bluuebunny/crossref_metadata_2025_split huggingface dataset:
B7‐H3 is a potent inhibitor of human T‐cell activation: No evidence for B7‐H3 and TREML2 interaction
Authors: Leitner Judith , Klauser Christoph , Pickl Winfried F. , Stöckl Johannes , Majdic Otto , Bardet Anaïs F. , Kreil David P. , Dong Chen , Yamazaki Tomohide , Zlabinger Gerhard , Pfistershammer Katharina , Steinberger Peter 
Published: June 2009

AbstractB7‐H3 belongs to the B7 superfamily, a group of molecules that costimulate or down‐modulate T‐cell responses. Although it was shown that B7‐H3 could inhibit T‐cell responses, several studies – most of them performed in murine systems – found B7‐H3 to act in a costimulatory manner. In this study, we have specifically addressed a potential functional dualism of human B7‐H3 by assessing the effect of this molecule under varying experimental conditions as well as on different T‐cell subsets. We show that B7‐H3 does not costimulate human T cells. In the presence of strong activating signals, B7‐H3 potently and consistently down‐modulated human T‐cell responses. This inhibitory effect was evident when analysing proliferation and cytokine production and affected naïve as well as pre‐activated T cells. Furthermore, we demonstrate that B7‐H3–T‐cell interaction is characterised by an early suppression of IL‐2 and that T‐cell inhibition can be reverted by exogenous IL‐2. Since the triggering receptor expressed on myeloid cells like transcript 2 (TREML2/TLT‐2) has been recently described as costimulatory receptor of murine B7‐H3 we have extensively analysed interaction of human B7‐H3 with TREML2/TLT‐2. In these experiments we found no evidence for such an interaction. Furthermore, our data do not point to a role for murine TREML2 as a receptor for murine B7‐H3.
Transcriptional and inflammasome‐mediated pathways for the induction of IL‐1β production by Mycobacterium tuberculosis
Authors: Kleinnijenhuis Johanneke , Joosten Leo A. B. , van de Veerdonk Frank L. , Savage Nigel , van Crevel Reinout , Kullberg Bart Jan , van der Ven Andre , Ottenhoff Tom H. M. , Dinarello Charles A. , van der Meer Jos W. M. , Netea Mihai G. 
Published: June 2009

AbstractProinflammatory cytokines of the IL‐1 family play an important role for the anti‐mycobacterial host defense mechanisms. In the present study we have deciphered the pathways leading from recognition of Mycobacterium tuberculosis to the production and release of IL‐1β, the most important member of the IL‐1 family. By stimulating cells defective in various pattern recognition receptors, we could demonstrate that IL‐1β production is induced by M. tuberculosis through pathways involving TLR2/TLR6 and NOD2 receptors. In contrast, TLR4, TLR9 and TLR1 receptors are not involved in IL‐1β induction. Recognition of M. tuberculosis by TLR and NOD2 leads to transcription of proIL‐1β through mechanisms involving ERK, p38 and Rip2, but not JNK. Interestingly, although caspase‐1 is necessary for the processing of proIL‐1β, activation of caspase‐1 is not dependent on the stimulation of cells by M. tuberculosis. Monocytes expressed constitutively active caspase‐1. The secretion of IL‐1β is dependent on the activation of P2X7‐induced pathways by endogenously released ATP. In conclusion, we have dissected the molecular mechanisms responsible for IL‐1β production by M. tuberculosis, and that may contribute to a deeper knowledge of the mechanisms of cell activation by M. tuberculosis.
IL‐23‐driven encephalo‐tropism and Th17 polarization during CNS‐inflammation in vivo
Authors: Gyülvészi Gabor , Haak Stefan , Becher Burkhard 
Published: June 2009

AbstractIL‐23 but not IL‐12 is essential for the development of autoimmune tissue inflammation in mice. Conversely, IL‐12 and IL‐23 impact on the polarization of Th1 and Th17 cells, respectively. While both polarized T helper populations can mediate autoimmune inflammation, their redundancy in the pathogenesis of EAE indicates that IL‐23 exerts its crucial influence on the disease independent of its T helper polarizing capacity. To study the impact of IL‐23 and IL‐12 on the behavior of encephalitogenic T cells in vivo, we generated BM‐chimeric mice in which we can trace individual populations of IL‐23 or IL‐12 responsive T helper cells during EAE. We observed that T cells, which lack IL‐12Rβ1 (no IL‐12 and IL‐23 signaling), fail to invade the CNS and do not acquire a Th17 phenotype. In contrast, loss of IL‐12 signaling prevents Th1 polarization but does not prevent T‐cell entry into the CNS. The loss of IL‐12R engagement does not appear to alter T‐cell expansion but leads to their accumulation in secondary lymphoid organs. We found that IL‐23 licenses T cells to invade the target tissue and to exert their effector function, whereas IL‐12 is critical for Th1 differentiation, but does not influence the pathogenic capacity of auto‐reactive T helper cells in vivo.
Deprotection of N‐Nosyl‐α‐amino Acids by Using Solid‐Supported Mercaptoacetic Acid
Authors: De Marco Rosaria , Di Gioia Maria Luisa , Leggio Antonella , Liguori Angelo , Viscomi Maria Caterina 
Published: June 2009

AbstractA simple and efficient synthesis of a solid‐supported thiol has been developed. Mercaptoacetic acid was first protected by the dimethoxytrityl group and then anchored to Wang resin through an ester bond. Deprotection of the thiol function led to resin‐supported mercaptoacetic acid, a useful supported thiol reagent that can be used in the polymer‐assisted solution‐phase removal of nosyl (Ns) groups from the amino function of α‐amino acids in peptide synthesis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Asymmetric Addition of Terminal Alkynes to N‐(Diphenylphosphinoyl)imines Promoted by Stoichiometric Amounts of a Proline‐Derived β‐Amino Alcohol
Authors: Yan Wenjin , Mao Bin , Zhu Shaoqun , Jiang Xianxing , Liu Zhongli , Wang Rui 
Published: June 2009

AbstractA new synthetic methodology for the preparation of optically active propargylamines is described. The alkynylation of aromatic, heteroaromatic, aliphatic and α,β‐unsaturated N‐(diphenylphosphinoyl)imines was investigated by using diethylzinc and a proline‐derived β‐amino alcohol. N‐(Diphenylphosphinoyl)‐protected propargylic amines can be synthesized in high yields and with good to excellent enantioselectivities. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Short and Stereoselective Total Synthesis of Δ‐11,13‐Didehydroguaianes and ‐guaianolides: Synthesis of (±)‐Achalensolide and (±)‐Pechueloic Acid; Revision of the Structure of (+)‐Rupestonic Acid
Authors: Sainte‐Luce Banchelin Thomas , Carret Sébastien , Giannini Audrey , Deprés Jean‐Pierre 
Published: June 2009

Abstract(±)‐Pechueloic acid (1), (±)‐rupestonic acid (3), and (±)‐achalensolide (5) (guaian‐8–12‐olide class) were prepared stereoselectively in only nine steps from the commercially available tropylium cation via central intermediate 6, which is used as a general and efficient precursor to bicyclo[5.3.0]decane sesquiterpenes. The method does not require function protection. It is highly regio‐ and stereoselective thanks to an efficient C‐1 epimerization, a selective C‐8,9 hydrogenation, and a stereocontrolled 1,6 conjugate addition of an acrylate equivalent. These Δ‐11,13‐didehydroguaianes and‐guaianolides are good Michael acceptors and hence biologically active. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Scaling of nucleic acid assays on microelectrophoresis array devices: High‐dynamic range multi‐gene readout from less than ten transcripts
Authors: Ueberfeld Joern , Ehrlich Daniel J. 
Published: June 2009

AbstractIn this paper we describe progress in using the prodigious data‐collecting ability of multilane microelectrophoresis instruments to bear on problems in scaled nucleic acid assays. We emphasize compound stacking and solid‐support loading as means to concentrate <100 pg samples for direct injection. Reaction Mapping is applied to readout quantitative polymerase chain reaction gene‐expression and as a way to practically overcome difficulty in interpreting amplification curves of multiplexed quantitative polymerase chain reaction at 20–50 gene/well complexity. We demonstrate multiplexed readout of gene expression over an abundancy range of 9 Log 2 units starting with reverse‐transcribed samples as small as five molecules in each sample.
A proteomic workflow for discovery of serum carrier protein‐bound biomarker candidates of alcohol abuse using LC‐MS/MS
Authors: Lai Xianyin , Liangpunsakul Suthat , Crabb David W. , Ringham Heather N. , Witzmann Frank A. 
Published: June 2009

AbstractThe diagnosis and care of patients with alcohol abuse and dependence is hampered by a lack of sensitive and specific screening and monitoring tests. Proteomics is a good approach to search for biomarkers of alcohol abuse. Serum carrier protein‐bound proteins have attracted significant interest because they remain a relatively un‐mined region of the proteome. In the present study, a proteomic workflow including LC‐MS/MS with enrichment of serum carrier protein‐bound biomarkers technique was applied to profile the changes in quality and quantity of serum carrier protein‐bound proteins for the discovery of novel biomarker candidates of alcohol abuse. In total, 311 proteins identified with high confidence were discovered to be bound to serum carrier proteins. Complement isoforms, Ig fragments, and apolipoprotein family proteins are the main serum carrier‐bound proteins. Protein quantification analysis with and without concern as to gender revealed that gender is a critical consideration for biomarker development in alcohol abuse. Identified proteins not previously associated with alcohol abuse include gelsolin, selenoprotein P, serotransferrin, tetranectin, hemopexin, histidine‐rich glycoprotein, plasma kallikrein, and vitronectin. Altered abundance of these proteins suggests that they may be potential novel biomarkers for alcohol abuse.
Chiral analysis of anti‐acquired immunodeficiency syndrome drug, 9‐(R)‐[2‐(phosphonomethoxy)propyl]adenine (tenofovir), and related antiviral acyclic nucleoside phosphonates by CE using β‐CD as chiral selector
Authors: Šolínová Veronika , Kašička Václav , Sázelová Petra , Holý Antonín 
Published: June 2009

AbstractA new CZE method has been developed for chiral analysis of an important anti‐acquired immunodeficiency syndrome drug, 9‐(R)‐[2‐(phosphonomethoxy)propyl]adenine ((R)‐PMPA, tenofovir), and six related antiviral acyclic nucleoside phosphonates using β‐CD as a chiral selector. The influence of the composition, concentration and pH of the BGE and the type and concentration of chiral selector on enantiomer resolution was investigated. Complete separations of (R,S)‐enantiomers of PMPA with very good resolution (Rs=1.50–3.64) were achieved within a short time (4–15 min) in 20–50 mM sodium borate or sodium tetraborate BGEs, pH 10.0, at 20 mg/mL concentration of β‐CD. (R,S)‐enantiomers of five similar PMPA analogs containing purine bases (adenine, diaminopurine or guanine) and hydroxyl or fluor substituents at C3 carbon atom of propyl chain were baseline separated within 10–17 min in 35 mM sodium tetraborate BGE, pH 10.0, at 20 mg/mL β‐CD concentration. Another important antiviral used by acquired immunodeficiency syndrome patients, derived from pyrimidine base cytosine, 1‐(S)‐[3‐hydroxy‐2‐(phosphonomethoxy)propyl]cytosine (cidofovir), and the (R)‐enantiomer of this drug were successfully separated in 50 mM sodium tetraborate BGE, pH 10.5, at 20 mg/mL β‐CD concentration within 45 min. Using the UV‐absorption detection at 206 nm, the concentration detection limits of the analyzed acyclic nucleoside phosphonates were determined in the submicromolar to micromolar range (0.15–2.51 μg/mL level).
Turbulent flow simulation using LES with dynamical mixed one‐equation subgrid models in complex geometries
Authors: Wang Wenquan , Zhang Lixiang , Yan Yan , Guo Yakun 
Published: June 2009

AbstractAn innovative computational model is presented for the large eddy simulation of multi‐dimensional unsteady turbulent flow problems in complex geometries. The main objectives of this research are (i) to better understand the structure of turbulent flows in complex geometry and (ii) to investigate the 3D characteristics of such complex fluid flow. The filtered Navier–Stokes equations are used to simulate large scales of the turbulence, while the energy transfer from large scales to subgrid‐scales (SGS) is simulated using dynamical mixed one‐equation subgrid models. In the proposed SGS model, the SGS kinetic energy, ksgs, is used for scaling the velocity for the eddy‐viscosity part of the model. The proposed SGS model contains not only some information on the small scales as described in traditional Smagorinsky model or Germano dynamical model but also includes additional scale‐similarity as that in the models of Ghosal et al. (J. Comput. Phys. 1995; 118:24–37) or Davidson (11th International Symposium on Turbulent Shear Flow, Grenoble, vol. 3, 1997; 26.1–26.6). The Navier–Stokes equations and the derived ksgs equation are solved using implicit finite‐volume method. The models have been applied to simulate the 3D flows over a backward‐facing step and in a strong 3D skew runner blade passage of a Francis hydro turbine, respectively. Good agreement between simulated results and experimental results as well as other numerical results was obtained. Copyright © 2009 John Wiley & Sons, Ltd.
Nowcasting and predicting data revisions using panel survey data
Authors: Matheson Troy D. , Mitchell James , Silverstone Brian 
Published: June 2009

AbstractThe qualitative responses that firms give to business survey questions regarding changes in their own output provide a real‐time signal of official output changes. The most commonly used method to produce an aggregate quantitative indicator from business survey responses—the net balance or diffusion index—has changed little in 40 years. This paper investigates whether an improved real‐time signal of official output data changes can be derived from a recently advanced method on the aggregation of survey data from panel responses. We find, in a New Zealand application, that exploiting the panel dimension to qualitative survey data gives a better in‐sample signal about official data than traditional methods. Out‐of‐sample, it is less clear that it matters how survey data are quantified, with simpler and more parsimonious methods hard to improve. It is clear, nevertheless, that survey data, exploited in some form, help to explain revisions to official data. Copyright © 2009 John Wiley & Sons, Ltd.
Forecasting key macroeconomic variables from a large number of predictors: a state space approach
Authors: Raknerud Arvid , Skjerpen Terje , Swensen Anders Rygh 
Published: June 2009

AbstractWe use state space methods to estimate a large dynamic factor model for the Norwegian economy involving 93 variables for 1978Q2–2005Q4. The model is used to obtain forecasts for 22 key variables that can be derived from the original variables by aggregation. To investigate the potential gain in using such a large information set, we compare the forecasting properties of the dynamic factor model with those of univariate benchmark models. We find that there is an overall gain in using the dynamic factor model, but that the gain is notable only for a few of the key variables. Copyright © 2009 John Wiley & Sons, Ltd.
Synthesis of aromatic amine phosphonato ester derivatives from the stereoselective reaction between triphenyl phosphite and dimethyl acetylenedicarboxylate in the presence of derivatives of aromatic amines
Authors: Maghsoodlou Malek Taher , Heydari Reza , Hazeri Nourallah , Habibi‐Khorassani Sayyed Mostafa , Nassiri Mahmoud , Ghasemzadeh Marjan , Salehzadeh Jaber , Gharechaei Zahra 
Published: June 2009

AbstractAromatic amine phosphonato esters 4a–d were obtained in excellent yields from the 1:1:1 addition reaction between triphenyl phosphite and dimethyl acetylenedicarboxylate in the presence of NH‐aromatic amines such as 2‐aminobenzophenone, 2‐aminoacetophenon, methyl‐2‐aminobenzoate, and 2‐aminobenzonitrile. In the recent works, the assignments of the configuration of 4a–d corresponding to the three‐bond carbon‐phosphorus coupling, 3Jpc, was determined on the basis of coupling constants by the Karplus equation as 2R*,3R*or 2S*,3S* while they were 2R*,3S* or 2S*,3R* in our previous works in the presence of same solvent. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:240–245, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20541
Deletion of interleukin-12p40 suppresses autoimmune cholangitis in dominant negative transforming growth factor β receptor type II mice #
Authors: Yoshida Katsunori , Yang Guo-Xiang , Zhang Weici , Tsuda Masanobu , Tsuneyama Koichi , Moritoki Yuki , Ansari Aftab A. , Okazaki Kazuichi , Lian Zhe-Xiong , Coppel Ross L. , Mackay Ian R. , Gershwin Eric M. 
Published: June 2009

Abstract
Our laboratory has reported that mice that express a dominant negative form of transforming growth factor β receptor restricted to T cells (dnTGFβRII) develop an inflammatory biliary ductular disease with elevated serum levels of interleukin (IL)-12p40 and other proinflammatory cytokines and antimitochondrial autoantibodies (AMAs) closely resembling human primary biliary cirrhosis (PBC). We have used this mouse model to address the potential mechanisms of immunomodulation of liver disease by creating two unique genetic strains: IL-12p40 knockout (KO)-dnTGFβRII mice and IFN-γ KO-dnTGFβRII mice. The two colonies of genetically modified mice—and, for purposes of controls, the dnTGFβRII mice—were monitored for liver immunopathology, AMAs, and intrahepatic cytokine production. Disease expression in the IFN-γ KO-dnTGFβRII mice, including liver immunopathology, were similar to those of dnTGFβRII mice, whereas the IL-12p40 KO-dnTGFβRII mice had a dramatic reduction in histological autoimmune cholangitis and significant decreases in levels of intrahepatic proinflammatory cytokines, but similar levels of AMAs compared with dnTGFβRII controls. Conclusion: These data indicate that in this mouse model of PBC, signaling by way of IL-12p40 is an essential requirement for the development of autoimmune cholangitis. The results of these studies will play an important role in identifying pathways and reagents that will selectively inhibit IL-12 signaling for the outlining of future therapeutic strategies for human PBC. (Hepatology 2009.)
The novel HSP90 inhibitor STA‐1474 exhibits biologic activity against osteosarcoma cell lines
Authors: McCleese Jennifer K. , Bear Misty D. , Fossey Stacey L. , Mihalek Robert M. , Foley Kevin P. , Ying Weiwen , Barsoum James , London Cheryl A. 
Published: June 2009

AbstractOsteosarcoma (OSA), the most common malignant bone tumor in dogs and children, exhibits a similar clinical presentation and molecular biology in both species. Unfortunately, 30–40% of children and 90% of dogs still die of disease despite aggressive therapy. The purpose of this study was to test the biologic activity of a novel heat shock protein 90 (HSP90) inhibitor, STA‐1474, against OSA. Canine and human OSA cell lines and normal canine osteoblasts were treated with STA‐1474 and evaluated for effects on proliferation (CyQuant), apoptosis (Annexin V, PARP cleavage, caspase 3/7 activation) and known HSP90 client proteins. HSP90 was immunoprecipitated from normal and malignant osteoblasts and Western blotting for co‐chaperones was performed. Mice bearing canine OSA xenografts were treated with STA‐1474, and tumors samples were evaluated for caspase‐3 activation and loss of p‐Akt/Akt. Treatment with STA‐1474 promoted loss of cell viability, inhibition of cell proliferation and induction of apoptosis in OSA cell lines. STA‐1474 and its active metabolite STA‐9090 also demonstrated increased potency compared to 17‐AAG. STA‐1474 exhibited selectivity for OSA cells versus normal canine osteoblasts, and HSP90 co‐precipitated with co‐chaperones p23 and Hop in canine OSA cells but not in normal canine osteoblasts. Furthermore, STA‐1474 downregulated the expression of p‐Met/Met, p‐Akt/Akt and p‐STAT3. Finally, STA‐1474 induced tumor regression, caspase‐3 activation and downregulation of p‐Met/Met and p‐Akt/Akt in OSA xenografts. Together, these data suggest that HSP90 represents a relevant target for therapeutic intervention in OSA. © 2009 UICC
FoxP3+ regulatory T cells are distinct from leukemia cells in HTLV‐1–associated adult T‐cell leukemia
Authors: Toulza Frederic , Nosaka Kisato , Takiguchi Masafumi , Pagliuca Tony , Mitsuya Hiroaki , Tanaka Yuetsu , Taylor Graham P. , Bangham Charles R.M. 
Published: June 2009

AbstractHuman T‐lymphotropic virus type 1 (HTLV‐1) is the causative agent of adult T‐cell leukemia/lymphoma (ATLL). It has been postulated that ATLL cells might act as regulatory T cells (Tregs) which, in common with ATLL cells, express both CD25 and FoxP3, and so contribute to the severe immune suppression typical of ATLL. We report here that the frequency of CD25+ cells varied independently of the frequency of FoxP3+ cells in both a cross‐sectional study and in a longitudinal study of 2 patients with chronic ATLL. Furthermore, the capacity of ATLL cells to suppress proliferation of heterologous CD4+CD25− cells correlated with the frequency of CD4+ FoxP3+ cells but was independent of CD25 expression. Finally, the frequency of CD4+FoxP3+ cells was inversely correlated with the lytic activity of HTLV‐1‐specific CTLs in patients with ATLL. We conclude that ATLL is not a tumor of FoxP3+ regulatory T cells, and that a population of FoxP3+ cells distinct from ATLL cells has regulatory functions and may impair the cell‐mediated immune response to HTLV‐1 in patients with ATLL. © 2009 UICC
Antagonism of chemokine receptor CXCR3 inhibits osteosarcoma metastasis to lungs
Authors: Pradelli Emmanuelle , Karimdjee‐Soilihi Babou , Michiels Jean‐François , Ricci Jean‐Ehrland , Millet Marie‐Ange , Vandenbos Fanny , Sullivan Timothy J. , Collins Tassie L. , Johnson Michael G. , Medina Julio C. , Kleinerman Eugenie S. , Schmid‐Alliana Annie , Schmid‐Antomarchi Heidy 
Published: June 2009

AbstractMetastasis continues to be the leading cause of mortality for patients with cancer. Several years ago, it became clear that chemokines and their receptors could control the tumor progress. CXCR3 has now been identified in many cancers including osteosarcoma and CXCR3 ligands were expressed by lungs that are the primary sites to which this tumor metastasize. This study tested the hypothesis that disruption of the CXCR3/CXCR3 ligands complexes could lead to a decrease in lungs metastasis. The experimental design involved the use of the CXCR3 antagonist, AMG487 and 2 murine models of osteosarcoma lung metastases. After tail vein injection of osteosarcoma cells, mice that were systematically treated with AMG487 according to preventive or curative protocols had a significant reduction in metastatic disease. Treatment of osteosarcoma cells in vitro with AMG487 led to decreased migration, decreased matrix metalloproteinase activity, decreased proliferation/survival and increased caspase‐independent death. Taken together, our results support the hypothesis that CXCR3 and their ligands intervene in the initial dissemination of the osteosarcoma cells to the lungs and stimulate the growth and expansion of the metastatic foci in later stages. Moreover, these studies indicate that targeting CXCR3 may specifically inhibit tumor metastasis without adversely affecting antitumoral host response. © 2009 UICC