bluuebunny/crossref_metadata_2025 huggingface dataset:
MONO-ENERGETIC ELECTRON GENERATION AND PLASMA DIAGNOSIS EXPERIMENTS IN A LASER PLASMA CATHODE
Authors: KINOSHITA K. , HOSOKAI T. , OHKUBO T. , MAEKAWA A. , KOBAYASHI K. , UESAKA M. , ZHIDKOV A.
Published: October 2007

Acceleration of plasma electrons by laser wake-filed is the most promising process to produce the next generation of compact accelerators because of its ultrahigh acceleration gradient. To achieve the efficient and stable mono-energetic acceleration of plasma electrons, we investigated the laser-plasma interaction and its correlation to electron acceleration through single shot measurements. We observed a thin laser channel when a mono-energetic spectrum was generated.
PRELIMINARY RESULTS FROM THE UCLA/SLAC ULTRA-HIGH GRADIENT CERENKOV WAKEFIELD ACCELERATOR EXPERIMENT
Authors: THOMPSON M. C. , BADAKOV H. , ROSENZWEIG J. B. , TRAVISH G. , HOGAN M. , ISCHEBECK R. , KIRBY N. , MUGGLI P. , SCOTT A. , SIEMANN R. , WALZ D. , YODER R.
Published: October 2007

The first phase of an experiment to study the performance of dielectric Cerenkov wakefield accelerating structures at extremely high gradients in the GV/m range has been completed. This experiment takes advantage of the unique SLAC FFTB electron beam and its demonstrated ultra-short pulse lengths and high currents (e.g., σz = 20 μ m at Q = 3 nC ). The FFTB electron beam has been successfully focused down and sent through varying lengths of fused silica capillary tubing with two different sizes: ID = 200 μ m / OD = 325 μ m and ID = 100 μ m / OD = 325 μ m . The pulse length of the electron beam was varied in the range 20 μ m < σz < 100 μ m which produced a range of electric fields between 2 and 20 GV/m at the inner surface of the dielectric tubes. We observed a sharp increase in optical emissions from the capillaries in the middle part of this surface field range which we believe indicates the transition between sustainable field levels and breakdown. If this initial interpretation is correct, the surfaced fields that were sustained equate to on axis accelerating field of several GV/m. In future experiments we plan to collect and measure coherent Cerenkov radiation emitted from the capillary tube to gain more information about the strength of the accelerating fields.
ON A “MICROSCOPIC HUBBLE CONSTANT” FROM RELATIVISTIC NUCLEAR COLLISIONS
Authors: JIPA ALEXANDRU , BEŞLIU CĂLIN , ZGURĂ ION SORIN , RISTEA OANA , RISTEA CĂTĂLIN , HORBUNIEV AMELIA , ARSENE IONUţ , ARGINTARU DĂNUŢ , CĂLIN MARIUS , EŞANU TIBERIU , COVLEA VANEA , ILIESCU BOGDAN
Published: October 2007

Similarities between cosmological scenarios on the Universe evolution after “Big Bang” and the behavior of the highly excited nuclear matter formed in relativistic nuclear collisions, immediately after collisions, are considered to do an estimation of a “microscopic Hubble parameter/constant” for the expansion rate in relativistic nuclear collisions, similar with the cosmological Hubble constant. Temporal connections between the evolution of the nuclear matter after impact and the scenarios on the Universe evolution after “Big Bang” are introduced. Experimental results on participants, fireball sizes (identical particle interferometry), densities, particle spectra and temperatures have been used. A “Hubble scale” for temporal evolution can be obtained. Satisfactory agreement with Buda-Lund model estimations has been obtained.
EFFECT OF CHEMICAL FREEZE OUT ON IDENTIFIED PARTICLE SPECTRA AT 200 AGeV Au-Au COLLISIONS AT RHIC USING SPheRIO
Authors: QIAN WEI-LIANG , ANDRADE RONE , GRASSI FRÉDÉRIQUE , SOCOLOWSKI OTAVIO , KODAMA TAKESHI , HAMA YOGIRO
Published: October 2007

We investigate the effect of chemical freeze-out on identified particle spectra at 200 A GeV Au - Au Collisions at RHIC, by utilizing a full three-dimensional hydrodynamical calculation. The hydrodynamical code SPheRIO we employed is based on the smoothed particle hydrodynamic algorithm. In order to describe the spectra of strange hadrons, the code has been further improved by explicitly incorporating the strangeness conservation and a chemical freeze-out mechanism. In our model, strange hadrons such as Λ, Ξ, Ω and φ undergo the chemical freeze-out immediately after the hadronization, and their multiplicities are fixed thereafter. At a lower temperature the thermal freeze-out takes place for all the particles. It is shown that the present model provides a reasonably good description for the spectra of identified particles, in particular, considerable improvement is observed for those of strange hadrons.
CENTRALITY DEPENDENCE OF CHARGED HADRON SPECTRA AT FORWARD RAPIDITIES IN Cu+Cu COLLISIONS AT $\sqrt{^SNN} = 200\ {\rm GeV}$
Authors:   for the BRAHMS Collaboration, BEKELE SELEMON
Published: October 2007

We present preliminary results for Cu + Cu collisions at [Formula: see text] at the BRAHMS experiment from charged hadron spectra and nuclear modification factors as a function of centrality and pseudo-rapidity. Deviations from binary scaling at intermediate and high-pT reveal themselves as a suppression in the transverse momentum distribution of produced particles. The observed suppression depends on the volume of the interaction region through which produced hadrons have to travel. While there is still significant suppression, Rcp seems to depend very little on pseudo-rapidity.
HYDJET SIMULATIONS OF ELLIPTIC FLOW IN HEAVY ION COLLISIONS AT THE LHC
Authors: KROFCHECK D. , MAK R. , ALLFREY P.
Published: October 2007

At the Relativistic Heavy Ion Collider (RHIC) elliptic flow signals (v2) appear to be stronger than those measured at lower center-of-mass energies. With the beginning of heavy ion beams at the Large Hadron Collider (LHC) it is important to have a reliable tool for simulating v2 at the LHC Pb – Pb center-of-mass energy of 5.5 A TeV. In this work we used the heavy ion simulation tool HYDJET to study elliptic flow at the event generator level. The generator level elliptic flow v2 for Pb – Pb collisions was two-particle and four-particle cumulants.
PROBING AWAY SIDE JET MODIFICATION WITH THREE PARTICLE CORRELATIONS
Authors:   for the PHENIX Collaboration, AJITANAND N. N.
Published: October 2007

Recent experimental investigations have focussed on the abnormal spatial distribution of away side jet fragments as signals of significant medium induced effects. A variety of theoretical models including recent string-theory based efforts have supported the notion of Mach Cone like effects in the low viscosity QGP fluid. However, the presence of significant flow fields may deflect the fragmentation direction producing a significantly differing type of jet topology from that of the Mach cone. Three particle correlation functions constitute a powerful method whereby the predominance of one or the other type of mechanism can be differentiated. In this work the use of such an approach will be demonstrated via simulations and the results of its application to RHIC data will be presented.
ARE THERE MACH CONES IN HEAVY ION COLLISIONS?
Authors:   for the STAR Collaboration, ULERY JASON GLYNDWR
Published: October 2007

We present results from STAR on 3-particle azimuthal correlations for a 3 < pT < 4 GeV /c trigger particle with two softer 1 ≤ pT ≤ 2 GeV /c particles. Results are shown for pp , d + Au and high statistics Au + Au collisions at [Formula: see text]. We observe a 3-particle correlation in central Au + Au collisions which may indicate the presence of conical emission. In addition, the dependence of the observed signal angular position on the pT of the associated particles can be used to distinguish conical flow from simple QCD-Čerenkov radiation. An important aspect of the analysis is the subtraction of combinatorial backgrounds. Systematic uncertainties due to this subtraction and the flow harmonics v2 and v4 are investigated in detail.
WHY THE xE DISTRIBUTION TRIGGERED BY A LEADING PARTICLE DOES NOT MEASURE THE FRAGMENTATION FUNCTION BUT DOES MEASURE THE RATIO OF THE TRANSVERSE MOMENTA OF THE AWAY-SIDE JET TO THE TRIGGER-SIDE JET
Authors: TANNENBAUM M. J.
Published: October 2007

Hard-scattering of point-like constituents (or partons) in p-p collisions was discovered at the CERN-ISR1 in 1972 by measurements utilizing inclusive single or pairs of hadrons with large transverse momentum (pT). Due to the steeply falling power-law pT spectrum of the hard-scattered partons, the inclusive single particle (e.g. π0) pTt spectrum from parton fragmentation to a jet is dominated by trigger fragments with large zt ~ 0.7–0.8, where zt = pTt/pTjet is the fragmentation variable. It was generally assumed, following Feynman, Field and Fox,2 as shown by data from the CERN-ISR experiments, that the pTa distribution of away side hadrons from a single particle trigger [with pTt], corrected for zt, would be the same as that from a jet-trigger and follow the same fragmentation function as observed in e+e− or DIS. PHENIX3 attempted to measure the fragmentation function from the away side xE ~ PTa/pTt distribution of charged particles triggered by a π0 in p − p collisions at RHIC and showed by explicit calculation that the xE distribution is actually quite insensitive to the fragmentation function. Illustrations of the original arguments and ISR results will be presented. Then the lack of sensitivity to the fragmentation function will be explained, and an analytic formula for the xE distribution given, in terms of incomplete Gamma functions, for the case where the fragmentation function is exponential. The away-side distribution in this formulation has the nice property that it both exhibits xE scaling and is directly sensitive to the ratio of the away jet [Formula: see text] to that of the trigger jet, [Formula: see text], and thus can be used, for example, to measure the relative energy loss of the two jets from a hard-scattering which escape from the medium in A + A collisions. Comparisons of the analytical formula to RHIC measurements will be presented, including data from STAR4,5 and PHENIX,3,6 leading to some interesting conclusions.
CHARM QUARK THERMALIZATION IN QUARK-GLUON PLASMA
Authors: YAN LI , ZHUANG PENGFEI , XU NU
Published: October 2007

The charm quark thermalization in quark-gluon plasma is described by a transport model in relaxation time approximation. Combining the transport equation for charm quarks with the hydrodynamic description for the medium, we calculated the charm quark transverse momentum distribution and discussed its dependence on the relaxation time.
J/ψ RAPIDITY DISTRIBUTIONS IN THE SATURATION REGIME
Authors: DURÃES F. O. , NAVARRA F. S. , NIELSEN M.
Published: October 2007

In this work we calculate the J/ψ production in the initial stage of hadronic and nuclear collisions at RHIC and LHC energies, taking into account the high parton density regime of Quantum Chromodynamics (QCD), where the physics of parton saturation is expected to be dominant. We perform a quantitative analysis of the rapidity distributions in these collisions with the Color Glass Condensate (CGC) approach. The ratio between distributions with or without saturated gluons shows that this mechanism produces a suppression of the J/ψ yield in the forward region only at very high energies.
SYSTEM SIZE AND ENERGY DEPENDENCE OF HIGH pT HADRON PRODUCTION MEASURED WITH PHENIX EXPERIMENT AT RHIC
Authors:   PHENIX Collaboration, SAKAGUCHI TAKAO
Published: October 2007

PHENIX has measured high transverse momentum (pT) identified hadrons in different collision species and energies in the last five RHIC runs. The systematic study of the high PT hadron production provides an idea on interaction of hard scattered partons and the matter created in relativistic heavy ion collision. The η/π0 ratio is measured in Au + Au collisions, which gives a hint on the system thermalization and particle production. A future measurement of hadron and photon measurement is discussed.
ACOUSTIC EQUATIONS IN THE PRESENCE OF RIGID POROUS MATERIALS ADAPTED TO THE FINITE-DIFFERENCE TIME-DOMAIN METHOD
Authors: ESCOLANO JOSÉ , PUEO BASILIO
Published: October 2007

Finite-difference time-domain (FDTD) method has been successfully developed to model electromagnetic systems in recent years. Since acoustics and electromagnetism share certain undulatory properties, a natural adaptation of this technique has been developed too. Several acoustics problems, such as room acoustics, require the use of fibrous tangles to attenuate the propagation speed of sound waves. Notwithstanding, although free air acoustic propagation is known, FDTD technique is not developed yet to model fibrous materials. To characterize this behavior, only a few and measurable set of parameters must be considered. In this paper, a new approach for modeling fibrous materials analysis using FDTD is presented and validated. A set of simulations covering various packing densities of a real fibrous material is performed. Loudspeaker cabinets, virtual acoustics and room acoustics are situations in which this method can be applied.
LOW-FREQUENCY ACOUSTIC SCATTERING OF A PLANE WAVE FROM A SOFT AND HARD TORUS
Authors: VENKOV GEORGE
Published: October 2007

A plane acoustic wave is scattered by either a soft or a hard small torus. The incident wave has a wavelength which is much larger than the characteristic dimension of the scatterer and thus the low-frequency approximation method is applicable to the scattering problem. It is shown that there exists exactly one toroidal coordinate system that fits the given geometry. The R-separation of variables is utilized to obtain the series expansion of the fields in terms of toroidal harmonics (half-integer Legendre functions of first and second kind). The scattering problem for the soft torus is solved analytically for the near field, governing the leading two low-frequency coefficients, as well as for the far field, where both the amplitude and the cross-section are evaluated. The scattering problem for the hard torus appears to be much more complicated in calculations. The Neumann boundary condition on the surface of the torus leads to a three-term recurrence relation for the series coefficients corresponding to the scattered fields. Thus, the potential boundary-value problem for the leading low-frequency approximations is reduced to infinite systems of linear algebraic equations with three-diagonal matrices. An analytical technique for solving systems of diagonal form is developed.
AZIMUTHAL LIMITATION IN 3D PE APPROXIMATION FOR UNDERWATER ACOUSTIC PROPAGATION
Authors: HSIEH LI-WEN , CHEN CHI-FANG , YUAN MEI-CHUN , LIN YING-TSONG
Published: October 2007

The azimuthal limitation of the Parabolic Equation (PE) approximation in solving the three-dimensional (3D) wave equation in cylindrical coordinate has been studied in this paper. Typically, 3D problems are dealt with an N × 2D approximation, which treats a 3D field as a fan-like composition of many 2D vertical slices (r - z plane in cylindrical coordinate) ignoring the θ-coupling terms. To deal with problems possessing 3D effects, the θ-coupling terms have to be considered in PE approximation. Nevertheless, the azimuthal limitation in the 3D PE approximation is not defined as well as the vertical angle limitation. Hence, the theoretical derivation estimating the azimuthal limitation is put forth in this work. Numerical results of a modified benchmark problem are also presented to validate the arguments and the wide angle version of the 3D PE model, FOR3D.
A QUESTION OF BALANCE IN INTEGRATED IMPACT ASSESSMENT: NEGOTIATING AWAY THE ENVIRONMENTAL INTEREST IN AUSTRALIA'S BASSLINK PROJECT
Authors: DUNCAN RONLYN , HAY PETE
Published: October 2007

It is argued that under the guise of integrated impact assessment, environmental capacity and quality is being eroded rather than enhanced. This proposition is examined in the context of a World Heritage Area and an integrated impact assessment process for a major energy infrastructure project in Australia known as Basslink. The case study, which charts the negotiations that took place between a proponent, environmental researchers, consultants, regulators and decision-makers for an environmental flow for the iconic Gordon River in Tasmania, describes the 'balance' that was struck in the name of sustainable development. It demonstrates that, while social and economic benefits tend to be identified as one and the same, the environment is constituted as an oppositional "good". We argue that this outcome is the rule rather than the exception and caution that integrated assessments could serve to 'fast-track' the loss of environmental capacity and quality.
CONSTRAINTS TO ENVIRONMENTAL IMPACT ASSESSMENT PRACTICE: A CASE STUDY OF CAMEROON
Authors: ALEMAGI DIEUDONNE , SONDO VENAN A. , ERTEL JÜRGEN
Published: October 2007

Environmental Impact Assessment (EIA) practice in Cameroon has been plagued with many constraints especially from the infrastructure and EIA resource perspective. The present legal and procedural disposition vis-à-vis EIA in Cameroon is monumental and manifest some clarity of exposition with regards to the practical and fundamental steps for EIA practice in the country. However, a number of impediments still prevail that deter the full efficiency of this legislation. In search for explanations to this trend, this study was conducted to examine the current framework governing EIA in Cameroon implemented in February 2005. Content analysis and interviews with stakeholders in the EIA process were undertaken to identify key barriers associated with EIA practice in Cameroon. The paper maintains that inadequate baseline data, procedural flaws in scoping, exorbitant administrative fees, absence of an appeal procedure, unclear proviso, incompetent personnel and over centralisation of EIA powers are key barriers that appear to impede a healthy EIA practice in Cameroon. In conclusion, it is submitted that for a robust EIA practice to prevail in Cameroon, there is an urgent need for a great deal of focus on the recommendations prescribed within the context of the paper.
Hyaluronan in Tissue Injury and Repair
Authors: Jiang Dianhua , Liang Jiurong , Noble Paul W.
Published: October 2007

A hallmark of tissue injury and repair is the turnover of extracellular matrix components. This review focuses on the role of the glycosaminoglycan hyaluronan in tissue injury and repair. Both the synthesis and degradation of extracellular matrix are critical contributors to tissue repair and remodeling. Fragmented hyaluronan accumulates during tissue injury and functions in ways distinct from the native polymer. There is accumulating evidence that hyaluronan degradation products can stimulate the expression of inflammatory genes by a variety of immune cells at the injury site. CD44 is the major cell-surface hyaluronan receptor and is required to clear hyaluronan degradation products produced during lung injury; impaired clearance of hyaluronan results in persistent inflammation. However, hyaluronan fragment stimulation of inflammatory gene expression is not dependent on CD44 in inflammatory macrophages. Instead, hyaluronan fragments utilize both Toll-like receptor (TLR) 4 and TLR2 to stimulate inflammatory genes in macrophages. Hyaluronan also is present on the cell surface of lung alveolar epithelial cells and provides protection against tissue damage by interacting with TLR2 and TLR4 on these parenchymal cells. The simple repeating structure of hyaluronan appears to be involved in a number of important aspects of noninfectious tissue injury and repair that are dependent on the size and location of the polymer as well as the interacting cells. Thus, the interactions between the endogenous matrix component hyaluronan and its signaling receptors initiate inflammatory responses, maintain structural cell integrity, and promote recovery from tissue injury.
Interleukin-21: Basic Biology and Implications for Cancer and Autoimmunity
Authors: Spolski Rosanne , Leonard Warren J.
Published: October 2007

Interleukin-21 (IL-21), a potent immunomodulatory four-α-helical-bundle type I cytokine, is produced by NKT and CD4+ T cells and has pleiotropic effects on both innate and adaptive immune responses. These actions include positive effects such as enhanced proliferation of lymphoid cells, increased cytotoxicity of CD8+ T cells and natural killer (NK) cells, and differentiation of B cells into plasma cells. Conversely, IL-21 also has direct inhibitory effects on the antigen-presenting function of dendritic cells and can be proapoptotic for B cells and NK cells. IL-21 is also produced by Th17 cells and is a critical regulator of Th17 development. The regulatory activity of IL-21 is modulated by the differentiation state of its target cells as well as by other cytokines or costimulatory molecules. IL-21 has potent antitumor activity but is also associated with the development of autoimmune disease. IL-21 transcription is dependent on a calcium signal and NFAT sites, and IL-21 requires Stat3 for its signaling. The key to harnessing the power of IL-21 will depend on better understanding its range of biological actions, its mechanism of action, and the molecular basis of regulation of expression of IL-21 and its receptor.
Linear relation between time constant of oxygen uptake kinetics, total creatine, and mitochondrial content in vitro
Authors: Glancy Brian , Barstow Thomas , Willis Wayne T.
Published: October 2007

Following the onset of moderate aerobic exercise, the rate of oxygen consumption (Jo) rises monoexponentially toward the new steady state with a time constant (τ) in the vicinity of 30 s. The mechanisms underlying this delay have been studied over several decades. Meyer's electrical analog model proposed the concept that the τ is given by τ = Rm· C, where Rm is mitochondrial resistance to energy transfer, and C is metabolic capacitance, determined primarily by the cellular total creatine pool (TCr = phosphocreatine + creatine). The purpose of this study was to evaluate in vitro the Jo kinetics of isolated rat skeletal muscle mitochondria at various levels of TCr and mitochondrial protein. Mitochondria were incubated in a medium containing 5.0 mM ATP, TCr pools of 0–1.5 mM, excess creatine kinase, and an ATP-splitting system of glucose + hexokinase (HK). Pyruvate and malate (1 mM each) were present as oxidative substrates. Jo was measured across time after HK was added to elicit one of two levels of Jo (40 and 60% of state 3). At TCr levels (in mM) of 0.1, 0.2, 0.3, 0.75, and 1.5, the corresponding τ values (s, means ± SE) were 22.2 ± 3.0, 36.3 ± 2.2, 65.7 ± 4.3, 168.1 ± 22.2, and 287.3 ± 25.9. Thus τ increased linearly with TCr ( R2 = 0.916). Furthermore, the experimentally observed τ varied linearly and inversely with the mitochondrial protein added. These in vitro results consistently conform to the predictions of Meyer's electrical analog model.
Trophic action of sphingosine 1-phosphate in denervated rat soleus muscle
Authors: Zanin Marika , Germinario Elena , Dalla Libera Luciano , Sandonà Dorianna , Sabbadini Roger A. , Betto Romeo , Danieli-Betto Daniela
Published: October 2007

Sphingosine 1-phosphate (S1P) mediates a number of cellular responses, including growth and proliferation. Skeletal muscle possesses the full enzymatic machinery to generate S1P and expresses the transcripts of S1P receptors. The aim of this work was to localize S1P receptors in rat skeletal muscle and to investigate whether S1P exerts a trophic action on muscle fibers. RT-PCR and Western blot analyses demonstrated the expression of S1P1 and S1P3 receptors by soleus muscle. Immunofluorescence revealed that S1P1 and S1P3 receptors are localized at the cell membrane of muscle fibers and in the T-tubule membranes. The receptors also decorate the nuclear membrane. S1P1 receptors were also present at the neuromuscular junction. The possible trophic action of S1P was investigated by utilizing the denervation atrophy model. Rat soleus muscle was analyzed 7 and 14 days after motor nerve cut. During denervation, S1P was continuously delivered to the muscle through a mini osmotic pump. S1P and its precursor, sphingosine (Sph), significantly attenuated the progress of denervation-induced muscle atrophy. The trophic effect of Sph was prevented by N, N-dimethylsphingosine, an inhibitor of Sph kinase, the enzyme that converts Sph into S1P. Neutralization of circulating S1P by a specific antibody further demonstrated that S1P was responsible for the trophic effects of S1P during denervation atrophy. Denervation produced the down regulation of S1P1 and S1P3 receptors, regardless of the presence of the receptor agonist. In conclusion, the results suggest that S1P acts as a trophic factor of skeletal muscle.
Intestinal Ca2+ wave dynamics in freely moving C. elegans coordinate execution of a rhythmic motor program
Authors: Nehrke K. , Denton Jerod , Mowrey William
Published: October 2007

Defecation in the nematode worm Caenorhabditis elegans is a highly rhythmic behavior that is regulated by a Ca2+ wave generated in the 20 epithelial cells of the intestine, in part through activation of the inositol 1,4,5-trisphosphate receptor. Execution of the defecation motor program (DMP) can be modified by external cues such as nutrient availability or mechanical stimulation. To address the likelihood that environmental regulation of the DMP requires integrating distinct cellular and organismal processes, we have developed a method for studying coordinate Ca2+ oscillations and defecation behavior in intact, freely behaving animals. We tested this technique by examining how mutations in genes known to alter Ca2+ handling [including egl-8/phospholipase C (PLC)-β, kqt-3/KCNQ1, sca-1/sarco(endo)plasmic reticulum Ca2+ ATPase, and unc-43/Ca2+-CaMKII] contribute to shaping the Ca2+ wave and asked how Ca2+ wave dynamics in the mutant backgrounds altered execution of the DMP. Notably, we find that Ca2+ waves in the absence of PLCβ initiate ectopically, often traveling in reverse, and fail to trigger a complete DMP. These results suggest that the normal supremacy of the posterior intestinal cells is not obligatory for Ca2+ wave occurrence but instead helps to coordinate the DMP. Furthermore, we present evidence suggesting that an underlying pacemaker appears to oscillate at a faster frequency than the defecation cycle and that arrhythmia may result from uncoupling the pacemaker from the DMP rather than from disrupting the pacemaker itself. We also show that chronic elevations in Ca2+ have limited influence on the defecation period but instead alter the interval between successive steps of the DMP. Finally, our results demonstrate that it is possible to assess Ca2+ dynamics and muscular contractions in a completely unrestrained model organism.
COOH-terminal association of human smooth muscle calcium channel Cav1.2b with Src kinase protein binding domains: effect of nitrotyrosylation
Authors: Kang Minho , Ross Gracious R. , Akbarali Hamid I.
Published: October 2007

The carboxyl terminus of the calcium channel plays an important role in the regulation of calcium entry, signal transduction, and gene expression. Potential protein-protein interaction sites within the COOH terminus of the L-type calcium channel include those for the SH3 and SH2 binding domains of c-Src kinase that regulates calcium currents in smooth muscle. In this study, we examined the binding sites involved in Src kinase-mediated phosphorylation of the human voltage-gated calcium channel (Cav) 1.2b (hCav1.2b) and the effect of nitrotyrosylation. Cotransfection of human embryonic kidney (HEK)-293 cells with hCav1.2b and c-Src resulted in tyrosine phosphorylation of the calcium channel, which was prevented by nitration of tyrosine residues by peroxynitrite. Whole cell calcium currents were reduced by 58 + 5% by the Src kinase inhibitor PP2 and 64 + 6% by peroxynitrite. Nitrotyrosylation prevented Src-mediated regulation of the currents. Glutathione S-transferase fusion protein of the distal COOH terminus of hCav1.2b (1809-2138) bound to SH2 domain of Src following tyrosine phosphorylation, while binding to SH3 required the presence of the proline-rich motif. Site-directed mutation of Y2134 prevented SH2 binding and resulted in reduced phosphorylation of hCav1.2b. Within the distal COOH terminus, single, double, or triple mutations of Y1837, Y1861, and Y2134 were constructed and expressed in HEK-293 cells. The inhibitory effects of PP2 and peroxynitrite on calcium currents were significantly reduced in the double mutant Y1837-2134F. These data demonstrate that the COOH terminus of hCav1.2b contains sites for the SH2 and SH3 binding of Src kinase. Nitrotyrosylation of these sites prevents Src kinase regulation and may be importantly involved in calcium influx regulation during inflammation.
Ectodomain shedding of pro-TGF-α is required for COX-2 induction and cell survival in renal medullary cells exposed to osmotic stress
Authors: Küper Christoph , Bartels Helmut , Fraek Maria-Luisa , Beck Franz X. , Neuhofer Wolfgang
Published: October 2007

In the renal medulla, cyclooxygenase (COX)-2 is induced by osmotic stress as present in this kidney region during antidiuresis. Increasing evidence suggests that EGF receptor (EGFR) signaling is involved in this process. The aim of the present study was to examine the mechanisms responsible for COX-2 expression and PGE2 production during hypertonic conditions and to identify potential autocrine/paracrine EGFR ligands. Immunohistochemisty and Western blot analysis revealed abundant expression of the pro-EGFR ligand pro-transforming growth factor (TGF)-α in renal medullary cells in vivo and in cultured Madin-Darby canine kidney cells. In Madin-Darby canine kidney cells, hypertonicity rapidly increased TNF-α converting enzyme (TACE)-dependent ectodomain shedding of pro-TGF-α; phosphorylation of EGFR, p38, and ERK1/2; expression of COX-2; and production of PGE2. Conversely, TACE inhibition prevented TGF-α release; EGFR, p38, and ERK1/2 activation; and COX-2 expression. Furthermore, cell survival was reduced substantially, a response that could be reversed by the addition of PGE2. Simultaneous addition of recombinant TGF-α during TACE inhibition restored EGFR and MAPK phosphorylation, COX-2 expression, PGE2 production, and cell survival during osmotic stress. These results indicate that hypertonicity induces TACE-mediated ectodomain shedding of pro-TGF-α, which subsequently activates COX-2 expression in an autocrine/paracrine fashion, via EGFR and MAPKs. We conclude that tonicity-induced TGF-α release is required for COX-2 expression, PGE2 synthesis, and survival of renal medullary cells during osmotic stress.
Effect of caveolin-1 scaffolding peptide and 17β-estradiol on intracellular Ca2+kinetics evoked by angiotensin II in human vascular smooth muscle cells
Authors: Méndez-Bolaina Enrique , Sánchez-González Javier , Ramírez-Sánchez Israel , Ocharán-Hernández Esther , Núñez-Sánchez Marisol , Meaney-Mendiolea Eduardo , Meaney Alejandra , Asbun-Bojalil Juan , Miliar-García Angel , Olivares-Corichi Ivonne , Ceballos-Reyes Guillermo
Published: October 2007

Caveolae are identifiable plasma membrane invaginations. The main structural proteins of caveolae are the caveolins. There are three caveolins expressed in mammals, designated Cav-1, Cav-2, and Cav-3. It has been postulated that Cav-1 acts as a scaffold protein for signaling proteins; these include ion channels, enzymes, and other ligand receptors like membrane-associated estrogen receptor (ER)α or ERβ. Caveolae-associated membrane proteins are involved in regulating some of the rapid estrogenic effects of 17β-estradiol. One important system related to the activity of ERα and caveolae is the renin-angiotensin system. Angiotensin II (ANG II) has numerous actions in vascular smooth muscle, including modulation of vasomotor tone, cell growth, apoptosis, phosphatidylinositol 3-kinase (PI3K)/Akt activation, and others. Many proteins associated with caveolae are in close relation with the scaffolding domain of Cav-1 (82–101 amino acid residues). It has been proposed that this peptide may acts as a kinase inhibitor. Therefore, to explore the ability of Cav-1 scaffolding peptide (CSP-1) to regulate ANG II function and analyze the relationship between ERα and ANG II type 1 and 2 (AT1and AT2) receptors, we decided to study the effects of CSP-1 on ANG II-induced intracellular Ca2+kinetics and the effect of 17β-estradiol on this modulation using human smooth muscle cells in culture, intracellular Ca2+concentration measurements, immuno- and double-immunocytochemistry confocal analysis of receptor expression, immunoblot analysis, and immunocoprecipitation assays to demonstrate coexpression. We hypothesized that CSP-1 inhibits ANG II-mediated increases in intracellular Ca2+concentrations by interfering with intracellular signaling including the PI3K/Akt pathway. We also hypothesize that AT2receptors associate with Cav-1. Our results show that there is a close association of AT1, AT2, and ERα with Cav-1 in human arterial smooth muscle cells in culture. CSP-1 inhibits ANG II-induced intracellular signaling.
Acute activation of ERα decreases food intake, meal size, and body weight in ovariectomized rats
Authors: Santollo Jessica , Wiley Mathew D. , Eckel Lisa A.
Published: October 2007

Estradiol exerts many of its actions by coupling with two nuclear estrogen receptor (ER) proteins, ERα, and ERβ.While the acute, anorexigenic effect of estradiol appears to involve such a mechanism, the relative contributions of ERα and ERβ are equivocal. To address this problem, food intake was monitored in ovariectomized (OVX) rats following acute administration of a selective ERα agonist (4,4′,4′′-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol, PPT; dose range = 0–200 μg), a selective ERβ agonist (2,3-bis(4-hydroxyphenyl)-propionitrile, DPN; dose range = 0–600 μg), and a physiological (4 μg) dose of estradiol benzoate (EB). While PPT-treated rats displayed dose-dependent decreases in daily food intake and body weight, neither of these measures was influenced by any dose of DPN. In addition, DPN failed to modulate the anorexigenic effect of PPT when the two ER agonists were coadministered. Meal pattern analysis revealed that the anorexigenic effect of 75 μg PPT (a dose of PPT that produced a similar decrease in daily food intake as 4 μg EB) was mediated by a decrease in meal size, not meal number. Thus, PPT, like EB and endogenous estradiol, decreases food intake by selectively affecting the controls of meal size. The finding that acute administration of 75 μg PPT failed to induce a conditioned taste aversion suggests that the anorexigenic effect of this dose of PPT is not secondary to malaise. Taken together, our findings demonstrate that selective activation of ERα decreases food intake, body weight, and meal size in the ovariectomized rat.
Load-dependent effects of duodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, and energy intake in healthy men
Authors: Pilichiewicz Amelia N. , Papadopoulos Penny , Brennan Ixchel M. , Little Tanya J. , Meyer James H. , Wishart Judith M. , Horowitz Michael , Feinle-Bisset Christine
Published: October 2007

Both load and duration of small intestinal lipid infusion affect antropyloroduodenal motility and CCK and peptide YY (PYY) release at loads comparable to and higher than the normal gastric emptying rate. We determined 1) the effects of intraduodenal lipid loads well below the mean rate of gastric emptying on, and 2) the relationships between antropyloroduodenal motility, CCK, PYY, appetite, and energy intake. Sixteen healthy males were studied on four occasions in double-blind, randomized fashion. Antropyloroduodenal motility, plasma CCK and PYY, and appetite perceptions were measured during 50-min IL (Intralipid) infusions at: 0.25 (IL0.25), 1.5 (IL1.5), and 4 (IL4) kcal/min or saline (control), after which energy intake at a buffet meal was quantified. IL0.25 stimulated isolated pyloric pressure waves (PWs) and CCK release, albeit transiently, and suppressed antral PWs, PW sequences, and hunger ( P < 0.05) but had no effect on basal pyloric pressure or PYY when compared with control. Loads ≥ 1.5 kcal/min were required for the stimulation of basal pyloric pressures and PYY and suppression of duodenal PWs ( P < 0.05). All of these effects were related to the lipid load ( R > 0.5 or < −0.5, P < 0.05). Only IL4 reduced energy intake (in kcal: control, 1,289 ± 62; IL0.25, 1,282 ± 44; IL1.5, 1,235 ± 71; and IL4, 1,139 ± 65 compared with control and IL0.25, P < 0.05). In conclusion, in healthy males the effects of intraduodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, appetite, and energy intake are load dependent, and the threshold loads required to elicit responses vary for these parameters.
Identification of BRAF as a new interactor of PLCε1, the protein mutated in nephrotic syndrome type 3
Authors: Chaib Hassan , Hoskins Bethan E. , Ashraf Shazia , Goyal Meera , Wiggins Roger C. , Hildebrandt Friedhelm
Published: October 2007

Steroid-resistant nephrotic syndrome is a malfunction of the kidney glomerular filter that leads to proteinuria, hypoalbuminemia, edema, and renal failure. Recently, we identified recessive mutations in the phospholipase C epsilon 1 gene ( PLCE1) as a new cause of early-onset nephrotic syndrome and demonstrated interaction of PLCε1 with IQGAP1. To further elucidate the mechanism by which PLCE1 mutations cause nephrotic syndrome, we sought to identify new protein interaction partners of PLCε1. We utilized information from the genetic interaction network of C. elegans. It relates the PLCE1 ortholog ( plc-1) to the C. elegans ortholog ( lin-45) of human BRAF ( v-raf murine sarcoma viral oncogene homolog B1). We hypothesized that this may indicate a functional protein-protein interaction. Using GST pull down of HEK293T cell lysates in vitro and coimmunoprecipation of mouse kidney lysates in vivo, we show that BRAF interacts with PLCε1. By immunohistochemistry in rat kidney, we demonstrate that both proteins are coexpressed and colocalize in developing and mature glomerular podocytes, reporting for the first time the expression of BRAF in the glomerular podocyte.
Heterogeneity of bronchoconstriction does not distinguish mild asthmatic subjects from healthy controls when supine
Authors: Kaminsky David A. , Irvin Charles G. , Lundblad Lennart K. A. , Thompson-Figueroa John , Klein Jeffrey , Sullivan Michael J. , Flynn Frank , Lang Sherburn , Bourassa Lorraine , Burns Stephanie , Bates Jason H. T.
Published: October 2007

Heterogeneity is a fundamental property of airway constriction; however, whether it is a distinguishing feature of mild asthma is not clear. We used computerized tomography and the forced oscillation technique to compare lung heterogeneity between 18 mildly asthmatic and 19 healthy control subjects at similar levels of bronchoconstriction while subjects were supine. We also assessed the effects of deep inhalation and albuterol on supine lung mechanics. Measures of heterogeneity included lung attenuation, from which we derived a novel index of air-space size, and the frequency dependence of respiratory system resistance between 1 and 20 Hz. We found that asthmatic subjects had airways hyperresponsiveness to methacholine in the sitting position compared with controls, but both groups had similar falls in forced expiratory volume in 1 s after inhaling methacholine while supine. There were no baseline differences between the groups in the frequency dependence of resistance, or lung attenuation, before methacholine, and both groups responded similarly with an increase in air-space size (+9.2% vs. +3.4%), air-space size heterogeneity (+9.8% vs. +4.2%), and frequency dependence of resistance (+76% vs. +86%) after methacholine. Deep inhalation did not affect resistance in either group, but albuterol significantly reduced resistance in both groups. We conclude that both computerized tomography and the forced oscillation technique demonstrate increased heterogeneity of airway narrowing during induced bronchoconstriction while supine and that this heterogeneity is equivalent between subjects with mild asthma and healthy controls when bronchoconstricted to the same degree. Thus heterogeneity appears to be a fundamental feature of bronchoconstriction and is not unique to mild asthma.
Two patterns of daily hypoxic exposure and their effects on measures of chemosensitivity in humans
Authors: Koehle Michael S. , Sheel A. William , Milsom William K. , McKenzie Donald C.
Published: October 2007

The purpose of this study was to compare chemoresponses following two different intermittent hypoxia (IH) protocols in humans. Ten men underwent two 7-day courses of poikilocapnic IH. The long-duration IH (LDIH) protocol consisted of daily 60-min exposures to normobaric 12% O2. The short-duration IH (SDIH) protocol comprised twelve 5-min bouts of 12% O2, separated by 5-min bouts of room air, daily. Isocapnic hypoxic ventilatory response (HVR) was measured daily during the protocol and 1 and 7 days following. Hypercapnic ventilatory response (HCVR) and CO2 threshold and sensitivity (by the modified Read rebreathing technique) were measured on days 1, 8, and 14. Following 7 days of IH, the mean HVR was significantly increased from 0.47 ± 0.07 and 0.47 ± 0.08 to 0.70 ± 0.06 and 0.79 ± 0.06 l·min−1·%SaO2−1 (LDIH and SDIH, respectively), where %SaO2 is percent arterial oxygen saturation. The increase in HVR reached a plateau after the third day. One week post-IH, HVR values were unchanged from baseline. HCVR increased from 3.0 ± 0.4 to 4.0 ± 0.5 l·min−1·mmHg−1. In both the hyperoxic and hypoxic modified Read rebreathing tests, the slope of the CO2/ventilation plot was unchanged by either intervention, but the CO2/ventilation curve shifted to the left following IH. There were no correlations between the changes in response to hypoxia and hypercapnia. There were no significant differences between the two IH protocols for any measures, indicating that comparable changes in chemoreflex control occur with either protocol. These results also suggest that the two methods of measuring CO2 response are not completely concordant and that the changes in CO2 control do not correlate with the increase in the HVR.
Neuronal Responses to Passive Movement in the Globus Pallidus Internus in Primary Dystonia
Authors: Chang Edward F. , Turner Robert S. , Ostrem Jill L. , Davis Valerie R. , Starr Philip A.
Published: October 2007

Abnormal sensory processing has been implicated in the pathophysiology of primary dystonia. In the globus pallidus internus (GPi), the primary output structure of the basal ganglia, many neurons respond to sensory (proprioceptive) stimulation. Here we have characterized GPi neuronal responses to passive movement of the contralateral limbs in 22 patients with primary dystonia undergoing microelectrode recording for placement of deep brain stimulator leads. We plotted coordinates of cells responding to limb movement in a common space. We observed distinct representations of leg and arm movement localized to the dorsal and ventral part of the posterior GPi, respectively. Comparing patients with generalized dystonia versus patients with segmental craniocervical dystonia, there was no difference in the volumes or separations of leg and arm related territories. In contrast to parkinsonism, only a small minority of units were responsive to movement across multiple joints. Abnormally increased directional selectivity was found in units responding to dystonic limbs compared with nondystonic limbs. Some affected GPi neurons therefore appear to have altered proprioceptive tuning for movement direction. There is an apparent preservation of GPi somatotopic organization in dystonia in comparison with prior studies of GPi somatotopic organization in non-human primates and humans with Parkinson's disease.
Motor Cortical Measures of Use-Dependent Plasticity Are Graded From Distal to Proximal in the Human Upper Limb
Authors: Krutky Matthew A. , Perreault Eric J.
Published: October 2007

In humans, it is well established that practicing simple, repetitive movements with the distal upper limb induces short-term plasticity in the neural pathways that control training. It is unknown how the neural response to similar training at more proximal joints differs. The purpose of this study was to quantify how ballistic training at proximal and distal upper limb joints influences measures of corticomotor plasticity. To accomplish this goal, we had subjects repetitively practice simple movements for 30 min using the index finger, wrist, or elbow. Before and after training, transcranial magnetic stimulation (TMS) was used to activate the corticomotor pathways innervating the trained joint. We assessed the effect of training by quantifying changes in TMS-elicited joint movements and motor-evoked potentials in the training agonists and antagonists. These measures of training-induced neural plasticity were graded from distal to proximal in the upper limb. Training had the greatest immediate effect on the pathways controlling the index finger and this effect decreased for more proximal joints. Our results suggest that the relative sizes and properties of the cortical areas controlling the proximal and distal upper limb influence the effect of training on the corticomotor pathways. These results have implications for how training influences the neural pathways controlling movement in the proximal and distal portions of the human upper limb and the degree to which these effects can be quantified using TMS.
Stomatin and Sensory Neuron Mechanotransduction
Authors: Martinez-Salgado Carlos , Benckendorff Anne G. , Chiang Li-Yang , Wang Rui , Milenkovic Nevena , Wetzel Christiane , Hu Jing , Stucky Cheryl L. , Parra Marilyn G. , Mohandas Narla , Lewin Gary R.
Published: October 2007

Somatic sensory neurons of the dorsal root ganglia are necessary for a large part of our mechanosensory experience. However, we only have a good knowledge of the molecules required for mechanotransduction in simple invertebrates such as the nematode Caenorhabiditis elegans. In C. elegans, a number of so-called mec genes have been isolated that are required for the transduction of body touch. One such gene, mec-2 codes for an integral membrane protein of the stomatin family, a large group of genes with a stomatin homology domain. Using stomatin null mutant mice, we have tested the hypothesis that the founding member of this family, stomatin might play a role in the transduction of mechanical stimuli by primary sensory neurons. We used the in vitro mouse skin nerve preparation to record from a large population of low- and high-threshold mechanoreceptors with myelinated A-fiber ( n = 553) and unmyelinated C-fiber ( n = 157) axons. One subtype of mechanoreceptor, the d-hair receptor, which is a rapidly adapting mechanoreceptor, had reduced sensitivity to mechanical stimulation in the absence of stomatin. Other cutaneous mechanoreceptors, including nociceptive C-fibers were not affected by the absence of a functional stomatin protein. Patch-clamp analysis of presumptive D-hair receptor mechanoreceptive neurons, which were identified by a characteristic rosette morphology in culture, showed no change in membrane excitability in the absence of the stomatin protein. We conclude that stomatin is required for normal mechanotransduction in a subpopulation of vertebrate sensory neurons.