bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homologous Silver Bismuth Chalcogenide Halides (N, x)P. I. Syntheses and Crystal Structures of the (0, 1)P Compound AgBi2S2Cl3 and of Three Members of the (1, x)P Solid Solution Series Ag2xBi4—2xS6—4xBr4x
Authors: Poudeu Poudeu Pierre Ferdinand , Söhnel Tilo , Ruck Michael 
Published: July 2004

AbstractAgBi2S2Cl3 and three members of the Ag2xBi4—2xS6—4xBr4x solid solution (x = 0.50 (I), x = 0.64 (II), and x = 0.73 (III)) were synthesized from Bi2S3, AgX and BiSX (X = Cl, Br) at 720 K. X‐ray diffraction on single crystals revealed that the compounds crystallize in the monoclinic space groups C2/m (No. 12) with a = 1257.3(3), b = 400.0(1), c = 804.1(2) pm, β = 111.0(1)° for AgBi2S2Cl3, a = 1331.3(5), b = 408.0(2), c = 972.0(3) pm, β = 90.8(1)° for (I), a = 1328.9(4), b = 408.5(1), c = 973.4(4) pm, β = 90.9(1)° for (II), and a = 1332.4(3), b = 409.3(1), c = 974.3(2) pm, β = 90.4(1)° for (III). AgBi2S2Cl3 adopts a variant of the InBi2S4Cl structure type, the isostructural compounds (I), (II) and (III) are related to the orthorhombic FeUS3 type. All four compounds belong to homologous series with general formula [BiSX]2·[AgxBi1—xS2—2xX2x—1]N+1 (X = Cl, Br), which resemble minerals of the pavonite series. They are characterized by the parameters N and x and are denoted (N, x)P. In the crystal structures, two kinds of layered modules, A and B, alternate. Modules of type B are composed of chains of edge‐sharing [MBr4Z2] octahedra (M = Ag/Bi; X = Cl, Br; Z = S/X) and vary in thickness N. Modules of type A uniformly consist of rows of paired monocapped trigonal prisms around Bi atoms with [MS4Z2] octahedra around mixed‐occupied metal positions (M = Ag/Bi) between them. AgBi2S2Cl3 comprises modules of type A only (N = 0) and is the silver‐rich end‐member (x = 1) in the series (0, x)P. (I) to (III) belong to the (1, x)P series with B modules of thickness N = 1. Calculations of the electronic band structures indicate that the compounds should act as indirect semiconductors with band gaps between 1.5 and 0.6 eV.
Targeting of Helicobacter pylori vacuolating toxin to lipid raft membrane domains analysed by atomic force microscopy
Authors: GEISSE Nicholas A. , COVER Timothy L. , HENDERSON Robert M. , EDWARDSON J. Michael 
Published: July 2004

The Helicobacter pylori vacuolating toxin VacA causes several effects on mammalian cells in vitro, including intracellular vacuolation, formation of pores in the plasma membrane and apoptosis. When added to cells, VacA becomes associated with detergent-resistant membranes, indicating that it binds preferentially to lipid rafts. In the present study, we have used atomic force microscopy to examine directly the association of VacA with lipid domains in supported lipid bilayers. VacA did not bind to lipid bilayers at pH 7.6. In contrast, at pH 4.0, VacA associated with the bilayers in the form of 26-nm oligomeric complexes. VacA bound to bilayers produced from either brain lipids or SM (sphingomyelin) plus cholesterol, each of which lacked detectable lipid domains. Bilayers composed of DOPC (dioleoylphosphatidylcholine), SM and cholesterol contained clearly visible raft-like domains, and VacA preferentially associated with these rafts. VacA bound poorly to raft-like domains in DOPC/SM bilayers, indicating that cholesterol is required for efficient association of VacA with lipid domains. When PS (phosphatidylserine), an anionic phospholipid that does not partition significantly into rafts, was added to the mixture of DOPC, SM and cholesterol, VacA was excluded from the rafts, indicating that it binds more avidly to PS than to the raft components. A typical plasma membrane exhibits pronounced lipid asymmetry, with SM enriched in the outer leaflet and PS in the inner leaflet. Therefore it is probable that the association of VacA with rafts in DOPC/SM/cholesterol bilayers represents a useful model for understanding the interactions of VacA with membranes in vivo.
Slow-tight-binding inhibition of enoyl-acyl carrier protein reductase fromPlasmodium falciparumby triclosan
Authors: KAPOOR Mili , REDDY C. Chandramouli , KRISHNASASTRY M. V. , SUROLIA Namita , SUROLIA Avadhesha 
Published: July 2004

Triclosan is a potent inhibitor of FabI (enoyl-ACP reductase, where ACP stands for acyl carrier protein), which catalyses the last step in a sequence of four reactions that is repeated many times with each elongation step in the type II fatty acid biosynthesis pathway. The malarial parasite Plasmodium falciparum also harbours the genes and is capable of synthesizing fatty acids by utilizing the enzymes of type II FAS (fatty acid synthase). The basic differences in the enzymes of type I FAS, present in humans, and type II FAS, present in Plasmodium, make the enzymes of this pathway a good target for antimalarials. The steady-state kinetics revealed time-dependent inhibition of FabI by triclosan, demonstrating that triclosan is a slow-tight-binding inhibitor of FabI. The inhibition followed a rapid equilibrium step to form a reversible enzyme–inhibitor complex (EI) that isomerizes to a second enzyme–inhibitor complex (EI*), which dissociates at a very slow rate. The rate constants for the isomerization of EI to EI* and the dissociation of EI* were 5.49×10−2 and 1×10−4 s−1 respectively. The Ki value for the formation of the EI complex was 53 nM and the overall inhibition constant Ki* was 96 pM. The results match well with the rate constants derived independently from fluorescence analysis of the interaction of FabI and triclosan, as well as those obtained by surface plasmon resonance studies [Kapoor, Mukhi, N. Surolia, Sugunda and A. Surolia (2004) Biochem. J. 381, 725–733].
Cellular effects of deoxynojirimycin analogues: uptake, retention and inhibition of glycosphingolipid biosynthesis
Authors: MELLOR Howard R. , NEVILLE David C. A. , HARVEY David J. , PLATT Frances M. , DWEK Raymond A. , BUTTERS Terry D. 
Published: July 2004

Deoxynojirimycin (DNJ) analogues are inhibitors of ceramide glucosyltransferase (CGT), which catalyses the first step in the glucosphingolipid (GSL) biosynthetic pathway. We have synthesized a series of DNJ analogues to study the contribution of N-alk(en)yl side chains (C4, C9 or C18) to the behaviour of these analogues in cultured HL60 cells. When cells were treated for 16 h at non-cytotoxic concentrations of inhibitor, a 40–50% decrease in GSL levels was measured by HPLC analysis of GSL-derived oligosaccharides following ceramide glycanase digestion of GSL and 2-aminobenzamide labelling of the released oligosaccharides. Using a novel technique for short-term [14C]galactose labelling of cellular GSL, we used compound inhibition of GSL biosynthesis as a marker for compound uptake into cells. Surprisingly, the uptake of all three of the DNJ analogues was extremely rapid and was not dependent upon the length of the N-alk(en)yl moiety. Compound uptake occurred in less than 1 min, as shown by the complete inhibition of GSL labelling in cells treated with all the DNJ analogues. Greatly increased cellular retention of N-cis-13-octadecenyl-DNJ was observed relative to the shorter-chain compounds, N-butyl-DNJ and N-nonyl-DNJ, as indicated by complete inhibition of CGT 24 h after removal of inhibitor from the culture medium. The present study further characterizes the properties of N-alk(en)ylated DNJs, and demonstrates that increasing the length of the side chain is a simple way of improving imino sugar retention and therefore inhibitory efficacy for CGT in cultured cells.
Cellular effects of deoxynojirimycin analogues: inhibition of N-linked oligosaccharide processing and generation of free glucosylated oligosaccharides
Authors: MELLOR Howard R. , NEVILLE David C. A. , HARVEY David J. , PLATT Frances M. , DWEK Raymond A. , BUTTERS Terry D. 
Published: July 2004

In the accompanying paper [Mellor, Neville, Harvey, Platt, Dwek and Butters (2004) Biochem. J. 381, 861–866] we treated HL60 cells with N-alk(en)yl-deoxynojirimycin (DNJ) compounds to inhibit glucosphingolipid (GSL) biosynthesis and identified a number of non-GSL-derived, small, free oligosaccharides (FOS) most likely produced due to inhibition of the oligosaccharide-processing enzymes α-glucosidases I and II. When HL60 cells were treated with concentrations of N-alk(en)ylated DNJ analogues that inhibited GSL biosynthesis completely, N-butyl- and N-nonyl-DNJ inhibited endoplasmic reticulum (ER) glucosidases I and II, but octadecyl-DNJ did not, probably due to the lack of ER lumen access for this novel, long-chain derivative. Glucosidase inhibition resulted in the appearance of free Glc1–3Man structures, which is evidence of Golgi glycoprotein endomannosidase processing of oligosaccharides with retained glucose residues. Additional large FOS was also detected in cells following a 16 h treatment with N-butyl- and N-nonyl-DNJ. When these FOS structures (&gt;30, including &gt;20 species not present in control cells) were characterized by enzyme digests and MALDI-TOF (matrix-assisted laser-desorption ionization–time-of-flight) MS, all were found to be polymannose-type oligosaccharides, of which the majority were glucosylated and had only one reducing terminal GlcNAc (N-acetylglucosamine) residue (FOS-GlcNAc1), demonstrating a cytosolic location. These results support the proposal that the increase in glucosylated FOS results from enzyme-mediated cytosolic cleavage of oligosaccharides from glycoproteins exported from the ER because of misfolding or excessive retention. Importantly, the present study characterizes the cellular properties of DNJs further and demonstrates that side-chain modifications allow selective inhibition of protein and lipid glycosylation pathways. This represents the most detailed characterization of the FOS structures arising from ER α-glucosidase inhibition to date.
Resistance to UV-induced apoptosis in Chinese-hamster ovary cells overexpressing phosphatidylserine synthases
Authors: YU Anan , McMASTER Christopher R. , BYERS David M. , RIDGWAY Neale D. , COOK Harold W. 
Published: July 2004

Externalization of PtdSer (phosphatidylserine) is an important event in signalling removal of apoptotic cells. In contrast with previous work [Yu, Byers, Ridgway, McMaster and Cook (2000) Biochim. Biophys. Acta 1487, 296–308] with U937 cells showing that specific stimulation of PtdSer biosynthesis during apoptosis was caspase dependent, PtdSer biosynthesis in CHO (Chinese-hamster ovary)-K1 increased 2.5-fold during UV-induced apoptosis but was not reversed by a caspase inhibitor, Z-VAD-FMK (benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone). Also, in CHO-K1 cells, stimulation of synthesis was less specific for PtdSer as similar levels of stimulation were observed for sphingomyelin biosynthesis. Involvement of PtdSer synthase isoforms was tested in CHO-K1 cells overexpressing PSS I (PtdSer synthase I) and PSS II. Both types of transformed cells showed resistance to UV-induced apoptosis based on the decreased levels of caspase 3 activation and morphology changes; externalization of PtdSer was reduced with UV treatment even though expression of endogenous scramblase increased slightly. Serine-labelling experiments showed that PSS I- or PSS II-expressing cells had higher basal levels of PtdSer biosynthesis compared with vector control cells. When cells were exposed to UV light to induce apoptosis, PtdSer biosynthesis was further stimulated 1.5- and 2-fold in PSS I- and PSS II-expressing cells respectively compared with UV-treated vector cells. Caspase activation was not required, as Z-VAD-FMK did not change PtdSer synthesis. Although enhanced PtdSer synthesis was supposed to facilitate apoptosis, cells overexpressing PSS I and II were actually resistant to UV-induced apoptosis. Whereas enhanced PtdSer synthesis was associated with apoptosis, potential anti-apoptotic effects were observed when excess activity of these synthetic enzymes was present. This suggests a tightly regulated role for PtdSer synthesis and/or an important dependence on compartmentation of PSS enzymes in association with scramblase facilitated enrichment of this phospholipid at the cell surface.
Transferrin receptor 2 protein is not expressed in normal erythroid cells
Authors: CALZOLARI Alessia , DEAGLIO Silvia , SPOSI Nadia Maria , PETRUCCI Eleonora , MORSILLI Ornella , GABBIANELLI Marco , MALAVASI Fabio , PESCHLE Cesare , TESTA Ugo 
Published: July 2004

Human TFR2 (transferrin receptor 2) is a membrane-bound protein homologous with TFR1. High levels of TFR2 mRNA were found mainly in the liver and, to a lesser extent, in erythroid precursors. However, although the presence of the TFR2 protein in hepatic cells has been confirmed in several studies, evidence is lacking about the presence of the TFR2 protein in normal erythroid cells. Using two anti-TFR2 monoclonal antibodies, G/14C2 and G/14E8, we have provided evidence that TFR2 protein is not expressed in normal erythroid cells at any stage of differentiation, from undifferentiated CD34+ cells to mature orthochromatic erythroblasts. In contrast, erythroleukaemic cells (K562 cells) exhibited a high level of expression of TFR2 at both the mRNA and the protein level. We can therefore conclude that an elevated expression of TFR2 protein is observed in leukaemic cells, but not in normal erythroblasts. The implications of this observation for the understanding of the phenotypic features of haemochromatosis due to mutation of the TFR2 gene are discussed.
Identification and biophysical characterization of a very-long-chain-fatty-acid-substituted phosphatidylinositol in yeast subcellular membranes
Authors: SCHNEITER Roger , BRÜGGER Britta , AMANN Clare M. , PRESTWICH Glenn D. , EPAND Raquel F. , ZELLNIG Günther , WIELAND Felix T. , EPAND Richard M. 
Published: July 2004

Morphological analysis of a conditional yeast mutant in acetyl-CoA carboxylase acc1ts/mtr7, the rate-limiting enzyme of fatty acid synthesis, suggested that the synthesis of C26 VLCFAs (very-long-chain fatty acids) is important for maintaining the structure and function of the nuclear membrane. To characterize this C26-dependent pathway in more detail, we have now examined cells that are blocked in pathways that require C26. In yeast, ceramide synthesis and remodelling of GPI (glycosylphosphatidylinositol)-anchors are two pathways that incorporate C26 into lipids. Conditional mutants blocked in either ceramide synthesis or the synthesis of GPI anchors do not display the characteristic alterations of the nuclear envelope observed in acc1ts, indicating that the synthesis of another C26-containing lipid may be affected in acc1ts mutant cells. Lipid analysis of isolated nuclear membranes revealed the presence of a novel C26-substituted PI (phosphatidylinositol). This C26-PI accounts for approx. 1% of all the PI species, and is present in both the nuclear and the plasma membrane. Remarkably, this C26-PI is the only C26-containing glycerophospholipid that is detectable in wild-type yeast, and the C26-substitution is highly specific for the sn-1 position of the glycerol backbone. To characterize the biophysical properties of this lipid, it was chemically synthesized. In contrast to PIs with normal long-chain fatty acids (C16 or C18), the C26-PI greatly reduced the bilayer to hexagonal phase transition of liposomes composed of 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE). The biophysical properties of this lipid are thus consistent with a possible role in stabilizing highly curved membrane domains.
Hypoxia-inducible factor-1 (HIF-1) promotes its degradation by induction of HIF-α-prolyl-4-hydroxylases
Authors: MARXSEN Jan H. , STENGEL Petra , DOEGE Kathrin , HEIKKINEN Pekka , JOKILEHTO Terhi , WAGNER Thomas , JELKMANN Wolfgang , JAAKKOLA Panu , METZEN Eric 
Published: July 2004

An important regulator involved in oxygen-dependent gene expression is the transcription factor HIF (hypoxia-inducible factor), which is composed of an oxygen-sensitive α-subunit (HIF-1α or HIF-2α) and a constitutively expressed β-subunit. In normoxia, HIF-1α is destabilized by post-translational hydroxylation of Pro-564 and Pro-402 by a family of oxygen-sensitive dioxygenases. The three HIF-modifying human enzymes have been termed prolyl hydroxylase domain containing proteins (PHD1, PHD2 and PHD3). Prolyl hydroxylation leads to pVHL (von-Hippel-Lindau protein)-dependent ubiquitination and rapid proteasomal degradation of HIF-1α. In the present study, we report that human PHD2 and PHD3 are induced by hypoxia in primary and transformed cell lines. In the human osteosarcoma cell line, U2OS, selective suppression of HIF-1α expression by RNA interference resulted in a complete loss of hypoxic induction of PHD2 and PHD3. Induction of PHD2 by hypoxia was lost in pVHL-deficient RCC4 cells. These results suggest that hypoxic induction of PHD2 and PHD3 is critically dependent on HIF-α. Using a VHL capture assay, we demonstrate that HIF-α prolyl-4-hydroxylase capacity of cytoplasmic and nuclear protein extracts was enhanced by prolonged exposure to hypoxia. Degradation of HIF-1α after reoxygenation was accelerated, which demonstrates functional relevance of the present results. We propose a direct, negative regulatory mechanism, which limits accumulation of HIF-1α in hypoxia and leads to accelerated degradation on reoxygenation after long-term hypoxia.
Insulin increases glycolysis without further vasodilation in porcine coronary arteries exposed to hypoxia
Authors: FRØBERT Ole , BAGGER Jens P. , SIMONSEN Ulf , LUND Sten , GRAVHOLT Claus H. 
Published: July 2004

In acute ischaemia, glucose–insulin–potassium administration reduces mortality and β-adrenoceptor antagonists have favourable effects on the outcome of ischaemic heart disease. The present study was designed to investigate whether insulin (1.4×10−7 M) and the β-adrenoceptor antagonist, propranolol (10−5 M), increase hypoxic vasodilation in correspondence with changes in glycolysis. Porcine coronary arteries, precontracted with 10−5 M prostaglandin F2α, were mounted in a pressure myograph and a microdialysis catheter was inserted in the tunica media. Hypoxic vasodilation, interstitial lactate/pyruvate ratio and interstitial glucose were measured at low (2 mM) and high (20 mM) glucose concentrations. Hypoxia (60 min) caused vasodilation and doubled the lactate/pyruvate ratio. Treatment with insulin quadrupled the lactate/pyruvate ratio during hypoxia, but did not change hypoxic vasodilation. Propranolol blocked isoprenaline-evoked vasodilation, but hypoxic increases in lactate/pyruvate ratio and vasodilation did not change. The combination of insulin and propranolol did not cause further changes compared with each drug added alone, although the combination increased vasoconstriction during reoxygenation. Interstitial glucose fell during hypoxia at an organ bath glucose concentration of 2 mM, and rose at a glucose concentration of 20 mM. Addition of insulin and propranolol alone or in combination had no effect on interstitial glucose concentration. Accordingly, arteries were found to contain only minute amounts of the glucose transporter isoform GLUT4. Our findings suggest that insulin increases arterial glycolysis, but treatment with insulin, propranolol, or both, is not associated with enhanced coronary vasodilation during hypoxia.
Muscle afferent inputs to cardiovascular control during isometric exercise vary with muscle group in patients with chronic heart failure
Authors: CARRINGTON Charlotte A. , FISHER James P. , DAVIES Mick K. , WHITE Michael J. 
Published: July 2004

It is not known whether the contribution of the muscle metaboreflex to the cardiovascular response to isometric exercise varies between different muscles in patients with CHF (chronic heart failure) or whether this depends upon muscle fibre type and training status. To resolve these issues BP (blood pressure) and HR (heart rate) responses were recorded in seven stable CHF patients (ejection fraction 30–40%; age 67±3 years) and in six healthy AMA (age-matched active) subjects. The experimental protocol consisted of 2 min of ischaemic isometric exercise at 30% maximum voluntary force, performed in separate trials by the calf plantar flexors (CALF) and handgrip muscles (FOREARM). To isolate the muscle metaboreflex a subsequent period of PECO (post-exercise circulatory occlusion) was performed following exercise. FOREARM and CALF produced similar increases in BP in both the AMA subjects and CHF patients. CHF patients elicited a significantly lower diastolic BP during PECO following CALF in comparison with that following FOREARM (5±5 compared with 12±3 mmHg respectively). A similar result was seen in AMA subjects. It may be that even the limited weight-bearing locomotor role of the calf muscles constitutes a conditioning stimulus in CHF patients, which leads to desensitization of the muscle metaboreflex, thus producing an attenuated BP elevation. We conclude that it would be incorrect to make general statements about muscle chemoreflex inputs to cardiovascular control in CHF patients based upon measurements made on only one muscle group and without reference to muscle fibre type and training status.
The JigCell Model Builder and Run Manager
Authors: Vass Marc , Allen Nicholas , Shaffer Clifford A. , Ramakrishnan Naren , Watson Layne T. , Tyson John J. 
Published: July 2004

Abstract
Summary: We describe the JigCell Model Builder (JCMB), a tool for creating biochemical reaction network models. JCMB is designed for ease of use and its interface uses the standard spreadsheet metaphor. The JigCell Run Manager (JCRM) is a tool for organizing the large collections of simulation runs typically required by reaction network modeling activities.
Availability: JCMB and JCRM are part of the JigCell suite available at http://jigcell.biol.vt.edu
Data exploration tools for the Gene Ontology database
Authors: Shoop Elizabeth , Casaes Paulo , Onsongo Getiria , Lesnett Lisa , Petursdottir Erla Osk , Donkor Edward Kofi Yeboah , Tkach Dennis , Cosimini Michael 
Published: July 2004

Abstract
Motivation: To improve the ability of biologists (both researchers and students) to ask biologically interesting questions of the Gene Ontology (GO) database and to explore the ontologies by seeing large portions of the ontology graphs in context, along with details of individual terms in the ontologies.
Results: GoGet and GoView are two new tools built as part of an extensible web application system based on Java 2 Enterprise Edition technology. GoGet has a user interface that enables users to ask biologically interesting questions, such as (1) What are the DNA binding proteins involved in DNA repair, but not in DNA replication? and (2) Of the terms containing the word triphosphatase, which have associated gene products from mouse, but not fruit fly? The results of such queries can be viewed in a collapsed tabular format that eases the burden of getting through large tables of data. GoView enables users to explore the large directed acyclic graph structure of the ontologies in the GO database. The two tools are coordinated, so that results from queries in GoGet can be visualized in GoView in the ontology in which they appear, and explorations started from GoView can request details of gene product associations to appear in a result table in GoGet.
Availability: Free access to the GoGet query tool and free download of the GoView ontology viewer are provided to all users at http://db.math.macalester.edu/goproject. In addition, source code for the GoView tool is also available from this site, along with a user manual for both tools.