bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medullary and spinal cord projections from cardiovascular responsive sites in the rostral ventromedial medulla
Authors: Babic Tanja , Ciriello John 
Published: January 2004

AbstractThe rostral ventromedial medulla (RVMM) is a sympathoexcitatory area. However, little is known about its efferent projections. In this study, biotinylated dextran amine (BDA) or Phaseolus vulgaris leucoagglutinin (PHA‐L) were used to investigate the medullary and spinal cord projections from pressor sites in RVMM. Initially, RVMM was systematically explored in urethane‐anesthetized rats using microinjection of L‐glutamate for sites that elicited increases in arterial pressure. A pressor area was identified that included the rostral magnocellular reticular and rostral lateral paragigantocellular reticular nuclei. In the second series of experiments, BDA or PHA‐L was iontophoretically injected into RVMM pressor sites. Anterograde labeling was observed throughout the brainstem and spinal cord, bilaterally, but with an ipsilateral predominance. Dense labeling was observed within the nucleus of the solitary tract (NTS); the greatest density of labeling was observed in the caudal dorsolateral, medial, and ventrolateral subnuclei. Additionally, light to moderately dense labeling was found within the nucleus substantia gelatinosus and commissural nucleus. In the nucleus ambiguus/ventrolateral medullary (Amb/VLM) region, the density of labeling was greatest in caudal regions. Within Amb, most of the labeling was localized to its external formation. Anterograde labeling was also found throughout the spinal cord. In the thoracolumbar segments, dense axonal labeling was observed within the dorsolateral funiculus. These labeled axons innervated the intermediolateral nucleus and the central autonomic area. Taken together, these data suggest that RVMM neurons elicit increases in sympathetic activity by likely providing a direct excitatory input to spinal sympathetic preganglionic neurons, and by a direct inhibitory input to medullary cardioinhibitory and depressor areas. J. Comp. Neurol. 469:391–412, 2004. © 2004 Wiley‐Liss, Inc.
Numerical solutions of fully non‐linear and highly dispersive Boussinesq equations in two horizontal dimensions
Authors: Fuhrman David R. , Bingham Harry B. 
Published: January 2004

AbstractThis paper investigates preconditioned iterative techniques for finite difference solutions of a high‐order Boussinesq method for modelling water waves in two horizontal dimensions. The Boussinesq method solves simultaneously for all three components of velocity at an arbitrary z‐level, removing any practical limitations based on the relative water depth. High‐order finite difference approximations are shown to be more efficient than low‐order approximations (for a given accuracy), despite the additional overhead. The resultant system of equations requires that a sparse, unsymmetric, and often ill‐conditioned matrix be solved at each stage evaluation within a simulation. Various preconditioning strategies are investigated, including full factorizations of the linearized matrix, ILU factorizations, a matrix‐free (Fourier space) method, and an approximate Schur complement approach. A detailed comparison of the methods is given for both rotational and irrotational formulations, and the strengths and limitations of each are discussed. Mesh‐independent convergence is demonstrated with many of the preconditioners for solutions of the irrotational formulation, and solutions using the Fourier space and approximate Schur complement preconditioners are shown to require an overall computational effort that scales linearly with problem size (for large problems). Calculations on a variable depth problem are also compared to experimental data, highlighting the accuracy of the model. Through combined physical and mathematical insight effective preconditioned iterative solutions are achieved for the full physical application range of the model. Copyright © 2004 John Wiley & Sons, Ltd.
Simulation of transient flow in pipelines for computer‐based operations monitoring
Authors: Emara‐Shabaik H. E. , Khulief Y. A. , Hussaini I. 
Published: January 2004

AbstractComputer models can provide the basis for real‐time monitoring and control of fluid flow in pipelines. Problems of fluid flow in pipelines are mathematically represented by a non‐linear system of coupled partial differential equations. In this paper, several numerical techniques are evaluated with respect to their suitability for the purpose of real‐time monitoring of fluid flow in pipelines. The proposed techniques are evaluated in terms of the L1, the L2, and the L∞ error norms. Moreover, the developed simulators will be compared in terms of their speed of response and settling time which are essential factors for an effective real‐time monitoring scheme. Finally, the selected simulation scheme is further tested under assumed pipeline leak conditions. Copyright © 2004 John Wiley & Sons, Ltd.
Numerical simulations of a filament in a flowing soap film
Authors: Farnell D. J. J. , David T. , Barton D. C. 
Published: January 2004

AbstractExperiments concerning the properties of soap films have recently been carried out and these systems have been proposed as experimental versions of theoretical two‐dimensional liquids. A silk filament introduced into a flowing soap film, was seen to demonstrate various stable modes, and these were, namely, a mode in which the filament oscillates and one in which the filament is stationary and aligns with the flow of the liquid. The system could be forced from the oscillatory mode into the non‐ oscillatory mode by varying the length of the filament. In this article we use numerical and computational techniques in order to simulate the strongly coupled behaviour of the filament and the fluid. Preliminary results are presented for the specific case in which the filament is seen to oscillate continuously for the duration of our simulation. We also find that the filament oscillations are strongly suppressed when we reduce the effective length of the filament. We believe that these results are reminiscent of the different oscillatory and non‐oscillatory modes observed in experiment. The numerical solutions show that, in contrast to experiment, vortices are created at the leading edge of the filament and are preferentially grown in the curvature of the filament and are eventually released from the trailing edge of the filament. In a similar manner to oscillating hydrofoils, it seems that the oscillating filaments are in a minimal energy state, extracting sufficient energy from the fluid to oscillate. In comparing numerical and experimental results it is possible that the soap film does have an effect on the fluid flow especially in the boundary layer where surface tension forces are large. Copyright © 2004 John Wiley & Sons, Ltd.
Numerical simulation on an interaction of a vortex street with an elliptical leading edge using an unstructured grid
Authors: Shin Sangmook , Kim Chan Ki , Bai Kwang June 
Published: January 2004

AbstractAn algorithm for a time accurate incompressible Navier–Stokes solver on an unstructured grid is presented. The algorithm uses a second order, three‐point, backward difference formula for the physical time marching. For each time step, a divergence free flow field is obtained based on an artificial compressibility method. An implicit method with a local time step is used to accelerate the convergence for the pseudotime iteration. To validate the code, an unsteady laminar flow over a circular cylinder at a Reynolds number of 200 is calculated. The results are compared with available experimental and numerical data and good agreements are achieved.Using the developed unsteady code, an interaction of a Karman vortex street with an elliptical leading edge is simulated. The incident Karman vortex street is generated by a circular cylinder located upstream. A clustering to the path of the vortices is achieved easily due to flexibility of an unstructured grid. Details of the interaction mechanism are analysed by investigating evolutions of vortices. Characteristics of the interactions are compared for large‐ and small‐scale vortex streets. Different patterns of the interaction are observed for those two vortex streets and the observation is in agreement with experiment. Copyright © 2004 John Wiley & Sons, Ltd.
Glutamate transporter expression and function in human glial progenitors
Authors: Maragakis Nicholas J. , Dietrich Joerg , Wong Victor , Xue Haipeng , Mayer‐Proschel Margot , Rao Mahendra S. , Rothstein Jeffrey D. 
Published: January 2004

AbstractGlutamate is the major neurotransmitter of the brain, whose extracellular levels are tightly controlled by glutamate transporters. Five glutamate transporters in the human brain (EAAT1–5) are present on both astroglia and neurons. We characterize the profile of three different human astroglial progenitors in vitro: human glial restricted precursors (HGRP), human astrocyte precursors (HAPC), and early‐differentiated astrocytes. EAAT 1, EAAT3, and EAAT4 are all expressed in GRPs with a subsequent upregulation of EAAT1 following differentiation of GRPs into GRP‐derived astrocytes in the presence of bone morphogenic protein (BMP‐4). This corresponds to a significant increase in the glutamate transport capacity of these cells. EAAT2, the transporter responsible for the bulk of glutamate transport in the adult brain, is not expressed as a full‐length protein, nor does it appear to have functional significance (as determined by the EAAT2 inhibitor dihydrokainate) in these precursors. A splice variant of EAAT2, termed EAAT2b, does appear to be present in low levels, however. EAAT3 and EAAT4 expression is reduced as glial maturation progresses both in astrocyte precursors and early‐differentiated astrocytes and is consistent with their role in adult tissues as primarily neuronal glutamate transporters. These human glial precursors offer several advantages as tools for understanding glial biology because they can be passaged extensively in the presence of mitogens, afford the potential to study the temporal changes in glutamate transporter expression in a tightly controlled fashion, and are cultured in the absence of neuronal coculture, allowing for the independent study of astroglial biology. © 2003 Wiley‐Liss, Inc.
Localization of neuregulin isoforms and erbB receptors in myelinating glial cells
Authors: Raabe Timothy D. , Deadwyler Gail , Varga Jonathan W. , Devries George H. 
Published: January 2004

AbstractNeuregulins (NRGs) are growth factors present in neurons and glial cells of the central and peripheral nervous systems and play a role in the survival, proliferation, and differentiation of these cells. We now report the localization of the two major isoforms of NRG (α and β) and their receptors (erbB) in cultured Schwann cells and oligodendrocytes isolated from neonatal rat pups. Immunocytochemistry and Western blots for NRG and erbB receptors in defined subcellular fractions were utilized to assess cellular localization. Less differentiated oligodendrocytes contain both NRG isoforms in the cell bodies but not the processes, while only NRG‐1β was found in the nucleus. In contrast, more differentiated oligodendrocytes contained neither isoform in the nucleus while both isoforms were colocalized in the cytoplasm and cell processes. In Schwann cells, both NRG‐1β and NRG‐1α were colocalized in the cytoplasm and processes. The Schwann cell nucleus had weak immunoreactivity for both NRG‐1 isoforms, although NRG‐1β was predominant. ErbB2 and erbB3 receptors, which transduce the NRG‐1 signal in Schwann cells, were found throughout the cytoplasm and in the processes and were also localized in the cell nucleus. The nuclear localization of NRG‐1 isoforms and/or erbB receptors in both cell types was confirmed by Western blotting of nuclear and cytoplasmic extracts. Stimulation of Schwann cells with mitotic agents increased NRG‐1β expression in the nucleus and dramatically suppressed NRG‐1α expression throughout the cell. The functional implications of this differential localization in myelinating cells are discussed. © 2003 Wiley‐Liss, Inc.
Signaling through JAK2‐STAT5 pathway is essential for IL‐3‐induced activation of microglia
Authors: Bright John J. , Natarajan Chandramohan , Sriram Subramaniam , Muthian Gladson 
Published: January 2004

AbstractMicroglia, the resident macrophage of the brain, mediates immune and inflammatory responses in the central nervous system (CNS). Activation of microglia and secretion of inflammatory cytokines associate with the pathogenesis of CNS diseases, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease, prion disease, and AIDS dementia. Microbial pathogens, cytokines, chemokines, and costimulatory molecules are potent inducers of microglial activation in the CNS. Signaling through its receptor, IL‐3 induces the activation of JAK‐STAT and MAP kinase pathways in microglial cells. In this study, we found that in vitro treatment of EOC‐20 microglial cells with tyrphostin AG490 blocked IL‐3‐induced tyrosine phosphorylation of JAK2, STAT5A, and STAT5B signaling proteins. Stable transfection of EOC‐20 cells with a dominant negative JAK2 mutant also blocked IL‐3‐induced tyrosine phosphorylation of JAK2, STAT5A, and STAT5B in microglia. The blockade of JAK2‐STAT5 pathway resulted in a decrease in IL‐3‐induced proliferation and expression of CD40 and major histocompatibility complex class II molecules in microglia. These findings highlight the fact that JAK2‐STAT5 signaling pathway plays a critical role in mediating IL‐3‐induced activation of microglia. © 2003 Wiley‐Liss, Inc.
Microglial tau undergoes phosphorylation‐independent modification after ischemia
Authors: Uchihara Toshiki , Nakamura Ayako , Arai Tetsuaki , Ikeda Kenji , Tsuchiya Kuniaki 
Published: January 2004

AbstractTau2 is a phosphorylation‐independent antibody that immunolabels neurofibrillary tangles (NFTs) of Alzheimer type and microglia around ischemic foci on formalin‐fixed, paraffin‐embedded sections. We found that copresence of polyethyleneglycol‐p‐isooctylphenyl ether (Triton X‐100; TX) with tau2 abolished its immunoreactivity (IR) in these microglia but not its IR on NFTs. Tau2‐immunoreactive bands, exclusively retrieved in Tris‐soluble fraction of brain homogenates from ischemic foci, normal human and bovine brains, were of similar electrophoretic mobility, indicating that tau2 IR in these microglia is unrelated to hyperphosphorylation of tau. These tau2‐immunoreactive bands except those from bovine brain were abolished in the copresence of TX. This was not due to washing out of tau, because similar immunoreactive bands were detectable with another antitau antibody even under a higher concentration of TX and because washing after TX exposure restored similar tau2 IR both on immunohistochemisty and immunoblot. These findings are explained if tau, modified after ischemia, undergoes a reversible conformational change on TX exposure. Because conformation at Ser101 of bovine tau is crucial for its affinity to tau2, this Ser‐like conformation mimicked by its human counterpart Pro may represent pathological modification of tau shared by microglia around ischemic foci and NFTs. Relative resistance of tau2 epitope in NFTs to TX exposure suggests that tau woven into NFTs confers additional stability to this pathological modification on tau2 epitope. Susceptibility of tau2 epitope to TX, seen in these microglia, is shared with glial cytoplasmic inclusions and will show its conformational state to be different from that in NFTs. © 2003 Wiley‐Liss, Inc.
Dystrophic microglia in the aging human brain
Authors: Streit Wolfgang J. , Sammons Nicole W. , Kuhns Amanda J. , Sparks D. Larry 
Published: January 2004

AbstractWe have studied microglial morphology in the human cerebral cortex of two nondemented subjects using high‐resolution LN‐3 immunohistochemistry. Several abnormalities in microglial cytoplasmic structure, including deramification, spheroid formation, gnarling, and fragmentation of processes, were identified. These changes were determined to be different from the morphological changes that occur during microglial activation and they were designated collectively as microglial dystrophy. Quantitative evaluation of dystrophic changes in microglia revealed that these were much more prevalent in the older subject (68‐year‐old) than in the younger one (38‐year‐old). Thus, we conclude that microglial dystrophy is a sign of microglial cell senescence. We hypothesize that microglial senescence could be important for understanding age‐related declines in cognitive function. © 2003 Wiley‐Liss, Inc.
Cell size‐proliferation relationship in rat glioma cells
Authors: Rouzaire‐Dubois Béatrice , Malo Michel , Milandri Jean‐Baptiste , Dubois Jean‐Marc 
Published: January 2004

AbstractThe homeostasis of the central nervous system is highly controlled by glial cells and is dramatically altered in the case of glioma. In this respect, the complex connection between cell size and division is of particular importance and needs clarifying. In order to investigate this connection, cell number and volume were measured in C6 rat glioma cells under different experimental conditions, including continuous cell culture, Cl− channel blockade, and anisotonicity, and in the presence of an inhibitory conditioned medium collected from cell cultures or in a medium containing a low level of fetal calf serum. The rate of cell proliferation changed with cell volume in a bell‐shaped manner, so that it is optimal within a cell volume window and appears to be controlled by low and high cell size checkpoints. The cell size‐proliferation relationship can be defined by Boltzmann‐like equations, which may reflect the effects of macromolecular crowding on proteins controlling the cell cycle progression. Altogether, these observations indicate that glioma cell proliferation is controlled predominantly but not exclusively by cell size‐dependent mechanisms. © 2003 Wiley‐Liss, Inc.
CNS axons retain their competence for myelination throughout life
Authors: Setzu Anna , Ffrench‐Constant Charles , Franklin Robin J.M. 
Published: January 2004

AbstractAn important question relevant to developing remyelination therapies is whether axons that remain without myelin sheaths after an episode of demyelination retain myelination competence. To resolve this, we have developed a model of transplantation into the nerve fibre layer of the adult rat retina, where the axons are unmyelinated. In the adult, these axons can be myelinated by transplantation of both the oligodendrocyte progenitor cells (OPCs) and an OPC line (CG4). The extent of myelination achieved following transplantation of OPCs is the same in young adult recipients (2 months old) as that which occurs in old adult recipients (12–18 months old), indicating that there are no changes in axons remaining unmyelinated for many months that would prevent effective remyelination. This finding suggests that chronically demyelinated regions of axons such as those in seen in multiple sclerosis are likely to remain competent to be remyelinated. © 2003 Wiley‐Liss, Inc.
Heregulin and forskolin‐induced cyclin D3 expression in Schwann cells: Role of a CCAAT promoter element and CCAAT enhancer binding protein
Authors: Fuentealba Luis , Schworer Charles , Schroering Allen , Rahmatullah Mohammed , Carey David J. 
Published: January 2004

AbstractHeregulin, a polypeptide growth factor, and forskolin, an adenylyl cyclase activator, synergistically stimulate expression of cyclin D3 and cell division in Schwann cells. Heregulin induces expression in Schwann cells of a luciferase reporter gene linked to the cyclin D3 promoter. Forskolin markedly augments reporter expression in the presence of heregulin. Deletion analysis identified several promoter sites that contribute to high‐level reporter expression in heregulin‐ and forskolin‐treated Schwann cells. A promoter fragment that contains 103 bp of 5′‐flanking sequence produced significant reporter expression in heregulin‐ and forskolin‐stimulated cells. Deletion of a consensus CCAAT site within this promoter fragment caused a nearly complete loss of reporter expression. Similar results were obtained when CCAAT site mutations were introduced into the promoter. Heregulin and forskolin increased steady‐state levels of CCAAT/enhancer binding protein‐β (C/EBPβ) in Schwann cells. Mobility shift assays identified proteins in Schwann cell nuclear extracts that formed stable complexes with the cyclin D3 CCAAT promoter element and were disrupted by anti‐C/EBPβ antibody. Transfection of Schwann cells with C/EBPβ cDNA increased cyclin D3 reporter expression. In contrast to these results, mutation of a cAMP response element in the cyclin D3 promoter had only a modest effect on heregulin‐ and forskolin‐stimulated reporter expression. These findings demonstrate that C/EBPβ plays a key role in the heregulin and cAMP‐dependent regulation of cyclin D3 expression in Schwann cells. © 2003 Wiley‐Liss, Inc.
Na,K‐ATPase α2 inhibition alters calcium responses in optic nerve astrocytes
Authors: Hartford April K. , Messer Miranda L. , Moseley Amy E. , Lingrel Jerry B. , Delamere Nicholas A. 
Published: January 2004

AbstractExperiments were conducted to test the effect of 1 μM ouabain, an Na,K‐ATPase inhibitor, on capacitative calcium entry (CCE) and calcium responses elicited by ATP in rat optic nerve astrocytes. In the rat, 1 μM ouabain is sufficient to inhibit the α2 Na,K‐ATPase, but not the α1. Immortalized astrocytes derived from Na,K‐ATPase α2 homozygous knockout (KO) mice and wild‐type (WT) littermates were also used. Cytosolic calcium and sodium concentrations were measured using Fura‐2 and SBFI, respectively. The magnitude of the increase in cytosolic calcium concentration during CCE was significantly greater in rat astrocytes exposed to 1 μM ouabain. To measure calcium release from stores, cells were exposed to ATP in the absence of extracellular calcium. In astrocytes exposed to 1 μM ouabain, a significantly greater calcium response to ATP was observed. 1 μM ouabain was shown to inhibit ATP hydrolysis in membrane material containing Na,K‐ATPase α2 and α1 isoforms (rat muscle) but not in membranes containing only Na,K‐ATPase α1 (rat kidney). In intact astrocytes, 1 μM ouabain did not alter the cell‐wide cytosolic sodium concentration. In mouse Na,K‐ATPase α2 KO astrocytes, the calcium increase during CCE was significantly higher than in WT cells, as was the magnitude of the calcium response to ATP. In KO astrocytes, but not WT, the cytosolic calcium increase during CCE was insensitive to 1 μM ouabain. Taken together, the results suggest that selective inhibition of the Na,K‐ATPase α2 isoform has the potential to change calcium signaling and CCE. © 2003 Wiley‐Liss, Inc.
Induction of chemokines in human astrocytes by picornavirus infection requires activation of both AP‐1 and NF‐κB
Authors: Kwon Daeho , Fuller Alyson C. , Palma Joann P. , Choi In‐Hong , Kim Byung S. 
Published: January 2004

AbstractInfection with different picornaviruses can cause meningitis/encephalitis in humans and experimental animals. To investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astrocytes was investigated following infection with Theiler's murine encephalomyelitis virus (TMEV), coxsackievirus B3 (CVB3), or coxsackievirus B4 (CVB4). We report that all these viruses are potent inducers for the expression of interleukin‐8 (IL‐8) and monocyte chemoattractant protein‐1 (MCP‐1) genes in primary human astrocytes, as well as in an established astrocyte cell line (U‐373MG). Further studies indicated that both activator protein‐1 (AP‐1) and NF‐κB transcription factors are required in the activation of chemokine genes in human astrocytes infected with various picornaviruses. Interestingly, the pattern of activated chemokine genes in human astrocytes is quite restricted compared to that in mouse astrocytes infected with the same viruses, suggesting species differences in gene activation. This may result in potential differences in the pathogenic outcome in each species. © 2003 Wiley‐Liss, Inc.