bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sphingosine 1‐phosphate effect on endothelial cell PAF synthesis: Role in cellular migration
Authors: Bernatchez Pascal N. , Tremblay François , Rollin Simon , Neagoe Paul‐Eduard , Sirois Martin G. 
Published: October 2003

AbstractSphingosine 1‐phosphate (S1P) and vascular endothelial growth factor (VEGF) are two inflammatory mediators capable of promoting endothelial cell (EC) migration and angiogenesis. As VEGF inflammatory effect is mediated by the synthesis of endothelial platelet‐activating factor (PAF) which is also contributing to VEGF chemotactic activity, we wanted to assess if S1P can trigger PAF synthesis in EC and if S1P‐induced migration is PAF‐dependent. Treatment of bovine aortic EC (BAEC) with S1P (10−10–10−6 M) increased dose‐ and time‐dependently the synthesis of PAF by up to 3.3‐fold above the basal level, with a maximal amount of PAF detected at 20 min post‐stimulation. This biological response was attenuated by inhibiting p38 mitogen‐activated protein kinase (MAPK), cytosolic or secreted phospholipase A2 (cPLA2, sPLA2) activity, suggesting that p38 MAPK activation by S1P promotes the conversion of membrane phospholipids into PAF through the combined activation of cPLA2 and sPLA2. Interestingly, pretreatment of BAEC with extracellular PAF receptor antagonists (BN52021, 10−5 M and CV3988, 10−6 M) reduced by up to 42% the cellular migration induced by S1P (10−6 M). These data demonstrate the capacity of S1P to induce PAF synthesis, which contributes in part to S1P chemotactic activity. © 2003 Wiley‐Liss, Inc.
Rho exchange factor ECT2 is induced by growth factors and regulates cytokinesis through the N‐terminal cell cycle regulator‐related domains
Authors: Saito Shin'ichi , Tatsumoto Takashi , Lorenzi Matthew V. , Chedid Marcio , Kapoor Veena , Sakata Hiromi , Rubin Jeffrey , Miki Toru 
Published: October 2003

AbstractThe ECT2 protooncogene plays a critical role in cytokinesis, and its C‐terminal half encodes a Dbl homology‐pleckstrin homology module, which catalyzes guanine nucleotide exchange on the Rho family of small GTPases. The N‐terminal half of ECT2 (ECT2‐N) contains domains related to the cell cycle regulator/checkpoint control proteins including human XRCC1, budding yeast CLB6, and fission yeast Cut5. The Cut5‐related domain consists of two BRCT repeats, which are widespread to repair/checkpoint control proteins. ECT2 is ubiquitously expressed in various tissues and cell lines, but elevated levels of ECT2 expression were found in various tumor cell lines and rapidly developing tissues in mouse embryos. Consistent with these findings, induction of ECT2 expression was observed upon stimulation by serum or various growth factors. In contrast to other oncogenes whose expression is induced early in G1, ECT2 expression was induced later, coinciding with the initiation of DNA synthesis. To test the role of the cell cycle regulator/checkpoint control protein‐related domains of ECT2 in cytokinesis, we expressed various ECT2 derivatives in U2OS cells, and analyzed their DNA content by flow cytometry. Expression of the N‐terminal half of ECT2, which lacks the catalytic domain, generated cells with more than 4N DNA content, suggesting that cytokinesis was inhibited in these cells. Interestingly, ECT2‐N lacking the nuclear localization signals inhibited cytokinesis more strongly than the derivatives containing these signals. Mutational analyses revealed that the XRCC1, CLB6, and BRCT domains in ECT2‐N are all essential for the cytokinesis inhibition by ECT2‐N. These results suggest that the XRCC1, CLB6, and BRCT domains of ECT2 play a critical role in regulating cytokinesis. Published 2003 Wiley‐Liss, Inc.
Melatonin reduces fenton reaction‐induced lipid peroxidation in porcine thyroid tissue
Authors: Karbownik Małgorzata , Lewiński Andrzej 
Published: October 2003

AbstractFree radicals and reactive oxygen species (ROS) participate in physiological and pathological processes in the thyroid gland. Bivalent iron cation (ferrous, Fe2+), which initiates the Fenton reaction (Fe2+ + H2O2 → Fe3+ + •OH + OH−) is frequently used to experimentally induce oxidative damage, including that caused by lipid peroxidation. Lipid peroxidation is involved in DNA damage, thus indirectly participating in the early steps of carcinogenesis. In turn, melatonin is a well‐known antioxidant and free radical scavenger. The aim of the study was to estimate the effect of melatonin on basal and iron‐induced lipid peroxidation in homogenates of the porcine thyroid gland. In order to determine the effect of melatonin on the auto‐oxidation of lipids, thyroid homogenates were incubated in the presence of that indoleamine in concentrations of 0.0, 0.00001, 0.0001, 0.001, 0.01, 0.1, 0.25, 0.5, 1.0, 2.5, or 5.0 mM. To study melatonin effects on iron‐induced lipid peroxidation, the homogenates were incubated in the presence of FeSO4 (40 μM) plus H2O2 (0.5 mM), and, additionally, in the presence of melatonin in the same concentrations as above. The degree of lipid peroxidation was expressed as the concentration of malondialdehyde + 4‐hydroxyalkenals (MDA + 4‐HDA) per mg protein. Melatonin, in a concentration‐dependent manner, decreased lipid peroxidation induced by Fenton reaction, without affecting the basal MDA + 4‐HDA levels. In conclusion, melatonin protects against iron + H2O2‐induced peroxidation of lipids in the porcine thyroid. Thus, the indoleamine would be expected to prevent pathological processes related to oxidative damage in the thyroid, cancer initiation included. © 2003 Wiley‐Liss, Inc.
Hepatic stellate cells uptake of retinol associated with retinol‐binding protein or with bovine serum albumin
Authors: Fortuna Vitor A. , Martucci Renata B. , Trugo Luiz C. , Borojevic Radovan 
Published: October 2003

AbstractRetinol is stored in liver, and the dynamic balance between its accumulation and mobilization is regulated by hepatic stellate cells (HSC). Representing less than 1% total liver protein, HSC can reach a very high intracellular retinoid (vitamin‐A and its metabolites) concentration, which elicits their conversion from the myofibroblast to the fat‐storing lipocyte phenotype. Circulating retinol is associated with plasma retinol‐binding protein (RBP) or bovine serum albumin (BSA). Here we have used the in vitro model of GRX cells to compare incorporation and metabolism of BSA versus RBP associated [3H]retinol in HSC. We have found that lipocytes, but not myofibroblasts, expressed a high‐affinity membrane receptor for RBP–retinol complex (KD = 4.93 nM), and both cell types expressed a low‐affinity one (KD = 234 nM). The RBP–retinol complex, but not the BSA‐delivered retinol, could be dislodged from membranes by treatments that specifically disturb protein–protein interactions (high RBP concentrations). Under both conditions, treatments that disturb the membrane lipid layer (detergent, cyclodextrin) released the membrane‐bound retinol. RBP‐delivered retinol was found in cytosol, microsomal fraction and, as retinyl esters, in lipid droplets, while albumin‐delivered retinol was mainly associated with membranes. Disturbing the clathrin‐mediated endocytosis did not interfere with retinol uptake. Retinol derived from the holo‐RBP complex was differentially incorporated in lipocytes and preferentially reached esterification sites close to lipid droplets through a specific intracellular traffic route. This direct influx pathway facilitates the retinol uptake into HSC against the concentration gradients, and possibly protects cell membranes from undesirable and potentially noxious high retinol concentrations. © 2003 Wiley‐Liss, Inc.
Exact mass measurement on an electrospray ionization time‐of‐flight mass spectrometer: error distribution and selective averaging
Authors: Wu Jiejun , McAllister Heather 
Published: October 2003

AbstractAn automated, accurate and reliable way of acquiring and processing flow injection data for exact mass measurement using a bench‐top electrospray ionization time‐of‐flight (ESI‐TOF) mass spectrometer is described. Using Visual Basic programs, individual scans were selected objectively with restrictions on ion counts per second for both the compound of interest and the mass reference peaks. The selected ‘good scans’ were then subjected to two different data‐processing schemes (‘combine‐then‐center’ and ‘center‐then‐average’), and the results were compared at various ion count limit settings. It was found that, in general, the average of mass values from individual scans is more accurate than the centroid mass value of the combined (same) scans. In order to acquire a large number of good scans in one injection (to increase the sampling size for statistically valid averaging), an on‐line dilution chamber was added to slow down the typically rapid mass chromatographic peak decay in flow‐injection analysis. This simple addition worked well in automation without the need for manual sample dilution. In addition, by dissolving the reference compound directly into the mobile phase, manual syringe filling can be eliminated. Twenty‐seven samples were analyzed with the new acquisition and process routines in positive electrospray ionization mode. For the best method found, the percentage of samples with RMS error less than 5 ppm was 100% with repetitive injection data (6 injections per sample), and 95% with single injection data. Afterwards, 31 other test samples were run (with MW ranging from 310 to 3493 Da, 21 samples in ESI+ and 10 in ESI− mode) and processed with similar parameters and 100% of them were mass‐calculated to RMS error less than 5 ppm also. Copyright © 2003 John Wiley & Sons, Ltd.
Utilisation of electrospray time‐of‐flight mass spectrometry for solving complex fragmentation patterns: application to benzoxazinone derivatives
Authors: Bonnington L. S. , Barcelò D. , Knepper T. P. 
Published: October 2003

AbstractIn this paper we describe the application of electrospray time‐of‐flight mass spectrometry (ESI‐TOFMS) to structural elucidation of the fragment ions formed from a range of natural and synthetic allelochemical derivatives. The extensive mass spectrometric characterisation of ten non‐glucosylated benzoxazinone derivatives using this method is described here for the first time. The analytes include six naturally occurring 1,4‐benzoxazin‐3(4H)‐one derivatives, including the hydroxamic acids DIMBOA [2,4‐dihydroxy‐7‐methoxy‐2H‐1,4‐benzoxazin‐3(4H)‐one] and DIBOA [2,4‐dihydroxy‐2H‐1,4‐benzoxazin‐3(4H)‐one], lactams HBOA [2‐hydroxy‐2H‐1,4‐benzoxazin‐3(4H)‐one] and HMBOA [2‐hydroxy‐7‐methoxy‐2H‐1,4‐benzoxazin‐3(4H)‐one], benzoxazolinones BOA [benzoxazolin‐2(3H)‐one] and MBOA [6‐methoxy‐benzoxazolin‐2(3H)‐one] and four synthetic variations, 2′H‐DIBOA [4‐hydroxy‐2H‐1,4‐benzoxazin‐3(4H)‐one], 2′OMe‐DIBOA [2‐methoxy‐4‐hydroxy‐2H‐1,4‐benzoxazin‐3(4H)‐one], 2′H‐HBOA [2H‐1,4‐benzoxazin‐3(4H)‐one] and 2′OMe‐HBOA [2‐methoxy‐2H‐1,4‐benzoxazin‐3(4H)‐one]. Assignments of the mass spectral fragments were aided by elemental composition calculation results, comparison of structural analogues and background literature, and acquired knowledge regarding feasible structures for the compounds. The influence of substituents on the chemical reactivity of the compounds with respect to the observed MS behaviour over varying nozzle potentials is addressed and, through comparison of the structural analogues, generic fragmentation patterns have also been identified. Copyright © 2003 John Wiley & Sons, Ltd.
Gas‐phase polar [4+ + 2] cycloaddition with ethyl vinyl ether: a structurally diagnostic ion–molecule reaction for 2‐azabutadienyl cations
Authors: Meurer Eduardo C. , Sparrapan Regina , Eberlin Marcos N. 
Published: October 2003

AbstractThe intrinsic reactivity of eight gaseous, mass‐selected 2‐azabutadienyl cations toward polar [4+ + 2] cycloaddition with ethyl vinyl ether has been investigated by pentaquadrupole mass spectrometric experiments. Cycloaddition occurs readily for all the ions and, with the only exception of those from the N‐acyl 2‐azabutadienyl cations (N‐acyliminium ions), the cycloadducts are found to dissociate readily upon collision activation (CID) both by retro‐Diels‐Alder reaction and by a characteristic loss of an ethanol (46u) neutral molecule. Ethanol loss from the intact polar [4+ + 2] cycloadduct functions therefore as a structurally diagnostic test: 72 u neutral gain followed by 46 u neutral loss, i.e., as a combined ion–molecule reaction plus CID ‘signature’ for N‐H, N‐alkyl and N‐aryl 2‐azabutadienyl cations. The two N‐acyliminium ions tested are exceptional as they form intact cycloadducts with ethyl vinyl ether which dissociate exclusively by the retro‐Diels‐Alder pathway. Copyright © 2003 John Wiley & Sons, Ltd.
Direct analysis of drug candidates in tissue by matrix‐assisted laser desorption/ionization mass spectrometry
Authors: Reyzer Michelle L. , Hsieh Yunsheng , Ng Kwokei , Korfmacher Walter A. , Caprioli Richard M. 
Published: October 2003

AbstractMatrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) has been used to directly analyze and image pharmaceutical compounds in intact tissue. The anti‐tumor drug SCH 226374 was unambiguously determined in mouse tumor tissue using MALDI‐QqTOFMS (QSTAR) by monitoring the dissociation of the protonated drug at m/z 695.4 to its predominant fragment at m/z 228.1. A second drug, compound A, was detected in slices of rat brain tissue following oral administration with doses ranging from 1–25 mg/kg. Quantitation of compound A from whole brain homogenates using routine high‐performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) procedures revealed that concentrations of the drug in whole brain varied from a low of 24 ng/g to a high of 1790 ng/g. The drug candidate was successfully detected by MALDI‐QqTOF in samples from each dose, covering a range of approximately two orders of magnitude. In addition, good correlation was observed between the MALDI‐QqTOFMS intensities at each dose with the HPLC/MS/MS results. Thus the MALDI‐MS response is proportional to the amount of drug in tissue. Custom software was developed to facilitate the imaging of small molecules in tissue using the MALDI‐QqTOF mass spectrometer. Images revealing the spatial localization of SCH 226374 in tumor tissue and compound A in brain tissue were acquired. Copyright © 2003 John Wiley & Sons, Ltd.
Peptide cation‐radicals. A computational study of the competition between peptide NCα bond cleavage and loss of the side chain in the [GlyPhe‐NH2 + 2H]+• cation‐radical
Authors: Tureček František , Syrstad Erik A. , Seymour Jennifer L. , Chen Xiaohong , Yao Chunxiang 
Published: October 2003

AbstractCation‐radicals and dications corresponding to hydrogen atom adducts to N‐terminus‐protonated Nα‐glycylphenylalanine amide (Gly‐Phe‐NH2) are studied by combined density functional theory and Møller‐Plesset perturbational computations (B3‐MP2) as models for electron‐capture dissociation of peptide bonds and elimination of side‐chain groups in gas‐phase peptide ions. Several structures are identified as local energy minima including isomeric aminoketyl cation‐radicals, and hydrogen‐bonded ion‐radicals, and ylid‐cation‐radical complexes. The hydrogen‐bonded complexes are substantially more stable than the classical aminoketyl structures. Dissociations of the peptide NCα bonds in aminoketyl cation‐radicals are 18–47 kJ mol−1 exothermic and require low activation energies to produce ion‐radical complexes as stable intermediates. Loss of the side‐chain benzyl group is calculated to be 44 kJ mol−1 endothermic and requires 68 kJ mol−1 activation energy. Rice‐Ramsperger‐Kassel‐Marcus (RRKM) and transition‐state theory (TST) calculations of unimolecular rate constants predict fast preferential NCα bond cleavage resulting in isomerization to ion‐molecule complexes, while dissociation of the CαCH2C6H5 bond is much slower. Because of the very low activation energies, the peptide bond dissociations are predicted to be fast in peptide cation‐radicals that have thermal (298 K) energies and thus behave ergodically. Copyright © 2003 John Wiley & Sons, Ltd.
Fragmentation of tunichrome Sp‐1 is dominated by an unusual gas‐phase intramolecular rearrangement
Authors: Taylor Steven W. , Kassel Daniel B. , Tincu J. Andy , Craig A. Grey 
Published: October 2003

AbstractTunichrome Sp‐1 is a modified pentapeptide from the ascidian Styela plicata, having the structure H‐DOPA‐DOPA‐Gly‐Pro‐dcΔDOPA (where DOPA = 3,4‐dihydroxyphenylalanine and dcΔDOPA = decarboxy‐(E)‐α,β‐dehydro‐DOPA). The tandem mass spectrum of the peptide is dominated by a number of abundant fragment ions that involve a gas‐phase rearrangement where the dcΔDOPA group becomes covalently attached to the N‐terminus. The high degree of rearrangement in Sp‐1 compared with a related octapeptide, plicatamide, allowed for detailed multiple mass spectrometric (MSn) (up to n = 6) experiments, and hence permitted a detailed assessment of the origin and routes to the formation of the various rearrangement ions. Analyses on both a triple‐quadrupole and a quadrupole time‐of‐flight mass spectrometer were made to ascertain whether the gas‐phase rearrangements observed for tunichrome Sp‐1 were unique to an ion trap mass spectrometer (i.e. the hypothesis being that perhaps the extended trapping times were required to facilitate this unusual gas‐phase rearrangement). Interestingly, analyses on both the triple‐quadrupole and quadruple time‐of‐flight mass spectrometers revealed an identical phenomenon, with the rearrangement fragment ions present at approximately the same abundance as the non‐rearranged a‐, b‐ and y‐type sequence ions. We suggest that the smaller size of tunichrome Sp‐1 compared with plicatamide facilitates the transfer of the dcΔDOPA group in this gas‐phase rearrangement. This rearrangement was not observed for peptide analogs of tunichrome Sp‐1 that did not contain the dcΔDOPA at the C‐terminus, confirming that the presence of dcΔDOPA is critical for the rearrangement. Copyright © 2003 John Wiley & Sons, Ltd.
Connection between Eastern Mediterranean seasonal mean 500 hPa height and sea‐level pressure patterns and the spatial rainfall distribution over Israel
Authors: Zangvil Abraham , Karas Svetlana , Sasson Anat 
Published: October 2003

AbstractThis study introduces a new conceptual model to explain the recently observed changes in winter precipitation over Israel. The model is based on our earlier published work (where a connection was reported between the occurrence of major rain days (MRDs) in different parts of the country and three prototypes, A, B and C, of the 500 hPa trough axis orientation prevailing on MRDs) and on additional results obtained by an extension of that work in the present paper.The first part of the present study is devoted to the extension of our early work. Composite techniques have been used on National Center for Atmospheric Research (NCAR)–National Meteorological Center grid‐point data for the rain seasons 1981–82 to 1985–86 to identify the sea‐level pressure (SLP) distribution associated with each of the three 500 hPa prototypes. Prototype A (trough axis oriented from northwest to southeast, earlier shown to be associated with MRDs in northern Israel) was found in the present work to be associated with a surface low in the vicinity of Antalya, southern Turkey. Prototype B (trough axis oriented from north to south, earlier shown to be associated with MRDs in central Israel) was found in the present work to be associated with a surface low over southeastern Turkey. Prototype C (trough axis oriented from northeast to southwest, earlier shown to be associated with MRDs in southern Israel) was found to be associated with elevated surface pressure over northwestern Turkey and a trough over eastern Turkey.In the second part of the study we used our results to construct a conceptual model of the mechanism responsible for the relative increases in seasonal (winter) rainfall over the southern part of the country and the decrease over the north. Using National Centers for Environmental Prediction–NCAR reanalysis data for the period 1982–2000, we demonstrated that the direct atmospheric agent responsible for this change in the spatial rainfall distribution is an increased frequency of occurrence of 500 hPa troughs oriented from northeast to southwest (Prototype C) accompanied by prominent positive SLP anomalies centred over Turkey. Our analysis further shows that these atmospheric systems are consistent with the persistence of a positive phase of the North Atlantic Oscillation on the one hand and with latest IPCC predictions of precipitation patterns over the eastern Mediterranean basin on the other hand. Copyright © 2003 Royal Meteorological Society
Variability of the impact of El Niño–southern oscillation on sea‐level pressure anomalies over the North Atlantic in January to March (1874–1996)
Authors: Gouirand I. , Moron V. 
Published: October 2003

AbstractSea‐level pressure (SLP) anomalies over the North Atlantic and European (NAE) sector (25–70°N, 100°W–50°E) and over a larger domain encompassing the entire North Pacific domain are studied to demonstrate that SLP anomalies (SLPAs) during boreal winter (January–March) vary widely between years characterized by the same El Niño–southern oscillation (ENSO) phase. The typical cold ENSO signal tends to be more stable than the warm one during the 1874–1996 period. The typical cold ENSO pattern (e.g. positive SLPA south of 55°N across the North Atlantic and negative SLPA in the northern North Atlantic) is similar to the positive phase of the North Atlantic oscillation (NAO) and occurs throughout the 20th century, except during the 1950s and 1960s when the basinwide westerlies are particularly slow. On the contrary, the typical warm ENSO pattern (e.g. positive SLPA from central Canada to Scandinavia and negative SLPA from the southeastern USA to central Europe, corresponding to the negative phase of the NAO) occurs mainly from 1930 to 1970. Another robust warm ENSO pattern is associated with a large positive (negative) SLPA between Newfoundland and western Europe (between Greenland and Scandinavia), and occurs mainly at the beginning and the end of the 20th century when the basinwide North Atlantic westerlies are strengthened. All these patterns stay statistically significant when the multi‐decadal variability is removed from the North Atlantic SLPA. It is shown that the low‐frequency variability of the north tropical Atlantic sea‐surface temperature anomalies could exert a modulating effect on the ENSO teleconnection. NAE SLPAs tend to be strong during warm (cold) ENSO winters and consistent with a negative (positive) phase of the NAO when the north tropical Atlantic is anomalously warm (cold). Lastly, the magnitude of the SLPA patterns over the NAE sector appears poorly related to the intensity of sea‐surface temperature anomalies in the central and eastern equatorial Pacific. Copyright © 2003 Royal Meteorological Society