bluuebunny/crossref_metadata_2025_split huggingface dataset:
Major Role of γδ T Cells in the Generation of IL-17+ Uveitogenic T Cells
Authors: Cui Yan , Shao Hui , Lan Chen , Nian Hong , O'Brien Rebecca L. , Born Willi K. , Kaplan Henry J. , Sun Deming 
Published: June 2009

Abstract
We show that in vitro activation of interphotoreceptor retinoid-binding protein (IRBP)-specific T cells from C57BL/6 mice immunized with an uveitogenic IRBP peptide (IRBP1–20) under TH17-polarizing conditions is associated with increased expansion of T cells expressing the γδ TCR. We also show that highly purified αβ or γδ T cells from C57BL/6 mice immunized with IRBP1–20 produced only small amounts of IL-17 after exposure to the immunizing Ag in vitro, whereas a mixture of the same T cells produced greatly increased amounts of IL-17. IRBP-induced T cells from IRBP-immunized TCR-δ−/− mice on the C57BL/6 genetic background produced significantly lower amounts of IL-17 than did wild-type C57BL/6 mice and had significantly decreased experimental autoimmune uveitis-inducing ability. However, reconstitution of the TCR-δ−/− mice before immunization with a small number of γδ T cells from IRBP-immunized C57BL/6 mice restored the disease-inducing capability of their IRBP-specific T cells and greatly enhanced the generation of IL-17+ T cells in the recipient mice. Our study suggests that γδ T cells are important in the generation and activation of IL-17-producing autoreactive T cells and play a major role in the pathogenesis of experimental autoimmune uveitis.
Multivalent Binding of Carbohydrates by the Human α-Defensin, HD5
Authors: Lehrer Robert I. , Jung Grace , Ruchala Piotr , Andre Sabine , Gabius Hans J. , Lu Wuyuan 
Published: June 2009

Abstract
Four of the six human α-defensins (human neutrophil peptides 1–3 and human α-defensin 5; HD5) have a lectin-like ability to bind glycosylated proteins. Using HD5 as a model, we applied surface plasmon resonance techniques to gain insights into this property. HD5 bound natural glycoproteins &gt; neoglycoproteins based on BSA &gt; nonglycosylated BSA ≫ free sugars. The affinity of HD5 for simple sugars covalently bound to BSA was orders of magnitude greater than its affinity for the same sugars in solution. The affinity of HD5 for protein-bound carbohydrates resulted from multivalent interactions which may also involve noncarbohydrate residues of the proteins. HD5 showed concentration-dependent self-association that began at submicromolar concentrations and proceeded to dimer and tetramer formation at concentrations below 5 μM. The (R9A, R28A) and (R13A, R32A) analogs of HD5 showed greatly reduced self-association as well as minimal binding to BSA and to BSA-affixed sugars. From this and other evidence, we conclude that the extensive binding of HD5 to (neo)glycoproteins results from multivalent nonspecific interactions of individual HD5 molecules with carbohydrate and noncarbohydrate moieties of the target molecule and that the primary binding events are magnified and enhanced by subsequent in situ assembly and oligomerization of HD5. Self-association and multivalent binding may play integral roles in the ability of HD5 to protect against infections caused by viruses and other infectious agents.
Aberrant Tissue Localization of Fungus-Specific CD4+ T Cells in IL-10-Deficient Mice
Authors: Rivera Amariliz , Collins Nichole , Stephan Matthias T. , Lipuma Lauren , Leiner Ingrid , Pamer Eric G. 
Published: June 2009

Abstract
Aspergillus fumigatus, a common environmental fungus, can cause lethal invasive infections in immunocompromised hosts. In immunocompetent individuals, however, inhaled A. fumigatus spores prime CD4+ T cells and activate immune responses that prevent invasive infection. Calibration of inflammatory responses to levels that prevent fungal invasion without inducing collateral tissue damage is essential for host survival, but the underlying regulatory mechanisms remain undefined. Although IL-10 is a validated regulatory cytokine that suppresses immune responses, and IL-10 deficiency or blockade generally enhances immune responses, we find that A. fumigatus-specific T cell frequencies are markedly reduced in airways of IL-10-deficient mice. T cell priming, proliferation, and survival were unaffected by IL-10 deficiency and did not account for decreased frequencies of A. fumigatus-specific T cells in the airways of IL-10-deficient mice. Instead, IL-10 deficiency results in redistribution of A. fumigatus-specific T cells from infected lungs to the gut, a process that is reversed by antibiotic-mediated depletion of intestinal microbes. Our studies demonstrate that disregulated immune responses in the gut can result in dramatic redistribution of pathogen-specific T cells within the host.
The Cytoplasmic Tail of the T Cell Receptor CD3 ε Subunit Contains a Phospholipid-Binding Motif that Regulates T Cell Functions
Authors: DeFord-Watts Laura M. , Tassin Tara C. , Becker Amy M. , Medeiros Jennifer J. , Albanesi Joseph P. , Love Paul E. , Wülfing Christoph , van Oers Nicolai S. C. 
Published: June 2009

Abstract
The CD3 ε subunit of the TCR complex contains two defined signaling domains, a proline-rich sequence and an ITAM. We identified a third signaling sequence in CD3 ε, termed the basic-rich stretch (BRS). Herein, we show that the positively charged residues of the BRS enable this region of CD3 ε to complex a subset of acidic phospholipids, including PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P3, and PI(4,5)P2. Transgenic mice containing mutations of the BRS exhibited varying developmental defects, ranging from reduced thymic cellularity to a complete block in T cell development. Peripheral T cells from BRS-modified mice also exhibited several defects, including decreased TCR surface expression, reduced TCR-mediated signaling responses to agonist peptide-loaded APCs, and delayed CD3 ε localization to the immunological synapse. Overall, these findings demonstrate a functional role for the CD3 ε lipid-binding domain in T cell biology.
SHIP1 Is a Repressor of Mast Cell Hyperplasia, Cytokine Production, and Allergic Inflammation In Vivo
Authors: Haddon D. James , Antignano Frann , Hughes Michael R. , Blanchet Marie-Renée , Zbytnuik Lori , Krystal Gerald , McNagny Kelly M. 
Published: June 2009

Abstract
SHIP1 inhibits immune receptor signaling through hydrolysis of the PI3K product phosphatidylinositol 3,4,5-trisphosphate, forming phosphatidylinositol 3,4-bisphosphate. In mast cells, SHIP1 represses FcεRI- and cytokine-mediated activation in vitro, but little is known regarding the function of SHIP1 in mast cells in vivo or the susceptibility of Ship1−/− mice to mast cell-associated diseases. In this study, we found that Ship1−/− mice have systemic mast cell hyperplasia, increased serum levels of IL-6, TNF, and IL-5, and heightened anaphylactic response. Further, by reconstituting mast cell-deficient mice with Ship1+/+ or Ship1−/− mast cells, we found that the above defects were due to loss of SHIP1 in mast cells. Additionally, we found that mice reconstituted with Ship1−/− mast cells suffered worse allergic asthma pathology than those reconstituted with Ship1+/+ mast cells. In summary, our data show that SHIP1 represses allergic inflammation and mast cell hyperplasia in vivo and exerts these effects specifically in mast cells.
Cutting Edge: Rapid and Efficient In Vivo Cytotoxicity by Cytotoxic T Cells Is Independent of Granzymes A and B
Authors: Regner Matthias , Pavlinovic Lisa , Koskinen Aulikki , Young Nicolie , Trapani Joseph A. , Müllbacher Arno 
Published: June 2009

Abstract
Cytotoxic T (Tc) cells lyse target cells via exocytosis of granules containing perforin (perf) and granzymes (gzm). In vitro, gzm delivery into the target cell cytosol results in apoptosis, and in the absence of gzm A and B the induction of apoptosis is severely impaired. However, using in vivo Tc cell killing assays, we find that virus-immune, gzm A × B-deficient (gzmA×B−/−) mice are competent to eliminate adoptively transferred target cells pulsed with an immunodominant Tc cell determinant as rapidly and completely as their wild-type counterparts. Specific target cell elimination occurred with similar kinetics in both spleen and lymph nodes. Thus, neither gzmA nor gzmB are required for rapid and efficient in vivo cytotoxicity by Tc cells.
Successful Treatment of Bacterial Infection Hinders Development of Acquired Immunity
Authors: Griffin Amanda , Baraho-Hassan Dahabo , McSorley Stephen J. 
Published: June 2009

Abstract
Antibiotics are routinely used to control bacterial infection, but the acquisition of acquired immunity following successful treatment has rarely been examined. We developed a model that allows visualization of acquired immunity during and following antibiotic treatment of typhoid. Pathogen-specific humoral and cellular immune responses were activated rapidly in antibiotic-treated mice, but were not sustained after successful antibiotic treatment and did not confer protection to secondary infection. In marked contrast, pathogen-specific Th1 and Ab responses matured over several weeks following immunization with a live vaccine strain. The deficiency in protective immunity following antibiotic treatment could be overcome by administering flagellin during antibiotic therapy. Thus, development of protective immunity is hindered by rapid therapeutic elimination of bacteria, but can be overcome by providing additional inflammatory and/or antigenic stimuli.
Prostaglandin E2 Differentially Modulates Proinflammatory/Prodestructive Effects of TNF-α on Synovial Fibroblasts via Specific E Prostanoid Receptors/cAMP
Authors: Kunisch Elke , Jansen Anne , Kojima Fumiaki , Löffler Ivonne , Kapoor Mohit , Kawai Shinichi , Rubio Ignacio , Crofford Leslie J. , Kinne Raimund W. 
Published: June 2009

AbstractThe present study investigated the influence of PGE2, E prostanoid (EP) receptors, and their signaling pathways on matrix metalloproteinase (MMP)-1 and IL-6 expression in synovial fibroblasts (SFs) from rheumatoid arthritis (RA) patients. RASFs expressed all four EP receptors, with selective induction of EP2 by TNF-α. TNF-α time-dependently increased intracellular cAMP/protein kinase A signaling (maximum, 6–12 h) and PGE2 secretion (maximum, 24 h). PGE2 and the EP2 agonists butaprost or ONO-AE1-259 ((16)-9-deoxy-9β-chloro-15-deoxy-16-hydroxy-17,17-trimethylene-19,20-didehydro PGE1), in turn, induced a rapid, time-dependent (maximum, 15–30 min) increase of cAMP. Additionally, cyclooxygenase-2 inhibition by NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide) reduced the TNF-α-induced increase in IL-6 mRNA/protein, which was restored by stimulation with PGE2 or EP2, EP3, and EP4 agonists. In contrast, TNF-α-induced MMP-1 secretion was not influenced by NS-398 and diminished by PGE2 via EP2. Finally, 3-isobutyl-1-methylxanthine enhanced the effects of PGE2 on MMP-1, but not on IL-6 mRNA. In conclusion, PGE2 differentially affects TNF-α-induced mRNA expression of proinflammatory IL-6 and prodestructive MMP-1 regarding the usage of EP receptors and the dependency on cAMP. Although specific blockade of EP2 receptors is considered a promising therapeutic strategy in RA, opposite regulation of proinflammatory IL-6 and prodestructive MMP-1 by PGE2 via EP2 may require more complex approaches to successfully inhibit the cyclooxygenase-1/2 cAMP axis.
Cytokine-Dependent Modification of IL-12p70 and IL-23 Balance in Dendritic Cells by Ligand Activation of Vα24 Invariant NKT Cells
Authors: Uemura Yasushi , Liu Tian-Yi , Narita Yayoi , Suzuki Motoharu , Nakatsuka Ryusuke , Araki Tomoyuki , Matsumoto Masahito , Iwai Leo Kei , Hirosawa Narumi , Matsuoka Yoshikazu , Murakami Mari , Kimura Takashi , Hase Makoto , Kohno Hirao , Sasaki Yutaka , Ichihara Yasuko , Ishihara Osamu , Kikuchi Hirosato , Sakamoto Yasushi , Jiao Shun-Chang , Senju Satoru , Sonoda Yoshiaki 
Published: June 2009

Abstract
CD1d-restricted invariant NKT (iNKT) cells play crucial roles in various types of immune responses, including autoimmune diseases, infectious diseases and tumor surveillance. The mechanisms underlying their adjuvant functions are well understood. Nevertheless, although IL-4 and IL-10 production characterize iNKT cells able to prevent or ameliorate some autoimmune diseases and inflammatory conditions, the precise mechanisms by which iNKT cells exert immune regulatory function remain elusive. This study demonstrates that the activation of human iNKT cells by their specific ligand α-galactosylceramide enhances IL-12p70 while inhibiting the IL-23 production by monocyte-derived dendritic cells, and in turn down-regulating the IL-17 production by memory CD4+ Th cells. The ability of the iNKT cells to regulate the differential production of IL-12p70/IL-23 is mainly mediated by a remarkable hallmark of their function to produce both Th1 and Th2 cytokines. In particular, the down-regulation of IL-23 is markedly associated with a production of IL-4 and IL-10 from iNKT cells. Moreover, Th2 cytokines, such as IL-4 and IL-13 play a crucial role in defining the biased production of IL-12p70/IL-23 by enhancement of IL-12p70 in synergy with IFN-γ, whereas inhibition of the IFN-γ-promoted IL-23 production. Collectively, the results suggest that iNKT cells modify the IL-12p70/IL-23 balance to enhance the IL-12p70-induced cell-mediated immunity and suppress the IL-23-dependent inflammatory pathologies. These results may account for the long-appreciated contrasting beneficial and adverse consequence of ligand activation of iNKT cells.
IL-23 Promotes the Production of IL-17 by Antigen-Specific CD8 T Cells in the Absence of IL-12 and Type-I Interferons
Authors: Curtis Meredith M. , Way Sing Sing , Wilson Christopher B. 
Published: June 2009

Abstract
In contrast to CD4 T cells, CD8 T cells inherently differentiate into IFN-γ-producing effectors. Accordingly, while generation of IFN-γ-producing Th1 CD4 T cells was profoundly impaired in mice deficient for both type-I IFN and IL-12 signaling in response to infection with Listeria monocytogenes, generation of Ag-specific, IFN-γ-producing CD8 T cells was unimpaired. However, a fraction of these CD8 T cells also produced IL-17 in an IL-23-dependent manner. Furthermore, the addition of IL-23 in vitro was sufficient for some naive CD8 T cells to differentiate into IFN-γ/IL-17 dual-producing cells and was associated with increased expression of ROR-γt and ROR-α. Addition of IL-6 and TGF-β to IL-23 further augmented ROR-γt and ROR-α expression and suppressed Eomes expression, thereby enhancing IL-17 production by CD8 T cells. A loss of cytotoxic function accompanied the production of IL-17, as the addition of IL-6 and TGF-β resulted in a marked reduction of granzyme B and perforin expression. Thus, CD8 T cells retain sufficient plasticity to respond to environmental cues and can acquire additional effector functions in response to their environmental context.
Links between habitat degradation, and social group size, ranging, fecundity, and parasite prevalence in the Tana River mangabey (Cercocebus galeritus)
Authors: Mbora David N.M. , Wieczkowski Julie , Munene Elephas 
Published: June 2009

AbstractWe investigated the effects of anthropogenic habitat degradation on group size, ranging, fecundity, and parasite dynamics in four groups of the Tana River mangabey (Cercocebus galeritus). Two groups occupied a forest disturbed by human activities, while the other two occupied a forest with no human disturbance. We predicted that the groups in the disturbed forest would be smaller, travel longer distances daily, and have larger home ranges due to low food tree abundance. Consequently, these groups would have lower fecundity and higher parasite prevalence and richness (number of parasite species). We measured the abundance of food trees and anthropogenic activity in the forests, the groups' daily travel distances and home range sizes, and censused social groups over 12 months. We also analyzed fecal samples for gastrointestinal parasites from three of the groups. The disturbed forest had a lower abundance of food trees, and groups in this forest traveled longer distances, had larger home range sizes, were smaller, and had lower fecundity. The groups in the disturbed forest had higher, although not statistically significant, parasite prevalence and richness. This study contributes to a better understanding of how anthropogenic habitat change influences fecundity and parasite infections in primates. Our results also emphasize the strong influence of habitat quality in determining daily travel distance and home range size in primates. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.
Synthesis, Antibacterial and Antifungal Activities of Novel 1,2,4‐Triazolium Derivatives
Authors: Luo Yan , Lu Yi‐Hui , Gan Lin‐Ling , Zhou Cheng‐He , Wu Jun , Geng Rong‐Xia , Zhang Yi‐Yi 
Published: June 2009

AbstractA series of novel 1,2,4‐triazolium derivatives was synthesized starting from commercially available 1H‐1,2,4‐triazole, 2,4‐dichlorobenzyl chloride, or 2,4‐difluorobenzyl bromide. Their antibacterial and antifungal activities were evaluated against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Bacillus proteus, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans ATCC 76615, and Aspergillus fumigatus. All structures of the new compounds were confirmed by NMR, IR, and MS spectra, and elemental analyses. The antimicrobial tests showed that most of synthesized triazolium derivatives exhibit significant antibacterial and antifungal activities in vitro. 1‐(2,4‐Difluorobenzyl)‐4‐dodecyl‐1H‐1,2,4‐triazol‐4‐ium bromide and 1‐(2,4‐Dichlorobenzyl)‐4‐dodecyl‐1H‐1,2,4‐ triazol‐4‐ium bromide were the most potent compounds against all tested strains with the MIC values ranging from 1.05 to 8.38 μM. They exhibited much stronger activities than the standard drugs chloramphenicol and fluconazole which are in clinical use. The results also showed that the antimicrobial activities of triazolium derivatives depend upon the type of substituent, the length of the alkyl chain, and the number of triazolium rings.
Design, Synthesis, and Biological Evaluation of Prenylated Chalcones as Vasorelaxant Agents
Authors: Dong Xiaowu , Chen Jing , Jiang Chaoyi , Liu Tao , Hu Yongzhou 
Published: June 2009

AbstractFive prenylated chalcones and one allylated chalcone were prepared according to the analysis based on support vector machine (SVM) classification model. Most of the synthesized chalcones showed potent vasorelaxant activities through evaluation in aortic rings with the endothelium pre‐contracted by phenylephrine (PE), indicating that the experimental activities were in good agreement with the theoretical ones. Structure‐activity relationship of these compounds showed that the substituent pattern and number of hydroxyl groups were crucial for their vasorelaxant activities and that the replacement of prenyl group with allyl group retained the potent activity.
Synthesis and Antibacterial Activities of Eperezolid Analogs with Glycinyl Substitutions
Authors: Wang Xiao‐Jun , Wu Ning , Du Guang‐Jian , Zhao Shuang‐Qi , Yan Ming , Gu Lian‐Quan 
Published: June 2009

AbstractA series of eperezolid analogs with glycinyl substitutions were prepared and their antibacterial activities were studied against a panel of susceptible and resistant Gram‐positive bacteria. The compounds with N‐arylacyl or N‐heteroarylacyl glycinyl structural units showed good antibacterial activities. The compounds 11b, 11c, and 11e were twofold more active than linezolid against Staphylococcus epidermidis and Enterococcus faecalis. Several pyridine analogs were also prepared and found to have poor antibacterial activity against most of the tested Gram‐positive bacteria, however, one of the compounds 12e showed very high activity against Enterococcus faecalis.
Design of tRNALys3 Ligands: Fragment Evolution and Linker Selection Guided by NMR Spectroscopy
Authors: Chung Florence , Tisné Carine , Lecourt Thomas , Seijo Bili , Dardel Frédéric , Micouin Laurent 
Published: June 2009

AbstractA fragment‐based approach for the synthesis of ligands of tRNALys3, the HIV reverse‐transcription primer, is described. The use of NMR spectroscopy has proved to be very useful in this approach, not only to detect low‐affinity complexes between small compounds and RNA, but also to provide information on their binding mode and on the way they can be connected. This NMR‐spectroscopy‐guided analysis enabled us to design micromolar ligands after the optimisation and connection of millimolar fragments with an appropriate linker. The influence of the linker region on the binding affinity and selectivity outlines the importance of having a flexible assemblage strategy with a variety of linkers in such an approach.
Emissive or Nonemissive? A Theoretical Analysis of the Phosphorescence Efficiencies of Cyclometalated Platinum(II) Complexes
Authors: Tong Glenna So‐Ming , Che Chi‐Ming 
Published: June 2009

AbstractWe herein report a theoretical analysis based on a density functional theory/time‐dependent density functional theory (DFT/TDDFT) approach to understand the different phosphorescence efficiencies of a family of cyclometalated platinum(II) complexes: [Pt(NCN)Cl] (1; NCN=1,3‐bis(2‐pyridyl)phenyl−), [Pt(CNN)Cl] (2; CNN=6‐phenyl‐2,2′‐bipyridyl−), [Pt(CNC)(CNPh)] (3; CNC=2,6‐diphenylpyridyl2−), [Pt(R‐CNN)Cl] (4; R‐CNN=3‐(6′‐(2′′‐naphthyl)‐2′‐pyridyl)isoquinolinyl−), and [Pt(R‐CNC)(CNPh)] (5; R‐CNC=2,6‐bis(2′‐naphthyl)pyridyl2−). By considering both the spin–orbit coupling (SOC) and the electronic structures of these complexes at their respective optimized singlet ground (S0) and first triplet (${{\rm T}{{1\hfill \atop {\rm opt}\hfill}}}$) excited states, we were able to rationalize the experimental findings that 1) 1 is a strong emitter while its isomer 2 is only weakly emissive in CH2Cl2 solution at room temperature; 2) although the cyclometalated ligand of 3 has a higher ligand‐field strength than that of 1, 3 is nonemissive in CH2Cl2 solution at 298 K; and 3) extension of π conjugation at the lateral aryl rings of the cyclometalated ligands of 2 and 3 to give 4 and 5, respectively, leads to increased emission quantum yields under the same conditions. We found that Jahn–Teller and pseudo‐Jahn–Teller effects are operative in complexes 2 and 3, respectively, on going from the optimized S0 ground state to the optimized ${{\rm T}{{1\hfill \atop {\rm opt}\hfill}}}$ excited state, and thus lead to large excited‐state structural distortions and hence fast nonradiative decay. Furthermore, a strong‐field ligand may push the two different occupied d orbitals so far apart that the SOC effect is small and the radiative decay rate is slow. This work is an example of electronic‐structure‐driven tuning of the phosphorescence efficiency, and the DFT/TDDFT approach is demonstrated to be a versatile tool for the design of phosphorescent materials with target characteristics.
Multicomponent Supramolecular Systems: Self‐Organization in Coordination‐Driven Self‐Assembly
Authors: Zheng Yao‐Rong , Yang Hai‐Bo , Ghosh Koushik , Zhao Liang , Stang Peter J. 
Published: June 2009

AbstractThe self‐organization of multicomponent supramolecular systems involving a variety of two‐dimensional (2 D) polygons and three‐dimensional (3 D) cages is presented. Nine self‐organizing systems, SS1–SS9, have been studied. Each involves the simultaneous mixing of organoplatinum acceptors and pyridyl donors of varying geometry and their selective self‐assembly into three to four specific 2 D (rectangular, triangular, and rhomboid) and/or 3 D (triangular prism and distorted and nondistorted trigonal bipyramidal) supramolecules. The formation of these discrete structures is characterized using NMR spectroscopy and electrospray ionization mass spectrometry (ESI‐MS). In all cases, the self‐organization process is directed by: 1)  the geometric information encoded within the molecular subunits and 2) a thermodynamically driven dynamic self‐correction process. The result is the selective self‐assembly of multiple discrete products from a randomly formed complex. The influence of key experimental variables ‐ temperature and solvent ‐ on the self‐correction process and the fidelity of the resulting self‐organization systems is also described.