bluuebunny/crossref_metadata_2025_split huggingface dataset:
A common site within factor H SCR 7 responsible for binding heparin, C‐reactive protein and streptococcal M protein
Authors: Giannakis Eleni , Jokiranta T. Sakari , Male Dean A. , Ranganathan Shoba , Ormsby Rebecca J. , Fischetti Vince A. , Mold Carolyn , Gordon David L. 
Published: March 2003

AbstractThe complement inhibitor factor H (fH) interacts via its seventh short consensus repeat (SCR) domain with multiple ligands including heparin, streptococcal M protein and C‐reactive protein (CRP). The aim of this study was to localize the residues in SCR 7 required for these interactions. We initially built a homology model of fH SCR 6–7 using the averaged NMR structures of fH SCR 15–16 and vaccinia control protein SCR 3–4 as templates. Electrostatic potentials of the model's surface demonstrated a co‐localization of three clusters of positively charged residues on SCR 7, labeled site A (R369 and K370), site B (R386 and K387) and site C (K392). These residues, localized to the linker region preceding SCR 7 and to the end of a "hypervariable loop" in SCR 7, were systematically replaced with uncharged alanine residues in an fH construct containing SCR 1–7. The resulting proteins were expressed in the methylotrophic yeast, Pichia pastoris. By ELISA analysis we demonstrated: first, that substituting site A inhibited heparin and CRP binding; secondly, that substituting site B inhibited binding to heparin, CRP and M protein; and thirdly, that substituting site C clearly inhibited only heparin binding.
B lymphocyte life span, rate of division and differentiation are regulated by total cell number
Authors: Agenès Fabien 
Published: March 2003

AbstractI analyzed how B cell survival, the rate of B cell division and the rate of B cell activation may be affected in mice with different numbers of peripheral B cells. For this purpose, I created bone marrow (BM) chimeras with different BM B cell production; I analyzed peripheral B cell dynamics in these animals and studied the fate of carboxyfluorescein succinimidyl ester‐labeled lymph node B cells transferred into these mice. I found that in lymphopenic mice, B cell life span is shortened and the rates of terminal B cell differentiation and cell death increased. As a consequence, I did not observe accumulation of B cells in mice with reduced but constant B‐cell‐poiesis. These results suggest that peripheral B cell survival relies not only on the number of competitors, as previously shown, but also on the rate of throughput of cells in a particular compartment.
KIR enrichment at the effector‐target cell interface is more sensitive than signaling to the strength of ligand binding
Authors: Borszcz Peter D. , Peterson Mary , Standeven Leah , Kirwan Sheryl , Sandusky Mina , Shaw Andrew , Long Eric O. , Burshtyn Deborah N. 
Published: March 2003

AbstractTarget cell lysis by natural killer cells is inhibited by killer cell immunoglobulin‐like receptors (KIR) that bind major histocompatibility complex class I molecules. Many lymphocyte receptors, including KIR, become enriched at the interface with ligand‐bearing cells. The contribution of the enrichment to inhibitory signaling has not been determined. We now describe a KIR variant with enhanced green fluorescent protein (EGFP) at the N terminus that can mediate inhibitory signaling, but its enrichment is markedly reduced. This receptor is only slightly weaker at inhibiting lysis than the same KIR tagged with EGFP in the cytoplasmic tail, even though the latter enriched as extensively as wild‐type KIR. A slight defect was also detected in the ability of the receptor to reduce adhesion to target cells and for binding of a soluble counterpart to cell surface HLA‐C. Our findings suggest that the strength of the interaction required to readily detect receptor enrichment exceeds that required for signaling.
Accumulation of type 2 cytokine+ T cells: differentiation‐independent proliferation of pre‐existing type 2 T cells
Authors: Loza Matthew J. , Perussia Bice 
Published: March 2003

AbstractAnalysis of proliferation and cytokine production at the single‐cell level indicated that proliferation of pre‐existing type 2 cytokine+ human peripheral naive T cells (CD4+ and CD8+) accounts for the accumulation of type 2 T cells in lymphocytes cultured with IL‐2, with or without IL‐4, and independently from TCR‐mediated stimulation. This is because: firstly,the number of cells progenitor to the type 2 cytokine+ T cells accumulated in culture is lower than that of the original cytokine+ cells; secondly, percentages and numbers of the accumulated type 2 cytokine+ T cells depend on those in the original lymphocyte population; thirdly, no accumulation occurs in cultures of lymphocytes experimentally depleted of type 2 cells; and fourthly, naive T cells do not require proliferation before producing type 2 cytokines. In contrast, accumulation of IFN‐γ+ T cells in cultures with IL‐12 can not be explained with induced proliferation of pre‐existing IFN‐γ+ cells, but depends on differentiation from more‐immature cells. These novel insights into the regulation of type 2 and type 1 cytokine+ T cells provide a new understanding of the cellular bases for the regulation of immune responses and for manipulating the immune system in clinical settings.
The VpreB1 enhancer drives developmental stage‐specific gene expression in vivo
Authors: Licence Steve , Persson Christine , Mundt Cornelia , Mårtensson Inga‐Lill 
Published: March 2003

AbstractIn adult mice, the VpreB genes are expressed in bone marrow progenitor (pro‐) and precursor (pre‐) B cells. As part of the pre‐B cell receptor, the proteins are crucial for the proliferation of these cells and consequently normal B lymphocyte development. Using cell lines, we identified a lineage‐ and developmental‐stage‐specific VpreB1 enhancer. Here, we analyze its specificity in vivo by generating transgenic mice in which expression of a reporter gene (human CD122) is regulated by the VpreB1 enhancer in the context of its own promoter. All transgenic lines expressed thereporter gene in the bone marrow in a copy number‐independent manner, whereas expression levels were integration site‐dependent. While the enhancer is not tissue specific, within the B cell lineage the expression pattern of human CD122 mimicked that of endogenous VpreB1. Thus, low levels were detected in pro‐B cells, high levels in pre‐BI and slightly lower levels in pre‐BII cells; no expression was detected in immature/mature B cells. Furthermore, when in vitro cultured transgenic pre‐B cells differentiated into immature B cells there was concomitant down‐regulation of human CD122 andendogenous VpreB1. Thus the VpreB1 enhancer is sufficient to ensure developmental stage‐specific expression of a reporter gene in B lymphocytes in vivo.
Dendritic cells transduced with TAT protein transduction domain‐containing tyrosinase‐related protein 2 vaccinate against murine melanoma
Authors: Shibagaki Naotaka , Udey Mark C. 
Published: March 2003

AbstractIncorporation of an 11 amino acid region of the HIV TAT protein transduction domain (TAT PTD) into proteins facilitates rapid, efficient entry into cells. We previously showed that rTAT‐PTD‐OVA‐transduced dendritic cells (DC) stimulated antigen (Ag)‐specific CTL and Th cells, and vaccinated against OVA‐expressing tumors. Here we studied B16 melanoma in C57BL/6 mice, using murine tyrosinase‐related protein 2 (Trp2) as a candidate tumor Ag. We produced a 472‐amino acid N‐terminal fragment of Trp2 protein (rTrp2Δ) with or without PTD. Although PTD‐deficient rTrp2Δ was ineffective, mice given rTAT‐PTD‐Trp2Δ‐transduced DC were efficiently primed for Trp2180–188 peptide‐specific and B16‐reactive CTL. In 58% of such mice, growth of melanomas was prevented. Trp2180–188 peptide‐pulsed DC protected 35% of recipients, and irradiated GM‐CSF‐producing B16 cells protected 75%. rTAT‐PTD‐Trp2Δ‐transduced DC induced a more vigorous memory response to B16 rechallenge than the other regimens, and protected 30% of recipients from progressive tumor development in treatment studies. In this setting, Trp2 peptide‐treated DC protected 20% and irradiated GM‐CSF‐producing cells protected 0%. Both tumor prevention and tumor treatment were CD8+ T cell dependent. Vaccination with rTAT‐PTD‐Trp2Δ‐transduced DC induced a robust CTL response and durable anti‐melanoma immunity. This approach should be clinically applicable, and offers theoretical and practical advantages to those that are in current use.
IL‐7 inhibits dexamethasone‐induced apoptosis via Akt/PKB in mature, peripheral T cells
Authors: Sade Hadassah , Sarin Apurva 
Published: March 2003

AbstractWe have investigated the mechanism of IL‐7‐mediated inhibition of dexamethasone‐induced apoptosis in T cells. Broad‐spectrum caspase inhibitors block dexamethasone‐triggered nuclear fragmentation, but not the loss of mitochondrial transmembrane potential or membrane integrity in CD3+ mature T cells isolated from adult mouse spleens. IL‐7 blocked dexamethasone‐induced apoptosis and the processing of caspase‐3 and caspase‐7. IL‐7 also blocked dexamethasone‐triggered dephosphorylation of the serine‐threonine kinase Akt/PKB and its target, the Ser136 residue in Bad. The loss of anti‐apoptotic proteins Bcl‐xL and inhibitor of apoptosis protein‐2 (IAP‐2) was also blocked by IL‐7. The protective effect was attenuated by pharmacological inhibitors of phosphatidylinositol‐3 kinase (PI3K) with one exception: inhibition of PI3K did not abrogate Bcl‐xL expression in the presence of IL‐7. The anti‐apoptotic role of Akt suggested by these experiments was tested by overexpression of constitutively active Akt, which blocked dexamethasone‐induced apoptosis and elevated IAP‐2 but not Bcl‐xL levels in a mature T cell line. Thus, IL‐7 regulates IAP‐2 expression and inhibits dexamethasone‐induced apoptosis by activating Akt via PI3K‐dependent signaling, but regulates Bcl‐xL expression via a PI3K‐independent pathway in mature T cells.
FcγRIIB deficiency with Fas mutation is sufficient for the development of systemic autoimmune disease
Authors: Yajima Kaori , Nakamura Akira , Sugahara Akiko , Takai Toshiyuki 
Published: March 2003

AbstractMRL.Faslpr/lpr mice, a model for systemic lupus erythematosus (SLE) and arthritis in humans, have a Fas mutation that results in spontaneous development of systemic autoimmune diseases and a short life span. Half of them die by 5–6 months of age due to massive progression of systemic autoimmune diseases, such as lupus nephritis. However, C57BL/6 (B6).Faslpr/lpr strain does not develop such disorders within the normal life span, indicating that suppressor gene(s) in B6 mice may control the onset and exacerbation of disease. Here, we show that the gene for a unique inhibitory Fc receptor for IgG (FcγRIIB) is a critical SLE suppressor. FcγRIIB‐deficient B6.Faslpr/lpr (B6.IIB–/–Faslpr/lpr) mice developed systemic autoimmune diseases, including anti‐DNA and anti‐type II collagen autoantibodies and cryoglobulin production, immune complex glomerulonephritis and arthritis. They were short‐lived, due to enhanced autoantibody production by B cells culminating in fatal lupus nephritis. Thus, FcγRIIB deletion with Fas mutation is sufficient for the development of systemic autoimmunity in B6 mice. The inhibitory signaling cascade via FcγRIIB may be critical for suppressing SLE in humans.
Toll‐like receptor expression in murine DC subsets: lack of TLR7 expression by CD8α+ DC correlates with unresponsiveness to imidazoquinolines
Authors: Edwards Alexander D. , Diebold Sandra S. , Slack Emma M. C. , Tomizawa Hideyuki , Hemmi Hiroaki , Kaisho Tsuneyasu , Akira Shizuo , Sousa Caetano Reis e 
Published: March 2003

AbstractToll‐like receptors (TLR) recognize microbial and viral patterns and activate dendritic cells (DC). TLR distribution among human DC subsets is heterogeneous: plasmacytoid DC (PDC) express TLR1, 7 and 9, while other DC types do not express TLR9 but express other TLR. Here, we report that mRNA for most TLR is expressed at similar levels by murine splenic DC sub‐types, including PDC, but that TLR3 is preferentially expressed by CD8α+ DC while TLR5 and TLR7 are selectively absent from the same subset. Consistent with the latter, TLR7 ligand activates CD8α– DC and PDC, but not CD8α+ DC as measured by survival ex vivo, up‐regulation of surface markers and production of IL‐12p40. These data suggest that the dichotomy in TLR expression between plasmacytoid and non‐plasmacytoid DC is not conserved between species. However, lack of TLR7 expression could restrict the involvement of CD8α+ DC in recognition of certain mouse pathogens.
What High‐Resolution Solid‐State NMR Spectroscopy Can Offer to Organic Chemists
Authors: Potrzebowski Marek J. 
Published: March 2003

AbstractNew applications of one‐ and two‐dimensional solid‐state NMR spectroscopy in structural studies of organic solids are presented. The review is organized into sections, the first part presenting recent progress in investigation of polymorphism and pseudo‐polymorphism phenomena. New advances in solid‐state NMR in studies of strong and weak hydrogen bonding are described in the second section, while the final part presents NMR spectroscopy as a tool with which to distinguish between enantiomers and racemates. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Selective Tetrafunctionalisation of α‐Cyclodextrin using the Supertrityl Protecting Group − Synthesis of the First C2‐Symmetric Tetraphosphane Based on a Cavitand (α‐TEPHOS)
Authors: Poorters Laurent , Armspach Dominique , Matt Dominique 
Published: March 2003

AbstractRegioselective tetraalkylation of α‐cyclodextrin using supertrityl chloride enables the preparation of new C2‐symmetric cavitands. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Arylation of Allylic Alcohols in Ionic Liquids Catalysed by a Pd‐Benzothiazole Carbene Complex
Authors: Caló Vincenzo , Nacci Angelo , Monopoli Antonio , Spinelli Michele 
Published: March 2003

AbstractThe reaction of aryl bromides with allylic alcohols catalysed by a Pd‐benzothiazole carbene complex, in tetrabutylammonium bromide as solvent, leads principally to β‐arylated carbonyl compounds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
A Convenient Generation of Acetic Acid Dianion
Authors: Parra Margarita , Sotoca Enrique , Gil Salvador 
Published: March 2003

AbstractThe lithium enediolate of acetic acid can be generated efficiently, as a 0.5 M solution in THF, using lithium amides prepared from n‐butyllithium in THF and either diethylamine or 1,3,3‐trimethyl‐6‐azabicyclo‐(3.2.1)‐octane (AZA). Its reaction with carbonyl compounds leads to the corresponding β‐hydroxy acids in good to moderate yields. Better yields are usually obtained when these amines are added in sub‐stoichiometric amounts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
First Synthesis, Isolation and Characterization of Enantiomerically Pure and Inherently Chiral Resorc[4]arenes by Lewis Acid Cyclization of a Resorcinol Monoalkyl Ether
Authors: Klaes Michael , Agena Ceno , Köhler Markus , Inoue Maki , Wada Takehiko , Inoue Yoshihisa , Mattay Jochen 
Published: March 2003

AbstractCyclization of resorcinol monoalkyl ethers with aliphatic aldehydes leads to the corresponding racemic mixtures of C4‐symmetric rccc‐resorc[4]arenes. Separation of these isomers was achieved by mono‐O‐functionalization of the rccc‐2,8,14,20‐tetramethylresorc[4]arene (2) with (S)‐(+)‐10‐camphorsulfonyl chloride leading to a diastereomeric mixture of (+)‐5a and (−)‐5b. After removal of the chiral auxiliary the inherently chiral pure enantiomers (+)‐2 and (−)‐2 were obtained. Further enantiomerically pure rccc‐resorc[4]arenes were obtained by cyclization of (+)‐3‐[(2S)‐2‐methylbutoxy]phenol (6) followed by chromatographic separation. The resulting diastereomeric resorc[4]arenes (+)‐7a and (−)‐7b were examined by CD spectroscopy, showing a perfect mirror image in all solvents examined. This indicates that the resorcarene cavities of (+)‐7a and (−)‐7b are essentially enantiomers of each other. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Sequential Stereoselective Catalysis: Two Single‐Flask Reactions of a Substrate in the Presence of a Bifunctional Chiral Ligand and Different Transition Metals
Authors: Annunziata Rita , Benaglia Maurizio , Cinquini Mauro , Cozzi Franco , Puglisi Alessandra 
Published: March 2003

AbstractA new bifunctional ligand capable of promoting different stereoselective catalytic transformations in combination with different transition metals has been prepared by connecting with a spacer a bis(oxazoline) to dihydroquinidine; this ligand was employed in a one‐flask procedure in which methyl (E)‐3‐(4‐vinylphenyl)propenoate underwent first cyclopropanation at the electron‐rich double bond and then dihydroxylation at the electron‐poor alkene to afford a product containing four stereocenters with complete regiocontrol and high stereoselectivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Covalent Linkage of Melamine and Cyanurate Improves the Thermodynamic Stability of Hydrogen‐Bonded Double Rosettes in Polar Solvents
Authors: Félix Olivier , Crego‐Calama Mercedes , Luyten Ingrid , Timmerman Peter , Reinhoudt David N. 
Published: March 2003

AbstractThis paper describes studies on the synthesis, self‐assembly behavior, and thermodynamic stabilities of eight different calix[4]arene di(melamine‐cyanurate) or di(melamine‐barbiturate) conjugates. The successful synthetic strategy comprises the preparation of amino‐n‐alkyl‐functionalized calix[4]arene dimelamines coupled with a carboxyl‐functionalized cyanurate or barbiturate by an amide bond‐forming reaction. 1H NMR experiments show that three of the eight conjugates form well‐defined double rosette assemblies. DMSO titration experiments illustrate that the covalent linkage between the cyanurate and dimelamine moieties produces a significant increase in the thermodynamic stabilities of these conjugates. The relative stability of the assemblies seems to be primarily governed by the structure of the component connecting the melamine and cyanurate units. The highest stability (χDMSO = 70%) was observed for the di(melamine‐cyanurate) assembly in which the components are connected through an n‐heptylamidomethyl linker. Increasing the linker size from n‐heptylamidomethyl to n‐decylamidomethyl slightly reduced the thermodynamic stability (ΔχDMSO ≈︁ 10%) of the corresponding double rosette assembly. The thermodynamic stability of the double rosette structure decreases drastically, however, on introduction of substituents at the position α to the methylcarbonyl group. With benzyl substituents (based on D‐phenylalanine), neither the n‐heptyl‐ nor the n‐decylamidomethyl‐linked compounds any longer form the double rosette structure in solution. For the conjugates with a methyl substituent at this position (based on L‐alanine), only the heptyl‐linked compound still forms the double rosette structure, the χDMSO value being reduced in this case by 15%. Neither of the di(melamine‐barbiturate) conjugates form double rosette structures at all. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Cover Picture: Formation of Triazinium‐Imidothioate Zwitterions and Their Role as Key Intermediates for Novel SN(ANRORC) Reaction Pathways (Eur. J. Org. Chem. 8/2003)
Authors: Wermann Kurt , Walther Martin , Günther Wolfgang , Görls Helmar , Anders Ernst 
Published: March 2003

AbstractThe cover picture shows a calculated [DFT‐(B3LYP/6‐311++G(d,p) level] “standardized” structure of the title compounds, the highly reactive triazinium‐imidothioates (center). These are readily accessible by the reaction of an amine with a bis(thiadiazolo)‐triazinium salt which is followed by deprotonation (top) and a spontaneous ring opening step. These zwitterions stabilize themselves by intramolecular cyclization reactions under the formation of either highly substituted guanidines (left) or triazolo‐thiadiazolo‐triazinium (center) or bis(triazolo)‐triazinium cations (right). Important reaction steps are initiated by negative hyperconjugation which controls the reaction modes of key intermediates. Experimental and theoretical details are discussed in the article by E. Anders et al. on p. 1389 ff.
RGD‐Porphyrin Conjugates: Synthesis and Potential Application in Photodynamic Therapy
Authors: Chaleix Vincent , Sol Vincent , Huang Yi‐Ming , Guilloton Michel , Granet Robert , Blais Jean Claude , Krausz Pierre 
Published: March 2003

AbstractWe report a convenient solid‐phase synthesis and characterisation of a new class of glycosylated porphyrins bearing the RGD tripeptide, designed for photodynamic cancer therapy. The photocytotoxicities of these compounds against the K562 leukemia cell line are also presented and compared to the effect of Photofrin II®. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Quantitative Gas‐Solid Diazotization of 3‐Aminopyrazolo[3,4‐b]pyridine Derivatives and Azo Dye Syntheses by Means of Solid‐Solid Reactions
Authors: Kaupp Gerd , Metwally Mohamed Abbas , Amer Fathy A. , Abdel‐latif Ehab 
Published: March 2003

AbstractGas‐solid and solid‐solid techniques allow for waste‐free quantitative syntheses and coupling reactions of the heterocyclic diazonium salts 2. The solid‐state diazotization of 1a with gaseous NO2 has been mechanistically investigated by atomic force microscopy (AFM). Azo couplings are achieved in quantitative yields by cautious co‐grinding of the solid diazonium salt 2a with five (thio)barbituric acids, six acetoacetanilides (these couplings are followed by internal cyclization in solid‐state cascades), β‐naphthol, and 2,6‐dimethylphenol. The solid diazonium salt 2a is quantitatively coupled with three solid anilines to give the tautomeric triazenes 16. The structures of the products were established with IR, NMR and mass spectroscopy, while the tautomeric properties of the compounds were judged by density functional calculations at the B3LYP/6−31G* and BLYP/6−31G** levels. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Palladium‐Catalyzed Synthesis of Nonsymmetrically Functionalized Bipyridines, Poly(bipyridines) and Terpyridines
Authors: Puglisi Alessandra , Benaglia Maurizio , Roncan Giulia 
Published: March 2003

AbstractPalladium‐catalyzed coupling reactions were employed to prepare nonsymmetric, densely functionalized bipyridines and oligo(bipyridines), featuring sensitive functionalities like alcohol, ester and aldehyde groups. Stille coupling between halo(poly)pyridine and the proper (poly)pyridyltin derivative afforded in good yields nonsymmetric, derivatized oligo(bipyridines), amenable to further synthetic modifications. The methodology was used also to synthesize highly functionalized terpyridines. A series of Suzuki and Stille palladium‐promoted coupling reactions allowed us to obtain in good yields terpyridines bearing two different and differently functionalizable groups, valuable building blocks for the construction of complex supramolecular frameworks. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Denitrification Performance of Pseudomonas denitrificans in a Fluidized‐Bed Biofilm Reactor and in a Stirred Tank Reactor
Authors: Cattaneo C. , Nicolella C. , Rovatti M. 
Published: March 2003

AbstractDenitrification of a synthetic wastewater containing nitrates and methanol as carbon source was carried out in two systems – a fluidized‐bed biofilm reactor (FBBR) and a stirred tank reactor (STR) – using Pseudomonas denitrificans over a period of five months. Nitrogen loading was varied during operation of both reactors to assess differences in the response to transient conditions. Experimental data were analyzed to obtain a comparison of denitrification kinetics in biofilm and suspended growth reactors. The comparison showed that the volumetric degradation capacity in the FBBR (5.36 kg N · m–3 · d–1) was higher than in the STR, due to higher biomass concentration (10 kg BM · m–3 vs 1.2 kg BM m–3).