bluuebunny/crossref_metadata_2025_split huggingface dataset:
A physical and functional link between cholesterol and tetraspanins
Authors: Charrin Stéphanie , Manié Serge , Thiele Christoph , Billard Martine , Gerlier Denis , Boucheix Claude , Rubinstein Eric 
Published: August 2003

AbstractBy interacting with each others, the tetraspanins are thought to assemble a network of molecular interactions, the tetraspanin web. These tetraspanin/tetraspanin interactions involve in part the palmitoylation of the proteins. We show that tetraspanins interact with cholesterol as indicated by the precipitation of tetraspanin/tetraspanin complexes by digitonin, a cholesterol‐precipitating reagent, and the labeling of the tetraspanins CD9, CD81 and CD82 with a photoactivatable cholesterol in vivo. Cholesterol may participate to the interaction of tetraspanins with each other since digitonin‐precipitation of tetraspanins was correlated with their mutual interaction, and because these interactions were disrupted following cholesterol depletion by methyl‐β‐cyclodextrin (MβCD) treatment, or cholesterol sequestration by saponin. A mutant CD9 molecule lacking all palmitoylation sites was not precipitated by digitonin under conditions in which wild‐type CD9 was precipitated, indicating a role of palmitoylation for the interaction with cholesterol. Finally, upon ligation of tetraspanins on the surface of a lymphoid B cell line, the tyrosine phosphorylation of several proteins, including the vav nucleotide exchange factor, was inhibited when cells were pretreated with MβCD, and increased when they were treated with MβCD/cholesterol complexes. Thus, there is a physical and functional link between tetraspanins and cholesterol.
Clearance of Theiler's virus infection depends on the ability to generate a CD8+ T cell response against a single immunodominant viral peptide
Authors: Mendez‐Fernandez Yanice V. , Johnson Aaron J. , Rodriguez Moses , Pease Larry R. 
Published: August 2003

AbstractTheiler's murine encephalomyelitis virus (TMEV) induces a chronic demyelinating disease in the central nervous system of susceptible mice. Resistance to persistent TMEV infection maps to he D locus of the major histocompatibility complex suggesting a prominent role of antiviral CTL in the protective immune response. Introduction of the Db gene into the FVB strain confers resistance to this otherwise susceptible mouse line. Infection of the FVB/Db mouse with TMEV provides a model where antiviral resistance is determined by a response elicited by a single class I molecule. Resistant mice of the H‐2b haplotype mount a vigorous H‐2Db‐restricted immunodominant response to the VP2 capsid protein. To investigate the extent of the contributionof the immunodominant T cell population in resistance to TMEV, FVB/Db mice were depleted of VP2‐specific CD8+ T cells by peptide treatment prior to virus infection. Peptide‐treated mice were not able to clear the virus and developed extensive demyelination. These findings demonstrate that the Db‐restricted CD8+ T cells specific for a single viral peptide can confer resistance to TMEV infection. Our ability to manipulate this cellular response provides a model for investigating the mechanisms mediating protection against virus infection by CD8+ T cells.
Autoimmune NZB/NZW F1 mice utilize B cell receptor editing for generating high‐affinity anti‐dsDNA autoantibodies from low‐affinity precursors
Authors: Yachimovich‐Cohen Nurit , Fischel Ruth , Bachar Neta , Yarkoni Yuval , Eilat Dan 
Published: August 2003

AbstractWe have previously constructed knock‐in (C57BL/6×BALB/c) F1 mice, each expressing an anti‐DNA heavy (H) chain (D42), combined with one of three different light (L) chains, namely Vκ1‐Jκ1, Vκ4‐Jκ4 or Vκ8‐Jκ5. All of these H/L chain combinations bind DNA with similar affinity and fine specificity. However, while mice carrying Vκ1‐Jκ1‐transgenic L chain were tolerized almost exclusively by L chain receptor editing, the mice expressing Vκ8‐Jκ5 L chains utilized clonal anergy as their principal mechanism of B cell tolerance. Vκ4‐Jκ4 targeted mice exhibited an intermediate phenotype. In the present study, these three H/L chain combinations were backcrossed onto the autoimmune NZB/NZW F1 mice. We find that the mechanism of clonal anergy is abrogated in these mice, but that receptor editing is maintained. Moreover, diseased NZB/NZW mice utilize L chain secondary rearrangements for the generation of high‐affinity, anti‐dsDNA‐producing B cells from low‐affinity precursors. The edited B cell clones are not deleted or anergized in the autoimmune animal; rather they are selected for activation, class‐switching and affinity maturation by somatic mutation. These results suggest that B cell receptor editing plays an important role not only in tolerance induction, but also in generating high‐affinity autoreactive B cells in autoimmune diseases.
Autoimmune uveitis induced by molecular mimicry of peptides from rotavirus, bovine casein and retinal S‐antigen
Authors: Wildner Gerhild , Diedrichs‐Möhring Maria 
Published: August 2003

AbstractAntigenic mimicry of infectious agents and autoantigens is a proposed pathomechanism for autoimmune diseases. Here, we describe antigenic mimicry of a peptide from rotavirus, a nutritional protein from bovine milk (αs2‐casein) and a peptide thereof as well as a highly pathogenic peptide from retinal S‐antigen (PDSAg), a major autoantigen in experimental autoimmune uveitis in Lewis rats. Immunization of rats with the peptides and the casein protein induced uveitis, an intraocular inflammation leading to decreased vision and even blindness. The peptides elicited cross‐reactive T cell responses and uveitis in rats and were also recognized by lymphocytes and sera from uveitis patients. Oral tolerization with PDSAg, but not with rotavirus‐ and casein‐derived peptides or caseinprotein, prevented PDSAg‐induced uveitis in rats. Cofeeding of casein with cholera toxin induced uveitis in rats, suggesting that breaking oral tolerance to casein during gastrointestinal infections might also be able to initiate uveitis in humans.
The activation of Csk by CD4 interferes with TCR‐mediated activatory signaling
Authors: Marinari Barbara , Simeoni Luca , Schraven Burkhart , Piccolella Enza , Tuosto Loretta 
Published: August 2003

AbstractCD4‐Lck recruitment to TCR/CD3, as well as Lck activation is essential for T cell activation. Indeed, the blockage of CD4‐Lck recruitment to TCR during antigen recognition exerts a drastic inhibitory effect on T cell activation by interfering with both early and late phases of T cell signaling. In the present work, we report a novel inhibitory mechanism by which CD4 can shut down proximal T cell‐activating signals. Indeed, we show that upon ligation of CD4 by antibodies the inhibitory kinase, p50csk, is strongly induced and prolonged during the time. In contrast, p50csk was not activated when TCR and CD4 were properly engaged by their ligands. We also demonstrate that anti‐CD4 treatment stimulated Csk kinase associated to the membrane adapter, PAG/Cbp, without affecting the total amount of Csk bound to PAG/Cbp. As a consequence, early tyrosine phosphorylation events as well as downstream signaling pathways leading to IL‐2 gene expression induced by TCRwere inhibited in anti‐CD4 pretreated cells. We suggest a new model to explain the activation of negative signals by CD4 molecule.
Different immunogenicity of H‐2 Kb‐restricted epitopes in natural variants of the hepatitis B surface antigen
Authors: Schirmbeck Reinhold , Böhm Waltraud , Fissolo Nicolas , Melber Karl , Reimann Jörg 
Published: August 2003

AbstractThe small hepatitis B surface antigen (HBsAg) of hepatitis B virus (HBV) has limited variability, but some serotypes and genotypes have been defined. Although no biological or pathogenetic differences could be traced to HBV serotypes, the clinical picture, response to treatment and long‐term prognosis of HBV infection may vary with the HBV genotype, possibly due to differences in specific T cell recognition of HBV antigens from different genotypes. We analyzed murine CD8+ T cell responses to two Kb‐restricted HBsAg epitopes primed by four different HBsAg variants using protein‐ and DNA‐based vaccination protocols. The Kb‐binding S208–215 epitope 1 is processed from exogenous but not endogenous HBsAg. Variants of epitope 1 differing at two positions within the epitope (ILSPFLPL in ayw/adr versus IVSPFIPL in adw2) efficiently primed cross‐reactive CD8+ T cell responses. In contrast, the exchange of an N‐terminal flanking residue (S to N) completely eliminated the immunogenicity of epitope 1. The Kb‐binding S190–197 epitope 2 is processed from endogenous but not exogenous HBsAg. A single‐residue exchange within the epitope (VWLSVIWM in ayw/adr versus VWLSAIWM in adw2) completely eliminated the immunogenicity of epitope 2. Single, conservative residue exchanges can thus give rise to diverging CD8+ T cell repertoires, suggesting an impressive complexity and flexibility of the CD8+ T cell repertoire to antigen variants from viruses with limited diversity.
In interleukin‐7‐transgenic mice, increasing B lymphopoiesis increases follicular but not marginal zone B cell numbers
Authors: Ceredig Rhodri , Bosco Nabil , Maye Patrice N. , Andersson Jan , Rolink Antonius 
Published: August 2003

AbstractFollicular and marginal zone B cells constitute the vast majority of mature B cells in the adult spleen. The inter‐relationships between these two functionally and phenotypically distinct subpopulations of B cells remain unclear. In situations of decreased bone marrow B lymphopoiesis, the proportion of spleen marginal zone B cells increases, but the consequence of increasing B lymphopoiesis on marginal zone B cells has not been investigated. Using interleukin‐7‐transgenic mice, in which B lymphopoiesis is significantly increased, we show that the number of follicular B cells increased about fivefold but the number of marginal zone B cells decreased. Functional and phenotypic analysis, including in vivo bromodeoxyuridine labeling experiments, showed that marginal zoneB cells in transgenic mice were indistinguishable from controls. Mixed radiation bone marrow chimeras showed that marginal zone B cells developed equally well from both normal and transgenic adult bone marrow B cell progenitors. Taken together, these results suggest that interleukin‐7 does not influence the lineage choice between follicular and marginal zone B cells and that the number of cells ineach compartment is independently regulated.
Role of the αI domain in ligand binding by integrin αEβ7
Authors: Corps Elaine M. , Robertson Alexis , Dauncey M. Joy , Kilshaw Peter J. 
Published: August 2003

AbstractThe I domain of integrin αE was modeled on the crystal structure of that in CD11b and mutated to produce an open (high affinity) or closed (low affinity) conformation. K562 transfectants expressing mutant αE and wild‐type β7 were tested for adhesion to E‐cadherin‐Fc. Downward displacement of the C terminus of the αI domain with a disulfide bridge enhanced adhesion and Mn2+ dependency. Adhesion greatly exceeded that observed using wild type integrin under similar conditions. The closed integrin gave poor adhesion which was greatly improved by PMA‐induced clustering. Blocking β7 function with a βI domain‐specific antibody inhibited the wild‐type but not the locked open integrin. Isolated open αI domain expressed on K562 cells showed strong Mn2+‐dependent adhesion to E‐cadherin, whereas the wild‐type version was ineffective. αEβ7 was shown to bind to monomeric E‐cadherin but to only one component of dimeric E‐cadherin. Finally, we report that M290, a function‐blocking antibody, bound to a conformation‐sensitive epitope near the rim of the αI domain MIDAS and recognized wild‐type and closed αI domain but not the open conformation. The results broadly support the paradigm for affinity regulation by conformational change that has been established for β2 integrins. Nevertheless, for αE, the fully open conformation may represent an extreme situation that does not occur physiologically.
Cloning and characterization of the mouse homologue of the human dendritic cell maturation marker CD208/DC‐LAMP
Authors: Salaun Bruno , de Saint‐Vis Blandine , Clair‐Moninot Valérie , Pin Jean‐Jacques , Barthélemy‐Dubois Clarisse , Kissenpfennig Adrien , Peronne Catherine , Bates Elizabeth , Mattei Marie‐Geneviève , Lebecque Serge 
Published: August 2003

AbstractDC‐LAMP, a member of the lysosomal‐associated membrane protein (LAMP) family, is specifically expressed by human dendritic cells (DC) upon activation and therefore serves as marker of human DCmaturation. DC‐LAMP is detected first in activated human DC within MHC class II molecules‐containing compartments just before the translocation of MHC class II‐peptide complexes to the cell surface, suggesting a possible involvement in this process. The present study describes the cloning and characterization of mouse DC‐LAMP, whose predicted protein sequence is over 50% identical to the human counterpart. The mouse DC‐LAMP gene spans over 25 kb and shares syntenic chromosomal localization (16B2‐B4 and 3q26) and conserved organization with the human DC‐LAMP gene. Analysis of mouse DC‐LAMP mRNA and protein revealed the expression in lung peripheral cells, but also its unexpected absence from mouse lymphoid organs and from mouse DC activated either in vitro or in vivo. In conclusion, mouse DC‐LAMP is not a marker of mature mouse DC and this observation raises new questions regarding the role of human DC‐LAMP in human DC.
Generation of a transgenic animal model of hyperthyroid Graves' disease
Authors: Kim‐Saijo Misa , Akamizu Takashi , Ikuta Koichi , Iida Yasuhiko , Ohmori Katsuyuki , Matsubara Kazumi , Matsuda Yoichi , Suzuki Misao , Matsuda Fumihiko , Nakao Kazuwa 
Published: August 2003

AbstractGraves' disease (GD) is an organ‐specific autoimmune disease characterized by hyperthyroidism. Agonistic anti‐thyrotropin receptor antibodies (thyroid‐stimulating antibodies, TSAb), whichmimic the thyrotropin (TSH) action, are thought to cause GD. The precise immunological mechanism of TSAb production, however, remains elusive. Previous immunization approaches using TSH receptor led to transient hyperthyroidism, but did not seem sufficient for comprehensive understanding of the development of autoimmune responses. To create GD‐related autoimmunity in mice, we here generated TSAb‐transgenic mice in which a patient‐derived TSAb is expressed in B cells. Expression of the human TSAb in mice resulted in various manifestations of hyperthyroidism including increased free thyroxine levels with concomitantly decreased TSH levels, increased thyroid uptake of technetium pertechnetate, hyperthermia and thyroid hyperplasia. We found a correlation between the serum levels of human TSAb immunoglobulin and free thyroxine. In addition, conventional B cells expressing the TSAb were partially deleted in the periphery while B1 cells expressing the TSAb persisted and accumulated in the peritoneal cavity, a finding consistent with previous demonstrations that the maintenance of B1 cells plays an important role in the development of autoimmune diseases. Thus, our transgenic mouse mayprovide a novel and useful animal model for elucidating the pathogenesis and pathophysiology of GD.
Synthesis of Polyhydroxylated Aminocyclopentanes
Authors: Kummeter Markus , Kazmaier Uli 
Published: August 2003

AbstractPolyhydroxylated aminocyclopentanes are an interesting class of glycosidase inhibitors. The reactions between chelated α‐allylglycine esters and crotonaldehyde gave the corresponding aldol products in good yields and selectivities. Those compounds could be converted into enantiopure polyhydroxylated aminocyclopentanes by ring‐closing metathesis, enzymatic separation and dihydroxylation. In the final deprotection step, three different protection groups were removed simultaneously in excellent yield, either by reduction or by basic hydrolysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Native Chemical Ligation with Aspartic and Glutamic Acids as C‐Terminal Residues: Scope and Limitations
Authors: Villain Matteo , Gaertner Hubert , Botti Paolo 
Published: August 2003

AbstractA new side reaction during Native Chemical Ligation (NCL) at aspartic and glutamic acid/cysteine ligation sites is reported. To exploit NCL at these sites, test peptides having either a C‐terminal unprotected aspartyl or glutamyl thioester were ligated with a peptide containing an N‐terminal free cysteine generating, in each case, two major compounds having equal masses but different retention times by HPLC analysis. Comparison of these ligation products with reference peptides of identical sequence synthesized by total SPPS (solid phase peptide synthesis) with both natural and unnatural backbones at the cysteinyl residue is in agreement with the hypothesis of migration of the thioester moiety on the side chain carboxyl group of both C‐terminal Asp and Glu residues. Enzymatic digestion of the purified ligation products with a V8‐protease further confirmed the nature of the side reaction, with a total resistance of the non‐natural backbone peptide to the protease. To overcome this problem the use of a protecting group stable to both HF cleavage and ligation conditions, but removable after ligation, became a necessity. A series of side‐chain protected derivatives were selected, specifically 9‐fluorenylmethyl ester (OFm), (phenylsulfonyl)ethyl ester (OPse), 2,2,2‐trichloroethyl ester (OTce), and phenacyl esters (OPac). For the glutamic acid, OPse gave the best results, generating the correct peptide and avoiding the isomerization at the γ‐carboxyl group. In the case of the aspartic residue, all the protecting groups were removed under basic conditions, worsening the problem and generating, for example, 70% yield of the β‐isomer after OFm deprotection. This prompted us to propose a protecting group derived from the phenacyl ester 1‐methyl‐2‐oxo‐2‐phenylethyl ester (OMop). This protecting group showed greater stability during the ligation reaction than OPac and OTce, and was easily removed by Zn/acetic acid reduction after the ligation step. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Pyrrolo‐Tetrathiafulvalenes and Their Applications in Molecular and Supramolecular Chemistry
Authors: Jeppesen Jan O. , Becher Jan 
Published: August 2003

AbstractAlthough tetrathiafulvalene and its derivatives have been extensively studied as π‐electron donors in the fields of molecular organic metals and electrically conducting materials for more than 30 years, the intriguing potential of tetrathiafulvalene as a building block in molecular and supramolecular chemistry has only recently been developed. Progress in synthetic tetrathiafulvalene chemistry has enabled the preparation of elaborate molecular architectures and, in recent years, tetrathiafulvalene has been incorporated into a number of molecular and supramolecular systems. In this microreview we describe the background to our interest in the development of the parent pyrrolo‐tetrathiafulvalenes, followed by a journey through their applications in macrocyclic, molecular, and supramolecular chemistry. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of Monocyclic and Bicyclic Imino Sugars
Authors: Kummeter Markus , Kazmaier Uli 
Published: August 2003

AbstractA diastereoselective aldol reaction between the chelated alanine ester enolate 5 and the protected threose derivative 6, followed by cyclization under Mitsunobu conditions, gave the pipecolinic acid derivative 9. This compound could easily be converted into the versatile protected derivative 11, which could be transformed in excellent yields either into the corresponding piperidine imino sugar 14 or into the unnatural amino acid 17. The imino alcohol 13, an intermediate in the synthesis of imino sugar 14, was also used in a straightforward approach to indolizidinone 19, involving an intramolecular Horner−Emmons reaction for ring‐closure. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis, NMR Spectroscopic Characterization and Polysiloxane‐Based Immobilization of the Three Regioisomeric Monooctenylpermethyl‐β‐cyclodextrins and Their Application in Enantioselective GC
Authors: Cousin H. , Trapp O. , Peulon‐Agasse V. , Pannecoucke X. , Banspach L. , Trapp G. , Jiang Z. , Combret J. C. , Schurig V. 
Published: August 2003

Abstract2I−VI,3I−VII,6I−VII‐Eicosa‐O‐methyl‐2I‐O‐(oct‐7‐enyl)cyclomaltoheptaose, 2I−VII,3I−VI,6I−VII‐eicosa‐O‐methyl‐3I‐O‐(oct‐7‐enyl)cyclomaltoheptaose, and 2I−VII,3I−VII,6I−VI‐eicosa‐O‐methyl‐6I‐O‐(oct‐7‐enyl)cyclomaltoheptaose were synthesized by selective introduction of an oct‐7‐enyl group at one of theO‐2,O‐3, orO‐6 positions of selectively methylated cyclomaltoheptaose (β‐cyclodextrin, CD) and, depending on the synthetic route, by a subsequent permethylation step. Each of the regioisomeric mono‐oct‐7‐enylated permethylated β‐cyclodextrin derivatives was anchored by hydrosilylation to a hydridomethyldimethylsiloxane copolymer to yield unambiguouslyO‐2‐,O‐3‐, andO‐6‐bonded chiral stationary phases (CSP) of Chirasil‐Dex, which were evaluated in enantioselective gas chromatography (GC).O‐6‐Chirasil‐Dex displayed slightly inferior enantioselectivity relative to eitherO‐3‐ orO‐2‐Chirasil‐Dex. The statistical synthesis of the CSP by mono‐oct‐7‐enylation of β‐CD under varying reactions conditions (base, solvent), without the use of hydroxy group protection chemistry, furnished a mixture ofO‐6‐ andO‐2‐Chirasil‐Dex in dimethylformamide and predominantly theO‐2‐regioisomer in dimethyl sulfoxide. Chirasil‐Dex, previously formulated exclusively as theO‐6 regioisomer, should be revised as anO‐2‐ andO‐6‐Chirasil‐Dex mixture. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of N‐Phenyl‐N′‐pyrimidylurea Derivatives by Selenium‐ or Selenium Dioxide‐Catalyzed Reductive Carbonylation of Nitroaromatics
Authors: Chen Jinzhu , Ling Gang , Lu Shiwei 
Published: August 2003

AbstractForty unsymmetric N‐phenyl‐N′‐pyrimidylurea derivatives were synthesized in moderate‐to‐good yields by one‐pot reductive carbonylation of nitroaromatics using selenium or selenium dioxide as the catalyst, aminopyrimidine derivatives as co‐reagents, and carbon monoxide as the carbonyl source. The reaction parameters were investigated, as was the reusability of the catalysts. We found that selenium‐ or selenium dioxide‐catalyzed reductive carbonylation of the nitroaromatics exhibited reaction‐controlled phase‐transfer phenomena of the catalysts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis and Electrochemical Studies of New Antimalarial Endoperoxides
Authors: Najjar Fadia , Baltas Michel , Gorrichon Liliane , Moreno Yolande , Tzedakis Theodore , Vial Henri , André‐Barrès Christiane 
Published: August 2003

AbstractStructural analogues of endoperoxides belonging to the family of G factors have been synthesized under Mannich‐type conditions. The structures of the different diastereoisomers have been established from NMR spectroscopic data. Their cathodic peak potentials have been determined by thin layer electrochemistry under potentiostatic conditions, and compared to artemisinin. These endoperoxides were evaluated in vitro against Plasmodium falciparum and showed moderate to good activity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
An Expeditious Preparation of 15‐Membered Nitrogen‐Containing Olefinic and Benzo Macrocycles
Authors: Sebastián Rosa M. , Moreno‐Mañas Marcial , Vallribera Adelina 
Published: August 2003

Abstract(E,E)‐1,6,11‐Tris(arenesulfonyl)‐3,4‐benzo‐1,6,11‐triazacyclopentadeca‐8,13‐dienes (2) and 1,6,11‐tris(arenesulfonyl)‐3,4; 8,9;13,14‐tribenzo‐1,6,11‐triazacyclopentadecanes (3) were prepared from arenesulfonamides, trans‐1,4‐dibromobutene, and 1,2‐bis(bromomethyl)benzene. They form unstable complexes with silver tetrafluoroborate. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)