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Otto Holst - One of the best experts on this subject based on the ideXlab platform.
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Core Region and lipid A components of lipopolysaccharides
Microbial Glycobiology, 2009Co-Authors: Otto Holst, Antonio MolinaroAbstract:Publisher Summary Lipopolysaccharides (LPSs), also known as endotoxins, are one of the major virulence factors of Gram-negative bacteria. LPSs represent amphiphilic molecules generally comprising three defined Regions that are distinguished by their genetics, structures, function, and biosynthesis. The first moiety, lipid A, is substituted by the second, the Core Region, which in turn carries a polysaccharide that may be the O-specific polysaccharide, a capsular polysaccharide, or the enterobacterial common antigen (only in Enterobacteriaceae). With regard to the structure–function relationships of LPSs, lipid A has been identified as the toxic principle of endotoxically active LPS. This toxicity depends mostly on lipid A chemical structure that defines the overall molecular conformation, but is also influenced by the Core Region. Thus, a complete structural analysis of lipid A and Core Region represent the prerequisite for the understanding of LPS functions. This chapter deals with the structural aspects of lipid A and the Core Region of LPSs. From the chemical point of view, the lipid A structure still remains a rather conserved architectural principle. The binding of the Core Region to lipid A occurs always via a Kdo residue (except in Acinetobacter). The Core Region is always negatively charged (provided by phosphoryl substituents and/or sugar acids like Kdo and uronic acids), which is believed to contribute to the rigidity of the Gram-negative cell wall. There are two types of Core structures: those containing and those without heptoses.
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The linkage between O-specific caryan and Core Region in the lipopolysaccharide of Burkholderia caryophylli is furnished by a primer monosaccharide
Carbohydrate Research, 2005Co-Authors: Cristina De Castro, Otto Holst, Antonio Molinaro, Rosa Lanzetta, Michelangelo ParrilliAbstract:Abstract From the lipopolysaccharide (LPS) fraction of the plant-pathogenic bacterium Burkholderia caryophylli , the linkage between O-specific caryan and Core Region was characterised. The LPS fraction was first treated with 48% aqueous HF at 4 °C and successively with 1% acetic acid at 100 °C. A main oligosaccharide representing the carbohydrate backbone of the Core Region and a portion of the caryan (three unit of caryose) was isolated by high-performance anion-exchange chromatography. Compositional and methylation analyses, matrix-assisted laser desorption/ionisation mass spectrometry and 2D NMR spectroscopy identified the structure: The above residues are α-linked pyranose rings, if not stated otherwise. Hep is L - glycero - D - manno -heptose, Car is 4,8-cyclo-3,9-dideoxy- L - erythro - D - ido -nonose and Kdo is 3-deoxy- D - manno -oct-2-ulosonic acid. This finding indicates that QuiNAc residue is the primer monosaccharide, which connects the Core oligosaccharide to caryan O-chain.
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a novel Core Region lacking heptose and phosphate of the lipopolysaccharide from the gram negative bacterium pseudomonas cichorii pseudomonadaceae rna group 1
European Journal of Organic Chemistry, 2004Co-Authors: Cristina De Castro, Antonio Molinaro, Rosa Lanzetta, Michelangelo Parrilli, Rosa Nunziata, Otto HolstAbstract:The extracted lipopolysaccharides (LPSs) fraction of the plant-pathogenic bacterium Pseudomonascichorii contained two different molecules, the first of them an LPS possessing an O-specific polysaccharide made up of four 2-acetamido-2,6-dideoxy sugars linked linearly in a tetrasaccharide repeating unit. The structure of the second LPS component is reported here: it was of the rough form and contained a novel type of Core Region. The rough form LPS of Ps. cichorii was de-O-acylated by mild hydrazinolysis and then de-N-acylated with hot 4 M KOH. The oligosaccharide representing the complete carbohydrate backbone of the LPS was isolated by high-performance anion-exchange chromatography. Its structural characterization employed compositional and methylation analyses, matrix-assisted laser desorption/ionisation mass spectrometry and 1H, 13C and 31P NMR spectroscopy, with application of various 1D and 2D experiments. The carbohydrate backbone of this Core Region consisted of a hexasaccharide that contained no heptoses, being made up of L-Rhap, D-GlcpN and D-GalpN, besides the characteristic α-(24)-linked 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) disaccharide. The first Kdo residue linking the Core Region to the lipid A was substituted by a GalpN residue. This Core Region thus represents one of the rather few cases in which this position is not substituted by a manno-configured sugar. The structure of the LPS carbohydrate backbone is shown in Scheme 1. If not stated otherwise, sugars were D-configured pyranoses. Kdo is 3-deoxy-D-manno-oct-2-ulosonic acid. The lipid A backbone is N- and O-acylated in the LPSs. − Molecular modelling studies of the LPS carbohydrate backbone and of some of its parts were performed, yielding a preferred conformation that was surprisingly inflexible between the two Kdo residues. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
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A Novel Core Region, Lacking Heptose and Phosphate, of the Lipopolysaccharide from the Gram‐Negative Bacterium Pseudomonas cichorii (Pseudomonadaceae RNA Group 1)
European Journal of Organic Chemistry, 2004Co-Authors: Cristina De Castro, Antonio Molinaro, Rosa Lanzetta, Michelangelo Parrilli, Rosa Nunziata, Otto HolstAbstract:The extracted lipopolysaccharides (LPSs) fraction of the plant-pathogenic bacterium Pseudomonascichorii contained two different molecules, the first of them an LPS possessing an O-specific polysaccharide made up of four 2-acetamido-2,6-dideoxy sugars linked linearly in a tetrasaccharide repeating unit. The structure of the second LPS component is reported here: it was of the rough form and contained a novel type of Core Region. The rough form LPS of Ps. cichorii was de-O-acylated by mild hydrazinolysis and then de-N-acylated with hot 4 M KOH. The oligosaccharide representing the complete carbohydrate backbone of the LPS was isolated by high-performance anion-exchange chromatography. Its structural characterization employed compositional and methylation analyses, matrix-assisted laser desorption/ionisation mass spectrometry and 1H, 13C and 31P NMR spectroscopy, with application of various 1D and 2D experiments. The carbohydrate backbone of this Core Region consisted of a hexasaccharide that contained no heptoses, being made up of L-Rhap, D-GlcpN and D-GalpN, besides the characteristic α-(24)-linked 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) disaccharide. The first Kdo residue linking the Core Region to the lipid A was substituted by a GalpN residue. This Core Region thus represents one of the rather few cases in which this position is not substituted by a manno-configured sugar. The structure of the LPS carbohydrate backbone is shown in Scheme 1. If not stated otherwise, sugars were D-configured pyranoses. Kdo is 3-deoxy-D-manno-oct-2-ulosonic acid. The lipid A backbone is N- and O-acylated in the LPSs. − Molecular modelling studies of the LPS carbohydrate backbone and of some of its parts were performed, yielding a preferred conformation that was surprisingly inflexible between the two Kdo residues. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
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Lipopolysaccharides Possessing Twol-Glycero-d-manno-heptopyranosyl-α-(1→5)-3-deoxy-d-manno-oct-2-ulopyranosonic Acid Moieties in the Core Region THE STRUCTURE OF THE Core Region OF THE LIPOPOLYSACCHARIDES FROM BURKHOLDERIA CARYOPHYLLI
Journal of Biological Chemistry, 2002Co-Authors: Antonio Molinaro, Cristina De Castro, Rosa Lanzetta, Antonio Evidente, Michelangelo Parrilli, Otto HolstAbstract:Abstract The carbohydrate backbone of the Core-lipid A Region was characterized from the lipopolysaccharides (LPSs) of the plant-pathogenic bacterium Burkholderia caryophylli. For the first time, the presence of two moieties ofl-glycero-d-manno-heptopyranosyl-α-(1→5)-3-deoxy-d-manno-oct-2-ulopyranosonic acid was identified in a Core Region, which is of particular interest with regard to the biosynthesis of this and of LPSs in general. The LPSs of B. caryophylli were degraded by mild hydrazinolysis (de-O-acylation), treatment with 48% aqueous HF at 4 °C (cleavage of phosphate groups and destruction of the O-specific polysaccharides), reduction with NaBH4, and de-N-acylation utilizing hot KOH. The major oligosaccharide representing the carbohydrate backbone of the Core Region and lipid A was isolated by high-performance anion-exchange chromatography. Its analysis employing compositional and methylation analyses, matrix-assisted laser desorption/ionization mass spectrometry, and1H and 13C NMR spectroscopy applying various one-dimensional and two-dimensional experiments identified the following structure. All sugars are pyranoses and α-linked, if not stated otherwise. Hep isl-glycero-d-manno-heptose, Kdo is 3-deoxy-d-manno-oct-2-ulosonic acid.
Witold K Surewicz - One of the best experts on this subject based on the ideXlab platform.
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conformational stability of mammalian prion protein amyloid fibrils is dictated by a packing polymorphism within the Core Region
Journal of Biological Chemistry, 2014Co-Authors: Nathan J Cobb, Marcin I Apostol, Shugui Chen, Vytautas Smirnovas, Witold K SurewiczAbstract:Mammalian prion strains are believed to arise from the propagation of distinct conformations of the misfolded prion protein PrPSc. One key operational parameter used to define differences between strains has been conformational stability of PrPSc as defined by resistance to thermal and/or chemical denaturation. However, the structural basis of these stability differences is unknown. To bridge this gap, we have generated two strains of recombinant human prion protein amyloid fibrils that show dramatic differences in conformational stability and have characterized them by a number of biophysical methods. Backbone amide hydrogen/deuterium exchange experiments revealed that, in sharp contrast to previously studied strains of infectious amyloid formed from the yeast prion protein Sup35, differences in β-sheet Core size do not underlie differences in conformational stability between strains of mammalian prion protein amyloid. Instead, these stability differences appear to be dictated by distinct packing arrangements (i.e. steric zipper interfaces) within the amyloid Core, as indicated by distinct x-ray fiber diffraction patterns and large strain-dependent differences in hydrogen/deuterium exchange kinetics for histidine side chains within the Core Region. Although this study was limited to synthetic prion protein amyloid fibrils, a similar structural basis for strain-dependent conformational stability may apply to brain-derived PrPSc, especially because large strain-specific differences in PrPSc stability are often observed despite a similar size of the PrPSc Core Region.
David Thompson - One of the best experts on this subject based on the ideXlab platform.
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a novel approach to vortex Core Region detection
VISSYM '02 Proceedings of the symposium on Data Visualisation 2002, 2002Co-Authors: Ming Jiang, Raghu Machiraju, David ThompsonAbstract:In this paper we present a simple and efficient vortex Core Region detection algorithm based on ideas derived from combinatorial topology. These ideas originated from Sperner's lemma, which by itself is of little value to detecting vortex Cores. However, we take these ideas from the lemma and apply them in a point-based fashion to detecting vortex Core Regions. The resulting algorithms for both 2D and 3D are quite simple and very efficient compared to existing ones. We applied our algorithms to both numerically simulated and procedurally generated datasets to illustrate the efficacy of our approach.
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VisSym - A novel approach to vortex Core Region detection
2002Co-Authors: Ming Jiang, Raghu Machiraju, David ThompsonAbstract:In this paper we present a simple and efficient vortex Core Region detection algorithm based on ideas derived from combinatorial topology. These ideas originated from Sperner's lemma, which by itself is of little value to detecting vortex Cores. However, we take these ideas from the lemma and apply them in a point-based fashion to detecting vortex Core Regions. The resulting algorithms for both 2D and 3D are quite simple and very efficient compared to existing ones. We applied our algorithms to both numerically simulated and procedurally generated datasets to illustrate the efficacy of our approach.
Norio Akuta - One of the best experts on this subject based on the ideXlab platform.
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amino acid substitution in hcv Core Region and genetic variation near the il28b gene affect viral dynamics during telaprevir peginterferon and ribavirin treatment
Intervirology, 2012Co-Authors: Norio Akuta, Fumitaka Suzuki, Miharu Hirakawa, Yusuke Kawamura, Hitomi Sezaki, Yoshiyuki Suzuki, Tetsuya Hosaka, Masahiro Kobayashi, Hiromi Yatsuji, Mariko KobayashiAbstract:Objectives: Genetic variation near the IL28B gene and substitution of aa 70 and 91 in the Core Region of HCV-1b are useful as predictors of tre
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amino acid substitutions in hepatitis c virus Core Region predict hepatocarcinogenesis following eradication of hcv rna by antiviral therapy
Journal of Medical Virology, 2011Co-Authors: Norio Akuta, Mariko Kobayashi, Fumitaka Suzuki, Miharu Hirakawa, Yusuke Kawamura, Hitomi Sezaki, Yoshiyuki Suzuki, Tetsuya Hosaka, Masahiro Kobayashi, Satoshi SaitohAbstract:Substitution of amino acid (aa) 70 and/or 91 in the Core Region of HCV genotype 1b (HCV-1b) is an important predictor of hepatocarcinogenesis, but its impact on the development of hepatocellular carcinoma (HCC) following eradication of HCV RNA by antiviral therapy is not clear. 1,273 patients with HCV-related chronic liver disease, with sustained virological response, defined as negative HCV RNA at 24 weeks after cessation of interferon monotherapy or interferon plus ribavirin combination therapy, were included in a follow-up study to evaluate the impact of aa substitution in the Core Region on hepatocarcinogenesis. Twenty six patients developed HCC during the follow-up. The cumulative rates of new HCC were 3.2%, 4.8%, and 8.6% at the end of 5, 10, and 15 years, respectively. The rates in patients infected with HCV-1b/Gln70(His70) [glutamine (histidine) at aa 70] were significantly higher than in patients infected with HCV-1b/Arg70 (arginine at aa 70) (P = 0.007; log-rank test) and HCV-2a/2b (P < 0.001; log-rank test). The rates in patients infected with HCV-1b/Arg70 were not significantly higher than in those infected with HCV-2a/2b (P = 0.617; log-rank test). Multivariate analysis identified HCV-1b/Gln70(His70) (HR 10.5, P < 0.001), advanced fibrosis (HR 9.03, P = 0.002), and old age (HR 3.09, P = 0.066) as determinants of hepatocarcinogenesis. In conclusion, aa substitution in the Core Region of HCV-1b at the start of antiviral therapy is an important predictor of HCC following eradication of HCV RNA. This study emphasizes the importance of detection of aa substitutions in the Core Region before antiviral therapy. J. Med. Virol. 83:1016–1022, 2011. © 2011 Wiley-Liss, Inc.
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Amino acid substitutions in hepatitis C virus Core Region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy.
Journal of Medical Virology, 2011Co-Authors: Norio Akuta, Mariko Kobayashi, Fumitaka Suzuki, Miharu Hirakawa, Yusuke Kawamura, Hitomi Sezaki, Yoshiyuki Suzuki, Tetsuya Hosaka, Masahiro Kobayashi, Satoshi SaitohAbstract:Substitution of amino acid (aa) 70 and/or 91 in the Core Region of HCV genotype 1b (HCV-1b) is an important predictor of hepatocarcinogenesis, but its impact on the development of hepatocellular carcinoma (HCC) following eradication of HCV RNA by antiviral therapy is not clear. 1,273 patients with HCV-related chronic liver disease, with sustained virological response, defined as negative HCV RNA at 24 weeks after cessation of interferon monotherapy or interferon plus ribavirin combination therapy, were included in a follow-up study to evaluate the impact of aa substitution in the Core Region on hepatocarcinogenesis. Twenty six patients developed HCC during the follow-up. The cumulative rates of new HCC were 3.2%, 4.8%, and 8.6% at the end of 5, 10, and 15 years, respectively. The rates in patients infected with HCV-1b/Gln70(His70) [glutamine (histidine) at aa 70] were significantly higher than in patients infected with HCV-1b/Arg70 (arginine at aa 70) (P = 0.007; log-rank test) and HCV-2a/2b (P
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A nucleotide sequence variation detection system for the Core Region of hepatitis C virus-1b.
Journal of Virological Methods, 2006Co-Authors: Katsura Okamoto, Norio Akuta, Hiromitsu Kumada, Mariko Kobayashi, Yuki Matsuo, Hiromitsu TazawaAbstract:Abstract Amino-acid substitution at positions 70 and 91 of the hepatitis C virus (HCV)-1b Core Region is a factor that contributes to a non-virological response in treatment using interferon/ribavirin combination. In this study, a system was developed for detection of nucleotide sequence variation in the Core Region that is simpler and less expensive than the current direct sequencing method. A PCR detection method using mutation-specific primers was developed, and amino acids at positions 70 and 91 were identified. The protein type was determined based on band intensity in electrophoresis, and classified into wild (70:R, 91:L), mutant (70:Q/H, 91:M) and competitive types. The detection rate, sensitivity and reproducibility were investigated in 108 patients with HCV-1b who were treated with interferon/ribavirin combination therapy, and correlation with the results of direct sequencing was examined. The detection rate was 94.4%, the sensitivity was 10 KIU/mL, the reproducibility was high, and in detectable cases the consistency with direct sequencing was 97.1%; inconsistency was noted in two competitive-type cases and in one case with an unusual amino-acid substitution. The results suggest that the system described in this paper provides an effective, simple and low-cost approach to detection of nucleotide sequence variation in the Core Region of HCV-1b.
Jeff L Weiner - One of the best experts on this subject based on the ideXlab platform.
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Functional characterization of kainate receptors in the rat nucleus accumbens Core Region.
Journal of Neurophysiology, 2002Co-Authors: Tara L. Crowder, Jeff L WeinerAbstract:The nucleus accumbens, a brain Region involved in motivation, attention, and reward, receives substantial glutamatergic innervation from many limbic structures. This excitatory glutamatergic input plays an integral role in both normal and pathophysiological states. Despite the importance of glutamatergic transmission in the nucleus accumbens, the specific receptor subtypes that mediate glutamatergic signaling in this brain Region have not been fully characterized. The current study sought to examine the possible role of the kainate subclass of glutamate receptor in the nucleus accumbens. Kainate receptors are relatively poorly understood members of the ionotropic glutamate receptor family and are highly expressed in the nucleus accumbens. Recent studies have highlighted a number of novel pre- and postsynaptic functions of kainate receptors in several other brain Regions. Using the whole cell patch-clamp technique, we report the first demonstration of functional kainate receptors on neurons within the Core Region of the nucleus accumbens. In addition, we present evidence that activation of kainate receptors in this brain Region inhibits excitatory synaptic transmission via a presynaptic mechanism.
