bluuebunny/crossref_metadata_2025_split huggingface dataset:
Th1 and Th2 cytokines exert regulatory effects upon islet microvascular areas in the NOD mouse
Authors: Papaccio Gianpaolo , Pisanti Francesco Aurelio , Montefiano Rosita Di , Graziano Antonio , Latronico Michael VG 
Published: October 2002

AbstractIn this study, we show that intra‐ and peri‐islet microvascular areas undergo different changes during the islet inflammation in the nonobese diabetes‐prone female mice. Actually, although the islet vascular area (IVA) considerably decreases while the infiltration progresses, at 15 weeks of age, the peri‐islet vascular bed is unexpectedly and significantly increased. On the contrary, the intra‐IVA is significantly decreased, due to vessel dilation. Later, by 20–25 weeks of age, a decrease of both IVA occur, due to a significant islet β cell loss. Moreover, a dramatic fall of natural free radical scavenger values, which, in turn, exert an influence upon vessels, is observed. These effects are completely counteracted by the administration of IL‐4, a Th2 protective cytokine; IL‐10, another putative Th2 cytokine, exerts direct effects upon endothelial cell (EC) function, as shown by the increase of endothelial nitric oxide synthase (eNOS) mRNA transcripts and by the release of endothelial NO which, in turn, exert vasodilatory effects; moreover, this cytokine significantly upregulates adhesion molecules on endothelia. On the other hand, IL‐1β, a Th1 proinflammatory cytokine, dramatically increases nitrite and nitrate levels, as well as inducible nitric oxide synthase (iNOS) transcripts and also upregulates islet ICAM‐1 expression as well as circulating ICAM‐1 levels. Taken together, our findings clearly show that cytokines and islet endothelia are directly involved in the pathophysiology of the disease. Their reciprocal influence gives new insight to understand the role of microvasculature during islet β cell attack. J. Cell. Biochem. 86: 651–664, 2002. © 2002 Wiley‐Liss, Inc.
Calibration of force‐field dependency in free energy landscapes of peptide conformations by quantum chemical calculations
Authors: Ono Satoshi , Kuroda Masataka , Higo Junichi , Nakajima Nobuyuki , Nakamura Haruki 
Published: October 2002

AbstractThe free energy landscapes of peptide conformations were calibrated by ab initio quantum chemical calculations, after the enhanced conformational diversity search using the multicanonical molecular dynamics simulations. Three different potentials of mean force for an isolated dipeptide were individually obtained by the multicanonical molecular dynamics simulations using the conventional force fields, AMBER parm94, AMBER parm96, and CHARMm22. Each potential of mean force was then calibrated based upon the umbrella sampling algorithm from the adiabatic energy map that was calculated separately by the ab initio molecular orbital method, and all of the calibrated potentials of mean force coincided well. The calibration method was also applied to the simulations of a peptide dimer in explicit water models, and it was shown that the calibrated free energy landscapes did not depend on the force field used in the classical simulations, as far as the conformational space was sampled well. The current calibration method fuses the classical free energy calculation with the quantum chemical calculation, and it should generally make simulations for biomolecular systems much more reliable when combining with enhanced conformational sampling. © 2002 Wiley Periodicals, Inc. J Comput Chem 4: 470–476, 2002; DOI 10.1002/jcc.10032
Accurate prediction of proton chemical shifts. II. Peptide analogues
Authors: Wang Bing , Hinton James F. , Pulay Peter 
Published: October 2002

AbstractProton chemical shifts of eight cyclic amide molecules were measured in DMSO and D2O solutions. The magnetic shieldings of the corresponding aliphatic, aromatic, and amide protons were calculated by Hartree‐Fock and DFT, using the 6‐311G**, 6‐311++G**, and TZVP basis sets. For aliphatic protons, all of these methods reproduce the experimental values in DMSO solutions excellently after linear regression. The Hartree‐Fock method tends to give slightly better agreement than DFT. The best performance is given by the HF/6‐311G** method, with an rms deviation of 0.068 ppm. The deviations from experimental chemical shifts in D2O solutions are only slightly larger than those in DMSO solutions. This suggests that we can use the calculated gas phase proton chemical shifts directly to predict experimental data in various solvents, including water. For amide protons, which exchange with water and form hydrogen bonds with DMSO, only modest agreement is obtained, as expected. The present studies confirm that the GIAO approach can reach high accuracy for the relative chemical shifts of aliphatic and aromatic protons at a low cost. Such calculations may provide constraints for the conformational analysis of proteins and other macromolecules. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 492–497, 2002; DOI 10.1002/jcc.10044
Modern protein force fields behave comparably in molecular dynamics simulations
Authors: Price Daniel J. , Brooks Charles L. 
Published: October 2002

AbstractSeveral molecular dynamics simulations were performed on three proteins—bovine apo‐calbindin D9K, human interleukin‐4 R88Q mutant, and domain IIA of bacillus subtilis glucose permease—with each of the AMBER94, CHARMM22, and OPLS‐AA force fields as implemented in CHARMM. Structural and dynamic properties such as solvent‐accessible surface area, radius of gyration, deviation from their respective experimental structures, secondary structure, and backbone order parameters are obtained from each of the 2‐ns simulations for the purpose of comparing the protein portions of these force fields. For one of the proteins, the interleukin‐4 mutant, two independent simulations were performed using the CHARMM22 force field to gauge the sensitivity of some of these properties to the specific trajectory. In general, the force fields tested performed remarkably similarly with differences on the order of those found for the two independent trajectories of interleukin‐4 with CHARMM22. When all three proteins are considered together, no force field showed any consistent trend in variations for most of the properties monitored in the study. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1045–1057, 2002
Molecular dynamics simulation of thymine glycol‐lesioned DNA reveals specific hydration at the lesion
Authors: Pinak Miroslav 
Published: October 2002

AbstractOne nanosecond molecular dynamics (MD) simulation of a thymine glycol (TG)‐lesioned part of human lymphoblast AG9387 was performed to determine structural changes in DNA molecule caused by the presence of a lesion. These changes can be significant for proper recognition of lesions by a repair enzyme. Thymine glycol is the DNA oxidative lesion formed by addition of OH radicals to C5 and C6 atoms of the thymine base. This lesion is known as causing Cockayne Syndrome—inherited genetic disorder. Distribution of water molecules in a hydration shell around the DNA molecule was analyzed for its contribution to the recognition of the TG lesion by the repair enzyme. The results of MD simulation show there is a specific DNA structural configuration formed at the lesion. After 500 ps the DNA is bent in a kink at the TG site. This change dislocates the glycosyl bond at C5′ to a position closer to the DNA surface, and thus its atoms are more exposed to the surrounding water shell. The increased number of water molecules that are close to the TG site indicates that the glycosyl bond may be easily contacted by the repair enzyme. In addition, the higher number of water molecules at the TG site substantiates the importance of water‐mediated hydrogen bonds created between the repair enzyme and the DNA upon formation of the complex. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1723–1731, 2001
Direct hydride transfer in the reaction mechanism of quinoprotein alcohol dehydrogenases: a quantum mechanical investigation
Authors: Jongejan A. , Jongejan J. A. , Hagen W. R. 
Published: October 2002

AbstractOxidation of alcohols by direct hydride transfer to the pyrroloquinoline quinone (PQQ) cofactor of quinoprotein alcohol dehydrogenases has been studied using ab initio quantum mechanical methods. Energies and geometries were calculated at the 6‐31G(d,p) level of theory. Comparison of the results obtained for PQQ and several derivatives with available structural and spectroscopic data served to judge the feasibility of the calculations. The role of calcium in the enzymatic reaction mechanism has been investigated. Transition state searches have been conducted at the semiempirical and STO‐3G(d) level of theory. It is concluded that hydride transfer from the Cα‐position of the substrate alcohol (or aldehyde) directly to the C(5) carbon of PQQ is energetically feasible. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1732–1749, 2001
Molecular mechanics and dynamics of biomolecules using a solvent continuum model
Authors: Fogolari F. , Esposito G. , Viglino P. , Molinari H. 
Published: October 2002

AbstractAn easy implementation of molecular mechanics and molecular dynamics simulation using a continuum solvent model is presented that is particularly suitable for biomolecular simulations. The computation of solvation forces is made using the linear Poisson–Boltzmann equation (polar contribution) and the solvent‐accessible surface area approach (nonpolar contribution). The feasibility of the methodology is demonstrated on a small protein and a small DNA hairpin. Although the parameters employed in this model must be refined to gain reliability, the performance of the method, with a standard choice of parameters, is comparable with results obtained by explicit water simulations. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1830–1842, 2001
Prediction of infinite dilution activity coefficients of chlorinated organic compounds in aqueous solution from quantum‐chemical descriptors
Authors: Delgado Eduardo J. , Alderete Joel B. 
Published: October 2002

AbstractA quantitative structure–property relationship (QSPR) model is developed to correlate the natural logarithm of infinite dilution activity coefficients, ln (γ∞), of 45 chlorinated organic compounds in aqueous solution from quantum‐chemical descriptors. The best correlation equation contains five theoretical molecular descriptors. All descriptors were obtained from the chemical structure of the compounds and have definite physical meaning corresponding to different intermolecular interactions. The model predicts ln (γ∞) with a correlation coefficients of 0.949 and a standard error of 0.442 ln  units. The obtained QSPR equation may be applied to the prediction of γ∞ of other chlorinated organic compounds not present in the data set used for the development of the present model. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1851–1856, 2001
Epidermal growth factor stimulates proton efflux from chondrocytic cells
Authors: Lui Kevin E.H. , Panchal Amiesha S. , Santhanagopal Anu , Dixon S. Jeffrey , Bernier Suzanne M. 
Published: October 2002

AbstractProton efflux from chondrocytes alters the extracellular pH and ionic composition of cartilage, and influences the synthesis and degradation of extracellular matrix. Epidermal growth factor (EGF) promotes chondrocyte proliferation during skeletal development and accumulates in the synovial fluid in rheumatoid arthritis. The purpose of this study was to investigate the effect of EGF on proton efflux from chondrocytes. When monitored using a Cytosensor microphysiometer, EGF was found to rapidly activate proton efflux from CFK2 chondrocytic cells and rat articular chondrocytes. The actions of EGF were concentration‐dependent with half‐maximal effects at 0.3–0.7 ng/ml. Partial desensitization and time‐dependent recovery of the response were observed following repeated exposures to EGF. EGF‐induced proton efflux was dependent on extracellular glucose, and inhibitors of Na+/H+ exchange (NHE) markedly attenuated the initial increase in proton efflux. The response was diminished by inhibitors of phosphatidylinositol 3‐kinase and phospholipase C, but not by inhibitors of MEK (MAPK/ERK kinase) or protein kinase A or C. Thus, EGF‐induced proton efflux involves glucose metabolism and NHE, and is regulated by a discrete subset of EGF‐activated signaling pathways. In vivo, proton efflux induced by EGF may lead to an acidic environment, enhancing turnover of cartilage matrix during development and in rheumatoid arthritis. © 2002 Wiley‐Liss, Inc.
Enhanced activity of Ca2+‐activated K+ channels by 1‐[2‐hydroxy‐3‐propyl‐4‐[(1H‐tetrazol‐5‐yl)butoxyl]phenyl] ethanone (LY‐171883) in neuroendocrine and neuroblastoma cell lines
Authors: Li Ping‐Chia , Liang Jin‐Tung , Huang Hung‐Tu , Lin Pei‐Hsuan , Wu Sheng‐Nan 
Published: October 2002

AbstractThe effects of LY‐171883, an orally active leukotriene antagonist, on membrane currents were examined in pituitary GH3 and in neuroblastoma IMR‐32 cells. In GH3 cells, LY‐171883 (1–300 μM) reversibly increased the amplitude of Ca2+‐activated K+ current in a concentration‐dependent manner with an EC50 value of 15 μM. In excised inside‐out patches recorded from GH3 cells, the application of LY‐171883 into cytosolic face did not modify single channel conductance of large‐conductance Ca2+‐activated K+ (BKCa) channels; however, it did increase the channel activity. The LY‐171883‐stimulated activity of BKCa channels is dependent on membrane potential, and results mainly from an increase in mean open time and a decrease in mean closed time. However, REV‐5901 (30 μM) suppressed the activity of BKCa channels and MK‐571 (30 μM) did not have any effect on it. Under the current‐clamp condition, LY‐171883 (30 μM) caused membrane hyperpolarization as well as decreased the firing rate of action potentials in GH3 cells. In neuroblastoma IMR‐32 cells, the application of LY‐171883 (30 μM) also stimulated BKCa channel activity in a voltage‐dependent manner. However, neither clofibrate (30 μM) nor leukotriene D4 (10 μM) affected the channel activity in IMR‐32 cells. Troglitazone (30 μM) decreased the channel activity, but ciglitazone (30 μM) enhanced it. This study clearly demonstrates that LY‐171883 stimulates the activity of BKCa channels in a manner unlikely to be linked to its blockade of leukotriene receptors or stimulation of peroxisome proliferator‐activated receptors. The stimulatory effects on these channels may, at least in part, contribute to the underlying cellular mechanisms by which LY‐171883 affects neuronal or neuroendocrine function. © 2002 Wiley‐Liss, Inc.
Actin machinery of phagocytic cells: Universal target for bacterial attack
Authors: Belyi Iouri F. 
Published: October 2002

AbstractUptake of microorganisms by eukaryotic cells depends on proper functioning of the actin machinery. It creates a driving force for the cell membrane deformations necessary for ingestion and killing of microbes by phagocytes. Therefore, specific alterations in the activity of the actin apparatus could be favorable for pathogenic bacteria, representing an efficient mechanism in their virulence. Such alterations are supposed to be achieved in two principle ways. One is accomplished via binding of bacterial ligands to certain surface receptors, which initiate subsequent actin cytoskeleton rearrangements. Another is to introduce cytoskeleton‐targeted products directly into eukaryotic cells and in this way modulate the activity of the actin apparatus. Indeed, Legionella and some other intracellular parasites possess ligands able to stimulate certain receptors on the surface of phagocytes and possess devices suitable for translocation of effector molecules into eukaryotic cytoplasm. The results of such events could be increased uptake of these microbes and their subsequent transportation to permit multiplication in their intracellular niche. On the contrary, representatives of Clostridium and a number of other extracellular pathogens create products which penetrate eukaryotic cells and disorganize the actin cytoskeleton network, thus making uptake of these pathogens by phagocytes impossible. Microsc. Res. Tech. 57:432–440, 2002. © 2002 Wiley‐Liss, Inc.
Are thrombocytes and platelets true phagocytes?
Authors: Meseguer José , Esteban M. Ángeles , Rodríguez Alejandro 
Published: October 2002

AbstractThrombocytes and platelets, beyond their primary function in hemostasis, seem to play an active role in inflammation. As regards their phagocytic ability, the results to date are confusing, incomplete, and somewhat contradictory. Whereas the interaction of avian thrombocytes or mammalian platelets with bacteria both in vitro and in vivo has received wide attention, almost no information exists on the topic in “lower” vertebrates. The aim of this work is to review the available information on the phagocytic properties of thrombocytes and platelets. Particular attention is payed to the ontogeny of these cells, the soluble factors involved in the inflammatory process derived from them, and their interaction with particulate material, mainly with bacteria. Microsc. Res. Tech. 57:491–497, 2002. © 2002 Wiley‐Liss, Inc.
Phosphorescent metalloporphyrins as labels in time‐resolved luminescence microscopy: Effect of mounting on emission intensity
Authors: Soini Aleksi E. , Seveus Lahja , Meltola Niko J. , Papkovsky Dmitri B. , Soini Erkki 
Published: October 2002

AbstractIn this study, we present an investigation of the effects of mounting media on the phosphorescence of metalloporphyrin stained microscopy samples. The samples were: (1) Platinum(II) coproporphyrin (=PtCP) stained porous Sephadex beads; (2) compact polystyrene microspheres coated with IgG‐PtCP conjugate; and (3) immunocytochemically labeled human peripheral blood neutrophils. The human neutrophils in a mixed leukocyte population were fixed, permeabilized, and then immunolabeled with PtCP conjugate of monoclonal mouse IgG directed to the intracellular antigen myeloperoxidase. The samples were mounted in twelve different mounting media and studied with quantitative time‐resolved luminescence imaging microscopy with respect to the intensity and stability of the phosphorescence signal. The results indicate that microscopy samples stained with PtCP exhibit the brightest phosphorescence emission in non‐mounted form or when mounted in non‐aqueous permanent mounting media. Microsc. Res. Tech. 58:125–131, 2002. © 2002 Wiley‐Liss, Inc.
Hg2+ affects the intracellular free Ca2+ oscillatory pattern and the correlated membrane conductance changes in Mg2+‐stimulated oocytes of the prawn Palaemon serratus
Authors: GOUDEAU MARIE , GOUDEAU HENRI 
Published: October 2002

AbstractThe impact of mercuric ions (Hg2+) on prawn oocytes was examined. Prawn oocytes constitute an unusual system in that they are activated at spawning by seawater Mg2+, which mediates correlated dynamic changes in intracellular free calcium concentration [(Ca2+)i] and membrane conductance associated with the meiosis resumption. Using a voltage clamp technique and intracellular calcium measurements, we observed that treatment with Hg2+ (5, 10, and 20 μM) resulted in simultaneous impairments of both (Ca2+)i and membrane current responses to external Mg2+. Treatment with Hg2+ also resulted in a gradual dose‐dependent slow increase in the baseline level of both (Ca2+)i and membrane conductance, independent of stimulation with external Mg2+. The effect of Hg2+ on (Ca2+)i and membrane conductance changes resulted from a block of the signal transduction pathway at some point before the InsP3 receptor channel involved in Ca2+ release from the endoplasmic reticulum (ER) stocks. The Hg2+‐dependent gradual increase in both (Ca2+)i and membrane conductance baseline levels may potentially result from a slow permeabi‐lization of the ER membrane, resulting in Ca2+ leaking into the cytosol. Indeed, this effect could be blocked with the cell permeable Hg2+ competitor dithiothreitol, which was able to displace Hg2+ from its intracellular target regardless of whether external Ca2+ was present or not. © 2002 Wiley‐Liss, Inc.
High‐level expression of naked DNA delivered to rat liver via tail vein injection
Authors: Maruyama H. , Higuchi N. , Nishikawa Y. , Kameda S. , Iino N. , Kazama J. J. , Takahashi N. , Sugawa M. , Hanawa H. , Tada N. , Miyazaki J. , Gejyo F. 
Published: October 2002

AbstractBackgroundHigh levels of foreign gene expression in mouse hepatocytes can be achieved by rapid tail vein injection of a large volume of a naked DNA solution, the ‘hydrodynamics‐based procedure’. Rats are more tolerant of the frequent phlebotomies required for monitoring blood parameters than mice, and thus are better for some biomedical research.MethodsWe tested this technique for the delivery of a therapeutic protein in normal rats, using a rat erythropoietin (Epo) expression plasmid vector, pCAGGS‐Epo.ResultsWe obtained maximal Epo expression when the DNA solution was injected in a volume of 25 ml (approximately 100 ml/kg body weight) within 15 s. We observed a dose‐response relationship between serum Epo levels and the amount of injected DNA up to 800 µg. Using quantitative real‐time PCR, the vector‐derived Epo mRNA expression was mainly detected in the liver. When a lacZ expression plasmid was injected similarly, β‐galactosidase was exclusively detected in the liver, mainly in hepatocytes. Toxicity attributable to the technique was mild and transient, as assessed by histochemical analysis. Epo gene expression and erythropoiesis occurred with Epo gene transfer in a dose‐dependent manner, and persisted for at least 12 weeks, the last time point examined. Repeated administration of the plasmid DNA also effectively led to erythropoiesis.ConclusionsThese results demonstrate that gene transfer into the liver via rapid tail vein injection can easily be achieved in the rat, which is more than 10 times larger than the mouse, and has significant value for gene function analysis in rats. Copyright © 2002 John Wiley & Sons, Ltd.
On the “largeur d'arborescence”
Authors: van der Holst Hein 
Published: October 2002

AbstractLet la(G) be the invariant introduced by Colin de Verdière [J. Comb. Theory, Ser. B., 74:121–146, 1998], which is defined as the smallest integer n≥0 such that G is isomorphic to a minor of Kn×T, where Kn is a complete graph on n vertices and where T is an arbitrary tree. In this paper, we give an alternative definition of la(G), which is more in terms of the tree‐width of a graph. We give the collection of minimal forbidden minors for the class of graphs G with la(G)≤k, for k=2, 3. We show how this work on la(G) can be used to get a forbidden minor characterization of the graphs with $\nu^{\cal R}_1$(G)≤3. Here, $\nu^{\cal R}_1$(G) is another graph parameter introduced in the above cited paper. © 2002 Wiley Periodicals, Inc. J Graph Theory 41: 24–52, 2002
Microwave applications in radiolabelling with short‐lived positron‐emitting radionuclides
Authors: Stone‐Elander Sharon , Elander Nils 
Published: October 2002

AbstractThe use of microwave dielectric heating to reduce reaction times in organic transformations is rapidly increasing worldwide. Besides the time gains from simply performing reactions faster, other advantages have been noted, e.g. cleaner reaction mixtures due to decreased sample decomposition and altered product distributions as well as improved chemical flexibility due to the ability to accelerate typically sluggish reactions of less activated substrates. Microwave applications in radiolabelling tracers for positron emission tomography, paralleling and sometimes preceding developments in other areas of microwave‐enhanced chemistry, are reviewed here. Copyright © 2002 John Wiley & Sons, Ltd.