bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of Cross-Priming of Naive CD8+ T Lymphocytes by Recombinant Bacillus Calmette-Guérin That Secretes Heat Shock Protein 70-Major Membrane Protein-II Fusion Protein
Authors: Mukai Tetsu , Maeda Yumi , Tamura Toshiki , Matsuoka Masanori , Tsukamoto Yumiko , Makino Masahiko 
Published: October 2009

AbstractBecause Mycobacterium bovis bacillus Calmette-Guérin (BCG) unconvincingly activates human naive CD8+ T cells, a rBCG (BCG-70M) that secretes a fusion protein comprising BCG-derived heat shock protein (HSP)70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was newly constructed to potentiate the ability of activating naive CD8+ T cells through dendritic cells (DC). BCG-70M secreted HSP70-MMP-II fusion protein in vitro, which stimulated DC to produce IL-12p70 through TLR2. BCG-70M-infected DC activated not only memory and naive CD8+ T cells, but also CD4+ T cells of both types to produce IFN-γ. The activation of these naive T cells by BCG-70M was dependent on the MHC and CD86 molecules on BCG-70M-infected DC, and was significantly inhibited by pretreatment of DC with chloroquine. Both brefeldin A and lactacystin significantly inhibited the activation of naive CD8+ T cells by BCG-70M through DC. Thus, the CD8+ T cell activation may be induced by cross-presentation of Ags through a TAP- and proteosome-dependent cytosolic pathway. When naive CD8+ T cells were stimulated by BCG-70M-infected DC in the presence of naive CD4+ T cells, CD62LlowCD8+ T cells and perforin-producing CD8+ T cells were efficiently produced. MMP-II-reactive CD4+ and CD8+ memory T cells were efficiently produced in C57BL/6 mice by infection with BCG-70M. These results indicate that BCG-70M activated DC, CD4+ T cells, and CD8+ T cells, and the combination of HSP70 and MMP-II may be useful for inducing better T cell activation.
Adoptive Transfer of T Lymphocytes Sensitized against the Prion Protein Attenuates Prion Invasion in Scrapie-Infected Mice
Authors: Gourdain Pauline , Grégoire Sylvie , Iken Saci , Bachy Véronique , Dorban Gauthier , Chaigneau Thomas , Debiec Hanna , Bergot Anne-Sophie , Renault Isabelle , Aucouturier Pierre , Carnaud Claude 
Published: October 2009

AbstractThere is to date no effective way of preventing or curing neurodegenerative diseases such as Alzheimer disease or transmissible spongiform encephalopathies. The idea of treating those conditions by immunological approaches has progressively emerged over the last ten years. Encouraging results have been reported in Alzheimer disease and in peripheral forms of mouse prion diseases following passive injection of Abs or active immunization against the peptides or proteins presumably at the origin of those disorders. Still, major difficulties persist due to some characteristics of those conditions such as slow evolution, brain location, uncertainties regarding precise pathogenic pathways, and, above all, the fact that the target Ag is self, meaning that it is poorly immunogenic and potentially harmful if tolerance was transgressed. To analyze some of those difficulties, we are developing adoptive cell transfer approaches. In this study, lymphocytes sensitized against the prion protein in nontolerant Prnp−/− mice were transferred into histocompatible wild-type recipients which were partly or totally devoid of their own lymphocytes. Under such conditions, we found that the engrafted T lymphocytes resisted peripheral tolerance, remained reactive for several months against epitopes of the prion protein, and significantly attenuated the progression of prions in secondary lymphoid organs with subsequent delay in the evolution of the neurological disease. Interestingly, those protective T lymphocytes secreted lymphokines and migrated more readily into the host CNS but did not appear to be engaged in cooperation with host B cells for Ab production.
Adenosine Blocks IFN-γ-Induced Phosphorylation of STAT1 on Serine 727 to Reduce Macrophage Activation
Authors: Barnholt Kimberly E. , Kota Rama S. , Aung Hnin Hnin , Rutledge John C. 
Published: October 2009

Abstract
Macrophages are activated by IFN-γ, a proinflammatory and proatherogenic cytokine that mediates its downstream effects primarily through STAT1. IFN-γ signaling induces phosphorylation of two STAT1 residues: Tyr701 (Y701), which facilitates dimerization, nuclear translocation, and DNA binding; and Ser727 (S727), which enables maximal STAT1 transcription activity. Immunosuppressive molecules such as adenosine in the cellular microenvironment can reduce macrophage inflammatory and atherogenic functions through receptor-mediated signaling pathways. We hypothesized that adenosine achieves these protective effects by interrupting IFN-γ signaling in activated macrophages. This investigation demonstrates that adding adenosine to IFN-γ-stimulated murine RAW 264.7 and human THP-1 macrophages results in unique modulation of STAT1 serine and tyrosine phosphorylation events. We show that adenosine inhibits IFN-γ-induced STAT1 S727 phosphorylation by &gt;30% and phosphoserine-mediated transcriptional activity by 58% but has no effect on phosphorylation of Y701 or receptor-associated JAK tyrosine kinases. Inhibition of the adenosine A3 receptor with a subtype-specific antagonist (MRS 1191 in RAW 264.7 cells and MRS 1220 in THP-1 cells) reverses this adenosine suppressive effect on STAT1 phosphoserine status by 25–50%. Further, RAW 264.7 A3 receptor stimulation with Cl-IB-MECA reduces IFN-γ-induced STAT1 transcriptional activity by 45% and STAT1-dependent gene expression by up to 80%. These data suggest that A3 receptor signaling is key to adenosine-mediated STAT1 modulation and anti-inflammatory action in IFN-γ-activated mouse and human macrophages. Because STAT1 plays a key role in IFN-γ-induced inflammation and foam cell transformation, a better understanding of the mechanisms underlying STAT1 deactivation by adenosine may improve preventative and therapeutic approaches to vascular disease.
Externally Triggered Egress Is the Major Fate of Toxoplasma gondii during Acute Infection
Authors: Tomita Tadakimi , Yamada Tatsuya , Weiss Louis M. , Orlofsky Amos 
Published: October 2009

Abstract
The apicomplexan parasite Toxoplasma gondii expands during acute infection via a cycle of invasion, intracellular replication, and lytic egress. Physiological regulation has not yet been demonstrated for either invasion or egress. We now report that, in contrast to cell culture systems, in which egress occurs only after five or more parasite divisions (2–3 days), intracellular residence is strikingly abbreviated in inflammatory cells in vivo, and early egress (after zero to two divisions) is the dominant parasite fate in acutely infected mice. Adoptive transfer experiments demonstrate rapid, reciprocal, kinetically uniform parasite transfer between donor and recipient compartments, with a t1/2 of ∼3 h. Inflammatory macrophages are major participants in this cycle of lytic egress and reinfection, which drives rapid macrophage turnover. Inflammatory triggering cells, principally macrophages, elicit egress in infected target macrophages, a process we term externally triggered egress (ETE). The mechanism of ETE does not require reactive oxygen or nitrogen species, the mitochondrial permeability transition pore, or a variety of signal transduction mediators, but is dependent on intracellular calcium and is highly sensitive to SB203580, an inhibitor of p38 MAPK as well as a related parasite-encoded kinase. SB203580 both inhibited the initiation of ETE and altered the progression of egress. Parasites recently completing a cycle of egress and reinfection were preferentially restricted in vivo, supporting a model in which ETE may favor host defense by a process of haven disruption. ETE represents a novel example of interaction between a parasite infectious cycle and host microenvironment.
Novel Role of Pin1 Induction in Type II Collagen-Mediated Rheumatoid Arthritis
Authors: Jeong Hye Gwang , Pokharel Yuba Raj , Lim Sung Chul , Hwang Yong Pil , Han Eun Hee , Yoon Jung-Hoon , Ahn Sang-Gun , Lee Kwang Yeol , Kang Keon Wook 
Published: October 2009

Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints and subsequent destruction of cartilage and bone. Inflammatory mediators such as PGs and proinflammatory cytokines contribute to RA progress. Pin1, a peptidyl prolyl isomerase, plays important pathophysiological roles in several diseases, including cancer and neurodegeneration. We found that both Pin1 and cyclooxygenase-2 (COX-2) were highly expressed in ankle tissues of type II collagen-induced RA mice. HTB-94 cells overexpressing Pin1 and primary cultured human chondrocytes showed increased basal expression of proinflammatory proteins (COX-2, inducible NO synthase, TNF-α, and IL-1β). Site-directed mutagenesis revealed that Pin1-mediated transcriptional activation of COX-2 was coordinately regulated by NF-κB, CREB, and C/EBP. Gel shift, reporter gene, and Western blot analyses confirmed that NF-κB, CREB, and C/EBP were consistently activated in chondrocytes overexpressing Pin1. Treatment of RA mice with juglone, a chemical inhibitor of Pin1, significantly reduced RA progress and COX-2 expression in the ankle tissues. Moreover, juglone dose dependently decreased the basal COX-2 expression in primary cultured chondrocytes from RA patients. These results demonstrate that Pin1 induction during RA progress stimulates proinflammatory protein expression by activating NF-κB, CREB, and C/EBP, and suggest that Pin1 is a potential therapeutic target of RA.
Apurinic/Apyrimidinic Endonuclease 1 Is a Key Modulator of Keratinocyte Inflammatory Responses
Authors: Lee Hye-Mi , Yuk Jae-Min , Shin Dong-Min , Yang Chul-Su , Kim Kwang-Kyu , Choi Dae-Kyoung , Liang Zhe-Long , Kim Jin-Man , Jeon Byeong Hwa , Kim Chang Deok , Lee Jeung-Hoon , Jo Eun-Kyeong 
Published: October 2009

Abstract
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1) functions in both DNA repair and redox signaling, making it an attractive emerging therapeutic target. However, the role of APE1 in cutaneous inflammatory responses is largely unknown. In this study, we report that APE1 is a key upstream regulator in TLR2-dependent keratinocyte inflammatory responses. We found that nuclear expression of APE1 in epidermal layers was markedly up-regulated in psoriatic skin. APE1 was essential for the transcriptional activation and nuclear translocation of hypoxia-inducible factor-1α and NF-κB, both of which are crucial for inflammatory signaling in keratinocytes. Moreover, APE1 played a crucial role in the expression of TLR2-mediated inflammatory mediators, including TNF-α, CXCL8, and LL-37, in HaCaT cells and human primary keratinocytes. Silencing of APE1 attenuated cyclin D1/cyclin-dependent kinase 4 expression and phosphorylation of ERK1/2 and Akt, thereby affecting keratinocyte proliferation. Importantly, TLR2-induced generation of reactive oxygen species contributed to the nuclear translocation and expression of APE1, suggesting an autoregulatory circuit in which the subcellular localization of APE1 is associated with the production of APE1 per se through reactive oxygen species-dependent signaling. Taken together, these findings establish a role for APE1 as a master regulator of TLR2-dependent inflammatory responses in human keratinocytes.
The Natural Cytotoxicity Receptor NKp46 Is Dispensable for IL-22-Mediated Innate Intestinal Immune Defense against Citrobacter rodentium
Authors: Satoh-Takayama Naoko , Dumoutier Laure , Lesjean-Pottier Sarah , Ribeiro Vera S. G. , Mandelboim Ofer , Renauld Jean-Christophe , Vosshenrich Christian A. J. , Di Santo James P. 
Published: October 2009

Abstract
Natural cytotoxicity receptors (including NKp30, NKp44, and NKp46 in humans and NKp46 in mice) are type I transmembrane proteins that signal NK cell activation via ITAM-containing adapter proteins in response to stress- and pathogen-induced ligands. Although murine NKp46 expression (encoded by Ncr1) was thought to be predominantly restricted to NK cells, the identification of distinct intestinal NKp46+ cell subsets that express the transcription factor Rorc and produce IL-22 suggests a broader function for NKp46 that could involve intestinal homeostasis and immune defense. Using mice carrying a GFP-modified Ncr1 allele, we found normal numbers of gut CD3−GFP+ cells with a similar cell surface phenotype and subset distribution in the absence of Ncr1. Splenic and intestinal CD3−NKp46+ cell subsets showed distinct patterns of cytokine secretion (IFN-γ, IL-22) following activation via NK1.1, NKp46, IL-12 plus IL-18, or IL-23. However, IL-22 production was sharply restricted to intestinal CD3−GFP+ cells with the CD127+NK1.1− phenotype and could be induced in an Ncr1-independent fashion. Because NKp46 ligands can trigger immune activation in the context of infectious pathogens, we assessed the response of wild-type and Ncr-1-deficient Rag2−/− mice to the enteric pathogen Citrobacter rodentium. No differences in the survival or clinical score were observed in C. rodentium-infected Rag2−/− mice lacking Ncr1, indicating that NKp46 plays a redundant role in the differentiation of intestinal IL-22+ cells that mediate innate defense against this pathogen. Our results provide further evidence for functional heterogeneity in intestinal NKp46+ cells that contrast with splenic NK cells.
Enterobacter sakazakii Targets DC-SIGN to Induce Immunosuppressive Responses in Dendritic Cells by Modulating MAPKs
Authors: Mittal Rahul , Bulgheresi Silvia , Emami Claudia , Prasadarao Nemani V. 
Published: October 2009

Abstract
Enterobacter sakazakii (ES) is an emerging pathogen that causes meningitis and necrotizing enterocolitis in infants. Dendritic cells (DCs) are professional phagocytic cells that play an essential role in host defense against invading pathogens; however, the interaction of ES with DCs is not known. In this study, we demonstrate that ES targets DC-specific ICAM nonintegrin (DC-SIGN) to survive in myeloid DCs for which outer membrane protein A (OmpA) expression in ES is critical, although it is not required for uptake. In addition, DC-SIGN expression was sufficient to cause a significant invasion by ES in HeLa cells and intestinal epithelial cells, which are normally not invaded by ES. OmpA+ ES prevented the maturation of DCs by triggering the production of high levels of IL-10 and TGF-β and by suppressing the activation of MAPKs. Pretreatment of DCs with Abs to IL-10 and TGF-β or of bacteria with anti-OmpA Abs significantly enhanced the maturation markers on DCs. Furthermore, DCs pretreated with various inhibitors of MAPKs prohibited the increased production of proinflammatory cytokines stimulated by LPS or OmpA− ES. LPS pretreatment followed by OmpA+ ES infection of DCs failed to induce maturation of DCs, indicating that OmpA+ ES renders the cells in immunosuppressive state to external stimuli. Similarly, OmpA+ ES-infected DCs failed to present Ag to T cells as indicated by the inability of T cells to proliferate in MLR. We conclude that ES interacts with DC-SIGN to subvert the host immune responses by disarming MAPK pathway in DCs.
Resistance to Vaccinia Virus Is Less Dependent on TNF under Conditions of Heterologous Immunity
Authors: Nie Siwei , Cornberg Markus , Selin Liisa K. 
Published: October 2009

Abstract
TNF has been shown to be important for controlling many pathogens. Here, we directly demonstrate using wild-type TNF−/− and TNFR1−/− mice that TNF does play a role in protection against vaccinia virus (VV) infection in naive mice. Since VV replication is also partially controlled in lymphocytic choriomeningitis virus (LCMV)-immune C57BL/6J mice through the process of heterologous immunity, we questioned whether TNF was required in mediating this protection. VV-infected LCMV-immune mice that were TNF-deficient as a consequence of genetic deletion or receptor blockade demonstrated normal recruitment and selective expansion of cross-reactive LCMV-specific memory CD8 T cells and controlled VV infection similar to LCMV-immune mice having TNF function. This indicates that neither TNF nor lymphotoxin, which uses the same receptor, was required in mediating protective heterologous immunity against VV. Indeed, prior immunity to LCMV made the role of TNF in protection against VV infection much less important, even under conditions of lethal dose inoculum. Thus, heterologous immunity may help explain why treatment of patients with anti-TNF compounds is reasonably well tolerated with relatively few infectious complications.
Activation of the Cholinergic Anti-Inflammatory System by Nicotine Attenuates Neuroinflammation via Suppression of Th1 and Th17 Responses
Authors: Nizri Eran , Irony-Tur-Sinai Michal , Lory Omer , Orr-Urtreger Avi , Lavi Ehud , Brenner Talma 
Published: October 2009

Abstract
The α7 nicotinic acetylcholine receptor (nAChR) was recently described as an anti-inflammatory target in both macrophages and T cells. Its expression by immune cells may explain the epidemiological data claiming a negative link between cigarette smoking and several inflammatory diseases. In this study, we determined the immunological effects of α7 nAChR activation by nicotine. Our results indicate that the α7 nAChR is expressed on the surface of CD4+ T cells and that this expression is up-regulated upon immune activation. Nicotine reduced T cell proliferation in response to an encephalitogenic Ag, as well as the production of Th1 (TNF-α and IFN-γ) and Th17 cytokines (IL-17, IL-17F, IL-21, and IL-22). IL-4 production was increased in the same setting. Attenuation of the Th1 and Th17 lineages was accompanied by reduced T-bet (50%) and increased GATA-3 (350%) expression. Overall, nicotine induced a shift to the Th2 lineage. However, α7−/−-derived T cells were unaffected by nicotine. Furthermore, nicotine reduced NF-κB-mediated transcription as measured by IL-2 and IκB transcription. In vivo, administration of nicotine (2 mg/kg s.c.) suppressed the severity of CD4+ T cell-mediated disease experimental autoimmune encephalomyelitis. α7−/− mice were refractory to nicotine treatment, although disease severity in those animals was reduced, due to impairment in Ag presentation. Accordingly, CD4+ and CD11b+ cells infiltration into the CNS, demyelination, and axonal loss were reduced. Our data implicate a role for the α7 nAChR in immune modulation and suggest that α7 nAChR agonists may be effective in the treatment of inflammatory disorders.
Synthesis of Biaryls and Aryl Ketones via Microwave‐Assisted Decarboxylative Cross‐Couplings
Authors: Gooßen Lukas J. , Zimmermann Bettina , Linder Christophe , Rodríguez Nuria , Lange Paul P. , Hartung Jens 
Published: October 2009

AbstractA protocol for the microwave‐assisted decarboxylative cross‐couplings of carboxylic acid salts with aryl halides has been developed that allows the synthesis of various biaryls and aryl ketones in high yields. After careful adaptation of the bimetallic catalyst system and reaction conditions, these mechanistically complex transformations can now be performed within only five minutes in concentrated solution in a sealed vessel. This greatly simplified reaction protocol is ideally suited for applications in parallel synthesis and drug discovery.
First Copper‐Catalyzed Intramolecular Amidation in Substituted 4‐Iodopyrazoles Leading to the Synthesis of Pyrazolo[4,3‐b]‐ pyridin‐5‐ones
Authors: Nag Somnath , Nayak Maloy , Batra Sanjay 
Published: October 2009

AbstractAn unprecedented copper‐catalyzed intramolecular amidation of substituted 4‐iodopyrazoles generated either via Baylis–Hillman or Horner–Wadsworth–Emmons chemistry for the synthesis of pyrazolo[4,3‐b]pyridine‐5‐ones is described. In addition, the effect of the stereochemistry of the acrylamide on the cross‐coupling reaction has been investigated and it is demonstrated that only the Z‐isomer is favoured to undergo the intramolecular cyclization.
Sedimentation behavior of droplets for the reactive extraction of zinc with D2EHPA
Authors: Kalem Murat , Altunok Mehmet Yücel , Pfennig Andreas 
Published: October 2009

AbstractThe sedimentation characteristics of the reactive standard test system zinc + D2EHPA are investigated in this work. Experiments with single droplets rising in a stagnant continuous phase have been carried out. The concentration of D2EHPA, zinc, and sulfuric acid as well as the diameter of the droplets are varied. The velocity of droplets is observed to be transient for several seconds. High mass‐transfer rates increase the velocity of single droplets for the case of reactive extraction whereas for physical systems contrary behavior is observed. Therefore, droplets seem to behave principally different in reactive and physical extraction. This is explained by the interfacially active properties of D2EHPA. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Simple model to predict gel formation in olefin‐diene copolymerizations catalyzed by constrained‐geometry complexes
Authors: Guzmán Job D. , Arriola Daniel J. , Karjala Teresa , Gaubert Joshua , Kolthammer Brian W. S. 
Published: October 2009

AbstractWe have developed an analytical model to predict the onset of gel formation in ethylene/1‐octene/1,9‐decadiene terpolymerizations using constrained‐geometry catalysts. The model relies on three kinetic parameters to characterize the catalyst response. Polymer resins have been synthesized in a continuous stirred‐tank reactor to determine the model parameters, and to validate the model predictions for polymer properties and for the onset of gel formation and reactor fouling. The experimental results indicate that the free double bonds in 1,9‐decadiene are as reactive as those found in 1‐octene, and that the reactivity of 1,9‐decadiene double bonds decreases after the 1,9‐decadiene molecules become part of a polymer chain. The model predictions of polymer properties agree well with chromatographic, density, and mass‐balance data. Moreover, the model was successful in preventing unintended reactor fouling during the duration of the experimental campaign. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Experimental validation of CFD simulations of a lab‐scale fluidized‐bed reactor with and without side‐gas injection
Authors: Min Jian , Drake Joshua B. , Heindel Theodore J. , Fox Rodney O. 
Published: October 2009

AbstractFluidized‐bed reactors are widely used in the biofuel industry for combustion, pyrolysis, and gasification processes. In this work, a lab‐scale fluidized‐bed reactor without and with side‐gas injection and filled with 500–600 μm glass beads is simulated using the computational fluid dynamics (CFD) code Fluent 6.3, and the results are compared to experimental data obtained using pressure measurements and 3D X‐ray computed tomography. An initial grid‐dependence CFD study is carried out using 2D simulations, and it is shown that a 4‐mm grid resolution is sufficient to capture the time‐ and spatial‐averaged local gas holdup in the lab‐scale reactor. Full 3D simulations are then compared with the experimental data on 2D vertical slices through the fluidized bed. Both the experiments and CFD simulations without side‐gas injection show that in the cross section of the fluidized bed there are two large off‐center symmetric regions in which the gas holdup is larger than in the center of the fluidized bed. The 3D simulations using the Syamlal‐O'Brien and Gidaspow drag models predict well the local gas holdup variation throughout the entire fluidized bed when compared to the experimental data. In comparison, simulations with the Wen‐Yu drag model generally over predict the local gas holdup. The agreement between experiments and simulations with side‐gas injection is generally good, where the side‐gas injection simulates the immediate volatilization of biomass. However, the effect of the side‐gas injection extends further into the fluidized bed in the experiments as compared to the simulations. Overall the simulations under predict the gas dispersion rate above the side‐gas injector. © 2009 American Institute of Chemical Engineers AIChE J, 2010