bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pro‐inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum‐free conditions
Authors: Jonuleit Helmut , Kühn Ulrich , Müller Gabriele , Steinbrink Kerstin , Paragnik Lydia , Schmitt Edgar , Knop Jürgen , Enk Alexander H. 
Published: March 2007

AbstractCulture conditions for human dendritic cells (DC) have been developed by several laboratories. Most of these culture methods, however, have used conditions involving fetal calf serum (FCS) to generate DC in the presence of granulocyte‐macrophage colony‐stimulating factor and interleukin (IL)‐4. Recently, alternative culture conditions have been described using an additional stimulation with monocyte‐conditioned medium (MCM) and FCS‐free media to generate DC. As MCM is a rather undefined cocktail, the yield and quality of DC generated by these cultures varies substantially. We report that a defined cocktail of tumor necrosis factor (TNF)‐α, IL‐1β and IL‐6 equals MCM in its potency to generate DC. Addition of prostaglandin (PG)E2 to the cytokine cocktail further enhanced the yield, maturation, migratory and immunostimulatory capacity of the DC generated. More importantly, culture conditions also influenced the outcome of the T cell response induced. DC cultured with TNF‐α/IL‐1/IL‐6 or MCM alone induced CD4+ T cells that release intermediate levels of interferon (IFN)‐γ and no IL‐4 or IL‐10. Production of IFN‐γ was significantly induced by addition of PGE2, while no effect on production of IL‐4 or IL‐10 was observed. Even more striking differences were observed for CD8+ T cells. While MCM conditions only induced IFN‐γlow, IL‐4neg cells, TNF‐α/IL‐1/IL‐6 promoted growth of IFN‐γintermediate, IL‐4neg CD8+ T cells. Addition of PGE2 again only further polarized this pattern enhancing IFN‐γ production by alloreactive CD8+ T cells in both cultures without inducing type 2 cytokines. Taken together, the data indicate that the defined cocktail TNF‐α/IL‐1/IL‐6 can substitute for MCM and that addition of PGE2 further enhances the yield and quality of DC generated. TNF‐α/IL‐1, IL‐6 + PGE2‐cultured DC seem to be optimal for generation of IFN‐γ‐producing CD4/CD8+ T cells.
Antigen presentation by T cells: T cell receptor ligation promotes antigen acquisition from professional antigen‐presenting cells
Authors: Arnold Paula Y. , Davidian Daniel K. , Mannie Mark D. 
Published: March 2007

AbstractThe purpose of this study was to determine whether the clonotypic specificity of the T cell receptor influences the specificity of T cell‐mediated antigen presentation. We have previously shown that myelin basic protein (MBP)‐specific Lewis rat GP2.E5/R1 (R1) T cells cultured with antigen, irradiated syngeneic splenocytes (IrrSPL) and tolerogenic monoclonal antibody become highly effective antigen‐presenting cells (APC). In the current studies, we investigated the transfer of specific (MBP) and unrelated (conalbumin) antigens from antigen‐pulsed SPL to R1 T cells. R1 T cells cultured with IrrSPL that were pulsed simultaneously with both MBP and conalbumin acquired and presented both antigens to the appropriate T cell responders in a secondary assay. These results suggested a physical transfer of major histocompatibility complex (MHC)/peptide complexes from professional APC to R1 T cells. Transfer of conalbumin from professional APC to R1 T cells required specific recognition of MBP and was optimal when both conalbumin and MBP were presented on the same group of professional APC. Antigens transfer did not occur when allogeneic SPL were used as APC. The anti‐I‐A mAb OX6 inhibited antigen transfer but only when added during the initiation of culture. OX6 also inhibited antigen acquisition by R1‐trans, a variant of the R1 T cell line which constitutively synthesizes high levels of I‐A, from MBP‐pulsed IrrSPL but blockade of I‐A did not inhibit antigen acquisition when soluble MBP was added directly to the culture. Despite constitutive synthesis of I‐A, R1‐trans T cells did not acquire guinea pig MBP from pulsed allogeneic APC. These studies demonstrate that although T cells of a particular specificity can present unrelated antigens, the cognate interaction of the T cell antigen receptor with the appropriate antigen/self‐MHC complex strongly promotes acquisition of these complexes from professional APC.
The minimal number of antigen‐major histocompatibility complex class II complexes required for activation of naive and primed T cells
Authors: Kimachi Kazuhiko , Croft Michael , Grey Howard M. 
Published: March 2007

AbstractAlthough previous studies have shown that 50–200 antigen‐major histocompatibility complex complexes (Ag‐MHC) are sufficient to stimulate significant secretion of interleukin (IL)‐2 from MHC class II‐restricted T cell hybridomas, there have been no studies of this nature on more physiologically relevant T cell populations. In this study we have analyzed the ligand requirements for stimulation of responses from naive and previously primed T cells derived from T cell receptor (TCR)‐transgenic animals whose TCR is specific for the pigeon cytochrome c (PCC) 88–104 peptide presented by I‐Ek. Primed T cells were as sensitive as the previously reported T cell hybridomas, requiring about 100 Ag‐MHC complexes to synthesize readily detectable quantities of IL‐2, whereas naive T cells required 15 times more ligand to produce equivalent quantities of IL‐2. Similarly, primed T cells required about 40 Ag‐MHC complexes to produce a significant proliferative response, whereas naive T cells required about 400 complexes. In contrast to these results, naive and primed T cells showed similar ligand requirements when early events in the T cell activation pathway were analyzed; i.e. TCR down‐modulation, CD69 and CD25 expression, and blast transformation. A further analysis of IL‐2 and IL‐2R expression indicated: 1) The first synthesis of IL‐2 was detected at the same ligand concentration in both primed and naive T cells, but primed T cells made much more IL‐2 as the ligand concentrations increased; 2) primed T cells expressed about fivefold more IL‐2 receptor (R) than naive T cells, despite the fact that the antigen doseresponse curves with respect to the percentage of cells expressing IL‐2R were identical. These results suggest that naive and primed T cells have the same threshold with respect to the number of Ag‐MHC complexes required to initiate T cell activation, but that due to the inefficient expression of IL‐2 and IL‐2R, engagement of more complexes is needed to enable naive T cells to synthesize the necessary amounts of these two molecules to allow T cells to go through a complete cycle of replication.
A dual participation of ZAP‐70 and scr protein tyrosine kinases is required for TCR‐induced tyrosine phosphorylation of Sam68 in Jurkat T cells
Authors: Lang Valérie , Mège Dominique , Semichon Monique , Gary‐Gouy Hélène , Bismuth Georges 
Published: March 2007

AbstractSam68 has been initially described as a substrate of src kinases during mitosis in fibroblasts. Recent evidence suggests that in T lymphocytes Sam68 may act as an adaptor protein and participate in the early biochemical cascade triggered after CD3 stimulation. A direct interaction between Sam68 and the two src kinases involved in T cell activation, p59fyn and p56lck, as well as a partnership of Sam68 with various key downstream signaling molecules, like phospholipase Cγ‐1 and Grb2, has been shown. In this study we analyze the contribution of p56lck, as well as the role of ZAP‐70, the second class of protein tyrosine kinase involved in T cell activation, in Sam68 tyrosine phosphorylation in the human Jurkat T cell line. Using the src inhibitor PP1 [4‐amino‐5‐(4‐methylphenyl)7‐(t‐butyl) pyrazolo [3,4‐d] pyrymidine] and cell variants with defective expression of p56lck or expressing a dominant negative form of ZAP‐70, we demonstrate that, while both p56lck and ZAP‐70 are dispensable for the low constitutive phosphorylation of Sam68 observed in Jurkat cells, a cooperation between the two kinases is required to increase its rapid phosphorylation observed in vivo after CD3 stimulation. We also show that recombinant forms of both p56lck and ZAP‐70 phosphorylate Sam68 in vitro. However, using CD2 stimulated cells, we observe that p56lck activation by itself does not induce Sam68 tyrosine phosphorylation. We conclude that p59lck and p56lck differently participate in regulating the phosphorylation state of Sam68 in T cells and that ZAP‐70 may contribute to Sam68 tyrosine phosphorylation and to the specific recruitment of this molecule after CD3 stimulation.
Critical test of hot spot motifs for immunoglobulin hypermutation
Authors: Bachl Juergen , Steinberg Charles , Wabl Matthias 
Published: March 2007

AbstractIn hypermutation at the immunoglobulin loci, some bases are much more mutable than others. The increased mutability of the hot spots has been attributed to their being embedded in short sequence motifs. Among the suggested motifs are palindromes, TAA and RGYW (i.e. A/G G C/T A/T). We have tested these proposed motifs in a transfection system in vitro, which ordinarily uses the hypermutable stop codon TAG. The stop codon TAA is not hypermutable in our system, even when embedded in the pentamer and hexamer palindromes TAATA and ATTAAT; in fact, the revertants isolated were due to deletions. Single or double base changes in an RGYW motif containing a hypermutable stop codon result in a reduction of one order of magnitude or more in point mutation frequency. When the nonamer GACTAGTAT, which includes the same RGYW motif, was moved over hundred base pairs upstream, hypermutability was reduced by an order of magnitude. Thus, while RGYW apparently is a hypermutability motif, it cannot be the sole determinant of mutability.
Immunostimulatory DNA: Sequence‐dependent production of potentially harmful or useful cytokines
Authors: Lipford Grayson B. , Sparwasser Tim , Bauer Marc , Zimmermann Stefan , Koch Eva‐Sophie , Heeg Klaus , Wagner Hermann 
Published: March 2007

AbstractCertain bacterial immunostimulatory (i.s.) DNA sequences containing unmethylated CpG motifs stimulate antigen‐presenting cells (APC) to express a full complement of costimulatory molecules and to produce cytokines including interleukin (IL)‐12 and tumor necrosis factor (TNF)‐α. While IL‐12 is key to their T helper cell (Th)1‐promoting adjuvant activity, secretion of toxic levels of TNF‐α is harmful in that it promotes toxic shock. Given the beneficial as well as harmful consequences of i.s. DNA, we investigated the possibility of identifying DNA sequences, i.e. CpG oligodeoxynucleotides (ODN) which differentially activate IL‐12 versus TNF‐α cytokine production in APC. Here, we describe an i.s. DNA sequence with these characteristics. While its potential to induce IL‐12 is preserved, its ability to trigger TNF‐α release is strongly curtailed both in vitro and in vivo. I.s. DNA could be segregated into lethal and non‐lethal in a mouse toxic shock model. The non‐toxic i.s. DNA was useful as an adjuvant, thus allowing cytotoxic T cell responses to the soluble protein ovalbumin and conferring a resistant Th 1 phenotype to BALB/c mice lethally infected with Leishmania major. This i.s. CpG motif may thus be prototypic for a useful immunostimulating DNA sequence that lacks harmful side effects.
Immunoregulation by interleukin‐12 in MB49.1 tumor‐bearing mice: Cellular and cytokine‐mediated effector mechanisms
Authors: Hunter Sharon E. , Waldburger Kristine E. , Thibodeaux Deborah K. , Schaub Robert G. , Goldman Samuel J. , Leonard John P. 
Published: March 2007

AbstractAdministration of recombinant murine interleukin (rmlL)‐12 to MB49.1 tumor‐bearing mice results in dose‐dependent regression of the primary tumor and the generation of protective antitumor immunity in the majority of animals. rmlL‐12 administration is associated with a marked increase in lymph node cellularity that is predominantly due to the expansion of B220+ B cells as well as CD8+ T cells. Stimulation of lymph node cells from rmlL‐12‐treated, but not control tumor‐bearing mice, with MB49.1 tumor cells in vitro was shown to enhance the secretion of interferon (IFN)‐γ. The magnitude of this in vitro response was dependent on the dose of rmlL‐12 administered in vivo and mirrored the change in circulating serum IFN‐γ. Furthermore, at the height of the in vitro response to tumor stimulation, the addition of a neutralizing antibody to murine IL‐12 suppressed IFN‐γ production, indicating a role for endogenous IL‐12 in this antigen‐specific cytokine response. Although studies in SCID mice confirmed that an appropriate T cell response was required for rmlL‐12‐mediated antitumor activity, in immunocompetent animals early tumor regression was not accompanied by cellular infiltration of the tumor. In contrast, a profound increase in tumor‐associated inducible nitric oxide synthase (iNOS) was observed in mice receiving rmlL‐12 which preceded T cell infiltration of the tumor which could be detected during the second week of IL‐12 treatment. Direct tumor killing through the cytotoxic actions of NO via the iNOS pathway may serve as a way of generating tumor antigen which enables the host to mount a subsequent T cell response against the tumor.
Ectopic expression of BcI‐2, but not BcI‐xL rescues Ramos B cells from Fas‐mediated apoptosis
Authors: Alam Mohammad K. , Davison Stephen , Siddiqui Nisha , Norton John D. , Murphy John J. 
Published: March 2007

AbstractThe human Burkitt lymphoma Ramos B cell line can be induced to undergo apoptosis in response to a variety of different agents, including calcium ionophores, anti‐immunoglobulin (Ig) and macromolecular synthesis inhibitors. In addition, following up‐regulation of the Fas (CD95) surface receptor by CD40 ligation, these cells also become susceptible to apoptosis induction by Fas ligation. We have previously shown that protection from calcium ionophore‐ and macromolecular synthesis inhibitor‐induced apoptosis by CD40 ligation is associated with a rapid up‐regulation of BcI‐xL followed by a more moderate and delayed up‐regulation of BcI‐2. We show here that overexpression of BcI‐xL, like BcI‐2, protects Ramos cells from apoptosis induction in response to calcium ionophore, anti‐Ig and macromolecular synthesis inhibition. However, in contrast to BcI‐2, ectopic overexpression of BcI‐xL does not rescue from Fas‐mediated apoptosis. Thus, in Ramos B cells, the Fas apoptotic pathway exhibits differential sensitivity to inhibition by BcI‐2 family members. These findings also suggest that CD40 signaling provides a switch which renders the cells susceptible to Fas‐ligand mediated apoptosis through up‐regulation of Fas whilst affording protection from anti‐Ig‐induced apoptosis through up‐regulation of BcI‐xL.
Synthesis, Characterization and Redox Behaviour of Mono‐ and Dicarbonyl Phosphane Rhenium(I) Complexes Bearing N‐, N,N‐ and N,O‐Type Ligands
Authors: Kirillov Alexander M. , Haukka Matti , Guedes da Silva M. Fátima C. , Pombeiro Armando J. L. 
Published: March 2007

AbstractNew mono‐ and dicarbonyl phosphane ReI complexes [ReCl(L)2(CO)(PPh3)2] {L = 3,5‐Me2‐Hpz (3), quin (4)} and [Re(L)n(CO)2(PPh3)2][BPh4]m {L = pz/Hpz, n = 2, m = 0 (2); L = 4,7‐Ph2‐phen, n = 1, m = 1 (5); L = 2‐Me‐dipic, n = 1, m = 0 (6)} were prepared by reaction of the dinitrogen ReI precursor [ReCl(N2)(CO)2(PPh3)2] (1), in refluxing methanol or methanol/benzene mixture, with 3,5‐dimethylpyrazole (3,5‐Me2‐Hpz), quinoline (quin), pyrazole (Hpz), 4,7‐diphenyl‐1,10‐phenanthroline (4,7‐Ph2‐phen) and dipicolinic acid (H2dipic), respectively, with esterification of the latter in 6 to afford the 2‐methoxycarbonyl‐6‐pyridinecarboxylate (2‐Me‐dipic) moiety. Complexes 2–6 were characterized by IR spectroscopy, 1H‐, 31P{1H}‐ and 13C{1H} NMR spectroscopy, FAB‐MS, cyclic voltammetry, elemental analyses and single‐crystal X‐ray diffraction (for 2, 5 and 6) analyses which indicate mutually trans triphenylphosphane ligands. The redox behaviour of the obtained complexes in solution was studied, and the Lever electrochemical ligand parameter EL was determined, for the first time, for 4,7‐Ph2‐phen. Compounds 2–6 represent the first examples of mono‐ and dicarbonyl Re complexes bearing these types of ligands.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
The Synthesis of 6‐Amidino‐2‐oxopurine Revisited: New Evidence for the Reaction Mechanism
Authors: Dias Alice M. , Cabral Isabel , Vila‐Chã A. Sofia , Costa Daniela S. , Proença M. Fernanda 
Published: March 2007

AbstractTreatment of N‐aryl‐ or N‐alkyl‐5‐amino‐4‐(cyanoformimidoyl)‐1H‐imidazoles 1 with benzoyl or ethoxycarbonyl isocyanates resulted in the formation of 5‐amino‐4‐[N‐benzoyl‐ or N‐(ethoxycarbonyl)carbamoylcyanoformimidoyl]‐1H‐imidazoles 2. In the presence of catalytic amounts of DBU (1,8‐diazabicyclo[5.4.0]undec‐7‐ene), these compounds cyclized to give the 5′‐amino‐5‐imino‐4,4′‐bi‐1H‐imidazol‐2(5H)‐ones 3. Compounds 3 efficiently rearrange to yield 6‐amidino‐2‐oxopurines 5 in ethanol or DMF solution. The formation of purines 5 both from imidazoles 2 and from bi‐imidazoles 3 was followed by 1H NMR, allowing a deeper understanding of the reaction mechanism. The rearrangements are acid‐catalysed (trifluoroacetic acid), but the use of one equivalent of acid produced different products, identified as the bi‐imidazoles 8.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Novel Spiroheterocycles by Aziridination of α‐Methylene‐γ‐ and ‐δ‐lactams
Authors: Loreto M. Antonietta , Migliorini Antonella , Tardella P. Antonio , Gambacorta Augusto 
Published: March 2007

AbstractNew potentially bioactive α‐spiroaziridino‐γ‐ and ‐δ‐lactams have been prepared by treatment of α‐methylene‐γ‐ and ‐δ‐lactams with ethyl N‐{[(4‐nitrophenyl)sulfonyl]oxy}carbamate (NsONHCO2Et) in the presence of CaO. These compounds, through reductive aziridine ring opening, can be intermediates for the synthesis of α‐ and β‐aminolactams, which are useful as conformational constraints in peptides. The above procedure has been successfully extended to one α‐methyleneoxindole to obtain a new spirooxindole derivative, a potential precursor of natural alkaloids. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis of a Spore Surface Pentasaccharide of Bacillus anthracis
Authors: Werz Daniel B. , Adibekian Alexander , Seeberger Peter H. 
Published: March 2007

AbstractAn analogue 2 of the pentasaccharide 1 found on the spore surface protein BclA of Bacillus anthracis was synthesized by a (3+2) glycosylation approach. A robust building block for 3‐linked α‐rhamnose is presented. Benzoate groups were used to ensure α‐selectivity for the rhamnose units. A radical‐initiated reduction with tributyltin hydride was shown to be able to convert the NHTCA group into an acetylated amine as well as an azido group into a free amine on one strike. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Cover Picture: The Structural Identification and Conformational Analysis of the Products from the Reaction of Acrolein with 2′‐Deoxycytidine, 1‐Methylcytosine and Calf Thymus DNA (Eur. J. Org. Chem. 9/2007)
Authors: Pawłowicz Agnieszka, J. , Klika Karel D. , Kronberg Leif 
Published: March 2007

AbstractThe cover picture shows that acrolein, a mutagenic environmental pollutant formed during incomplete combustion, reacts with the cytosine base to yield exocyclic ring adducts. Identification and characterization of adducts are discussed in detail in the article by A. J. Pawłowicz, K. D. Klika, and L. Kronberg on p. 1429 ff.
Wavelet transformation of mode shape difference function for structural damage location identification
Authors: Poudel Upendra P. , Fu Gongkang , Ye Jian 
Published: March 2007

AbstractIn this paper, a new approach to structural damage detection is presented using mode shape difference between the reference and damage states. In order to capture and display the signal of damage, wavelet transformation is performed upon the mode shape difference function. Results show that this presentation of signal is effective for damage detection. Furthermore, practical aspects of damage identification are investigated, including understanding and using the frequency contents of the mode shape difference function, the mother wavelet function and the resulting wavelet coefficients due to the band‐limited filtering of wavelet transformation. This proposition is experimented. Results are assertive of the proposed concept. Copyright © 2007 John Wiley & Sons, Ltd.
What can we learn from two‐center three‐electron bonding with the topological analysis of ELF?
Authors: Fourré I. , Silvi B. 
Published: March 2007

AbstractIn this paper, a review is presented of the abundant literature on the two‐center three‐electron (2c‐3e) bonding, which plays a crucial role in electron transfer and radical chemistry. Important questions regarding this peculiar type of interaction are (1) Is a three‐electron bonded complex a molecule or an assembly of molecules?, (2) Since an unpaired electron is involved, where is the spin density located?, and (3) Is there a descriptor of electron fluctuation, which is a central phenomenon in this type of bonding? We demonstrate that the topological analysis of the electron localization function (ELF), which provides a convenient mathematical framework to study chemical bond in molecules and solids, is able to answer these questions. First, examples of potentially 3e‐bonded complexes proposed by Pauling are reinvestigated. Second, the electron attachment process on molecules of the HnXYHmtype with X,Y = Cl, S, P, Si andn, m= 0–2 is considered. Finally, the ELF‐based topology of some prototypical radicals containing the SO bond is examined. From these studies, several topological signatures of the 3e bonding have been elaborated. No disynaptic basin, well known as the topological signature of a covalent shared‐electron pair interaction, is found between two 3e‐bonded atoms. Therefore, to distinguish 3e bonds from ionic or hydrogen bonds, a core valence bifurcation (CVB) index has been introduced, similar to the one previously defined by Fuster and Silvi (Theor Chem Acc 2000,104,13) to differentiate weak and medium H‐bonds. Moreover, in 3e‐bonded systems, the spin density is mainly localized within the lone‐pair basins of the heavy atoms. To quantify the electron fluctuation, a topological delocalization index has been defined. An unambiguous characterization of the 3e bonding is thus obtained, which is in agreement with other theoretical approaches, such as the valence bond method. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:135–160, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20325
The role of functional nitro and cyano groups in the self‐assembly of 1,3‐dithiole‐2‐thione–halogen adducts
Authors: Skabara Peter J. , Kanibolotsky Alexander , Render Simon , Berridge Rory , Crouch David J. , Bricklebank Neil , Coles Simon J. , Gelbrich Thomas , Hursthouse M. B. 
Published: March 2007

AbstractThe synthesis of five new dihalogen/interhalogen charge transfer adducts featuring cyano and nitro functionalized 1,3‐dithiole‐2‐thiones have been prepared and characterized by x‐ray crystallography. The structures feature a complex series of intermolecular close contacts between heteroatoms, as well as hydrogen bonding, to give highly ordered, polymeric assemblies. The adduct 4.IBr crystallizes in a noncentrosymmetric chiral space group and features a stack of molecules assembled through hydrogen bonds. The functional groups of all adducts participate in networks of close contacts, but do not affect the coordination environment of the dihalogen/interhalogen species. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:176–184, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20327