bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of Bap31 and MHC Class I Molecules and Their Traffic Out of the Endoplasmic Reticulum
Authors: Abe Fumiyoshi , Van Prooyen Nancy , Ladasky John J. , Edidin Michael 
Published: April 2009

Abstract
The endoplasmic reticulum (ER) protein Bap31 associates with nascent class I MHC molecules. It appears to mediate the export of class I MHC molecules from the ER and may also be involved in their quality control. In this study, we use Förster resonance energy transfer and quantitative fluorescence imaging to show that in human, HeLa cells, Bap31 clusters with MHC class I (HLA-A2) molecules in the ER, and traffics via export vesicles to the ER/Golgi intermediate compartment. Förster resonance energy transfer between Bap31 and HLA-A2 and forward traffic increases when MHC class I molecules are loaded with a pulse of peptide. The increased forward traffic is blocked by overexpression of Bap29, a partner protein for Bap31, which localizes to the ER. Thus, in HeLa cells, Bap31 is involved in the exit of peptide-loaded MHC class I from the ER, and its function is regulated by its interaction with its homologue, Bap29.
Heat Shock Protein 96 Is Elevated in Rheumatoid Arthritis and Activates Macrophages Primarily via TLR2 Signaling
Authors: Huang Qi-Quan , Sobkoviak Rudina , Jockheck-Clark Angela R. , Shi Bo , Mandelin Arthur M. , Tak Paul Peter , Haines G. Kennith , Nicchitta Christopher V. , Pope Richard M. 
Published: April 2009

Abstract
Macrophages are important mediators of chronic inflammation and are prominent in the synovial lining and sublining of patients with rheumatoid arthritis (RA). Recently, we demonstrated increased TLR2 and TLR4 expression and increased response to microbial TLR2 and TLR4 ligands in macrophages from the joints of RA. The current study characterized the expression of the 96-kDa heat shock glycoprotein (gp96) in the joints of RA and its role as an endogenous TLR ligand to promote innate immunity in RA. gp96 was increased in RA compared with osteoarthritis and arthritis-free control synovial tissues. The expression of gp96 strongly correlated with inflammation and synovial lining thickness. gp96 was increased in synovial fluid from the joints of RA compared with disease controls. Recombinant gp96 was a potent activator of macrophages and the activation was mediated primarily through TLR2 signaling. The cellular response to gp96 was significantly stronger with RA synovial macrophages compared with peripheral blood monocytes from RA or healthy controls. The transcription of TLR2, TNF-α, and IL-8, but not TLR4, was significantly induced by gp96, and the induction was significantly greater in purified RA synovial macrophages. The expression of TLR2, but not TLR4, on synovial fluid macrophages strongly correlated with the level of gp96 in the synovial fluid. The present study documents the potential role of gp96 as an endogenous TLR2 ligand in RA and provides insight into the mechanism by which gp96 promotes the chronic inflammation of RA, identifying gp96 as a potential new therapeutic target.
IL-9 Promotes IL-13-Dependent Paneth Cell Hyperplasia and Up-Regulation of Innate Immunity Mediators in Intestinal Mucosa
Authors: Steenwinckel Valérie , Louahed Jamila , Lemaire Muriel M. , Sommereyns Caroline , Warnier Guy , McKenzie Andrew , Brombacher Frank , Van Snick Jacques , Renauld Jean-Christophe 
Published: April 2009

Abstract
IL-9 contributes to lung inflammatory processes such as asthma, by promoting mast cell differentiation, B cell activation, eosinophilia, and mucus production by lung epithelial cells. The observation that IL-9 overexpressing mice show increased mast cell numbers in the intestinal mucosa suggests that this cytokine might also play a role in intestinal inflammation. In colons from IL-9 transgenic mice, the expression of Muc2, a major intestinal mucin gene, was up-regulated, together with that of CLCA3 chloride channel and resistin like α, which are goblet cell-associated genes. Additional IL-9 up-regulated genes were identified and included innate immunity genes such as angiogenin 4 and the PLA2g2a phospholipase A2, which are typical Paneth cell markers. Histochemical staining of Paneth cells by phloxine/tartrazine showed that IL-9 induces Paneth cell hyperplasia in Lieberkühn glands of the small intestine, and in the colonic mucosa, where this cell type is normally absent. Expression of Paneth cell markers, including angiogenin 4, PLA2g2a, and cryptdins, was induced in the colon of wild-type mice after two to four daily administrations of IL-9. By crossing IL-9 transgenic mice with IL-13−/− mice, or by injecting IL-9 into IL-4R−/− mice, we showed that IL-13 was required for the up-regulation of these Paneth cell-specific genes by IL-9. Taken together, our data indicate that Paneth cell hyperplasia and expression of their various antimicrobial products contribute to the immune response driven by TH2 cytokines, such as IL-9 and IL-13 in the intestinal mucosa.
Costimulation of Dendritic Epidermal γδ T Cells by a New NKG2D Ligand Expressed Specifically in the Skin
Authors: Whang Michael I. , Guerra Nadia , Raulet David H. 
Published: April 2009

Abstract
Dendritic epidermal T cells (DETCs) are a highly specialized population of γδ T cells that resides in the murine skin and participates in wound healing and tumor surveillance. Despite the expression of other stimulatory receptors on these cells, mechanisms involving activation have focused primarily on the invariant Vγ3-Vδ1 TCR expressed by DETCs. All DETCs also express the activating NKG2D receptor, but the role of NKG2D in DETC activation remains unclear, as does the identity of NKG2D ligands that are functionally expressed in the skin. In this study, we document the cloning of an NKG2D ligand H60c that is expressed specifically in the skin and in cultured keratinocytes and demonstrate its role in the activation of DETCs and NK cells. The ligand is unique among NKG2D ligands in being up-regulated in cultured keratinocytes, and its interaction with NKG2D is essential for DETC activation. Importantly, it is shown that engagement of NKG2D is not sufficient to activate DETCs, but instead provides a costimulatory signal that is nevertheless essential for activating DETCs in response to stimulation with keratinocytes.
IL-22-Dependent Attenuation of T Cell-Dependent (ConA) Hepatitis in Herpes Virus Entry Mediator Deficiency
Authors: Wahl Christian , Wegenka Ursula Maria , Leithäuser Frank , Schirmbeck Reinhold , Reimann Jörg 
Published: April 2009

Abstract
Coinhibitors and costimulators control intrahepatic T cell responses that trigger acute hepatitis. We used the ConA-induced hepatitis model in the mouse to test if the coinhibitor herpes virus entry mediator (HVEM) modulates hepatitis-inducing T cell responses. Compared with ConA-injected, wild-type (wt) C57BL/6 (B6) mice, HVEM-deficient (HVEM−/−) B6 mice showed lower serum transaminase levels and lower proinflammatory IFN-γ, but higher protective IL-22 serum levels and an attenuated liver histopathology. The liver type I invariant NKT cell population that initiates acute hepatitis in this model was reduced in HVEM−/− mice but their surface phenotype was similar to that of untreated or ConA-treated wt controls. In response to mitogen injection, liver invariant NKT cells from HVEM−/− B6 mice produced in vivo more IL-22 but lower amounts of IFN-γ and IL-4 than wt controls. Bone marrow chimeras showed that HVEM deficiency of the liver nonparenchymal cell population, but not of the parenchymal cell population, mediated the attenuated course of the dendritic cell- and T cell-dependent ConA hepatitis. IL-22 is produced more efficiently by liver NKT cells from HVEM−/− than from wt mice, and its Ab-mediated neutralization of IL-22 aggravated the course of hepatitis in wt and HVEM−/− mice. Hence, HVEM expression promotes pathogenic, proinflammatory Th1 responses but down-modulates protective IL-22 responses of T cells in this model of acute hepatitis.
Nerve Growth Factor and Neurotrophin-3 Mediate Survival of Pulmonary Plasma Cells during the Allergic Airway Inflammation
Authors: Abram Melanie , Wegmann Michael , Fokuhl Verena , Sonar Sanchaita , Luger Elke Olga , Kerzel Sebastian , Radbruch Andreas , Renz Harald , Zemlin Michael 
Published: April 2009

Abstract
Allergen-specific Abs play a pivotal role in the induction and maintenance of allergic airway inflammation. During secondary immune responses, plasma cell survival and Ab production is mediated by extrinsic factors provided by the local environment (survival niches). It is unknown whether neurotrophins, a characteristic marker of allergic airway inflammation, influence plasma cell survival in the lung. Using a mouse model of allergic asthma, we found that plasma cells from the lung and spleen are distinct subpopulations exhibiting differential expression patterns of neurotrophins and their receptors (Trks). In vitro, the nerve growth factor (NGF) and neurotrophin-3 (NT3) led to a dose-dependent increase in viability of isolated pulmonary plasma cells due to up-regulation of the antiapoptotic Bcl2 pathway. In parallel, the expression of transcription factors that stimulate the production of immunoglobulins (X-box binding protein 1 and NF-κB subunit RelA) was enhanced in plasma cells treated with NGF and NT3. These findings were supported in vivo. When the NGF pathway was blocked by intranasal application of a selective TrkA inhibitor, sensitized mice showed reduced numbers of pulmonary plasma cells and developed lower levels of allergen-specific and total serum IgE in response to OVA inhalation. This suggests that in the allergic airway inflammation, NGF/TrkA-mediated pulmonary IgE production contributes significantly to serum-IgE levels. We conclude that the neurotrophins NGF and NT3 act as survival factors for pulmonary plasma cells and thus are important regulators of the local Ab production in the allergic airway disease.
Mitocryptide-2: Purification, Identification, and Characterization of a Novel Cryptide That Activates Neutrophils
Authors: Mukai Hidehito , Seki Tetsuo , Nakano Hiroko , Hokari Yoshinori , Takao Toshifumi , Kawanami Masanori , Tsukagoshi Hiroyuki , Kimura Hirokazu , Kiso Yoshiaki , Shimonishi Yasutsugu , Nishi Yoshisuke , Munekata Eisuke 
Published: April 2009

Abstract
Neutrophils are a class of leukocytes involved in innate immunity by monitoring and scavenging invading microorganisms and toxic substances. The actions of neutrophils in damaged tissues are still not well understood, particularly in the early stage of inflammation, and as-yet-unknown neutrophil-activating substances are proposed to induce their acute transmigration and activation. Here, we isolated and identified from porcine hearts a neutrophil-activating peptide. Structural analyses indicated that the primary structure of this peptide is formyl-Met-Thr-Asn-Ile-Arg-Lys-Ser-His-Pro-Leu-Met-Lys-Ile-Ile-Asn, which is identical to that of the N-terminal pentadecapeptide of porcine mitochondrial cytochrome b; we therefore named the newly isolated peptide “mitocryptide-2” (MCT-2), since we have recently purified and identified mitocryptide-1, a different class of a neutrophil-activating peptide. Synthetic MCT-2 and its human homolog hMCT-2 induced β-hexosaminidase release in and chemotaxis of HL-60 cells differentiated into neutrophilic/granulocytic cells. The induction of β-hexosaminidase release, chemotaxis, and the increase in the intracellular free Ca2+ concentration by hMCT-2 were completely suppressed by pertussis toxin, indicating the involvement of Gi- or Go-type G proteins in the signaling pathways. Moreover, MCT-2 and hMCT-2 also stimulated β-hexosaminidase secretion in human neutrophils isolated from peripheral blood in a concentration-dependent manner. Additionally, these peptides partially competed with [3H]formyl-Met-Leu-Phe binding to HL-60 cells differentiated into neutrophilic/granulocytic cells, presenting the possibility that the receptor for MCT-2 and hMCT-2 is one of the formyl peptide receptors. These results demonstrate that MCT-2 and its human homolog hMCT-2 are cryptides that activate neutrophils, thus suggesting the presence of regulatory mechanisms involving such mitocryptides in innate immunity.
Lipocalin 2 Is Required for Pulmonary Host Defense against Klebsiella Infection
Authors: Chan Yvonne R. , Liu Jessica S. , Pociask Derek A. , Zheng Mingquan , Mietzner Timothy A. , Berger Thorsten , Mak Tak W. , Clifton Matthew C. , Strong Roland K. , Ray Prabir , Kolls Jay K. 
Published: April 2009

Abstract
Antimicrobial proteins comprise a significant component of the acute innate immune response to infection. They are induced by pattern recognition receptors as well as by cytokines of the innate and adaptive immune pathways and play important roles in infection control and immunomodulatory homeostasis. Lipocalin 2 (siderocalin, NGAL, 24p3), a siderophore-binding antimicrobial protein, is critical for control of systemic infection with Escherichia coli; however, its role in mucosal immunity in the respiratory tract is unknown. In this study, we found that lipocalin 2 is rapidly and robustly induced by Klebsiella pneumoniae infection and is TLR4 dependent. IL-1β and IL-17 also individually induce lipocalin 2. Mucosal administration of IL-1β alone could reconstitute the lipocalin 2 deficiency in TLR4 knockout animals and rescue them from infection. Lipocalin 2-deficient animals have impaired lung bacterial clearance in this model and mucosal reconstitution of lipocalin 2 protein in these animals resulted in rescue of this phenotype. We conclude that lipocalin 2 is a crucial component of mucosal immune defense against pulmonary infection with K. pneumoniae.
Critical and Multiple Roles for the CD3ε Intracytoplasmic Tail in Double Negative to Double Positive Thymocyte Differentiation
Authors: Brodeur Jean-Francois , Li Samantha , Martins Maria da Silva , Larose Louise , Dave Vibhuti P. 
Published: April 2009

Abstract
The preTCR is associated with signal-transducing CD3γ, δ, ε, and ζ polypeptides. It is generally agreed that CD3 chains play redundant roles in the receptor-mediated signal transduction. In the present study, we show that the intracytoplasmic (IC) domain of CD3ε is essential for early thymocyte maturation. We demonstrate that the IC domain-deleted CD3ε fails to restore the double negative (DN) to double positive (DP) thymocyte development in CD3ε-deficient mice. Additional experiments show that the membrane proximal basic amino acid rich sequence in the IC domain of CD3ε is sufficient for the DN to DP differentiation, whereas the proline rich sequence is required for efficient proliferation. This is probably due to impaired ligand independent recruitment of Nck to the proline rich sequence motif of CD3ε within the context of the preTCR. The data presented in this study elucidates mechanistic basis for the preTCR-induced proliferation of the DN thymocytes and have identified distinct roles for individual motifs of CD3ε in the preTCR-mediated differentiation and proliferation. These data provide the first genetic and phenotypic evidence for requirement of the IC domain of a CD3 chain in thymocyte development.
Association of HIV-Specific and Total CD8+ T Memory Phenotypes in Subtype C HIV-1 Infection with Viral Set Point
Authors: Burgers Wendy A. , Riou Catherine , Mlotshwa Mandla , Maenetje Pholo , de Assis Rosa Debra , Brenchley Jason , Mlisana Koleka , Douek Daniel C. , Koup Richard , Roederer Mario , de Bruyn Guy , Karim Salim Abdool , Williamson Carolyn , Gray Clive M. ,   and the CAPRISA 002 Acute Infection Study Team
Published: April 2009

Abstract
Understanding early immunological events during HIV-1 infection that may set the course of disease progression is important for identifying correlates of viral control. This study explores the association of differentiation profiles of HIV-specific and total memory CD8+ T cells with viral set point. A cohort of 47 HIV-1-infected individuals, with differing viral set points at 12 mo, were recruited during acute infection. We identified that the magnitude of IFN-γ+ T cell responses at 6 mo postinfection did not associate with viral set point at 12 mo. A subset of 16 individuals was further studied to characterize CD8+ T cells for expression patterns of markers for memory differentiation, survival (CD127), senescence (CD57), and negative regulation (programmed death-1). We show that viral control and the predicted tempo of HIV disease progression in the first year of infection was associated with a synchronous differentiation of HIV-specific and total CD8+ memory subpopulations. At 6–9 mo postinfection, those with low viral set points had a significantly higher proportion of early differentiated HIV-specific and total memory CD8+ cells of a central memory (CD45RO+CD27+CCR7+) and intermediate memory (CD45RO−CD27+CCR7−) phenotype. Those with high viral set points possessed significantly larger frequencies of effector memory (CD45RO+CD27−CCR7−) cells. The proportions of memory subsets significantly correlated with CD38+CD8+ T cells. Thus, it is likely that a high Ag burden resulting in generalized immune activation may drive differentiation of HIV-specific and total memory CD8+ T cells.
Thrombin Binding Predicts the Effects of Sequence Changes in a Human Monoclonal Antiphospholipid Antibody on Its In Vivo Biologic Actions
Authors: Giles Ian , Pericleous Charis , Liu Xiaowei , Ehsanullah Jasmine , Clarke Lindsey , Brogan Paul , Newton-West Marvin , Swerlick Robert , Lambrianides Anastasia , Chen Pojen , Latchman David , Isenberg David , Pierangeli Silvia , Rahman Anisur 
Published: April 2009

Abstract
The mechanisms by which antiphospholipid Abs (aPL) cause thrombosis are not fully understood. It is clear that binding to a number of phospholipid-associated Ags is important but it is difficult to identify which Ag-binding properties are most closely linked to the ability to cause biologic effects such as promotion of thrombosis and activation of endothelial cells. We have previously used an in vitro expression system to produce a panel of human monoclonal IgG molecules between which we engineered small differences in sequence leading to significant well-defined changes in binding properties. In this study, we assess the properties of five of these IgG molecules in assays of biologic function in vitro and in vivo. The i.p. injection of these IgG into mice subjected to a femoral vein pinch stimulus showed that only those IgG that showed strong binding to thrombin promoted in vivo venous thrombosis and leukocyte adherence. However, this finding did not hold true for the effects of these IgG on activation of cultured endothelial cells in vitro, where there was a less clear relationship between binding properties and biologic effects.
Using PATIMDB to Create Bacterial Transposon Insertion Mutant Libraries
Authors: Urbach Jonathan M. , Wei Tao , Liberati Nicole , Grenfell‐Lee Daniel , Villanueva Jacinto , Wu Gang , Ausubel Frederick M. 
Published: April 2009

AbstractPATIMDB is a software package for facilitating the generation of transposon mutant insertion libraries. The software has two main functions: process tracking and automated sequence analysis. The process tracking function specifically includes recording the status and fates of multiwell plates and samples in various stages of library construction. Automated sequence analysis refers specifically to the pipeline of sequence analysis starting with ABI files from a sequencing facility and ending with insertion location identifications. The protocols in this unit describe installation and use of PATIMDB software. Curr. Protoc. Mol. Biol. 86:19.7.1‐19.7.34. © 2009 by John Wiley & Sons, Inc.
Two‐Hybrid Dual Bait System
Authors: Kotova Elena , Coleman Thomas , Serebriiskii Ilya 
Published: April 2009

AbstractThe yeast two‐hybrid system, or interaction trap, is one of the most versatile methods available with which to identify and establish protein‐protein interactions. The dual bait system is one adaptation of the classic approach. This system facilitates the simultaneous comparison of two distinct baits with one prey. One protein of interest is expressed as a fusion to the DNA‐binding protein LexA (bait 1), while a second protein of interest is expressed as a fusion to the DNA‐binding protein cI (bait 2). Strains of yeast engineered for screening of these dual baits possess four separate reporter genes. A plasmid expressing an activation domain‐fused protein (prey), which can be either a defined protein interactor or a cDNA library, is also expressed to allow dual hybrid‐mediated transcriptional activation. Curr. Protoc. Mol. Biol. 86:20.7.1‐20.7.32. © 2009 by John Wiley & Sons, Inc.
Breaking the Dogma of the Metal‐Coordinating Carboxylate Group in Integrin Ligands: Introducing Hydroxamic Acids to the MIDAS To Tune Potency and Selectivity
Authors: Heckmann Dominik , Laufer Burkhardt , Marinelli Luciana , Limongelli Vittorio , Novellino Ettore , Zahn Grit , Stragies Roland , Kessler Horst 
Published: April 2009

AbstractA suitable substitute: All integrin receptors bind their ligands, which contain an aspartate residue, in the metal‐ion‐ dependent adhesion site (MIDAS). So far all attempts to replace the carboxyl group of aspartate with other, pharmacologically favorable isosteric groups have failed. Now it has been shown that a hydroxamic acid group can replace the carboxyl group; the resulting ligand retains its high binding activity. The picture shows one such ligand in the binding site of αvβ3.magnified image
Synthesis of highly efficient D‐naproxen imprinted polymer and investigation of their specific performance
Authors: Zhang Zhiliang , Wang Bing 
Published: April 2009

AbstractD‐naproxen was selected as the imprinted molecule. An original ultraviolet spectrum analysis method based on proof of solvent effects was designed to verify the realization of the noncovalent self‐assembly between naproxen and functional monomers under the influence of the solvents with different nature. The facts proved that it is a more scientific way to effectively implement the pre‐selection of functional monomer. Then, a series of molecular imprinted polymers (MIPs) were synthesized by different ratios of raw materials. These products were detected by infrared spectroscopy as well as adsorption experimentation to analyze their structure and performance. Meanwhile, the transmission electron microscopy (TEM) was first used to observe the morphology of MIPs, by which the pore‐forming mechanism and the effect of the solvent (porogen) were investigated. The MIPs with morphology of different structure were also tested in the adsorption kinetics experiments to testify the influence of morphology factors on the materials' adsorption properties. Through the evaluation of the imprinting efficiency, the best condition accessing to the preparation of highly efficient D‐naproxen imprinted polymer was obtained. The apparent imprinting efficiency of the ultimate product was as high as 90.39%. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009