bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Overexpression of Heparin-Binding Epidermal Growth Factor Is Responsible for Th17-Induced Airway Remodeling in an Experimental Asthma Model
Authors: Wang Qing , Li Hequan , Yao Yinan , Xia Dajing , Zhou Jianying 
Published: June 2010

Abstract
Th17 cells that produce IL-17 have been found to participate in the development of allergy-triggered asthma. However, whether they play a causative role in the pathogenesis of airway remodeling in chronic asthma remains unclear. In this study, we investigated the role of Th17 cells in airway remodeling and the possible involvement of epidermal growth factor (EGF) receptor signals downstream of Th17. We established a C57BL/6 mouse model of prolonged allergen challenge that exhibits many characteristics of airway remodeling. Prolonged allergen challenge induced a progressive increase in the number of airway-infiltrating Th17 cells, and Th17 counts positively correlated with the severity of airway remodeling. Increases in mucus production, airway smooth muscle (ASM) mass, peribronchial collagen deposition, and airway heparin-binding EGF (HB-EGF) expression have been observed in sensitized mice following prolonged allergen exposure or adoptive Th17 transfer; remarkably, these effects can be abrogated by treatment with anti–IL-17 mAb. Both the EFGR inhibitor AG1478 and an anti–HB-EGF mAb ameliorated all of these effects, except for peribronchial collagen deposition in the presence of high levels of IL-17. In vitro, Th17 cells enhanced the airway epithelial expression of HB-EGF in a coculture of the two cells. The conditioned medium obtained from this coculture system effectively promoted ASM proliferation; this response was dramatically abolished by anti–HB-EGF mAb but not Abs against other EGF receptor ligands or IL-17. These observations demonstrated that overexpression of airway HB-EGF induced by IL-17 secreted from redundant expanding Th17 cells might contribute to excessive mucus expression and ASM proliferation in chronic asthma.
Mouse Mast Cell Protease-4 Deteriorates Renal Function by Contributing to Inflammation and Fibrosis in Immune Complex-Mediated Glomerulonephritis
Authors: Scandiuzzi Lisa , Beghdadi Walid , Daugas Eric , Åbrink Magnus , Tiwari Neeraj , Brochetta Cristiana , Claver Julien , Arouche Nassim , Zang Xingxing , Pretolani Marina , Monteiro Renato C. , Pejler Gunnar , Blank Ulrich 
Published: June 2010

Abstract
Mast cells exert protective effects in experimental antiglomerular basement membrane-induced glomerulonephritis (GN), yet the responsible mediators have not been identified. In this study, we investigated the role of mouse mast cell protease (mMCP)-4, the functional homolog of human chymase, using mMCP-4–deficient mice. Compared with wild type animals, mMCP-4–deficient mice exhibited lower proteinuria, blood creatinine, and blood urea nitrogen levels, indicating an aggravating role of mMCP-4. Kidney histology confirmed less severe renal damage in mMCP-4–deficient mice with reduced deposits, glomerular and interstitial cellularity, and fibrosis scores. High amounts of mMCP-4 were detected in renal capsules, but not in the whole kidney, from wild type mice. Its expression in renal capsules was markedly decreased after GN induction, suggesting that locally released enzyme by degranulated mast cells could contribute to the functional and physiopathological hallmarks of GN. Supporting a proinflammatory role, glomerular and interstitial macrophage and T cell infiltration, levels of proinflammatory TNF and MCP-1 mRNA, and the expression of the profibrotic peptide angiotensin II together with type I collagen were markedly downregulated in kidneys of mMCP-4−deficient mice. We conclude that mMCP-4 chymase, contrary to the global anti-inflammatory action of mast cells, aggravates GN by promoting kidney inflammation. These results highlight the complexity of mast cell-mediated inflammatory actions and suggest that chymase inhibition may represent a novel therapeutic target in GN.
Slam Haplotypes Modulate the Response to Lipopolysaccharide In Vivo through Control of NKT Cell Number and Function
Authors: Aktan Idil , Chant Alan , Borg Zachary D. , Damby David E. , Leenstra Paige C. , Lilley Graham W. G. , Petty Joseph , Suratt Benjamin T. , Teuscher Cory , Wakeland Edward K. , Poynter Matthew E. , Boyson Jonathan E. 
Published: June 2010

Abstract
CD1d-restricted NKT cells make up an innate-like T cell subset that plays a role in amplifying the response of innate immune leukocytes to TLR ligands. The Slam locus contains genes that have been implicated in innate and adaptive immune responses. In this study, we demonstrate that divergent Slam locus haplotypes modulate the response of macrophages to the TLR4 ligand LPS through their control of NKT cell number and function. In response to LPS challenge in vivo, macrophage TNF production in Slam haplotype-2+ 129S1/SvImJ and 129X1/SvJ mice was significantly impaired in comparison with macrophage TNF production in Slam haplotype-1+ C57BL/6J mice. Although no cell-intrinsic differences in macrophage responses to LPS were observed between strains, 129 mice were found to be deficient in liver NKT cell number, in NKT cell cytokine production in response to the CD1d ligand α-galactosylceramide, and in NKT cell IFN-γ production after LPS challenge in vivo. Using B6.129c1 congenic mice and adoptive transfer, we found that divergent Slam haplotypes controlled the response to LPS in vivo, as well as the diminished NKT cell number and function, and that these phenotypes were associated with differential expression of signaling lymphocytic activation molecule family receptors on NKT cells. These data suggest that the polymorphisms that distinguish two Slam haplotypes significantly modulate the innate immune response in vivo through their effect on NKT cells.
Conformation-Dependent High-Affinity Monoclonal Antibodies to Prion Proteins
Authors: Stanker Larry H. , Serban Ana V. , Cleveland Elisa , Hnasko Robert , Lemus Azucena , Safar Jiri , DeArmond Stephen J. , Prusiner Stanley B. 
Published: June 2010

Abstract
Prion diseases are fatal, neurodegenerative illnesses caused by the accumulation of PrPSc, an aberrantly folded isoform of the normal, cellular prion protein. Detection of PrPSc commonly relies on immunochemical methods, a strategy hampered by the lack of Abs specific for this disease-causing isoform. In this article, we report the generation of eight mAbs against prion protein (PrP) following immunization of Prnp-null mice with rPrP. The eight mAbs exhibited distinct differential binding to cellular prion protein and PrPSc from different species as well as PrP-derived synthetic peptides. Five of the eight mAbs exhibited binding to discontinuous PrP epitopes, all of which were disrupted by the addition of 2-ME or DTT, which reduced the single disulfide bond found in PrP. One mAb F20-29 reacted only with human PrP, whereas the F4-31 mAb bound bovine PrP; the KD values for mAbs F4-31 and F20-29 were ~500 pM. Binding of all five conformation-dependent mAbs to PrP was inhibited by 2-ME in ELISA, Western blots, and histoblots. One conformation-dependent mAb F4-31 increased the sensitivity of an ELISA-based test by nearly 500-fold when it was used as the capture Ab. These new conformation-dependent mAbs were found to be particularly useful in histoblotting studies, in which the low backgrounds after treatment with 2-ME created unusually high signal-to-noise ratios.
Asymmetric Cell Division of T Cells upon Antigen Presentation Uses Multiple Conserved Mechanisms
Authors: Oliaro Jane , Van Ham Vanessa , Sacirbegovic Faruk , Pasam Anupama , Bomzon Ze’ev , Pham Kim , Ludford-Menting Mandy J. , Waterhouse Nigel J. , Bots Michael , Hawkins Edwin D. , Watt Sally V. , Cluse Leonie A. , Clarke Chris J. P. , Izon David J. , Chang John T. , Thompson Natalie , Gu Min , Johnstone Ricky W. , Smyth Mark J. , Humbert Patrick O. , Reiner Steven L. , Russell Sarah M. 
Published: June 2010

Abstract
Asymmetric cell division is a potential means by which cell fate choices during an immune response are orchestrated. Defining the molecular mechanisms that underlie asymmetric division of T cells is paramount for determining the role of this process in the generation of effector and memory T cell subsets. In other cell types, asymmetric cell division is regulated by conserved polarity protein complexes that control the localization of cell fate determinants and spindle orientation during division. We have developed a tractable, in vitro model of naive CD8+ T cells undergoing initial division while attached to dendritic cells during Ag presentation to investigate whether similar mechanisms might regulate asymmetric division of T cells. Using this system, we show that direct interactions with APCs provide the cue for polarization of T cells. Interestingly, the immunological synapse disseminates before division even though the T cells retain contact with the APC. The cue from the APC is translated into polarization of cell fate determinants via the polarity network of the Par3 and Scribble complexes, and orientation of the mitotic spindle during division is orchestrated by the partner of inscuteable/G protein complex. These findings suggest that T cells have selectively adapted a number of evolutionarily conserved mechanisms to generate diversity through asymmetric cell division.
Mapping of Conformational Epitopes on Human Proteinase 3, the Autoantigen of Wegener’s Granulomatosis
Authors: Kuhl Angelika , Korkmaz Brice , Utecht Bert , Kniepert Andrea , Schönermarck Ulf , Specks Ulrich , Jenne Dieter E. 
Published: June 2010

Abstract
Anti-neutrophil cytoplasmic Abs (cANCAs) against conformational epitopes of proteinase 3 (PR3) are regarded as an important pathogenic marker in Wegener’s granulomatosis (WG). Although the three-dimensional structure of PR3 is known, binding sites of mAbs and cANCAs have not been mapped to date. Competitive binding and biosensor experiments suggested the existence of four nonoverlapping areas on the PR3 surface. In this paper, we present an approach to identify these discontinuous surface regions that cannot be mimicked by linear peptides. The very few surface substitutions found in closely related PR3 homologs from primates, which were further varied by the construction of functional human-gibbon hybrids, resulted in the differential loss of three Ab binding sites, two of which were mapped to the N-terminal β-barrel and one to the linker segment connecting the N- and C-terminal barrels of PR3. The sera from WG patients differed in their binding to gibbon PR3 and the gibbon-human PR3 hybrid, and could be divided into two groups with similar or significantly reduced binding to gibbon PR3. Binding of almost all sera to PR3–α1-protease inhibitor (α1–PI) complexes was even more reduced and often absent, indicating that major antigenic determinants overlap with the active site surface on PR3 that associates with α1-PI. Similarly, the mouse mAbs CLB12.8 and 6A6 also did not react with gibbon PR3 and PR3–α1-PI complexes. Our data strongly suggest that cANCAs from WG patients at least in part recognize similar surface structures as do mouse mAbs and compete with the binding of α1-PI to PR3.
Dicer-Dependent MicroRNAs Control Maturation, Function, and Maintenance of Langerhans Cells In Vivo
Authors: Kuipers Harmjan , Schnorfeil Frauke M. , Fehling Hans-Jörg , Bartels Helmut , Brocker Thomas 
Published: June 2010

Abstract
Dendritic cells (DCs) are central for the induction of T cell immunity and tolerance. Fundamental for DCs to control the immune system is their differentiation from precursors into various DC subsets with distinct functions and locations in lymphoid organs and tissues. In contrast to the differentiation of epidermal Langerhans cells (LCs) and their seeding into the epidermis, LC maturation, turnover, and MHC class II Ag presentation capacities are strictly dependent on the presence of Dicer, which generates mature microRNAs (miRNAs). Absence of miRNAs caused a strongly disturbed steady-state homeostasis of LCs by increasing their turnover and apoptosis rate, leading to progressive ablation of LCs with age. The failure to maintain LCs populating the epidermis was accompanied by a proapoptotic gene expression signature. Dicer-deficient LCs showed largely increased cell sizes and reduced expression levels of the C-type lectin receptor Langerin, resulting in the lack of Birbeck granules. In addition, LCs failed to properly upregulate MHC class II, CD40, and CD86 surface molecules upon stimulation, which are critical hallmarks of functional DC maturation. This resulted in inefficient induction of CD4 T cell proliferation, whereas Dicer-deficient LCs could properly stimulate CD8 T cells. Taken together, Dicer-dependent generation of miRNAs affects homeostasis and function of epidermal LCs.
Tumor-Conditioned Macrophages Secrete Migration-Stimulating Factor: A New Marker for M2-Polarization, Influencing Tumor Cell Motility
Authors: Solinas Graziella , Schiarea Silvia , Liguori Manuela , Fabbri Marco , Pesce Samantha , Zammataro Luca , Pasqualini Fabio , Nebuloni Manuela , Chiabrando Chiara , Mantovani Alberto , Allavena Paola 
Published: June 2010

Abstract
Tumor-associated macrophages (TAMs) are key orchestrators of the tumor microenvironment directly affecting neoplastic cell growth, neoangiogenesis, and extracellular matrix remodeling. In turn, the tumor milieu strongly influences maturation of TAMs and shapes several of their features. To address the early macrophage (Mϕ) differentiation phase in a malignant context, we mimicked a tumor microenvironment by in vitro coculturing human blood monocytes with conditioned media from different cancer cell lines. Only 2 out of 16 tumor cell lines induced Mϕ differentiation due to secreted M-CSF isoforms, including high molecular mass species. A global gene profiling of tumor-conditioned Mϕ was performed. Comparison with other datasets (polarized M1-Mϕ, M2-Mϕ, and TAMs isolated from human tumors) highlighted the upregulation of several genes also shared by TAM and M2-polarized Mϕ. The most expressed genes were selenoprotein 1, osteoactivin, osteopontin, and, interestingly, migration-stimulating factor (MSF), a poorly studied oncofoetal isoform of fibronectin. MSF (present in fetal/cancer epithelial and stromal cells but not in healthy tissues) was never identified in Mϕ. MSF production was confirmed by immunohistochemistry in human TAMs. MSF was induced by M-CSF, IL-4, and TGFβ but not by proinflammatory stimuli. RNA and protein analysis clearly demonstrated that it is specifically associated with the M2 polarization of Mϕ. Tumor-conditioned Mϕ-derived MSFs strongly stimulated tumor cell migration, thus contributing to the motile phenotype of neoplastic cells. In conclusion, MSF is a new molecule associated with the M2 polarization of Mϕ and expressed by TAMs. Its biological function may contribute to Mϕ-mediated promotion of cancer cell invasion and metastasis.
Intracellular Sequestration of the NKG2D Ligand ULBP3 by Human Cytomegalovirus
Authors: Bennett Neil J. , Ashiru Omodele , Morgan Fiona J. E. , Pang Yin , Okecha Georgina , Eagle Rob A. , Trowsdale John , Sissons J. G. Patrick , Wills Mark R. 
Published: June 2010

Abstract
Human CMV (HCMV) encodes multiple genes that control NK cell activation and cytotoxicity. Some of these HCMV-encoded gene products modulate NK cell activity as ligands expressed at the cell surface that engage inhibitory NK cell receptors, whereas others prevent the infected cell from upregulating ligands that bind to activating NK cell receptors. A major activating NKR is the homodimeric NKG2D receptor, which has eight distinct natural ligands in humans. It was shown that HCMV is able to prevent the surface expression of five of these ligands (MIC A/B and ULBP1, 2, and 6). In this article, we show that the HCMV gene product UL142 can prevent cell surface expression of ULBP3 during infection. We further show that UL142 interacts with ULBP3 and mediates its intracellular retention in a compartment that colocalizes with markers of the cis-Golgi complex. In doing so, UL142 prevents ULBP3 trafficking to the surface and protects transfected cells from NK-mediated cytotoxicity. This is the first description of a viral gene able to mediate downregulation of ULBP3.
Hepatitis B Virus DNA in Serum of Hepatitis B Surface Antigen Negative Hemodialysis Patients
Authors: Sabry Dina , Ahmed Rasha , Abosaif Nihal , Talkhan Hala , Abdallah Sayed 
Published: June 2010

Hepatitis B virus (HBV) infection remains a serious issue in the dialysis population. Transmission of HBV through dialysis machines or other sources as well as seroconversion from HBV negative patients to positive ones is still not well understood. Seventy patients were selected from our chronic hemodialysis (HD) center. They were divided into two groups: Group (I) included 35 patients with negative hepatitis B surface antigen (HBsAg), while another 35 already known to have HBsAg positive were chosen as a control group (Group II). The aim of the study was to detect the presence of HBV DNA by analyzing the serum PCR of the negative (HBsAg) patients (Group I) then analyzing the viral sequencing of 5 of them in compari-son to 5 of the known HBsAg positive. All patients received blood transfusions, were positive for HCV but negative for HDV and HIV. In group I, HBV DNA by PCR was detected in serum of 17/35 (48.5%) patients. Only 3 of them were positive for HBcAb. In group II, HBV DNA by PCR was detected in serum of 35/35 (100%) patients. The alanine transaminase enzyme (ALT) level was significantly higher than negative patients. Sequencing of the virus showed some mutated segments in 5 of the positive DNA by PCR compared to already positive HBsAg positive patients in Group II. In conclusion, a high proportion of HBsAg-negative hemodialysis patients were found to have positive HBV DNA by PCR. Sequencing of the virus revealed some mutated segments of the DNA. These findings are of major importance for the planning of future screening of patients on hemodialysis. We recom-mend measuring HBV DNA of all negative HBsAg patients on HD as this can change the management and prognosis of this particular group on chronic HD.
Are Perceptions about Worksite Neighborhoods and Policies Associated with Walking?
Authors: Schwartz Michael A. , Aytur Semra A. , Evenson Kelly R. , Rodríguez Daniel A. 
Published: June 2010

Purpose. To examine associations of the built environment surrounding worksites and of work policies with walking behaviors. Design. Cross-sectional convenience sample survey. Setting. Workplace. Subjects. Employed adults residing in Montgomery County, Maryland. Measures. Four different step measures taken at or near work as recorded using an accelerometer and a fifth measure indicated self-reported walking from work. Participants reported on eight built environment characteristics surrounding the worksite (e.g., the presence of sidewalks, crosswalks, and pedestrian signals) and on four worksite policies (e.g., the presence of exercise facilities and exercise programs). Analysis. Cross-sectional associations of self-reported built environment characteristics surrounding worksites and worksite policies with walking behavior were examined. Results. Although participants reported worksites exhibiting built environment characteristics that were supportive of walking (seven of eight characteristics were reported by >50% of participants), no built environment characteristic was associated with walking more than the median number of average weekday steps (p > .05). All four worksite policies were associated with walking more than the median number of average weekday steps (p < .05). In addition, a perception of few cul-de-sacs and of the presence of litter, sidewalks, crosswalks, and pedestrian signals surrounding the worksites was associated with a higher proportion of participants taking at least one walking trip from work in the past month (p < .05). Conclusions. Locating worksites in walkable environments and implementing worksite policies may favorably influence employee walking. Future studies should consider a prospective design and examine a larger, more diverse employee population and worksite environment to examine these associations.
Providing Calorie Information on Fast-Food Restaurant Menu Boards: Consumer Views
Authors: Fitch Rebecca C. , Harnack Lisa J. , Neumark-Sztainer Dianne R. , Story Mary T. , French Simone A. , Oakes J. Michael , Rydell Sarah A. 
Published: June 2010

Purpose. To gather consumer input about approaches to providing energy composition information for foods on fast-food restaurant menus. Design. We asked a subset of individuals (n = 150) in an experimental study about the influence of nutrition labeling on fast-food meal choices to evaluate calorie information on mock fast-food menus in various formats. Setting. Three community sites in the Minneapolis-St. Paul, Minnesota, metropolitan area. Subjects. Adolescents and adults who ate fast food at least once per week were recruited. Measures. Via a series of open- and close-ended questions, participants gave feedback about several formats for providing energy composition information for foods on fast-food restaurant menus. Analysis. Means and frequencies were calculated, and χ2 tests were conducted. Results. When asked to compare a menu that provided calorie information for each menu item with a menu that provided the number of minutes of running that would be required to burn the calories contained in each menu item, 71.0% of participants preferred the calorie information over the physical activity information. Participants also compared two approaches to providing caloric reference information on the menu (average daily calorie needs per day vs. per meal), and 61.3% preferred the calorie needs—per-meal format. Conclusion. Our results may be useful in designing approaches to providing energy composition information for foods on fast-food restaurant menus.
Equal Channel Angular Pressing of a Mg–3Al–1Zn Alloy with Back Pressure
Authors: Kang Feng , Liu Jin Qiang , Wang Jing Tao , Zhao Xiang 
Published: June 2010

AbstractAn extruded Mg–3Al–1Zn alloy bar is subjected to 1–4 passes equal channel angular pressing (ECAP) with or without 125 MPa backpressure via route Bc at 200 °C. Both strength and ductility are significantly increased after ECAP with backpressure; this is in strong contrast to the case of ECAP without backpressure, where significant improvement in ductility is accompanied by obvious decrease in yield strength from texture softening. Compared to ECAP without backpressure, much enhanced grain refinement, and the split of the dominant texture component of (0002) pole were observed with scatter intensity peaks in the case after ECAP with backpressure. This turns out to be resulted mainly from the activation of new slip system together with enhanced dynamic recrystallization under the effect of backpressure. The improvement of both strength and ductility in Mg–3Al–1Zn alloy through ECAP with back pressure provides a better approach to meet the engineering requests on comprehensive performance of this light alloy.