bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of presynaptic glycine receptors facilitates glycine release from presynaptic terminals synapsing onto rat spinal sacral dorsal commissural nucleus neurons
Authors: Jeong Hyo‐Jin , Jang Il‐Sung , Moorhouse Andrew J. , Akaike Norio
Published: May 2003

Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Here we report the novel finding that presynaptic glycine autoreceptors modulate release from terminals synapsing onto rat spinal sacral dorsal commissural nucleus (SDCN) neurons. In mechanically dissociated SDCN neurons, in which functional presynaptic nerve terminals remain adherent to the isolated neurons, exogenously applied glycine (3 μM) increased the frequency of glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs) without affecting their amplitudes or decay times. This suggests that glycine acts presynaptically to increase glycine release probability. Picrotoxin, at a concentration that had little direct effect on sIPSC frequency and amplitude (30 μM), significantly attenuated glycine‐induced presynaptic sIPSC facilitation. The glycine‐induced sIPSC frequency facilitation was completely abolished either in a Ca2+‐free external solution or in the presence of 100 μM Cd2+, suggesting the involvement of extracellular Ca2+ influx into the nerve terminals. The glycine action was also completely occluded in the presence of 300 nM tetrodotoxin. In recordings from SDCN neurons in spinal cord slices, glycine (10 μM) increased evoked IPSC (eIPSC) amplitude and decreased the extent of paired‐pulse facilitation. In response to brief high frequency stimulus trains the eIPSCs displayed a profound frequency‐dependent facilitation that was greatly reduced by picrotoxin (30 μM). These results indicate that glycine acts at presynaptic autoreceptors, causing depolarization of the glycinergic nerve terminals, the subsequent activation of voltage‐dependent Na+ and Ca2+ channels, and facilitation of glycine release. Furthermore, this presynaptic facilitation was observed under more physiological conditions, suggesting that these glycinergic autoreceptors may contribute to the integration of local inhibitory inputs to SDCN neurons.
Temperature dependence of NADPH oxidase in human eosinophils
Authors: Morgan Deri , Cherny Vladimir V. , Murphy Ricardo , Xu Wei , Thomas Larry L. , DeCoursey Thomas E.
Published: May 2003

The phagocyte NADPH oxidase helps kill pathogens by producing superoxide anion, O2−. This enzyme is electrogenic because it translocates electrons across the membrane, generating an electron current, Ie. Using the permeabilized patch voltage‐clamp technique, we studied the temperature dependence of Ie in human eosinophils stimulated by phorbol myristate acetate (PMA) from room temperature to > 37°C. For comparison, NADPH oxidase activity was assessed by cytochrome c reduction. The intrinsic temperature dependence of the assembled, functioning NADPH oxidase complex measured during rapid temperature increases to 37°C was surprisingly weak: the Arrhenius activation energy Ea was only 14 kcal mol−1 (Q10, 2.2). In contrast, steady‐state NADPH oxidase activity was strongly temperature dependent at 20–30°C, with Ea 25.1 kcal mol−1 (Q10, 4.2). The maximum Ie measured at 34°C was −30.5 pA. Above 30°C, the temperature dependence of both Ie and O2− production was less pronounced. Above 37°C, Ie was inhibited reversibly. After rapid temperature increases, a secondary increase in Ie ensued, suggesting that high temperature promotes assembly of additional NADPH oxidase complexes. Evidently, about twice as many NADPH oxidase complexes are active near 37°C than at 20°C. Thus, the higher Q10 of steady‐state Ie reflects both increased activity of each NADPH oxidase complex and preferential assembly of NADPH oxidase complexes at high temperature. In summary, NADPH oxidase activity in intact human eosinophils is maximal precisely at 37°C.
Cannabinoid1 Receptor in the Dorsal Vagal Complex Modulates Lower Oesophageal Sphincter Relaxation in Ferrets
Authors: Partosoedarso E. R. , Abrahams T. P. , Scullion R. T. , Moerschbaecher J. M. , Hornby P. J.
Published: May 2003

Delta9‐tetrahydrocannabinol (Δ9‐THC) is an effective anti‐emetic; however, other potential gastrointestinal therapeutic effects of Δ9‐THC are less well‐known. Here, we report a role of Δ9‐THC in a vago‐vagal reflex that can result in gastro‐oesophageal reflux, that is, gastric distension‐evoked lower oesophageal sphincter (LOS) relaxation. Oesophageal, LOS and gastric pressures were measured using a miniaturized, manometric assembly in decerebrate, unanaesthetized ferrets. Gastric distension (30 ml) evoked LOS relaxation (70 ± 8 % decrease from baseline). Δ9‐THC administered systemically (0.2 mg kg−1, I.V.) or directly to the dorsal hindbrain surface (0.002 mg), significantly attenuated the nadir of the gastric distention‐evoked LOS relaxation, and time to reach maximal response. Similar increases to maximal effect were observed after treatment with the cannabinoid receptor agonist WIN 55,212–2 (0.2 mg kg−1, I.V.). The effect of systemic Δ9‐THC on gastric distention‐evoked LOS relaxation was reversed by a selective cannabinoid1 (CB1) receptor antagonist, SR141617A (1 mg kg−1, I.V.). Since this reflex is vagally mediated, we used a CB1 receptor antiserum and immunocytochemistry to determine its distribution in ferret vagal circuitry. CB1 receptor staining was present in cell bodies within the area postrema, nucleus tractus solitarius (NTS) and nodose ganglion. Intense terminal‐like staining was noted within the NTS and dorsal motor vagal nucleus (DMN). Neither nodose ganglionectomy nor vagotomy altered the CB1 receptor terminal‐like staining in the dorsal vagal complex. Retrogradely labelled gastric‐ or LOS‐projecting DMN neurones did not express CB1 receptors within their soma. Therefore, CB1 receptor staining in the NTS and DMN is not due to primary vagal afferents or preganglionic neurones. These novel findings suggest that Δ9‐THC can modulate reflex LOS function and that the most likely site of action is via the CB1 receptor within the NTS. This effect of Δ9‐THC may have implications in treatment of gastro‐oesophageal reflux and other upper gut disorders.
Mist/Steam Heat Transfer With Jet Impingement Onto a Concave Surface
Authors: Li Xianchang , Gaddis J. Leo , Wang Ting
Published: May 2003

Internal mist/steam blade cooling technology is proposed for the future generation of Advanced Turbine Systems (ATS). Fine water droplets about 5 μm were carried by steam through a slot jet onto a concave heated surface in a confined channel to simulate inner surface cooling at the leading edge of a turbine blade. Experiments covered Reynolds numbers from 7500 to 22,000 and heat fluxes from 3 to 21 kW/m2. Results indicate that the cooling is enhanced significantly near the stagnation point by the mist, decreasing downstream. Unlike impingement onto a flat target where the enhancement vanished at six jet diameters downstream, the cooling enhancement over a concave surface prevails at all points downstream. Similar to the results of the flat surface, the cooling enhancement declines at higher heat fluxes. Up to 200 % cooling enhancement at the stagnation point was achieved by injecting approximately 0.5 % of mist.
Numerical Analysis of the Transverse Thermal Conductivity of Composites With Imperfect Interfaces
Authors: Graham Samuel , McDowell David L.
Published: May 2003

Estimation of the transverse thermal conductivity of continuous fiber reinforced composites containing a random fiber distribution with imperfect interfaces was performed using finite element analysis. FEA results were compared with the classical solution of Hasselman and Johnson to determine limits of applicability. The results show that the Hasselman and Johnson model predicts the effective thermal conductivity within 3 percent of the numerical estimates for interfacial conductance values of 1×10−2−1×103W/m2K, fiber-matrix conductivity ratios between 1 and 100, and fiber volume fractions up to 50 percent which are properties typical of ceramic composites. The results show that the applicability of the classical dilute concentration model can not be determined by constituent volume fraction, but by the degree of interaction between the microstructural heterogeneities.
Numerical Simulation of Reciprocating Flow Forced Convection in Two-Dimensional Channels
Authors: Sert Cuneyt , Beskok Ali
Published: May 2003

Numerical simulations of laminar, forced convection heat transfer for reciprocating, two-dimensional channel flows are performed as a function of the penetration length, Womersley (α) and Prandtl (Pr) numbers. The numerical algorithm is based on a spectral element formulation, which enables high-order spatial resolution with exponential decay of discretization errors, and second-order time-accuracy. Uniform heat flux and constant temperature boundary conditions are imposed on certain regions of the top surface, while the bottom surface is kept insulated. Periodicity of velocity and temperature fields is imposed on the side boundaries, while the flow is driven by an oscillating pressure gradient. These sets of boundary conditions enable time-periodic solution of the problem. Instantaneous and time-averaged surface and bulk temperature distributions, and Nusselt number variations are presented. For high α flows, the temperature field is significantly affected by the Richardson’s annular effect. Overall, forced convection increases by increasing the penetration length, α and Pr. Corresponding steady-flow simulations are performed by matching the volumetric flowrate. For the limited parameter space investigated in this paper, steady unidirectional forced convection is more effective than the reciprocating flow forced convection.
Influence of Flatness and Waviness of Rough Surfaces on Surface Contact Conductance
Authors: Sunil Kumar S. , Ramamurthi K.
Published: May 2003

The effect of surface roughness, waviness and flatness deviations on thermal contact conductance is predicted. Threshold values of the surface parameters which do not adversely influence thermal contact conductance are determined. Flatness deviations less than ten times the average roughness and waviness less than about four times the average roughness do not significantly affect the contact conductance. A correlation is developed for contact conductance in terms of the surface parameters, the material properties and the contact pressure at the joint. Experiments are conducted in vacuum with rough, non-flat and wavy surfaces and the experimental results are demonstrated to agree well with the predictions.
Mechanism of Annular Two-Phase Flow Heat Transfer Enhancement and Pressure Drop Penalty in the Presence of a Radial Electric Field—Turbulence Analysis
Authors: Feng Y. , Seyed-Yagoobi J.
Published: May 2003

The mechanism of heat transfer enhancement and pressure drop penalty in the presence of a radial electric field for the two-phase (liquid/vapor) annular flow is presented. The turbulence spectral theory shows that the radial electric field fluctuation changes the turbulent energy distribution, especially in the radial direction. Consequently, the Reynolds stresses are directly affected by the applied electric field. The analysis reveals that the influence of the applied electric field on the turbulence distribution in an annular two-phase flow leads to the changes in the heat transfer and the pressure drop. The magnitudes of the heat transfer enhancement and the pressure drop penalty are strongly related to the ratio of the radial pressure difference generated by the EHD force to the axial frictional pressure drop. The existing experimental data agree with the predictions of the analysis presented in this paper. The analysis developed here can be a valuable tool in properly predicting the two-phase annular flow heat transfer enhancement and pressure drop penalty in the presence of a radial electric field for both convective boiling and condensation processes.
Reattachment of Three-Dimensional Flow Adjacent to Backward-Facing Step
Authors: Nie J. H. , Armaly B. F.
Published: May 2003

Numerical simulations for incompressible three-dimensional laminar forced convection flow adjacent to backward-facing step in rectangular duct are performed to examine the reattachment region of the separated flow on the stepped wall. The feasibility of utilizing the two-dimensional flow definition and the limiting streamline definition for identifying the reattachment line/region was examined. The downwash and the “jet-like” flow that develops near the sidewall creates significant spanwise flow adjacent to the stepped wall, making it difficult to identify a reattachment line/region both numerically and experimentally. The use of the line/region that identifies the location on a plane adjacent to the stepped wall where the gradient of the mean streamwise velocity component is zero ∂u/∂y|y=0=0 is recommended for code and apparatus validation of three-dimensional separated flow.
CD2-Associated Protein Haploinsufficiency Is Linked to Glomerular Disease Susceptibility
Authors: Kim Jeong M. , Wu Hui , Green Gopa , Winkler Cheryl A. , Kopp Jeffrey B. , Miner Jeffrey H. , Unanue Emil R. , Shaw Andrey S.
Published: May 2003

Loss of CD2-associated protein (CD2AP), a component of the filtration complex in the kidney, causes death in mice at 6 weeks of age. Mice with CD2AP haploinsufficiency developed glomerular changes at 9 months of age and had increased susceptibility to glomerular injury by nephrotoxic antibodies or immune complexes. Electron microscopic analysis of podocytes revealed defects in the formation of multivesicular bodies, suggesting an impairment of the intracellular degradation pathway. Two human patients with focal segmental glomerulosclerosis had a mutation predicted to ablate expression of one CD2AP allele, implicating CD2AP as a determinant of human susceptibility to glomerular disease.
Influence of Satellite Data Uncertainties on the Detection of Externally Forced Climate Change
Authors: Santer B. D. , Wigley T. M. L. , Meehl G. A. , Wehner M. F. , Mears C. , Schabel M. , Wentz F. J. , Ammann C. , Arblaster J. , Bettge T. , Washington W. M. , Taylor K. E. , Boyle J. S. , Brüggemann W. , Doutriaux C.
Published: May 2003

Two independent analyses of the same satellite-based radiative emissions data yield tropospheric temperature trends that differ by 0.1°C per decade over 1979 to 2001. The troposphere warms appreciably in one satellite data set, while the other data set shows little overall change. These satellite data uncertainties are important in studies seekingto identify human effects on climate. A model-predicted “fingerprint” of combined anthropogenic and natural effects is statistically detectable only in the satellite data set with a warmingtroposphere. Our findings show that claimed inconsistencies between model predictions and satellite tropospheric temperature data (and between the latter and surface data) may be an artifact of data uncertainties.
Thin-Film Transistor Fabricated in Single-Crystalline Transparent Oxide Semiconductor
Authors: Nomura Kenji , Ohta Hiromichi , Ueda Kazushige , Kamiya Toshio , Hirano Masahiro , Hosono Hideo
Published: May 2003

We report the fabrication of transparent field-effect transistors using a single-crystalline thin-film transparent oxide semiconductor, InGaO
3
(ZnO)
5
, as an electron channel and amorphous hafnium oxide as a gate insulator. The device exhibits an on-to-off current ratio of ∼10
6
and a field-effect mobility of ∼80 square centimeters per volt per second at room temperature, with operation insensitive to visible light irradiation. The result provides a step toward the realization of transparent electronics for next-generation optoelectronics.
Derivation of Oocytes from Mouse Embryonic Stem Cells
Authors: Hübner Karin , Fuhrmann Guy , Christenson Lane K. , Kehler James , Reinbold Rolland , De La Fuente Rabindranath , Wood Jennifer , Strauss Jerome F. , Boiani Michele , Schöler Hans R.
Published: May 2003

Continuation of mammalian species requires the formation and development of the sexually dimorphic germ cells. Cultured embryonic stem cells are generally considered pluripotent rather than totipotent because of the failure to detect germline cells under differentiating conditions. Here we show that mouse embryonic stem cells in culture can develop into oogonia that enter meiosis, recruit adjacent cells to form follicle-like structures, and later develop into blastocysts. Oogenesis in culture should contribute to various areas, including nuclear transfer and manipulation of the germ line, and advance studies on fertility treatment and germ and somatic cell interaction and differentiation.
A Modular PIP
2
Binding Site as a Determinant of Capsaicin Receptor Sensitivity
Authors: Prescott Elizabeth D. , Julius David
Published: May 2003

The capsaicin receptor (TRPV1), a heat-activated ion channel of the pain pathway, is sensitized by phosphatidylinositol-4,5-bisphosphate (PIP
2
) hydrolysis after phospholipase C activation. We identify a site within the C-terminal domain of TRPV1 that is required for PIP
2
-mediated inhibition of channel gating. Mutations that weaken PIP
2
-TRPV1 interaction reduce thresholds for chemical or thermal stimuli, whereas TRPV1 channels in which this region is replaced with a lipid-binding domain from PIP
2
-activated potassium channels remain inhibited by PIP
2
. The PIP
2
-interaction domain therefore serves as a critical determinant of thermal threshold and dynamic sensitivity range, tuning TRPV1, and thus the sensory neuron, to appropriately detect heat under normal or pathophysiological conditions.
Uncoupling of Leading- and Lagging-Strand DNA Replication During Lesion Bypass in Vivo
Authors: Pagès Vincent , Fuchs Robert P.
Published: May 2003

Numerous agents attack DNA, forming lesions that impair normal replication. Specialized DNA polymerases transiently replace the replicative polymerase and copy past lesions, thus generating mutations, the major initiating cause of cancer. We monitored, in
Escherichia coli
, the kinetics of replication of both strands of DNA molecules containing a single replication block in either the leading or lagging strand. Despite a block in the leading strand, lagging-strand synthesis proceeded further, implying transient uncoupling of concurrent strand synthesis. Replication through the lesion requires specialized DNA polymerases and is achieved with similar kinetics and efficiencies in both strands.
n
-Type Conducting CdSe Nanocrystal Solids
Authors: Yu Dong , Wang Congjun , Guyot-Sionnest Philippe
Published: May 2003

A bottleneck limiting the widespread application of semiconductor nanocrystal solids is their poor conductivity. We report that the conductivity of thin films of
n
-type CdSe nanocrystals increases by many orders of magnitude as the occupation of the first two electronic shells, 1S
e
and 1P
e
, increases, either by potassium or electrochemical doping. Around half-filling of the 1S
e
shell, a peak in the conductivity is observed, indicating shell-to-shell transport. Introducing conjugated ligands between nanocrystals increases the conductivities of these states to ∼10
–
2
siemens per centimeter.
Using 1-Hz GPS Data to Measure Deformations Caused by the Denali Fault Earthquake
Authors: Larson Kristine M. , Bodin Paul , Gomberg Joan
Published: May 2003

The 3 November 2002 moment magnitude 7.9 Denali fault earthquake generated large, permanent surface displacements in Alaska and large-amplitude surface waves throughout western North America. We find good agreement between strong ground-motion records integrated to displacement and 1-hertz Global Positioning System (GPS) position estimates collected ∼140 kilometers from the earthquake epicenter. One-hertz GPS receivers also detected seismic surface waves 750 to 3800 kilometers from the epicenter, whereas these waves saturated many of the seismicinstruments in the same region. High-frequency GPS increases the dynamic range and frequency bandwidth of ground-motion observations, providing another tool for studying earthquake processes.
Coronavirus Main Proteinase (3CL
pro
) Structure: Basis for Design of Anti-SARS Drugs
Authors: Anand Kanchan , Ziebuhr John , Wadhwani Parvesh , Mesters Jeroen R. , Hilgenfeld Rolf
Published: May 2003

A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (M
pro
, also called 3CL
pro
), which controls the activities of the coronavirus replication complex, is an attractive target for therapy. We determined crystal structures for human coronavirus (strain 229E) M
pro
and for an inhibitor complex of porcine coronavirus [transmissible gastroenteritis virus (TGEV)] M
pro
, and we constructed a homology model for SARS coronavirus (SARS-CoV) M
pro
. The structures reveal a remarkable degree of conservation of the substrate-binding sites, which is further supported by recombinant SARS-CoV M
pro
-mediated cleavage of a TGEV M
pro
substrate. Molecular modeling suggests that available rhinovirus 3C
pro
inhibitors may be modified to make them useful for treating SARS.
Gene Regulation at the RNA Layer: RNA Binding Proteins in Intercellular Signaling Networks
Authors: Lasko Paul
Published: May 2003

Transcriptional regulators are sometimes believed to be the only targets through which signal transduction pathways regulate gene expression. Although it is certainly true that many well-characterized intercellular signaling pathways operate by modifying the activity of specific transcription factors, an increasing body of evidence indicates that external signals can modulate gene expression by posttranscriptional mechanisms. RNA binding motifs are combined with other conserved domains, such as protein-interaction domains and consensus phosphorylation motifs, to allow gene expression to be regulated at the level of the RNA in response to extracellular signals. In this review, I discuss evidence that reveals how a particular family of RNA binding proteins, called signal transduction and activation of RNA (STAR) proteins, function in signaling and in the development of multicellular organisms. Furthermore, insulin and related growth factors regulate cell growth, at least in part, by moderating the activity of eukaryotic initiation factor 4E (eIF4E)-binding protein (4EBP), a protein that does not bind RNA directly but inhibits the activity of eIF4E, which is an mRNA cap-binding protein. I discuss the evidence linking insulin signaling to 4EBP phosphorylation. Finally, several other genes have been identified from invertebrate model organisms that encode RNA binding proteins and whose mutant phenotypes implicate them in intercellular signaling, but for which the mechanisms of function currently are unclear. The study of these and other similar genes is likely to uncover a diversity of roles for RNA binding proteins in signal transduction.
PDZ Domain Proteins: Plug and Play!
Authors: Nourry Claire , Grant Seth G. N. , Borg Jean-Paul
Published: May 2003

Protein-protein interactions are key elements in building functional protein complexes. Among the plethora of domains identified during the last 10 years, PDZ domains are one of the most commonly found protein-protein interaction domains in organisms from bacteria to humans. Although they may be the sole protein interaction domain within a cytoplasmic protein, they are most often found in combination with other protein interaction domains (for instance, SH3, PTB, WW) participating in complexes that facilitate signaling or determine the localization of receptors. Diversity of PDZ-containing protein function is provided by the large number of PDZ proteins that Mother Nature has distributed in the genome and implicates this protein family in the wiring of a huge number of molecules in molecular networks from the plasma membrane to the nucleus. Although at first sight their binding specificity appeared rather monotonous, involving only binding to the carboxyl-terminus of various proteins, it is now recognized that PDZ domains interact with greater versatility through PDZ-PDZ domain interaction; they bind to internal peptide sequences and even to lipids. Furthermore, PDZ domain-mediated interactions can sometimes be modulated in a dynamic way through target phosphorylation. In this review, we attempt to describe the structural basis of PDZ domain recognition and to give some functional insights into their role in the scaffolding of protein complexes implicated in normal and pathological biological processes.
The Structure and Function of Proline Recognition Domains
Authors: Zarrinpar Ali , Bhattacharyya Roby P. , Lim Wendell A.
Published: May 2003

One particularly abundant group of modular recognition domains consists of those that bind proline-rich motifs. Such modules, including the SH3, WW, and EVH1 domains, play a critical role in the assembly and regulation of many intracellular signaling complexes. These domains use strikingly similar molecular mechanisms of proline recognition. We discuss some of the potential biological advantages conferred by proline recognition, which may explain its widespread use in signaling.
Calcium and the Failing Heart: Phospholamban, Good Guy or Bad Guy?
Authors: Schwinger Robert H. G. , Frank Konrad F.
Published: May 2003

In cardiac cells, phospholamban is a potent inhibitor of sarcoplasmic reticulum calcium (Ca
2+
) transport. Overexpression of mutant forms of phospholamban may result in beneficial or detrimental effects on intracellular Ca
2+
handling and cardiac systolic and diastolic function. Mutations in phospholamban have also been linked to human cardiomyopathies, providing important insights into the underlying disease mechanisms and the key role of phospholamban in myocardial excitation-contraction coupling. This Perspective discusses new advances in our understanding of the role of phospholamban in intracellular Ca
2+
handling and the development of human and murine cardiomyopathies.
Angiotensin Type 2 Receptor (AT2R): A Challenging Twin
Authors: Berk Bradford C.
Published: May 2003

Angiotensin II (AngII) regulates such physiological responses as salt and water balance, blood pressure, and vascular tone, and thus plays a critical role in the pathogenesis of diabetes, hypertension, myocardial infarction, congestive heart failure, and stroke. These effects are mediated through at least three receptors: AT1R, AT2R, and AT4R, which are expressed under different developmental, tissue-specific, and disease-specific conditions and which couple to distinct effector pathways. Signaling through the AT1R, a classical G protein-coupled receptor, has been extensively studied and is well understood. Less is known about signaling through the AT2R, which often antagonizes the effects of signaling through the AT1R, but intriguing data are beginning to emerge concerning the signaling strategies and pathways that the AT2R employs.
Iron Regulatory Proteins as NO Signal Transducers
Authors: Bouton Cécile , Drapier Jean-Claude
Published: May 2003

The iron regulatory proteins (IRPs) are an example of different proteins regulating the same metabolic process, iron uptake and metabolism. IRP1 is an iron-sulfur cluster-containing protein that can be converted from a cytosolic aconitase to an RNA binding posttranscriptional regulator in response to nitric oxide (NO). IRP2 lacks aconitase activity and its expression is decreased by NO signaling. In macrophages, NO is produced in response to such inflammatory ligands as interferon-γ, which is expressed in response to mitogenic and antigenic stimuli, and lipopolysaccharide, a marker of bacterial invasion. Until recently, research results predict that the cellular response to increased NO production should be a decrease in ferritin synthesis, due to IRP1 binding to ferritin mRNA, and an increase in transferrin receptor biosynthesis, due to IRP1 binding to the transferrin mRNA. Surprisingly, however, macrophages exhibit decreased transferrin receptor concentration in response to inflammatory ligands. Bouton and Drapier discuss the physiological role and the mechanisms that may underlie this contradictory response.
Imaging Zinc: Old and New Tools
Authors: Frederickson Christopher
Published: May 2003

As recently as 20 years ago, all zinc in biological systems was believed to be tightly bound to proteins, and the idea of imaging zinc was considered heretical. Beginning with Maske's research with dithizonate staining of the hippocampus in the 1950s, however, zinc-sensitive dyes have indicated that, in mammalian cells, free zinc can exist in at least three separate pools. These pools include vesicular zinc sequestered in presynaptic vesicles and secretory granules, zinc released from these vesicles into the extracellular space after physiological stimulation, and transient increases in zinc in cells in the regions where extracellular release of zinc has occurred. This Perspective covers the zinc-imaging tools, from dithizonate to the newest FRET-based sensors, that have galvanized biomedical science.
Do We Need Zinc to Think?
Authors: Li Yang V. , Hough Christopher J. , Sarvey John M.
Published: May 2003

Chelatable Zn
2+
, which is found in the synaptic vesicles of certain glutamatergic neurons in several regions of the forebrain, is released during neuronal activity. Zn
2+
exhibits numerous effects on ligand-gated and voltage-dependent ion channels, and released Zn
2+
is therefore likely able to modulate synaptic transmission. The physiologically relevant actions of Zn
2+
,

however, have remained unclear. Recent research exploiting improved Zn
2+
-sensitive optical probes has suggested some intriguing effects for synaptically released Zn
2+
, including heterosynaptic regulation of
N
-methyl-
D
-aspartate (NMDA) receptor function, and a novel role as a trans-synaptic second messenger that may enter postsynaptic neurons to modulate various signal transduction pathways.
Comparison of Human Immunodeficiency Virus Type 1 Viral Loads in Kenyan Women, Men, and Infants during Primary and Early Infection
Authors: Richardson Barbra A. , Mbori-Ngacha Dorothy , Lavreys Ludo , John-Stewart Grace C. , Nduati Ruth , Panteleeff Dana D. , Emery Sandra , Kreiss Joan K. , Overbaugh Julie
Published: May 2003

Steady-state levels of human immunodeficiency virus type 1 (HIV-1) RNA in plasma reached at approximately 4 months postinfection are highly predictive of disease progression. Several studies have investigated viral levels in adults or infants during primary and early infection. However, no studies have directly compared these groups. We compared differences in peak and set point plasma HIV-1 RNA viral loads among antiretrovirus-naive Kenyan infants and adults for whom the timing of infection was well defined. Peak and set point viral loads were significantly higher in infants than in adults. We did not observe any gender-specific differences in viral set point in either adults or infants. However, infants who acquired HIV-1 in the first 2 months of life, either in utero, intrapartum, or through early breast milk transmission, had significantly higher set point HIV-1 RNA levels than infants who were infected after 2 months of age through late breast milk transmission or adults who were infected through heterosexual transmission.
Simian Virus 5 Is a Poor Inducer of Chemokine Secretion from Human Lung Epithelial Cells: Identification of Viral Mutants That Activate Interleukin-8 Secretion by Distinct Mechanisms
Authors: Young Virginia A. , Parks Griffith D.
Published: May 2003

We have compared chemokine secretion from human lung A549 cells infected with simian virus 5 (SV5) with other members of the
Rubulavirus
genus of paramyxoviruses. High levels of the chemokines interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) were secreted from A549 cells infected with
Human parainfluenza virus type 2
(HPIV-2) but not from cells infected with wild-type (WT) SV5. The lack of IL-8 secretion from SV5-infected cells was not due to a global block in all signal transduction pathways leading to IL-8 secretion, since SV5-infected A549 cells secreted IL-8 after stimulation with exogenously added tumor necrosis factor alpha or by coinfection with HPIV-2. A previously described, recombinant SV5 containing substitutions in the shared region of the P/V gene (rSV5-P/V-CPI−) induced IL-8 secretion by a mechanism that was dependent on viral gene expression. By contrast, an SV5 variant isolated from persistently infected cells (Wake Forest strain of
Canine parainfluenza virus
) induced IL-8 secretion by a mechanism that was largely not affected by inhibitors of viral gene expression. Together, these data demonstrate that SV5 is unusual compared to other closely related paramyxoviruses, since SV5 is a very poor inducer of the cytokines IL-8 and MCP-1. The isolation of two recombinant SV5 mutants that are defective in preventing chemokine induction will allow an identification of mechanisms utilized by WT SV5 to avoid activation of host cell innate immune responses to infection.
An unusual new archosauromorph reptile from the Upper Triassic Wolfville Formation of Nova Scotia
Authors: Sues Hans-Dieter
Published: May 2003

An unusual new reptile, Teraterpeton hrynewichorum, is described based on a partial skeleton. The holotype comes from the Upper Triassic Wolfville Formation (Newark Supergroup) of Nova Scotia. The temporal region of the skull is of the euryapsid type. The premaxillary rostrum and dentary symphysis are elongate and edentulous. The dentition comprises distinctive, occluding upper and lower teeth. A phylogenetic analysis shows that Teraterpeton hrynewichorum is an archosauromorph reptile. Trilophosaurus buettneri from the Upper Triassic Dockum Group of Texas may represent a closely related species.
Growth patterns and ontogenetic variation of the teeth and jaws of the Middle Jurassic sphenodontian Cynosphenodon huizachalensis (Reptilia: Rhynchocephalia)
Authors: Reynoso Víctor-Hugo
Published: May 2003

Growth patterns in teeth and jaws of the Middle Jurassic sphenodontian Cynosphenodon huizachalensis are compared to those of the extant Sphenodon, showing extreme similarity. Both taxa share the unique presence of a hatchling tooth series divided into anterior uniform size and posterior alternating size tooth regions by the eruption of successional teeth early in life, an ever-growing second-generation successional tooth that becomes a caniniform tooth in adults, and a symphysial region that grows anteriorly but with a differential faster rate in the dorsal margin, enlarging considerably the length between the caniniform tooth and the anterior tip of the dentary, and increasing the angle of the anterior margin of the symphysis. The sister-group relationships of Sphenodon and Cynosphenodon have been supported by the simple presence of a single caniniform tooth, but this tooth is shown to be a complex structure involving several other ontogenetic related synapomorphies as follows: (i) it is a second-generation successional tooth that replaces a first-generation successional tooth; (ii) it emerges between the anterior hatchling teeth and the alternating size hatchling series, replacing some teeth of the latter; (iii) it grows continuously in height and width during life at a rate faster than that of tooth wear; (iv) it denotes regionalization in the symphysis, marking previously undetected growing points of the dentary; and (v) it shows the posterior limit of the edentulous anterior margin diagnostic to Sphenodontinae. New developmental information about the caniniform tooth strongly supports the structure as a homologous character, endorsing the sister-group relationships of Cynosphenodon and Sphenodon. Developmental comparisons can provide good evidence concerning the homology of a similar character present in two or more taxa. These studies are particularly useful if a clade is weakly supported by a single character.
Geology of Denman and Hornby islands, British Columbia: implications for Nanaimo Basin evolution and formal definition of the Geoffrey and Spray formations, Upper Cretaceous Nanaimo Group
Authors: Katnick Deanne C , Mustard Peter S
Published: May 2003

The Upper Cretaceous Nanaimo Group of southwest British Columbia is a >4 km-thick succession consisting mostly of deep marine siliciclastics deposited directly on the Insular Superterrane. As such, this succession has been the focus of several paleomagnetic, isotope geochemistry, paleontology, and sedimentology studies in attempts to elucidate the tectonic history and paleolatitude of the Insular Superterrane and associated entities during the critical time of Nanaimo Group deposition (ca. 9065 Ma). However, disagreement as to whether deposition occurred into a single or multiple basins has led to confusion concerning the formal stratigraphy and formation names for the succession, and has resulted in problems with both local and regional correlations. The upper two-thirds of the succession is continuously and well exposed on Denman and Hornby islands and represents the best example of this part of the succession in the northern half of what we consider the single Nanaimo Basin. This area includes the previously only informally defined type areas for the Geoffrey and Spray formations, defined here formally for the first time with type sections and detailed descriptions. New interpretations of the geology of these islands demonstrate that previously interpreted major faults do not exist, resulting in stratigraphic and age controls that are both different and simpler than previously interpreted. The redefined stratigraphy of the northern part of the basin is remarkably similar to that of southern areas in both type and age, affirming both a single basin evolution and a single stratigraphic nomenclature.
Effect of Feeding Acacia abyssinica and of Its Extracts Given by Different Routes on Rats
Authors: AL-Redhaiman K. N. , Salad M. A. , Adam S. E. I.
Published: May 2003

The effect of a diet consisting of 2% and 10% of Acacia abyssinica bark on Wistar rats treated for 6 weeks was examined. A 2% A. abyssinica diet was not toxic to rats. Impairment of growth and hepatonephropathy were observed in rats on a 10% A. abyssinica diet. By whatever route it was administered, either intraperitoneally (i.p.) or orally (p.o.), the ethyl acetate extract in daily doses of 500 mg/kg body weight was the most toxic and lethal to rats and caused hepatonephropathy, widespread hemorrhage and congestion and fibrinous peritonitis following i.p. administration. The aqueous and ethanol extracts in similar doses to ethyl acetate extract were only lethal to rats when given via the i.p. route. Lesions were accompanied by anemia, leukopenia and alterations in serum AST activity and concentrations of urea, total protein and albumin.
In Vitro Cytotoxic, Antiviral and Immunomodulatory Effects of Plantago major and Plantago asiatica
Authors: Chiang Lien-Chai , Chiang Wen , Chang Mei-Yin , Lin Chun-Ching
Published: May 2003

Plantago major Linn. and P. asiatica Linn. (Plantaginaceae) are commonly used as folk medicine in Taiwan for treating infectious diseases related to the respiratory, urinary and digestive tracts. In this study, we investigated the antiviral, cytotoxic and immunomodulatory activities of hot water extracts of these two species in vitro on a series of viruses, namely herpesviruses (HSV-1 and HSV-2), adenoviruses (ADV-3, ADV-8 and ADV-11), and on various human leukemia, lymphoma and carcinoma cells with XTT, BrdU and IFN-γ kits. Results showed that hot water extract of P. asiatica possessed significant inhibitory activity on the proliferation of lymphoma (U937) and carcinoma (bladder, bone, cervix, kidney, lung and stomach) cells and on viral infection (HSV-2 and ADV-11). P. major and P. asiatica both exhibited dual effects of immunodulatory activity, enhancing lymphocyte proliferation and secretion of interferon-γ at low concentrations (< 50 μg/ml), but inhibiting this effect at high concentration (< 50 μg/ml). The present study concludes that hot water extracts of P. major and P. asiatica possess a broad-spectrum of antileukemia, anticarcinoma and antiviral activities, as well as activities which modulate cell-mediated immunity. Further investigations to elucidate the active component(s) of P. asiatica and P. major and to evaluate their clinical application are warranted.
The Effect of Liu-Wei-Di-Huang Wan on Cytokine Gene Expression from Human Peripheral Blood Lymphocytes
Authors: Shen Jiann-Jong , Lin Chun-Jing , Huang Jing-Long , Hsieh Kue-Hsiung , Kuo Ming-Ling
Published: May 2003

Liu-Wei-Di-Huang Wan (LWDHW) has been used by traditional Chinese doctors to treat asthma patients. This study was to examine the potential effect of this decoction on the regulation of T helper (Th)1- and Th2-type cytokine gene expression in vitro. Peripheral blood mononuclear cells (PBMC) were activated with mitogen for 24 hours in the presence or absence of LWDHW extracts. Concentrations of different cytokines in the culture supernatants were determined with ELISA. RNA isolated from cultured cells was subjected to RT-PCR analysis. The results showed that the expression of all cytokines (Th2-type: IL-4, IL-5, IL-10, or IL-13 and Th1-type: IL-2 and IFN-γ) examined was inhibited at both RNA and protein levels by LWDHW. Since the cell viability was similar in all cultures, the reduction of cytokine production was not due to the toxicity of LWDHW. Moreover, the cells either retained or increased their capacity to respond to mitogen stimulation after incubation with the LWDHW decoction. Therefore, the data suggest that LWDHW functioned directly on cytokine gene expression from activated PBMC.
Effects of Hwangryunjihwang-tang on In Vitro Fertilization and Ovulation in Mice Fed a High-fat Diet
Authors: Choi H. G. , Kwak D. H. , Kim J. Y. , Choi Y. J. , Kil B. S. , Kim H. A. , Jung K. Y. , Shin M. K. , Lee H. S. , Choo Y. K.
Published: May 2003

It has been generally accepted that Hwangryunjihwang-tang (H-tang) is a useful prescription for treating polydipsia and to prevent obesity induced by a high-fat diet. The aim of this study was to clarify whether H-tang improved reproductive dysfunction caused by obesity in mice. Mice were fed a high density protein and lipid diet for 4 weeks, followed by administration of H-tang at 480 mg/kg body weight per day for 4 days. Thereafter, changes of body weight, ovulation rate, in vitro and in vivo fertilization, embryonic development and implantation rate were measured. H-tang markedly reduced the body weight of obese mice fed a high-fat diet, but not mice fed a normal diet. H-tang significantly improved ovulation rates, in vitro and in vivo fertilization rates and embryonic development. These results indicate pharmacological reversal of reproductive dysfunction caused by obesity, perhaps by adjusting internal secretions and metabolic functions.
Establishing the Existence of the Active Stomach Point in the Auricle Utilizing Radial Artery Tonometry
Authors: Ikezono Etsutaro , Ikezono Tetsuo , Ackerman John
Published: May 2003

One component of Oriental medicine diagnosis utilizes the palpation of the radial pulse both for internal medicine and also to help clinicians accurately choose body acupuncture treatment points. In the mid-1980s, an attempt was made to capture diagnostic information with three pressure transducers positioned bilaterally over the radial arteries in such a fashion as to simulate classical Chinese pulse diagnosis (Yoon and Ikezono, 1986 and 1987). The results of this pilot study were subsequently difficult to replicate. In the early 1950s, Paul Nogier in Lyon, France introduced a different pulse diagnostic technique (Nogier, 1976). By touching an acupuncture needle on an active auricular acupuncture point, the radial artery wall over the styloid process changes in tone more prominently than when inactive points on the acuricle are touched. This dermal/cardiovascular reflex of pulse diagnostic technique helps, then to localize salient auricular points to treat regarding a patient's illness. Objective digitalized measurements of the Nogier radial arterial pulse wave were performed by computerized tonometry. This demonstrated that when an active stomach point in the auricle (n = 11) was detected utilizing an imperceptible electric current, the initial upstroke of the pressure wave, the pulse pressure and the peak-to-peak interval of the radial artery pulse wave all increased significantly compared to placebo point electronic detection. Thus, the existence of an active auricular point on the auricle was verified by radial artery tonometry.
Interactions Between Modern and Chinese Medicinal Drugs: A General Review
Authors: Cheng K. F. , Leung K. S. , Leung P. C.
Published: May 2003

While the use of health food and over-the-counter drugs for health promotion and adjuvant therapy is becoming increasingly popular, the concern about adverse effects is mounting. The possible adverse effects that may arise from drug interactions between these herbal preparations and standard modern therapy are equally worrying. Herbal toxicity and adverse effects are well documented in classical Chinese medicinal volumes. Interactions between herbal preparations and standard modern therapy are unknown. Extensive work needs to be done before useful guidelines can be established. However, based on available reports and clinical observations, some commonly used herbs and Chinese medicines have already demonstrated the need for special attention when used together with modern therapy. This paper analyzes the important material already available, and would serve as a preliminary checklist for patients who are taking herbal preparations, while at the same time receiving treatment from modern medicine.
COUPLED CLUSTER EXPANSIONS FOR (2 + 1) DIMENSIONAL U(1) LATTICE GAUGE THEORY WITH IMPROVED HAMILTONIAN
Authors: FANG XI-YAN , GUO SHUO-HONG , LIU JIN-MING
Published: May 2003

Using coupled cluster method, we calculate the vacuum wave function and the mass gaps of (2 + 1)-dimensional U(1) lattice gauge theory with improved Hamiltonian up to the seventh order. The results are compared with those from the unimproved Hamiltonian.
INTERACTING SIX-DIMENSIONAL TOPOLOGICAL FIELD THEORIES
Authors: GIERES F. , NIEDER H. , PISAR T. , POPP L. , SCHWEDA M.
Published: May 2003

We study the gauge-fixing and symmetries (BRST-invariance and vector supersymmetry) of various six-dimensional topological models involving Abelian or non-Abelian two-form potentials.
THE ENERGY DISTRIBUTION IN A STATIC SPHERICALLY SYMMETRIC NONSINGULAR BLACK HOLE SPACE–TIME
Authors: RADINSCHI I.
Published: May 2003

We calculate the energy distribution in a static spherically symmetric nonsingular black hole space–time by using the Tolman's energy–momentum complex. All the calculations are performed in quasi-Cartesian coordinates. The energy distribution is positive everywhere and equal to zero at the origin. We get the same result as obtained by I.-C. Yang by using the Einstein's and Weinberg's prescriptions.
GENERALIZED ABELIAN COSET CONFORMAL FIELD THEORIES
Authors: BRATCHIKOV A. V.
Published: May 2003

The reductions of conformal field theories which lead to generalized Abelian cosets are studied. Primary fields and correlation functions of arbitrary Abelian coset conformal field theory are explicitly expressed in terms of those of the original theory. The coset theory has global Abelian symmetry.
REVIEW OF RECENT SEARCHES FOR RARE AND FORBIDDEN DILEPTON DECAYS OF CHARMED MESONS
Authors: SANDERS DAVID A.
Published: May 2003

I briefly review the results of recent searches for flavor-changing neutral current and lepton-flavor and lepton-number violating decays of D+, [Formula: see text] and D0 mesons (and their antiparticles) into modes containing muons and electrons. The primary focus is the results from Fermilab charm hadroproduction experiment E791. E791 examined 24 πℓℓ and Kℓℓ decay modes of D+ and [Formula: see text] and ℓ+ℓ- decay modes of D0. Limits presented by E791 for 22 rare and forbidden dilepton decays of D mesons were more stringent than those obtained from previous searches,1 or else were the first reported.