bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac expression of the drosophila Transglutaminase (CG7356) gene is directly controlled by myocyte enhancer factor‐2
Authors: Iklé Jennifer , Elwell Jennifer A. , Bryantsev Anton L. , Cripps Richard M. 
Published: July 2008

AbstractThe myocyte enhancer factor‐2 (MEF2) family of transcription factors plays key roles in the activation of muscle structural genes. In Drosophila, MEF2 accumulates at high levels in the embryonic muscles, where it activates target genes throughout the mesoderm. Here, we identify the Transglutaminase gene (Tg; CG7356) as a direct transcriptional target of MEF2 in the cardiac musculature. Tg is expressed in cells forming the inflow tracts of the dorsal vessel, and we identify the enhancer responsible for this expression. The enhancer contains three binding sites for MEF2, and can be activated by MEF2 in tissue culture and in vivo. Moreover, loss of MEF2 function, or removal of the MEF2 binding sites from the enhancer, results in loss of Tg expression. These studies identify a new MEF2 target in the cardiac musculature. These studies provide a possible mechanism for the activation of transglutaminase genes. Furthermore, given the relevance of transglutaminase genes to human disease, these studies provide a possible mechanism for their activation. Developmental Dynamics 237:2090–2099, 2008. © 2008 Wiley‐Liss, Inc.
Functional characterization of lmo2‐Cre transgenic zebrafish
Authors: Wang Lei , Zhang Yong , Zhou Ting , Fu Yan‐Fang , Du Ting‐Ting , Jin Yi , Chen Yi , Ren Chun‐Guang , Peng Xiao‐Lan , Deng Min , Liu Ting Xi 
Published: July 2008

AbstractCre/loxP system is a powerful tool to manipulate the genome. Transgenic animals expressing Cre recombinase in specific tissues or cells have been widely used for conditional gene targeting, lineage tracing, and other genetic analyses. In zebrafish, the transgenic line with stable expression of Cre in specific tissues and cell subtypes has not been generated and its functional activity remains to be defined. Here we report the establishment of a stable transgenic fish Tg(zlmo2:Cre), which specifically expresses Cre in the primitive hematopoietic progenitors and vascular endothelial cells, under the control of lmo2 promoter. Our result shows that the Cre expression pattern recapitulates the endogenous lmo2 expression pattern during embryogenesis. Crossing of the Tg(zlmo2:Cre) line with another established transgenic reporter line Tg(zlmo2:loxP‐DsRed‐loxP‐EGFP), induces a robust recombination activity in hematopoietic progenitors and vascular endothelial cells. Thus, the Tg(zlmo2:Cre) transgenic line provides an invaluable tool to dissect genetic pathways in hematopoietic development and diseases. Developmental Dynamics 237:2139–2146, 2008. © 2008 Wiley‐Liss, Inc.
Engagement of Toll‐like receptor 2 in mouse macrophages infected with Mycobacterium avium induces non‐oxidative and TNF‐independent anti‐mycobacterial activity
Authors: Gomes M. Salomé , Sousa Fernandes Sofia , Cordeiro João V. , Silva Gomes Sandro , Vieira André , Appelberg Rui 
Published: July 2008

AbstractToll‐like receptor (TLR) 2 plays an important role in the immune response to mycobacterial infections, being required for optimal immunity against certain virulent Mycobacterium avium strains. Here we analyzed the role of TLR2 in the intra‐macrophagic growth of M. avium, using macrophages from TLR2‐deficient mice. We found that the engagement of TLR2/TLR6 and/or TLR2/TLR1 receptors induced bacteriostasis of M. avium inside bone marrow‐derived macrophages in a MyD88‐dependent way. Additionally, lipoproteins from the cell envelope of M. avium with a molecular mass of 20–25 kDa triggered this TLR2 pathway, leading to a decrease in the growth of the mycobacteria. Although TLR2 engagement induced the production of TNF, this cytokine as well as nitric oxide and superoxide molecules were not necessary for TLR2‐mediated bacteriostasis. Finally, TLR ligation did not induce the expression of the 47‐kDa guanosine triphosphatase (LRG‐47) but it promoted an increased maturation of the phagosome with regards to acquisition of LAMP1. Our data show that triggering TLR2 inhibited M. avium growth by an as‐yet‐unknown mechanism that may involve increased phagosome maturation.
Efficient antitumor immunity in a murine colorectal cancer model induced by CEA RNA‐electroporated B cells
Authors: Park Mi‐Young , Kim Hye‐Sung , Woo Sun‐Je , Kim Chang‐Hyun , Park Jung‐Sun , Sohn Hyun‐Jung , Kim Hyung‐Jin , Oh Seong‐Taek , Kim Tai‐Gyu 
Published: July 2008

AbstractRNA electroporation as a gene delivery method is more feasible and safer as compared with viral vectors. RNA‐loaded dendritic cells (DC) have been used to induce T cell responses against tumor rejection antigens and B cells can also act as antigen‐presenting cells for cellular vaccines. In this study, we compared B cells and DC, after electroporation with carcinoembryonic antigen (CEA) RNA, for their capacity to generate cytotoxic T lymphocytes and antitumor immunity. Vaccination using these B cells induced levels of IFN‐γ‐secreting T cells and cytotoxic T cells comparable to those induced by DC. Intravenous administration was the optimum route for the B cell vaccine, while subcutaneous administration was the optimum route for the DC vaccine. The B cell vaccine predominantly generated CEA‐specific CD4+ T cells, whereas the DC vaccine generated CD8+ T cells. Moreover, the B cell vaccine induced higher levels of anti‐CEA antibodies than the DC vaccine. A heterogeneous prime‐boost using B cells and DC failed to show any synergistic effects; however, the B cell vaccine did inhibit tumor growth and prolonged survival to a similar extent as the DC vaccine. Such RNA‐electroporated B cells may prove useful as cellular tumor vaccines with potential clinical application.
Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group 1 CD1 molecules
Authors: Kaser Arthur , Hava David L. , Dougan Stephanie K. , Chen Zhangguo , Zeissig Sebastian , Brenner Michael B. , Blumberg Richard S. 
Published: July 2008

AbstractLipid antigens are presented to T cells by the non‐polymorphic MHC class I‐related CD1 molecules. Microsomal triglyceride transfer protein (MTP) is an endoplasmic reticulum (ER)‐resident chaperone that has been shown to lipidate the group 2 CD1 molecule CD1d and thus to regulate its function. We now report that MTP also regulates the function of group 1 CD1 molecules CD1a, CD1b, and CD1c. Pharmacological inhibition of MTP in monocyte‐derived dendritic cells and lymphoblastoid B cell lines transfected with group 1 CD1 resulted in a substantial decrease in endogenous self lipid antigen presentation to several CD1‐restricted T cell lines. Silencing MTP expression in CD1c‐transfected HeLa cells similarly resulted in decreased self reactivity. Unexpectedly, inhibition of ER‐resident MTP, which was confirmed by confocal microscopy, also markedly decreased presentation of exogenous, endosomally loaded, mycobacterial lipid antigens by CD1a and CD1c to T cells. Thus, these studies indicate that MTP, despite its ER localization, regulates endogenous as well as exogenous lipid antigen presentation, and suggest a broad role for MTP in the regulation of CD1 antigen presentation.
Deficiency of Act1, a critical modulator of B cell function, leads to development of Sjögren's syndrome
Authors: Qian Youcun , Giltiay Natalia , Xiao Jianhua , Wang Yue , Tian Jun , Han Shuhua , Scott Martin , Carter Robert , Jorgensen Trine N. , Li Xiaoxia 
Published: July 2008

AbstractCD40L and B lymphocyte‐activating factor (BAFF), members of the TNF superfamily, play critical roles in B cell survival and activation, and in the regulation of humoral immunity. We previously reported that the adaptor molecule Act1 functions as a negative regulator of CD40‐ and BAFF‐mediated B cell survival. Here we demonstrated that mice deficient in Act1 developed systemic autoimmune disease with histological and serological features of human Sjögren's syndrome (SS), in association with systemic lupus erythematosus‐like nephritis. Analyses of Act1−/−CD40−/− and Act1−/−BAFF−/− double‐deficient mice revealed that Act1 regulates different stages of the disease development through its impact on both CD40‐ and BAFF‐mediated pathways. We found that Act1 modulates the survival of autoreactive B cells mainly through its negative regulatory role in BAFF‐mediated cell survival, while the effect of Act1 on autoantibody production is likely through modulation of CD40‐mediated T cell‐dependent antibody response. The impact of Act1 on both BAFF and CD40 pathways establishes Act1‐deficient mice as a unique model to study distinct steps of autoimmunity and regulation of self tolerance.
Inhibition of apoptosis in Bacteroides fragilis enterotoxin‐stimulated intestinal epithelial cells through the induction of c‐IAP‐2
Authors: Kim Jung Mogg , Lee Jin Young , Kim Yeong‐Jeon 
Published: July 2008

AbstractEnterotoxigenic Bacteroides fragilis produces an approximately 20‐kDa heat‐labile enterotoxin (BFT) that plays an essential role in generating mucosal inflammation. Although it is well known that proinflammatory signals are expressed in BFT‐stimulated intestinal epithelial cells, cell death processes have not been elucidated. BFT induced apoptosis in HT‐29 cells, but the apoptosis was first apparent 36 h after stimulation. During the early period of BFT stimulation, expression of cellular inhibitor of apoptosis protein‐2 (c‐IAP2) increased, and inhibition of c‐IAP2 augmented the apoptotic cell death. Inhibition of BFT‐induced COX‐2 expression decreased prostaglandin E2 (PGE2) production, which led not only to a decrease of c‐IAP2 activity but also to an enhancement of DNA fragmentation in the early period of BFT stimulation. Furthermore, apoptosis inhibition through PGE2 and c‐IAP2 was mainly regulated by a p38 mitogen‐activated protein kinase (MAPK). These results suggest that the inhibition of apoptosis may be mediated by a sequential pathway, including MAPK, COX‐2, PGE2 and c‐IAP2, in the early period of stimulation. The delay in the onset of epithelial cell apoptosis after enterotoxigenic B. fragilis infection may be important to the host since it can provides sufficient time for epithelial cells to generate signals for the activation of mucosal inflammation and it may increase the chances of bacterial colonization.
DNA fusion gene vaccination mobilizes effective anti‐leukemic cytotoxic T lymphocytes from a tolerized repertoire
Authors: Rice Jason , Dossett Michelle L. , Öhlén Claes , Buchan Sarah L. , Kendall Timothy J. , Dunn Stuart N. , Stevenson Freda K. , Greenberg Philip D. 
Published: July 2008

AbstractThe majority of known human tumor‐associated antigens derive from non‐mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide‐specific CTL. Key foreign sequences from tetanus toxin activate tolerance‐breaking CD4+ T cell help. Candidate MHC class I‐binding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia‐associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitope derived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag‐transgenic (gag‐Tg) mice. Vaccination with the construct induced epitope‐specific IFN‐γ‐producing CD8+ T cells in normal and gag‐Tg mice. The frequency and avidity of activated cells were reduced in gag‐Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag‐specific cytotoxicity in vitro and in vivo. Also, epitope‐specific CTL killed FBL‐3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti‐microbial T cell help to activate epitope‐specific polyclonal CD8+ T cell responses from a residual tolerized repertoire.
Dysregulation of the host mevalonate pathway during early bacterial infection activates human TCR γδ cells
Authors: Kistowska Magdalena , Rossy Emmanuel , Sansano Sebastiano , Gober Hans‐Jürgen , Landmann Regine , Mori Lucia , De Libero Gennaro 
Published: July 2008

AbstractPrimates, but not rodents, have T cell receptor Vγ9‐Vδ2 T cells bridging innate and adaptive antimicrobial immunity. This T cell population is activated by prenyl pyrophosphates isolated from microbial or eukaryotic cells. Although the microbial metabolites are more active than the cellular ones, their involvement in TCR γδ activation during infection has not been studied. Here, we show that, during the initial phases of infections withEscherichia coliandStaphylococcus aureus, TCR γδ cells are activated by endogenous mevalonate metabolites. Infections with low bacteria inocula up‐regulate the production and accumulation of host‐derived TCR γδ stimulatory antigens within 1 h, which is followed by a peak of TCR γδ cell activation at 5 h. Infections induce the accumulation and dephosphorylation of the hydroxymethylglutaryl‐coenzyme A reductase, the rate‐limiting enzyme of the mevalonate pathway, resulting in increased activity of this enzyme and in increased synthesis of intermediate metabolites. Thus, primates have evolved the ability to readily respond to bacterial infection by sensing the dysregulation of the mevalonate pathway within infected cells, as a mechanism of immediate antimicrobial immunity.Supporting Information for this article is available at http://www.wiley‐vch.de/contents/jc_2040/2008/38366_s.pdf
Evidence that the KIR2DS5 gene codes for a surface receptor triggering natural killer cell function
Authors: Chiesa Mariella Della , Romeo Elisa , Falco Michela , Balsamo Mirna , Augugliaro Raffaella , Moretta Lorenzo , Bottino Cristina , Moretta Alessandro , Vitale Massimo 
Published: July 2008

AbstractIn this study, after immunization with NK cells from a KIR2DS5+ donor and screening on cell transfectants expressing different members of the killer immunoglobulin‐like receptor (KIR) family, we generated a mAb, DF200, reacting with several KIR2D receptors including KIR2DL1/L2/L3, KIR2DS1/S2 and KIR2DS5. By the analysis of peripheral blood NK cells and in vitro derived NK cell clones, we have demonstrated for the first time that KIR2DS5 is expressed at the cell surface in discrete subsets of NK cells and, after DF200 mAb‐mediated engagement, can induce both cytotoxicity and cytokine release. Using co‐transfection and co‐immunoprecipitation, we found that KIR2DS5 associates with the DAP12 signaling polypeptide. Finally, soluble KIR2DS5‐Fc fusion protein does not bind to cell transfectants expressing different HLA‐C alleles, suggesting that, if KIR2DS5 does recognize HLA‐C molecules, this may only occur in the presence of certain peptides.
The Nlrp3 inflammasome is critical for aluminium hydroxide‐mediated IL‐1β secretion but dispensable for adjuvant activity
Authors: Franchi Luigi , Núñez Gabriel 
Published: July 2008

AbstractAluminum hydroxide (alum) is the most widely used adjuvant in human vaccines, but the immune mechanisms that are activated by alum remain poorly understood. Alum has recently been shown to promote caspase‐1 activation and IL‐1β secretion, but the cellular pathways involved remain elusive. Here we report that the release of IL‐1β triggered by alum is abrogated in macrophages deficient in the NLR family, pyrin domain containing 3 (Nlrp3) protein and the apoptosis‐associated speck‐like protein containing a caspase recruitment domain (Asc) but not the NLR family, CARD domain containing 4 (Nlrc4) protein. The requirement of the Nlrp3 inflammasome was specific for IL‐1β in that secretion of TNF‐α was independent of Nlrp3 or Asc. Consistently, processing of pro‐caspase‐1 induced by alum was abolished in macrophages lacking Nlrp3 or Asc. Unlike caspase‐1 processing and IL‐1β secretion triggered by LPS, alum‐mediated activation of the inflammasome did not require exogenous ATP. Importantly, induction of IgG production against human serum albumin by alum was unimpaired in mice deficient in Nlrp3. These results indicate that alum induces IL‐1β via the Nlrp3 inflammasome but this activity is dispensable for alum‐mediated adjuvant activity.See accompanying article: http://dx.doi.org/10.1002/eji.200838648
Intrasplenic trafficking of natural killer cells is redirected by chemokines upon inflammation
Authors: Grégoire Claude , Cognet Céline , Chasson Lionel , Coupet Charles‐Antoine , Dalod Marc , Reboldi Andrea , Marvel Jacqueline , Sallusto Federica , Vivier Eric , Walzer Thierry 
Published: July 2008

AbstractThe spleen is a major homing site for NK cells. How they traffic to and within this site in homeostatic or inflammatory conditions is, however, mostly unknown. Here we show that NK cells enter the spleen through the marginal sinus and home to the red pulp via a pertussis toxin‐insensitive mechanism. Upon inflammation induced by poly(I:C) injection or mouse cytomegalovirus infection, many NK cells left the red pulp while others transiently entered the white pulp, predominantly the T cell area. This migration was dependent on both CXCR3 and CCL5, suggesting a synergy between CXCR3 and CCR5, and followed the path lined by fibroblastic reticular cells. Thus, the entry of NK cells in the white pulp is limited by the expression of pro‐inflammatory chemokines. This phenomenon ensures the segregation of NK cells outside of the white pulp and might contribute to the control of immunopathology.
An Overview of Palladium Nanocatalysts: Surface and Molecular Reactivity
Authors: Durand Jérôme , Teuma Emmanuelle , Gómez Montserrat 
Published: July 2008

AbstractThe use of metallic nanoparticles in catalysis under homogeneous conditions leads to a discussion of their catalytic nature: whether the catalyst behaves as a molecular species or, on the contrary, the metallic surface is directly involved in the reactivity. This dilemma is intrinsically associated to the kinetic stability of the nanoclusters, favouring their agglomeration, and also to the formation of molecular species by reaction of the atoms placed at low‐coordination positions at the metallic surface. In particular, for palladium‐catalyzed processes, a large number of contributions have been reported in the last decade involving nanoparticles, but few of them analyze the mechanistic aspects. The present review aims to collect the more relevant research carried out in catalysis involving palladium nanoparticles in the liquid phase and addressing the nature of the catalytically active species. This kind of work is mainly focused on hydrogenation and C–C coupling processes.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Synthesis and Anion‐Binding Properties of Novel Redox‐Active Calixarene Receptors
Authors: Métay Estelle , Duclos Marie Christine , Pellet‐Rostaing Stéphane , Lemaire Marc , Schulz Jürgen , Kannappan Ramu , Bucher Christophe , Saint‐Aman Eric , Chaix Carole 
Published: July 2008

AbstractA novel synthetic approach towards redox‐active calixarene‐based receptors is described in which ferrocene fragments were introduced at the lower rim through anion‐binding urea or amide connections. These derivatives were prepared in one pot by treating an amine‐containing calixarene with ferrocenecarboxylic acid in the presence of diphenylphosphoryl azide and diisopropylethylamine. This method allows a convergent approach to these receptors and is readily adaptable to the introduction of other urea substituents. The anion‐binding properties of these artificial receptors have been revealed by NMR spectroscopy and thoroughly investigated by electrochemical methods. We have assessed the importance of the urea–phosphate bonds in the observed electrochemical response by studying receptors in which the ferrocene reporters and binding fragments are closely associated or fully disconnected through a long alkyl chain. The experimental results clearly show the utmost importance of ion‐pairing effects in the electrochemical recognition process, which account for most of the transduction signal in organic apolar media. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Remarkable Stability of Imino Macrocycles in Water
Authors: Saggiomo Vittorio , Lüning Ulrich 
Published: July 2008

AbstractImines 3, 5 and 7 generated from 4‐methoxypyridine‐2,6‐dicarbaldehyde (1) and several amines 2, 4 and 6 show a remarkable stability in water. The 18‐membered macrocyclic diimine 5 is stable and could be synthesized in good yield by using 2 equiv. of calcium ions as template in pure water, and even the non‐macrocyclic diimine 3 survives in water/methanol (50:50) without any template effect. In a mixture of pyridinedicarbaldehyde 1 and two glycol‐derived diamines 4 and 6, a calcium template ion selects the 18‐membered macrocycle 5 over the 20‐membered one (7). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Have newer cardiovascular drugs reduced hospitalization? Evidence from longitudinal country‐level data on 20 OECD countries, 1995–2003
Authors: Lichtenberg Frank R. 
Published: July 2008

AbstractThis study examines the effect of changes in the vintage distribution of cardiovascular system drugs on hospitalization and mortality due to cardiovascular disease using longitudinal country‐level data. The vintage of a drug is the first year in which it was marketed anywhere in the world. We use annual data on the utilization of over 1100 cardiovascular drugs (active ingredients) in 20 OECD countries during the period 1995–2003.Countries with larger increases in the share of cardiovascular drug doses that contained post‐1995 ingredients had smaller increases in the cardiovascular disease hospital discharge rate, controlling for the quantity of cardiovascular medications consumed per person, the use of other medical innovations (computed tomography scanners and magnetic resonance imaging units), potential risk factors (average consumption of calories, tobacco, and alcohol), and demographic variables (population size and age structure, income, and educational attainment). The estimates also indicate that the use of newer cardiovascular drugs has reduced the average length of stay and the age‐adjusted cardiovascular mortality rate, but not the number of potential years of life lost due to cardiovascular disease before age 70 per 100 000 population.The estimates indicate that if drug vintage had not increased during 1995–2004, hospitalization and mortality would have been higher in 2004. We estimate that per capita expenditure on cardiovascular hospital stays would have been 70% ($89) higher in 2004 had drug vintage not increased during 1995–2004. Per capita expenditure on cardiovascular drugs would have been lower in 2004 had drug vintage not increased during 1995–2004. However, our estimate of the increase in expenditure on cardiovascular hospital stays is about 3.7 times as large as our estimate of the reduction in per capita expenditure for cardiovascular drugs that would have occurred ($24). Copyright © 2008 John Wiley & Sons, Ltd.