bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Receptors Trigger Human NK Cell-Mediated Cytotoxicity against Porcine Chondrocytes
Authors: Sommaggio Roberta , Cohnen André , Watzl Carsten , Costa Cristina 
Published: January 2012

Abstract
Xenotransplantation of genetically engineered porcine chondrocytes may provide a therapeutic solution for the repair of cartilage defects of various types. However, the mechanisms underlying the humoral and cellular responses that lead to rejection of xenogeneic cartilage are not well understood. In this study, we investigated the interaction between human NK cells and isolated porcine costal chondrocytes (PCC). Our data show that freshly isolated NK cells adhere weakly to PCC. Consequently, PCC were highly resistant to cytolysis mediated by freshly isolated NK cells. However, the presence of human natural Abs in the coculture was often sufficient to trigger cytotoxicity against PCC. Furthermore, IL-2 stimulation of NK cells or activation of PCC with the proinflammatory cytokines TNF-α or IL-1α resulted in increased adhesion, which was paralleled by increased NK cell-mediated lysis of PCC. NK cell adhesion to PCC could be blocked by Abs against human LFA-1 and porcine VCAM-1. NKG2D and NKp44 were involved in triggering cytotoxicity against PCC, which expressed ligands for these activating NK cell receptors. Our data further suggest that NKp30 and NKp46 may contribute to the activation of NK cells by PCC under certain conditions. Finally, comparative studies confirmed that PCC are more resistant than porcine aortic endothelial cells to human NK cell-mediated lysis. Thus, the data demonstrate that human NK cells can kill pig chondrocytes and may therefore contribute to rejection of xenogeneic cartilage. In addition, we identify potential targets for intervention to prevent the NK cell response against pig xenografts.
MicroRNA-127 Inhibits Lung Inflammation by Targeting IgG Fcγ Receptor I
Authors: Xie Ting , Liang Jiurong , Liu Ningshan , Wang Qingguo , Li Yuhang , Noble Paul W. , Jiang Dianhua 
Published: January 2012

Abstract
The molecular mechanisms of acute lung injury are incompletely understood. MicroRNAs (miRNAs) are crucial biological regulators that act by suppressing their target genes and are involved in a variety of pathophysiologic processes. miR-127 appears to be downregulated during lung injury. We set out to investigate the role of miR-127 in lung injury and inflammation. Expression of miR-127 significantly reduced cytokine release by macrophages. Looking into the mechanisms of regulation of inflammation by miR-127, we found that IgG FcγRI (CD64) was a target of miR-127, as evidenced by reduced CD64 protein expression in macrophages overexpressing miR-127. Furthermore, miR-127 significantly reduced the luciferase activity with a reporter construct containing the native 3′ untranslated region of CD64. Importantly, we demonstrated that miR-127 attenuated lung inflammation in an IgG immune complex model in vivo. Collectively, these data show that miR-127 targets macrophage CD64 expression and promotes the reduction of lung inflammation. Understanding how miRNAs regulate lung inflammation may represent an attractive way to control inflammation induced by infectious or noninfectious lung injury.
Decoy Receptor 3 Enhances Tumor Progression via Induction of Tumor-Associated Macrophages
Authors: Tai Shyh-Kuan , Chang Hsin-Chuan , Lan Keng-Li , Lee Chun-Ting , Yang Chih-Ya , Chen Nien-Jung , Chou Teh-Ying , Tarng Der-Cherng , Hsieh Shie-Liang 
Published: January 2012

Abstract
Tumor-associated macrophages (TAMs) are the major component of tumor-infiltrating leukocytes. TAMs are heterogeneous, with distinct phenotypes influenced by the microenvironment surrounding tumor tissues. Decoy receptor 3 (DcR3), a member of the TNFR superfamily, is overexpressed in tumor cells and is capable of modulating host immunity as either a neutralizing decoy receptor or an effector molecule. Upregulation of DcR3 has been observed to correlate with a poor prognosis in various cancers. However, the mechanisms underlying the DcR3-mediated tumor-promoting effect remain unclear. We previously demonstrated that DcR3 modulates macrophage activation toward an M2-like phenotype in vitro and that DcR3 downregulates MHC class II expression in TAMs via epigenetic control. To investigate whether DcR3 promotes tumor growth, CT26-DcR3 stable transfectants were established. Compared with the vector control clone, DcR3-transfectants grew faster and resulted in TAM infiltration. We further generated CD68 promoter-driven DcR3 transgenic (Tg) mice to investigate tumor growth in vivo. Compared with wild-type mice, macrophages isolated from DcR3-Tg mice displayed higher levels of IL-10, IL-1ra, Ym1, and arginase activity, whereas the expression of IL-12, TNF-α, IL-6, NO, and MHC class II was downregulated. Significantly enhanced tumor growth and spreading were observed in DcR3-Tg mice, and the enhanced tumor growth was abolished by arginase inhibitor N-ω-hydroxy-l-norarginine and histone deacetylase inhibitor sodium valproate. These results indicated that induction of TAMs is an important mechanism for DcR3-mediated tumor progression. Our findings also suggest that targeting DcR3 might help in the development of novel treatment strategies for tumors with high DcR3 expression.
A Metalloproteinase Karilysin Present in the Majority of Tannerella forsythia Isolates Inhibits All Pathways of the Complement System
Authors: Jusko Monika , Potempa Jan , Karim Abdulkarim Y. , Ksiazek Miroslaw , Riesbeck Kristian , Garred Peter , Eick Sigrun , Blom Anna M. 
Published: January 2012

Abstract
Tannerella forsythia is a poorly studied pathogen despite being one of the main causes of periodontitis, which is an inflammatory disease of the supporting structures of the teeth. We found that despite being recognized by all complement pathways, T. forsythia is resistant to killing by human complement, which is present at up to 70% of serum concentration in gingival crevicular fluid. Incubation of human serum with karilysin, a metalloproteinase of T. forsythia, resulted in a decrease in bactericidal activity of the serum. T. forsythia strains expressing karilysin at higher levels were more resistant than low-expressing strains. Furthermore, the low-expressing strain was significantly more opsonized with activated complement factor 3 and membrane attack complex from serum compared with the other strains. The high-expressing strain was more resistant to killing in human blood. The protective effect of karilysin against serum bactericidal activity was attributable to its ability to inhibit complement at several stages. The classical and lectin complement pathways were inhibited because of the efficient degradation of mannose-binding lectin, ficolin-2, ficolin-3, and C4 by karilysin, whereas inhibition of the terminal pathway was caused by degradation of C5. Interestingly, karilysin was able to release biologically active C5a peptide in human plasma and induce migration of neutrophils. Importantly, we detected the karilysin gene in &gt;90% of gingival crevicular fluid samples containing T. forsythia obtained from patients with periodontitis. Taken together, the newly characterized karilysin appears to be an important virulence factor of T. forsythia and might have several important implications for immune evasion.
Concurrent Bacterial Stimulation Alters the Function of Helminth-Activated Dendritic Cells, Resulting in IL-17 Induction
Authors: Perona-Wright Georgia , Lundie Rachel J. , Jenkins Stephen J. , Webb Lauren M. , Grencis Richard K. , MacDonald Andrew S. 
Published: January 2012

Abstract
Infection with schistosome helminths is associated with granulomatous inflammation that forms around parasite eggs trapped in host tissues. In severe cases, the resulting fibrosis can lead to organ failure, portal hypertension, and fatal bleeding. Murine studies identified IL-17 as a critical mediator of this immunopathology, and mouse strains that produce high levels of IL-17 in response to schistosome infection show increased mortality. In this article, we demonstrate that schistosome-specific IL-17 induction by dendritic cells from low-pathology C57BL/6 mice is normally regulated by their concomitant induction of IL-10. Simultaneous stimulation of schistosome-exposed C57BL/6 dendritic cells with a heat-killed bacterium enabled these cells to overcome IL-10 regulation and induce IL-17, even in wild-type C57BL/6 recipients. This schistosome-specific IL-17 was dependent on IL-6 production by the copulsed dendritic cells. Coimmunization of C57BL/6 animals with bacterial and schistosome Ags also resulted in schistosome-specific IL-17, and this response was enhanced in the absence of IL-10–mediated immune regulation. Together, our data suggest that the balance of pro- and anti-inflammatory cytokines that determines the severity of pathology during schistosome infection can be influenced not only by host and parasite, but also by concurrent bacterial stimulation.
Brain-Derived Antigens in Lymphoid Tissue of Patients with Acute Stroke
Authors: Planas Anna M. , Gómez-Choco Manuel , Urra Xabier , Gorina Roser , Caballero Miguel , Chamorro Ángel 
Published: January 2012

AbstractIn experimental animals, the presence of brain-derived constituents in cervical lymph nodes has been associated with the activation of local lymphocytes poised to minimize the inflammatory response after acute brain injury. In this study, we assessed whether this immune crosstalk also existed in stroke patients. We studied the clinical course, neuroimaging, and immunoreactivity to neuronal derived Ags (microtubule-associated protein-2 and N-methyl d-aspartate receptor subunit NR-2A), and myelin-derived Ags (myelin basic protein and myelin oligodendrocyte glycoprotein) in palatine tonsils and cervical lymph nodes of 28 acute stroke patients and 17 individuals free of neurologic disease. Stroke patients showed greater immunoreactivity to all brain Ags assessed compared with controls, predominantly in T cell zones. Most brain immunoreactive cells were CD68+ macrophages expressing MHC class II receptors. Increased reactivity to neuronal-derived Ags was correlated with smaller infarctions and better long-term outcome, whereas greater reactivity to myelin basic protein was correlated with stroke severity on admission, larger infarctions, and worse outcome at follow-up. Patients also had more CD69+ T cells than controls, indicative of T cell activation. Overall, the study showed in patients with acute stroke the presence of myelin and neuronal Ags associated with lymph node macrophages located near activated T cells. Whether the outcome of acute stroke is influenced by Ag-specific activation of immune responses mediated by CD69 lymphocytes deserves further investigation.
Strain-Dependent Airway Hyperresponsiveness and a Chromosome 7 Locus of Elevated Lymphocyte Numbers in Cystic Fibrosis Transmembrane Conductance Regulator-Deficient Mice
Authors: Bazett Mark , Stefanov Anguel N. , Paun Alexandra , Paradis Josee , Haston Christina K. 
Published: January 2012

Abstract
We previously observed the lungs of naive BALB/cJ Cftrtm1UNC mice to have greater numbers of lymphocytes, by immunohistochemical staining, than did BALB wild type littermates or C57BL/6J Cftrtm1UNC mice. In the present study, we initially investigated whether this mutation in Cftr alters the adaptive immunity phenotype by measuring the lymphocyte populations in the lungs and spleens by FACS and by evaluating CD3-stimulated cytokine secretion, proliferation, and apoptosis responses. Next, we assessed a potential influence of this lymphocyte phenotype on lung function through airway resistance measures. Finally, we mapped the phenotype of pulmonary lymphocyte counts in BALB × C57BL/6J F2 Cftrtm1UNC mice and reviewed positional candidate genes. By FACS analysis, both the lungs and spleens of BALB Cftrtm1UNC mice had more CD3+ (both CD4+ and CD8+) cells than did littermates or C57BL/6J Cftrtm1UNC mice. Cftrtm1UNC and littermate mice of either strain did not differ in anti-CD3–stimulated apoptosis or proliferation levels. Lymphocytes from BALB Cftrtm1UNC mice produced more IL-4 and IL-5 and reduced levels of IFN-γ than did littermates, whereas lymphocytes from C57BL/6J Cftrtm1UNC mice demonstrated increased Il-17 secretion. BALB Cftrtm1UNC mice presented an enhanced airway hyperresponsiveness to methacholine challenge compared with littermates and C57BL/6J Cftrtm1UNC mice. A chromosome 7 locus was identified to be linked to lymphocyte numbers, and genetic evaluation of the interval suggests Itgal and Il4ra as candidate genes for this trait. We conclude that the pulmonary phenotype of BALB Cftrtm1UNC mice includes airway hyperresponsiveness and increased lymphocyte numbers, with the latter trait being influenced by a chromosome 7 locus.
The IKKα-Dependent NF-κB p52/RelB Noncanonical Pathway Is Essential To Sustain a CXCL12 Autocrine Loop in Cells Migrating in Response to HMGB1
Authors: Kew Richard R. , Penzo Marianna , Habiel David M. , Marcu Kenneth B. 
Published: January 2012

Abstract
HMGB1 is a chromatin architectural protein that is released by dead or damaged cells at sites of tissue injury. Extracellular HMGB1 functions as a proinflammatory cytokine and chemoattractant for immune effector and progenitor cells. Previously, we have shown that the inhibitor of NF-κB kinase (IKK)β- and IKKα-dependent NF-κB signaling pathways are simultaneously required for cell migration to HMGB1. The IKKβ-dependent canonical pathway is needed to maintain expression of receptor for advanced glycation end products, the ubiquitously expressed receptor for HMGB1, but the target of the IKKα non-canonical pathway was not known. In this study, we show that the IKKα-dependent p52/RelB noncanonical pathway is critical to sustain CXCL12/SDF1 production in order for cells to migrate toward HMGB1. Using both mouse bone marrow-derived macrophages and mouse embryo fibroblasts (MEFs), it was observed that neutralization of CXCL12 by a CXCL12 mAb completely eliminated chemotaxis to HMGB1. In addition, the HMGB1 migration defect of IKKα KO and p52 KO cells could be rescued by adding recombinant CXCL12 to cells. Moreover, p52 KO MEFs stably transduced with a GFP retroviral vector that enforces physiologic expression of CXCL12 also showed near normal migration toward HMGB1. Finally, both AMD3100, a specific antagonist of CXCL12’s G protein-coupled receptor CXCR4, and an anti-CXCR4 Ab blocked HMGB1 chemotactic responses. These results indicate that HMGB1-CXCL12 interplay drives cell migration toward HMGB1 by engaging receptors of both chemoattractants. This novel requirement for a second receptor-ligand pair enhances our understanding of the molecular mechanisms regulating HMGB1-dependent cell recruitment to sites of tissue injury.
MicroRNA miR-150 Is Involved in Vα14 Invariant NKT Cell Development and Function
Authors: Zheng Quanhui , Zhou Li , Mi Qing-Sheng 
Published: January 2012

Abstract
CD1d-restricted Vα14 invariant NKT (iNKT) cells play an important role in the regulation of diverse immune responses. MicroRNA-mediated RNA interference is emerging as a crucial regulatory mechanism in the control of iNKT cell differentiation and function. Yet, roles of specific microRNAs in the development and function of iNKT cells remain to be further addressed. In this study, we identified the gradually increased expression of microRNA-150 (miR-150) during the maturation of iNKT cells in thymus. Using miR-150 knockout (KO) mice, we found that miR-150 deletion resulted in an interruption of iNKT cell final maturation in both thymus and periphery. Upon activation, iNKT cells from miR-150KO mice showed significantly increased IFN-γ production compared with wild-type iNKT cells. Bone marrow-transferring experiments demonstrated the cell-intrinsic characteristics of iNKT cell maturation and functional defects in mice lacking miR-150. Furthermore, miR-150 target c-Myb was significantly upregulated in miR-150KO iNKT cells, which potentially contribute to iNKT cell defects in miR-150KO mice. Our data define a specific role of miR-150 in the development and function of iNKT cells.
Skewed Primary Igκ Repertoire and V–J Joining in C57BL/6 Mice: Implications for Recombination Accessibility and Receptor Editing
Authors: Aoki-Ota Miyo , Torkamani Ali , Ota Takayuki , Schork Nicholas , Nemazee David 
Published: January 2012

AbstractPrevious estimates of the diversity of the mouse Ab repertoire have been based on fragmentary data as a result of many technical limitations, in particular, the many samples necessary to provide adequate coverage. In this study, we used 5′-coding end amplification of Igκ mRNAs from bone marrow, splenic, and lymph node B cells of C57BL/6 mice combined with amplicon pyrosequencing to assess the functional and nonfunctional Vκ repertoire. To evaluate the potential effects of receptor editing, we also compared V/J associations and usage in bone marrows of mouse mutants under constitutive negative selection or an altered ability to undergo secondary recombination. To focus on preimmune B cells, our cell sorting strategy excluded memory B cells and plasma cells. Analysis of ∼90 Mbp, representing &gt;250,000 individual transcripts from 59 mice, revealed that 101 distinct functional Vκ genes are used but at frequencies ranging from ∼0.001 to ∼10%. Usage of seven Vκ genes made up &gt;40% of the repertoire. A small class of transcripts from apparently nonfunctional Vκ genes was found, as were occasional transcripts from several apparently functional genes that carry aberrant recombination signals. Of 404 potential V–J combinations (101 Vκs × 4 Jκs), 398 (98.5%) were found at least once in our sample. For most Vκ transcripts, all Jκs were used, but V–J association biases were common. Usage patterns were remarkably stable in different selective conditions. Overall, the primary κ repertoire is highly skewed by preferred rearrangements, limiting Ab diversity, but potentially facilitating receptor editing.
The Lanthanides, Rare Earth Elements
Authors: Wells Willard H. , Wells Vickie L. 
Published: January 2012

AbstractThe lanthanides (or lanthanons) are a group of 15 elements of atomic numbers from 57 through 71 in which scandium (atomic number 21) and yttrium (atomic number 39) are sometimes included. The lanthanide series proper is that group of chemical elements that follow lanthanum in its group IIIB column position of the periodic table. Their distinguishing atomic feature is that they fill the 4felectronic subshell. Actually, only those elements with atomic numbers 58–71 are lanthanides. Most chemists also include lanthanum in the series because, although it does not fill the 4fsubshell, its properties are very much like those of the lanthanides. The elements scandium and yttrium are also known as the “rare earths” because they were originally discovered together with the lanthanides in rare minerals and isolated as oxides, or “earths.” Collectively, these metals are also called rare earth elements (REEs). In comparison with many other elements, however, the rare earths are not really rare, except for promethium, which has only radioactive isotopes. Yttrium, lanthanum, cerium, and neodymium are all more abundant than lead in the earth's crust. All except promethium, which probably does not occur in nature, are more abundant than cadmium. The relative abundance and atomic numbers are provided. The more common lanthanide compounds are listed in Section 1.Scandium is a silvery white metallic chemical element, the first member of the first transition‐metal series in the periodic table. The name is derived from Scandinavia, where the element was discovered in the minerals euxenite and gadolinite. In 1876, L. F. Nilson prepared about 2 g of high purity scandium oxide. It was subsequently established that scandium corresponds to the element “ekaboron,” predicted by Mendeleyev on the basis of a gap in the periodic table. Scandium occurs in small quantities in more than 800 minerals and causes the blue color of aquamarine beryl.Yttrium is one of the four chemical elements (the others are erbium, terbium, and ytterbium) named after Ytterby, a village in Sweden that is rich in unusual minerals and rare earths. Yttrium is a metal with a silvery luster and properties closely resembling those of rare earth metals. It is the first member of the second series of transition metals. Yttrium is found in several minerals and is produced primarily from the ore material xenotime.Lanthanum is a white, malleable metal; it is the first member of the third series of transition metals, and the first of the rare earths. Lanthanum is found with other lanthanides in the ore minerals monazite, bastnaesite, and xenotime, and in other minerals. It was discovered in 1839 by the Swedish chemist Carl G. Mosander. Scientists have created many radioactive isotopes of lanthanum.
Measuring Domain Sizes and Compositional Heterogeneities in P3HT‐PCBM Bulk Heterojunction Thin Films with 1H Spin Diffusion NMR Spectroscopy
Authors: Nieuwendaal Ryan C. , Ro Hyun Wook , Germack David S. , Kline R. Joseph , Toney Michael F. , Chan Calvin K. , Agrawal Amit , Gundlach David , VanderHart David L. , Delongchamp Dean M. 
Published: January 2012

AbstractThe application of 1H spin diffusion nuclear magnetic resonance (NMR) is expanded to polymer‐fullerene blends for bulk heterojunction (BHJ) organic photovoltaics (OPV) by developing a new experimental methodology for measuring the thin films used in poly‐3‐hexylthiophene–phenyl C61‐butyric acid methyl ester (P3HT‐PCBM) OPV devices and by creating an analysis framework for estimating domain size distributions. It is shown that variations in common P3HT‐PCBM BHJ processing parameters such as spin‐coating speed and thermal annealing can significantly affect domain size distributions, which in turn affect power conversion efficiency. 1H spin diffusion NMR analysis reveals that films spin‐cast at fast speeds in dichlorobenzene are primarily composed of small (<10 nm) domains of each component; these devices exhibit low power conversion efficiencies (η = 0.4%). Fast‐cast films improve substantially by thermal annealing, which causes nanometer‐scale coarsening leading to higher efficiency (η = 2.2%). Films spin‐cast at slow speeds and then slowly dried exhibit larger domains and even higher efficiencies (η = 2.6%), but do not benefit from thermal annealing. The 1H spin diffusion NMR results show that a significant population of domains tens of nanometers in size is a common characteristic of samples with higher efficiencies.
Shedding Light on the Operation of Polymer Light‐Emitting Electrochemical Cells Using Impedance Spectroscopy
Authors: Munar Antoni , Sandström Andreas , Tang Shi , Edman Ludvig 
Published: January 2012

AbstractA combination of impedance spectroscopy, device characterization, and modeling is used to pinpoint key processes in the operation of polymer light‐emitting electrochemical cells (LECs). At low applied voltage, electric double layers with a thickness of ≈2–3 nm are shown to exist at the electrode interfaces. At voltages exceeding the bandgap potential of the conjugated polymer (V ≥ 2.5 V for superyellow), a light‐emitting p–n junction forms in situ, with a steady‐state structure that is found to depend strongly on the applied voltage. This is exemplified by that the effective p–n junction thickness (dpn) for a device with an interelectrode gap of 90 nm decreases from ≈23 nm at 2.5 V to ≈6 nm at 3.9 V. The current increases with decreasing dpn in a concerted manner, while the brightness reaches its peak at V = 3.4 V when dpn ≈ 10 nm. The existence of an optimum dpn for high brightness in LECs is attributed to an offset between an increase in the exciton formation rate with decreasing dpn, due to an increasing current, and a simultaneous decrease in the exciton radiative decay rate, when an increasing fraction of excitons diffuses away from the p–n junction into the surrounding non‐radiative doping regions.