhibitors helenalin (10 μmol/L) and MG-132 (1 μmol/L) independently antagonized H/R-impaired Ach-induced vasodilation without affecting dilator response to sodium nitroprusside, an endothelium-independent vasodilator.

Conclusions—

These results indicate that superoxide mediates cerebral endothelial dysfunction after hypoxia/reoxygenation largely via activation of NADPH oxidase and possibly activation of NF-κB pathway.