bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulus Dependence of the Action of Small‐Molecule Inhibitors in the CD3/CD28 Signalling Network
Authors: Köhler Karsten , Ganser Alexander , André Thomas , Roth Günter , Grosse‐Hovest Ludger , Jung Gundram , Brock Roland 
Published: July 2008

AbstractCells in the body are exposed simultaneously to a multitude of various signals. Inside a cell, molecular signalling networks integrate this information into a physiologically meaningful response. Interestingly, in the cellular testing of drug candidates, this complexity is largely ignored. Compounds are tested for cells that are challenged with one stimulus only. The activation of T lymphocytes through engagement of the T cell receptor (TCR)–CD3 complex and CD28 coreceptor is a prominent example for a cellular response that depends on the integration of signals. We investigated the cellular response characteristics of this network at different strengths of receptor and coreceptor activation. A novel cellular microarray‐based approach, in which various combinations of antibodies directed against the CD3 complex and CD28 were spotted, was employed for analysing the stimulus dependence of activation of the transcription factor NFAT and actin reorganisation. For both responses, quantitative differences in inhibitor activity were observed. Remarkably, for IL‐2 expression, which was detected by standard ELISA, low doses of the Src‐family kinase inhibitor PP2 strongly potentiated IL‐2 expression at high‐level, but not at low‐level, CD28 co‐engagement. Therefore, for a physiologically highly relevant signalling network, the cellular response might vary qualitatively with only quantitative variations of a stimulus. This level of complexity should be considered in early cellular drug testing.
Global hybrid modeling and control of a buck converter: A novel concept
Authors: Hejri Mohammad , Mokhtari Hossein 
Published: July 2008

AbstractSeveral attempts have been made to design suitable controllers for DC–DC converters. However, these designs suffer from model inaccuracy or their inability to desirably function in both continuous and discontinuous current modes. This paper presents a novel switching scheme based on hybrid modeling to control a buck converter using mixed logical dynamical (MLD) methodologies. The proposed method is capable of globally controlling the converter in both continuous and discontinuous current modes of operation by considering all constraints in the physical plant such as maximum inductor current and capacitor voltage limits. Different loads and input voltage disturbances are simulated in MATLAB and results are presented to demonstrate the suitability of the controller. The transient and steady‐state performance of the closed‐loop control over a wide range of operating points shows satisfactory operation of the proposed controller. Copyright © 2008 John Wiley & Sons, Ltd.
Flow cytometric detection of perforin upregulation in human CD8 T cells
Authors: Hersperger Adam R. , Makedonas George , Betts Michael R. 
Published: July 2008

AbstractPerforin and granzymes work synergistically to induce apoptosis in target cells recognized by cytotoxic T lymphocytes. While perforin is readily detectable by flow cytometry in resting CD8 T cells, upregulation of perforin in activated cells is thought to require proliferation. However, perforin undergoes numerous conformational changes during its maturation, which may affect the ability of conventional antibodies to recognize newly synthesized perforin. Polychromatic flow cytometry was used to detect perforin and cytokine production following stimulation of ex vivo human CD8 T cells. Two different anti‐perforin antibodies, clones B‐D48 and δG9, were used to discriminate various forms of perforin after cellular activation. We provide evidence for the rapid upregulation of perforin protein, which may contribute to the ability of CD8 T cells to kill multiple targets over time. The δG9 clone recognizes the granule‐associated conformation of perforin, while the B‐D48 clone is able to detect perforin in multiple forms. Finally, we show there is variability in the ability of CD8 T cells to upregulate perforin. Human CD8 T cells are capable of new perforin production immediately following activation. This work defines a novel flow cytometric procedure that can be used to more completely assess the cytotoxic capacity of human CD8 T cells. © 2008 International Society for Advancement of Cytometry
Transcription of PRDM1, the master regulator for plasma cell differentiation, depends on an SP1/SP3/EGR‐1 GC‐box
Authors: Mora‐López Francisco , Pedreño‐Horrillo Nuria , Delgado‐Pérez Luis , Brieva José A. , Campos‐Caro Antonio 
Published: July 2008

AbstractThe positive regulatory domain containing 1, encoded by the PRDM1 gene, is a transcriptional repressor considered as a master regulator that is required and sufficient for plasma cell differentiation. In the present study we have performed sequence analysis of the upstream region of the human PRDM1 gene to detect the minimal promoter region necessary for PRDM1 gene transcription. This region comprises the region upstream of the initiation site, as well as the first exon. Collectively, deletion and mutation analysis in conjunction with luciferase reporter assays, EMSA and supershift assays identified a phylogenetically conserved GC‐box as an essential element for PRDM1 expression. This GC‐box element matches to a binding site for multiple transcription factors such as SP1 and SP3 isoforms as well as early growth response 1. Chromatin immunoprecipitation assays confirmed the in vivo binding capability of these factors to the human PRDM1 promoter. These studies together characterize for the first time the basal activity of the human PRDM1 promoter, through which several factors, including SP1, SP3 and early growth response 1, modulate its expression through a conserved GC‐box.
Expression profiles of prion and doppel proteins and of their receptors in mouse splenocytes
Authors: Cordier‐Dirikoc Sevda , Zsürger Nicole , Cazareth Julie , Ménard Baptiste , Chabry Joëlle 
Published: July 2008

AbstractDoppel (Dpl) shares common structural features with the prion protein (PrP) whose pathologic isoform is considered as the causative agent of prion diseases. Although their physiological functions in the immune system remain largely unknown, we demonstrated that substantial amounts of PrP and Dpl are expressed by spleen cells notably B lymphocytes, granulocytes and DC, but not T lymphocytes and NK. To characterize trans‐interacting partners of PrP and Dpl on mouse splenocytes, fluorescent PrP and Dpl tetramers were produced and used as tracers. Both tetramers specifically bind to B lymphocytes, dendritic cells, macrophages and granulocytes and in a lesser extend to T lymphocytes. No binding was observed on NK, follicular dendritic cells and mesenchymal spleen cells. The activation of intracellular transduction signals (i.e. intracellular calcium concentration and activation of the MAP kinase pathway) suggested that PrP and Dpl tetramers bind to functional receptors on B cells. None of the previously described PrP partners account for the binding sites characterized here. Our study suggests a possible role for PrP and Dpl in the cell‐cell interactions in the immune system.
Activating and inhibitory Fcγ receptors can differentially modulate T cell‐mediated autoimmunity
Authors: Iruretagoyena Mirentxu I. , Riedel Claudia A. , Leiva Eduardo D. , Gutiérrez Miguel A. , Jacobelli Sergio H. , Kalergis Alexis M. 
Published: July 2008

AbstractThe molecular bases responsible for the loss of T cell tolerance to myelin antigens leading to the onset of multiple sclerosis remain obscure. It has been shown that balanced signaling through activating and inhibitory receptors is critical for the maintenance of tolerance to self antigens in autoimmune disorders. However, although FcγR have been shown to influence experimental autoimmune encephalomyelitis (EAE) development, their role during pathogenesis remains controversial. Here we have evaluated whether relative expression of activating (FcγRIII) and inhibitory (FcγRIIb) FcγR can modulate myelin‐specific T cell response, as well as the susceptibility to develop EAE in mice. While FcγRIIb–/– mice showed a significant increase in EAE severity, an FcγRIII deficiency protected mice from disease. In addition, FcγRIIb–/– mice showed enhanced activation of myelin‐specific effector T cells, which were significantly more effective at causing EAE in adoptive transfer experiments than were T cells from wild‐type mice. In contrast, FcγRIII–/– mice showed a significantly reduced activation of myelin‐specific T cells and these cells failed to adoptively transfer EAE. Consistently, increased expansion of regulatory T cells (Treg) during EAE was observed only for FcγRIII–/– mice, which were able to suppress disease when adoptively transferred to recipient mice. These findings suggest that the balance between activating and inhibitory FcγR signaling can contribute to the maintenance of T cell tolerance to myelin antigens and modulate EAE progression.
CD40L‐expressing CD8 T cells prime CD8α+ DC for IL‐12p70 production
Authors: Wong Kok Loon , Lew Fei Chuin , MacAry Paul A. , Kemeny David M. 
Published: July 2008

AbstractCD8α+ DC are implicated as the principle DC subset for cross‐presentation and cross‐priming of cytotoxic CD8 T cell responses. In this study, we demonstrate another unique facet of the CD8α+ DC and CD8 T cell relationship, by showing that CD8 T cells reciprocally activate CD8α+ DC, but not CD8α– DC, for IL‐12p70 production, the key Th1‐promoting cytokine. This effect was observed during an antigen‐specific interaction between DC and activated CD8 T cells, along with secondary TLR stimulation of DC by LPS. Activated CD8 T cells use a combination of IFN‐γ and CD40L, which is rapidly up‐regulated post‐stimulation, to prime DC for IL‐12p70 production during an antigen‐specific response. Our results suggest that the interaction between CD8α+ DC and antigen‐primed CD8 T cells may form an important component of Th1‐mediated immunity through the induction of IL‐12p70.
IκBα is required for marginal zone B cell lineage development
Authors: Ellinghaus Ursula , Rupec Rudolf A. , Pabst Oliver , Ignatius Ralf , Förster Reinhold , Dörken Bernd , Jundt Franziska 
Published: July 2008

AbstractInactivation of members of the nuclear factor‐κB (NF‐κB) family results in the decrease or defect of marginal zone B (MZB) cells. It is not known which inhibitors of the NF‐κB family (IκB) are required for MZB cell development. Here, we show that mice with B cell‐specific inactivation of the main NF‐κB inhibitor IκBα have a marked decrease of MZB cells and their presumed precursors. They exhibited increased mortality rates after blood‐borne bacterial infection, indicating the importance of MZB cells for bacterial clearance. In contrast, response to T cell‐dependent and ‐independent antigens resulted only in minor changes in immunoglobulin production. Our data demonstrate the importance of the intact NF‐κB/IκBα pathway for proper MZB cell development.
Base‐Induced Formation of Two Magnesium Metal‐Organic Framework Compounds with a Bifunctional Tetratopic Ligand
Authors: Dietzel Pascal D. C. , Blom Richard , Fjellvåg Helmer 
Published: July 2008

AbstractTwo coordination polymers constructed from magnesium and the tetratopic organic linker 2,5‐dihydroxyterephthalic acid are reported, denominated CPO‐26‐Mg and CPO‐27‐Mg. The organic component carries two different types of protic functional groups. The degree of deprotonation of the organic component can be regulated by the amount of sodium hydroxide employed in the synthesis, thus determining which of the compounds forms. In CPO‐26‐Mg, only the carboxylic acid groups of the linker are deprotonated and take part in the construction of the three‐dimensional framework. The structure is non‐porous, and its topology is based on the PtS net. In CPO‐27‐Mg, both the carboxylic acid and the hydroxy groups are deprotonated and involved in the construction of a microporous three‐dimensional framework which is based on a honeycomb motif containing large solvent‐filled channels. The metal atoms are arranged in chiral chains along the intersection of the honeycomb and contain one water molecule in their coordination sphere, which allows for the creation of coordinatively unsaturated metal sites upon dehydration. CPO‐27‐Mg is a potentially useful lightweight adsorbent with a pore volume of 60 % of the total volume of the structure and an apparent Langmuir surface area of up to 1030 m2 g–1. Its thermal stability was investigated by thermogravimetry and variable‐temperature powder X‐ray diffraction, which shows framework degradation to commence at 160 °C in air, at 235 °C under nitrogen, and at 430 °C in a dynamic vacuum. Thermogravimetric dehydration and re‐hydration experiments at miscellaneous temperatures indicate that it is possible to obtain open metal sites in CPO‐27‐Mg, but the water is more tightly bound in this material than in the previously reported isostructural nickel compound.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
μ‐1,3‐ (trans) and μ‐1,2‐ (cis) Bonding in Squarato‐Bridged Dinuclear Copper(II) and Nickel(II) Complexes Derived from Polypyridyl Amines
Authors: Massoud Salah S. , Mautner Franz A. , Vicente Ramon , Louka Febee R. 
Published: July 2008

AbstractA novel series of dinuclear squarato‐bridged copper(II) and nickel(II) complexes [Cu2(TPA)2(μ1,3‐C4O4)](ClO4)2·4H2O (1), [Cu2(MeDPA)2(μ1,3‐C4O4)(H2O)4](ClO4)2 (2) and [Ni2(TPA)2(μ1,2‐C4O4)(H2O)2](ClO4)2 (3) [C4O42– = dianion of 3,4‐dihydroxycyclobut‐3‐en‐1,2‐dione (squaric acid), MeDPA = N‐methylbis(2‐pyridylmethyl)amine, TPA = tris(2‐pyridylmethyl)amine] were synthesized and structurally characterized by X‐ray crystallography. The spectral and structural characterizations as well as their magnetic properties are reported. In this series, the structures consist of the ClO4– groups as counterions and the C4O42– anions bridging the two MII centers in a μ‐1,3‐ (1 and 2) or in a μ‐1,2‐bis(monodentate) (3) bonding fashion. The coordination geometry around the five‐coordinate CuII centers in 1 is a distorted trigonal bipyramid, where the coordination environment is achieved by the four N‐donor atoms of the TPA ligand and one oxygen atom of the bridging squarato ligand. The complexes 2 and 3 adopt a distorted octahedral geometry. The six‐coordinate 4+2 environment in 2 is achieved by the three N‐atoms of the MeDPA ligand, by an oxygen atom of a bridging squarato ligand and, at longest distances, by two oxygen atoms from coordinated water molecules. In the nickel complex 3, the geometry is attained by the four N‐atoms of TPA and by two oxygen atoms supplied by a coordinated water molecule and by a bridging squarato ligand. The results manifested the effects of the blocking amine variations on the structure and on the bonding mode of the bridging squarato ligand. The complexes show antiferromagnetic coupling with |J| = 9.1 and 1.2 cm–1 in the μ‐1,3‐bridged squarato compounds 1 and 2, and with J = –1.4 cm–1 in the corresponding μ‐1,2‐bridged squarato complex 3. The magnetic properties are discussed in relation to other related compounds and the structural data.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Functionalization of Gold Nanoparticles by Iron(III) Complexes Derived from Schiff Base Ligands
Authors: Mayer Cédric R. , Cucchiaro Gregory , Jullien Josseline , Dumur Frédéric , Marrot Jérôme , Dumas Eddy , Sécheresse Francis 
Published: July 2008

AbstractA series of iron(III) complexes derived from a variety of pentadentate Schiff base ligands, namely salten [H2salten = bis(3‐salicylideneaminopropyl)amine] derivatives, have been synthesized and further used to stabilize and functionalize gold nanoparticles (Au‐NPs). The iron complexes have been specifically designed to interact with the Au‐NPs through an ambidentate thiocyanate ligand or through a pendant thiol group carried by the salten derivative ligand. The gold nanocomposites have been synthesized either by direct reduction of AuIII in the presence of iron complexes or by coordination chemistry on prefunctionalized gold nanoparticles; in the latter case Au‐NPs bearing pendant empty salten cages have been treated with FeIII to generate the iron complexes. Steric and electrostatic repulsions have been tuned to obtain stable colloidal solutions or to induce the precipitation of the gold nanocomposites. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
On the Role of Tyrosine as Catalytic Base in Nitrile Hydratase
Authors: Hopmann Kathrin H. , Himo Fahmi 
Published: July 2008

AbstractNitrile Hydratases (NHases) catalyze the conversion of nitriles to their corresponding amides. Two NHase classes exist, the FeIII‐NHases and the CoIII‐NHases. Both harbour an intriguing active site, with a low‐spin metal ion coordinated to deprotonated back‐bone amides and oxidized cysteine residues. So far it has not been possible to conclusively determine the reaction mechanism of NHase. Here we employ density functional theory to investigate the recent proposal that a fully conserved second‐shell tyrosine residue is the catalytic base of nitrile hydratase (J. Biol. Chem. 2007, 282, 7397–7404). In the proposed mechanism, the tyrosine is suggested to be in the tyrosinate state and to mediate nitrile hydration through activation of a water molecule, which attacks the metal‐bound substrate. We have explored this mechanism employing quantum chemical active site models on the basis of the CoIII‐NHase from P. thermophila JCM 3095 and the FeIII‐NHase from R. erythropolis N‐771. Potential energy curves and optimized transition states are presented. The computed barriers for the two models are a few kcal/mol above the experimental value, indicating that the conserved second‐shell tyrosine could function as the catalytic base of NHase. To further evaluate the likelihood of this mechanism, we estimated the pKa value of the second‐shell tyrosine in each model. We also provide estimates of the energy involved in the exchange of a metal‐bound water molecule with a nitrile substrate. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
The Reaction of N,N′‐Di‐tert‐butylthiourea (dtbtu) with Antimony(III) Halides – Formation of the Triply Bridged [(dtbtu)SbX2(μ‐X)2(μ‐dtbtu)SbX2(dtbtu)] (X = Cl, Br) Dimers
Authors: Barnes Nicholas A. , Godfrey Stephen M. , Pritchard Robin G. , Ratcliffe Shane 
Published: July 2008

AbstractThe reactions of N,N′‐di‐tert‐butylthiourea (dtbtu) with SbX3 (X = Cl, Br) in a 2:1 dtbtu/SbX3 ratio unexpectedly lead to products with a 3:2 dtbtu/SbX3 ratio. These complexes have been shown by X‐ray crystallographic studies to exist as triply bridged dimers, [(dtbtu)SbX2(μ‐X)2(μ‐dtbtu)SbX2(dtbtu)], (X = Cl, 1; X = Br, 2), which feature one bridging dtbtu ligand and two bridging halides. The geometry at antimony is highly distorted octahedral. This distortion is partly due to the bridging ligands, but there is also evidence for the presence of stereochemically active lone pairs. In 1 the lone pair appears to be located towards an edge of the octahedron between a terminal and a bridging halide. The situation is similar in 2, but the distortion is considerably greater at one of the antimony atoms than at the other. In contrast, the reaction of dtbtu with SbI3 yields a 1:1 complex, [SbI3(dtbtu)] (3), which is likely to be polymeric with bridging iodide ligands. The low solubility of the iodide complex has precluded characterisation by X‐ray crystallography. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Structure and Shape Evolution of Bi1–xLaxFeO3 Perovskite Microcrystals by Molten Salt Synthesis
Authors: Chen Jun , Yu Ranbo , Li Lihong , Sun Ce , Zhang Teng , Chen Houwen , Xing Xianran 
Published: July 2008

AbstractA facile and environmentally friendly synthesis method has been employed to prepare micron or submicron single‐crystal Bi1–xLaxFeO3 with different particle shapes. Various forms of the crystallite are obtained, such as cubic, tetragonal, and semi‐sphere crystallites, by means of molten salt synthesis. The thermal stability of BiFeO3 perovskite is greatly enhanced by substitution with LaFeO3. The pure phase ofBi1–xLaxFeO3 can be obtained without the use of the rapid thermal technique by introducing with small amounts of LaFeO3 into BiFeO3. The structure of Bi1–xLaxFeO3 changes from rhombohedral BiFeO3 (R3c) to orthorhombic LaFeO3 (Pnma) with an intermediate orthorhombic phase (C222), which is demonstrated by the X‐ray diffraction, Raman spectoscopy, and electron diffraction. The formation of Bi1–xLaxFeO3 can be completed in a short time (i.e. 30 min), as the reaction temperature reaches the melting point of NaCl. For the synthesis of Bi0.4La0.6FeO3, the nuclei occur with an irregular tetragonal shape in the initial nucleation stage and then grow with a regular tetragonal profile in the following growth stage. The Bi1–xLaxFeO3 crystal growth was revealed to follow the Ostwald ripening mechanism.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
19F NMR Spectroscopic Investigation of the Reaction of Bis(pentafluorophenyl)borinic Acid with a “Proton Sponge”: Deprotonation, Trimerization and Stepwise Dearylation
Authors: Donghi Daniela , Maggioni Daniela , Beringhelli Tiziana , D'Alfonso Giuseppe 
Published: July 2008

AbstractThe reaction of Ar2BOH (1, Ar = C6F5) with the proton sponge bis(dimethylamino)naphthalene (DMAN) in CD2Cl2 solution caused a series of strictly interlaced processes that have been investigated by variable‐temperature 1H and 19F NMR spectroscopy. The very slow equilibrium between the monomeric and cyclic trimeric forms of Ar2BOH was strongly accelerated by the presence of a catalytic amount of DMAN. Upon addition of stoichiometric DMAN (0.33 equiv.), all Ar2BOH was converted into a mixture of two boroxinate anions, namely [Ar6B3O3H2]– (2) and [Ar5B3O3H]– (3), in which the ratio of the two anions varied according to the reaction conditions. The formation of the dearylated anion 3 (accompanied by equimolar pentafluorobenzene) has been attributed to a reaction process parallel to that leading to the hexaaryl anion 2, involving base‐catalyzed hydrolysis of monomeric perfluoroborinic acid to its boronic analogue, followed by aggregation and condensation. Water plays a catalytic role in this process. In the presence of a small excess of DMAN, complete and instantaneous dearylation of 2 to 3 was observed. At temperatures lower than 233 K, the pentaaryl anion 3 was in equilibrium with its conjugate base. Slow further dearylation occurred at temperatures higher than 263 K, cleanly affording the tetraaryl anion [Ar4B3O3]– (5). Anions 3 and 5 have also been obtained in high yields from the condensation reaction between Ar2BOH and ArB(OH)2 (in the ratio 2:1 and 1:2, respectively), in the presence of stoichiometric DMAN. Mechanisms responsible for the stepwise dearylation from 2 to 3 and then from 3 to 5 have been discussed.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Hydrocarboxylation of Terminal Alkenes in Supercritical Carbon Dioxide
Authors: Tortosa Estorach Clara , Orejón Arantxa , Ruiz Núria , Masdeu‐Bultó Anna M. , Laurenczy Gábor 
Published: July 2008

AbstractThe catalytic hydrocarboxylation of linear alkenes to carboxylic acids using supercritical carbon dioxide as a solvent was studied. High selectivities in acids have been obtained. The best results were achieved when adding a perfluorinated surfactant to the reaction mixture (93 % conversions and ca. 80 % selectivity). Comparative multinuclear high‐pressure NMR spectroscopic studies in [D8]THF and in supercritical CO2show the formation of Pd0species. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)